Tag: large-scale study

Cell-mediated immune function and the outcome of chronic fatigue syndrome

Abstract:

This study examined the importance of cell-mediated immunity in determining the long-term outcome of patients diagnosed with chronic fatigue syndrome (CSF).

A total of 103 patients (74%) of 139 previously enrolled in one of two treatment trials conducted within a university hospital referral center was reviewed a mean of 3.2 yr after trial entry. Ongoing symptom severity, levels of disability and immunological function were assessed at follow-up. The relationship between immunological function at trial entry and measures of outcome was also evaluated.

Sixty-five patients (63%) had improved, while only 6 (6%) reported no current symptoms. Thirty-one subjects (30%) were unable to perform any form of work and 26 (25%) were on a disability benefit directly attributable to CFS. Cell-mediated immune function, as measured at trial entry or follow-up, did not appear to affect outcome.

Whilst improvement occurred in the majority of patients with CFS, a substantial proportion (37%) remained functionally impaired. Impairment of cell-mediated immunological function measured during the course of the illness may not be an important factor in determining long-term outcome.

 

Source: Wilson A, Hickie I, Lloyd A, Hadzi-Pavlovic D, Wakefield D. Cell-mediated immune function and the outcome of chronic fatigue syndrome. Int J Immunopharmacol. 1995 Aug;17(8):691-4. http://www.ncbi.nlm.nih.gov/pubmed/8847164

 

Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients

Abstract:

Coxsackie B enteroviruses have been implicated repeatedly as agents associated with chronic fatigue syndrome (CFS). The objective of this study was to compare the serological evidence for the presence of Coxsackie B virus neutralising antibody, with the polymerase chain reaction (PCR) detecting a portion of the 5′ nontranslated region (NTR) of the enterovirus genome.

Serum samples from 100 chronic fatigue patients and from 100 healthy comparison patients were used in this study. In the CFS study group, 42% patients were positive for enteroviral sequences by PCR, compared to only 9% of the comparison group. Using the neutralisation assay, 34% of study patients were positive, compared to 41% of comparison patients.

In the study group, 66/100 patient results correlated, i.e., they were either positive/positive or negative/negative for both tests. Of those that did not correlate, the majority were PCR-positive/Coxsackie B antibody-negative (21/34).

In the comparison group, 58/100 patient results correlated. Of those that did not, the majority were PCR-negative/Coxsackie B antibody-positive (37/42).

The Coxsackie B antibody neutralisation assay was not able to differentiate the CFS study group from the healthy comparison group, and thus the clinical relevance of this assay may be questioned. The PCR assay did differentiate the two groups with significantly more CFS patients having evidence of enterovirus than the comparison group.

Source: Nairn C, Galbraith DN, Clements GB. Comparison of coxsackie B neutralisation and enteroviral PCR in chronic fatigue patients. J Med Virol. 1995 Aug;46(4):310-3. http://www.ncbi.nlm.nih.gov/pubmed/7595406

 

Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system

Abstract:

OBJECTIVES: To investigate the point prevalence of the chronic fatigue syndrome and unexplained debilitating chronic fatigue in a community-based sample of persons and to describe demographic, clinical, and psychosocial differences among those with the chronic fatigue syndrome, those with chronic fatigue, and healthy controls.

DESIGN: Prospective cohort study.

SETTING: A health maintenance organization in Seattle, Washington.

PARTICIPANTS: A random sample of 4000 members of the health maintenance organization was surveyed by mail for the presence of chronic fatigue.

MEASUREMENTS: Persons with chronic fatigue were evaluated using a questionnaire that requested information about medical history and fatigue and related symptoms; validated measures of functional status and psychological distress; a physical examination; and standardized blood tests. A structured psychiatric interview was done in persons who appeared to meet the original Centers for Disease Control and Prevention (CDC) criteria for the chronic fatigue syndrome. Participants completed self-report measures at 12 and 24 months. Those with chronic fatigue were reevaluated in person 1 year after study enrollment.

RESULTS: 3066 (77%) of the 4000 members surveyed responded. Chronic fatigue was reported by 590 persons (19%). Of these, 388 (66%) had a medical or psychiatric condition that could account for the fatigue. Of the 74 persons (37%) with chronic fatigue who were enrolled in the study, only 3 met the CDC criteria for the chronic fatigue syndrome. The remaining 71 persons were designated as having chronic fatigue alone. Seventy-four healthy, age- and sex-matched controls who were drawn from the same sample but who denied having chronic fatigue were also studied. Demographic characteristics were similar in persons with the chronic fatigue syndrome, persons with chronic fatigue alone, and controls. Those with the chronic fatigue syndrome or chronic fatigue alone had more frequent cervical and axillary adenopathy, poorer functional status, and greater psychological distress than controls. Women and minorities were not overrepresented among cases with chronic fatigue.

CONCLUSIONS: Using different assumptions about the likelihood that persons who did not participate in the study had the chronic fatigue syndrome, the estimated crude point prevalence of the syndrome in this community ranged from 75 to 267 cases per 100,000 persons. The point prevalence of chronic fatigue alone was strikingly higher; it ranged from 1775 to 6321 cases per 100,000 persons.

 

Source: Buchwald D, Umali P, Umali J, Kith P, Pearlman T, Komaroff AL. Chronic fatigue and the chronic fatigue syndrome: prevalence in a Pacific Northwest health care system. Ann Intern Med. 1995 Jul 15;123(2):81-8. http://www.ncbi.nlm.nih.gov/pubmed/7778839

 

Clinical laboratory test findings in patients with chronic fatigue syndrome

Abstract:

BACKGROUND: Results of readily available clinical laboratory tests in patients with chronic fatigue syndrome were compared with results in healthy control subjects.

METHODS: Cases consisted of all 579 patients who met either the Centers for Disease Control and Prevention, Atlanta, Ga, British, or Australian case definition for chronic fatigue syndrome. They were from chronic fatigue clinics in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood donors who denied chronic fatigue. Outcome measures were the results of 18 clinical laboratory tests.

RESULTS:Age- and sex-adjusted odds ratios of abnormal results, comparing cases with control subjects, were as follows: circulating immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0-37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95% CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0% in the control subjects. The results of these tests were generally comparable for the cases from Seattle and Boston. Although these tests served to discriminate the population of patients from healthy control subjects, at the individual level they were not as useful.

CONCLUSIONS: Patients with chronic fatigue syndrome who were located in two geographically distant areas had abnormalities in the results of several readily available clinical laboratory tests compared with healthy control subjects. The immunologic abnormalities are in accord with a growing body of evidence suggesting chronic, low-level activation of the immune system in chronic fatigue syndrome. While each of these laboratory findings supports the diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a diagnostic test. Furthermore, the specificity of these findings relative to other organic and psychiatric conditions that can produce fatigue remains to be established.

Comment in: Clinical laboratory test findings in patients with chronic fatigue syndrome. [Arch Intern Med. 1995]

 

Source: Bates DW, Buchwald D, Lee J, Kith P, Doolittle T, Rutherford C, Churchill WH, Schur PH, Wener M, Wybenga D, et al. Clinical laboratory test findings in patients with chronic fatigue syndrome. Arch Intern Med. 1995 Jan 9;155(1):97-103. http://www.ncbi.nlm.nih.gov/pubmed/7632202

 

Studies on enterovirus in patients with chronic fatigue syndrome

Abstract:

A large study on 121 patients with the chronic fatigue syndrome (CFS) that examined muscle biopsy samples for enterovirus by means of polymerase chain reaction analysis was carried out. The results were compared with those obtained from 101 muscle biopsy specimens from patients with a variety of other neuromuscular disorders (OND), including neurogenic atrophies, dystrophies, and mitochondrial, metabolic, and endocrine myopathies.

Thirty-two (26.4%) of the biopsy specimens from the group of patients with CFS were positive, compared with 20 (19.8%) from the group of patients with OND, a difference that was not significant.

This finding is in contrast to those of our previous smaller study in which significantly more patients with CFS than control subjects (53% [32 of 60] vs. 15% [6 of 41]) had enterovirus RNA sequences in their muscle. It was concluded that it is unlikely that persistent enterovirus infection plays a pathogenetic role in CFS, although an effect in initiating the disease process cannot be excluded.

 

Source: Gow JW, Behan WM, Simpson K, McGarry F, Keir S, Behan PO. Studies on enterovirus in patients with chronic fatigue syndrome. Clin Infect Dis. 1994 Jan;18 Suppl 1:S126-9. http://www.ncbi.nlm.nih.gov/pubmed/8148439

 

Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes

Abstract:

375 patients with chronic fatigue syndrome (CFS) were examined using a standardized questionnaire and subsequent interview on 11 risk factors and 45 symptoms. Additionally immunologic, serologic, toxicologic, neuroradiologic, neurophysiologic and cardiologic investigations were performed.

Immunologic tests showed cellular immunodeficiences particularly in functional regard (pathological lymphocyte stimulation in 50% of the patients, disorders of granulocyte function in 44%). Furthermore variable deviations were found in the lymphocyte subpopulations (CD3, CD4, CD8, CD19, DR, Leu 11 + 19).

In the humoral part tendencies to low IgG-3- and IgG-1-subclass-levels occurred (59% respectively 11% of the patients) also as decreases in complement system (CH50, C3, C4, C1-esterase-inhibitor). In the group of activation markers and cytokines 42% of the investigated patients had circulating immune complexes (CIC), 47% increases of tumor-necrosis-factor (TNF-a) and 21% increases of soluble interleukin-2-receptor (IL-2-R).

The increased occurrence of autoantibodies in the CFS-patients (specially antinuclear anti-bodies [ANA], microsomal thyroid antibodies) suggest, that CFS is associated with or the beginning of manifest autoimmune disease.

Under the pathogens 78% of the patients had a striking serological constellation of Epstein-Barr-Virus (EBV-EA positive, low EBNA-titers), in the HHV-6-Virus 47% showed increased antibody-titers. Tests on further herpes viruses and on Borreliae, Chlamydiae, Candida and Amoebae were positive in 8 to 36% of the examined patients. Furthermore there were found variable deficits of vitamins and trace elements also as hormonal disturbances.

In 26% of the patients there were hints of pollutants (e.g. wood preservatives), in 32 patients blood-levels of pentachlorphenol (PCP) and gamma-hexachlorcyclohexan (γ-HCH, lindan) were measured, which showed vanable increases.

178 (83%) of 225 investigated patients showed disturbances of perfusion in cerebral SPECT imaging, 65 (29%) of 218 patients cerebral punctuate signal changes in cranial magnetic resonance imaging (MRI).

Neurophysiologic measurements (motor evoked potentials, MEP) showed in about 50% of 112 patients prolonged central motor conduction times. 62 patients were additionally investigated by myocardial SPECT-imaging, which was abnormal under exercise in 73%. Our data confirm the concept, that CFS must be considered as a complex psycho-neuro-immunological disorder.

 

Source: Hilgers A, Frank J. Chronic fatigue syndrome: immune dysfunction, role of pathogens and toxic agents and neurological and cardial changes. Wien Med Wochenschr. 1994;144(16):399-406.[Article in German] http://www.scopus.com/record/display.uri?eid=2-s2.0-0027940724&origin=inward&txGid=0

and http://www.ncbi.nlm.nih.gov/pubmed/7856214

 

 

Epidemiology of chronic fatigue syndrome: the Centers for Disease Control Study

Abstract:

The US Centers for Disease Control initiated physician-based chronic fatigue syndrome (CFS) surveillance systems in four cities in September 1989 to determine the prevalence, incidence, course and impact of the illness. The participating physicians have referred to our surveillance system 590 patients who were ill during the first two years of surveillance with severe, debilitating, unexplained fatigue for at least the preceding six months.

Referred patients were screened for psychiatric disorders preceding, concurrent with, and subsequent to the onset of their fatigue by specially trained nurses using a modified Diagnostic Interview Schedule. Complete health histories were obtained by interview and review of medical records and a basic panel of standard laboratory diagnostic tests were conducted. Four physicians have independently reviewed the health information of 337 of the patients for classification.

Approximately 26% of patients referred to the surveillance system met the CFS case definition in all regards, 14% lacked one or more of the required eight symptom criteria, 15% were judged to have another possible or known medical illness which could account for the severe fatigue, and the remaining 45% did not meet the case definition because of histories of psychiatric disorders preceding the onset of fatigue.

Minimum prevalence rates for the period 1 September 1989 to 1 September 1991 ranged from 2.0 to 7.3 per 100,000 of the general population across the four study sites and rates based on prorated data ranged from 4.6 to 11.3 per 100,000. More than 80% of the CFS cases were female, most were white, and their average age at onset was approximately 30 years.

 

Source: Gunn WJ, Connell DB, Randall B. Epidemiology of chronic fatigue syndrome: the Centers for Disease Control Study. Ciba Found Symp. 1993;173:83-93; discussion 93-101. http://www.ncbi.nlm.nih.gov/pubmed/8387910

 

Epstein-Barr virus serology in the chronic fatigue syndrome

Abstract:

The antibody profiles against Epstein-Barr virus were studied in 136 patients presenting with chronic fatigue syndromes. These profiles were compared with a panel of sera from blood donors. The patients exhibited higher titres in a combined assay for antibodies to the Restricted (R) and Diffuse (D) components of the Early Antigen complex than controls (P less than 0.001) but titres against these antigens were not useful on an individual patient basis. The patients who displayed elevated titres of antibodies to Early Antigens did not differ clinically from those displaying titres in the control range. Four of nine patients who had increased antibodies to Early Antigens also had evidence of active enterovirus infection.

 

Source: Woodward CG, Cox RA. Epstein-Barr virus serology in the chronic fatigue syndrome. J Infect. 1992 Mar;24(2):133-9. http://www.ncbi.nlm.nih.gov/pubmed/1314860