Tag: 2001

A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome

Comment on: Editorial response: microbial persistence and idiopathic dilated cardiomyopathy. [Clin Infect Dis. 1999]

 

SIR—We have presented controlled and observational data that are consistent with the hypothesis that subsets of cases of chronic fatigue syndrome (CFS) result from cardiac disease due to a single, persisting infection caused by Epstein-Barr virus (EBV) or, in turn, to a single, persisting infection caused by human cytomegalovirus (HCMV) in immunocompetent patients [1]. Patients who have a separate subset of CFS have simultaneous coinfection with EBV and HCMV. Cardiomyopathic changes are observed in right ventricular endomyocardial biopsy specimens obtained from such patients, and abnormal findings on Holter monitoring (e.g., oscillating abnormal T-wave flattenings and T-wave inversions) are “uniformly” present [2–4]. Left ventricular dysfunction is manifested by sinus tachycardia at rest, abnormal cardiac-wall motion, and decreased left ventricular ejection fractions (rest/stress) in those patients with CFS who are most ill [5]. These findings belie the relatively normal findings observed on standard 12-lead electrocardiograms [6].

In January 1995, a double-blinded, placebo-controlled, phase III crossover study of patients with CFS was initiated. Eleven patients who had CFS (10 of whom were women) were each followed for 18 consecutive months. The mean patient age was 42.7 years, and the mean duration of CFS was 35.1 months. Before antiviral nucleosides were administered, endomyocardial biopsies were performed. Cardiac tissues and blood samples tested negative for isolation of HCMV in cultures of human fibroblast tissues. Two cardiac biopsy specimens that were obtained from patients who had CFS tested positive for HCMV nucleic acids by means of PCR. No cardiac specimen that was obtained from a patient with CFS tested positive for EBV nucleic acids. (Cardiac tissue samples that were obtained from 4 of 21 control patients who had coronary artery disease but who did not have CFS also tested positive for HCMV nucleic acids.) Cardiomyopathic degenerative findings (e.g., myofiber disarray, interstitial fibrosis, increased intracellular granules, and interstitial fat) were noted in patients who had CFS. One patient who had CFS had myocarditis with focal lymphocytic infiltrates.

You can read the rest of this article here: http://cid.oxfordjournals.org/content/32/11/1657.long

 

Source: Lerner AM, Zervos M, Chang CH, Beqaj S, Goldstein J, O’Neill W, Dworkin H, Fitgerald T, Deeter RG. A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome. Clin Infect Dis. 2001 Jun 1;32(11):1657-8. http://cid.oxfordjournals.org/content/32/11/1657.long (Full article)

 

Detection of immunologically significant factors for chronic fatigue syndrome using neural-network classifiers

Abstract:

Neural-network classifiers were used to detect immunological differences in groups of chronic fatigue syndrome (CFS) patients that heretofore had not shown significant differences from controls. In the past linear methods were unable to detect differences between CFS groups and non-CFS control groups in the nonveteran population.

An examination of the cluster structure for 29 immunological factors revealed a complex, nonlinear decision surface. Multilayer neural networks showed an over 16% improvement in an n-fold resampling generalization test on unseen data. A sensitivity analysis of the network found differences between groups that are consistent with the hypothesis that CFS symptoms are a consequence of immune system dysregulation.

Corresponding decreases in the CD19(+) B-cell compartment and the CD34(+) hematopoietic progenitor subpopulation were also detected by the neural network, consistent with the T-cell expansion. Of significant interest was the fact that, of all the cytokines evaluated, the only one to be in the final model was interleukin-4 (IL-4). Seeing an increase in IL-4 suggests a shift to a type 2 cytokine pattern. Such a shift has been hypothesized, but until now convincing evidence to support that hypothesis has been lacking.

 

Source: Hanson SJ, Gause W, Natelson B. Detection of immunologically significant factors for chronic fatigue syndrome using neural-network classifiers. Clin Diagn Lab Immunol. 2001 May;8(3):658-62. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC96120/ (Full article)

 

Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome

Abstract:

Chronic Fatigue Syndrome (CFS) is an unexplained illness that is characterized by severe fatigue. Some have suggested that CFS is a “functional somatic syndrome” in which symptoms of fatigue are inappropriately attributed to a serious illness. However, brain magnetic resonance imaging (MRI) data suggest that there may be an organic abnormality associated with CFS.

To understand further the significance of brain MRI abnormalities, we examined the relationship between MRI identified brain abnormalities and self-reported physical functional status in 48 subjects with CFS who underwent brain MR imaging and completed the Medical Outcomes Study SF-36. Brain MR images were examined for the presence of abnormalities based on 5 general categories previously shown to be sensitive to differentiating CFS patients from healthy controls.

There were significant negative relationships between the presence of brain abnormalities and both the physical functioning (PF) (rho=-.31, p=.03), and physical component summary PCS (rho=-.32, p=.03) subscales of the SF-36. CFS patients with MRI identified brain abnormalities scored significantly lower on both PF (t(1,46) =2.3, p=.026) and the PCS (t(1,41) =2.4, p=.02) than CFS subjects without an identified brain abnormality. When adjusted for age differences only the PF analysis remained significant. However, the effect sizes for both analyses were large indicating meaningful differences in perceived functional status between the groups.

These results demonstrate that the presence of brain abnormalities in CFS are significantly related to subjective reports of physical function and that CFS subjects with MRI brain abnormalities report being more physically impaired than those patients without brain abnormalities.

 

Source: Cook DB, Lange G, DeLuca J, Natelson BH. Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome. Int J Neurosci. 2001 Mar;107(1-2):1-6. http://www.ncbi.nlm.nih.gov/pubmed/11328679

 

Chronic illness — a disruption in life: identity-transformation among women with chronic fatigue syndrome and fibromyalgia

Abstract:

BACKGROUND: People with chronic illnesses often suffer from identity-loss. Empirical research concerning patients with chronic fatigue syndrome (CFS) or fibromyalgia has not, however, adequately addressed the consequences of these illnesses for identity.

AIM: The aim of this article is to describe how women with CFS and fibromyalgia create new concepts of identity after the onset of illness, and how they come to terms with their newly arisen identities. I aim to illuminate the biographical work done by these individuals, which includes a re-evaluation of their former identity and life. This process is illustrated by the following themes: An earlier identity partly lost and Coming to terms with a new identity.

METHOD: The study is based on interviews with 25 women in Sweden, 12 with the diagnosis of CFS and 13 diagnosed with fibromyalgia. A grounded theory orientated approach was used when collecting and analysing the data.

FINDINGS: The main findings are that: (1) the illnesses can involve a radical disruption in the women’s biography that has profound consequences for their identity, particularly in relation to work and social life, (2) biographical disruptions are partial rather than total, calling for different degrees of identity transformation, (3) many of the women also experience illness gains in relation to the new identity.

CONCLUSIONS: Thus, the biographical disruption and illness experience comprised both losses and illness gains that had consequences for identity.

 

Source: Asbring P. Chronic illness — a disruption in life: identity-transformation among women with chronic fatigue syndrome and fibromyalgia. J Adv Nurs. 2001 May;34(3):312-9. http://www.ncbi.nlm.nih.gov/pubmed/11328436

 

Chronic fatigue syndrome following a toxic exposure

Abstract:

Chronic fatigue syndrome (CFS) is a clinical entity characterized by severe fatigue lasting more than 6 months and other well-defined symptoms. Even though in most CFS cases the etiology is still unknown, sometimes the mode of presentation of the illness implicates the exposure to chemical and/or food toxins as precipitating factors: ciguatera poisoning, sick building syndrome, Gulf War syndrome, exposure to organochlorine pesticides, etc.

In the National Reference Center for CFS Study at the Department of Infectious Diseases of ‘G. D’Annunzio’ University (Chieti) we examined five patients (three females and two males, mean age: 37.5 years) who developed the clinical features of CFS several months after the exposure to environmental toxic factors: ciguatera poisoning in two cases, and exposure to solvents in the other three cases. These patients were compared and contrasted with two sex- and age-matched subgroups of CFS patients without any history of exposure to toxins: the first subgroup consisted of patients with CFS onset following an EBV infection (post-infectious CFS), and the second of patients with a concurrent diagnosis of major depression.

All subjects were investigated by clinical examination, neurophysiological and immunologic studies, and neuroendocrine tests. Patients exposed to toxic factors had disturbances of hypothalamic function similar to those in controls and, above all, showed more severe dysfunction of the immune system with an abnormal CD4/CD8 ratio, and in three of such cases with decreased levels of NK cells (CD56+). These findings may help in understanding the pathogenetic mechanisms involved in CFS.

 

Source: Racciatti D, Vecchiet J, Ceccomancini A, Ricci F, Pizzigallo E. Chronic fatigue syndrome following a toxic exposure. Sci Total Environ. 2001 Apr 10;270(1-3):27-31. http://www.ncbi.nlm.nih.gov/pubmed/11327394

 

Characterization of a 2′,5′-oligoadenylate (2-5A)-dependent 37-kDa RNase L: azido photoaffinity labeling and 2-5A-dependent activation

Erratum in: J Biol Chem 2001 Aug 24;276(34):32392.

Abstract:

Upregulation of key components of the 2′,5′-oligoadenylate (2-5A) synthetase/RNase L pathway has been identified in extracts of peripheral blood mononuclear cells from individuals with chronic fatigue [corrected] syndrome, including the presence of a low molecular weight form of RNase L. In this study, analysis of 2′,5′-Oligoadenylate (2-5A) binding and activation of the 80- and 37-kDa forms of RNase L has been completed utilizing photolabeling/immunoprecipitation and affinity assays, respectively. Saturation of photolabeling of the 80- and the 37-kDa RNase L with the 2-5A azido photoprobe, [(32)P]pApAp(8-azidoA), was achieved. Half-maximal photoinsertion of [(32)P]pApAp(8-azidoA) occurred at 3.7 x 10(-8) m for the 80-kDa RNase L and at 6.3 x 10(-8) m for the 37-kDa RNase L. Competition experiments using 100-fold excess unlabeled 2-5A photoaffinity probe, pApAp(8-azidoA), and authentic 2-5A (p(3)A(3)) resulted in complete protection against photolabeling, demonstrating that [(32)P]pApAp(8-azidoA) binds specifically to the 2-5A-binding site of the 80- and 37-kDa RNase L. The rate of RNA hydrolysis by the 37-kDa RNase L was three times faster than the 80-kDa RNase L. The data obtained from these 2-5A binding and 2-5A-dependent activation studies demonstrate the utility of [(32)P]pApAp(8-azidoA) for the detection of the 37-kDa RNase L in peripheral blood mononuclear cell extracts.

 

Source: Shetzline SE, Suhadolnik RJ. Characterization of a 2′,5′-oligoadenylate (2-5A)-dependent 37-kDa RNase L: azido photoaffinity labeling and 2-5A-dependent activation. J Biol Chem. 2001 Jun 29;276(26):23707-11. Epub 2001 Apr 25. http://www.jbc.org/content/276/26/23707.long (Full article)

 

Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome

Abstract:

The pathophysiological basis for chronic fatigue syndrome (CFS) remains poorly understood. Certain symptoms of CFS, namely fatigue, neurocognitive symptoms and sleep disturbance, are similar to those of acute jet lag and shift work syndromes thus raising the possibility that CFS might be a condition associated with disturbances in endogenous circadian rhythms.

In this study, we tested this hypothesis by examining the circadian rhythm of core body temperature (CBT) in CFS and control subjects. Continuous recordings of CBT were obtained every 5 min over 48 h in a group of 10 subjects who met the Center for Disease Control (CDC) definition of CFS and 10 normal control subjects. Subjects in the two groups were age, sex and weight-matched and were known to have normal basal metabolic rates and thyroid function.

CBT recordings were performed under ambulatory conditions in a clinical research centre with the use of an ingestible radio frequency transmitter pill and a belt-worn receiver-logger. CBT time series were analysed by a cosinor analysis and by a harmonic-regression-plus-correlated-noise model to estimate the mean, amplitude and phase angle of the rhythm. The goodness of fit of each model was also compared using the Akaike Information Criterion (AIC) and sigma2. Average parameters for each group were compared by Student’s t-test.

By cosinor analysis, the only significant difference between CFS and control groups was in the phase angle of the third harmonic (P=0.02). The optimal harmonic-regression-plus-correlated-noise models selected were ARMA(1,1): control 7, CFS 6; ARMA(2,0): control 1, CFS 4; and ARMA(2,1): control 2 subjects. The optimal fit ARMA model contained two harmonics in eight of 10 control subjects but was more variable in the CFS subjects (1 harmonic: 5 subjects; 2 harmonics: 1 subject; 3 harmonics: 4 subjects). The goodness of fit measures for the optimal ARMA model were also better in the control than the CFS group, but the differences were not statistically significant.

We conclude that, measured under ambulatory conditions, the circadian rhythm of CBT in CFS is nearly indistinguishable from that of normal control subjects although there was a tendency for greater variability in the rhythm. Hence, it is unlikely that the symptoms of CFS are because of disturbance in the circadian rhythm of CBT.

 

Source: Hamilos DL, Nutter D, Gershtenson J, Ikle D, Hamilos SS, Redmond DP, Di Clementi JD, Schmaling KB, Jones JF. Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome. Clin Physiol. 2001 Mar;21(2):184-95. http://www.ncbi.nlm.nih.gov/pubmed/11318826

 

Evaluation of a recombinant line blot for diagnosis of Epstein-Barr Virus compared with ELISA, using immunofluorescence as reference method

Abstract:

A commercial line blot using recombinant antigens was compared with a commercial ELISA and ‘in-house’ IFA (reference test). Two panels were evaluated: Panel A was selected to distinguish between primary infections (89), past infections (20) and seronegatives (8) in immunocompetent individuals. In panel B, patients with a high number of reactivations were included: immunosuppressed patients (37), lymphoma (19), nasopharyngeal carcinoma (10), chronic fatigue syndrome (14). Blood donors (43) and cross-reactive sera (29) were added as controls.

Line blot and IFA were concordant in 94% of primary infections, 100% of seronegatives and 100% of past infections, similar to ELISA. Results differed significantly with regard to reactivations. When compared with IFA, the incidence of reactivations was overestimated by the blot, 24 and 58% in blood donors and cross-reactive sera, respectively. ELISA showed a similar problems with 21 and 34% indeterminate results, respectively.

The line blot is easy to carry out, has a good concordance with the reference IFA for primary infections, and is, therefore, a sufficient choice for distinguishing primary infection from seronegative and past infection. EBV reactivation assessment will require other methods such as EBV viral load.

 

Source: Gärtner BC, Fischinger JM, Roemer K, Mak M, Fleurent B, Mueller-Lantzsch N. Evaluation of a recombinant line blot for diagnosis of Epstein-Barr Virus compared with ELISA, using immunofluorescence as reference method. J Virol Methods. 2001 Apr;93(1-2):89-96. http://www.ncbi.nlm.nih.gov/pubmed/11311347

 

Working memory deficits associated with chronic fatigue syndrome

Abstract:

Cognitive impairments are among the most frequently reported and least investigated components of the chronic fatigue syndrome (CFS). As part of a multifaceted study of the CFS, the present study investigated the cognitive functioning of chronic fatigue patients.

The performance of 20 CFS patients was compared to that of controls (N = 20) on 4 tests of working memory (WM). Digit Span Forward was used to assess the storage capacity of WM. Multiple aspects of central executive functioning were assessed using several standard measures: Digit Span Backward, and Trails A and Trails B. More recently developed measures of WM were used to assess control of processing under temporal demands (working memory task) and resistance to interference (a sustained attention task).

Deficits were restricted to more demanding tasks, requiring resistance to interference and efficient switching between processing routines. The overall results clearly implicate deficits in the control aspects of central executive function in CFS.

 

Source: Dobbs BM, Dobbs AR, Kiss I. Working memory deficits associated with chronic fatigue syndrome. J Int Neuropsychol Soc. 2001 Mar;7(3):285-93. http://www.ncbi.nlm.nih.gov/pubmed/11311029

 

Discriminating between chronic fatigue syndrome and depression: a cognitive analysis

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) and depression share a number of common symptoms and the majority of CFS patients meet lifetime criteria for depression. While cognitive factors seem key to the maintenance of CFS and depression, little is known about how the cognitive characteristics differ in the two conditions.

METHODS: Fifty-three CFS patients were compared with 20 depressed patients and 38 healthy controls on perceptions of their health, illness attributions, self-esteem, cognitive distortions of general and somatic events, symptoms of distress and coping. A 6 month follow-up was also conducted to determine the stability of these factors and to investigate whether CFS-related cognitions predict ongoing disability and fatigue in this disorder.

RESULTS: Between-group analyses confirmed that the depressed group was distinguished by low self-esteem, the propensity to make cognitive distortions across all situations, and to attribute their illness to psychological factors. In contrast, the CFS patients were characterized by low ratings of their current health status, a strong illness identity, external attributions for their illness, and distortions in thinking that were specific to somatic experiences. They were also more likely than depressed patients to cope with their illness by limiting stress and activity levels. These CFS-related cognitions and behaviours were associated with disability and fatigue 6 months later.

CONCLUSIONS: CFS and depression can be distinguished by unique cognitive styles characteristic of each condition. The documented cognitive profile of the CFS patients provides support for the current cognitive behavioural models of the illness.

 

Source: Moss-Morris R, Petrie KJ. Discriminating between chronic fatigue syndrome and depression: a cognitive analysis. Psychol Med. 2001 Apr;31(3):469-79. http://www.ncbi.nlm.nih.gov/pubmed/11305855