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Posted to Co-Cure Tue, Wed, 25 Apr 2001 10:55:19 -0400 by Fred Springfield

Circadian rhythm of core body temperature in subjects with CFS

Full Title: Circadian rhythm of core body temperature in subjects with chronic fatigue syndrome.

Journal: Clin Physiol 2001 Mar;21(2):184-195

Authors: Hamilos DL, Nutter D, Gershtenson J, Ikle D, Hamilos SS, Redmond DP, Di Clementi JD, Schmaling KB, Jones JF.

Affiliations: Washington University School of Medicine, Division of Allergy and Immunology, Euclid Avenue, St Louis, Missouri; National Jewish Medical and Research Center, Denver, Colorado; Walter Reed Army Institute of Research, Division of Neuropsychology, Washington, District of Columbia, USA.

NLM Citation: PMID: 11318826

Summary: 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.

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Posted to Co-Cure Tue, 1 May 2001 15:21:16 -0400 by Fred Springfield

Chronic fatigue syndrome following a toxic exposure

Full Title: Chronic fatigue syndrome following a toxic exposure.

Journal: Sci Total Environ 2001 Apr 10;270(1-3):27-31

Authors: Racciatti D, Vecchiet J, Ceccomancini A, Ricci F, Pizzigallo E.

Affiliation: Department of Infectious Diseases, G. D'Annunzio University, Chieti Scalo, Italy.

NLM Citation: PMID: 11327394

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.

Full Text of Article

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Posted to Co-Cure Mon, 23 Apr 2001 23:00:09 -0400 by Kimberly Hare

Effects of pool-based and land-based aerobic exercise on women with FM/chronic widespread muscle pain

Full Title: Effects of pool-based and land-based aerobic exercise on women with fibromyalgia/chronic widespread muscle pain.

Journal: Arthritis Rheum 2001 Feb;45(1):42-7

Authors: Jentoft ES, Kvalvik AG, Mengshoel AM.

Affiliation: Haugesund Sanitetsforening Rheumatism Hospital, Norway.

NLM Citation: PMID: 11308060

OBJECTIVE: To examine the effects of pool-based (PE) and land-based (LE) exercise programs on patients with fibromyalgia.

METHODS: The outcomes were assessed by the Fibromyalgia Impact Questionnaire, the Arthritis Self-Efficacy Scale, and tests of physical capacity.

RESULTS: Eighteen subjects in the PE group and 16 in the LE group performed a structured exercise program. After 20 weeks, greater improvement in grip strength was seen in the LE group compared with the PE group (P < 0.05). Statistically significant improvements were seen in both groups in cardiovascular capacity, walking time, and daytime fatigue. In the PE group improvements were also found in number of days of feeling good, self-reported physical impairment, pain, anxiety, and depression. The results were mainly unchanged at 6 months followup.

CONCLUSION: Physical capacity can be increased by exercise, even when the exercise is performed in a warm-water pool. PE programs may have some additional effects on symptoms.

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Posted to Co-Cure Mon, 23 Apr 2001 22:46:35 -0400 by Fred Springfield

Working memory deficits associated with CFS

Full Title: Working memory deficits associated with chronic fatigue syndrome.

Journal: J Int Neuropsychol Soc 2001 Mar;7(3):285-93

Authors: Dobbs BM, Dobbs AR, Kiss I.

Affiliation: Department of Psychology, University of Alberta, Edmonton, Canada.

NLM Citation: PMID: 11311029

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.

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Posted to Co-Cure Sat, 23 Jun 2001 23:02:43 -0400 by Fred Springfield

Clinical and Immunologic Effects of Autologous Lymph Node Cell Transplant in CFS

Full Title: Clinical and Immunologic Effects of Autologous Lymph Node Cell Transplant in Chronic Fatigue Syndrome

Journal: Journal of Chronic Fatigue Syndrome, Vol. 8(1) 2001, pp. 39-55

Authors: Nancy G. Klimas, MD; Roberto Patarca-Montero, MD, PhD; Kevin Maher, PhD; Mack Smith, RN, ARNP; Oliver Bathe, MD; Mary Ann Fletcher, PhD

Affiliations: Nancy G. Klimas, Roberto Patarca-Montero, Kevin Maher, and Mary Ann Fletcher are Directors, E. M. Papper Laboratory of Clinical Immunology and Researchers at the Center for Behavioral Medicine Research, Miami Veterans Administration Medical Center, University of Miami School of Medicine, PO. Box 016960 (R-42), Miami, FL 33101.
Mack Smith is Research Nurse at the Center for Behavioral Medicine Research.
Oliver Bathe is affiliated with the Department of Surgery, Tom Baker Cancer Centre, University of Calgary, 1331/29th Street North West, Calgary, AB, T2N 4N2, Canada.
Address correspondence to: Nancy G. Klimas at the above address (E-mail: ).

This work was supported, in part, by a grant from the CFIDS Association of America, by NIH Center Grant 1UD1-AI 45940-02, and by funds from Neoprobe Corp. and Ciratech Corp.

ABSTRACT: 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.

KEYWORDS. Chronic fatigue syndrome, T-helper type 1 and type 2 cytokines, immune activation, cognitive difficulties, natural killer cells, autologous lymph node cell transplant

INTRODUCTION: Previous research from this laboratory and others indicates that people who have Chronic Fatigue Syndrome (CFS) frequently have two interrelated problems with immune function: (a) immune activation, as demonstrated by elevated numbers and proportions of T lymphocytes expressing surface markers of activation (CD26, CD38), as well as elevated circulating levels of cytokines (1-3); and (b) poor cellular function, with low natural killer cell cytotoxicity (NKCC) and poor lymphocyte response to mitogens in culture (1,2,4,5).

The decreased NKCC and lymphoproliferative activities and increased allergic and autoimmune manifestations in CFS support the hypothesis that the immune system of affected individuals is biased towards a T helper(Th)2-type, or humoral immunity-oriented cytokine pattern (6). The factors that could lead to a Th2-type shift among CFS patients are unknown, although stress, infection or exposure to vaccines have been shown to lead to long-term, non-specific shifts in cytokine balance (7,8). Therapeutic regimens that induce a systemic Th1-type bias are being tested and include poly(1)-poly (C12U) (9) and bacterial vaccines (Staphylococcus and Mycobacterium vaccae) [see international published patents number WO-09829133 by Goeteborg University Science Invest AB (Carl-Gerhard Gottfries and Bjoern Regland) and number WO-09826790 by Stanford Rook Limited (Graham Rook, John Stanford and Alimuddin Zumla)]. The present study describes a therapeutic intervention aimed to induce a more favorable cytokine expression pattern though the use of ex vivo lymphocyte manipulation with interleukin (IL)-2 and anti-CD3 followed by adoptive cell transplant. IL-2 is a Th1-type cytokine and a Th1-response inducer. Both IL-2 and anti-CD3 help activate T cells. The lymph node cells cultured under conditions designed to favor a Th1-type pattern are then reinfused into the donor who is monitored for adverse events and potential clinical benefit.

[Article copies available for a fee from The Haworth Document Delivery Service: 1-800-342-9678. E-mail address: Website: ]

2001 by The Haworth Press, Inc. All rights reserved.
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Posted to Co-Cure Mon, 23 Apr 2001 22:43:44 -0400 by Fred Springfield

Discriminating between CFS and depression: a cognitive analysis

Full Title: Discriminating between chronic fatigue syndrome and depression: a cognitive analysis.

Journal: Psychol Med 2001 Apr;31(3):469-79

Authors: Moss-Morris R, Petrie KJ.

Affiliations: Health Psychology Research Group, Faculty of Medical and Health Science, The University of Auckland, New Zealand.

NLM Citation: PMID: 11305855

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.

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Posted to Co-Cure Tue, 5 Jun 2001 23:16:12 -0400 by Fred Springfield

Neuropsychological function in patients with CFS, MS, and depression

Full Title: Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression.

Journal: Appl Neuropsychol 2001;8(1):12-22

Authors: Daly E, Komaroff AL, Bloomingdale K, Wilson S, Albert MS.

Affiliation: Department of Psychiatry, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02129, USA.

NLM Citation: PMID: 11388119

Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability.

A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability.

Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls. After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory.

The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.

Full Text

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Posted to Co-Cure Tue, 4 Apr 2001 23:16:12 -0400 by Fred Springfield

Anti-nuclear envelope antibodies: Clinical associations

Full-Title: Anti-nuclear envelope antibodies: Clinical associations.

Journal: Semin Arthritis Rheum 2001 Apr;30(5):313-320

Authors: Nesher G, Margalit R, Ashkenazi YJ.

Affiliations: Department of Rheumatology Service, Hebrew University Medical School, Jerusalem, and the Departments of Internal Medicine and Hematology, Shaare-Zedek Medical Center, Jerusalem., Gideon Nesher, MD: Adjunct Associate Professor, St. Louis University School of Medicine, Senior Lecturer, The Hebrew University Medical School, and Director of Rheumatology Service, Shaare-Zedek Medical Center, Jerusalem, Israel; Ruth Margalit, MD: Former Resident, Department of Internal Medicine, Shaare-Zedek Medical Center, Jerusalem, Israel; Yaacov J. Ashkenazi, MD: Director of Internal Medicine-Hematology Day-Care Center, Shaare-Zedek Medical Center, Jerusalem, Israel.

NLM Citation: PMID: 11303304


OBJECTIVES: Characterization of the clinical associations and clinical implications of antibodies reacting with antigens of the nuclear envelope.

METHODS: Description of an illustrative case and a MEDLINE search-assisted literature review of relevant cases.

RESULTS: With indirect immunofluorescence, autoantibodies directed against various antigens of the nuclear envelope stain the nucleus in a ring-like (rim) pattern. Autoantibodies against 5 antigenic components of the nuclear envelope have been described: anti-gp210, p62, lamina, lamina-associated polypeptides, and lamin B receptor. Antibodies to antigens of the nuclear pore complex, such as gp210 and p62, are highly specific (>95%) for primary biliary cirrhosis and may aid in the serologic diagnosis of this condition, especially in cases in which antimitochondrial antibodies are not detectable. In contrast, antilamin antibodies are not disease-specific but seem to be associated with lupus anticoagulant or anticardiolipin antibodies, antiphospholipid syndrome, thrombocytopenia, autoimmune liver diseases, and arthralgia. High-titered antilamin antibodies help to define a subset of lupus patients with antiphospholipid antibodies who are at a lower risk of developing thrombotic events. In addition, preliminary data suggest that the presence of antilamin antibodies may be helpful in the diagnosis of chronic fatigue syndrome.

CONCLUSIONS: Each of the antibodies reacting with nuclear membrane antigens has its own spectrum of disease associations.

RELEVANCE: Determination of anti-nuclear envelope antibody pattern by indirect immunofluorescence, with subsequent determination of the specific antibody, carries important diagnostic and prognostic implications in various autoimmune conditions.

Copyright 2001 by W.B. Saunders Company

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Posted to Co-Cure Thu, 12 Apr 2001 19:21:58 -0400 by Kimberly Hare

Decreased Nocturnal Levels of Prolactin and Growth Hormone in Women with Fibromyalgia

Full Title: Decreased Nocturnal Levels of Prolactin and Growth Hormone in Women with Fibromyalgia.

Journal: J Clin Endocrinol Metab 2001 Apr 1;86(4):1672-1678

Authors: Landis CA, Lentz MJ, Rothermel J, Riffle SC, Chapman D, Buchwald D, Shaver JL.

Affiliations: Biobehavioral Nursing and Health Systems (C.A.L., M.J.L., J.R., S.C.R.), Chronic Fatigue Clinic (D.C.), Department of Medicine, Chronic Fatigue Syndrome Cooperative Research Center (D.B.), University of Washington, Seattle, Washington 98195.

NLM Citation: PMID: 11297602


Fibromyalgia (FM) is a complex syndrome, primarily of women, characterized by chronic pain, fatigue, and sleep disturbance. Altered function of the somatotropic axis has been documented in patients with FM, but little is known about nocturnal levels of PRL.

As part of a laboratory study of sleep patterns in FM, we measured the serum concentrations of GH and PRL hourly from 2000-0700 h in a sample of 25 women with FM (mean, 46.9 +/- 7.6 yr) and in 21 control women (mean, 42.6 +/- 8.1 yr).

The mean (+/-SEM ) serum concentrations (micrograms per L) of GH and of PRL during the early sleep period were higher in control women than in patients with FM [GH, 1.6 +/- 0.4 vs. 0.6 +/- 0.2 (P < 0.05); PRL, 23.2 +/- 2.2 vs. 16.9 +/- 2.0 (P < 0.025)]. The mean serum concentrations of GH and PRL increased more after sleep onset in control women than in patients with FM [GH, 1.3 +/- 0.4 vs. 0.3 +/- 0.2 (P < 0.05); PRL, 16.2 +/- 2.4 vs. 9.7 +/- 1.5 (P < 0.025)]. Sleep efficiency and amounts of sleep or wake stages on the blood draw night were not different between groups. There was a modest inverse relationship between sleep latency and PRL and a direct relationship between sleep efficiency and PRL in FM. There was an inverse relationship between age and GH most evident in control women. Insulin-like growth factor I levels were not different between the groups.

These data demonstrate altered functioning of both the somatotropic and lactotropic axes during sleep in FM and support the hypothesis that dysregulated neuroendocrine systems during sleep may play a role in the pathophysiology of FM.

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Posted to Co-Cure Sat, 7 Apr 2001 19:16:53 -0700 by Melissa O'Toole

Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of CFS patients...

Full Title: Increased sensitivity to glucocorticoids in peripheral blood mononuclear cells of chronic fatigue syndrome patients, without evidence for altered density or affinity of glucocorticoid receptors.

Journal: J Investig Med 2001 Mar;49(2):195-204

Authors: Visser J, Lentjes E, Haspels I, Graffelman W, Blauw B, de Kloet R, Nagelkerken L.

Affiliation: Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.

NLM Citation: PMID: 11288761

BACKGROUND: In this study we tested the hypothesis that the increased sensitivity to glucocorticoids in chronic fatigue syndrome (CFS)-patients can be attributed to an altered functioning of their glucocorticoid receptors (GR).

METHODS: For this purpose, affinity and distribution of the GR were studied in purified, peripheral blood mononuclear cells (PBMC) of 10 CFS patients and 14 controls along with the responsiveness of these cells to glucocorticoids in vitro.

RESULTS: Affinity (Kd) and number of GR was not different in PBMC of CFS patients when compared with the controls (Kd, 12.9 +/- 8.9 nmol vs 18.8 +/- 16.2 nmol and GR number, 4,839 +/- 2,824/ cell vs 4,906 +/- 1,646/cell). Moreover, RT-PCR revealed no differences in GR messenger RNA expression. Nevertheless, PBMC from CFS patients showed an increased sensitivity to glucocorticoids in vitro. In CFS patients 0.01 micromol dexamethasone suppressed PBMC proliferation by 37%, whereas the controls were only suppressed by 17% (P < 0.01). Addition of phorbol 12-myristate 13-acetate to the cultures rendered the cells resistant to dexamethasone with regard to proliferation and IL-10 and IFN-gamma production, but not to IL-2 and TNF-alpha production in both patients and controls. No difference between patients and controls was observed in this respect

CONCLUSIONS: In conclusion, PBMC of CFS patients display an increased sensitivity to glucocorticoids, which cannot be explained by number or affinity of the GR but should rather be attributed to molecular processes beyond the actual binding of the ligand to the GR.

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