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Posted to Co-Cure Fri, 11 May 2001 12:36:54 -0400 by Barbara Evans

FM developed after administration of gonadotrophin-releasing hormone analogue

Full Title: Fibromyalgia developed after administration of gonadotrophin-releasing hormone analogue.

Journal: Clin Rheumatol 2001;20(2):150-2

Authors: Toussirot E, Wendling D.

Affiliation: University Hospital Jean Minjoz, Besancon, France.

NLM Citation: PMID: 11346231

We report the case of a woman treated with a gonadotrophin-releasing hormone analogue for endometriosis who developed typical clinical features of fibromyalgia, with widespread musculoskeletal pain, sleep difficulties, neuropsychological complaints and tender points on clininal examination. The gonadotrophin-releasing hormone analogue treatment probably induced disturbances in the neuroendocrine system and the secretion of neurotransmitters, and may be suspected to be the cause of this case of fibromyalgia.

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Posted to Co-Cure Fri, 11 May 2001 11:41:25 -0400 by Fred Springfield

A Review of the Evidence for Overlap among Unexplained Clinical Conditions

Full Title: A Review of the Evidence for Overlap among Unexplained Clinical Conditions.

Journal: Ann Intern Med 2001 May 1;134(9):868-881

Authors: Aaron LA, Buchwald D.

Affiliation: Department of Medicine, Division of Internal Medicine, Harborview Medical Center, 325 Ninth Avenue, Box 359780, Seattle, WA 98104.

NLM Citation: PMID: 11346323

PURPOSE: Unexplained clinical conditions share features, including symptoms (fatigue, pain), disability out of proportion to physical examination findings, inconsistent demonstration of laboratory abnormalities, and an association with "stress" and psychosocial factors. This literature review examines the nature and extent of the overlap among these unexplained clinical conditions and the limitations of previous research.

DATA SOURCES: English-language articles were identified by a search of the MEDLINE database from 1966 to January 2001 by using individual syndromes and their hallmark symptoms as search terms.

STUDY SELECTION: Studies that assessed patients with at least one unexplained clinical condition and that included information on symptoms, overlap with other unexplained clinical conditions, or physiologic markers. Conditions examined were the chronic fatigue syndrome, fibromyalgia, the irritable bowel syndrome, multiple chemical sensitivity, temporomandibular disorder, tension headache, interstitial cystitis, and the postconcussion syndrome.

DATA EXTRACTION: Information on authorship, patient and control groups, eligibility criteria, case definitions, study methods, and major findings.

DATA SYNTHESIS: Many similarities were apparent in case definition and symptoms, and the proportion of patients with one unexplained clinical condition meeting criteria for a second unexplained condition was striking. Tender points on physical examination and decreased pain threshold and tolerance were the most frequent and consistent objective findings. A major shortcoming of all proposed explanatory models is their inability to account for the occurrence of unexplained clinical conditions in many affected patients.

CONCLUSIONS: Overlap between unexplained clinical conditions is substantial. Most studies are limited by methodologic problems, such as case definition and the selection and recruitment of case-patients and controls.

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Posted to Co-Cure Fri, 11 May 2001 11:42:18 -0400 by Fred Springfield

Chronic Fatigue: Symptom and Syndrome

Full Title: Chronic Fatigue: Symptom and Syndrome.

Journal: Ann Intern Med 2001 May 1;134(9):838-843

Author: Wessely S.

Affiliation: Guy's, King's, and St Thomas's School of Medicine and Institute of Psychiatry, London, United Kingdom.

NLM Citation: PMID: 11346319

Chronic fatigue is common, is difficult to measure, can be associated with considerable morbidity, and is rarely a subject of controversy. The chronic fatigue syndrome also presents problems in definition and measurement, is associated with even more morbidity than chronic fatigue itself, and is often controversial.

Particularly unclear is the way in which chronic fatigue and the chronic fatigue syndrome relate to each other: Is one the severe form of the other, or are they qualitatively and quantitatively different? We know that many things can cause chronic fatigue, and this is probably true for the chronic fatigue syndrome, too.

We can anticipate that discrete causes of the chronic fatigue syndrome will be found in the future, even if these causes are unlikely to fall neatly along the physical-psychological divide that some expect. The causes of chronic fatigue are undoubtedly many, both in a population and in any individual person, even when a discrete cause, such as depression or cancer, is identified.

Social, behavioral, and psychological variables are important in both chronic fatigue and the chronic fatigue syndrome. Interventions that address these general variables can be successful, and currently they are often more successful than interventions directed at specific causes.

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Posted to Co-Cure Tue, 5 Jun 2001 20:42:26 -0700 by Melissa O'Toole

Antioxidant status and lipoprotein peroxidation in CFS

Full Title: Antioxidant status and lipoprotein peroxidation in chronic fatigue syndrome.

Journal: Life Sci 2001 Mar 16;68(17):2037-49

Authors: Manuel y Keenoy B, Moorkens G, Vertommen J, De Leeuw I.

Affiliation: University Hospital, University of Antwerp, Belgium.

NLM Citation: PMID: 11388705

The aetiology and pathogenesis of the Chronic Fatigue Syndrome (CFS) are still largely unresolved.

Accompanying metabolic disorders such as selective n-6 fatty acid depletion suggest that oxidative stress and more specifically lipid peroxidation might play a role in its pathogenesis.

In order to investigate this hypothesis, oxidant-antioxidant status and its impact on lipoprotein peroxidation in vitro was examined in 61 patients with unexplained fatigue lasting more than 1 month.

They were subdivided into 2 groups: group CFS+ (33 subjects) fulfilled the 1988 Center of Disease Control criteria for CFS and group CFS- did not but was similar as regards age, sex distribution and clinical characteristics.

Antioxidant status was similar in the 2 groups except for lower serum transferrin in the CFS + (mean (95 % CI) 2.41 (2.28-2.54) versus 2.73 (2.54-2.92) g/L in the CFS-, p = 0.009) and higher lipoprotein peroxidation in vitro: 6630 (5949-7312) versus 5581 (4852-6310) nmol MDA/mg LDL and VLDL cholesterol x minutes, p = 0.035). CFS intensified the influence of LDL cholesterol (p = 0.012) and of transferrin (p = 0.045) on peroxidation in vitro, suggesting additional pro-oxidant effects.

These results indicate that patients with CFS have increased susceptibility of LDL and VLDL to copper-induced peroxidation and that this is related both to their lower levels of serum transferrin and to other unidentified pro-oxidising effects of CFS.

Full Article

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Posted to Co-Cure Sat, 5 May 2001 12:00:37 -0400 by Fred Springfield

Thirteen-Year Follow-Up of Children and Adolescents With CFS

Full Title: Thirteen-Year Follow-Up of Children and Adolescents With Chronic Fatigue Syndrome

Journal: PEDIATRICS Vol. 107 No. 5 May 2001, pp. 994-998

Authors: David S. Bell MD*, Karen Jordan+, and Mary Robinson*

Affiliations: * Primary Care Pediatrics, Lyndonville, New York; and the +University of Illinois at Chicago, Chicago, Illinois.

Received May 12, 2000; accepted Aug 25, 2000.


Objective. To describe the educational, social, and symptomatic outcome of children and adolescents with chronic fatigue syndrome 13 years after illness onset.

Methods. Between January 1984 and December 1987, 46 children and adolescents developed an illness suggestive of chronic fatigue syndrome. Follow-up questionnaires were obtained from 35 participants an average of 13 years after illness onset. Data were obtained concerning subsequent medical diagnoses, amount of school missed, presence and severity of current symptoms, and subjective assessment of degree of illness resolution.

Results. Of the 35 participants, 24 were female (68.6%) and 11 were male (31.4%). Average age at illness onset was 12.1 years. Eight participants (22.9%) had an acute onset of symptoms, 27 (77.1%) had a gradual onset. No participant received an alternative medical diagnosis that could have explained the symptom complex between illness onset and follow-up. Thirteen participants (37.1%) considered themselves resolved of illness at follow-up; 15 participants (42.9%) considered themselves well but not resolved; 4 (11.4%) considered themselves chronically ill; and 3 (8.6%) considered themselves more ill than during the early years of illness. Correlation with the Medical Outcomes Study Short Form Health Survey was good for current level of symptoms and degree of recovery. Eight participants (22.9%) missed >2 years of school, and 5 of these were still ill at follow-up. Amount of school missed correlated with both illness severity at follow-up and perceived social impact of the illness.

Conclusions. These data demonstrate the presence of an illness consistent with the current definition of chronic fatigue syndrome. Eighty percent of children and adolescents affected had a satisfactory outcome from their fatiguing illness, although the majority of these participants had mild to moderate persisting symptoms. Twenty percent of participants remain ill with significant symptoms and activity limitation 13 years after illness onset. Chronic fatigue syndrome in children and adolescents may result in persistent somatic symptoms and disability in a minority of those affected.

Key words: chronic fatigue syndrome, pediatric chronic fatigue syndrome.

Copyright 2001 by the American Academy of Pediatrics.

Full Text of article in PDF format
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Posted to Co-Cure Tue, 1 May 2001 17:26:09 -0400 by Bernice Melsky

Fibromyalgia syndrome and serotonin

Full Title: Fibromyalgia syndrome and serotonin.

Journal: Clin Exp Rheumatol 2001 Mar-Apr;19(2):205-10

Authors: Alnigenis MN, Barland P.

Affiliation: Division of Rheumatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.

NLM Citation: PMID: 11326487

Although disturbances in the musculoskeletal system, in the neuroendocrine system and in the central nervous system (CNS) have been implicated in the pathophysiology of fibromyalgia syndrome (FMS), the primary mechanisms underlying the etiopathogenesis of FMS remain elusive.

It has been postulated that disturbances in serotonin metabolism and transmission, along with disturbances in several other chemical pain mediators, are present in patients with FMS.

In this article we review published studies on the pathophysiological role of serotonin in FMS. Although studies that indirectly measured the function of serotonin in the CNS in FMS revealed some abnormalities in the metabolism and transmission of serotonin, the role of serotonin in the pathophysiology of syndrome remains inconclusive and warrants more studies.

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Posted to Co-Cure Tue, 1 May 2001 17:13:50 -0400 by Kimberly Hare

Eeg beta 1 oscillation and sucrose sensitization in FM with chemical intolerance

Full Title: Eeg beta 1 oscillation and sucrose sensitization in fibromyalgia with chemical intolerance.

Journal: Int J Neurosci 2001 May;108(1-2):31-42

Authors: Bell IR, Baldwin CM, Stoltz E, Walsh BT, Schwartz GE.

NLM Citation: PMID: 11328700

Patients with fibromyalgia (FM) have diffuse musculoskeletal pain; half report concomitant intolerance for low levels of environmental chemicals (CI). Previous investigators have hypothesized that the chronic pain and chemical intolerance reflect sensitization of different central nervous system limbic and/or mesolimbic reward pathways.

We evaluated electroencephalographic (EEG) beta activity and blood glucose responses of FM patients with and without CI and normals during three repeated sucrose ingestion sessions and during a final, water-only session (testing for conditioning).

The FM with CI exhibited oscillation (reversal in direction of change from session to session) at rest and then sensitization (progressive amplification) of EEG beta 1 over time across the 3 sucrose sessions versus controls. FM with CI showed sensitization of blood glucose over the 3 sucrose sessions, which, like the EEG findings, reverted toward baseline in the final water-only session.

The data suggest that the subset of FM patients with CI have increased susceptibility to oscillation and physiological sensitization without conditioning, perhaps contributing to fluctuations in their chronic course.

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Posted to Co-Cure Tue, 1 May 2001 12:32:26 -0700 by Melissa O'Toole

Relationship of brain MRI abnormalities and physical functional status in CFS

Full Title: Relationship of brain MRI abnormalities and physical functional status in chronic fatigue syndrome.

Journal: Int J Neurosci 2001 Mar;107(1-2):1-6

Authors: Cook DB, Lange G, DeLuca J, Natelson BH.

Affiliation: Department of Neurosciences,; UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.

NLM Citation: PMID: 11328679

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.

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Posted to Co-Cure Tue, 1 May 2001 15:21:29 -0400 by Fred Springfield

Detection of Immunologically Significant Factors for CFS Using Neural-Network Classifiers

Full Title: Detection of Immunologically Significant Factors for Chronic Fatigue Syndrome Using Neural-Network Classifiers.

Journal: Clin Diagn Lab Immunol 2001 May;8(3):658-662

Authors: Hanson SJ, Gause W, Natelson B.

Affiliation: Rutgers University, Newark, New Jersey.

NLM Citation: PMID: 11329477

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.

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Posted to Co-Cure Sat, 28 Apr 2001 19:19:45 -0700 by Melissa O'Toole

EMG activity and pain development in FM patients exposed to mental stress of long duration

Full Title: EMG activity and pain development in fibromyalgia patients exposed to mental stress of long duration.

Journal: Scand J Rheumatol 2001;30(2):92-8

Authors: Bansevicius D, Westgaard RH, Stiles T.

Affiliation: Norwegian University of Science and Technology, Division of Organization and Work Science, Trondheim.

NLM Citation: PMID: 11324796

OBJECTIVE: To examine the distribution of stress-induced upper-body pain in fibromyalgia patients, and the possible association of pain with electromyographic activity in muscles near the sites of pain development.

METHODS: Fifteen fibromyalgia patients and 15 pain-free subjects were exposed to low-level mental strain over a one-hour period. EMG was recorded from frontalis, temporalis, trapezius, and splenius capitis. Pain in the corresponding locations was recorded before the test, every 10 minutes during the test, and the 30-minute posttest period.

RESULTS: The fibromyalgia patients developed pain during the test in all the above body locations. Pain development in all locations associated with trapezius EMG activity, but not with EMG activity in underlying muscles for forehead, temples, and neck.

CONCLUSION: Stress-induced pain in fibromyalgia patients is not generally caused by muscle activity. The trapezius EMG response may be part of a general stress response that cause pain independently of motor activity in muscles.

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Posted to Co-Cure Fri, 27 Apr 2001 11:54:19 -0400 by Barbara Evans

Treating fibromyalgia with a brief interdisciplinary program...

Full Title: Treating fibromyalgia with a brief interdisciplinary program: initial outcomes and predictors of response.

Journal: Mayo Clin Proc 2001 Apr;76(4):384-90

Authors: Worrel LM, Krahn LE, Sletten CD, Pond GR.

Affiliation: Mayo Medical School, Mayo Clinic, Rochester, Minn 55905, USA.

NLM Citation: PMID: 11322354

OBJECTIVES: To evaluate the efficacy of a brief, intense treatment program for fibromyalgia and to determine which patient characteristics are associated with a better treatment response.

PATIENTS AND METHODS: Two self-report measures, the Fibromyalgia Impact Questionnaire (FIQ) and the Multidimensional Pain Inventory (MPI), were administered before patients completed treatment and 1 month after participating in the program. The main outcome measure was the difference in FIQ score and MPI scale before and after program participation.

RESULTS: Of 139 patients who met the American College of Rheumatology criteria for fibromyalgia, 100 chose to participate in the 1 1/2-day Fibromyalgia Treatment Program at the Mayo Clinic, Rochester, Minn. Of these 100 patients, 74 completed the follow-up surveys. Patients were less affected by fibromyalgia after participation in the treatment program. This was demonstrated by a posttreatment improvement in the total FIQ score (P<.001), the MPI pain severity score (P<.001), and the MPI interference score (P=.01). The 1 patient characteristic found to be significantly associated (P<.001) with a better response to treatment was a high pretreatment level of impairment from fibromyalgia, as measured by the pretreatment FIQ score.

CONCLUSIONS: A brief interdisciplinary program for treating fibromyalgia reduced some associated symptoms. Patients more severely affected by fibromyalgia may benefit most from this approach. Clinicians may apply these findings to develop beneficial and convenient treatment programs for patients with fibromyalgia.

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Posted to Co-Cure Fri, 27 Apr 2001 11:34:58 -0400 by Fred Springfield

Azido Photolabeling of 37-kDa RNase L in CFS PBMC

Full Title: Characterization of a 2-5A dependent 37-kDa RNase L. 2. Azido photoaffinity labeling and 2-5A Dependent activation.

Journal: J Biol Chem 2001 Apr 25; [epub ahead of print]

Authors: Shetzline SE, Suhadolnik RJ.

Affiliation: Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140.

NLM Citation: PMID: 11323422

The preceding paper in this issue described the characterization of the molecular structure of the 37-kDa RNase L identified in peripheral blood mononuclear cell (PBMC) extracts from individuals with chronic fatigue syndrome (CFS) [Shetzline, S., et al., (2001) J. Biol. Chem. (preceding paper in this issue)].

In this study, analysis of 2-5A binding and activation of the 80-kDa and the 37-kDa forms of RNase L has been completed utilizing photolabeling/immunoprecipitation and affinity assays, respectively. Saturation of photolabeling of the 80-kDa and the 37-kDa RNase L with the 2-5A azido photoprobe, [32P]pApAp(8-azidoA), was achieved.

Half-maximal photoinsertion of [32P]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 (p3A3) resulted in complete protection against photolabeling, demonstrating that [32P]pApAp(8-azidoA) binds specifically to the 2-5A binding site of the 80-kDa and the 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 [32P]pApAp(8-azidoA) for the detection of the 37-kDa RNase L in PBMC extracts.

[Please note that the accepted manuscript version is available for free in PDF format at]
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