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Posted to Co-Cure Fri, 15 Jun 2001 17:29:51 -0400 by Fred Springfield

Orthostatic Intolerance: A Review with Application to CFS

Full Title: Orthostatic Intolerance: A Review with Application to the Chronic Fatigue Syndrome

Journal: Journal of Chronic Fatigue Syndrome, Vol. 8 (2) 2001, pp. 45-64

Author: Julian M. Stewart, MD, PhD

Affiliation: Department of Pediatrics and Physiology, The Center for Pediatric Hypotension, New York Medical College, Valhalla, NY 10595.

Address correspondence to: Julian M. Stewart, MD, PhD, Professor of Pediatrics, Research Professor of Physiology, The Center for Neurovascular Disease in Children, and the Division of Pediatric Cardiology, Suite 618, Munger Pavilion, New York Medical College, Valhalla, NY 10595 (E-mail:

Supported in part by 1R03-AI45954 from NIH/NIAID

ABSTRACT. The symptoms of the chronic fatigue syndrome closely match those of chronic orthostatic intolerance and research suggests that orthostatic intolerance plays a role in the symptomatology of CFS. Recent investigations support the hypothesis that findings in CFS patients result at least in part from impaired blood pressure and heart rate regulation. Orthostatic intolerance has been implicated.

Effective and specific treatment for chronic orthostatic intolerance can only be developed when a specific etiology or etiologies are discovered.

KEYWORDS. Syncope, head-up tilt test, dysautonomia, postural orthostatic tachycardia syndrome

A chronically ill patient is evaluated by two different physicians. There is a 10 month history of fatigue, neurocognitive and sleep disorders, lightheadedness, tremulousness, nausea, abdominal pain, weakness, new onset headache, anxiety/palpitations present on a day to day basis. She has been extensively evaluated by previous physicians over the course of many months. The patient appears slightly pale but vital signs are normal although the heart rate is higher than average. Symptoms worsen when the patient is upright. A diagnosis of chronic fatigue syndrome is made by one physician, while a diagnosis of chronic orthostatic intolerance is made by the other. Who is right?

Much has been stated and written about orthostatic intolerance (OI) as it applies to the chronic fatigue syndrome (CFS) which has been confusing at best. Some of the confusion originates from recent appreciation of the clinical variants of orthostatic intolerance, some from our emerging understanding that diverse pathophysiologies underlie the OI, and some from nomenclature which seems to change from year-to-year or faster.

In order to address orthostatic intolerance in CFS, we have chosen to adopt a scheme which includes a lot of background material:

1. A definition of Orthostatic Intolerance
2. What's syncope? (Not all syncope is orthostatic intolerance)
3. Physiology of orthostasis
4. A clinical approach using a well-known orthostatic stress test, the tilt table, to define clinical variants of orthostatic intolerance
5. A specific discussion of OI research in CFS
6. Some suggestions concerning screening for OI in CFS patients
7. An approach to treatment.

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

© 2001 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Thu, 14 Jun 2001 21:37:40 -0400 by Kimberly Hare

Classification, epidemiology, and natural history of fibromyalgia

Full Title: Classification, epidemiology, and natural history of fibromyalgia.

Journal: Curr Pain Headache Rep 2001 Aug;5(4):320-9

Authors: White KP, Harth M.

Affiliation: Department of Medicine, University of Western Ontario, K289, 268 Grosvenor Street, P.O. Box 5777, London, Ontario N6A 4V2, Canada.

NLM Citation: PMID: 11403735

Fibromyalgia (FM), also known as fibromyalgia syndrome (FMS) and fibrositis, is a common form of nonarticular rheumatism that is associated with chronic generalized musculoskeletal pain, fatigue, and a long list of other complaints.

Some have criticized the classification of FM as a distinct medical entity, but existing data suggest that individuals meeting the case definition for FM are clinically somewhat distinct from those with chronic widespread pain who do not meet the full the FM definition.

Clinic studies have found FM to be common in countries worldwide; these include studies in specialty and general clinics. The same is true of general population studies, which show the prevalence of FM to be between 0.5% and 5%.

Knowledge about risk factors for FM is limited. Females are at greater risk, and risk appears to increase through middle age, then decline. Although some authors claim that an epidemic of FM has been fueled by an over-generous Western compensation system, there are no data that demonstrate an increasing incidence or prevalence of FM; moreover, existing data refute any association between FM prevalence and compensation.

Claims that the FM label itself causes illness behavior and increased dependence on the medical system also are not supported by existing research.

This article reviews the classification, epidemiology, and natural history of FM.

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Posted to Co-Cure Wed, 13 Jun 2001 21:33:39 -0400 by Fred Springfield

Clinical Features of Fibromyalgia Syndrome in a Bangladeshi Population

Full Title: Clinical Features of Fibromyalgia Syndrome in a Bangladeshi Population

Journal: Journal of Musculoskeletal Pain, Vol. 9(1)2001, pp. 25-33

Authors: Amal K. Choudhury, Muhammad B. Yunus, Syed A. Haq, Mohammad N. Alam, Flora Sebrina, Jean C. Aldag

Affiliations: Amal K. Choudhury, MBBS, FCPS, is affiliated with National Institute of Cardio­vascular Diseases, Dhaka, Bangladesh.
Muhammad B. Yunus, MD, FACP, FACR, FRCPE, and Jean C. Aldag, PhD, are affiliated with the University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
Mohammad N. Alain, MBBS, FRCP, FCPS, and Syed A. Haq, MBBS, MD, FCPS, are affiliated with Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh.
Flora Sebrina, MBBS, MPH, is affiliated with National Institute of Public Health and Social Studies, Mohakhali, Dhaka, Bangladesh.
Address correspondence to: Dr. Syed A. Haq, House-9/1, Road-5, Dhanmondi, Dhaka 1205, Bangladesh [E-mail:].

Submitted: May 26, 2000.
Accepted without revision: August 25, 2000.

Objective: The study was designed to describe various clinical features of fibromyalgia syndrome [FMS] in a Bangladeshi population seen at a university rheumatology clinic.

Methods: Thirty consecutive patients with FMS were compared with the next patient with rheumatoid arthritis [RA] as well as a healthy painfree normal control [NC], of the same sex and similar age. All subjects were evaluated by a physician-administered questionnaire.

Results: Virtually all clinical and psychological features were more common in FMS than NCs as well as RA. The frequency of clinical and psychological features of FMS, e.g., fatigue, sleep difficulties, swollen feeling, paresthesia, irritable bowel syndrome, tension-type headaches as well as global anxiety, stress, and depression were similar to those reported in Europe and North America.

Conclusion: Characteristics.of FMS in a Bangladeshi population are similar to those described in the West.

KEYWORDS. Fibromyalgia, epidemiology, rheumatoid arthritis, clini­cal features

Fibromyalgia syndrome [FMS] is now a well described condition that has been reported from various parts of the world (1-5), including Japan (4) and Turkey (5). Most of the published descriptions, howev­er, are based on studies of Western populations. Recognizing that manifestations of a disease or an illness may be influenced by ethnic and cultural differences, it will be useful to study FMS in various nationalities or geographic locations. The frequency or prevalence of clinical manifestations of FMS in a Bengali population is unknown. We, therefore, undertook a study to determine if the frequency and characteristics of FMS in an academic rheumatology clinic in Bangla­desh are generally similar to, or different from, those described in Western populations. In the present study, we describe the clinical and psychological features of FMS as compared with two control groups, i.e., rheumatoid arthritis [RA] and healthy, painfree normal controls [NCs].

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

© 2001 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Sun, 10 Jun 2001 16:01:10 -0400 by Kimberly Hare

Prevalence of fibromyalgia, anxiety and depression in chronic hepatitis C virus infection...

Full Title: Prevalence of fibromyalgia, anxiety and depression in chronic hepatitis C virus infection: relationship to RT-PCR status and mode of acquisition.

Journal: Eur J Gastroenterol Hepatol 2001 May;13(5):507-11

Authors: Goulding C, O'Connell P, Murray FE.

Affiliation: Department of Gastroenterology and Rheumatology, Beaumont Hospital, Dublin, Ireland.

NLM Citation: PMID: 11396529

BACKGROUND: Musculoskeletal complaints, dry eyes, fatigue and anxiety are common symptoms in patients with hepatitis C virus (HCV) infection, but there are few controlled data evaluating this.

AIM: To assess the prevalence of rheumatological disease, fatigue and anxiety in different groups of patients with chronic HCV infection.

PATIENTS AND METHODS: Seventy-seven patients with HCV were evaluated. Of these, 49 (64%) had been infected via contaminated anti-D immunoglobulin, 25 (33%) were intravenous drug users (IVDUs), and three were transfusion related; 78% were female. Twenty-five age- and sex-matched controls were also evaluated. Assessment was performed by history, physical examination, the Fibromyalgia Impact Questionnaire (FIQ) and the Hospital Anxiety and Depression Score (HADS).

RESULTS: Four (5%) patients fulfilled the criteria for fibromyalgia. All were infected via anti-D immunoglobulin, and three were PCR positive. The mean number of tender points in anti-D patients was 5.0 (+/- 4.07) compared with 2.8 (+/- 2.7) in controls (P= 0.028) and 2.5 (+/- 2.2) in IVDUs (P< 0.004). There was no significant difference in the number of tender points between PCR-positive and PCR-negative patients (P= 0.23). Anxiety and depression scores were significantly higher in anti-D patients (P= 0.0001) and IVDUs (P= 0.005) compared with controls. Forty per cent of the HCV patients had a positive Schirmer test. Forty-two per cent of PCR-positive patients had a positive rheumatoid factor (RF, > 1/80).

CONCLUSION: This study reveals a moderate increase in prevalence of fibromyalgia in HCV patients. The number of tender points was related to mode of acquisition but not to PCR status. Anxiety and depression levels are also increased in HCV patients compared with controls. Prevalence of RF was higher in PCR-positive patients compared with controls and those who had cleared the virus.

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Posted to Co-Cure Sun, 10 Jun 2001 11:56:19 -0500 by Barbara Evans

Cardiovascular response to upright tilt in fibromyalgia differs from that in chronic fatigue syndrome

Full Title: Cardiovascular response to upright tilt in fibromyalgia differs from that in chronic fatigue syndrome.

Journal: J Rheumatol 2001 Jun;28(6):1356-60

Authors: Naschitz JE, Rozenbaum M, Rosner I, Sabo E, Priselac RM, Shaviv N, Ahdoot A, Ahdoot M, Gaitini L, Eldar S, Yeshurun D.

Affiliations: Departments of Internal Medicine A, Rheumatology, Anesthesiology, and Surgery, Bnai Zion Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

NLM Citations: PMID: 11409131

OBJECTIVE: To compare the cardiovascular response during postural challenge of patients with fibromyalgia (FM) to those with chronic fatigue syndrome (CFS).

METHODS: Age and sex matched patients were studied, 38 with FM, 30 with CFS, and 37 healthy subjects. Blood pressure (BP) and heart rate (HR) were recorded during 10 min of recumbence and 30 min of head-up tilt. Differences between successive BP values and the last recumbent BP, their average, and standard deviation (SD) were calculated. Time curves of BP differences were analyzed by computer and their outline ratios (OR) and fractal dimensions (FD) were measured. HR differences were determined similarly. Based on the latter measurements, each subject's discriminant score (DS) was computed.

RESULTS: For patients and controls average DS values were: FM: -3.68 (SD 2.7), CFS: 3.72 (SD 5.02), and healthy controls: -4.62 (SD 2.24). DS values differed significantly between FM and CFS (p < 0.0001). Subgroups of FM patients with and without fatigue had comparable DS values.

CONCLUSION: The DS confers numerical expression to the cardiovascular response during postural challenge. DS values in FM were significantly different from DS in CFS, suggesting that homeostatic responses in FM and CFS are dissimilar. This observation challenges the hypothesis that FM and CFS share a common derangement of the stress-response system.

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Posted to Co-Cure Thu, 5 Jul 2001 16:09:00 -0400 by Fred Springfield

Delayed-type hypersensitivity and CFS: the usefulness of assessing T-cell activation by flow cytometry

Full Title: Delayed-type hypersensitivity and chronic fatigue syndrome: the usefulness of assessing T-cell activation by flow cytometry--preliminary study.

Journal: Allerg Immunol (Paris) 2001 Apr;33(4):166-72

Authors: Brunet JL, Liaudet AP, Later R, Peyramond D, Cozon GJ.

Affiliation: Infectious Diseases Department-Hopital de la Croix-Rousse-69317 Lyon, France.

NLM Citation: PMID: 11434196

Chronic fatigue syndrome or benign myalgic encephalomyelitis has been extensively described and investigated. Although numerous immunological abnormalities have been linked with the syndrome, none have been found to be specific. This article describes the detection of delayed-type hypersensitive responses to certain common environmental antigens in almost fifty per cent of patients with this syndrome.

Such hypersensitivity can be detected by the intradermal administration of antigens derived from commensal organisms like the yeast Candida albicans albicans, and then monitoring for a systemic reaction over the following six to forty-eight hours. This approach can be consolidated by performing lymphocyte activation tests in parallel and measuring in vitro T-cell activation by Candida albicans albicans antigens by three-colour flow cytometry based on CD3, CD4 and either CD69 or CD25.

Another useful parameter is the kinetics of neopterin excretion in the urine over the course of the skin test. The results showed that the intensity of the DTH response correlated with the number of T-cells activated in vitro. Various factors have been implicated in the fatigue of many patients, notably lack of sleep. However, it remains difficult to establish causality in either one direction or the other.

This work is in the spirit of a multifactorial approach to the group of conditions referred to as "chronic fatigue syndrome".

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Posted to Co-Cure Sat, 9 Jun 2001 11:35:54 -0400 by Fred Springfield

Bone Mass in the Calcaneus in Patients with Fibromyalgia

Full Title: Bone Mass in the Calcaneus in Patients with Fibromyalgia

Journal: Journal of Musculoskeletal Pain, Vol.9(1) 2001, pp. 17-23

Authors: Bo Zerahn, Henning Bliddal, Per Møller, Arne Borgwardt, Bente Danneskiold-Samsøe

Affiliations: Bo Zerahn, MD, Henning Bliddal, Dr med Sc, Per MøIler, Medical Student, and Bente Danneskiold-Samsøe, Dr med Sc. are affiliated with The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Frederiksberg.
Bo Zerahn, MD, is also affiliated with the Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Herlev.
Arne Borgwardt, MD, is affiliated with the Department of Orthopaedic Surgery, Copenhagen University Hospital, Frederiksberg.
Address correspondence to: Bo Zerahn, The Parker Institute, Department of Rheumatology, Copenhagen University Hospital, Frederiksberg, DK-2000, Frederiksberg, Denmark [E-mail: ].

Submitted: April 10.2000.
Revision accepted: July 17, 2000.

Objectives: To determine hone mineral density [BMD] of the calcaneus in premenopausal women with fibromyalgia [FMS] as compared to age matched controls.

Methods: We measured BMD of the calcaneus in 116 premenopau­sal women with FMS and made comparisons with 141 age matched controls. Additionally, muscle strength of the thigh was measured in patients with FMS.

Results: Patients with FMS and controls were comparable regarding BMD and age, but the controls were slightly taller and had a lower body mass than the patients with FMS. Calcaneus BMD per kg body mass was lower in patients with FMS compared to controls [P < 0.004]. There was no demonstrable correlation between muscle strength of the thigh and BMD of the calcaneus.

Conclusions: Patients with FMS maintain normal levels of bone mass in the calcaneus despite a self-reported low level of physical activity. The patients with FMS were obese compared to the controls. This obesity increases the loading on the calcaneus and may preserve bone mass.

KEYWORDS. Fibromyalgia, bone mineral density, calcaneus, body weight


Fibromyalgia [FMS] is a common rheumatic syndrome mainly characterized by muscular pain (1), causing a relatively low level of physi­cal activity. Its prevalence is reported to be from 0.66 to 2% (2,3) and the majority of patients are women. Because of the reduction in physi­cal activity in these patients it has been feared that they would have a lower bone mass and thus an increased fracture risk. Both Appelboom (4) and Jacobsen et al. (5) have found an increased bone turnover in patients with FMS. But they have not demonstrated any signs of low bone mass in these patients. Both studies, however, were of limited size and focused on bone mineral density of the lumbar spine and femoral neck.

Our objective was to determine bone mineral density [BMD] of the calcaneus in FMS patients as compared to a group of healthy preme­nopausal women. We also studied the relation between bone mass of the calcaneus with muscle strength, various diagnostic criteria, and symptom duration. We have studied bone mass of the calcaneus, be­cause it is closely related to the loading of the legs as well as physical activity (6,7).


[Note: calcaneus (pl. calcanei) The heel bone, or os calcis. It articulates with the cuboid bone and with the talus.

"Taber's Cyclopedic Medical Dictionary," Copyright © 1999 by F. A. Davis Co., Phil., PA]


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

© 2001 by The Haworth Press, Inc. All rights reserved.

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Posted to Co-Cure Fri, 8 Jun 2001 16:34:13 -0400 by Fred Springfield

Cobalamin Used in CFS Therapy Is a Nitric Oxide Scavenger

Full Title: Cobalamin Used in Chronic Fatigue Syndrome Therapy Is a Nitric Oxide Scavenger

Journal: Journal of Chronic Fatigue Syndrome, Vol.8 (2) 2001, pp. 39-44

Author: Martin L. Pall, PhD

Affiliation: School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4660 USA (E-mail:

ABSTRACT. Cobalamin (vitamin B12) in the form of hydroxocobalamin or cyanocobalamin injections has been widely used to treat chronic fa­tigue syndrome (CFS). Hydroxocobalamin is a nitric oxide scavenger and is proposed here to act as such a scavenger in CFS treatment. Its pos­sible efficacy in CFS treatment, if further substantiated, may provide confirmation of a prediction of the elevated nitric oxide/peroxynitrite theory of CFS etiology. This interpretation of the possible role of cobalamin in CFS treatment suggests a useful perspective for confirming and optimizing this treatment.

KEYWORDS. Vitamin B12, reactive nitrogen species, peroxynitrite, therapeutic agents, vicious cycle mechanism, antioxidant, oxidative stress


Cobalamin (vitamin B12) injections in the form of hydroxocobalamin or cyanocobalamin have been used to treat chronic fatigue syndrome (CFS) in the United States, Canada and several European countries. While an early review of this practice questioned the efficacy of this treatment (I), more recent reports have suggested that extensive clinical experience provides support for the usefulness of such injections in CFS treatment (2-5). No placebo-controlled clinical trials have been performed with hydroxocobalamin or cyanocobalamin injections in CFS to follow up on the clinical observations. The mechanism of action of cobalamin in CFS treatment, if any, is not known, although it has been suggested that it may act to remove a vitamin B12 deficiency (2). The current paper is focused on an alternative interpretation, suggest­ing that cobalamin may be acting in CFS treatment primarily as a nitric oxide scavenger.

Elevated nitric oxide and its potent oxidant product, peroxynitrite, has been suggested to be central to the etiology of CFS (6,7) and nitric oxide, peroxynitrite and related mechanisms have been proposed to generate the symptoms of CFS (7). The most direct evidence supporting the view that nitric oxide levels are elevated in CFS is that levels of neopterin, a marker of the induction of the inducible nitric oxide synthase (8-10), are elevated (11-15) in CFS. In addition, the levels of several inflammatory cytokines known to induce the inducible nitric oxide synthase (TNF-alpha, IL-I, IL-6, IFN-y) are also reported to show el­evation in CFS (12,14,17-24). This proposed mechanism of CFS etiol­ogy predicts that scavengers of nitric oxide may be useful in CFS treatment. It may be of interest, therefore, that hydroxocobalamin has been found to be a nitric oxide scavenger, both in vitro and in vivo.

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

© 2001 by The Haworth Press, Inc. All rights reserved.

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