Isr Med Assoc Oct

Document Sample
Isr Med Assoc Oct Powered By Docstoc
					ME Research UK — Database of Research Publications 2000

 Authors                     Author Address                Title                          Publication                  Abstract
 Aaron LA, Buchwald D.       Seattle, Wash.                Tobacco use and chronic        Arch Intern Med 2000 Aug
                                                           fatigue syndrome,              14;160(15):2398-401
                                                           fibromyalgia, and
                                                           temporomandibular disorder
 Aaron LA, Burke MM,         Department of Medicine,       Overlapping conditions         Arch Intern Med 2000 Jan     BACKGROUND: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), and
 Buchwald D.                 University of Washington,     among patients with chronic    24;160(2):221-7Comment in:   temporomandibular disorder (TMD) share many clinical illness features such as myalgia, fatigue, sleep
                             Seattle, USA.                 fatigue syndrome,              Arch Intern Med. 2000 Aug    disturbances, and impairment in ability to perform activities of daily living as a consequence of these
                          fibromyalgia, and              14-28;160(15):2398, 2401     symptoms. A growing literature suggests that a variety of comorbid illnesses also may commonly coexist in
                                                           temporomandibular disorder.                                 these patients, including irritable bowel syndrome, chronic tension-type headache, and interstitial cystitis.
                                                                                                                       OBJECTIVE: To describe the frequency of 10 clinical conditions among patients with CFS, FM, and TMD
                                                                                                                       compared with healthy controls with respect to past diagnoses, degree to which they manifested symptoms
                                                                                                                       for each condition as determined by expert-based criteria, and published diagnostic criteria. METHODS:
                                                                                                                       Patients diagnosed as having CFS, FM, and TMD by their physicians were recruited from hospital-based
                                                                                                                       clinics. Healthy control subjects from a dermatology clinic were enrolled as a comparison group. All
                                                                                                                       subjects completed a 138-item symptom checklist and underwent a brief physical examination performed
                                                                                                                       by the project physicians. RESULTS: With little exception, patients reported few past diagnoses of the 10
                                                                                                                       clinical conditions beyond their referring diagnosis of CFS, FM, or TMD. In contrast, patients were more
                                                                                                                       likely than controls to meet lifetime symptom and diagnostic criteria for many of the conditions, including
                                                                                                                       CFS, FM, irritable bowel syndrome, multiple chemical sensitivities, and headache. Lifetime rates of
                                                                                                                       irritable bowel syndrome were particularly striking in the patient groups (CFS, 92%; FM, 77%; TMD,
                                                                                                                       64%) compared with controls (18%) (P<.001). Individual symptom analysis revealed that patients with
                                                                                                                       CFS, FM, and TMD share common symptoms, including generalized pain sensitivity, sleep and
                                                                                                                       concentration difficulties, bowel complaints, and headache. However, several symptoms also distinguished
                                                                                                                       the patient groups. CONCLUSIONS: This study provides preliminary evidence that patients with CFS, FM,
                                                                                                                       and TMD share key symptoms. It also is apparent that other localized and systemic conditions may
                                                                                                                       frequently co-occur with CFS, FM, and TMD. Future research that seeks to identify the temporal
                                                                                                                       relationships and other pathophysiologic mechanism(s) linking CFS, FM, and TMD will likely advance our
                                                                                                                       understanding and treatment of these chronic, recurrent conditions.
 Ablashi DV, Eastman HB,     Department of Microbiology,   Frequent HHV-6 reactivation    J Clin Virol 2000            BACKGROUND: HHV-6 is a ubiquitous virus and its infection usually occurs in childhood and then
 Owen CB, Roman MM,          Georgetown University,        in multiple sclerosis (MS)     May;16(3):179-91             becomes a latent infection. HHV-6 reactivation has been shown to play a role in the pathogenesis of AIDS
 Friedman J, Zabriskie JB,   School of Medicine,           and chronic fatigue syndrome                                and several other diseases. OBJECTIVES: To determine what role HHV-6 infection or reactivation plays in
 Peterson DL, Pearson GR,    Washington, DC, USA.          (CFS) patients.                                             the pathogenesis of multiple sclerosis (MS) and chronic fatigue syndrome (CFS). RESULTS: Twenty-one
 Whitman JE.                                                                           MS and 35 CFS patients were studied and followed clinically. In these patients, we measured HHV-6 IgG
                                                                                                                       and IgM antibody levels and also analyzed their peripheral blood mononuclear cells (PBMCs) for the
                                                                                                                       presence of HHV-6, using a short term culture assay. In both MS and CFS patients, we found higher levels
                                                                                                                       of HHV-6 IgM antibody and elevated levels of IgG antibody when compared to healthy controls. Seventy
                                                                                                                       percent of the MS patients studied contained IgM antibodies for HHV-6 late antigens (capsid), while only
                                                                                                                       15% of the healthy donors (HD) and 20% of the patients with other neurological disorders (OND) had
                                                                                                                       HHV-6 IgM antibodies. Higher frequency of IgM antibody was also detected in CFS patients (57.1%)
                                                                                                                       compared to HD (16%). Moreover, 54% of CFS patients exhibited antibody to HHV-6 early protein
                                                                                                                       (p41/38) compared to only 8.0% of the HD. Elevated IgG antibody titers were detected in both the MS and
                                                                                                                       the CFS patients. PBMCs from MS, CFS and HD were analyzed in a short term culture assay in order to
                                                                                                                       detect HHV-6 antigen expressing cells and to characterize the viral isolates obtained as either Variant A or
                                                                                                                       B. Fifty-four percent of MS patients contained HHV-6 early and late antigen producing cells and 87% of
                                                                                                                       HHV-6 isolates were Variant B. Isolates from CFS, patients were predominately Variant A (70%) and
                                                                                                                       isolates from HD were predominately Variant B (67%). Moreover, one isolate from OND was also Variant
                                                                                                                       B. Persistent HHV-6 infection was found in two CFS patients over a period of 2.5 years and HHV-6
                                                                                                                       specific cellular immune responses were detected in PBMCs from ten CFS patients. CONCLUSION: In
                                                                                                                       both MS and CFS patients, we found increased levels of HHV-6 antibody and HHV-6 DNA. A decrease in
                                                                                                                       cellular immune responses was also detected in CFS patients. These data suggest that HHV-6 reactivation
ME Research UK — Database of Research Publications 2000

                                                                                                                       plays a role in the pathogenesis of these disorders.
 Addington JW.                                            Chronic Fatigue Syndrome:       Journal of Chronic Fatigue   Chronic fatigue syndrome is a severe, often disabling disorder with prevalence as high as 422 cases per
                                                          A Dysfunction of the            Syndrome 2000; 7(2): 63      100,000 in the United States. Aside from the adverse effects to patients' quality of life, sequela of the
                                                          Hypothalamic-Pituitary-                                      disorder include a negative impact on the economy as well as a burden on public health care costs. Some
                                                          Adrenal Axis                                                 avenues of current research into the possible genesis of the syndrome are neurally mediated hypotension,
                                                                                                                       viral pathogen, immunological disorders, lymphocyte enzyme system abnormalities, or a purely
                                                                                                                       psychological root. This paper is a review of the literatures as to a neuroendocrinologic cause, namely
                                                                                                                       dysfunction of the hypothalamic-pituitary-adrenal axis.
 Afari N, Eisenberg DM,     Department of Medicine,       Use of alternative treatments   1096-2190 2000 Mar           Background: Patients with chronic fatigue syndrome (CFS) have been faced with difficulties in diagnosis
 Herrell R, Goldberg J,     University of Washington,     by chronic fatigue syndrome     21;2(2):97-103               and lack of effective treatments. Anecdotal evidence suggests that use of alternative treatments may be
 Kleyman E, Ashton S,       Seattle, WA, USA              discordant twins.                                            common in these patients. Our primary objective was to compare the prevalence and patterns of alternative
 Buchwald D.                                                                                                           medicine use among twins who met the Centers for Disease Control and Prevention (CDC) CFS criteria to
                                                                                                                       that of their non-CFS co-twins. Secondary goals were to assess how often alternative medicine use was
                                                                                                                       discussed with physicians and the perceived benefit of these therapies. Methods: Sixty-three twin pairs
                                                                                                                       discordant for CFS completed a survey about their use of 22 alternative therapies. Matched pair odds ratios
                                                                                                                       and 95% confidence intervals were used to examine differences in the use between CFS twins and their
                                                                                                                       non-CFS co-twins. Results: 91% of twins with CFS and 71% of non-CFS twins had used at least 1
                                                                                                                       alternative treatment in their lifetime. Twins with CFS were more likely to use homeopathy, mega-vitamins,
                                                                                                                       herbal therapies, biofeedback, relaxation/meditation, guided imagery, massage therapy, energy healing,
                                                                                                                       religious healing by others, and self-help groups than their non-CFS counterparts. A large proportion of all
                                                                                                                       twins found alternative therapies helpful; however, only 42% of those with CFS and 23% of those without
                                                                                                                       CFS discussed their use of alternative medicine with a physician. Conclusions: Individuals with CFS
                                                                                                                       frequently used alternative medical treatments yet rarely communicated this use to their medical doctor.
                                                                                                                       Future research should ascertain the usefulness of alternative practices in the management of CFS.
 Afari N, Schmaling KB,     Department of Medicine,       Coping strategies in twins      J Psychosom Res 2000         OBJECTIVES: Individuals with chronic fatigue and chronic fatigue syndrome (CFS) face debilitating
 Herrell R, Hartman S,      University of Washington,     with chronic fatigue and        Jun;48(6):547-54             symptoms as well as stressful life situations that may result from their condition. The goal of this study was
 Goldberg J, Buchwald DS.   Seattle, WA 98104, USA.       chronic fatigue syndrome.                                    to examine the coping strategies used by fatigue-discordant twin pairs. METHODS: We utilized a co-twin
                                                                                       design to assess how twin pairs discordant for chronic fatigue and CFS cope with stress. All twin pairs were
                                                                                                                       administered the Revised Ways of Coping Checklist. RESULTS: Overall, the pattern of coping strategies
                                                                                                                       was similar for fatigued and non-fatigued twins. However, twins with chronic fatigue or CFS utilized more
                                                                                                                       avoidance strategies than their non-fatigued counterparts; those with chronic fatigue also used more
                                                                                                                       avoidance relative to problem-focused coping than their co-twins. CONCLUSIONS: These results suggest
                                                                                                                       that while fatigue-discordant twins generally exhibit similar behavior patterns in order to cope with stress,
                                                                                                                       there may be an association between fatigue and avoidance coping. Future research should focus on the
                                                                                                                       role of avoidance and its relationship to fatiguing illnesses.
 Albrecht F.                                              Chronic fatigue syndrome.       J Am Acad Child Adolesc
                                                                                          Psychiatry 2000
                                                                                          Jul;39(7):808-9 Comment
                                                                                          on: J Am Acad Child
                                                                                          Adolesc Psychiatry. 1999
 Apel-Paz M, Lior B,                                      [Chronic fatigue syndrome--     Harefuah 2000 Aug;139(3-
 Shemesh-Kigli R.                                         the disease and approaches to   4):141-9
                                                          treatment].[article in
 Asa PB, Cao Y, Garry RF.   Department of Microbiology,   Antibodies to squalene in       Exp Mol Pathol 2000          Gulf War Syndrome (GWS) is a multisystemic illness afflicting many Gulf War-era veterans. The
                            Tulane Medical School, 1430   Gulf War syndrome.              Feb;68(1):55-64              molecular pathological basis for GWS has not been established. We sought to determine whether the
                            Tulane Avenue, New                                                                         presence of antibodies to squalene correlates with the presence of signs and symptoms of GWS.
                            Orleans, Louisiana, 70112,                                                                 Participants in this blinded cohort study were individuals immunized for service in Desert Shield/Desert
                            USA.                                                                          Storm during 1990-1991. They included 144 Gulf War-era veterans or military employees (58 in the
                                                                                                                       blinded study), 48 blood donors, 40 systemic lupus erythematosus patients, 34 silicone breast implant
ME Research UK — Database of Research Publications 2000

                                                                                                                         recipients, and 30 chronic fatigue syndrome patients. Serum antibodies to squalene were measured. In our
                                                                                                                         small cohort, the substantial majority (95%) of overtly ill deployed GWS patients had antibodies to
                                                                                                                         squalene. All (100%) GWS patients immunized for service in Desert Shield/Desert Storm who did not
                                                                                                                         deploy, but had the same signs and symptoms as those who did deploy, had antibodies to squalene. In
                                                                                                                         contrast, none (0%) of the deployed Persian Gulf veterans not showing signs and symptoms of GWS have
                                                                                                                         antibodies to squalene. Neither patients with idiopathic autoimmune disease nor healthy controls had
                                                                                                                         detectable serum antibodies to squalene. The majority of symptomatic GWS patients had serum antibodies
                                                                                                                         to squalene. Copyright 2000 Academic Press.
 Ax S.                                                     Coping Differences Between       Journal of Chronic Fatigue   The main objective of the present study is to describe the extent to which CFS sufferers and their carers
                                                           Chronic Fatigue Syndrome         Syndrome 2000; 5(2): 27      reported to have used a number of coping strategies over the course of the illness, and to find out if reports
                                                           Sufferers and Their Carers                                    of coping differ between groups of these. In addition, associations between married sufferers and carers
                                                                                                                         were investigated. From a methodological point of view, the factorial structure and the usefulness of the
                                                                                                                         Ways of Coping Questionnaire (Folkman & Lazarus, 1988) in CFS was studied. The results indicate no
                                                                                                                         gender differences. There are also no differences between sufferers supported and not supported by a carer.
                                                                                                                         However, the results indicate reduced coping responses of carer husbands. From a methodological point of
                                                                                                                         view, the emergence of comparable factors for sufferers and carers, which were also closely related to the
                                                                                                                         original emotion and problem-focused factors, suggested that the use of the questionnaire was appropriate.
                                                                                                                         The importance of these findings for coping research and therapy are discussed.
 Axe E, Satz P.              Departments of                Psychiatric correlates in        Ann Epidemiol 2000 Oct       PURPOSE: This study presents psychiatric correlates in Chronic Fatigue Syndrome (CFS) that emerged
                             Epidemiology and              chronic fatigue syndrome.        1;10(7):458                  from the CDC's Surveillance Study. It seeks to determine the time of onset and rates of syndromal
                             Neuropsychology, University                                                                 psychiatric disorders and identify the predominant disorder. Other goals are to ascertain whether depression
                             of California-Los Angeles,                                                                  is associated with CFS symptomatology, compare syndromal to self- reported depression, and test for the
                             Los Angeles, CA, USA                                                                        specificity of the 1988 CDC case definition for CFS.METHODS: All 565 enrolled subjects had fatiguing
                                                                                                                         illnesses and were evaluated for CFS. They completed the Diagnostic Interview Schedule for the DSM-III-R
                                                                                                                         and the Beck Depression Inventory. Prevalence estimates for current syndromal psychiatric disorders were
                                                                                                                         calculated. CFS symptoms were compared by depression status. Syndromal and self-reported depression
                                                                                                                         were contrasted. Groups that did and did not meet the case definition were compared by three outcome
                                                                                                                         variables.RESULTS: Rates of current psychiatric disorders were high in CDC subjects compared to the
                                                                                                                         community. The predominant disorder was depression. Although prior disorders tended to persist (75%),
                                                                                                                         many disorders were incident to the fatiguing illness (57%). Depression was not associated with increased
                                                                                                                         CFS symptomatology. There was only weak agreement between measures of syndromal and self-reported
                                                                                                                         depression (kappa = 0.3219). Subjects designated as CFS had similar rates of syndromal psychiatric
                                                                                                                         disorders, syndromal depression, and self-reported depression as did non-CFS subjects.CONCLUSIONS:
                                                                                                                         Current syndrome; psychiatric disorders appear associated with fatiguing illnesses. While prior psychiatric
                                                                                                                         disorders are risk factors for current, the onset was largely concurrent with the fatiguing illnesses. The BDI
                                                                                                                         should probably not be used as a measure for psychiatric morbidity in CFS subjects. Regardless of
                                                                                                                         outcome, there was no evidence of specificity of psychiatric features to the CDC case definition.
 Azpiroz F, Dapoigny M,      Digestive System Research     Nongastrointestinal disorders    Digestion 2000;62(1):66-72   A large proportion of irritable bowel syndrome (IBS) patients also complain of other functional disorders,
 Pace F, Muller-Lissner S,   Unit, Hospital General Vall   in the irritable bowel                                        such as headache, noncardiac chest pain, low back pain, and dysuria. Some of these features, particularly
 Coremans G, Whorwell P,     d'Hebron, Barcelona, Spain.   syndrome.                                                     headache, may have a negative influence on the outcome of IBS. In a large proportion of female IBS
 Stockbrugger RW, Smout                                                                                                  patients, sexual intercourse triggers the symptoms, and frequently IBS symptoms exacerbate during
 A.                                                                                                                      menses. These gynecological-type symptoms often mislead the patients to the gynecological clinic, which
                                                                                                                         may imply unnecessary investigations and inappropriate treatments. The diagnostic criteria of the
                                                                                                                         fibromyalgia syndrome include IBS, and hence, the apparent relationship of both syndromes is difficult to
                                                                                                                         analyze. On the other hand, no convincing evidence has been produced to date to sustain an association
                                                                                                                         between IBS and the chronic fatigue syndrome. Copyright 2000 S. Karger AG, Basel
 Baraniuk JN, Naranch K,                                   Irritant Rhinitis in Allergic,   Journal of Chronic Fatigue   Background: Irritation symptoms after exposure to ``nonspecific'' stimuli are often attributed to nonallergic
 Maibach H, Clauw DJ.                                      Nonallergic, Control and         Syndrome 2000; 7(2): 3       rhinitis (vasomotor rhinitis). This is a heterogeneous syndrome of exclusion based on nasal symptoms with
                                                           Chronic Fatigue Syndrome                                      negative allergy skin tests. Method: Control (n = 114) and Chronic Fatigue Syndrome (CFS, n = 120)
                                                           Populations                                                   subjects scored the severity of nasal congestion and rhinorrhea sensations that they attributed to 9 irritants.
                                                                                                                         The sum was the ``Irritant Rhinitis Score'' (IRS, maximum 72). A positive IRS of w 19 defined ``Irritant
ME Research UK — Database of Research Publications 2000

                                                                                                           Rhinitis.'' Demographic, allergy skin test and other assessments were done to characterize the Irritant
                                                                                                           Rhinitis population. Results: Irritant Rhinitis was present in 11% of Control and 47% of CFS subjects. In
                                                                                                           multivariate analysis, positive IRS was correlated with a history of rhinitis complaints, systemic complaints
                                                                                                           such as fatigue, sensations of congestion and rhinorrhea induced by meteorological conditions, tobacco
                                                                                                           smoke, odors, perfumes, and other volatile materials, and diagnoses of CFS and Multiple Chemical
                                                                                                           Sensitivity (MCS). Although atopy was not correlated to Irritant Rhinitis, 51% of allergic rhinitis subjects
                                                                                                           had a positive IRS. Conclusions: The Irritant Rhinitis Score defined a population with irritant-induced
                                                                                                           nasal congestion and rhinorrhea who also had significant systemic complaints. Similar neural mechanisms
                                                                                                           may underlie the spectrum of Irritant Rhinitis, CFS and MCS.
 Baraniuk JN, Naranch K,                        Tobacco Sensitivity in        Journal of Chronic Fatigue   Background: Mechanisms responsible for sensitivity to irritants such as tobacco smoke are poorly
 Maibach H, Clauw DJ.                           Chronic Fatigue Syndrome      Syndrome 2000; 7(2): 33      understood. A Tobacco Score questionnaire was developed to identify and characterize subjects with this
                                                (CFS)                                                      sensitivity. For this pilot study, scores were assessed in populations of self-selected controls and a group
                                                                                                           with irritant sensitivity (Chronic Fatigue Syndrome, CFS). Method: Subjects graded the severity of 21
                                                                                                           symptoms associated with tobacco exposure. Results were compared with other instruments and a measure
                                                                                                           of pain sensitivity (dolorimetry) in 116 control and 103 CFS subjects. Results: The Tobacco Score was
                                                                                                           positive in 16% of control and 51% of CFS subjects. Significant correlations were found between Tobacco
                                                                                                           Score, Irritant Rhinitis Score, and history of sinusitis. Intermediate relationships were found with history of
                                                                                                           allergic rhinitis, Systemic Complaints Score, and Multiple Chemical Sensitivity. Factors having no
                                                                                                           influence included gender, the severity of CFS symptoms, pain thresholds, and allergy skin tests.
                                                                                                           Conclusions: Tobacco sensitivity was correlated with measures of upper airway irritation and nonallergic
                                                                                                           sensitivity to triggers such as weather changes. The spectrum of symptoms, high prevalence in CFS, and
                                                                                                           absence of a relationship to atopy suggest that these nonallergic irritant syndromes may share a common
 Baschetti R.                                   The 1microg Synacthen test    Clin Endocrinol (Oxf) 2000
                                                in chronic fatigue syndrome   Jun;52(6):797-9 Comment
                                                                              on: Clin Endocrinol (Oxf).
                                                                              1998 Jun;48(6):733-7 Clin
                                                                              Endocrinol (Oxf). 1999
 Baschetti R.                                   Chronic fatigue syndrome: a   J Intern Med 2000
                                                form of Addison's disease.    Jun;247(6):737-9
 Behan WMH, Holt IJ, Kay                        In vitro Study of Muscle      Journal of Chronic Fatigue   The purpose of this study was to establish if muscle aerobic metabolism is abnormal in chronic fatigue
 DH, Moonie P.                                  Aerobic Metabolism in         Syndrome 2000; 5(1): 3       syndrome (CFS). Myoblast cultures from muscle biopsies of 16 patients with CFS and 10 healthy controls
                                                Chronic Fatigue Syndrome                                   were established. Micromethods were used to determine the lactate/pyruvate (L/P) ratio, respiratory chain
                                                                                                           function and cytochrome oxidase and lactic dehydrogenase activities. Mitochondrial DNA (mtDNA)
                                                                                                           volume was measured and mtDNA rearrangements sought. The results showed that myoblasts from ten of
                                                                                                           16 cases of CFS had defects in aerobic metabolism: two had increased L/P ratios, suggestive of a defect in
                                                                                                           oxidative phosphorylation while eight had decreased ratios, consistent with a deficiency in pyruvate
                                                                                                           dehydrogenase. There was a statistically significant broader range of L/P ratios in the patients' cultures,
                                                                                                           compared to controls (p = 0.011). No mtDNA rearrangements were present. This in vitro study confirms
                                                                                                           that there is convincing evidence of mild aerobic defects in skeletal muscle in some cases of CFS.
 Bell IR, Bootzin RR,                           Differing Patterns of         Journal of Chronic Fatigue   The purpose of the present study was to compare specific neuropsychological, psychological, and family
 Schwartz GER, Baldwin                          Cognitive Dysfunction and     Syndrome 2000; 5(2): 3       history patterns, as well as cardiovascular reactivity of three community-recruited groups of nonsmoking,
 CM, Ballesteros F.                             Heart Rate Reactivity in                                   nonalcoholic middle-aged individuals with and without the symptom of intolerance to low levels of
                                                Chemically-Intolerant                                      environmental chemicals (CI). CI is a common symptom in chronic fatigue syndrome and fibromyalgia.
                                                Individuals With and                                       The groups included: (i) CI who had made associated lifestyle changes because of the CI (CI/LSC); (ii) CI
                                                Without Lifestyle Changes                                  who had not made such changes (CI); and (iii) normals without CI (N). All subjects underwent an
                                                                                                           evaluation session followed by two laboratory cognitive and psychophysiological test sessions one week
                                                                                                           apart. The CI/LSC diverged from the other groups in exhibiting poorer performance on the Continuous
                                                                                                           Visual Memory Test (CVMT) in terms of more false alarms and fewer correct hits, but normal performance
                                                                                                           on a visuospatial test of divided attention (DAT). In contrast, the CI group showed progressively poorer
ME Research UK — Database of Research Publications 2000

                                                                                                                       performance on the DAT with practice, but were like the N on the CVMT. The CI group showed a complex
                                                                                                                       sensitization (amplification) of heart rate response to the DAT over time. In addition, the CI/LSC had the
                                                                                                                       highest rate of family histories of alcohol problems and of attention deficit disorder, as well as of
                                                                                                                       antihypertensive medication treatment and self-reported past emotional/physical abuse. Taken together, the
                                                                                                                       data suggest that individuals with CI comprise a heterogeneous population requiring careful definition of
                                                                                                                       subtypes for future studies.
 Bottero P.                                               Role of Rickettsiae and         Journal of Chronic Fatigue   Objective: To demonstrate the probable role of intracellular bacteria like Rickettsiae and Chlamydiae in the
                                                          Chlamydiae in the               Syndrome 2000; 6(3/4): 147   development of certain chronic psychopathological conditions and according to the efficiency of antibiotic
                                                          Psychopathology of Chronic                                   regimes (cyclines and/or macrolides). The latter aim is based on the fact that all the patients that I have seen
                                                          Fatigue Syndrome (CFS)                                       since 1981 had a sera reaction positive for Rickettsiae and/or Chlamydiae using the micro-agglutination on
                                                          Patients: A Diagnostic and                                   blade technique of P. Giroud and M.L. Giroud (MAG) by Prof. J.B. Jadin of Antwerpen, Belgium with
                                                          Therapeutic Report                                           special antigens cultured on guinea pig lungs and chicken embryos. Methods: This is an open study which
                                                                                                                       began in 1981 in a private medical practice, not versus placebo; but with random choice. Treatment was for
                                                                                                                       a minimum of six months (cyclines and/or macrolides together with vasodilatory medication; chloroquine;
                                                                                                                       warm baths). Group one: 98 CFS cases; women: 78, men: 20; for 67 cases, the ancientness of symptoms is
                                                                                                                       more than 2 years. Group two: 59 psycho-somatic cases; 5 schizophrenia; 3 borderline; 10 children with
                                                                                                                       agressivity, excitement; 1 autistic child; 1 delirium with relapses. Results: Group one: 79.5% good and very
                                                                                                                       good results; 4.1% fairly good; 16.4% failed. Group two: 82.3% good and very good results; 2.5% fairly
                                                                                                                       good; 15. 2% failed. Conclusion: This diagnostic and therapeutic study began in 1981. All of the Dr.
                                                                                                                       Bottero's therapeutic results are confirmed since 1991 by Dr. Cecile Jadin of Randburg (South Africa) for
                                                                                                                       more than 3000 CFS and other psychopathological states (300): Sydney 98 CFS Conference, Australia. We
                                                                                                                       have shown that Rickettsiae and Chlamydiae are probably causative factors in many ``psychopathologies.''
 Bottero P.                                               Chronic Psychopathologies       Journal of Chronic Fatigue   For 60 cases of diseases that are called ``Psychic'' associated with persistent rickettsiae; we have: 55 good
                                                          Associated with Persistant      Syndrome 2000; 6(3/4): 163   and excellent result, 5 failure, but we still have to wait a confirmation in course of time for many patients.
                                                          Rickettsiae and/or Similar
                                                          Germs (Chlamydiae)
 Brace MJ, Scott Smith M,   Department of Psychiatry,     Family reinforcement of         J Dev Behav Pediatr 2000     Parental encouragement of illness behavior is hypothesized to correlate with psychosocial dysfunction in
 McCauley E, Sherry DD.     University of Washington,     illness behavior: a             Oct;21(5):332-9              adolescents with chronic illness. To explore this hypothesis, adolescents aged 11 to 17 years with chronic
                            Seattle, USA.                 comparison of adolescents                                    fatigue syndrome (CFS) (n = 10), juvenile rheumatoid arthritis (JRA) (n = 16), and healthy adolescents (n =
                                                          with chronic fatigue                                         14) were recruited for the study. Measures included the Achenbach parent and youth self report forms, the
                                                          syndrome, juvenile arthritis,                                Family Adaptability and Cohesion Evaluation Scale-II (FACES II), the Children's Depression Rating Scale,
                                                          and healthy controls.                                        and number of days absent from school. The Illness Behavior Encouragement Scale (IBES) generated
                                                                                                                       measures of parental reinforcement of illness behavior. As predicted, the teens with CFS scored statistically
                                                                                                                       higher on measures of depression, total competence, and number of days of school missed in the previous 6
                                                                                                                       months (mean = 40). Children with JRA scored significantly lower than the CFS group on the measure of
                                                                                                                       parental reinforcement of illness behavior. The healthy group produced intermediate scores. Results and
                                                                                                                       implications for future clinical and research activity are discussed.
 Bradley LA, McKendree-     Division of Clinical          Pain complaints in patients     Curr Rev Pain                Individuals with fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) report arthralgias and myalgias.
 Smith NL, Alarcon GS.      Immunology and                with fibromyalgia versus        2000;4(2):148-57             However, only persons with FM alone exhibit abnormal pain responses to mild levels of stimulation, or
                            Rheumatology, University of   chronic fatigue syndrome.                                    allodynia. We identify the abnormalities in the neuroendocrine axes that are common to FM and CFS as
                            Alabama at Birmingham,                                                                     well as the abnormalities in central neuropeptide levels and functional brain activity that differentiate these
                            School of Medicine, 475                                                                    disorders. These two sets of factors, respectively, may account for the similarities and differences in the
                            Boshell Diabetes Building,                                                                 pain experiences of persons with FM and CFS.
                            1808 7th Avenue South,
                            Birmingham, AL 35294,
 Brooks JC, Roberts N,      Magnetic Resonance and        Proton magnetic resonance       Br J Radiol 2000             Seven patients with chronic fatigue syndrome (CFS) were matched with ten healthy control subjects of
 Whitehouse G, Majeed T.    Image Analysis Research       spectroscopy and                Nov;73(875):1206-8           similar age. Hippocampal volume, obtained from magnetic resonance images using an unbiased method,
                            Centre, University of         morphometry of the                                           showed no difference between the two groups, whereas proton magnetic resonance spectroscopy showed a
                            Liverpool, Pembroke Place,    hippocampus in chronic                                       significantly reduced concentration of N-acetylaspartate in the right hippocampus of CFS patients (p =
ME Research UK — Database of Research Publications 2000

                             Liverpool L69 3BX, UK.         fatigue syndrome.                                            0.005).
 Buskila D.                  Ben Gurion University of the   Fibromyalgia, chronic fatigue   Curr Opin Rheumatol 2000     Fibromyalgia and widespread pain were common in Gulf War veterans with unexplained illness referred to
                             Negev, Faculty of Health       syndrome, and myofascial        Mar;12(2):113-23             a rheumatology clinic. Increased tenderness was demonstrated in the postmenstrual phase of the cycle
                             Sciences, Soroka Medical       pain syndrome.                                               compared with the intermenstrual phase in normally cycling women but not in users of oral contraceptives.
                             Center, Beer Sheva, Israel.                                                                 Patients with fibromyalgia had high levels of symptoms that have been used to define silicone implant-
                                                                                                                         associated syndrome. Tender points were found to be a common transient finding associated with acute
                                                                                                                         infectious mononucleosis, but fibromyalgia was an unusual long-term outcome. The common association
                                                                                                                         of fibromyalgia with other rheumatic and systemic illnesses was further explored. A preliminary study
                                                                                                                         revealed a possible linkage of fibromyalgia to the HLA region. Patients with fibromyalgia were found to
                                                                                                                         have an impaired ability to activate the hypothalamic pituitary portion of the hypothalamic pituitary
                                                                                                                         adrenal axis as well as the sympathoadrenal system, leading to reduced corticotropin and epinephrine
                                                                                                                         response to hypoglycemia. Much interest has been expressed in the literature on the possible role of
                                                                                                                         autonomic dysfunction in the development or exacerbation of fatigue and other symptoms in chronic
                                                                                                                         fatigue syndrome. Mycoplasma genus and mycoplasma fermentans were detected by polymerase chain
                                                                                                                         reaction in patients with chronic fatigue syndrome. It was reported that myofascial temporomandibular
                                                                                                                         disorder does not run in families. No major therapeutic trials in fibromyalgia, chronic fatigue syndrome, or
                                                                                                                         myofascial pain syndrome were reported over the past year. The effectiveness of cognitive behavioral
                                                                                                                         therapy and behavior therapy for chronic pain in adults was emphasized. A favorable outcome of
                                                                                                                         fibromyalgia and chronic fatigue syndrome in children and adolescents was reported.
 Byrne E.                    Department of Clinical         Aetiological considerations     J Clin Neurosci 2000
                             Neurosciences, St Vincent's    on some conditions in the       Jan;7(1):9-12
                             Hospital, Fitzroy Victoria,    borderlands of neurology:
                             Australia.                     chronic fatigue syndrome,
                                pan allergy syndrome and
                                                            repetitive strain injury--a
                                                            personal view.
 Cabane J, Renaud MC,                                       The Biorhythm of Fatigue in     Journal of Chronic Fatigue   Evidence is provided for a rhythmic interpretation of fatigue in CFS.
 Tiev KP.                                                   Chronic Fatigue Syndrome        Syndrome 2000; 6(3/4): 109
 Caccappolo E, Kipen H,      University of Medicine and     Odor perception: multiple       J Occup Environ Med 2000     Patients with multiple chemical sensitivities (MCS) often report heightened sensitivity to odors. Odor
 Kelly-McNeil K, Knasko S,   Dentistry of New Jersey,       chemical sensitivities,         Jun;42(6):629-38             detection thresholds to phenyl ethyl alcohol (PEA) and pyridine (PYR) were evaluated as a measure of odor
 Hamer RM, Natelson B,       Robert Wood Johnson            chronic fatigue, and asthma.                                 sensitivity for 33 MCS subjects, 13 chronic fatigue syndrome subjects, 16 asthmatic subjects, and 27
 Fiedler N.                  Medical School,                                                                             healthy controls. Odor identification ability (based on University of Pennsylvania Smell Identification Test
                             Environmental and                                                                           results) and ratings in response to four suprathreshold levels of PEA and PYR were also assessed. Odor
                             Occupational Health                                                                         detection thresholds for PEA and PYR and odor identification ability were equivalent for all groups;
                             Sciences Institute,                                                                         however, when exposed to suprathreshold concentrations of PEA, MCS subjects reported significantly
                             Piscataway 08854, USA.                                                                      more trigeminal symptoms and lower esthetic ratings of PEA. No group differences were found in response
                                                                                                                         to suprathreshold concentrations of PYR. In summary, MCS subjects did not demonstrate lower olfactory
                                                                                                                         threshold sensitivity or enhanced ability to identify odors accurately. Furthermore, they were differentiated
                                                                                                                         from the other groups in their symptomatic and esthetic ratings of PEA, but not PYR.
 Chaudhuri A, Behan PO.                                     Neurological Dysfunction in     Journal of Chronic Fatigue   Chronic fatigue syndrome (CFS), popularly known in Europe as myalgic encephalomyelitis (ME), is a
                                                            Chronic Fatigue Syndrome        Syndrome 2000; 6(3/4): 51    common but not a new illness. CFS/ME was classified as a neurological disease by the World Health
                                                                                                                         Organisation in 1993. Neurological dysfunction is considered the principal mechanism of both physical
                                                                                                                         and mental fatigue in this condition. This article reviews the neurological symptoms of the epidemic and
                                                                                                                         sporadic forms of the illness. Paroxysmal changes in the severity of symptoms (fatigue and
                                                                                                                         neuropsychiatric) are the hallmark features in the natural history of this disease. Ion channel abnormality
                                                                                                                         leading to neuronal instability in selective anatomical pathways (basal ganglia circuitry) is proposed as the
                                                                                                                         possible mechanism of fluctuating fatigue and related symptoms in CFS.
 Chaudhuri A, Watson WS,     University Department of       The symptoms of chronic         Med Hypotheses 2000          The pathogenesis of chronic fatigue syndrome (CFS) is unknown but one of the most characteristic features
 Pearn J, Behan PO.          Neurology, Institute of        fatigue syndrome are related    Jan;54(1):59-63Comment in:   of the illness is fluctuation in symptoms which can be induced by physical and/or mental stress. Other
                             Neurological Sciences,         to abnormal ion channel         Med Hypotheses. 2000         conditions in which fluctuating fatigue occurs are caused by abnormal ion channels in the cell membrane.
                             Southern General Hospital,     function                        Dec;55(6):524 Med            These include genetically determined channelopathies, e.g. hypokalemic periodic paralysis, episodic ataxia
ME Research UK — Database of Research Publications 2000

                             Glasgow, UK.                                                      Hypotheses. 2000             type 2 and acquired conditions such as neuromyotonia, myasthenic syndromes, multiple sclerosis and
                                                                                               Nov;55(5):457.               inflammatory demyelinating polyneuropathies. Our hypothesis is that abnormal ion channel function
                                                                                                                            underlies the symptoms of CFS and this is supported also by the finding of abnormal cardiac-thallium201
                                                                                                                            SPECT scans in CFS, similar to that found in syndrome X, another disorder of ion channels. CFS and
                                                                                                                            syndrome X can have identical clinical symptoms. CFS may begin after exposure to specific toxins which
                                                                                                                            are known to produce abnormal sodium ion channels. Finally, in CFS, increased resting energy expenditure
                                                                                                                            (REE) occurs, a state influenced by transmembrane ion transport. The hypothesis that ion channels are
                                                                                                                            abnormal in CFS may help to explain the fluctuating fatigue and other symptoms.
 Cichon MJ, Farrell DL,                                       A Case Series Survey of          Journal of Chronic Fatigue   Objective: To survey the symptoms of a large group of breast implant patients displaying illness and to
 Ganio SH, Sadler GM.                                         Silicone Breast Implant          Syndrome 2000; 5(3/4): 119   determine if any clinical or serological features predominate. Design: A case series survey. Setting: A
                                                              Patients                                                      private internal medicine practice. Patients: A referred sample of 415 patients with fatigue of long duration,
                                                                                                                            followed by muscle/joint pain, cognition problems, polyneuropathy, and localized breast pain. Conclusion:
                                                                                                                            Silicone adjuvant breast disease may be a novel disorder, possibly autoimmune, producing atypical
                                                                                                                            syndromes that do not fit within the classic diagnostic criteria of known conditions. Furthermore, the
                                                                                                                            diversity and distinction of silicone adjuvant breast disease may require the medical community to accept it
                                                                                                                            as a new entity, encompassing a neurological and connective tissue disorder.
 Clarke JN.                  Sociology Department,            The search for legitimacy and    Soc Work Health Care         Some "diseases" appear to be recognized first by sufferers. At times these diseases may be disclaimed by
                             Wilfrid Laurier University,      the "expertization" of the lay   2000;30(3):73-93             medical doctors and elusive to scientific categorization and description. In these cases sufferers may
                             Waterloo, Ontario, Canada.       person: the case of chronic                                   organize themselves together in support groups and lobby for money to finance the discovery of diagnostic
                                                              fatigue syndrome.                                             markers that would legitimate and medicalize the constellation of symptoms that they experience. Chronic
                                                                                                                            fatigue syndrome is such a disease; and it is characterized by varied and changing symptomatology. Its
                                                                                                                            diagnostic markers are in the process of being refined. Presently, its diagnosis primarily originates in
                                                                                                                            reports of subjective experience of extreme fatigue. Often-times people diagnose themselves after attending
                                                                                                                            a support group and find a doctor through a support group network who believes in the disease. Sometimes,
                                                                                                                            people then return to their own family doctors with information and try to teach their doctors about what
                                                                                                                            they believe to be the nature of their disease, its prognosis and treatment. Through such paths as described
                                                                                                                            in the paper, patients become "experts": they may often know more about the illness than doctors and non-
                                                                                                                            suffering others. This paper moves beyond the experience of chronic illness to describe the processes
                                                                                                                            through which people seek confirmation and legitimation for the way that they feel and in a sense become
                                                                                                                            the "experts."
 Cleare AJ, Sookdeo SS,      Department of Psychological      Integrity of the growth          J Clin Endocrinol Metab      GH deficiency states and chronic fatigue syndrome (CFS) share several characteristics, and preliminary
 Jones J, O'Keane V, Miell   Medicine, Guy's King's and       hormone/insulin-like growth      2000 Apr;85(4):1433-9        studies have revealed aspects of GH dysfunction in CFS. This study assessed indexes of GH function in 37
 JP.                         St. Thomas' School of            factor system is maintained                                   medication-free CFS patients without comorbid psychiatric illness and 37 matched healthy controls. We
                             Medicine, and the Institute of   in patients with chronic                                      also assessed GH function before and after treatment with low dose hydrocortisone, which has been shown
                             Psychiatry, London, United       fatigue syndrome.                                             recently to reduce fatigue in CFS. We measured basal levels of serum insulin-like growth factor I (IGF-I),
                             Kingdom.                                                                                       IGF-II, IGF-binding protein-1 (IGFBP-1), IGFBP-2 and IGFBP-3 together with 24-h urinary GH excretion.
                                                                                            We also performed 2 dynamic tests of GH function: a 100-microg GHRH test and an insulin stress test
                                                                                                                            using 0.15 U/kg BW insulin. There were no differences between patients and controls in basal levels of
                                                                                                                            IGF/IGFBP or in urinary GH excretion. GH responses to both the GHRH test and the insulin stress test
                                                                                                                            were no different in patients and controls. CFS patients did have a marginally reduced suppression of
                                                                                                                            IGFBP-1 during the insulin stress test. Hydrocortisone treatment had no significant effect on any of these
                                                                                                                            parameters. There is no evidence of GH deficiency in CFS. At the doses used, hydrocortisone treatment
                                                                                                                            appears to have little impact on GH function.
 Cocchetto AM, McNamara                                       Human Herpes Virus 6             Journal of Chronic Fatigue   Using evidence-based medical research techniques, current knowledge about the presence of active HHV-6
 ME, Jordan EF.                                               (HHV-6) Infection in             Syndrome 2000; 6(3/4): 41    infections, in a sub-population of patients with chronic fatigue syndrome (CFS), has been reviewed and
                                                              Patients with Chronic Fatigue                                 implications to activation-induced cell death are presented. Therapeutic intervention methods are also
                                                              Syndrome and Its                                              disclosed with a call for clinical studies to test the hypothesis presented.
                                                              Relationship to Activation-
                                                              Induced Cell Death
 Colquhoun D, Senn S.                                         Is NADH effective in the         Ann Allergy Asthma
                                                              treatment of chronic fatigue     Immunol 2000
ME Research UK — Database of Research Publications 2000

                                                         syndrome?                       Jun;84(6):639-40 Comment
                                                                                         on: Ann Allergy Asthma
                                                                                         Immunol. 1999
 Couper J.               Department of Psychiatry, St    Chronic fatigue syndrome        Aust N Z J Psychiatry 2000   OBJECTIVE: The aim of this paper is to outline the opportunities and dangers the chronic fatigue
                         Vincent's Hospital, The         and Australian psychiatry:      Oct;34(5):762-9              syndrome (CFS) issue presents to Australian psychiatry. METHOD: The scientific literature of the last 50
                         University of Melbourne,        lessons from the UK                                          years on CFS in adults was reviewed and samples of recent media portrayals of CFS in the UK and
                         Fitzroy, Victoria, Australia.   experience.                                                  Australia were collected. The author has worked in both the UK and Australia managing adult CFS patients
                                                                                        in specialist outpatient consultation-liaison (C-L) psychiatry settings. RESULTS: Chronic fatigue
                                                                                                                      syndrome has been at the heart of an acrimonious debate in the UK, both within the medical profession and
                                                                                                                      in the wider community. UK psychiatry has been drawn into the debate, at times being the target of strong
                                                                                                                      and potentially damaging criticism, yet UK psychiatry, especially the C-L subspecialty, has played a crucial
                                                                                                                      role in clarifying appropriate research questions and in devising management strategies. The issue has
                                                                                                                      served to enhance and broaden psychiatry's perceived research and clinical role at the important medicine-
                                                                                                                      psychiatry interface in that country. CONCLUSIONS: Handled properly, the CFS issue offers Australian
                                                                                                                      psychiatry, especially C-L psychiatry, an opportunity to make a useful contribution to patient care in a
                                                                                                                      clinically difficult and contentious area, while at the same time serving to help broaden psychiatry's scope
                                                                                                                      in the Australian medical landscape.
 Cox DL, Findley LJ.                                     Severe and Very Severe          Journal of Chronic Fatigue   The Chronic Fatigue Syndrome (CFS) Service within the Essex Neuroscience's Centre has been developing
                                                         Patients with Chronic Fatigue   Syndrome 2000; 7(3): 33      since 1990. The service was established as a comprehensive diagnostic and management service in July
                                                         Syndrome: Perceived                                          1994. From May 1990 to March 1998, 318 patients with CFS were admitted into the programme and since
                                                         Outcome Following an                                         November 1994, 1189 patients seen as outpatients. A previous survey indicated a positive perceived
                                                         Inpatient Programme                                          change in level of ability following the inpatient programme for all levels of CFS from mild to very severe.
                                                                                                                      Of those admitted since 1990, 14% (43/318) were severely affected (extremely restricted mobility) and 9%
                                                                                                                      (29/318) very severely affected (totally bedbound). Most studies on CFS do not include the more severe
                                                                                                                      expressions of the disease; therefore, this descriptive paper aims to show the perceived outcome of these
                                                                                                                      more severely affected patients following the inpatient programme. In particular, the eventual diagnosis, the
                                                                                                                      specific approach to treatment and management and grading of patients will be described and the potential
                                                                                                                      influence of the programme presented. The patients not diagnosed with CFS on discharge appeared to do
                                                                                                                      least well at follow up.
 Cruess SE, Klimas N,                                    Immunologic Status              Journal of Chronic Fatigue   The purpose of the present study was to investigate the relationship between immunologic status and
 Antoni MH, Helder L,                                    Correlates with Severity of     Syndrome 2000; 7(1): 39      physical symptoms in Chronic Fatigue Syndrome (CFS) patients. Twenty-seven patients diagnosed with
 Maher K, Keller R,                                      Physical Symptoms and                                        CFS were included. Participants completed a questionnaire including selected subscales of the Sickness
 Fletcher MA.                                            Perceived Illness Burden in                                  Impact Profile, the Cognitive Difficulties Scale, and frequency and severity of CFS-related physical
                                                         Chronic Fatigue Syndrome                                     symptoms. Cellular immune markers measured included number and percent of T-helper/inducer cells
                                                         Patients                                                     (CD3+CD4+), T-cytotoxic/suppressor cells (CD3+CD8+), activated T-lymphocytes (CD26+CD2+ CD3+),
                                                                                                                      activated T cytotoxic/suppressor cells (CD38+HLA-DR+CD8+), and CD4/CD8 ratio. Spearman's
                                                                                                                      correlation coefficients revealed significant associations between a number of immunologic measures and
                                                                                                                      severity of illness suggesting that the degree of cellular immune activation was associated with the severity
                                                                                                                      of CFS-related physical symptoms, cognitive complaints, and perceived impairment secondary to CFS.
                                                                                                                      Specifically, elevations in T-helper/inducer cells, activated T-cells, activated cytotoxic/suppressor T-cells,
                                                                                                                      and CD4/CD8 ratio were associated with greater severity of several symptoms. Furthermore, reductions in
                                                                                                                      T-suppressor/cytotoxic cells also appeared related to greater severity of some CFS-related physical
                                                                                                                      symptoms and illness burden. Multiple regression analyses demonstrated that decreased percentage of
                                                                                                                      CD3+CD8+ cells and increased number of CD38+HLA-DR+CD8+ cells were the strongest predictors of
                                                                                                                      total illness burden and fatigue severity, accounting for almost 30% of the variance in these measures.
 Cukor D, Tiersky L,                                     Psychiatric Comorbidity and     Journal of Chronic Fatigue   The purpose of this study was to examine if type of Chronic Fatigue Syndrome (CFS) onset suggested two
 Natelson BH.                                            Somatic Distress in Sudden      Syndrome 2000; 7(4): 33      distinct illness patterns within CFS. One hundred and seventeen patients diagnosed with CFS by a
                                                         and Gradual Onset Chronic                                    multidisciplinary team were divided into two groups: sudden versus gradual onset of symptoms. These two
                                                         Fatigue Syndrome                                             subgroups were compared on the presence of lifetime comorbid Axis I diagnoses, the pattern of medically
                                                                                                                      unexplained symptoms, and the number of patients who met criteria for Somatization Disorder (SD). The
ME Research UK — Database of Research Publications 2000

                                                                                                                            two subgroups did not differ in any of the experimental variables indicating that onset type is not
                                                                                                                            distinguished by either comorbid psychopathology or medically unexplained symptoms. Implications of
                                                                                                                            these findings are discussed.
 Dalby JT.                                                  Chronic fatigue syndrome          Scand J Rheumatol
                                                            and memory complaints.            2000;29(4):271-2
 Davis SD, Kator SF,        Preventive Medicine, Evans      Neurally mediated                 Am J Med Sci 2000             BACKGROUND: Many patients with chronic fatigue syndrome (CFS) have neurally mediated hypotension
 Wonnett JA, Pappas BL,     US Army Community               hypotension in fatigued Gulf      Feb;319(2):89-95              when subjected to head-up tilt, suggesting autonomic nervous system dysfunction. Some Gulf War veterans
 Sall JL.                   Hospital, Fort Carson,          War veterans: a preliminary                                     have symptoms similar to CFS. Whether they also tend to have neurally mediated hypotension is unknown.
                            Colorado, USA.                  report.                                                         METHODS: We performed 3-stage tilt-table testing on 14 Gulf War veterans with chronic fatigue, 13
                                                                                          unfatigued control Gulf War veterans, and 14 unfatigued control subjects who did not serve in the Gulf
                                                                                                                            War. Isoproterenol was used in stages 2 and 3 of the tilt protocol. RESULTS: More fatigued Gulf War
                                                                                                                            veterans than unfatigued control subjects had hypotensive responses to tilt (P < 0.036). A positive response
                                                                                                                            to the drug-free stage 1 of the tilt was observed in 4 of 14 fatigued Gulf War veterans versus 1 of 27
                                                                                                                            unfatigued control subjects (P < 0.012). Heart rate and heart rate variation during stage 1 was significantly
                                                                                                                            greater in the fatigued group (P < 0.05). CONCLUSION: We conclude that more fatigued Gulf War
                                                                                                                            veterans have neurally mediated hypotension than unfatigued control subjects, similar to observations in
                                                                                                                            CFS. Autonomic nervous system dysfunction may be present in some fatigued Gulf War veterans.
 De Becker P, Roeykens J,   Human Performance               Erratum in: Arch Intern Med       Arch Intern Med 2000 Nov      BACKGROUND: Patients with chronic fatigue syndrome (CFS) suffer from various symptoms, including
 Reynders M, McGregor N,    Laboratory and Department       2001 Sep 10;161(16):2051-2        27;160(21):3270-7             debilitating fatigue, muscle pain, and muscle weakness. Patients with CFS can experience marked
 De Meirleir K.             of Internal Medicine, Faculty   Exercise capacity in chronic                                    functional impairment. In this study, we evaluated the exercise capacity in a large cohort of female patients
                            of Physical Education and       fatigue syndrome.                                               with CFS. METHODS: Patients with CFS and matched sedentary control subjects performed a maximal
                            Physical Therapy, Vrije                                                                         test with graded increase on a bicycle ergometer. Gas exchange ratio was continuously measured. In a
                            Universiteit Brussel, LK-                                                                       second stage, we examined only those persons who achieved a maximal effort as defined by 2 end points: a
                            Third Floor, Pleinlaan 2,                                                                       respiratory quotient of at least 1.0 and an age-predicted target heart rate of at least 85%. Data were assessed
                            1050 Brussels, Belgium.                                                                         using univariate and multivariate statistical methods. RESULTS: The resting heart rate of the patient group
                                                                                             was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The
                                                                                                                            maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those
                                                                                                                            achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test,
                                                                                                                            similar findings were observed. CONCLUSIONS: When compared with healthy sedentary women, female
                                                                                                                            patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities
                                                                                                                            to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor
                                                                                                                            of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances. Arch
                                                                                                                            Intern Med. 2000;160:3270-3277.
 De Meirleir K, Bisbal C,   Department of Human             A 37 kDa 2-5A binding             Am J Med 2000                 PURPOSE: Recent studies have revealed abnormalities in the ribonuclease L pathway in peripheral blood
 Campine I, De Becker P,    Physiology and Medicine,        protein as a potential            Feb;108(2):99-105Comment      mononuclear cells of patients with the chronic fatigue syndrome. We conducted a blinded study to detect
 Salehzada T, Demettre E,   Vrije Universiteit Brussels,    biochemical marker for            in: Am J Med. 2000 Aug        possible differences in the distribution of 2-5A binding proteins in the cells of patients with chronic fatigue
 Lebleu B.                  Belgium.                        chronic fatigue syndrome          15;109(3):257-9 Am J Med.     syndrome and controls. PATIENTS AND METHODS: We studied 57 patients with chronic fatigue
                                                                                              2000 Dec 15;109(9):744 Am     syndrome and 53 control subjects (28 healthy subjects and 25 patients with depression or fibromyalgia). A
                                                                                              J Med. 2000 Feb;108(2):169-   radioactive probe was used to label 2-5A binding proteins in unfractionated peripheral blood mononuclear
                                                                                              71 Am J Med. 2000             cell extracts and to compare their distribution in the three groups. RESULTS: A 37 kDa 2-5A binding
                                                                                              Feb;108(2):172-3.             polypeptide was found in 50 (88%) of the 57 patients with chronic fatigue syndrome compared with 15
                                                                                                                            (28%) of the 53 controls (P < 0.01). When present, the amount of 37 kDa protein was very low in the
                                                                                                                            control groups. When expressed as the ratio of the 37 kDa protein to the 80 kDa protein, 41 (72%) of the
                                                                                                                            57 patients with chronic fatigue syndrome had a ratio > 0.05, compared with 3 (11%) of the 28 healthy
                                                                                                                            subjects and none of the patients with fibromyalgia or depression. CONCLUSION: The presence of a 37
                                                                                                                            kDa 2-5A binding protein in extracts of peripheral blood mononuclear cells may distinguish patients with
                                                                                                                            chronic fatigue syndrome from healthy subjects and those suffering from other diseases.
 Deale A, Wessely S.        Department of Psychological     Diagnosis of psychiatric          J R Soc Med 2000              The overlap of symptoms in chronic fatigue syndrome (CFS) and psychiatric disorders such as depression
                            Medicine, King's College,       disorder in clinical evaluation   Jun;93(6):310-2               can complicate diagnosis. Patients often complain that they are wrongly given a psychiatric label. We
                            London, UK.                     of chronic fatigue syndrome.                                    compared psychiatric diagnoses made by general practitioners and hospital doctors with diagnoses
                                                                                            established according to research diagnostic criteria. 68 CFS patients referred to a hospital fatigue clinic
ME Research UK — Database of Research Publications 2000

                                                                                                             were assessed, and psychiatric diagnoses were established by use of a standardized interview schedule
                                                                                                             designed to provide current and lifetime diagnoses. These were compared with psychiatric diagnoses
                                                                                                             previously given to patients. Of the 31 patients who had previously received a psychiatric diagnosis 21
                                                                                                             (68%) had been misdiagnosed: in most cases there was no evidence of any past or current psychiatric
                                                                                                             disorder. Of the 37 patients who had not previously received a psychiatric diagnosis 13 (35%) had a
                                                                                                             treatable psychiatric disorder in addition to CFS. These findings highlight the difficulties of routine clinical
                                                                                                             evaluation of psychiatric disorder in CFS patients. We advise doctors to focus on subtle features that
                                                                                                             discriminate between disorders and to use a brief screening instrument such as the Hospital Anxiety and
                                                                                                             Depression Scale.
 Donnay A, Ziem G.                              Prevalence and Overlap of       Journal of Chronic Fatigue   Background: Several studies have reported on extensive two-way overlaps found among chronic fatigue
                                                Chronic Fatigue Syndrome        Syndrome 2000; 5(3/4): 71    syndrome (CFS), fibromyalgia syndrome (FMS) and multiple chemical sensitivity syndrome (MCS) but
                                                and Fibromyalgia Syndrome                                    none have yet reported on the overlap of all three. This study assesses the prevalence of pure MCS, MCS-
                                                Among 100 New Patients                                       CFS, MCS-FMS and the overlap of all three among 100 consecutive new patients evaluated for MCS in a
                                                with Multiple Chemical                                       private practice specializing in occupational and environmental medicine. Methods: Sixty-eight females
                                                Sensitivity Syndrome                                         and 32 males diagnosed with MCS-based on a medical history of multiple chronic symptoms in multiple
                                                                                                             organs triggered by multiple chemical exposures at or below previously tolerated levels-were also evaluated
                                                                                                             for CFS and FMS using the diagnostic criteria of the US Centers for Disease Control and the American
                                                                                                             College of Rheumatology, respectively. Results: Eighty-eight percent of the 100 MCS patients met criteria
                                                                                                             for CFS, 49% met criteria for FMS, and 47% met both. Slightly more male than female MCS patients had
                                                                                                             CFS: 91% vs. 87%; while FMS was more than twice as common among female MCS patients: 59% vs.
                                                                                                             28%. The majority of women, 56%, met criteria for all three disorders, and an additional 31% had both
                                                                                                             MCS and CFS. This pattern was reversed in men, only 28% of whom had all three, compared to 63% with
                                                                                                             MCS and CFS but no FMS. MCS alone was diagnosed in only 10% of the women and 9% of the men.
                                                                                                             Even rarer was the overlap of MCS and FMS without any CFS, found in just 2 women. Conclusions: At
                                                                                                             least in this clinic population, MCS seldom occurs alone. The enormous range of diagnostic overlaps
                                                                                                             reported here and in previous studies of various overlaps among CFS, FMS and MCS highlights the need to
                                                                                                             screen for all three disorders in studies of any one and to report results in these terms. We recommend this
                                                                                                             be made standard practice in both clinical settings and research protocols.
 Duley JA, Garrick DP,                          Raised Plasma Adenosine         Journal of Chronic Fatigue   Plasma adenosine levels were measured in a small trial study of eighteen volunteers, aged 36-85 years.
 Pratt DA.                                      Associated with Chronic         Syndrome 2000; 7(3): 77      Volunteers comprised nine with chronic fatigue syndrome (CFSs), four with `other fatigue' illnesses, and
                                                Fatigue Syndrome: A                                          five with no history of fatigue illnesses but some of whom were related to chronic fatigue sufferers. Plasma
                                                Preliminary Study                                            adenosine was slightly raised above the minimum detectable level (approx. 1 micromole/L) in one healthy
                                                                                                             non-fatigued volunteer and grossly raised (greater than 5 micromoles/L) in two non-fatigued volunteers,
                                                                                                             both of whom were related to CFSs. Among the nine CFSs, all had plasma adenosine raised above baseline,
                                                                                                             and seven were grossly raised. High adenosine levels were also seen in two of the volunteers with `other
                                                                                                             fatigue.' Raised adenosine occurred among certain families, suggesting a genetic metabolic element.
                                                                                                             Instability of adenosine in frozen stored plasma was noted. High levels of adenosine probably do not exist
                                                                                                             freely within peripheral plasma but may be released from blood cells locally within tissues or in response to
                                                                                                             venipuncture stress or other factors. The results may be highly relevant to other pathologies such as heart
 Duncan RB.                                     Latency Immunity and            Journal of Chronic Fatigue   Organ cells of the body retain an Immune Activity System comparable to protozoa. The cells' immunity
                                                Therapy: A Clinical Study of    Syndrome 2000; 5(2): 77      memory templates are latent proteins, microbes, their toxins and chemicals (latentees). Excess latentees are
                                                Latent Epstein Barr Virus                                    detected and excreted by latency therapy. Their excretion induces immediate and/or delayed symptoms and
                                                Incidence in 297 Idiopathic                                  signs recognized by the patient. Foreign latent materials (latentors) enter the body and bypass the Natural
                                                Chronic Fatigue Patients with                                Immune System to be taken up selectively by organ cell groups. Active infection/disease and allergens
                                                Plausible Hypotheses                                         (antigens) involve the Natural Immune System antibodies. Latent infection/disease and allergens (latentors)
                                                                                                             involve the Organ Cell Immunity as intracellular latentees. Clinical laboratory testing is inappropriate. This
                                                                                                             Clinical Anecdotal Study compiles 297 patients who obtained little or no relief from conventional and
                                                                                                             alternative medicine (duration: 63% > three years.) Patients provoked symptoms to two or more of 16
                                                                                                             viruses, in particular Epstein Barr Virus. Latency therapy (heat, saunas, massage, tolerated exercise and
                                                                                                             sweating during sleep, the auto-sauna) dilutions stimulated excretion until symptoms/signs cleared. The
ME Research UK — Database of Research Publications 2000

                                                                                                            principals were Epstein Barr Virus 67.3%, 200 patients; 13 individual viruses 30.0%, 89 patients; non-viral
                                                                                                            2.6%, 8 patients. Latency therapy < 50% improvement = 16.5%; 50% to 80% = 26.6%; 80% to 100% =
                                                                                                            46. 7%; failures = 11%. Fourteen patients gave positive Epstein Barr Virus serology. A latency immunity
                                                                                                            concept explains affected subjective symptoms and illnesses and offers a treatment which complements
                                                                                                            related medical therapies.
 Dunstan RH, McGregor                           The Development of             Journal of Chronic Fatigue   Background: The diagnosis of chronic fatigue syndrome (CFS) requires the exclusion of other known
 NR, Roberts T K, Butt H,                       Laboratory-Based Tests in      Syndrome 2000; 7(1): 23      fatigue-related diseases because the core symptoms of CFS represent a general host response to many well-
 Niblett SH, Rothkirch T.                       Chronic Pain and Fatigue: 1.                                defined diseases. The patient set derived by this process is heterogeneous in their polysymptomatic
                                                Muscle Catabolism and                                       presentation and has proved very difficult to study clinically and scientifically. Objectives: To investigate
                                                Coagulase Negative                                          the alterations in urine excretion and microbiology in patients with CFS. Results: CFS patients had multiple
                                                Staphylococci Which                                         anomalies in their amino and organic acid homeostasis. Sub-groups of CFS patients could be delineated on
                                                Produce Membrane                                            the basis of their urine excretion and their symptom presentation. The most common feature was an active
                                                Damaging Toxins                                             muscle catabolism resulting in a depletion of amino acids and associated organic and keto-acids. The
                                                                                                            extent of muscle catabolism was directly correlated to pain severity. The carriage of toxin-producing
                                                                                                            coagulase negative staphylococci (MDT-CoNS) was strongly correlated with the catabolic response and
                                                                                                            pain severity. Conclusions: An hypothesis has been constructed where an occult pathogen, such as MDT-
                                                                                                            CoNS, may be an aetiological agent contributing to the sustenance of a chronic fatigue/pain disorder, a
                                                                                                            comorbid pathogen. Urine analysis offers an opportunity for assessment of muscle catabolism and sub-
                                                                                                            classification of chronic fatigue patients leading to a number of management options. The detection of
                                                                                                            MDT-CoNS identifies potentially treatable agents that contribute to the fatigue and pain condition.
 Dunstan RH, McGregor                           The Development of             Journal of Chronic Fatigue   Background: The diagnosis of chronic fatigue syndrome (CFS) requires the exclusion of other known
 NR, Roberts T K, Butt H,                       Laboratory-Based Tests in      Syndrome 2000; 7(2): 53      fatigue-related diseases because the core symptoms of CFS represent a general host response to many well-
 Niblett SH, Rothkirch T.                       Chronic Pain and Fatigue: 1.                                defined diseases. The patient set derived by this process is heterogeneous in their polysymptomatic
                                                Muscle Catabolism and                                       presentation and has proved very difficult to study clinically and scientifically. Objectives: To investigate
                                                Coagulase Negative                                          the alterations in urine excretion and microbiology in patients with CFS. Results: CFS patients had multiple
                                                Staphylococci Which                                         anomalies in their amino acid and organic acid homeostasis. Sub-groups of CFS patients could be
                                                Produce Membrane                                            delineated on the basis of their urine excretion and their symptom presentation. The most common feature
                                                Damaging Toxins                                             was an active muscle catabolism resulting in a depletion of amino acids and associated organic and keto-
                                                                                                            acids. The extent of muscle catabolism was directly correlated to pain severity. The carriage of toxin-
                                                                                                            producing coagulase negative staphylococci (MDT-CoNS) was strongly correlated with the catabolic
                                                                                                            response and pain severity. Conclusions: An hypothesis has been constructed where an occult pathogen,
                                                                                                            such as MDT-CoNS, may be an aetiological agent contributing to the sustenance of a chronic fatigue/pain
                                                                                                            disorder, a comorbid pathogen. Urine analysis offers an opportunity for assessment of muscle catabolism
                                                                                                            and sub-classification of chronic fatigue patients leading to a number of management options. The
                                                                                                            detection of MDT-CoNS identifies potentially treatable agents that contribute to the fatigue and pain
 Dunstan RH, McGregor                           The Development of             Journal of Chronic Fatigue   Objectives: To investigate fatty acid and sterol homeostasis in patients with CFS. Methods: Plasma samples
 NR, Roberts T K, Butt H,                       Laboratory-Based Tests in      Syndrome 2000; 7(2): 59      were collected from CFS and control subjects and analyzed for lipid composition by GC-MS metabolic
 Taylor WG, Carter A.                           Chronic Pain and Fatigue: 2.                                profiling techniques. Results: CFS patients had significantly different profiles of fatty acids and sterols
                                                Essential Fatty Acids and                                   compared with control subjects. The 1st and 2nd most important factors discriminating the CFS patients
                                                Cholesterol                                                 from the controls, were a decrease in elaidic acid (trans-9-octadecenoic acid) and an increase in stearic acid
                                                                                                            (octadecanoic acid), respectively. The CFS patients also had lower levels of cholesterol, which has potential
                                                                                                            impact on membrane integrity and function, steroid hormone synthesis, energy metabolism and bile
                                                                                                            production. The CFS patients could also be subdivided into subgroups based on their fatty acid and sterol
                                                                                                            composition. The results of cluster analyses and multivariate analyses revealed that several types of
                                                                                                            homeostasis exist in different types of CFS patients, whereas the control group was largely homogeneous.
                                                                                                            Viral infections can contribute to the nature of the lipid-based anomalies in CFS patients and lipid profiles
                                                                                                            from patients with prior viral infections could be differentiated from those without viral histories.
                                                                                                            Conclusions: The assessment of fatty acids and sterols in fasting plasma samples can indicate essential
                                                                                                            fatty acid deficits, suggest appropriate types of essential fatty acid oils for formulations, indicate potential
                                                                                                            cholesterol deficit-associated anomalies, provide evidence for mitochondrial dysfunction and categorize
ME Research UK — Database of Research Publications 2000

                                                                                                                     CFS patients into biochemical subgroups. These evaluations provide a basis for devising individually
                                                                                                                     tailored patient management protocols.
 Durstine JL, Painter P,   Department of Exercise            Physical activity for the       Sports Med 2000         Exercise prescription principles for persons without chronic disease and/or disability are based on well
 Franklin BA, Morgan D,    Science, University of South      chronically ill and disabled.   Sep;30(3):207-19        developed scientific information. While there are varied objectives for being physically active, including
 Pitetti KH, Roberts SO.   Carolina, Columbia 29208,                                                                 enhancing physical fitness, promoting health by reducing the risk for chronic disease and ensuring safety
                           USA.                                                                                      during exercise participation, the essence of the exercise prescription is based on individual interests,
                                                                                 health needs and clinical status, and therefore the aforementioned goals do not always carry equal weight.
                                                                                                                     In the same manner, the principles of exercise prescription for persons with chronic disease and/or
                                                                                                                     disability should place more emphasis on the patient's clinical status and, as a result, the exercise mode,
                                                                                                                     intensity, frequency and duration are usually modified according to their clinical condition. Presently, these
                                                                                                                     exercise prescription principles have been scientifically defined for clients with coronary heart disease.
                                                                                                                     However, other diseases and/or disabilities have been studied less (e.g. renal failure, cancer, chronic fatigue
                                                                                                                     syndrome, cerebral palsy). This article reviews these issues with specific reference to persons with chronic
                                                                                                                     diseases and disabilities.
 Elenkov IJ, Wilder RL,    Inflammatory Joint Diseases       The sympathetic nerve--an       Pharmacol Rev 2000      The brain and the immune system are the two major adaptive systems of the body. During an immune
 Chrousos GP, Vizi ES.     Section, Arthritis and            integrative interface between   Dec;52(4):595-638       response the brain and the immune system "talk to each other" and this process is essential for maintaining
                           Rheumatism Branch,                two supersystems: the brain                             homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-
                           National Institute of Arthritis   and the immune system.                                  adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS
                           and Musculoskeletal and                                                                   in neuroimmune interactions, an area that has received much less attention than the role of HPA axis.
                           Skin Diseases, National                                                                   Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for
                           Institutes of Health,                                                                     neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs
                           Bethesda, Maryland, USA.                                                                  receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the
                                                                                                                     sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors. Through
                                                                                                                     stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine,
                                                                                                                     affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the
                                                                                                                     functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in
                                                                                                                     the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the
                                                                                                                     sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely
                                                                                                                     modest. In addition, recent evidence is discussed that NE and epinephrine, through stimulation of the
                                                                                                                     beta(2)-adrenoreceptor-cAMP-protein kinase A pathway, inhibit the production of type 1/proinflammatory
                                                                                                                     cytokines, such as interleukin (IL-12), tumor necrosis factor-alpha, and interferon-gamma by antigen-
                                                                                                                     presenting cells and T helper (Th) 1 cells, whereas they stimulate the production of type 2/anti-
                                                                                                                     inflammatory cytokines such as IL-10 and transforming growth factor-beta. Through this mechanism,
                                                                                                                     systemically, endogenous catecholamines may cause a selective suppression of Th1 responses and cellular
                                                                                                                     immunity, and a Th2 shift toward dominance of humoral immunity. On the other hand, in certain local
                                                                                                                     responses, and under certain conditions, catecholamines may actually boost regional immune responses,
                                                                                                                     through induction of IL-1, tumor necrosis factor-alpha, and primarily IL-8 production. Thus, the activation
                                                                                                                     of SNS during an immune response might be aimed to localize the inflammatory response, through
                                                                                                                     induction of neutrophil accumulation and stimulation of more specific humoral immune responses,
                                                                                                                     although systemically it may suppress Th1 responses, and, thus protect the organism from the detrimental
                                                                                                                     effects of proinflammatory cytokines and other products of activated macrophages. The above-mentioned
                                                                                                                     immunomodulatory effects of catecholamines and the role of SNS are also discussed in the context of their
                                                                                                                     clinical implication in certain infections, major injury and sepsis, autoimmunity, chronic pain and fatigue
                                                                                                                     syndromes, and tumor growth. Finally, the pharmacological manipulation of the sympathetic-immune
                                                                                                                     interface is reviewed with focus on new therapeutic strategies using selective alpha(2)- and beta(2)-
                                                                                                                     adrenoreceptor agonists and antagonists and inhibitors of phosphodiesterase type IV in the treatment of
                                                                                                                     experimental models of autoimmune diseases, fibromyalgia, and chronic fatigue syndrome.
 Enbom M, Linde A,                                           No evidence of active           J Clin Microbiol 2000
 Evengard B.                                                 infection with human            Jun;38(6):2457
                                                             herpesvirus 6 (HHV-6) or
                                                             HHV-8 in chronic fatigue
ME Research UK — Database of Research Publications 2000

 Endicott NA.                                                Chronic Fatigue Syndrome in      Journal of Chronic Fatigue       Forty-six patients with chronic fatigue syndrome (CFS) were matched with two control groups: one chosen
                                                             Psychiatric Patients:            Syndrome 2000; 5(1): 29          on the basis of relatively good physical health (N = 92) and the other without regard to physical health (N =
                                                             Evidence of Premorbid                                             46). All patients were from the same psychiatric practice. The groups were compared on 20 anomalous
                                                             Anomalous Patterns of Brain                                       brain conditions or phenomena (ABCP) used as markers of patterns of brain organization. The results
                                                             Organization                                                      suggest that psychiatric patients who subsequently develop CFS have a higher number of pre-CFS ABCP,
                                                                                                                               of both childhood and adult onset, than psychiatric patients who have not developed this condition.
 Enserink M. News                                            Chronic fatigue syndrome.        Science 2000 Jan
                                                             CDC struggles to recover         7;287(5450):22-3 Comment
                                                             from debacle over earmark        on: Science. 2000 Jan
 Evans P.                                                    Chronic fatigue syndrome         Aust Fam Physician 2000
                                                                                              Jul;29(7):625-6 Comment
                                                                                              on: Aust Fam Physician.
                                                                                              2000 Jan;29(1):76-7.
 Feinberg M.                                                 Chronic fatigue syndrome         Aviat Space Environ Med
                                                             and the aviator.                 2000 Sep;71(9 Pt 1):965
 Ferrari R.                                                  The biopsychosocial model--      Baillieres Best Pract Res Clin   Rheumatologists grapple in daily practice with many controversial syndromes including fibromyalgia, late
                                                             a tool for rheumatologists.      Rheumatol 2000                   whiplash syndrome, chronic fatigue syndrome, Gulf War syndrome, the adverse outcomes of silicon breast
                                                                                              Dec;14(4):787-95                 implants and so on. For decades, much of the debate surrounding, and the approach to these controversial
                                                                                                                               syndromes has centred on a model creating two camps-organic versus non-organic. While each camp has
                                                                                                                               its support, this model seems to have failed in achieving the desired understanding of these syndromes,
                                                                                                                               most particularly in offering the rheumatologist a practical and coherent approach to effective treatment.
                                                                                                                               This chapter will thus introduce the biopsychosocial model, its elements, its advantages over the traditional
                                                                                                                               model and the practical application of this model. Examples will be given of how rheumatologists can
                                                                                                                               approach the treatment of these syndromes through patient education and the implementation of a change
                                                                                                                               in illness behaviour. Copyright 2000 Harcourt Publishers Ltd.
 Fiedler N, Lange G,          Department of                  Stressors, personality traits,   J Psychosom Res 2000             OBJECTIVES: preliminary surveys of Persian Gulf veterans revealed a significant prevalence of self-
 Tiersky L, DeLuca J,         Environmental and              and coping of Gulf War           Jun;48(6):525-35                 reported symptoms consistent with chronic fatigue syndrome (CFS). The purpose of this study was to
 Policastro T, Kelly-McNeil   Community Medicine,            veterans with chronic fatigue.                                    compare self-reported life stressors, combat, and chemical exposures, personality and coping between Gulf
 K, McWilliams R, Korn L,     UMDNJ-Robert Wood                                                                                War veterans with CFS and healthy veterans. METHODS: following a complete physical, psychiatric, and
 Natelson B.                  Johnson Medical School, 170                                                                      neuropsychological evaluation, 45 healthy veterans, 35 veterans with CFS and co-morbid psychiatric
                              Frelinghuysen Road,                                                                              disorder, and 23 veterans with CFS and no co-morbid psychiatric disorder completed questionnaires
                              Piscataway, NJ 08854, USA.                                                                       assessing war and non-war-related life stressors, self-reports of environmental exposure (e.g. oil well fires,
                                                                                           pesticides), personality, and coping. RESULTS: measures of personality, self-reported combat and
                                                                                                                               chemical exposures, and negative coping strategies significantly differentiated healthy veterans from those
                                                                                                                               with CFS. CONCLUSION: a biopsychosocial model of veterans' illness was supported by the fact that
                                                                                                                               personality, negative coping strategies, life stress after the war, and environmental exposures during the war
                                                                                                                               were significant predictors of veterans' current physical function.
 Fletcher MA, Maher K,                                       Comparative Analysis of          Journal of Chronic Fatigue       Blood and lymph node samples were obtained from patients with chronic fatigue syndrome (CFS) who had
 Patarca-Montero R, Klimas                                   Lymphocytes in Lymph             Syndrome 2000; 7(3): 65          volunteered to undergo a lymph node biopsy while participating in a phase 1 clinical trial of a novel
 N.                                                          Nodes and Peripheral Blood                                        immunomodulatory therapy. The surface marker phenotypes of the peripheral blood and lymph node
                                                             of Patients with Chronic                                          samples were examined using four-color flow cytometry and compared to published proportions of cells in
                                                             Fatigue Syndrome                                                  peripheral blood and lymph nodes from control individuals. While a greater proportion of T lymphocytes
                                                                                                                               from both lymph nodes and peripheral blood of control subjects are immunologically ``naive'' (CD45RA+),
                                                                                                                               the proportions of lymphocytes with a ``memory'' phenotype predominate in lymph nodes and peripheral
                                                                                                                               blood of CFS patients. CFS has been proposed to be a disease of autoimmune etiology and in this respect it
                                                                                                                               is interesting to note that decreased proportions of CD45RA+ T (``naive'') cells are also seen in the
                                                                                                                               peripheral blood of patients with autoimmune diseases.
 Friedberg F, Dechene L,      Department of Mathematics,     Symptom patterns in long-        J Psychosom Res 2000             OBJECTIVE: Our objective was to evaluate symptom patterns in patients with chronic fatigue syndrome
 McKenzie MJ 2nd,             Fitchburg State College, MA,   duration chronic fatigue         Jan;48(1):59-68                  (CFS) who were ill for 10 or more years. METHODS: This cross-sectional self-report study compared
ME Research UK — Database of Research Publications 2000

 Fontanetta R.                 USA.                          syndrome.                                                     patient groups with long-duration (median = 18 years; n = 258) and short-duration (median = 3 years; n =
                                                                                                                           28) CFS to a group of healthy significant others (n = 79) on symptomatic, neurocognitive, and
                                                                                                                           psychological variables. Data were gathered from a 574-item postal questionnaire. RESULTS: A principal-
                                                                                                                           components analysis of CFS symptom data yielded a three-factor solution: cognitive problems; flu-like
                                                                                                                           symptoms; and neurologic symptoms. Compared with the short-duration CFS group, the long-duration
                                                                                                                           group had significantly higher CFS symptom severity scores (p < 0.04), largely attributable to increased
                                                                                                                           cognitive difficulties. A subgroup comparison of subjects ill for < 3 years versus those ill 4-7 years
                                                                                                                           suggested that denial coping strategies were more likely in those participants with the shorter illness
                                                                                                                           duration. Significant differences between both CFS groups and healthy controls were found in a number of
                                                                                                                           comorbid disorders. Participants with CFS most often endorsed immune/viral abnormalities and persistent
                                                                                                                           stress as important perceived causes of their illness. CONCLUSION: Participants with long-duration CFS
                                                                                                                           reported a large number of specific cognitive difficulties that were greater in severity than those reported by
                                                                                                                           participants with short-duration CFS. The pattern of comorbid disorders in the CFS groups was consistent
                                                                                                                           with hypersensitivity and viral reactivation hypotheses.
 Friedberg F.                                                A Subgroup Analysis of           Journal of Chronic Fatigue   Several studies of graded activity-oriented cognitive behavioral treatment for chronic fatigue syndrome
                                                             Cognitive-Behavioral             Syndrome 2000; 5(3/4): 149   (CFS), all conducted in England, have reported dramatic improvements in functioning and substantial
                                                             Treatment Studies                                             reductions in symptomatology. On the other hand, cognitive behavioral intervention studies conducted in
                                                                                                                           Australia and the United States have not found significant improvements in functioning or CFS symptoms.
                                                                                                                           Based on a review and synthesis of data from these clinical trials, naturalistic outcome investigations, and
                                                                                                                           illness comparison studies, this articles argues that two CFS subgroups, distinguished by functional status
                                                                                                                           and symptom severity, may account, in part, for the differences in outcome in cognitive behavioral
                                                                                                                           treatment studies. It is also argued that differences in treatment duration may have influenced clinical
                                                                                                                           outcomes. This article concludes with recommendations for specific cognitive behavioral interventions in
 Friedberg F.                                                An Overview of                   Journal of Chronic Fatigue   The assessment of a number of behavioral and psychosocial domains may be important in baseline and
                                                             Psychometric Assessment          Syndrome 2000; 5(3/4): 161   outcome evaluations of CFS patients. These domains include mood disturbance, functional status, sleep
                                                                                                                           disturbance, global well-being (i.e., psychiatric status), pain, behavioral coping, social support, locus of
                                                                                                                           control, illness behavior and illness attribution. This article describes a variety of pen-and-paper measures
                                                                                                                           designed to assess these behavioral dimensions and summarizes their psychometric properties and
                                                                                                                           applicability to CFS populations.
 Fulcher KY, White PD.         National Sports Medicine                                       J Neurol Neurosurg           OBJECTIVE: To measure strength, aerobic exercise capacity and efficiency, and functional incapacity in
                               Institute, St Bartholomew's                                    Psychiatry 2000              patients with chronic fatigue syndrome (CFS) who do not have a current psychiatric disorder. METHODS:
                               and the Royal London School                                    Sep;69(3):302-7Comment in:   Sixty six patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and
                               of Medicine and Dentistry,                                     J Neurol Neurosurg           15 patients with a current major depressive disorder were recruited into the study. Exercise capacity and
                               Charterhouse Square,                                           Psychiatry. 2000             efficiency were assessed by monitoring peak and submaximal oxygen uptake, heart rate, blood lactate,
                               London EC1M 6BQ, UK.                                           Sep;69(3):289 Strength and   duration of exercise, and perceived exertion during a treadmill walking test. Strength was measured using
                                                                                              physiological response to    twitch interpolated voluntary isometric quadriceps contractions. Symptomatic measures included physical
                                                                                              exercise in patients with    and mental fatigue, mood, sleep, somatic amplification, and functional incapacity. RESULTS: Compared
                                                                                              chronic fatigue syndrome.    with sedentary controls, patients with CFS were physically weaker, had a significantly reduced exercise
                                                                                                                           capacity, and perceived greater effort during exercise, but were equally unfit. Compared with depressed
                                                                                                                           controls, patients with CFS had significantly higher submaximal oxygen uptakes during exercise, were
                                                                                                                           weaker, and perceived greater physical fatigue and incapacity. Multiple regression models suggested that
                                                                                                                           exercise incapacity in CFS was related to quadriceps muscle weakness, increased cardiovascular response
                                                                                                                           to exercise, and body mass index. The best model of the increased exercise capacity found after graded
                                                                                                                           exercise therapy consisted of a reduction in submaximal heart rate response to exercise. CONCLUSIONS:
                                                                                                                           Patients with CFS were weaker than sedentary and depressed controls and as unfit as sedentary controls.
                                                                                                                           Low exercise capacity in patients with CFS was related to quadriceps muscle weakness, low physical
                                                                                                                           fitness, and a high body mass ratio. Improved physical fitness after treatment was associated with increased
                                                                                                                           exercise capacity. These data imply that physical deconditioning helps to maintain physical disability in
                                                                                                                           CFS and that a treatment designed to reverse deconditioning helps to improve physical function.
 Fulle S, Mecocci P, Fano G,   Lab. Interuniversitario di    Specific oxidative alterations   Free Radic Biol Med 2000     Chronic fatigue syndrome (CFS) is a poorly understood disease characterized by mental and physical
ME Research UK — Database of Research Publications 2000

 Vecchiet I, Vecchini A,      Miologia, Dip. Biologia       in vastus lateralis muscle of    Dec 15;29(12):1252-9         fatigue, most often observed in young white females. Muscle pain at rest, exacerbated by exercise, is a
 Racciotti D, Cherubini A,    Cellulare e Molecolare,       patients with the diagnosis of                                common symptom. Although a specific defect in muscle metabolism has not been clearly defined, yet
 Pizzigallo E, Vecchiet L,    Universita di Perugia,        chronic fatigue syndrome.                                     several studies report altered oxidative metabolism. In this study, we detected oxidative damage to DNA
 Senin U, Beal MF.            Perugia, Italy.                                                                             and lipids in muscle specimens of CFS patients as compared to age-matched controls, as well as increased
                                                                                                                          activity of the antioxidant enzymes catalase, glutathione peroxidase, and transferase, and increases in total
                                                                                                                          glutathione plasma levels. From these results we hypothesize that in CFS there is oxidative stress in muscle,
                                                                                                                          which results in an increase in antioxidant defenses. Furthermore, in muscle membranes, fluidity and fatty
                                                                                                                          acid composition are significantly different in specimens from CFS patients as compared to controls and to
                                                                                                                          patients suffering from fibromyalgia. These data support an organic origin of CFS, in which muscle suffers
                                                                                                                          oxidative damage.
 Furst G.                                                   Measuring Fatigue in             Journal of Chronic Fatigue   Fatigue is a common symptom occurring in a wide range of acute and chronic illnesses. It is
                                                            Chronic Fatigue Syndrome:        Syndrome 2000; 5(3/4): 55    multidimensional and subjective and because of this it has been difficult to define and quantify. Fatigue is
                                                            Why and How                                                   one of several significant symptoms in diseases such as rheumatoid arthritis and multiple sclerosis, but for
                                                                                                                          persons with chronic fatigue syndrome (CFS), it is often the most debilitating symptom. The need for valid
                                                                                                                          and reliable assessments of fatigue is necessary for health care providers as we are increasingly required to
                                                                                                                          document outcomes of care for professional and insurance purposes.
 Gelman IH, Unger ER,         Department of Microbiology,   Chronic fatigue syndrome is      Mol Diagn 2000
 Mawle AC, Nisenbaum R,       Mount Sinai School of         not associated with              Jun;5(2):155-6
 Reeves WC.                   Medicine, New York, NY,       expression of endogenous
                              USA.                          retroviral p15E.
 Gilbert RB, Kaan R, Lipkin                                 Chronic fatigue: syndrome or     JAMA 2000 Feb
 DM, Lepp M.                                                disease?                         9;283(6):744-5
 Gimenez HB, Cash P,                                        Cytokine Expression and          Journal of Chronic Fatigue   Although underlying metabolic cause of chronic fatigue syndrome (CFS) is unknown, specific defects have
 Laing RBS, Douglas JG.                                     Morphology of in vitro           Syndrome 2000; 5(1): 47      been proposed to exist in the skeletal muscle, the immune system and the neuroendocrine system.
                                                            Grown Monocytes from                                          Peripheral blood mononuclear cells from CFS patients and healthy controls were fractionated as adherent
                                                            Patients with Chronic Fatigue                                 cells (monocyte-enriched fraction) and non-adherent cells. We have investigated some activities of the
                                                            Syndrome                                                      former during in vitro culture. It was observed that the morphology (shape and size) of adherent cells from
                                                                                                                          CFS patients, co-cultivated with homologous non-adherent cells, differed between CFS patients and
                                                                                                                          healthy controls for 21 out of 25 (84%) paired samples (i.e., CFS patient and healthy control). Cytokine
                                                                                                                          expression was examined for the adherent cell population collected from 14 CFS patients and 12 healthy
                                                                                                                          controls. Unstimulated and LPS stimulated tumour necrosis factor-a (TNFa) expression was higher for
                                                                                                                          monocytes from 7 out of 14 CFS patients. Unstimulated interleukin-1b (IL-1b) expression was higher for
                                                                                                                          monocytes from 10 out of 14 CFS patients, whereas LPS-stimulated IL-1b expression was higher for 8 out
                                                                                                                          of 14 CFS patients. The proportional increase of IL-1b and TNFa following LPS stimulation was lower for
                                                                                                                          the majority of the CFS patients studied, suggesting that the monocytes from CFS patients were less
                                                                                                                          responsive to LPS than the respective healthy controls. The basis for the abnormal in vitro monocyte
                                                                                                                          maturation, the elevated unstimulated levels of IL-1b expression and the abnormal response of the
                                                                                                                          monocytes to LPS is unknown. The relevance of these findings to CFS pathogenesis is discussed.
 Glass RT.                                                  The Human/Animal                 Journal of Chronic Fatigue   Objective: To evaluate the interaction between Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
                                                            Interaction in Myalgic           Syndrome 2000; 6(2): 65      (ME/CFS) patients and domestic animals (pets). Design: Retrospective study of criteria-met ME/CFS
                                                            Encephalomyelitis/Chronic                                     patients using a standardized questionnaire which included patient comments. Setting: University medical
                                                            Fatigue Syndrome: A Look at                                   center and ME/CFS support groups throughout the United States. Patients: A total of 127 patients met the
                                                            127 Patients                                                  surveillance criteria of the Centers for Disease Control and Prevention (CDC) for the establishment of the
                                                                                                                          diagnosis of ME/CFS and were included in the study. Measurements: Information from the standardized
                                                                                                                          questionnaire was compiled and appropriate statistical tests, including mean, median, Z test, multivariant
                                                                                                                          analysis, and Chi-square test, were used. This information was compared to national statistical information
                                                                                                                          on animal interaction compiled by the American Veterinary Medicine Association. Results: The most
                                                                                                                          striking result of the study was the association between ME/CFS patients and animals (usually indoor pets)
                                                                                                                          and the number of animals per ME/CFS patient. 97% of the ME/CFS patients had animal contact (expected
                                                                                                                          national contact: 57.9%), with only 2 males and 2 females not reporting animal contact. Reported dog
                                                                                                                          ownership/household for ME/CFS males was 9.5 and for ME/CFS females was 7.9 (expected national
ME Research UK — Database of Research Publications 2000

                                                                                                                     average: 1.52). Reported cat ownership/household for ME/CFS males was 6.1 and for ME/CFS females
                                                                                                                     was 8.7 (expected national average: 1.95). 106 of the respondents (83.5%) reported that their animals (pets)
                                                                                                                     had atypical diseases with symptoms which mimicked ME/CFS in humans. Of the 106 ME/CFS patients,
                                                                                                                     100 (94.3%) either were the primary caregiver for the sick animals or had intimate contact (sleeping with,
                                                                                                                     being bitten or scratched by, or kissing the animal). Conclusions: ME/CFS patients have a significant
                                                                                                                     animal interaction and a large number of these animals have atypical or unusual diseases which at least
                                                                                                                     mimic ME/CFS.
 Glass RT.                                               Abnormal Signs Found in        Journal of Chronic Fatigue   Objective: To evaluate the abnormal signs found in the domestic animals (pets) of Myalgic
                                                         Animals of Myalgic             Syndrome 2000; 6(2): 73      Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. Design: Retrospective study of the
                                                         Encephalomyelitis/Chronic                                   domestic animals (pets) of criteria-met ME/CFS patients using a standardized questionnaire which
                                                         Fatigue Syndrome Patients:                                  included patient comments. Setting: University medical center and ME/CFS support groups throughout the
                                                         A Look at 463 Animals                                       United States. Patients: A total of 127 patients met the surveillance criteria of the Centers for Disease
                                                                                                                     Control and Prevention (CDC) for the establishment of the diagnosis of ME/CFS and were included in the
                                                                                                                     study. This group of patients had a total of 463 domestic animals (pets), of which 348 animals
                                                                                                                     demonstrated abnormal signs and 115 were considered healthy. Measurements: Information from the
                                                                                                                     standardized questionnaire was compiled and appropriate statistical tests, including mean, median, Z test,
                                                                                                                     multivariant analysis, and Chi-square test, were used. Results: One hundred six (83%) of the 127 ME/CFS
                                                                                                                     surveyed reported that at least one of their animals (predominantly domestic pets) showed a wide range of
                                                                                                                     unusual or atypical signs, many of which mimicked the signs and symptoms of ME/CFS. The sick animals'
                                                                                                                     signs were divided into General (40%), Neurological (35%), Gastrointestinal (10%),
                                                                                                                     Reticuloendothelial/Blood (9%), Neoplasia (4%), and Endocrine (2%). One of the most striking result of
                                                                                                                     the study was that 113 of the 127 ME/CFS patients surveyed felt their ME/CFS symptoms were somehow
                                                                                                                     associated with their animals contact. Ninety (71%) of the 127 ME/CFS patients reported that they were
                                                                                                                     the primary caretakers for multiple animals. Other less common findings were: the onset of ME/CFS being
                                                                                                                     associated with obtaining the animal; the onset of ME/CFS being associated with a flea bite episode; prior
                                                                                                                     residents having sick animals and ME/CFS; other family member contracting ME/CFS from their close
                                                                                                                     association with the sick animal (as opposed to their association with the family members who had
                                                                                                                     ME/CFS); ME/CFS symptoms decreasing after the pet leaving or dying. Conclusions: A large number of
                                                                                                                     animals of ME/CFS patients have atypical or unusual diseases which at least mimic ME/CFS. Most of the
                                                                                                                     127 ME/CFS patients surveyed have significant animal interactions.
 Goodwin SS.              Pacific Lutheran University,   Couples' perceptions of        Issues Ment Health Nurs      The purpose of this descriptive correlational study was to describe the differences in couples' perceptions of
                          Tacoma, WA 98447, USA.         wives' CFS symptoms,           2000 Jun;21(4):347-63        wives' Chronic Fatigue Syndrome (CFS) symptoms and to describe the relationship between changing
                               symptom change, and impact                                  symptoms and the marital relationship. The convenience sample of 131 wives with CFS and their spouses
                                                         on the marital relationship.                                reported symptom changes similarly. However, wives reported significantly higher problem levels for
                                                                                                                     constitutional, fatigue, cognition, central nervous system (CNS), musculoskeletal, and allergy symptom
                                                                                                                     domains and significantly less problem levels of mood disturbance domain than their husbands. Husbands
                                                                                                                     who reported more symptom changes also reported lower marital adjustment, less empathy and support
                                                                                                                     from their wives, and more conflict within the relationship. Wives who reported more symptom changes
                                                                                                                     reported lower marital adjustment, less empathy for their husbands, and more conflict within the
                                                                                                                     relationship and had husbands who reported lower marital adjustment and less empathy and support by the
 Gordon R, Michalewski                                   Premovement and Cognitive      Journal of Chronic Fatigue   Brain potentials from normals and patients with Chronic Fatigue Syndrome (CFS) were recorded in four
 HJ, Nguyen T, Starr A.                                  Brain Potentials in Chronic    Syndrome 2000; 5(3/4): 137   different experimental tasks: (1) Auditory target detection, (2) Short-term memory scanning, (3) Fore-
                                                         Fatigue Syndrome                                            warned reaction time (contingent negative variation) and, (4) Self-paced movement. In the auditory target
                                                                                                                     detection task, a slow negative potential shift (maximum at Cz), appears prior to stimulus onset in normals,
                                                                                                                     but is markedly reduced in amplitude in patients with CFS. However, all other sensory and cognitive brain
                                                                                                                     potentials do not differ between normals and CFS. Reaction times are slower in CFS compared to normals.
                                                                                                                     In the memory task, a slow negative shift associated with memory scanning is reduced in patients with
                                                                                                                     CFS. For the fore-warned reaction time and self-paced movement tasks, no differences were found between
                                                                                                                     the patients and normals. The finding of premovement related potential abnormalities in CFS supports the
                                                                                                                     concept that central motor preparation and execution are impaired in CFS. In certain tasks, measures of
ME Research UK — Database of Research Publications 2000

                                                                                                                         neural processes related to sensory processing and attention are normal for these patients. Results from the
                                                                                                                         memory task suggest that neural processes related to short-term memory are also altered in CFS.
 Goudsmit E.                                                Chronic fatigue syndrome        Br J Psychiatry 2000
                                                            and depression                  Nov;177:470 Comment on:
                                                                                            Br J Psychiatry. 2000
 Green J, Romei J, Natelson                                 Stigma and Chronic Fatigue      Journal of Chronic Fatigue   We predicted that the largely female population seeking relief from the incapacitating symptoms of chronic
 BH.                                                        Syndrome                        Syndrome 2000; 5(2): 63      fatigue syndrome (CFS), an enigmatic illness, would feel stigmatized, and that attribution of CFS
                                                                                                                         symptoms to psychological causes by physicians would contribute significantly to the CFS-related stigma.
                                                                                                                         Most subjects scored high on measures of stigma: 95% had feelings of estrangement, 70% believed that
                                                                                                                         others attributed their CFS symptoms to psychological causes, 77% coped by using an educational strategy
                                                                                                                         (disclosure) and 39% saw a need to be secretive about their symptoms in some circumstances. Most
                                                                                                                         subjects (77%) were labeled as `psychological cases' by one or more of the physicians (mean = 8)
                                                                                                                         consulted, but of the 4 stigma measures, only disclosure was related to physician labeling. Such factors as
                                                                                                                         duration of illness and unemployment, dissatisfaction with spouse, and symptom severity correlated
                                                                                                                         significantly with measures of stigma. That many physicians were reportedly ignorant or skeptical of CFS
                                                                                                                         (male more so than female M.D.'s) may influence attempts of CFS patients to legitimize their symptoms by
                                                                                                                         disclosure and lead to high rates of health care system use.
 Greenlee JE, Rose JW.        Neurology Service, Veterans   Controversies in neurological   Semin Neurol                 The past several years have seen major advances in our understanding of neurological infectious diseases,
                              Affairs Medical Center and    infectious diseases.            2000;20(3):375-86            their diagnosis, and their treatment. Along with these advances, however, new information about infectious
                              Department of Neurology,                                                                   agents and new therapeutic options have also introduced both uncertainty and controversy in the approach
                              University of Utah Health                                                                  and management of patients with diseases of the central nervous system. Here, we discuss six such areas:
                              Science Center, Salt Lake                                                                  the long-term efficacy of HAART therapy in treatment of HIV infection; the role of viral infection in
                              City 84148-001, USA.                                                                       chronic fatigue syndrome; Rasmussen's encephalitis as an infectious or autoimmune disease; the spectrum
                                                                                                                         of neurological diseases caused by rickettsial infection; the role of Mycoplasma pneumoniae in human
                                                                                                                         central nervous system disease; and the possible association of Chlamydia pneumoniae and human
                                                                                                                         herpesvirus 6 with multiple sclerosis. Review, Academic
 Grimaud J.                   Service de Neurologie A,      [Relationship between           Rev Neurol (Paris) 2000
                              Hopital Neurologique et       fatigue in multiple sclerosis   Nov;156(11):1044-5
                              Neurochirurgical Pierre       and the chronic fatigue
                              Wertheimer, Lyon.             syndrome].[article in French]
 Hack AD.                                                   Divalent Cations, Hormones,     Journal of Chronic Fatigue   Objectives: The steroid hormone, vitamin D and the peptide hormone, parathormone are reported to
                                                            Psyche and Soma: Four Case      Syndrome 2000; 6(3/4): 117   influence not only bone metabolism, but also other metabolic and nervous, cardiovascular and immune
                                                            Reports                                                      functions, and mood. Regular actions of these hormones depend highly on intracellular magnesium content.
                                                                                                                         Although symptoms are recognized, they usually are not correlated to these hormones. Foregoing case
                                                                                                                         studies have revealed that vitamin D and/or parathormone disorders are common causes of CFS-
                                                                                                                         fibromyalgia like symptoms. Methods: Four patients with chronic fatigue-like symptoms and vitamin D
                                                                                                                         (25OHD3) and parathormone (PTH intact) disorders are illustrated to demonstrate conflicting laboratory
                                                                                                                         results. Patients were treated with 5,000 to 10,000 IU cholecalciferol, plus multiminerals and trace
                                                                                                                         elements. Clinical outcome was assessed and treatment difficulties are reported. Results: Diagnostic pitfalls
                                                                                                                         are shown. Vitamin D and parathormone disorders are not completely detectable by calcium and phosphate
                                                                                                                         screening. In 2 of this 4 demonstrated cases treatable diagnosis would have been missed without
                                                                                                                         endocrinological screening. In the case of undetected long-standing disorder of these hormones,
                                                                                                                         intracellular mineral derangement follows, thus inducing vitamin D resistance and parathormone
                                                                                                                         ineffectiveness which makes therapy difficult. Combining vitamin D therapy with multiminerals possibly
                                                                                                                         may overcome these obstacles. Conclusions: Vitamin D and parathormone disturbance should not be
                                                                                                                         overlooked in chronic fatigue. Appropriate therapy is easy, inexpensive and harmless. Early diagnosis and
                                                                                                                         treatment might be essential to avoid chronic fatigue syndrome. The complexity of diagnosis, therapy and
                                                                                                                         scientific background may lead to a new understanding of ``psycho-somatic'' disease. The relation between
                                                                                                                         intracellular minerals, trace elements, cellular energy supply and responsible hormones should become
ME Research UK — Database of Research Publications 2000

 Hadzi-Pavlovic D, Hickie   Mood Disorders Unit, Prince    Screening for prolonged         Soc Psychiatry Psychiatr     BACKGROUND: The identification of syndromes characterised by persistent and disabling mental and/or
 IB, Wilson AJ, Davenport   of Wales Hospital,             fatigue syndromes: validation   Epidemiol 2000               physical fatigue is of renewed interest in psychiatric epidemiology. This report details the development of
 TA, Lloyd AR, Wakefield    Randwick, NSW, Australia.      of the SOFA scale.              Oct;35(10):471-9             two specific instruments: the SOFA/CFS for identification of patients with chronic fatigue syndrome (CFS)
 D.                         D.Hadzi-                                                                                    in specialist clinics and the SOFA/GP for identification of prolonged fatigue syndromes (PFS) in
                                                                                          community and primary care settings. METHODS: Patients with clinical diagnoses of CFS (n = 770) and
                                                                                                                        consecutive attenders at primary care (n = 1593) completed various self-report questionnaires to assess
                                                                                                                        severity of current fatigue-related symptoms and other common somatic and psychological symptoms.
                                                                                                                        Quality receiver operating characteristic curves were used to derive appropriate cut-off scores for each of
                                                                                                                        the instruments. Comparisons with other self-report measures of anxiety, depression and somatic distress
                                                                                                                        are noted. Various multivariate statistical modelling techniques [latent class analysis (LCA), longitudinal
                                                                                                                        LCA] were utilised to define the key features of PFS and describe its longitudinal characteristics.
                                                                                                                        RESULTS: The SOFA/CFS instrument performs well in specialist samples likely to contain a high
                                                                                                                        proportion of patients with CFS disorders. Cut-off scores of either 1/2 or 2/3 can be used, depending on
                                                                                                                        whether the investigators wish to preferentially emphasise false-negatives or false-positives. Patients from
                                                                                                                        these settings can be thought of as consisting not only of those with a large number of unexplained medical
                                                                                                                        symptoms, but also those with rather specific musculoskeletal and pain syndromes. The SOFA/GP
                                                                                                                        instrument has potential cut-off scores of 1/2 or 2/3, with the latter preferred as it actively excludes all non-
                                                                                                                        PFS cases (sensitivity = 81%, specificity = 100%). Patients with these syndromes in the community
                                                                                                                        represent broader sets of underlying classes, with the emergence of not only musculoskeletal and
                                                                                                                        multisymptomatic disorders, but also persons characterised by significant cognitive subjective impairment.
                                                                                                                        Twelve-month longitudinal analyses of the primary care sample indicated that the underlying class
                                                                                                                        structure was preserved over time. Comparisons with other measures of psychopathology indicated the
                                                                                                                        relative independence of these constructs from conventional notions of anxiety and depression.
                                                                                                                        CONCLUSIONS: The SOFA/GP instrument (which is considerably modified from the SOFA/CFS in terms
                                                                                                                        of anchor points for severity and chronicity) is preferred for screening in primary care and community
                                                                                                                        settings. Patients with PFS and CFS present a range of psychopathology that differs in its underlying
                                                                                                                        structure, cross-sectionally and longitudinally, from coventional notions of anxiety and depression.
 Hannan KL, Berg DE,        Osceola Hospital,              Activation of the coagulation   Blood Coagul Fibrinolysis    Most symptoms of Gulf War Illness (GWI) are similar to Chronic Fatigue Syndrome (CFS) and/or
 Baumzweiger W, Harrison    Kissimmee, Orlando, Florida,   system in Gulf War Illness: a   2000 Oct;11(7):673-8         Fibromyalgia (FM). We investigated whether these symptoms are associated with an activated coagulation
 HH, Berg LH, Ramirez R,    USA.                           potential pathophysiologic                                   system as has been reported in some cases of CFS/FM. The coagulation assays include activation markers
 Nichols D.                                                link with chronic fatigue                                    of the cascade, platelet activation and hereditary risk factors. Our findings show activation of the
                                                           syndrome. A laboratory                                       coagulation system in GWI. This evidence of a hypercoagulable state suggests that symptoms may be due
                                                           approach to diagnosis.                                       to poor blood flow and, therefore, a basis for the potential utility of anticoagulant therapy.
 Hart B, Grace VM.          Department of Feminist         Fatigue in chronic fatigue      Health Care Women Int 2000   Chronic fatigue syndrome (CFS) is a debilitating condition. Approximately 75% of sufferers are women.
                            Studies, University of         syndrome: a discourse           Apr-May;21(3):187-201        The etiology of CFS is debated, but remains inconclusive. "Fatigue" is ill defined and conceptually
                            Canterbury, Christchurch,      analysis of women's                                          problematic. The international multidisciplinary literature on CFS reveals a paucity of studies on women.
                            New Zealand.                   experiential narratives.                                     Qualitative research to analyze women's discourses on CFS is virtually absent. Eleven New Zealand women
                                                                                       of European descent with experience of CFS were interviewed in depth. Within the complex facets of CFS,
                                                                                                                        this article reports specifically on an analysis of discourses on "fatigue." The predominant theme that
                                                                                                                        emerged was that fatigue is articulated as "lack" or absence, which is not representable as an identifiable
                                                                                                                        entity in biomedical terms. Parallels with chronic pain are briefly drawn. We conclude that approaches to
                                                                                                                        CFS must respond to the diverse and complex constructions of the experience of fatigue evident in
                                                                                                                        women's narratives.
 Hazendonk KM, Crowe SF.    School of Psychological        A neuropsychological study      Neuropsychiatry              OBJECTIVE: This study aimed to examine cognitive functioning in postpolio syndrome (PPS) after
                            Science, La Trobe              of the postpolio syndrome:      Neuropsychol Behav Neurol    controlling for the effects of depression and illness behavior. BACKGROUND: Few studies have
                            University, Bundoora,          support for depression          2000 Apr;13(2):112-8         investigated the possible cognitive sequelae of PPS, despite widespread documented subjective complaints
                            Victoria, Australia.           without neuropsychological                                   of "mental fatigue." METHOD: A total of 23 PPS sufferers, 20 polio survivors without PPS, and 22
                                                           impairment.                                                  matched controls were compared using the Beck Depression Inventory-II; the Illness Behaviour
                                                                                                                        Questionnaire; a chronic fatigue syndrome symptom checklist; and several measures of memory, attention,
                                                                                                                        and concentration, including the Brown-Petersen Task, Stroop Test, Austin Maze, California Verbal
                                                                                                                        Learning Test, Trail Making Test, Controlled Oral Word Association Test, and Symbol-Digit Modalities
ME Research UK — Database of Research Publications 2000

                                                                                                                             Test. RESULTS: In those participants with a medically confirmed diagnosis of PPS, there was a
                                                                                                                             significantly higher level of depressive and hypochondriacal symptomatology as compared with the other
                                                                                                                             two groups. Nevertheless, no significant differences existed between the three groups on
                                                                                                                             neuropsychological measures. CONCLUSIONS: These results indicate that the attention and memory
                                                                                                                             difficulties reported by PPS sufferers may be linked to the physical or psychological manifestations of the
                                                                                                                             illness rather than to objective decrements in cognitive performance.
 Heim C, Ehlert U,            Center for Psychobiological       The potential role of            Psychoneuroendocrinology    Representing a challenge for current concepts of stress research, a number of studies have now provided
 Hellhammer DH.               and Psychosomatic Research,       hypocortisolism in the           2000 Jan;25(1):1-35         convincing evidence that the adrenal gland is hypoactive in some stress-related states. The phenomenon of
                              University of Trier, Germany.     pathophysiology of stress-                                   hypocortisolism has mainly been described for patients, who experienced a traumatic event and
                                                                related bodily disorders.                                    subsequently developed post-traumatic stress disorder (PTSD). However, as presented in this review,
                                                                                                                             hypocortisolism does not merely represent a specific correlate of PTSD, since similar findings have been
                                                                                                                             reported for healthy individuals living under conditions of chronic stress as well as for patients with several
                                                                                                                             bodily disorders. These include chronic fatigue syndrome, fibromyalgia, other somatoform disorders,
                                                                                                                             rheumatoid arthritis, and asthma, and many of these disorders have been related to stress. Although
                                                                                                                             hypocortisolism appears to be a frequent and widespread phenomenon, the nature of the underlying
                                                                                                                             mechanisms and the homology of these mechanisms within and across clinical groups remain speculative.
                                                                                                                             Potential mechanisms include dysregulations on several levels of the hypothalamic-pituitary adrenal axis.
                                                                                                                             In addition, factors such as genetic vulnerability, previous stress experience, coping and personality styles
                                                                                                                             may determine the manifestation of this neuroendocrine abnormality. Several authors proposed theoretical
                                                                                                                             concepts on the development or physiological meaning of hypocortisolism. Based on the reviewed findings,
                                                                                                                             we propose that a persistent lack of cortisol availability in traumatized or chronically stressed individuals
                                                                                                                             may promote an increased vulnerability for the development of stress-related bodily disorders. This
                                                                                                                             pathophysiological model may have important implications for the prevention, diagnosis and treatment of
                                                                                                                             the classical psychosomatic disorders.
 Hickie IB, Wilson AJ,        School of Psychiatry,             A randomized, double-blind       J Clin Psychiatry 2000      BACKGROUND: Chronic fatigue syndrome is characterized by prolonged and disabling fatigue and a
 Wright JM, Bennett BK,       University of New South           placebo-controlled trial of      Sep;61(9):643-8             range of neuropsychiatric symptoms including depressed and/or irritable mood. To date, no medical or
 Wakefield D, Lloyd AR.       Wales, Sydney, Australia.         moclobemide in patients with                                 psychotropic therapies have provided clear symptomatic benefit. METHOD: Ninety patients with chronic
                                  chronic fatigue syndrome.                                    fatigue syndrome, diagnosed with our system that approximates CDC criteria, participated in a
                                                                                                                             randomized, placebo-controlled, double-blind trial of 450 to 600 mg/day of moclobemide, a novel
                                                                                                                             reversible inhibitor of monoamine oxidase-A. RESULTS: Fifty-one percent (24/47) of patients receiving
                                                                                                                             moclobemide improved compared with 33% (14/43) of patients receiving placebo (odds ratio = 2.16, 95%
                                                                                                                             confidence interval [CI] = 0.9 to 5.1). Drug response was best characterized symptomatically by an
                                                                                                                             increase in the subjective sense of vigor and energy rather than a reduction in depressed mood. The effect
                                                                                                                             of moclobemide on subjective energy was detectable within the first 2 weeks of treatment and increased
                                                                                                                             across the course of the study. The greatest reduction in clinician-rated disability was in patients with
                                                                                                                             concurrent immunologic dysfunction (mean difference in standardized units of improvement = 0.8, 95% CI
                                                                                                                             = 0.03 to 1.6). CONCLUSION: Moclobemide produces some improvement in key symptoms experienced
                                                                                                                             by patients with chronic fatigue syndrome. This effect is not dependent on the presence of concurrent
                                                                                                                             psychological distress and is likely to be shared with other monoamine oxidase inhibitors.
 Hoskin L, Clifton-Bligh P,   Department of Diabetes,           Bone density and body            Ann N Y Acad Sci 2000
 Hansen R, Fulcher G,         Endocrinology, and                composition in young women       May;904:625-7
 Gates F.                     Metabolic Medicine, Royal         with chronic fatigue
                              North Shore Hospital, St.         syndrome.
                              Leonards, New South Wales,
 Huber M.                     Institut und der Poliklinik fur   [Aspects of occupational         Versicherungsmedizin 2000   In 1997, 30% of the persons going into early retirement because of occupational disability and received
                              Psychosomatik und                 disability in psychosomatic      Jun 1;52(2):66-75           pensions were psychosomatically ill. An additional large number of retirees suffered from untreatable pain
                              Psychotherapie der                disorders].[article in German]                               such as chronic low back pain, some of them might as well have a chronic somatoform pain disorder. The
                              Universitat zu Koln.                                                                           article describes frequent psychosomatic diseases like somatization disorder, fibromyalgia and chronic
ME Research UK — Database of Research Publications 2000

                                                                                                                         fatigue syndrome with respect to their pathophysiology and psychological aspects as well as therapeutic
                                                                                                                         advancements. It is postulated that an interdisciplinary access to these patients early in the course of their
                                                                                                                         illness involving both somatic medical and psychiatric competence is the most promising means to tackle
                                                                                                                         this enormous medical and health protection problem.
 Hurwitz BE, Brownley KA,                                    Chronic Fatigue Syndrome:      Journal of Chronic Fatigue   Chronic Fatigue Syndrome (CFS) is a disorder characterized by a prolonged, debilitating fatigue of
 Fletcher MA, Klimas NG.                                     Evidence Supporting the        Syndrome 2000; 6(2): 45      unknown etiology. In addition, patients with CFS frequently report enhanced fatigue symptoms following
                                                             Hypothesis of a                                             even mild physical exertion, and their tolerance for physical exercise is limited relative to healthy
                                                             Behaviorally-Activated                                      individuals. The physiological mechanisms underlying the excessive fatigue and weakness common to this
                                                             Neuromodulator of Fatigue                                   disorder remain an issue of scientific debate. Collectively, the available data suggest that fatigue in CFS is
                                                                                                                         not due to any neuromuscular dysfunction, per se, but possibly is caused or influenced by some centrally
                                                                                                                         acting mediator that is released during behavioral activities that require physical or mental exertion. In
                                                                                                                         addition to persistent fatigue, there is growing evidence that many CFS patients exhibit alterations in
                                                                                                                         hypothalamic-pituitary-adrenal (HPA) axis and autonomic function, including the inability to maintain the
                                                                                                                         blood pressure response to orthostatic challenge. When an individual engages in mental or physical
                                                                                                                         behavioral activation, there is a release of numerous centrally acting neuromodulators, some of which have
                                                                                                                         been postulated to influence fatigue. This paper examines the evidence supporting a common pathway
                                                                                                                         through which these centrally-mediated psychological and autonomic abnormalities may be linked. It is
                                                                                                                         hypothesized that as a consequence of behavioral activation there is an abnormality in neuromodulator
                                                                                                                         release or action in individuals with CFS, and that this abnormal neuromodulator activity results in
                                                                                                                         increased fatigue. Furthermore, it is postulated that the CNS initiates a counter-regulatory mechanism to
                                                                                                                         reduce the activity of those systems responsible for the production of the neuromodulator; and that the
                                                                                                                         consequence of this counter-regulatory maneuver is the prevailing dysregulation of the autonomic and HPA
                                                                                                                         axes and other dysfunctional cardiovascular and immunological sequelae.
 Jadin CL.                                                   Common Clinical and            Journal of Chronic Fatigue   From 1991, links between CFS and Rickettsial Diseases were uncovered because of their similar clinical
                                                             Biological Windows of CFS      Syndrome 2000; 6(3/4): 133   presentation. Further research linked them even more. Five Rickettsia strains, suspected to be the cause, or
                                                             and Rickettsial Diseases                                    an important factor in CFS, were identified by means of the Giroud Micro-Agglutination test and were
                                                                                                                         widely found to be positive in patients' serum, diagnosed as suffering from CFS, Fibromyalgia,
                                                                                                                         Rheumatoid Arthritis, Multiple Sclerosis, Depression, Psychosis, Heart Diseases, and Auto-Immune
                                                                                                                         Diseases. This finding leads us to submit those originally differently diagnosed patients to the same
                                                                                                                         Tetracycline treatment. This proved to be a great success. The increasing number of patients gave us the
                                                                                                                         opportunity to establish a biological checklist (regardless of the diversity of the pathology) of infections,
                                                                                                                         organs' functions and auto-immune profile. We found the differences in positivity to depend on four
                                                                                                                         factors: length of illness, virulence of germs, cohabitation of germs, and the state of the host immune
                                                                                                                         system. These studies suggest that auto-immune diseases could have an infectious origin. Better knowledge
                                                                                                                         and mastery of the co-factors would be determinant in speeding recovery. With this approach, CFS patients
                                                                                                                         are being treated for the cause of their illness rather than symptomatically.
 Jason LA, Fennell PA,                                       An Investigation of the        Journal of Chronic Fatigue   The present study examined the factor structure of the Fennell Phase Inventory, an instrument designed to
 Klein S, Fricano G, Halpert                                 Different Phases of the CFS    Syndrome 2000; 5(3/4): 35    measure the phases of the illness known as chronic fatigue syndrome. Four hundred participants were
 J.                                                          Illness                                                     recruited and randomly assigned to two equally sized groups. A similar three-factor solution emerged for
                                                                                                                         both samples, suggesting that three phases characterize this illness: a Crisis phase, a Stabilization phase,
                                                                                                                         and an Integration phase. Factor scores on the Crisis Factor were significantly related to levels of fatigue
                                                                                                                         and disability. The Fennell Phase Inventory appears to be a promising way of differentiating the different
                                                                                                                         phases that are experienced by patients with CFS. The implications of these findings are discussed.
 Jason LA, Fennell                                           An Empirical Verification of   Journal of Chronic Fatigue   The Fennell Phase Inventory is an instrument designed to measure the phases typically experienced by
 PA,Taylor RR, Fricano G,                                    the Fennell Phases of the      Syndrome 2000; 6(1): 47      individuals with chronic fatigue syndrome. In a previous study, a three-factor solution emerged. A cluster
 Halpert JA.                                                 CFS Illness                                                 analysis was then conducted using the three mean scores for each individual, and four clusters emerged.
                                                                                                                         These clusters matched the four phases predicted by Fennell. The Fennell Phase Inventory appears to be a
                                                                                                                         promising way of differentiating the phases that are experienced by individuals with CFS.
 Jason LA, Fricano G,          Department of Psychology,     Chronic fatigue syndrome: an   J Clin Psychol 2000          The present study examined the Fennell Phase Inventory, an instrument designed to measure the phases
 Taylor RR, Halpert J,         DePaul University, Chicago,   examination of the phases.     Dec;56(12):1497-508          typically experienced by individuals with chronic fatigue syndrome (CFS). This inventory yields three
 Fennell PA, Klein S, Levine   IL 60614, USA.                                                                            factor scores of Crisis, Stabilization, and Integration. These factor scores have been employed in a cluster
ME Research UK — Database of Research Publications 2000

 S.                                                                                 analysis, yielding four clusters that matched the four phases predicted by Fennell: Crisis, Stabilization,
                                                                                                                      Resolution, and Integration. The present study represents a partial replication study of a prior investigation
                                                                                                                      of the Fennell Phase Inventory by Jason et al. (in press), but that earlier study did not have an independent
                                                                                                                      physician examination to diagnose patients with CFS. In the present study, 65 patients diagnosed with
                                                                                                                      chronic fatigue syndrome by a physician were recruited and administered the Fennell Phase Inventory and
                                                                                                                      other measures assessing CFS-related symptoms, disability, and coping. Each of the 65 patients was
                                                                                                                      classified into one of four predefined clusters measuring a Crisis phase, a Stabilization phase, a Resolution
                                                                                                                      phase, and an Integration phase. Relationships were explored between three of these cluster groupings and
                                                                                                                      measures of symptoms, disability, and coping. Results confirmed Fennell's model, revealing significant
                                                                                                                      differences between the three clusters in terms of levels of disability and modes of coping. Results suggest
                                                                                                                      that the Fennell Phase Inventory accurately differentiates phases of adaptation to illness experienced by
                                                                                                                      individuals with CFS.
 Jason LA, King CP,                                     Defining Chronic Fatigue         Journal of Chronic Fatigue   Accurate diagnosis of Chronic Fatigue Syndrome (CFS) is greatly complicated by the vague wording of
 Taylor RR, Kennedy C.                                  Syndrome: Methodological         Syndrome 2000; 7(3): 17      many of the major diagnostic criteria (i.e., substantial reductions in previous levels of occupational,
                                                        Challenges                                                    educational, social, or personal activities) and the absence of guidelines for health care professionals to
                                                                                                                      follow. The lack of operationally explicit criteria has forced health care professionals to rely heavily on
                                                                                                                      their own clinical judgement, which may be biased by personal and highly idiosyncratic factors. Thus, in
                                                                                                                      the case of CFS, the lack of consensus among clinicians regarding the interpretation and application of the
                                                                                                                      diagnostic criteria has likely produced problems in diagnostic reliability. Data from a recent community
                                                                                                                      based epidemiologic study are presented to illustrate these problems and provide recommendations for
                                                                                                                      improving criterion reliability.
 Jason LA, King CP,                                     U.S. Case Definition of          Journal of Chronic Fatigue   In 1994, researchers from the U.S. Centers for Disease Control and Prevention developed a revised case
 Richman JA, Taylor RR,                                 Chronic Fatigue Syndrome:        Syndrome 2000; 5(3/4): 3     definition of chronic fatigue syndrome (CFS) (1), a complex illness characterized by debilitating fatigue
 Torres SR, Song S.                                     Diagnostic and Theoretical                                    and a number of accompanying flu-like symptoms. Although Fukuda and associates intended to resolve
                                                        Issues                                                        complexities surrounding the classification of individuals with CFS stemming from previous definitional
                                                                                                                      criteria (1), significant problems with the revised criteria endure. This article highlights reliability issues
                                                                                                                      and other conceptual and operational difficulties inherent in the current U.S. definition of CFS (1). We
                                                                                                                      employ case studies derived from a community-based epidemiological study of chronic fatigue syndrome
                                                                                                                      (2) to illustrate examples of the potential for misclassification of individuals with CFS using the current U.
                                                                                                                      S. criteria (1). Moreover, we suggest alternative approaches to classification and ways to operationalize
                                                                                                                      specific concepts embedded in the current U.S. criteria (1).
 Jason LA, Taylor RR,     Department of Psychology,     Chronic fatigue syndrome:        Eval Health Prof 2000        Most chronic fatigue syndrome (CFS) studies are based on information about patients from primary or
 Kennedy CL, Jordan K,    DePaul University, Chicago,   sociodemographic subtypes        Sep;23(3):243-63             tertiary care settings. These patients might not be typical of patients in the general population. This
 Song S, Johnson DE,      Illinois 60614, USA.          in a community-based                                          investigation involved examinations of individuals with CFS from a community-based study. A random
 Torres SR.                                             sample.                                                       sample of 18,675 in Chicago was interviewed by telephone. Individuals with chronic fatigue and at least
                                                                                                                      four minor symptoms associated with CFS were given medical and psychiatric examinations. A group of
                                                                                                                      physicians then diagnosed individuals with CFS, who were then subclassified based on three
                                                                                                                      sociodemographic categories--gender, ethnicity, and work status. Sociodemographic subgroups were
                                                                                                                      analyzed in terms of symptom severity, functional disability, coping, optimism, perceived stress, and
                                                                                                                      psychiatric comorbidity. Women, minorities, and nonworking individuals with CFS reported greater levels
                                                                                                                      of functional disability, symptom severity, and poorer psychosocial functioning than men, Caucasians, and
                                                                                                                      working individuals, suggesting sociodemographic characteristics may be associated with poorer outcomes
                                                                                                                      in urban, community-based samples of CFS individuals.
 Jason LA, Taylor RR,     Department of Psychology,     Chronic fatigue syndrome:        J Nerv Ment Dis 2000         Most studies of chronic fatigue syndrome (CFS) have been based on patients recruited from primary or
 Kennedy CL, Song S,      DePaul University, Chicago,   occupation, medical              Sep;188(9):568-76            tertiary care settings. Patients from such settings might not be typical of patients in the general population.
 Johnson D, Torres S.     Illinois 60614, USA.          utilization, and subtypes in a                                The present investigation involved examining individuals with CFS from a community-based study. A
                                                        community-based sample.                                       random sample of 18,675 respondents in Chicago was first interviewed by telephone. A group of
                                                                                                                      individuals with chronic fatigue accompanied by at least four minor symptoms associated with CFS were
                                                                                                                      given medical and psychiatric examinations. From this sample, a physician review group diagnosed
                                                                                                                      individuals with CFS. Those diagnosed with CFS were subclassified based on a variety of categories,
                                                                                                                      including duration of illness, mode of illness onset, and presence or absence of a stressful life event directly
ME Research UK — Database of Research Publications 2000

                                                                                                                  preceding onset. In addition, we examined medical utilization among those diagnosed with CFS, as well as
                                                                                                                  whether individuals with CFS were disproportionately represented in health care professions. Important
                                                                                                                  differences emerged on measures of sociodemographics, symptoms, and functional disability. The
                                                                                                                  implications of these findings and others are discussed.
 Jason LA, Taylor RR,    Department of Psychology,    Chronic fatigue syndrome,      Psychosom Med 2000 Sep-      OBJECTIVE: The aim of this study was to determine illness comorbidity rates for individuals with chronic
 Kennedy CL.             DePaul University, Chicago   fibromyalgia, and multiple     Oct;62(5):655-63             fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivities (MCS). An additional
                         60614, IL, USA.              chemical sensitivities in a                                 objective was to identify characteristics related to the severity of fatigue, disability, and psychiatric
                    community-based sample of                                   comorbidity in each of these illness groups. METHODS: A random sample of 18,675 residents in Chicago,
                                                      persons with chronic fatigue                                Illinois, was first interviewed by telephone. A control group and a group of individuals with chronic fatigue
                                                      syndrome-like symptoms.                                     accompanied by at least four minor symptoms associated with CFS received medical and psychiatric
                                                                                                                  examinations. RESULTS: Of the 32 individuals with CFS, 40.6% met criteria for MCS and 15.6% met
                                                                                                                  criteria for FM. Individuals with MCS or more than one diagnosis reported more physical fatigue than
                                                                                                                  those with no diagnosis. Individuals with more than one diagnosis also reported greater mental fatigue and
                                                                                                                  were less likely to be working than those with no diagnosis. Individuals with CFS, MCS, FM, or more than
                                                                                                                  one diagnosis reported greater disability than those with no diagnosis. CONCLUSIONS: Rates of
                                                                                                                  coexisting disorders were lower than those reported in prior studies. Discrepancies may be in part
                                                                                                                  attributable to differences in sampling procedures. People with CFS, MCS, or FM endure significant
                                                                                                                  disability in terms of physical, occupational, and social functioning, and those with more than one of these
                                                                                                                  diagnoses also report greater severity of physical and mental fatigue. The findings illustrate differences
                                                                                                                  among the illness groups in the range of functional impairment experienced.
 Jay SJ.                                              Tobacco use and chronic        Arch Intern Med 2000 Aug
                                                      fatigue syndrome,              14-28;160(15):2398, 2401
                                                      fibromyalgia, and              Comment on: Arch Intern
                                                      temporomandibular disorder.    Med. 2000 Jan
 Jiaxu C, Weiyi Y.                                    Treatment of Chronic Fatigue   Journal of Chronic Fatigue   Chronic fatigue syndrome (CFS) is a severe, debilitating disorder, which prominently features self-reported
                                                      Syndrome with Chinese          Syndrome 2000; 5(1): 61      impairments in concentration and short-term memory, and disturbances in sleep and emotions, all of which
                                                      Medicine                                                    can affect any one and seriously affect quality of life. In 1987, the Centers for Disease Control and
                                                                                                                  Prevention (CDC) defined CFS as persistent or relapsing fatigue, with at least 50% reduction of baseline
                                                                                                                  activity level lasting for at least 6 months, as one of the main symptoms. Since its cause is still unknown,
                                                                                                                  treatment of CFS has been palliative and has included usually orally administered products, such as
                                                                                                                  vitamin B12, vitamin C, folic acid, iron, magnesium, essential fatty acids, coenzyme Q10 and nicotinamide
                                                                                                                  adenine dinucleotide (NADH), among others. The latter therapeutic modalities can only relieve some
                                                                                                                  symptoms to some extent, but cannot fundamentally eliminate fatigue. It is, therefore, urgent to seek safe
                                                                                                                  and effective drugs for the treatment of fatigue. We propose here that regulating homeostasis and
                                                                                                                  enhancing immunity are important for the treatment of fatigue. In China, many Chinese herbs with such
                                                                                                                  functions have been proven effective, an observation which opens the possibility of a new therapeutic
                                                                                                                  method of eliminating fatigue with traditional Chinese medicine (TCM).
 Jordan KM, Ayers PM.                                 Prevalence of Fatigue and      Journal of Chronic Fatigue   A community-based screening of over 12,000 households was conducted in order to determine the
 Jahn SC, Taylor KK,                                  Chronic Fatigue Syndrome-      Syndrome 2000; 6(1): 3       prevalence of fatigue and CFS-like illness in a sample of 5 to 17 year olds. Results indicate that over 4% of
 Huang C-F, Richman J,                                Like Illness in Children and                                the sample was fatigued and that 2. 05% were diagnosed with CFS-like illness. Adolescents had a slightly
 Jason LA.                                            Adolescents                                                 higher rate of CFS-like illness (2.91%) than did pre-pubescent children (1.96%). Those with CFS-like
                                                                                                                  illness were almost evenly divided between male (47.5%) and female (52. 5%). Youngsters of Latino origin
                                                                                                                  had the highest representation in the CFS-like group. Symptom data, family patterns, and other data are
                                                                                                                  presented for both the CFS-like group and the entire sample.
 Kahn MF.                                             Chronic fatigue syndrome.      Joint Bone Spine
                                                      New developments.              2000;67(5):359-61
 Kaur G, Kulkarni SK.                                 Comparative Study of           Journal of Chronic Fatigue   This study examined the effects and comparative efficacy of various antidepressants and herbal
                                                      Antidepressants and Herbal     Syndrome 2000; 6(2): 23      psychotropic drugs in a mouse model of chronic fatigue. Animals were subjected daily to forced swimming
                                                      Psychotropic Drugs in a                                     (Porsolt's forced swimming test) and the duration of the immobility period was recorded in 6-minute
                                                      Mouse Model of Chronic                                      sessions on each day for 7 days. Chronic forced swimming resulted in significant increases in immobility
ME Research UK — Database of Research Publications 2000

                                                       Fatigue                                                      time on day 7 as compared to day 1 in control mice. Pretreatment with imipramine (10 mg/kg, i.p.),
                                                                                                                    desipramine (10 mg/kg, i.p.), tranylcypromine (10 mg/kg, i.p.), alprazolam (0.5 mg/kg, i.p.), fluoxetine (10
                                                                                                                    mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) produced significant decreases in immobility time as compared
                                                                                                                    to controls on each day. Similar decreases in immobility periods were observed with herbal psychotropic
                                                                                                                    preparations-Withania somnifera root extract (100 mg/kg, p.o.), BR-16AR (200 mg/kg, p.o.), siotoneR
                                                                                                                    granules (200 mg/kg, p.o.) and evening primrose oil (0.2 ml/20g, p.o.). However, trazodone and idazoxan
                                                                                                                    failed to modify the immobility times on all the days. The present observations underscore the established
                                                                                                                    use of antidepressants in providing symptomatic relief of fatigue in Chronic Fatigue Syndrome (CFS)
                                                                                                                    patients and further reinforce the potential therapeutic usefulness of herbal psychotropic preparations in
                                                                                                                    CFS patients.
 Kavelaars A, Kuis W,    Department of Pediatric       Disturbed neuroendocrine-       J Clin Endocrinol Metab      The present study was designed to investigate the interaction between neuroendocrine mediators and the
 Knook L, Sinnema G,     Immunology, Wilhelmina        immune interactions in          2000 Feb;85(2):692-6         immune system in chronic fatigue syndrome (CFS). We examined the sensitivity of the immune system to
 Heijnen CJ.             Children's Hospital of the    chronic fatigue syndrome.                                    the glucocorticoid agonist dexamethasone and the beta2-adrenergic agonist terbutaline in 15 adolescent
                         University Medical Center                                                                  girls with CFS and 14 age- and sex-matched controls. Dexamethasone inhibits T-cell proliferation in
                         Utrecht, The Netherlands.                                                                  healthy controls and in CFS patients. However, the maximal effect of dexamethasone on T-cell
                                                                                    proliferation is significantly reduced in CFS patients as compared with controls. The beta2-adrenergic
                                                                                                                    receptor agonist terbutaline inhibits tumor necrosis factor-alpha production and enhances interleukin-10
                                                                                                                    production by monocytes. Our data demonstrate that the capacity of a beta2-adrenergic agonist to regulate
                                                                                                                    the production of these two cytokines is also reduced in CFS patients. We did not observe differences in
                                                                                                                    baseline or CRH-induced cortisol and ACTH between CFS patients and controls. Baseline noradrenaline
                                                                                                                    was similar in CFS and controls, whereas baseline adrenaline levels were significantly higher in CFS
                                                                                                                    patients. We conclude that CFS is accompanied by a relative resistance of the immune system to regulation
                                                                                                                    by the neuroendocrine system. Based on these data, we suggest CFS should be viewed as a disease of
                                                                                                                    deficient neuroendocrine-immune communication.
 Kerr JR, Cunniffe VS.   Departments of Medical        Antibodies to parvovirus B19    Rheumatology (Oxford) 2000   OBJECTIVE: To determine the incidence and significance of antibodies to the parvovirus B19 non-
                         Microbiology and Virology,    non-structural protein are      Aug;39(8):903-8              structural (NS1) protein in B19-infected persons during acute infection and convalescence. METHODS:
                         Manchester Royal Infirmary,   associated with chronic but                                  The B19 NS1 protein was expressed in SF9 cells using the baculovirus expression system and was used to
                         Oxford Road, Manchester       not acute arthritis following                                prepare immunofluorescence slides. These were used in a fluorescent antibody test to determine anti-B19
                         M13 9WL, UK.                  B19 infection.                                               NS1 IgG in a well-characterized cohort of 53 persons at the time of acute B19 infection and again after a
                                                                                                                    follow-up period of 26-85 months. Results were examined for statistical significance by the use of Fisher's
                                                                                                                    exact test. RESULTS: NS1 antibodies were detected in five of 32 persons with acute B19 infection (four
                                                                                                                    with arthritis) and 10 of 53 persons with past B19 infection (six with chronic arthritis and two with chronic
                                                                                                                    arthritis and chronic fatigue syndrome). Regarding the correlation of NS1 antibodies and arthritis, at the
                                                                                                                    time of acute infection four of 24 persons with arthritis had NS1 antibodies detected compared with one of
                                                                                                                    eight persons with any other symptoms (P: = 1). During convalescence, eight of 20 persons with chronic
                                                                                                                    arthritis had NS1 antibodies compared with two of 33 with symptoms of any other category (all except one
                                                                                                                    were asymptomatic) (P: = 0.007). All 10 patients with NS1 antibodies during convalescence had arthritis
                                                                                                                    during acute infection, which persisted in eight persons until the time of follow-up. CONCLUSION:
                                                                                                                    Antibodies to parvovirus B19 NS1 protein are associated with chronic but not with acute arthritis after B19
 Klimas N, Wallace M.                                  Toward optimal health: the      J Womens Health Gend
                                                       experts discuss chronic         Based Med 2000
                                                       fatigue syndrome: interview     Jun;9(5):477-82
                                                       by Jodi Godfrey Meisler.
 Knook L, Kavelaars A,   Department of Pediatric       High nocturnal melatonin in     J Clin Endocrinol Metab      Decreased quality of sleep is frequently reported by chronic fatigue syndrome (CFS) patients. The pineal
 Sinnema G, Kuis W,      Immunology, Wilhelmina        adolescents with chronic        2000 Oct;85(10):3690-2       hormone melatonin is involved in regulation of sleep. We analyzed the nocturnal rise in melatonin in 13
 Heijnen CJ.             Children Hospital of the      fatigue syndrome.                                            adolescent CFS patients and 15 healthy age-matched controls. Saliva samples were collected at hourly
                         University Medical Center                                                                  intervals between 1700 and 0200 h. Nocturnal saliva melatonin levels were significantly higher in CFS
                         Utrecht, The Netherlands.                                                                  patients, compared with controls, at midnight, 0100 h, and 0200 h (P < 0.001). No differences were
                                                                                                                    observed in timing of melatonin increase in saliva between patients and controls. Time of sleep onset and
                                                                                                                    duration of sleep did not differ significantly between patients and controls. However, all CFS patients and
ME Research UK — Database of Research Publications 2000

                                                                                                                       only one of the controls in our study group reported unrefreshing sleep. Our data demonstrate that sleep
                                                                                                                       problems in adolescents with CFS are associated with increased melatonin levels during the first part of the
                                                                                                                       night. Based on these data, we suggest that there is no indication for melatonin supplementation in
                                                                                                                       adolescents with CFS.
 Komaroff AL. Editorial                                    The biology of chronic          Am J Med 2000
                                                           fatigue syndrome.               Feb;108(2):169-71Comment
                                                                                           in: Am J Med. 2000 Aug
                                                                                           15;109(3):257-9 Comment
                                                                                           on: Am J Med. 2000
 Korszun A, Young EA,        Department of Psychological   Follicular phase                J Rheumatol 2000            OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are clinically overlapping stress
 Engleberg NC, Masterson     Medicine, University of       hypothalamic-pituitary-         Jun;27(6):1526-30           associated disorders. Neuroendocrine perturbations have been noted in both syndromes, and they are more
 L, Dawson EC, Spindler K,   Wales College of Medicine,    gonadal axis function in                                    common in women, suggesting abnormalities of gonadal steroid hormones. We tested the hypothesis that
 McClure LA, Brown MB,       Cardiff, UK.                  women with fibromyalgia                                     women with FM and CFS manifest abnormalities of the hypothalamic-pituitary-gonadal (HPG) hormonal
 Crofford LJ.                  and chronic fatigue                                         axis. METHODS: We examined the secretory characteristics of estradiol, progesterone, follicle stimulating
                                                           syndrome.                                                   hormone (FSH), and luteinizing hormone (LH), including a detailed analysis of LH in premenopausal
                                                                                                                       women with FM (n = 9) or CFS (n = 8) during the follicular phase of the menstrual cycle compared to
                                                                                                                       matched healthy controls. Blood was collected from an indwelling intravenous catheter every 10 min. over
                                                                                                                       a 12 h period. LH was assayed from every sample; pulses of LH were identified by a pulse-detection
                                                                                                                       program. FSH and progesterone were assayed from a pool of hourly samples for the 12 h period and
                                                                                                                       estradiol from samples pooled over four 3 h time periods. RESULTS: There were no significant differences
                                                                                                                       in FSH, progesterone, or estradiol levels in patients versus controls. There were no significant differences in
                                                                                                                       pulsatile secretion of LH. CONCLUSION: There is no indication of abnormal gonadotropin secretion or
                                                                                                                       gonadal steroid levels in this small, but systematic, study of HPG axis function in patients with FM and
 Korszun A.                  Department of Psychological   Sleep and circadian rhythm      Curr Rheumatol Rep 2000     Fibromyalgia (FM) is a syndrome of generalized muscle pain that is also associated with equally distressing
                             Medicine, University of       disorders in fibromyalgia.      Apr;2(2):124-30             symptoms of sleep disturbance and fatigue. FM shows clinical overlap with other stress-associated
                             Wales College of Medicine,                                                                disorders, including chronic fatigue syndrome (CFS) and depression. All of these conditions have the
                             Heath Park Cardiff CF4                                                                    features of disrupted sleep patterns and dysregulated biologic circadian rhythms, such as stress hormone
                             4XN, UK.                                                                                  secretion. This review focuses on the role of sleep and circadian rhythm disorders in FM and, in the
                                                                                           absence of any specific treatment for FM, presents a pragmatic therapeutic approach aimed at identifying
                                                                                                                       and treating comorbid sleep and depressive disorders, optimizing sleep habits, and judicious use of
                                                                                                                       pharmacologic agents.
 Kuratsune H.                Department of Hematology      [Chronic fatigue                Ryoikibetsu Shokogun
                             and Oncology, Osaka           syndrome].[article in           Shirizu 2000;(32):531-4
                             University Graduate School    Japanese]
                             of Medicine.
 Lane R.                     Division of Clinical          Chronic fatigue syndrome: is    West J Med 2000
                             Neurosciences and             it physical?                    Dec;173(6):416-7
                             Psychological Medicine
                             Imperial College School of
                             Medicine London UK
 Lane R. Editorial                                         Chronic fatigue syndrome: is    J Neurol Neurosurg
                                                           it physical                     Psychiatry 2000
                                                                                           Sep;69(3):289 Comment on:
                                                                                           J Neurol Neurosurg
                                                                                           Psychiatry. 2000
 Lawrie SM, MacHale SM,      Department of Psychiatry,     The difference in patterns of   Psychol Med 2000            BACKGROUND: Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) share many
 Cavanagh JT, O'Carroll      University of Edinburgh.      motor and cognitive function    Mar;30(2):433-42            symptoms and aetiological factors but may have different neurobiological underpinnings. We wished to
ME Research UK — Database of Research Publications 2000

 RE, Goodwin GM.                                          in chronic fatigue syndrome                                   determine the profile of the biological variables disturbed in CFS and MDD, and identify any critical
                                                          and severe depressive illness.                                factors that differentiate the disorders. METHODS: Thirty patients with CFS, 20 with MDD and 15 healthy
                                                                                                                        controls matched group-wise for age and sex were recruited. Subjects were given a detailed battery of
                                                                                                                        motor and cognitive tests, including measures of psychomotor speed, memory and maximal voluntary
                                                                                                                        muscle contraction in both the morning and evening that were balanced to avoid order effects. RESULTS:
                                                                                                                        CFS patients generally performed worse on cognitive tests than healthy controls, but better than patients
                                                                                                                        with MDD. Both patient groups had markedly impaired motor function compared with healthy controls.
                                                                                                                        MDD subjects showed a significantly greater diurnal improvement in maximal voluntary contraction than
                                                                                                                        healthy controls. CONCLUSIONS: Patients with CFS and MDD show similarly substantial motor
                                                                                                                        impairment, but cognitive deficits are generally more marked in MDD. Diurnal changes in some functions
                                                                                                                        in MDD may differentiate the disorder from CFS.
 Laylander JA.                                            A Nutrient/Toxin Interaction     Journal of Chronic Fatigue   Recent research suggests that Chronic Fatigue Syndrome (CFS), Fibromyalgia Syndrome (FMS), and
                                                          Theory of the Etiology and       Syndrome 2000; 5(1): 67      Persian Gulf Syndrome (PGS) may represent the effects of dysfunctions involving the central and/or
                                                          Pathogenesis of Chronic                                       peripheral nervous system, neuroendocrine system, neuromuscular system, immune system, metabolism, or
                                                          Pain-Fatigue Syndromes:                                       sleep patterns. Each systemic dysfunction is accepted here as being central to these syndromes but not
                                                          Part I                                                        causal. This two-part review introduces the theory that the syndromes listed above represent finitely
                                                                                                                        variable combinations of multiple systemic dysfunctions which all share a common underlying etiology at
                                                                                                                        the subcellular level: magnesium deficiency plus concomitant fluoride excess (MDFE). The theory is
                                                                                                                        introduced in Part I; detailed evidence which supports the theory is presented in Part II. Treatment
                                                                                                                        suggestions are listed at the end of Part II through a call for clinical trials to test this theory.
 Laylander JA.                                            A Nutrient/Toxin Interaction     Journal of Chronic Fatigue   This second part of the review paper covers the evidence in favor of the theory which proposes that Chronic
                                                          Theory of the Etiology and       Syndrome 2000; 5(1): 93      Fatigue Syndrome, Fibromyalgia Syndrome, and Persian Gulf Syndrome represent finitely variable
                                                          Pathogenesis of Chronic                                       combinations of multiple systemic dysfunctions which share a common underlying etiology at the
                                                          Pain-Fatigue Syndromes:                                       subcellular level: magnesium deficiency plus concomitant fluoride excess (MDFE). Treatment suggestions
                                                          Part II                                                       are listed at the end of the manuscript through a call for clinical trials to test the theory presented.
 Le Bon O, Hoffmann G,       Brugmann University          How significant are primary      Sleep Res Online             In order to study both the prevalence of Primary Sleep Disorders (PSD) and sleepiness, and their
 Murphy J, De Meirleir K,    Hospital, Brussels 1020,     sleep disorders and sleepiness   2000;3(2):43-8               association to the Chronic Fatigue Syndrome (CFS), 46 unselected outpatients (34 women, mean age 36.5)
 Cluydts R, Pelc I.          Belgium.                     in the chronic fatigue                                        were examined clinically and underwent two nights of all-night polysomnography and multiple sleep
                         syndrome?                                                     latency tests (MSLT). Forty-six percent presented with a Sleep Apnea/Hypopnea Syndrome Index
                                                                                                                        (AHI>=5), 5% with a Periodic Limb Movements syndrome. No subject received a diagnosis of Narcolepsy
                                                                                                                        or Idiopathic Hypersomnia. Thirty percent showed the presence of objective sleepiness as measured by
                                                                                                                        MSLT<10 minutes. Objective and subjective measures of sleepiness were not associated with CFS, nor
                                                                                                                        with the double diagnosis of CFS and a PSD. The presence of PSD or sleepiness was not associated with
                                                                                                                        any of the clinical scales that were used to measure anxiety, depression, somatisation, physical or mental
                                                                                                                        fatigue, or functional status impairment. Fifty-four percent of CFS patients had no PSD, and 69% no
                                                                                                                        sleepiness. These patients could not be distinguished clinically from patients having a PSD or from those
                                                                                                                        with sleepiness. Therefore, it is unlikely that CFS is simply a somatic expression of any PSD observed in
                                                                                                                        our sample or of sleepiness per se.
 Lee S, Yu H, Wing Y, Chan   Department of Psychiatry,    Psychiatric morbidity and        Am J Psychiatry 2000         OBJECTIVE: The authors' goal was to examine the prevalence and experience of psychiatric morbidity
 C, Lee AM, Lee DT, Chen     The Chinese University of    illness experience of primary    Mar;157(3):380-4             among primary care patients with chronic fatigue in Hong Kong. METHOD: One hundred adult patients
 C, Lin K, Weiss MG.         Hong Kong, Prince of Wales   care patients with chronic                                    with medically unexplained fatigue for 6 or more months were assessed with the Explanatory Model
                             Hospital, Shatin.            fatigue in Hong Kong.                                         Interview Catalogue, psychopathological rating scales, and an enhanced version of the Structured Clinical
                                                                                           Interview for DSM-III-R. RESULTS: The lifetime prevalence of DSM-III-R depressive and anxiety
                                                                                                                        disorders was 54%. Current depressive and anxiety disorders were identified in 28 patients, who exhibited
                                                                                                                        more psychopathology and functional impairment than other patients. Thirty-three patients had somatoform
                                                                                                                        pain disorder, and 30 had undifferentiated somatoform disorder, but most of them could also be diagnosed
                                                                                                                        as having shenjing shuairuo (weakness of nerves) and, to a lesser extent, ICD-10 neurasthenia. Chronic
                                                                                                                        fatigue syndrome diagnosed according to the 1988 Centers for Disease Control criteria was rare (3%) and
                                                                                                                        atypical. Generally, patients mentioned fatigue if asked, but pains (36%), insomnia (20%), and worries
                                                                                                                        (13%) were the most troublesome symptoms. Most patients attributed illness onset to psychosocial sources.
                                                                                                                        CONCLUSIONS: Psychiatric morbidity was common among primary care patients with chronic fatigue.
ME Research UK — Database of Research Publications 2000

                                                                                                                    Subthreshold psychiatric morbidity was very common and was more validly represented by the disease
                                                                                                                    construct of shenjing shuairuo or neurasthenia than somatoform disorder.
 Leonhardt T.                Medicinkliniken i         [Chronic fatigue syndrome--     Lakartidningen 2000 Jan
                             Vanersborg-Trollhattan.   old wine in new                 19;97(3):182-4
                                                       bottles].[article in Swedish]
 Levine PH, Clauw DJ,                                  Silicone Breast Implants,       Journal of Chronic Fatigue   Clinical studies have continued to suggest a relationship between silicone breast implants and chronic
 Claman HC, Robertson                                  Chronic Fatigue Syndrome        Syndrome 2000; 7(1): 53      fatigue syndrome. Extensive epidemiologic studies, however, indicate that such a relationship is likely to
 AD, Ketch L.                                          and Fibromyalgia                                             be by chance and the successful lawsuits against producers of silicone breast implants are based on factors
                                                                                                                    other than scientific proof. We present several perspectives on this issue which are probably relevant to
                                                                                                                    other reports of putative etiologic agents for chronic fatigue syndrome.
 Levine PH, Pilkington D,                              Chronic Fatigue Syndrome        Journal of Chronic Fatigue   Several studies have indicated a link between chronic fatigue syndrome (CFS) and cancer, most of them
 Strickland P, Peterson D.                             and Cancer                      Syndrome 2000; 7(1): 29      based on anecdotal observations. We have attempted to use more population-based data to determine if the
                                                                                                                    reported relationship is meaningful. Two outbreaks of a fatiguing illness which included well documented
                                                                                                                    cases of CFS were evaluated ten years after the reported outbreak for long-term effects, particularly cancer.
                                                                                                                    We found an unusual pattern of cancer which, in view of an increased incidence of brain tumors and non-
                                                                                                                    Hodgkin's lymphoma (NHL) reported in other studies involving CFS, indicates the need for further study.
                                                                                                                    At the present time this link, which is often presumed to be due to immune dysfunction, has not yet been
                                                                                                                    documented. Not all CFS patients have apparent dysregulation of the immune system and a single
                                                                                                                    causative agent is highly unlikely, making the study of two heterogeneous illnesses, CFS and cancer, highly
                                                                                                                    problematic. With the continuing focus on subgroups, however, this area of research may prove to be more
 Levine S.                                             Borna Disease Virus Proteins    Journal of Chronic Fatigue   Bornavirus is a member of a newly recognized virus family, Bornaviridae, and is neurotropic for a wide
                                                       in Patients with CFS            Syndrome 2000; 5(3/4): 199   range of animal species, including birds, rodents, horses, and humans. Although little is known about its
                                                                                                                    mode of transmission and it has not been clearly linked to any human disease, an association between
                                                                                                                    bornaviruses and neuropsychiatric disorders has been suggested. Several researchers have also isolated this
                                                                                                                    organism from patients who meet the clinical criteria for the Chronic Fatigue Syndrome (CFS). However,
                                                                                                                    due to non-standardization of assay protocols, lack of a large study population and the possibility of
                                                                                                                    contamination in certain laboratory settings, the true prevalence of Bornaviral proteins and their possible
                                                                                                                    role in the pathogenesis of at least a subgroup of CFS patients remains undefined. We analyzed the serum
                                                                                                                    immune reactivity to Borna Disease Virus (BDV) in 77 CFS patients and in 33 healthy normal controls
                                                                                                                    using an ELISA based assay of 3 different recombinant BDV proteins. Of the 6 samples that displayed
                                                                                                                    immunoreactivity to 2 or more BDV proteins, S were from patients (83.3%). Two samples, both from CFS
                                                                                                                    patients, displayed immunoreactivity to 3 BDV proteins.
 Lindberg NE, Lindberg E.                              [Use available knowledge--      Lakartidningen 2000 May
                                                       also when it is not complete.   24;97(21):2651-2
                                                       Current example: chronic
                                                       fatigue syndrome,
                                                       fibromyalgia].[Article in
 Lloyd AR, Hickie IB,                                  Illness or disease? The case    Med J Aust 2000 May
 Loblay RH.                                            of chronic fatigue syndrome.    15;172(10):471-2
 Lofqvist AH.                                          Functional Somatic              Journal of Chronic Fatigue   This hypothesis deals with reactions described in functional somatic syndromes and postulates that these
                                                       Syndromes-A Matter of           Syndrome 2000; 7(2): 75      reactions be described in terms of active/passive and external/internal. The reflex character of these
                                                       Stress Response Patterns?                                    reactions explain the variation in symptom intensity which in turn is projected to doctors as feelings of
                                                                                                                    lacking understanding, especially when disease parameters are normal.
 Loganovsky KN.                                        Vegetative-Vascular             Journal of Chronic Fatigue   The aim of this study was to determine whether the Chronic Fatigue Syndrome (CFS) definition could be
                                                       Dystonia and Osteoalgetic       Syndrome 2000; 7(3): 3       applicable to the assessment of the medical aftermath of radioecological disasters and to investigate a
                                                       Syndrome or Chronic Fatigue                                  possible psychophysiological basis of fatigue in Chernobyl accident survivors. One hundred randomly
                                                       Syndrome as a Characteristic                                 selected clean-up workers of the Chernobyl accident who presented with complains of fatigue were
                                                       After-Effect of                                              examined neuropsychiatrically using MMPI profiles, Quantitative Electroencephalography (QEEG) and
                                                       Radioecological Disaster:                                    Somatosensory evoked potentials (SSEP). Twenty-six percent of them met the CFS diagnostic criteria.
ME Research UK — Database of Research Publications 2000

                                                           The Chernobyl Accident                                         Their absorbed radiation doses were less than 0.3 Sv, an exposure level that is not expected to produce a
                                                           Experience                                                     clear deterministic radiation effect. Clinical symptomatology included persistent fatigue, odd skin
                                                                                                                          sensations, bizarre feelings in bones, muscles and joints, irritability, headache, vertigo, pain in the chest
                                                                                                                          area, emotional lability, irritability, lack of concentration and memory, cognitive deterioration, depression
                                                                                                                          signs and sleep disorders. Liquidators with CFS had the characteristic MMPI profile with increased
                                                                                                                          hypochondria, depression, clear hypochondria, schizophrenia, hysteria, psychasthenia, and bizarre sensory
                                                                                                                          perception scales. Spectral analysis of QEEG showed lateralised (left-sided) increase of q-power (P <
                                                                                                                          0.001) and lateralised (left-sided) decrease of a-power (P < 0.001) and lateralised (left-sided) increase of b-
                                                                                                                          power (P < 0.01). SSEP were characterized by increased latencies and decreased amplitudes. SSEP
                                                                                                                          significantly differed by topographic abnormalities in the left temporoparietal area in liquidators with CFS.
                                                                                                                          Associations between schizophrenia-like, hypochondriac and psychasthenic psychopathology and an
                                                                                                                          increase of latency of SSEP P300 and N400 in liquidators with CFS were revealed. Thus, ``Vegetative-
                                                                                                                          Vascular Dystonia'' and ``Osteoalgetic Syndrome'' cases following exposure to ionizing radiation as a result
                                                                                                                          of the Chernobyl accident can be classified as CFS cases. The psychophysiological basis of fatigue in
                                                                                                                          liquidators consists of dysfunction of the cortico-limbical structures of the left, dominating, hemisphere.
                                                                                                                          CFS is one of the most important consequences of radioecological disaster, which results from an
                                                                                                                          interaction of different hazardous environmental factors.
 MacHale SM, Lawrie SM,     University Department of                                       192: Br J Psychiatry 2000      BACKGROUND: Patients with chronic fatigue syndrome (CFS) and depressive illness share many, but not
 Cavanagh JT, Glabus MF,    Psychiatry, Royal Edinburgh                                    Jun;176:550-6Comment in:       all, features. AIMS: To test the hypothesis that patients with CFS have abnormal cerebral perfusion, that
 Murray CL, Goodwin GM,     Hospital.                                                      Br J Psychiatry. 2000          differs from that in patients with depressive illness. METHOD: We recruited 30 patients with CFS who
 Ebmeier KP.                                                                               Nov;177:470 Cerebral           were not depressed, 12 depressed patients and 15 healthy volunteers. Regional cerebral perfusion at rest
                                                                                           perfusion in chronic fatigue   was assessed using region of interest (ROI) and voxel-based statistical parametric mapping (SPM)
                                                                                           syndrome and depression.       techniques. RESULTS: On SPM analysis there was increased perfusion in the right thalamus, pallidum and
                                                                                                                          putamen in patients with CFS and in those with depressive illness. CFS patients also had increased
                                                                                                                          perfusion in the left thalamus. Depressed patients differed from those with CFS in having relatively less
                                                                                                                          perfusion of the left prefrontal cortex. The results were similar on ROI analysis. CONCLUSIONS:
                                                                                                                          Abnormal cerebral perfusion patterns in CFS subjects who are not depressed are similar but not identical to
                                                                                                                          those in patients with depressive illness. Thalamic overactivity may be a correlate of increased attention to
                                                                                                                          activity in CFS and depression; reduced prefrontal perfusion in depression may be associated with the
                                                                                                                          greater neuropsychological deficits in that disorder.
 Mahowald ML, Mahowald      Department of Medicine,        Nighttime sleep and daytime     1389-9457 2000 Jul             For the past 25 years, the 'alpha-delta NREM sleep abnormality' has been used by some as a defining or
 MW.                        Minneapolis Veteran's          functioning (sleepiness and     1;1(3):195-207                 legitimizing marker for poorly defined rheumatic diseases such as fibromyalgia and chronic fatigue
                            Administration Medical         fatigue) in less well-defined                                  syndrome. Comprehensive review of the literature reveals no support for such a conclusion. Most studies
                            Center, University of          chronic rheumatic diseases                                     involve small numbers of patients. The lack of control subjects, non-standardized recording techniques, and
                            Minnesota Medical School,      with particular reference to                                   confusion between tonic and phasic alpha frequency activity patterns make comparison difficult. There is
                            MN, Minneapolis, USA           the 'alpha-delta NREM sleep                                    much evidence that this sleep EEG pattern is not only non-specific, but may actually reflect a sleep
                                                           anomaly'                                                       maintaining process. The 'sleep fragmentation' theory of the complaint of non-restorative sleep in this
                                                                                                                          patient population is invalidated by the fact that conditions characterized by severe sleep fragmentation,
                                                                                                                          such as obstructive sleep apnea, are not associated with musculoskeletal symtoms. It is difficult to attribute
                                                                                                                          musculoskeletal symptoms to disorders of sleep in view of the fact that the only organ of the body known to
                                                                                                                          benefit from sleep, or to be adversely affected by lack of sleep, is the brain. It is concluded that
                                                                                                                          fibromyalgia and chronic fatigue syndrome are associated with subjective sleep complaints, but do not
                                                                                                                          represent sleep disorders.
 Manu P. Editorial Review                                  Chronic fatigue syndrome:       Am J Med 2000
 Review, Tutorial                                          the fundamentals still apply    Feb;108(2):172-3Comment
                                                                                           in: Am J Med. 2000 Aug
                                                                                           15;109(3):257-9 and Am J
                                                                                           Med. 2000 Feb;108(2):99-
 Manuel y Keenoy B,         Laboratory of Endocrinology,   Magnesium status and            J Am Coll Nutr 2000            OBJECTIVE: Magnesium deficiency and oxidative stress have both been identified as pathogenic factors
 Moorkens G, Vertommen J,   University of Antwerp,         parameters of the oxidant-      Jun;19(3):374-82               in aging and in several age-related diseases. The link between these two factors is unclear in humans
ME Research UK — Database of Research Publications 2000

 Noe M, Neve J, De Leeuw I.   Belgium.                      antioxidant balance in                                         although, in experimental animals, severe Mg deficiency has been shown to lead to increased oxidative
                                                            patients with chronic fatigue:                                 stress. METHODS: The relationship between Mg body stores, dietary intakes and supplements on the one
                                                            effects of supplementation                                     hand and parameters of the oxidant-antioxidant balance on the other was investigated in human subjects.
                                                            with magnesium.                                                RESULTS: The study population consisted of 93 patients with unexplained chronic fatigue (median age 38
                                                                                                                           years, 25% male, 16% smokers and 54% with Chronic Fatigue Syndrome (CFS). Mg deficient patients
                                                                                                                           (47%) had lower total antioxidant capacity in plasma (p=0.007) which was related to serum albumin. Mg
                                                                                                                           deficient patients whose Mg body stores did not improve after oral supplementation with Mg (10
                                                                                                                           mg/kg/day) had persistently lower blood glutathione levels (p=0.003). In vitro production of thiobarbituric
                                                                                                                           acid reactive substances (TBARS) by non-HDL lipoproteins incubated with copper was related to serum
                                                                                                                           cholesterol (p<0.001) but not to Mg or antioxidants and did not improve after Mg supplementation. In
                                                                                                                           contrast, velocity of formation of fluorescent products of peroxidation (slope) correlated with serum
                                                                                                                           vitamin E (p<0.001), which was, in turn, related to Mg dietary intakes. Both slope and serum vitamin E
                                                                                                                           improved after Mg supplementation (p<0.001). CONCLUSIONS: These results show that the lower
                                                                                                                           antioxidant capacity found in moderate Mg deficiency was not due to a deficit in Mg dietary intakes and
                                                                                                                           was not accompanied by increased lipid susceptibility to in vitro peroxidation. Nevertheless, Mg
                                                                                                                           supplementation was followed by an improvement in Mg body stores, in serum vitamin E and its
                                                                                                                           interrelated stage of lipid peroxidation.
 Maquet D, Croisier JL,       Universite de Liege,          [Fibromyalgia in the year        Rev Med Liege 2000            Musculoskeletal pain is common in the population. Several pathologies like fibromyalgia (FM), chronic
 Crielaard JM.                Medecine de l'Appareil        2000].[article in French]        Nov;55(11):991-7              fatigue syndrome (CFS) or spasmophilia are associated with functional myalgia. The etiology of FM
                              Locomoteur.                                                                                  remains elusive, but the diagnosis is well established. The criteria for the classification are widespread pain
                                                                                                                           combined with tenderness at 11 or more of the 18 specific tender points sites. The prevalence is 2% in the
                                                                                                                           general population. This article reviews recent data on the pathophysiology and treatment of FM.
 Martinsen EW.                Psykiatrisk klinikk,          [Physical activity for mental    Tidsskr Nor Laegeforen 2000   BACKGROUND: About 50% of the population will be affected by a mental disorder during their lifetime;
                              Sentralsjukehuset i Sogn og   health].[article in Norwegian]   Oct 20;120(25):3054-6         the most common forms are mood and anxiety disorders and abuse of or dependence on drugs or alcohol.
                              Fjordane, Forde.                                                                             The standard forms of therapy are medication and various forms of psychotherapy. The cost of treating
                                                                                                 disease is escalating, and the health care system will never be able to meet the need for treatment in this
                                                                                                                           large group of patients. Hence, development of effective self help strategies is important. MATERIAL
                                                                                                                           AND METHODS: In this paper, the scientific basis for promoting exercise as treatment for mental
                                                                                                                           disorders is evaluated on the basis of a review of the literature. RESULTS: Beneficial psychological effects
                                                                                                                           of exercise are best documented for mild to moderate forms of unipolar depression and chronic fatigue
                                                                                                                           syndrome; in these disorders, exercise is an alternative to traditional forms of treatment. A therapeutic
                                                                                                                           effect may also be achieved in panic and generalised anxiety disorder, schizophrenia, conversion and
                                                                                                                           somatoform pain disorder, and alcohol abuse and dependence. INTERPRETATION: Beneficial effects of
                                                                                                                           exercise are well documented. A simple and inexpensive approach like exercise is helpful and might be
                                                                                                                           important for public health.
 McGregor NR, Niblett S,                                    The Biochemistry of Chronic      Journal of Chronic Fatigue    Background: Chronic pain and fatigue represent major reasons for seeking medical treatments, however,
 Clifton Bligh P, Dunstan                                   Pain and Fatigue                 Syndrome 2000; 7(1): 3        the mechanisms are poorly understood. Onset of these disorders has been associated with events
 RH, Fulcher G, Hoskin L,                                                                                                  (infections, trauma, stress) which initiate a host response requiring increased energy demands. Objectives:
 Butt HL, Roberts TK,King                                                                                                  To investigate the biochemical mechanisms of chronic pain and fatigue. Methods: Data will be presented
 K, Klineberg I.                                                                                                           from 4 separate investigations of CFS and myofascial pain syndrome (MFPS) patients, and from age/sex-
                                                                                                                           matched controls, using metabolite profiling techniques. Results: Several types of chronic pain and fatigue
                                                                                                                           disorders were discerned on the basis of their biochemistry. The metabolic events associated with chronic
                                                                                                                           pain were distinct from those associated with chronic fatigue. The investigations have shown that chronic
                                                                                                                           pain was associated with reductions in serum sodium, changes in urinary volume and output of amino and
                                                                                                                           organic acids, increases in levels of markers of tissue damage (ALT, AST), and increases in the tyrosine:
                                                                                                                           leucine ratio, which represents alterations in protein turnover. Fatigue was associated with alterations in
                                                                                                                           urine excretion of amino and organic acids associated with tricarboxylic acid cycle (TCA) function. Levels
                                                                                                                           of RNase-L were correlated with the expression of chronic fatigue related symptoms and were a good
                                                                                                                           marker for CFS. Increased carriage of toxin-producing coagulase negative staphylococci was evident in
                                                                                                                           MFPS and CFS patients, and this carriage was correlated with increased tyrosine: leucine ratios and pain
                                                                                                                           severity. The toxin producing staphylococci appear to be a co-morbid pathogen that contributes to CFS
ME Research UK — Database of Research Publications 2000

                                                                                                                            patient morbidity. Conclusion: These studies indicated that changes in nitrogen homeostasis were
                                                                                                                            associated with pain and fatigue symptoms and carriage of certain pathogens may sustain or exaggerate the
                                                                                                                            chronic disorder.
 McKenzie R, Reynolds JC,      Division of Microbiology        Decreased bone mineral          J Rheumatol 2000             OBJECTIVE: While osteoporosis and bone fractures are clearly recognized side effects of high dose
 O'Fallon A, Dale J, Deloria   and Infectious Diseases,        density during low dose         Sep;27(9):2222-6             glucocorticoids, the effect of low dose glucocorticoids remains controversial. We investigated the effect of
 M, Blackwelder W, Straus      National Institute of Allergy   glucocorticoid administration                                3 months of low dose hydrocortisone on bone mineral density (BMD). METHODS: Subjects, 18 to 55
 SE.                           and Infectious Diseases,        in a randomized, placebo                                     years old with chronic fatigue syndrome and no medical or psychiatric illness requiring medication, were
                               National Institute of Health,   controlled trial.                                            randomized in a double blind, placebo controlled trial to receive oral hydrocortisone, 13 mg/m2 body
                               Bethesda, Maryland , USA.                                                                    surface area every morning and 3 mg/m2 every afternoon (25 to 35 mg/day, equivalent to about 7.5 mg
                                                                                                                            prednisone/day) or placebo for 12 weeks. Before and after treatment BMD of the lumbar spine was
                                                                                                                            measured by dual energy x-ray absorptiometry. RESULTS: We studied 23 subjects (19 women, 4 men). For
                                                                                                                            the 11 hydrocortisone recipients there was a mean decrease in BMD: mean change from baseline of the
                                                                                                                            lateral spine was -2.0% (95% CI -3.5 to -0.6. p = 0.03) and mean change of the anteroposterior spine was -
                                                                                                                            0.8% (95% CI -1.5 to -0.1, p = 0.06). Corresponding changes for the 12 placebo recipients were +1.0%
                                                                                                                            (95% CI -1.0 to 3.0, p = 0.34) and +0.2% (95% CI -1.4 to 1.5, p = 0.76). CONCLUSION: A 12 week
                                                                                                                            course of low dose glucocorticoids given to ambulatory subjects with chronic fatigue syndrome was
                                                                                                                            associated with a decrease in BMD of the lumbar spine. This decrease was statistically significant in lateral
                                                                                                                            spine measurements and nearly so in anteroposterior spine measurements.
 Merz S.                        [Chronic fatigue syndrome.      Lakartidningen 2000 Aug
                                                               Different definitions are       23;97(34):3642-4
                                                               confusing].[article in
 Moorkens G, Berwaerts J,      Departments of Internal         Characterization of pituitary   Clin Endocrinol (Oxf) 2000   OBJECTIVE: Previous studies have revealed that hormonal disturbances may accompany the chronic
 Wynants H, Abs R.             Medicine; Endocrinology,        function with emphasis on       Jul;53(1):99-106             fatigue syndrome (CFS). Changes in the secretion of the pituitary-adrenal axis have been demonstrated, as
                               University Hospital Antwerp,    GH secretion in the chronic                                  well as abnormalities in the GH-IGF-I axis. However, data have not always been well characterized and
                               Belgium.                        fatigue syndrome.                                            were sometimes conflicting. The small number of CFS patients investigated in earlier studies may have
                                                                                                                            played a role in the interpretation of the results. SUBJECTS AND DESIGN: Hormonal testing was
                                                                                                                            performed in 73 nonobese CFS patients and nonobese 21 age-and gender-matched healthy controls. We
                                                                                                                            investigated GH, ACTH and cortisol responses to insulin-induced hypoglycaemia. In a subgroup of patients
                                                                                                                            arginine and clonidine stimulation for GH was also performed. Nocturnal secretion of GH, ACTH and
                                                                                                                            cortisol were determined. Serum levels of IGF-I, prolactin, TSH, and free thyroxine were also measured.
                                                                                                                            Visceral fat mass was assessed by CT scanning. RESULTS: GH response to insulin induced hypoglycaemia
                                                                                                                            assessed by peak value (17.0 +/- 13.1 microg/l vs. 22. 1 +/- 9.8 microg/l; P = 0.01) and by AUC (450.0 +/-
                                                                                                                            361.3 microg/l vs. 672.3 +/- 393.0 microg/l; P = 0.002) was significantly decreased in CFS patients vs.
                                                                                                                            controls. Nocturnal GH secretion assessed by GH peak value (5.4 +/- 3.7 vs. 9.0 +/- 5.1 microg/l; P = 0.44)
                                                                                                                            and by AUC (34.4 +/- 20.2 vs. 67.4 +/- 43.1; P = 0.045) was also significantly impaired in CFS patients.
                                                                                                                            Arginine and clonidine administration showed no differences in GH secretion between CFS patients and
                                                                                                                            controls. In the CFS group, GH peak values were significantly higher after ITT than after arginine (P =
                                                                                                                            0.017) or clonidine (P = 0.001). No differences in serum IGF-I levels were found between CFS patients and
                                                                                                                            controls. Except for a significantly lower nocturnal cortisol peak value, no differences were found in ACTH
                                                                                                                            and cortisol secretion between CFS patients and controls. Significantly higher serum prolactin levels (7.4
                                                                                                                            +/- 4.7 microg/l vs. 4.4 +/- 1.3 microg/l; P = 0.004) and significantly higher serum TSH levels (1.6 +/- 1.0
                                                                                                                            mU/l vs. 1.0 +/- 0.4 mU/l; P = 0.011) were found in CFS patients. Serum free thyroxine was comparable in
                                                                                                                            both groups. Visceral fat mass was significantly higher in CFS patients (86.6 +/- 34.9 cm2 vs. 51.5 +/- 15.7
                                                                                                                            cm2; P < 0.001). CONCLUSIONS: We observed a significant impairment of GH response during insulin-
                                                                                                                            induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These changes did, however,
                                                                                                                            not lead to different concentrations in serum IGF-I. The clinical expression of this inadequate GH secretion
                                                                                                                            can thus be questioned, although the alteration in body composition may be related to this relative GH
                                                                                                                            deficiency. Significantly increased prolactin and TSH levels were found when compared to controls. These
                                                                                                                            findings give support to the hypothesis of a decreased dopaminergic tone in CFS. Further investigations are
                                                                                                                            required in order to identify specific adaptations within the neurotransmitter system in CFS and to
ME Research UK — Database of Research Publications 2000

                                                                                                                          determine the clinical importance of the impaired GH homeostasis.
 Naschitz JE, Rosner I,       Department of Internal        The capnography head-up tilt     Semin Arthritis Rheum 2000   OBJECTIVES: To compare the hemodynamic and ventilatory responses to autonomic challenge evoked by
 Rozenbaum M, Gaitini L,      Medicine A, Bnai Zion         test for evaluation of chronic   Oct;30(2):79-86              upright tilt table testing in patients with chronic fatigue syndrome (CFS) to healthy individuals.
 Bistritzki I, Zuckerman E,   Medical Center and Bruce      fatigue syndrome.                                             METHODS: Thirty-two consecutive patients with CFS and 32 healthy volunteers were evaluated with the
 Sabo E, Yeshurun D.          Rappaport Faculty of                                                                        aid of the recently introduced capnography head-up tilt test (CHUTT). The main outcome measures were
                              Medicine, Technion-Israel                                                                   values of blood pressure (BP), heart rate (HR), respiratory rate (RR), and end-tidal pressure of co2
                              Institute of Technology,                                                                    (ETPco2) recorded during recumbence and tilt. In addition, the end points of vasodepressor and
                              Haifa, Israel.                                                                              cardioinhibitory reactions, hyperventilation (defined by ETPco2 <25 mm Hg) and the postural tachycardia
                                                                                                                          syndrome, were recorded. RESULTS: The BP, HR, RR, and ETPco2 recorded during recumbence were
                                                                                                                          similar in both groups. During tilt, patients with CFS developed significantly lower systolic BP, diastolic
                                                                                                                          BP, and ETPco2, and a significant rise in HR and RR (P<.01). In CFS patients, the postural tachycardia
                                                                                                                          syndrome occurred in 44%, vasodepressor reaction in 41%, cardioinhibitory reaction in 13%, and
                                                                                                                          hyperventilation in 31% of cases. One or more end points of the CHUTT were reached in 78% of patients
                                                                                                                          with CFS but in none of the controls (P<.0001). CONCLUSIONS: In most patients with CFS, a spectrum
                                                                                                                          of abnormal homeostatic reactions is diagnosed with the aid of the CHUTT. Data provided by the CHUTT
                                                                                                                          may reinforce the clinical diagnosis by adding objective and unbiased criteria to the subjective assessment
                                                                                                                          of CFS.
 Nawab SS, Miller CS, Dale    Section on Biological         Self-reported sensitivity to     Psychiatry Res 2000 Jul      Two hundred and twenty-five subjects, including normal volunteers and patients with previously
 JK, Greenberg BD,            Rhythms, National Institute   chemical exposures in five       24;95(1):67-74               documented seasonal affective disorder (SAD), chronic fatigue syndrome (CFS), Cushing's syndrome,
 Friedman TC, Chrousos        of Mental Health, Bethesda,   clinical populations and                                      Addison's disease and obsessive-compulsive disorder (OCD), completed a self-rated inventory of reported
 GP, Straus SE, Rosenthal     MD 20892-1390, USA.           healthy controls.                                             sensitivity to various chemical exposures. Patients with CFS, Addison's disease and SAD self-reported
 NE.                                                                                         more sensitivity to chemical exposures than normal controls. In addition, women reported more sensitivity
                                                                                                                          than men. This report suggests that chemical sensitivity may be a relevant area to explore in certain medical
                                                                                                                          and psychiatric populations. A possible relationship between reported chemical sensitivity and
                                                                                                                          hypothalamic-pituitary-adrenal (HPA)-axis functioning is discussed.
 Neeck G, Crofford LJ.        Department of                 Neuroendocrine                   Rheum Dis Clin North Am      A large body of data from a number of different laboratories worldwide has demonstrated a general
                              Rheumatology, University of   perturbations in fibromyalgia    2000 Nov;26(4):989-1002      tendency for reduced adrenocortical responsiveness in CFS. It is still not clear if this is secondary to CNS
                              Giessen, Bad Nauheim,         and chronic fatigue                                           abnormalities leading to decreased activity of CRH- or AVP-producing hypothalamic neurons. Primary
                              Germany.                      syndrome.                                                     hypofunction of the CRH neurons has been described on the basis of genetic and environmental influences.
                                                                                      Other pathways could secondarily influence HPA axis activity, however. For example, serotonergic and
                                                                                                noradrenergic input acts to stimulate HPA axis activity. Deficient serotonergic activity in CFS has been
                                                                                                                          suggested by some of the studies as reviewed here. In addition, hypofunction of sympathetic nervous
                                                                                                                          system function has been described and could contribute to abnormalities of central components of the
                                                                                                                          HPA axis. One could interpret the clinical trial of glucocorticoid replacement in patients with CFS as
                                                                                                                          confirmation of adrenal insufficiency if one were convinced of a positive therapeutic effect. If patient
                                                                                                                          symptoms were related to impaired activation of central components of the axis, replacing glucocorticoids
                                                                                                                          would merely exacerbate symptoms caused by enhanced negative feedback. Further study of specific
                                                                                                                          components of the HPA axis should ultimately clarify the reproducible abnormalities associated with a
                                                                                                                          clinical picture of CFS. In contrast to CFS, the results of the different hormonal axes in FMS support the
                                                                                                                          assumption that the distortion of the hormonal pattern observed can be attributed to hyperactivity of CRH
                                                                                                                          neurons. This hyperactivity may be driven and sustained by stress exerted by chronic pain originating in
                                                                                                                          the musculoskeletal system or by an alteration of the CNS mechanism of nociception. The elevated activity
                                                                                                                          of CRH neurons also seems to cause alteration of the set point of other hormonal axes. In addition to its
                                                                                                                          control of the adrenal hormones, CRH stimulates somatostatin secretion at the hypothalamic level, which,
                                                                                                                          in turn, causes inhibition of growth hormone and thyroid-stimulating hormone at the pituitary level. The
                                                                                                                          suppression of gonadal function may also be attributed to elevated CRH because of its ability to inhibit
                                                                                                                          hypothalamic luteinizing hormone-releasing hormone release; however, a remote effect on the ovary by the
                                                                                                                          inhibition of follicle-stimulating hormone-stimulated estrogen production must also be considered.
                                                                                                                          Serotonin (5-HT) precursors such as tryptophan (5-HTP), drugs that release 5-HT, or drugs that act directly
                                                                                                                          on 5-HT receptors stimulate the HPA axis, indicating a stimulatory effect of serotonergic input on HPA
                                                                                                                          axis function. Hyperfunction of the HPA axis could also reflect an elevated serotonergic tonus in the CNS
ME Research UK — Database of Research Publications 2000

                                                                                                                         of FMS patients. The authors conclude that the observed pattern of hormonal deviations in patients with
                                                                                                                         FMS is a CNS adjustment to chronic pain and stress, constitutes a specific entity of FMS, and is primarily
                                                                                                                         evoked by activated CRH neurons.
 Neerinckx E, Van            Department of                  Attributions in chronic         J Rheumatol 2000             OBJECTIVE: To evaluate the attributions of patients with chronic fatigue syndrome (CFS) and
 Houdenhove B, Lysens R,     Psychosomatic                  fatigue syndrome and            Apr;27(4):1051-5             fibromyalgia (FM) consulting at a university fatigue and pain clinic. METHODS: Consecutive attenders (n
 Vertommen H, Onghena P.     Rehabilitation, University     fibromyalgia syndrome in                                     = 192) who met the CFS criteria (n = 95) or FM criteria (n = 56) or who had medically unexplained chronic
                             Hospital Katholieke            tertiary care.                                               pain and/or fatigue without meeting both criteria (CPF) (n = 41) were evaluated. All subjects completed an
                             Universiteit Leuven,                                                                        extended form of the Cause of Illness Inventory. Descriptive statistics, frequency analyses, chi-square tests,
                             Belgium.                                                                                    one-way analysis of variance, and sequential Fisher least significant difference tests were performed.
                             eneerinckx@mail.phlimburg.                                                                  RESULTS: In total, 48 patients reported physical causes only and 10 patients psychosocial causes only; the
                             be                                                                                          majority (70%) mentioned both types of causes. With regard to the contents, "a chemical imbalance in my
                                                                                                                         body" (61%), "a virus" (51%), "stress" (61%), and "emotional confusion" (40%) were reported most
                                                                                                                         frequently. The diagnostic label did not have a significant influence on number and type of attributions.
                                                                                                                         Small to moderate effect sizes were registered concerning the association of specific attributions and
                                                                                                                         diagnosis, sex, duration of the symptoms, contact with a self-help group, and premorbid depression.
                                                                                                                         CONCLUSION: The majority of patients with CFS, FM, and CPF reported a great diversity of attributions
                                                                                                                         open to a preferably personalized cognitive behavioral approach. Special attention should be paid to
                                                                                                                         patients with symptoms existing for more than one year and those who had previous contacts with a self-
                                                                                                                         help group. They particularly show external, stable, and global attributions that may compromise feelings
                                                                                                                         of self-efficacy in dealing with the illness.
 Nicolson GL. Nasralla MY,                                  Role of Mycoplasmal             Journal of Chronic Fatigue   Bacterial and viral infections are purported to be associated with several fatigue illnesses, including
 Franco AR, De Meirleir K,                                  Infections in Fatigue           Syndrome 2000; 6(3/4): 23    Chronic Fatigue Syndrome (CFS), Fibromyalgia Syndrome (FMS), Gulf War Illnesses (GWI) and
 Nicolson NL, Ngwenya R,                                    Illnesses: Chronic Fatigue                                   Rheumatoid Arthritis (RA), as causative agents, cofactors or opportunistic infections. We and others have
 Haier J.                                                   and Fibromyalgia                                             looked for the presence of invasive pathogenic mycoplasmal infections in patients with CFS, FMS, GWI
                                                            Syndromes, Gulf War Illness                                  and RA and have found significantly more mycoplasmal infections in CFS, FMS, GWI and RA patients
                                                            and Rheumatoid Arthritis                                     than in healthy controls. Most patients had multiple mycoplasmal infections (more than one species).
                                                                                                                         Patients with chronic fatigue as a major sign often have different clinical diagnoses but display overlapping
                                                                                                                         signs/symptoms similar to many of those found in CFS/FMS. When a chronic fatigue illness, such as GWI,
                                                                                                                         spreads to immediate family members, they present with similar signs/symptoms and mycoplasmal
                                                                                                                         infections. CFS/FMS/GWI patients with mycoplasmal infections generally respond to particular antibiotics
                                                                                                                         (doxycycline, minocycline, ciprofloxacin, azithromycin and clarithromycin), and their long-term
                                                                                                                         administration plus nutritional support, immune enhancement and other supplements appear to be
                                                                                                                         necessary for recovery. Examination of the efficacy of antibiotics in recovery of chronic illness patients
                                                                                                                         reveals that the majority of mycoplasma-positive patients respond and many eventually recover. Other
                                                                                                                         chronic infections, such as viral infections, may also be involved in various chronic fatigue illnesses with
                                                                                                                         or without mycoplasmal and other bacterial infections, and these multiple infections could be important in
                                                                                                                         causing patient morbidity and difficulties in treating these illnesses.
 Nisenbaum R, Jones A,       Centers for Disease Control    Longitudinal analysis of        Ann Epidemiol 2000 Oct       PURPOSE: To determine the effect of chronic fatigue syndrome (CFS) illness duration and onset type on
 Jones J, Reeves W.          and Prevention, Atlanta, GA,   symptoms reported by            1;10(7):458                  the likelihood of reporting a symptom during successive follow-up periods.METHODS: In 1997, a two-
                             USA                            patients with chronic fatigue                                phase RDD survey in Wichita, Kansas, was conducted to estimate the prevalence of CFS. Phase I identified
                                                            syndrome.                                                    56,154 respondents 18-69 years of age and screened for severe fatigue, extreme tiredness or exhaustion
                                                                                                                         lasting for 1 month or longer. In phase II an equal number of fatigued (n = 7,176) and randomly selected
                                                                                                                         non-fatigued subjects were asked about 8 CFS and 13 non-CFS symptoms, as well as the presence of
                                                                                                                         specific medical and psychiatric conditions. Eligible respondents were clinically evaluated to establish CFS
                                                                                                                         diagnosis. Phase II respondents were re-contacted at 12- (n = 4,331) and 24-months (n = 4,266) for
                                                                                                                         additional follow-up and diagnosis. In this study we considered symptoms reported as being present most
                                                                                                                         of the time during each successive observation period. Generalized estimating equations were used to
                                                                                                                         model symptoms over time and to address study questions. Such a model accounts for correlations among
                                                                                                                         repeated symptoms for each subject. We used an auto-regressive structure for the correlation matrix,
                                                                                                                         assuming the correlations between each pair of repeated symptoms should decrease as the time between
                                                                                                                         symptoms increased.RESULTS: There were 74 CFS patients who had been ill for 1 to 20 years (median =
ME Research UK — Database of Research Publications 2000

                                                                                                                         6.3 years). Among these, 46 reported gradual and 28 reported sudden onset. Symptoms fluctuated over the
                                                                                                                         course of illness. However, only stomach pain (non-CFS symptom) was more likely to be reported as
                                                                                                                         duration of illness increased (p < 0.05). There was no association between onset type and the likelihood of
                                                                                                                         reporting a symptom during an interview, except that chills and severe headaches were more likely to be
                                                                                                                         reported by sudden cases.CONCLUSIONS: The likelihood of expressing CFS and non-CFS symptom
                                                                                                                         "most of the time" is the same across years of illness. More analyses are warranted to consider expression
                                                                                                                         of symptoms for >/=6 months and severe symptoms.
 Nores J-M.                                                The Philosophy of Pain: New      Journal of Chronic Fatigue   This article examines the concept of physical pain and its relationship to philosophy within the context of
                                                           Concepts                         Syndrome 2000; 5(2): 99      ethics. The first question posing a problem is: should pain be added to or included in the list of the five
                                                                                                                         senses? Whether sensation is present or not, pain does exist. Pain is part of the ``immediate data of
                                                                                                                         consciousness'' dear to philosophers. Pain is at the heart of ontology, philosophy of the being and
                                                                                                                         existential ontology, which places existence above essence. Pain is mine and teaches me that I exist. Pain
                                                                                                                         conveys my existence more than thought. Why shouldn't we enrich Descartes's cogito? ``I suffer, therefore I
                                                                                                                         exist'' rather than ``I think, therefore I exist'' or even ``I am something which suffers'' rather than ``I am a
                                                                                                                         thing which thinks'' by Descartes. As pain is the witness of their existence, other beings resemble me. The
                                                                                                                         use of physical pain to cause harm is the best transition towards the following question, that is, what is the
                                                                                                                         relationship between pain and evil or harm? This is a question which is primordial and concerns
                                                                                                                         philosophers, moralists and theologians. There is just pain which is harmful and is our enemy to be
                                                                                                                         conquered. This would seem to be what philosophy has to teach those of us who are doctors fighting pain.
 Nowotny N, Kolodziejek J.                                 9 Demonstration of borna         J Infect Dis 2000
                                                           disease virus nucleic acid in    May;181(5):1860-2
                                                           a patient with chronic fatigue   Comment on: J Infect Dis.
                                                           syndrome                         1999 Nov;180(5):1695-.
 Oldmeadow M.                                              Chronic fatigue syndrome.        Aust Fam Physician 2000
                                                                                            Jan;29(1):76-7Comment in:
                                                                                            Aust Fam Physician. 2000
 Pall ML.                                                  Elevated Peroxynitrite as the    Journal of Chronic Fatigue   In an earlier paper, I proposed that chronic fatigue syndrome (CFS) is caused by a response to infection,
                                                           Cause of Chronic Fatigue         Syndrome 2000; 7(4): 45      involving the induction of inflammatory cytokines which induce, in turn, the inducible nitric oxide
                                                           Syndrome: Other Inducers                                      synthase, producing elevated nitric oxide. Nitric oxide reacts with superoxide to form the potent oxidant,
                                                           and Mechanisms of                                             peroxynitrite. Six positive feedback loops were proposed by which peroxynitrite may stay elevated, acting
                                                           Symptom Generation                                            to increase levels of both nitric oxide and superoxide, which react to form more peroxynitrite. This vicious
                                                                                                                         cycle based on known biochemistry is proposed to be the central cause of CFS. The current paper discusses
                                                                                                                         additional inducers which may act by increasing nitric oxide (physical or psychological trauma) or
                                                                                                                         increasing superoxide (hypoxia) and the role of orthostatic intolerance, Ehlers-Danlos syndrome, excessive
                                                                                                                         exercise, exercise intolerance and carbon monoxide in inducing hypoxia and consequently superoxide and
                                                                                                                         peroxynitrite. The major symptoms of CFS can all be interpreted as relatively direct consequences of the
                                                                                                                         pathophysiology predicted by the elevated peroxynitrite theory of CFS. Attractive mechanisms are
                                                                                                                         proposed by which elevated peroxynitrite, nitric oxide and/or related physiological changes may induce
                                                                                                                         CFS symptoms including fatigue, immune dysfunction, learning and memory dysfunction, multi-organ
                                                                                                                         pain, exercise intolerance/postexertional malaise and orthostatic intolerance. Roles are discussed for six
                                                                                                                         factors likely to influence the frequency of CFS induction in response to infection or other inducing events.
 Pall ML.                    Department of                 Elevated, sustained              Med Hypotheses 2000          The etiology of chronic fatigue syndrome (CFS) has been both obscure and highly contentious, leading to
                             Biochemistry/Biophysics and   peroxynitrite levels as the      Jan;54(1):115-25             substantial barriers to both clear diagnosis and effective treatment. I propose here a novel hypothesis of
                             Program in Basic Medical      cause of chronic fatigue                                      CFS in which either viral or bacterial infection induces one or more cytokines, IL-1beta IL-6, TNF-alpha
                             Sciences, Washington State    syndrome.                                                     and IFN-gamma. These induce nitric oxide synthase (iNOS), leading to increased nitric oxide levels. Nitric
                             University, Pullman 99164-                                                                  oxide, in turn, reacts with superoxide radical to generate the potent oxidant peroxynitrite. Multiple
                             4660, USA.                                                                                  amplification and positive feedback mechanisms are proposed by which once peroxynitrite levels are
                                                                                              elevated, they tend to be sustained at a high level. This proposed mechanism may lower the HPA axis
                                                                                                                         activity and be maintained by consequent lowered glucocorticoid levels. Similarities are discussed among
                                                                                                                         CFS and autoimmune and other diseases previously shown to be associated with elevated peroxynitrite.
ME Research UK — Database of Research Publications 2000

                                                                                                                     Multiple pharmacological approaches to the treatment of CFS are suggested by this hypothesis.
 Patarca-Montero R, Mark                                Immunology of Chronic           Journal of Chronic Fatigue   A review of the literature on the immunology of CFS reveals that people who have Chronic Fatigue
 T, Fletcher MA, Klimas                                 Fatigue Syndrome                Syndrome 2000; 6(3/4): 69    Syndrome (CFS) have two basic problems with immune function that have been documented by most
 NG.                                                                                                                 research groups: 1. immune activation, as demonstrated by elevation of activated T lymphocytes, including
                                                                                                                     cytotoxic T cells, as well as elevations of circulating cytokines; and 2. poor cellular function, with low
                                                                                                                     natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent
                                                                                                                     immunoglobulin deficiencies, most often IgG1 and IgG3. These findings have a waxing and waning
                                                                                                                     temporal pattern which is consistent with episodic immune dysfunction (with predominance of so called T-
                                                                                                                     helper type 2 and proinflammatory cytokines and low NKCC and lymphoproliferation) that can be
                                                                                                                     associated as cause or effect of the physiological and psychological function derangement and/or activation
                                                                                                                     of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of
                                                                                                                     disease with remission/exacerbation cycles. Therapeutic intervention aimed at induction of a more
                                                                                                                     favorable cytokine expression pattern and immune status is discussed.
 Pearn J.                                               Differential Diagnosis: The     Journal of Chronic Fatigue   The chronic fatigue syndrome comprises one of the most challenging issues in contemporary medicine. The
                                                        Challenge of Chronic Fatigue    Syndrome 2000; 7(4): 17      condition remains distressing for patients and perplexing to medical science. Clinicians face a management
                                                                                                                     path which has no ``gold standard'' of investigational mileposts; and are locked into a progression where
                                                                                                                     the extremes of either undertreatment or over-investigation may lead to iatrogenic disaster. The themes of
                                                                                                                     investigation, diagnosis and management of patients with the chronic fatigue syndrome remain
                                                                                                                     controversial. This condition joins in historical perspective a series of other diseases such as pink disease,
                                                                                                                     post traumatic stress disorder (by a variety of names), the Royal Free disease, Q Fever, Ross River disease
                                                                                                                     and chronic ciguatera-all of which have occupied windows of historical time in the twentieth century
                                                                                                                     during which their genesis remained an enigma. In some cases, they still do. New and puzzling diseases
                                                                                                                     will undoubtedly arise in the future. Both patients and medical science are best served if the formal
                                                                                                                     discipline of differential diagnosis is followed unswervingly under these circumstances or ``new'' diseases.
                                                                                                                     The rigour of this discipline-the rank listing of formal possibilities after the clinical history and objective
                                                                                                                     signs have been elicited-forms the pivot of best-practice contemporary medicine. An example of its power
                                                                                                                     is no more dramatically illustrated by the example of a ``new'' enigmatic disease, chronic ciguatera, which
                                                                                                                     ``reappeared'' in the 1950s. Ciguatoxins are some of the most potent biological substances known. Their
                                                                                                                     neurotropic effects produce a protean array of symptoms which are distressing in the acute-phase syndrome
                                                                                                                     and which are enervating throughout the often-prolonged progression of convalescence. It is now
                                                                                                                     appreciated that such effects are due to sodium channel activation and subsequent dysfunction at the
                                                                                                                     receptor sites on the cell surface of all excitable tissues. Dr. A. Melvin Ramsay, the Honorary Consultant
                                                                                                                     Physician in Infectious Diseases at the Royal Free Hospital in London, was at the clinical epicentre of the
                                                                                                                     presentation of another new disease in July 1955. His approach to its diagnosis, in the best traditions of
                                                                                                                     differential diagnosis, is an exemplar of the objective response to the appearance of a new or enigmatic
                                                                                                                     disease; and especially to that type in which experience has not generated sufficient case familiarity to
                                                                                                                     define syndrome barriers or to establish pathogenesis. Under such conditions, the correct diagnostic
                                                                                                                     paradigm is to follow the discipline of differential diagnosis, an evolved phenomenon of the last one
                                                                                                                     hundred years of medicine. This paper traces the evolution of the process of differential diagnosis, in the
                                                                                                                     perspective of the enigma of chronic fatigue, which remains an unmet challenge today.
 Pearn J.                  Australian Defence Force,    Traumatic stress disorders: a   Mil Med 2000                 The management and prevention of acute and post-traumatic stress disorders are current themes of great
                           Royal Children's Hospital,   classification with             Jun;165(6):434-40            importance to the defense health services of many nations. Currently, between 2% and 8% of service
                           Brisbane, Queensland,        implications for prevention                                  members deployed on combat operations, United Nations peacekeeping tasks, and humanitarian and
                           Australia.                   and management.                                              disaster relief operations present with one or more stress disorders within 3 years of deployment. The
                                                                                                                     management of acute stress disorders and the prevention and management of post-traumatic stress
                                                                                                                     disorders necessitate an understanding of the nosology of this group of illnesses. Research into some
                                                                                                                     preventive options--such as critical incident stress debriefing--also necessitates the selection of syndrome-
                                                                                                                     specific subjects during case finding if controversies about the efficacy of such interventions are to be
                                                                                                                     resolved. Diagnostic features, a summary of the nosological evolution, and key points of differential
                                                                                                                     treatment options are presented for 5 acute operational stress disorders (acute combat stress disorder,
                                                                                                                     conversion reactions, the counter-disaster syndrome, peacekeeper's acute stress syndrome, and the
ME Research UK — Database of Research Publications 2000

                                                                                                                         Stockholm syndrome) and for 11 post-traumatic disorders, including classic post-traumatic stress disorder,
                                                                                                                         chronic fatigue syndrome, Gulf War syndrome, peacekeeper's stress syndrome, survivor's guilt syndrome,
                                                                                                                         and the syndrome of lifestyle and cultural change.
 Peckerman A, LaManca JJ,     Center for Environmental      Cardiovascular stress           Psychosom Med. 2000 Jul-     OBJECTIVE: The objective of this study was to examine whether inappropriate cardiovascular responses
 Smith SL, Taylor A,          Hazards Research,             responses and their relation    Aug;62(4):509-16.            to stressors may underlie symptoms in Gulf War veterans with chronic fatigue. METHODS:
 Tiersky L, Pollet C, Korn    Environmental and             to symptoms in Gulf War                                      Psychophysiological stress testing was performed on 51 Gulf War veterans with chronic fatigue (using the
 LR, Hurwitz BE,              Occupational Health           veterans with fatiguing                                      1994 case definition of the Centers for Disease Control and Prevention) and 42 healthy veterans.
 Ottenweller JE, Natelson     Sciences Institute, Robert    illness.                                                     Hemodynamic responses to cold pressor, speech, and arithmetic stressors were evaluated using impedance
 BH.                          Wood Johnson Medical                                                                       cardiography. RESULTS: Veterans with chronic fatigue had diminished blood pressure responses during
                              School, Piscataway, NJ,                                                                    cognitive (speech and arithmetic) stress tests due to unusually small increases in total peripheral resistance.
                              USA.                                                                                       The cold pressor test, however, evoked similar blood pressure responses in the chronic fatigue and control
                                                                                        groups. Low reactivity to cognitive stressors was associated with greater fatigue ratings among ill veterans,
                                                                                                                         whereas an opposite relation was observed among healthy veterans. Self-reported neurocognitive decline
                                                                                                                         was associated with low reactivity to the arithmetic task. CONCLUSIONS: These results suggest a
                                                                                                                         physiological basis for some Gulf War veterans' reports of severe chronic fatigue. A greater deficit with
                                                                                                                         responses processed through cerebral centers, as compared with a sensory stimulus (cold pressor), suggests
                                                                                                                         a defect in cortical control of cardiovascular function. More research is needed to determine the specific
                                                                                                                         mechanisms through which the dissociation between behavioral and cardiovascular activities identified in
                                                                                                                         this study may be contributing to symptoms in Gulf War veterans.
 Petzke F, Clauw DJ.          Division of Rheumatology,     Sympathetic nervous system      Curr Rheumatol Rep 2000      This review focuses on studies of the sympathetic nervous system in fibromyalgia (FM). First, a brief
                              Immunology, and Allergy,      function in fibromyalgia.       Apr;2(2):116-23              review of the sympathetic system, and its relationship to the human stress response, is outlined. Then
                              Georgetown University                                                                      various studies of functional assessment of sympathetic function in FM are highlighted. Certain methods of
                              Medical Center, LL Gorman                                                                  assessment (eg, heart rate variability, biochemical, and psychophysical responses to various stressors) that
                              Building, 3800 Reservoir                                                                   we believe to be of specific importance for future research are discussed in greater detail. Finally, findings
                              Road NW, Washington, DC                                                                    on autonomic function in related disorders--specifically, chronic fatigue syndrome, irritable bowel
                              20007.                                                                                     syndrome, and migraine--will be briefly presented.
 Podell RN.                                                 Chronic fatigue syndrome:       Am J Med 2000 Jun
                                                            the fundamentals still apply.   1;108(8):677
 Poole J, Herrell R, Ashton   Harborview Medical Center,    Results of isoproterenol tilt   Arch Intern Med 2000 Dec     BACKGROUND: The pathogenesis of chronic fatigue syndrome (CFS) is unknown. Neurally mediated
 S, Goldberg J, Buchwald D.   325 Ninth Ave, Box 359780,    table testing in monozygotic    11-25;160(22):3461-8         hypotension (NMH) has been suggested as a common comorbid condition or a potential underlying cause.
                              Seattle, WA 98104, USA.       twins discordant for chronic                                 METHODS: We conducted a cotwin control study of 21 monozygotic twins who were discordant for CFS.
                                                            fatigue syndrome.                                            One twin met the 1994 Centers for Disease Control and Prevention criteria for CFS, and the other twin was
                                                                                                                         healthy and denied chronic fatigue. The twins were selected from a volunteer twin registry in which at least
                                                                                                                         1 member reported persistent fatigue. As part of a 7-day clinical evaluation, all 21 twin pairs were
                                                                                                                         evaluated with a 3-stage tilt table test with isoproterenol hydrochloride for the assessment of NMH. The
                                                                                                                         presence of NMH was defined as syncope or presyncope associated with a decrease of 25 mm Hg in blood
                                                                                                                         pressure and no associated increase in heart rate. RESULTS: A positive tilt table test result was observed in
                                                                                                                         4 twins with CFS (19%) and in 4 healthy twins (19%). This difference was not statistically significant
                                                                                                                         (matched pair odds ratio, 1.0; 95% confidence interval, 0.2-5.4; P>.90). Compared with the healthy twins,
                                                                                                                         the twins with CFS reported more severe symptoms of CFS and NMH both in the week before and during
                                                                                                                         the tilt table test. CONCLUSIONS: These results do not support a major role for NMH in CFS. They
                                                                                                                         highlight the importance of selecting well-matched control subjects, as well as the unique value of the
                                                                                                                         monozygotic cotwin control design in the study of this illness. Arch Intern Med. 2000;160:3461-3468.
 Price JR, Couper J.          Department of Psychiatry,     Cognitive behaviour therapy     Cochrane Database Syst Rev   OBJECTIVES: 1. To systematically review all randomised controlled trials of cognitive-behaviour therapy
                              University of Oxford, The     for adults with chronic         2000;(2):CD001027            (CBT) for adults with chronic fatigue syndrome (CFS); 2. To test the hypothesis that CBT is more effective
                              Warneford Hospital, Oxford,   fatigue syndrome.                                            than orthodox medical management or other interventions in adults with CFS. SEARCH STRATEGY: 1.
                              UK, OX3 7JX.                                                                               Electronic searching of bibliographic databases, including Medline, PsycLIT, Biological Abstracts,
                                                                                    Embase, SIGLE, Index to Theses, Index to Scientific and Technical Proceedings, and Science Citation
                              uk                                                                                         Index, using multiple search terms in order to perform a highly sensitive search. 2. Electronic searching of
ME Research UK — Database of Research Publications 2000

                                                                                                             the Trials Register of the Depression, Anxiety and Neurosis group. 3. Citation lists of relevant studies and
                                                                                                             reviews were perused for other relevant trials. 4. Contact with the principal authors of relevant studies, and
                                                                                                             with researchers in the field. SELECTION CRITERIA: All randomised controlled trials were included in
                                                                                                             which - adult patients with CFS; - received CBT or a control intervention, being either orthodox medical
                                                                                                             management or another intervention; - and whose outcomes were assessed in an appropriate way. CBT
                                                                                                             could be either type 'A' (encouraging return to 'normal' levels of rest and activity) or type 'B' (encouraging
                                                                                                             rest and activity which were within levels imposed by the disorder). DATA COLLECTION AND
                                                                                                             ANALYSIS: The two reviewers worked independently throughout the selection of trials and data
                                                                                                             extraction, comparing findings only when there was disagreement. Relevant trials were allocated to one of
                                                                                                             three quality categories. Full data extraction, using a standardised data extraction sheet, was performed on
                                                                                                             studies which were of high or moderate quality. Trials of low quality were excluded from the review. The
                                                                                                             comparisons made to test the review hypothesis were of type 'A' CBT versus other intervention(s), and of
                                                                                                             type 'B' CBT versus other intervention(s). Functional outcome was used as the main outcome for
                                                                                                             comparison, but other appropriate outcomes were compared where possible. Results were synthesised using
                                                                                                             the Review Manager software. For dichotomous data, the odds ratio was calculated for each study. For
                                                                                                             continuous data, effect sizes were obtained and the standardised mean difference, with 95% confidence
                                                                                                             intervals, was calculated. MAIN RESULTS: Only three relevant trials of adequate quality were found.
                                                                                                             These trials demonstrated that CBT significantly benefits physical functioning in adult out-patients with
                                                                                                             CFS when compared to orthodox medical management or relaxation. It is necessary to treat about two
                                                                                                             patients to prevent one additional unsatisfactory physical outcome about six months after treatment end.
                                                                                                             CBT appeared highly acceptable to the patients in these trials. There is no satisfactory evidence for the
                                                                                                             effectiveness of CBT in patients with the milder forms of CFS found in primary care or in patients who are
                                                                                                             so disabled that they are unable to attend out-patients. Additionally, there is no satisfactory evidence for the
                                                                                                             effectiveness of group CBT. REVIEWER'S CONCLUSIONS: Cognitive behaviour therapy appears to be
                                                                                                             an effective and acceptable treatment for adult out-patients with chronic fatigue syndrome. CFS is a
                                                                                                             common and disabling disorder. Its sufferers deserve the medical profession to be more aware of the
                                                                                                             potential of this therapy to bring lasting functional benefit, and health service managers to increase its
                                                                                                             availability. Further research is needed in this important area. Trials should conform to accepted standards
                                                                                                             of reporting and methodology. The effectiveness of CBT in more and less severely disabled patients than
                                                                                                             those usually seen in out-patient clinics needs to be assessed. Trials of group CBT and in-patient CBT
                                                                                                             compared to orthodox medical management, and of CBT compared to graded activity alone, also need to be
                                                                                                             conducted. Review, Academic
 Prins JB, Bleijenberg G,                       Doctor-Patient Relationship     Journal of Chronic Fatigue   Background: Chronic Fatigue Syndrome (CFS) is characterized by severe debilitating fatigue for at least six
 Rouweler EK, van Weel C,                       in Primary Care of Chronic      Syndrome 2000; 7(4): 3       months. The lack of a known origin could have consequences for the way general practitioners deal with
 van der Meer JWM.                              Fatigue Syndrome:                                            the diagnosis CFS and their perception of CFS patients. The aims of the study were to investigate the use of
                                                Perspectives of the Doctor                                   the diagnosis CFS by GPs and their reactions to self-diagnosis and to explore opinions of GPs about causes
                                                and the Patient                                              of CFS and the communication with CFS patients as well as opinions of CFS patients about their GPs.
                                                                                                             Method: One hundred twenty-one GPs completed questionnaires and 12 were interviewed. Data of 211
                                                                                                             CFS patients were analyzed as well. Results: Only half of the GPs used the diagnosis CFS. The main reason
                                                                                                             for not diagnosing CFS was ignorance of the criteria. GPs reported self-diagnosis in 68% of the CFS
                                                                                                             patients. More than half of the GPs could sympathize less with the complaints of CFS patients compared
                                                                                                             with other patients. These GPs experienced more problems in communicating with CFS patients and
                                                                                                             judged co-operation and contact as poor. As to the causes for CFS a discrepancy was found. GPs mainly
                                                                                                             attributed the complaints to psychosocial factors, whereas patients mainly had physical attributions.
                                                                                                             Conclusion: In CFS, GPs should be explicit about the diagnosis. As to the discrepancy in presumed causes
                                                                                                             of CFS between GPs and CFS patients, it may be helpful for GPs to discuss the distinction between
                                                                                                             initiating and perpetuating factors of CFS. We argue that this attitude of GPs would be beneficial to the
                                                                                                             course of the complaints of CFS patients.
 Racciatti D, Barberio                          Clinical and Pathogenetical     Journal of Chronic Fatigue   Prolonged fatigue is a common complaint in the community and is usually transitory. If fatigue continues
 A,Vecchiet J, Pizzigallo E.                    Characterization of 238         Syndrome 2000; 5(3/4): 61    for more than six months, is disabling, and is accompanied by other constitutional and neuropsychiatric
                                                Patients of a Chronic Fatigue                                symptoms, then a diagnosis of chronic fatigue syndrome (CFS) should be considered. CFS probably is an
                                                Syndrome Italian Center                                      heterogeneous disease, maybe multifactorial, or it includes different pathologies which manifest with the
ME Research UK — Database of Research Publications 2000

                                                                                                                     same symptoms. In some cases, the mode of presentation of the illness implicate the exposure to chemical
                                                                                                                     and/or food toxins as precipitating factors (e.g., ciguatera poisoning, Gulf War Syndrome, etc.). In other
                                                                                                                     CFS cases, the etiology is still unknown: there are various hypotheses on pathogenetic events which, alone
                                                                                                                     or in association with each other, may precipitate the illness. In fact, it is probable an involvement of
                                                                                                                     multiple events in CFS onset where different precipitating factors can interact each other, even if not
                                                                                                                     always all present in the single patient: latent and/or chronic viral infections, immunologic and
                                                                                                                     neuroendocrine dysfunctions, psychological, environmental and mood factors. In accordance to this theory,
                                                                                                                     we consider various subgroups of CFS patients on the basis of the pathway and the mode of presentation of
                                                                                                                     the disease. The Clinic of Infectious Diseases of ``G. D'Annunzio'' University of Chieti is one of the main
                                                                                                                     National Reference Centers for the CFS Study in Italy. From January 1992 to January 1998, 238 patients
                                                                                                                     came to our observation: 89 of them met CDC criteria for CFS (1994), 127 did not; the other 22 patients
                                                                                                                     are still under evaluation. Our patients underwent physical examination (including tests for searching for
                                                                                                                     the possible coexistence of a fibromyalgia syndrome), psychiatric interview with several
                                                                                                                     neuropsychological tests, laboratory tests (including magnesium determination on serum), neuroendocrine
                                                                                                                     evaluation (circadian rhythm of several hormones, buspirone challenge test), SPECT scans to evaluate
                                                                                                                     cerebral perfusion, and other examinations where necessary in according to the symptomatology of each
                                                                                                                     patient (e.g., orthopedic, ORL, EMG, muscle biopsy, etc.). According to our preliminary results, we
                                                                                                                     subdivided our patients in different subgroups and we studied them comparatively. We report the more
                                                                                                                     significant data collected from this evaluation that might lead to a better understanding of the syndrome
                                                                                                                     and in particular of its pathways course, a knowledge that will help is choosing appropriate therapies for
                                                                                                                     each subgroups.
 Rangel L, Garralda E,    Academic Unit of Pediatrics,   Personality in adolescents   Eur Child Adolesc Psychiatry   Our aim was to study the presence of personality traits and disorder in adolescents with Chronic Fatigue
 Levin M, Roberts H.      Imperial College School of     with chronic fatigue         2000 Mar;9(1):39-45            Syndrome (CFS). Personality was then compared to other measures of functioning such as presence of
                          Medicine, London, UK.          syndrome.                                                   psychiatric disorder and rating on the Child Behavior Checklist 4-18 (CBCL) and in relation to CFS
                                                                                                                     outcome. Twenty-five adolescents with CFS followed-up after contacts with tertiary paediatric/psychiatric
                                                                                                                     clinics were compared with 15 matched healthy controls. Interviews and questionnaires from parents and
                                                                                                                     youngsters included Personality Assessment Schedule (PAS), Kiddie-SADS Psychiatric Interview, Child
                                                                                                                     Behavior Checklist. CFS subjects were significantly more likely than controls to have personality difficulty
                                                                                                                     or disorder. Personality features significantly more common amongst them were conscientiousness,
                                                                                                                     vulnerability, worthlessness and emotional lability. There was a nonsignificant association between
                                                                                                                     personality disorder and worse CFS outcome. Personality difficulty or disorder was significantly associated
                                                                                                                     with psychological symptoms and decreased social competence on the CBCL but it was distinguishable
                                                                                                                     from episodic psychiatric disorder. Personality difficulty and disorder are increased in adolescents with a
                                                                                                                     history of CFS. Personality disorder may be linked to poor CFS outcome.
 Rangel L, Garralda ME,   Academic Unit of Child and                                  J R Soc Med 2000               Little has been reported on prognostic indicators in children with chronic fatigue syndrome (CFS). We used
 Levin M, Roberts H.      Adolescent Psychiatry,                                      Mar;93(3):129-34Comment        interviews with children and parents, a mean of 45.5 months after illness onset, to follow up 25 cases of
                          Imperial College School of                                  in: J R Soc Med. 2000          CFS referred to tertiary paediatric psychiatric clinics. At its worst, the illness had been markedly
                          Medicine, St Mary's                                         Jun;93(6):337-8 The course     handicapping (prolonged bed-rest and school absence in two-thirds); mean time out of school was one
                          Hospital, London, UK.                                       of severe chronic fatigue      academic year. Two-thirds, however, had recovered and resumed normal activities--mean duration of
                                                                                      syndrome in childhood.         illness to recovery/assessment 38 months--and none had developed other medical conditions. Recovery was
                                                                                                                     associated with specific physical triggers to the illness, with start of illness in the autumn school term and
                                                                                                                     with higher socioeconomic status. Severe fatigue states in children can cause serious and longlasting
                                                                                                                     handicap but most children recover.
 Ray DE.                  Medical Research Council       Pesticide neurotoxicity in   Neurotoxicology 2000 Feb-      The same classes of pesticides are used all over the world, but conditions of use vary widely, and public
                          Toxicology Unit, Leicester,    Europe: real risks and       Apr;21(1-2):219-21             perceptions of risk vary more widely still. Within Western Europe pesticide residues in commercially
                          United Kingdom.                perceived risks.                                            traded foodstuffs are subject to international standards and are closely monitored. Hence risks to consumers
                                                                                               from such foods are negligible. The major hazards are poisoning associated with high acute/chronic
                                                                                                                     operator exposures due to occasional pesticide misuse. In addition pesticides provide a convenient means
                                                                                                                     of attempting suicide in agricultural areas. In contrast, public perception of risks from pesticides centres on
                                                                                                                     low level exposures, and is heightened by several factors. These are: poisonings associated with pesticide
                                                                                                                     misuse; the indirect nature of the benefit to the consumer (cf. medicines or public health uses); and
ME Research UK — Database of Research Publications 2000

                                                                                                                   commercially motivated marketing of pesticide-free produce. In press reports pyrethroid insecticides have
                                                                                                                   been linked to "Multiple Chemical Sensitivity" in Germany, and organophosphates to "Chronic Fatigue
                                                                                                                   Syndrome" in the UK. A number of pressure groups are actively campaigning to ban all uses of
                                                                                                                   organophosphorus pesticides. Unfortunately evaluation of the real risks of pesticide exposure is rendered
                                                                                                                   less certain by the lack of any very useful retrospective exposure measures with which biological effects of
                                                                                                                   uncertain aetiology might be correlated. This means that although we can be sure that pesticides pose no
                                                                                                                   gross threat to health in the general population, subtle effects on more highly exposed sub-populations are,
                                                                                                                   as yet, more difficult to rule out.
 Redman DA.                American University,           Ruscus aculeatus (butcher's    J Altern Complement Med   CONTEXT: Chronic orthostatic hypotension (OH) is frequently a severely debilitating disease that affects
                           Washington, DC, USA.           broom) as a potential          2000 Dec;6(6):539-49      large groups of the population with autonomic insufficiency--the elderly; patients with diabetes,
                                                          treatment for orthostatic                                Parkinson's disease, and chronic fatigue syndrome; and anyone on drugs that affect the autonomic nervous
                                                          hypotension, with a case                                 system. Unfortunately, even though more than 60 medications are currently being used to treat OH, none of
                                                          report.                                                  them is particularly or consistently effective. Ruscus aculeatus, a phytotherapeutic agent that is well known
                                                                                                                   in Europe, may, however, change this. Its vasoconstrictive and venotonic properties make it ideally suited
                                                                                                                   to treat the pooling of blood in the limbs, lack of venous tone, and lack of neurally mediated
                                                                                                                   vasoconstriction that frequently characterize OH. Although it has never been suggested as a treatment for
                                                                                                                   OH, it already has a long, proven record of use in Europe for treating a variety of circulatory disorders.
                                                                                                                   OBJECTIVE: To provide evidence for what appears to be an effective, safe, inexpensive botanical therapy
                                                                                                                   for OH and encourage further studies on the efficacy of Ruscus for OH patients. DESIGN: Review of OH
                                                                                                                   and therapies currently available for OH and evaluation of the properties of Ruscus aculeatus, its
                                                                                                                   mechanism of action, and its suitability as a therapeutic agent for treatment of OH. RESULTS: A review of
                                                                                                                   the many pharmacologic and nonpharmacologic agents for treating OH reveals that all of the drug therapies
                                                                                                                   are disappointing and marginally useful. Although nonpharmacologic management is preferred, in the
                                                                                                                   many cases in which OH becomes debilitating, pharmacologic intervention becomes a last resort. But drug
                                                                                                                   therapy may not always be necessary, because Ruscus aculeatus, a phytotherapeutic agent containing
                                                                                                                   ruscogenins and flavonoids, may prove useful for the treatment of OH if denervation is not so advanced
                                                                                                                   that it has compromised receptor activity at the venous wall. Ruscus aculeatus is an alpha-adrenergic
                                                                                                                   agonist that causes venous constriction by directly activating postjunctional alpha1- and alpha2-receptors,
                                                                                                                   in turn stimulating the release of noradrenaline at the level of the vascular wall. It also possesses venotonic
                                                                                                                   properties: it reduces venous capacity and pooling of blood in the legs and exerts protective effects on
                                                                                                                   capillaries, the vascular endothelium, and smooth muscle. Its flavonoid content strengthens blood vessels,
                                                                                                                   reduces capillary fragility, and helps maintain healthy circulation. Unlike most of the drug therapies used to
                                                                                                                   treat OH, Ruscus aculeatus does not cause supine hypertension. It also appears to do something no other
                                                                                                                   therapy can offer--alleviate the worsening effects of OH in environmentally hot conditions. Finally, it is an
                                                                                                                   extremely safe, inexpensive, over-the-counter botanical medicine. CONCLUSION: With proven
                                                                                                                   phlebotherapeutic properties, including vasoconstrictive action and venotonic properties, Ruscus aculeatus
                                                                                                                   shows great promise for ameliorating the symptoms of OH and improving the quality of life for large
                                                                                                                   groups in the population. It clearly deserves to be the object of wider research and study as a treatment for
 Reeves WC, Stamey FR,     Division of Viral and          Human herpesviruses 6 and 7    Clin Infect Dis 2000      We conducted this study to determine whether infection with human herpesvirus (HHV) 6A, HHV-6B, or
 Black JB, Mawle AC,       Rickettsial Diseases,          in chronic fatigue syndrome:   Jul;31(1):48-52           HHV-7 differed between patients with chronic fatigue syndrome and control subjects. We recruited 26
 Stewart JA, Pellett PE.   National Center for            a case-control study.                                    patients and 52 nonfatigued matched control subjects from Atlanta. Serum samples were tested by enzyme
                           Infectious Diseases, Centers                                                            immunoassay for seroreactivity to HHV-6, and all were seropositive. Lymphocyte specimens were
                           for Disease Control and                                                                 cocultivated with cord blood lymphocytes and assayed for HHV-6 and HHV-7; neither virus was isolated.
                           Prevention, Atlanta, GA,                                                                Finally, lymphocytes were tested by use of 3 polymerase chain reaction methods for HHV-6A, HHV-6B,
                           30333, USA.                                                                and HHV-7 DNA. HHV-6A or HHV-6B DNA was detected in 17 (22.4%) of 76 samples, and there were
                                                                                                                   no significant differences (by matched analyses) between patients (3 [11.5%] of 26) and control subjects
                                                                                                                   (14 [28%] of 50). HHV-7 DNA was detected in 14 subjects, and although control subjects (12 [24%]) were
                                                                                                                   more likely than patients (2 [7.7%]) to be positive, the difference was not statistically significant. We found
                                                                                                                   no evidence that active or latent infection with HHV-6A, HHV-6B, HHV-7, or any combination these 3
                                                                                                                   HHVs is associated with chronic fatigue syndrome.
ME Research UK — Database of Research Publications 2000

 Regland B.                                                 [Two contributions on          Lakartidningen 2000 Mar
                                                            chronic fatigue syndrome:      8;97(10):1168
                                                            biological causes are
                                                            involved in most cases].
                                                            [Article in Swedish]
 Reid S, Chalder T, Cleare   Guy's, Kings, and St           Chronic fatigue syndrome.      BMJ 2000 Jan
 A, Hotopf M, Wessely S.     Thomas's School of Medicine                                   29;320(7230):292-6
                             and Institute of Psychiatry,
                             London SE5 8AZ.
 Reyes M, Dobbins JG,                                       Chronic Fatigue Syndrome       Journal of Chronic Fatigue   Objective: To examine the presence of symptoms associated with chronic fatigue syndrome (CFS) over the
 Nisenbaum R, Subedar NS,                                   Progression and Self-Defined   Syndrome 2000; 5(1): 17      course of the illness and determine the probability of self-defined recovery by duration of illness. Design:
 Randall B, Reeves C.                                       Recovery: Evidence from the                                 Follow-up study. Subjects: One hundred fifty-five CFS patients enrolled in the Centers for Disease Control
                                                            CDC Surveillance System                                     and Prevention's (CDC) CFS surveillance system between August 1989 and July 1993 and followed to
                                                                                                                        November 1997. Measurements: Presence of symptoms, a self-defined period of recovery from CFS, and
                                                                                                                        demographic differences between patients reporting and not reporting recovery. Period life-table methods
                                                                                                                        were used to compute the probability of recovery from CFS for specific years of illness duration. Results:
                                                                                                                        At illness onset, the most commonly reported CFS symptoms (w 45%) were sore throat, fever, tender lymph
                                                                                                                        nodes, general weakness, and muscle pain. As the illness progressed, the percentages of patients reporting
                                                                                                                        symptoms fluctuated. At illness onset, patients with a sudden onset of CFS reported significantly higher
                                                                                                                        frequencies of sore throat, fever, tender lymph nodes, chills, hypersomnia, difficulty thinking or
                                                                                                                        concentrating, and depression when compared to patients with a gradual onset. As the illness progressed,
                                                                                                                        these differences disappeared, but gradual onset cases reported more hypersomnia than sudden onset cases
                                                                                                                        (p = 0.001). The cumulative probability of recovery from CFS was 31.4% during the first 5 years of illness
                                                                                                                        and 48.1% during the first 10 years of illness. For each year of illness through year 15, both sudden and
                                                                                                                        gradual onset cases had similar recovery probabilities. Thereafter, gradual onset cases had higher recovery
                                                                                                                        probabilities, but these differences were not statistically significant. Patients reporting recovery and those
                                                                                                                        remaining ill were similar demographically. Conclusions: A period of recovery could be reported at any
                                                                                                                        time during the course of CFS, but was more likely in the early years. Additional longitudinal studies are
                                                                                                                        required to adequately describe the course of CFS in the early stages of illness, determine if the illness
                                                                                                                        recurs over time, and predict the occurrence of symptoms over the course of illness. We recommend that
                                                                                                                        researchers develop a standard definition of recovery from CFS and that future studies take into account the
                                                                                                                        variable duration of illness and follow-up
 Richards RS, Roberts TK,    Department of Biological       Free radicals in chronic       Redox Rep 2000;5(2-3):146-   We have demonstrated that certain morphological and biochemical changes occur in chronic fatigue
 Dunstan RH, McGregor        Sciences, University of        fatigue syndrome: cause or     7                            syndrome (CFS) and in rheumatoid arthritis (RA). These changes in RA can be explained by the well-
 NR, Butt HL.                Newcastle, New South           effect?                                                     established inappropriate increase in free radical generation. The similar changes in CFS suggest a similar
                             Wales, Australia.                                                                          explanation and a possible role for free radicals in the aetiology of this condition.
 Richards RS, Roberts TK,                                   Erythrocyte Morphology in      Journal of Chronic Fatigue   Erythrocyte deformability and erythrocyte membrane stability are dependent on the erythrocyte
 Mathers D, Dunstan RH,                                     Rheumatoid Arthritis and       Syndrome 2000; 6(1): 23      cytoskeleton and its relationship with the contents of the cell. Certain internal occurrences such as
 McGregor NR, Butt HL.                                      Chronic Fatigue Sydrome: A                                  oxidation of sulphydryl groups on the membrane cytoskeleton or the haemoglobin molecule could alter this
                                                            Preliminary Study                                           relationship and as a consequence, alter the membrane properties and the shape of the cell. It is thus
                                                                                                                        conceivable that in conditions where there is a potential increase in the generation of free radicals,
                                                                                                                        erythrocyte shape could be altered. We investigated the possibility that predictable shape changes occur in
                                                                                                                        erythrocytes from patients with rheumatoid arthritis (RA), a condition associated with free radical damage.
                                                                                                                        We also investigated this possibility in patients with chronic fatigue syndrome (CFS) and whether any such
                                                                                                                        change could be correlated with those seen in RA. Patients with CFS could be divided into two groups
                                                                                                                        based on their erythrocyte morphology. Patients in one of these groups had increased numbers of
                                                                                                                        stomatocytes. Patients with RA had increased numbers of leptocytes.
 Richards RS, Roberts TK,                                   Investigation of Erythrocyte   Journal of Chronic Fatigue   A role of free radical scavenging for erythrocytes has previously been demonstrated, which is additional to
 Mathers D, Dunstan RH,                                     Oxidative Damage in            Syndrome 2000; 6(1): 37      their established role of gas exchange. In carrying out this role, erythrocytes become damaged by oxidation,
 McGregor NR, Butt HL.                                      Rheumatoid Arthritis and                                    which consumes endogenous reducing substances. It was therefore proposed that there exists a link
ME Research UK — Database of Research Publications 2000

                                                        Chronic Fatigue Syndrome                                      between erythrocyte metabolism (particularly redox metabolism) and erythrocyte shape and that both of
                                                                                                                      these should be related to erythrocyte deformability. To look for evidence of oxidative damage in vivo, the
                                                                                                                      erythrocytes were assessed for reduced glutathione (GSH), malondialdehyde (MDA), methaemoglobin
                                                                                                                      (metHb) and 2,3-diphosphoglyceric acid (2,3-DPG) in patients suffering from rheumatoid arthritis (RA),
                                                                                                                      chronic fatigue syndrome (CFS) and healthy control subjects. Full blood counts, serum vitamin B12,
                                                                                                                      erythrocyte folate, serum ferritin, serum iron, serum iron binding capacity and erythrocyte magnesium were
                                                                                                                      also performed on all samples. Patients with RA had increased 2, 3-DPG, GSH and metHb when compared
                                                                                                                      with the control group as well as the expected decreased haemoglobin, haematocrit, and serum iron. There
                                                                                                                      was evidence of oxidative damage in CFS with 2,3-DPG metHb and MDA increased in this group. An
                                                                                                                      increase in GSH could also be demonstrated in a sub-group of the CFS patients. This damage may explain
                                                                                                                      the shape changes (presumably accompanied by increased rigidity) that have been reported in erythrocytes
                                                                                                                      in patients suffering from CFS and suggests a role for free radicals in the pathogenesis of CFS.
 Richards RS, Roberts TK,   Department of Biological    Blood parameters indicative      Redox Rep 2000;5(1):35-41    Full blood counts, ESR, CRP, haematinics and markers for oxidative stress were measured for 33 patients
 McGregor NR, Dunstan       Sciences, University of     of oxidative stress are                                       diagnosed with chronic fatigue syndrome (CFS) and 27 age and sex matched controls. All participants also
 RH, Butt HL.               Newcastle, Australia.       associated with symptom                                       completed symptom questionnaires. CFS patients had increases in malondialdehyde (P <0.006),
                                                        expression in chronic fatigue                                 methaemoglobin (P <0.02), mean erythrocyte volume (P <0.02) and 2,3-diphosphoglycerate (P <0.04)
                                                        syndrome.                                                     compared with controls. Multiple regression analysis found methaemoglobin to be the principal component
                                                                                                                      that differentiated between CFS patients and control subjects. Methaemoglobin was found to be the major
                                                                                                                      component associated with variation in symptom expression in CFS patients (R(2) = 0.99, P <0.00001),
                                                                                                                      which included fatigue, musculoskeletal symptoms, pain and sleep disturbance. Variation in levels of
                                                                                                                      malondialdehyde and 2,3-diphosphoglycerate were associated with variations in cognitive symptoms and
                                                                                                                      sleep disturbance (R(2) = 0.99, P <0.00001). These data suggest that oxidative stress due to excess free
                                                                                                                      radical formation is a contributor to the pathology of CFS and was associated with symptom presentation.
 Richardson J.                                          Four Cases of Pesticide          Journal of Chronic Fatigue   Objectives: 1. To demonstrate in four patients, in whom the correct diagnosis of pesticide poisoning had
                                                        Poisoning, Presenting as         Syndrome 2000; 6(2): 11      been missed, the injustices inflicted on them when they are told ME does not exist. 2. To show how closely
                                                        ``ME,'' Treated with a                                        the features of such poisoning, especially by organochlorines, resemble those of the much more classic ME
                                                        Choline and Ascorbic Acid                                     which is usually due, at least in the author's practice in the northern region of the UK, to persistent
                                                        Mixture                                                       enteroviral infection. 3. To draw attention to a new and apparently successful form of treatment with an
                                                                                                                      oral mixture of choline and ascorbic acid. 4. To suggest reasons why this treatment merits further scientific
                                                                                                                      investigation. Setting: A charity based private practice involved in the investigation of viral mediated
                                                                                                                      disease. Subjects: Four patients, two male and two female, each referred with a diagnosis of ME.
                                                                                                                      Intervention: a. Samples of blood were sent to Biolab Medical Unit where a variety of pesticide residues,
                                                                                                                      including the very persistent organochlorines, were identified, and progress in detoxification was
                                                                                                                      monitored. b. All four cases were treated orally with a choline and ascorbic acid mixture. Results: After a
                                                                                                                      variable number of months, during the early phase of which the blood levels of some of the toxins rose,
                                                                                                                      possibly due to mobilization from fatty stores, all symptoms cleared as blood levels fell. KEY Messages:
                                                                                                                      The term ME comprises a number of clinical features, characterizing a patient who is ill. To refuse to
                                                                                                                      recognize their existence does the patient much injustice. Some cases of ME may be found to have
                                                                                                                      pesticide poisoning. The possibility of it should always be borne in mind. The source may be either in the
                                                                                                                      UK or abroad. A positive enquiry and a single blood test will provide a diagnosis. Organochlorines may
                                                                                                                      persist in the body for many years, as may the symptoms derived from them. A detoxification program
                                                                                                                      based on oral administration of a choline and ascorbic acid mixture has shown much promise and deserves
                                                                                                                      verification of its value. Conclusions: Amongst the group of clinical features known as ME, the possibility
                                                                                                                      of pesticide poisoning should always be borne in mind. Treatment with choline and ascorbic acid mixture
                                                                                                                      is worth trying, pending its more formal investigation.
 Richman JA, Jason LA,      Department of Psychiatry,   Feminist perspectives on the     Health Care Women Int 2000   We contrast Western medical views of chronic fatigue syndrome (CFS) etiology, diagnosis, and treatment
 Taylor RR, Jahn SC.        University of Illinois,     social construction of chronic   Apr-May;21(3):173-85         with views maintained by a predominantly female CFS population. We argue that the failure of Western
                            Chicago 60612, USA.         fatigue syndrome.                                             medicine to demonstrate a viral etiology for CFS led to a paradigmatic shift in research perspectives, which
                                                                                            then embraced psychiatric and sociocultural explanations for CFS. As a result, CFS was delegitimized as a
                                                                                                                      biomedical phenomenon within medical, academic, governmental, and public arenas. We compare
                                                                                                                      alternative social constructions of CFS with issues pertaining to multiple sclerosis (MS), an illness that
ME Research UK — Database of Research Publications 2000

                                                                                                                     similarly predominates among women. Patient perspectives suggest that the history of medical attitudes
                                                                                                                     toward CFS may eventually parallel the transformations that occurred in relation to MS. In particular, the
                                                                                                                     discovery of biological markers for CFS may lay to rest the categorization of CFS as largely within the
                                                                                                                     psychiatric realm. Review Literature
 Rosner I, Rozenbaum M,    Department of Hematology,   Dysautonomia in chronic          Isr Med Assoc J 2000 Dec;2
 Naschitz JE, Sabo E,      Bnai Zion Medical Center,   fatigue syndrome vs.             Suppl:23-4
 Yeshurun D.               Haifa, Israel.              fibromyalgia.
 Rowe KS.                                              Five-Year Follow-Up of           Journal of Chronic Fatigue   Three and 5 year follow-up studies of eighty-nine young people with Chronic Fatigue Syndrome who
                                                       Young People with Chronic        Syndrome 2000; 5(3/4): 97    completed a double blind randomized controlled trial of intravenous gammaglobulin has been conducted to
                                                       Fatigue Syndrome Following                                    determine whether the improvement following the intravenous gammaglobulin was sustained. Initial
                                                       the Double Blind                                              telephone contact and a questionnaire that assessed functional outcomes including, physical activity, social
                                                       Randomised Controlled                                         activities, work/school attendance and work/school workload was used. Strategies and treatment that were
                                                       Intravenous Gammaglobulin                                     found helpful and ways to improve management were also asked. Follow-up data were obtained on 86 of
                                                       Trial                                                         89 after the study concluded. The 3-year follow-up yielded a 75% response to the questionnaire. A 78%
                                                                                                                     follow up response rate at 5 years was achieved for those enrolled in the study with 84% (n = 74) of those
                                                                                                                     who completed the study being traced. The mean follow-up time from commencement of illness was 56
                                                                                                                     months (s.d. 25 months), range 15-112 months. There was no persistent deterioration in function related to
                                                                                                                     CFS in any young person. Four had reported recurrence of symptoms lasting 3-8 months and again
                                                                                                                     improved. Others remained `improved' or continued to improve. Seventeen per cent of those who
                                                                                                                     responded were still moderately unwell with another 23% `not back to normal yet.' Sixty per cent of
                                                                                                                     participants considered they were `well' at the last follow-up with 45% scoring 10/10. Seventeen (20%) had
                                                                                                                     another condition during or after their illness. Anergy or hypoergy did not predict functional outcome at
                                                                                                                     five years after the trial, although an earlier improvement was noted in those who were anergic and who
                                                                                                                     received gammaglobulin. There was no deterioration in overall function over the 5 years following
                                                                                                                     participation in the gammaglobulin trial, and young people continued to improve although a significant
                                                                                                                     number were still disabled. The significance of the abnormal delayed type hypersensitivity reaction for the
                                                                                                                     response to gammaglobulin is uncertain and warrants further investigation.
 Sachs L, Evengard B.      Tema Kommunikation,         [The special physician-          Lakartidningen 2000 Jan
                           Linkopings universitet.     patient relation in connection   19;97(3):176-8, 181
                                                       to chronic fatigue syndrome.
                                                       Anthropologists and
                                                       physicians search for a new
                                                       contact-model].[article in
 Sadlier M, Evans JR,                                  A Preliminary Study into the     Journal of Chronic Fatigue   In this preliminary study twenty-eight heterogeneous Chronic Fatigue Syndrome (CFS) patients were
 Phillips C, Broad A.                                  Effectiveness of Multi-          Syndrome 2000; 7(1): 93      treated with Multi-Convergent Therapy (MCT). This form of therapy has been used successfully for over
                                                       Convergent Therapy in the                                     ten years in the treatment of Irritable Bowel Syndrome, Tinnitus, Hyperventilation Syndrome, Chronic Pain
                                                       Treatment of Heterogeneous                                    and Anxiety Disorders. This small study was undertaken to assess whether MCT is effective in the
                                                       Patients with Chronic Fatigue                                 treatment of CFS and to examine whether a more extensive investigation is warranted. Due to heterogeneity
                                                       Syndrome                                                      of symptoms, outcome measures were established on the basis of a shared decision-making process
                                                                                                                     between patient and therapist. One patient dropped out of the study. All twenty-seven remaining patients
                                                                                                                     achieved significant recoveries. Twelve patients recorded a mean improvement on baseline symptoms of
                                                                                                                     61%, eight patients who completed a Quality of Life questionnaire demonstrated a mean change from 2.4
                                                                                                                     to 6.3 (out of 10). Five patients reported a return to full normal function and two patients returned to school
                                                                                                                     or work and regular exercise. At follow up nine-months to one-year later all eighteen patients who
                                                                                                                     responded reported either continued improvements or maintenance of a well state. The findings of this
                                                                                                                     study support the use of MCT in the management of patients with Chronic Fatigue Syndrome and justify
                                                                                                                     the implementation of a major clinical trial.
 Schmaling KB, Smith WR,   University of Washington,   Significant other responses      Psychosom Med 2000 May-      OBJECTIVE: The predictive power of partners' responses to illness behavior for illness outcomes was
 Buchwald DS.              Seattle 98195-6560, USA.    are associated with fatigue      Jun;62(3):444-50             investigated among couples in which one person had chronic fatigue syndrome (CFS). METHODS: One
                      and functional status among                                   hundred nineteen participants who met case-definition criteria for CFS and were living with a significant
ME Research UK — Database of Research Publications 2000

                                                             patients with chronic fatigue                                other (SO) completed self-report measures of relationship satisfaction, responses of their SO to fatigue
                                                             syndrome.                                                    symptoms, and outcome measures of fatigue and functional status. RESULTS: The results indicated that
                                                                                                                          more frequent solicitous SO responses to illness behavior were predictive of greater fatigue-related severity
                                                                                                                          and bodily pain. Solicitous SO responses to fatigue behavior were particularly influential in the context of a
                                                                                                                          satisfactory relationship. In highly satisfactory relationships, solicitous SO responses were associated with
                                                                                                                          significantly greater fatigue severity and fatigue-related disability than in relationships characterized by low
                                                                                                                          or average satisfaction. CONCLUSIONS: Solicitous SO responses to CFS-related symptoms are associated
                                                                                                                          with poorer patient outcomes, especially in the context of a satisfactory intimate relationship. Because of
                                                                                                                          the cross-sectional nature of the study, the direction of effects cannot be interpreted unambiguously. SOs
                                                                                                                          may be inadvertently positively reinforcing illness-related behavior: Solicitous partners may help the
                                                                                                                          patient more with tasks of daily living, thereby decreasing the patient's activity level, which may lead to
                                                                                                                          deconditioning and disability. Alternatively, patients with more severe symptoms and disability may
                                                                                                                          present more opportunities for concerned SO responses, which again may be heightened in the context of a
                                                                                                                          caring, satisfactory relationship. In either case, the results suggest that additional research on the role of
                                                                                                                          solicitous SO responses is warranted.
 Schwartz SN, Jones R.                                       Measuring Outcomes of           Journal of Chronic Fatigue   Purpose: To compare the outcome of treatment of chronic fatigue syndrome measured by a validated
                                                             Treatment in Chronic Fatigue    Syndrome 2000; 6(2): 3       outcome instrument to patients' perception of outcome based on simple questioning. Subjects and Methods:
                                                             Syndrome: A Comparison of                                    Results of a single self-report question (``Are you much better, better, about the same, worse or much
                                                             Simple Questioning vs. Use                                   worse?'') at the end of approximately one year of treatment of 45 patients were compared to results of the
                                                             of a Validated Outcome                                       Short Form 36 obtained at the beginning and end of that year. Results: There was no correlation between
                                                             Instrument (Short Form 36)                                   the results of the single self-report question and the interval change in the Short Form 36 summary scales
                                                                                                                          and 7 of 8 component scales. Conclusions: Appropriate outcomes measurements can increase reliability of
                                                                                                                          clinical practice results as well as treatment trials. Studies based only on answers to simple self-report
                                                                                                                          questions may yield unreliable results.
 Scott LV, Svec F, Dinan T.   Department of Psychiatry,      A preliminary study of          Psychiatry Res 2000 Dec      Abnormalities of the production of dehydroepiandrosterone (DHEA), the adrenal androgen, have been
                              Trinity College Medical        dehydroepiandrosterone          4;97(1):21-8                 linked with disorders such as obesity and psychological disorders such as major depression.
                              School, St. James' Hospital,   response to low-dose ACTH                                    Adrenocorticotropin (ACTH) is the primary stimulant of DHEA, and cortisol, from the adrenal. We chose
                              8, Dublin, Ireland.            in chronic fatigue syndrome                                  to examine the DHEA and DHEA/cortisol response to the novel low-dose ACTH test in healthy subjects
                                                             and in healthy subjects.                                     and a cohort with chronic fatigue syndrome (CFS): this test is useful in assessing subtle irregularities of
                                                                                                                          pituitary-adrenal activity. Nineteen CFS subjects (diagnosed by CDC criteria) and 10 healthy subjects were
                                                                                                                          examined. We demonstrated that 1 &mgr;g ACTH significantly elevates DHEA levels, with no difference
                                                                                                                          in output between CFS and healthy subjects. The DHEA/cortisol ratio decreased in response to ACTH
                                                                                                                          stimulation in healthy subjects but not in the CFS cohort. We suggest this divergence of response between
                                                                                                                          the two groups represents an imbalance in the relative synthetic pathways of the CFS group which, if
                                                                                                                          present chronically and if comparable to daily stressors, may manifest itself as an inappropriate response to
                                                                                                                          stress. This difference may be important in either the genesis or propagation of the syndrome.
 Shannon M, Clovis LL.                                       Health Care Workers,            Journal of Chronic Fatigue   ``Cluster Outbreaks'' of Chronic Fatigue (Immune Dysfunction) Syndrome CFIDS)/ Myalgic
                                                             Predominant Gender Females      Syndrome 2000; 7(1): 75      Encephalomyelitis (ME) have been well documented in the Healthcare professions. Large bodies of
                                                             at High Risk: Turning the                                    scientific evidence suggest that the endocrine system is very involved. In fact, it may be the most critical
                                                             Spotlight on the Endocrine                                   piece of the puzzle that needs to be examined in all future research. Although some subtle immunologic
                                                             System                                                       changes have been documented in persons with ME/CFIDS, recent studies on the endocrine system suggest
                                                                                                                          that several hormonal abnormalities may account for the myriad of symptoms. Calkins and colleagues at
                                                                                                                          Johns Hopkins have found that most patients have delayed orthostatic hypotension. Streeten and Bell
                                                                                                                          extended these studies finding that most patients studied have severe hypovolemia. Hormones that prevent
                                                                                                                          these conditions in healthy people are controlled by the pituitary and hypo-thalamus. It is interesting that
                                                                                                                          the symptoms experienced by patients with Pan-Hypothyroidism are virtually identical to CFIDS/ME
                                                                                                                          Endocrine research shows that most patients have low Cortisol levels. Overwhelming research shows a
                                                                                                                          similar pattern to the many autoimmune diseases that occur predominantly in females. What looks like a
                                                                                                                          multi-systemic disease, therefore, could be an endocrine disorder and could possibly explain the
                                                                                                                          predisposition of the female gender. As health care professionals living with the disease, we would like to
                                                                                                                          bridge the gap and help you help us return to our normal, pre-CFIDS/ME lives as best we can.
ME Research UK — Database of Research Publications 2000

 Soderlund A, Skoge AM,       Department of Public Health    "I could not lift my arm        Scand J Prim Health Care     OBJECTIVES: To explore and describe symptoms and their consequences for patients suffering from
 Malterud K.                  and Primary Health Care,       holding the fork...". Living    2000 Sep;18(3):165-9         chronic fatigue syndrome (CFS). DESIGN: Qualitative data from a group interview, written answers to a
                              University of Bergen,          with chronic fatigue                                         questionnaire and a follow-up meeting analysed in accordance with Giorgi's phenomenological approach.
                              Norway.                        syndrome.                                                    SUBJECTS: Purposeful sample of 10 women and 2 men of various ages recruited from the local self-help
                                                                                                                          patient organisation. MAIN OUTCOME MEASURES: Descriptions reflecting the nature, extent and
                                                                                                                          consequences of symptoms regarded as the most substantial by the informants across the group. RESULTS:
                                                                                                                          Extreme exhaustion exceeding the nature of everyday weariness was reported as the worst symptom. The
                                                                                                                          informants perceived reduced muscular strength, continuous weakness and recurrent pain, problems related
                                                                                                                          to memory and concentration, sleep disturbances and excessive sensitivity towards smell, light and sound.
                                                                                                                          Learning abilities had deteriorated, and housework, conversation, reading and watching TV were
                                                                                                                          characterised as exhausting, leading to an unpredictability of everyday life-disturbing social relations.
                                                                                                                          CONCLUSION: The extent and nature of symptoms suggest that CSF is an essentially different and far
                                                                                                                          more serious condition than the strains of everyday life. Our findings suggest immunological processes
                                                                                                                          affecting the neuromuscular and central neural system comparable to the effects of cytostatic medication.
 Soetekouw PM, Wevers         Department of Medicine,        Normal carnitine levels in      Neth J Med 2000              BACKGROUND: Patients with chronic fatigue syndrome (CFS) complain of muscle pain and impaired
 RA, Vreken P, Elving LD,     Division of General Internal   patients with chronic fatigue   Jul;57(1):20-4               exercise tolerance. Previous studies show that this is due to systemic carnitine deficiency. We investigated
 Janssen AJ, van der Veen     Medicine 541, University       syndrome.                                                    the hypothesis that carnitine deficiency plays an important role in CFS in female CFS patients and
 Y, Bleijenberg G, van der    Medical Center St. Radboud,                                                                 compared their results with neighbourhood controls. METHODS: The level of total carnitine, free carnitine,
 Meer JW.                     P.O. Box 9101, 6500 HB,                                                                     acylcarnitine and carnitine esters were measured in 25 female CFS patients and 25 healthy matched
                              Nijmegen, The Netherlands.                                                                  neighbourhood controls in a blinded fashion. RESULTS: The previously reported decreased level of
                                                                                          acylcarnitine in CFS patients was not confirmed. There were also no significant differences in levels of
                                                                                                                          total carnitine, free carnitine and 20 carnitine esters between CFS patients and controls. CONCLUSIONS:
                                                                                                                          The present study demonstrates that serum carnitine deficiency does not contribute to or causes the
                                                                                                                          symptoms in many CFS patients.
 Spath M, Welzel D, Farber    Friedrich-Baur-Institut,       Treatment of chronic fatigue    Scand J Rheumatol Suppl      OBJECTIVE: The serotonin system presumably is involved in the pathogenesis of chronic fatigue
 L.                           University of Munich,          syndrome with 5-HT3             2000;113:72-7                syndrome (CFS). Results from a few studies led to the hypothesis of a "postsynaptic hyperresponsiveness"
                              MunchenGermany.                receptor antagonists--                                       in CFS. Therefore we intended to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of
                              Michael.Spaeth@LRZ.uni-        preliminary results.                                         CFS. PATIENTS AND METHODS: 2 patient groups (10 patients each; CFS according to the CDC
                                                                                                     classification criteria) received either oral tropisetron (5 mg once daily) or oral ondansetron (2 x 8 mg
                                                                                                                          daily), open-labelled. Treatment duration was 15 days. Treatment response was evaluated by visual analog
                                                                                                                          scales (VAS) for fatigue and capability. RESULTS: 19 patients finished their respective study. In the
                                                                                                                          tropisetron group 6/9 (VAS fatigue) and 7/9 (VAS capability) patients documented benefit, 8/10 rsp. 8/10
                                                                                                                          patients in the ondansetron group. The score changes (VAS before and after treatment) in case of response
                                                                                                                          were more pronounced in the tropisetron group. The frequency of concomitant symptoms did not differ
                                                                                                                          significantly in the treatment groups. The overall analysis of both studies showed a remarkable
                                                                                                                          improvement (> or = 35%) of approximately one third of the patients in both VAS. Treatment was well
                                                                                                                          tolerated. CONCLUSION: Our preliminary results encourage to perform placebo-controlled, double-blind
                                                                                                                          studies to further evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.
 Spence VA, Khan F, Belch     University Department of       Enhanced sensitivity of the     Am J Med 2000 Jun
 JJ.                          Medicine, Ninewells Hospital   peripheral cholinergic          15;108(9):736-9Comment in:
                              and Medical School, Dundee,    vascular response in patients   Am J Med. 2000 Dec
                              Scotland.                      with chronic fatigue            15;109(9):744
 Starr A, Scalise A, Gordon   Department of Neurology,       Motor cortex excitability in    Clin Neurophysiol 2000       OBJECTIVE: To use transcranial magnetic stimulation (TMS) to define motor cortical excitability in
 R, Michalewski HJ,           University of California,      chronic fatigue syndrome.       Nov;111(11):2025-31          chronic fatigue syndrome (CFS) subjects during a repetitive, bilateral finger movement task. METHODS:
 Caramia MD.                  Irvine, CA 92697-4290,                                                                      A total of 14 CFS patients were tested and compared with 14 age-matched healthy control subjects. TMS of
                              USA.                                                                         the motor cortex (5% above threshold) was used to elicit motor evoked potentials (MEPs). Subjects
                                                                                                                          performed regular (3-4/s) repetitive bilateral opening-closing movements of the index finger onto the
                                                                                                                          thumb. MEPs of the first dorsal interosseus (FDI) were measured before, immediately following exercise
                                                                                                                          periods of 30, 60 and 90 s, and after 15 min of rest. RESULTS: Performance, defined by rate of movement,
                                                                                                                          was significantly slower in CFS subjects (3.5/s) than in controls (4. 0/s) independent of the hand measured.
ME Research UK — Database of Research Publications 2000

                                                                                                                          The rate, however, was not significantly affected by the exercise duration for either group. The threshold of
                                                                                                                          TMS to evoke MEPs from the FDI muscle was significantly higher in CFS than in control subjects,
                                                                                                                          independent of the hemisphere tested. A transient post-exercise facilitation of MEP amplitudes
                                                                                                                          immediately after the exercise periods was present in controls independent of the hemisphere tested, but
                                                                                                                          was absent in CFS subjects. A delayed facilitation of MEPs after 15-30 min of rest was restricted to the
                                                                                                                          non-dominant hemisphere in controls; delayed facilitation was absent in CFS subjects. CONCLUSIONS:
                                                                                                                          Individuals with CFS do not show the normal fluctuations of motor cortical excitability that accompany
                                                                                                                          and follow non-fatiguing repetitive bimanual finger movements.
 Steven ID, McGrath B,      Royal Australian College of    General practitioners' beliefs,   Aust Fam Physician 2000      OBJECTIVE: To undertake a survey of Australian general practitioners (GPs) to explore their beliefs,
 Qureshi F, Wong C, Chern   General Practitioners, South   attitudes and reported actions    Jan;29(1):80-5               attitudes and reported actions with respect to chronic fatigue syndrome (CFS). METHOD: A random
 I, Pearn-Rowe B.           Australia.                     towards chronic fatigue                                        sample of 2090 Australian GPs, stratified by state, was surveyed in May-August 1995. RESULTS: A 77%
                                                           syndrome.                                                      response rate was obtained. For the majority of practitioners who pursue a diagnosis of CFS, six symptoms
                                                                                                                          were considered to be of significance: chronic unremitting fatigue for over 6 months; failure to recover
                                                                                                                          energy after rest; reduced exercise tolerance; prostration for several days after exercise; generalised myalgia
                                                                                                                          and poor concentration. Individual counselling was the most frequently used treatment. Thirty-one percent
                                                                                                                          of practitioners reported that they did not believe that CFS is a distinct syndrome. Of these, 70% reported
                                                                                                                          that the most likely cause of chronic fatigue was depression. CONCLUSION: There is considerable
                                                                                                                          diversity of opinion between practitioners about CFS. The diversity extends from questioning whether the
                                                                                                                          syndrome even exists to different strategies for diagnosis and management.
 Stewart JM.                Department of Pediatrics,      Autonomic nervous system          Pediatr Res 2000             The objective was to determine the nature of autonomic and vasomotor changes in adolescent patients with
                            The Center for Pediatric       dysfunction in adolescents        Aug;48(2):218-26             orthostatic tachycardia associated with the chronic fatigue syndrome (CFS) and the postural orthostatic
                            Hypotension, New York          with postural orthostatic                                      tachycardia syndrome (POTS). Continuous electrocardiography and arterial tonometry was used to
                            Medical College, Valhalla      tachycardia syndrome and                                       investigate the heart rate and blood pressure responses before and 3-5 min after head-up tilt in 22
                            10595, USA.                    chronic fatigue syndrome is                                    adolescents with POTS and 14 adolescents with CFS, compared with control subjects comprising 10
                                                           characterized by attenuated                                    healthy adolescents and 20 patients with simple faint. Heart rate and blood pressure variability, determined
                                                           vagal baroreflex and                                           baroreceptor function using transfer function analysis, and measured cardiac vagal and adrenergic
                                                           potentiated sympathetic                                        autonomic responses were calculated using timed breathing and the quantitative Valsalva maneuver. Two
                                                           vasomotion.                                                    of 10 healthy controls and 14 of 20 simple faint patients experienced vasovagal syncope during head-up
                                                                                                                          tilt. By design, all CFS and POTS patients experienced orthostatic tachycardia, often associated with
                                                                                                                          hypotension. R-R interval and heart rate variability were decreased in CFS and POTS patients compared
                                                                                                                          with control subjects and remained decreased with head-up tilt. Low-frequency (0.05-0.15 Hz) blood
                                                                                                                          pressure variability reflecting vasomotion was increased in CFS and POTS patients compared with control
                                                                                                                          subjects and increased further with head-up tilt. This was associated with depressed baroreflex transfer
                                                                                                                          indicating baroreceptor attenuation through defective vagal efferent response. Only the sympathetic
                                                                                                                          response remained. Heart rate variability declined progressively from normal healthy control subjects
                                                                                                                          through syncope to POTS to CFS patients. Timed breathing and Valsalva maneuver were most often
                                                                                                                          normal in CFS and POTS patients, although abnormalities in select individuals were found. Heart rate and
                                                                                                                          blood pressure regulation in POTS and CFS patients are similar and indicate attenuated efferent vagal
                                                                                                                          baroreflex associated with increased vasomotor tone. Loss of beat-to-beat heart rate control may contribute
                                                                                                                          to a destabilized blood pressure resulting in orthostatic intolerance. The dysautonomia of orthostatic
                                                                                                                          intolerance in POTS and in chronic fatigue are similar.
 Stough C, Withers G.                                      Sleep Disturbance in Patients     Journal of Chronic Fatigue   To examine whether the identification of patients with Chronic Fatigue Syndrome can be made using more
                                                           with Chronic Fatigue              Syndrome 2000; 6(2): 37      objective criteria than presently available (1), we compared 14 patients with Chronic Fatigue Syndrome
                                                           Syndrome and Chronic                                           and 12 patients with chronic fatigue (but who did not meet the criteria for Chronic Fatigue Syndrome) on
                                                           Fatigue                                                        sleep architecture, continuity, and sleep abnormalities from polysomnography recordings. No differences in
                                                                                                                          sleep continuity or architecture were found between the two groups, except that patients with Chronic
                                                                                                                          Fatigue Syndrome recorded significantly increased sleep latencies. There were no differences in the
                                                                                                                          frequency of sleep disorders. Results indicated that apart from sleep latency, other sleep variables do not
                                                                                                                          adequately differentiate patients with CFS from those with chronic fatigue and that other variables should
                                                                                                                          be examined, which may validly diagnose patients with CFS.
 Streeten DH, Thomas D,     Department of Medicine,        The roles of orthostatic          Am J Med Sci 2000            BACKGROUND: Orthostatic hypotension during upright tilt is an important physical disorder in patients
ME Research UK — Database of Research Publications 2000

 Bell DS.                     State University of New York   hypotension, orthostatic        Jul;320(1):1-8               with chronic fatigue syndrome. We have tested its occurrence during prolonged standing, whether it is
                              Health Science Center,         tachycardia, and subnormal                                   correctable, and whether reduced circulating erythrocyte volume is present. METHODS: Fifteen patients
                              Syracuse 13210, USA.           erythrocyte volume in the                                    were randomly selected from a large population of patients with chronic fatigue syndrome, studied, and
                                                             pathogenesis of the chronic                                  observed for several years (by DSB). Blood pressure (BP) and heart rate (HR) measured with Dinamap
                                                             fatigue syndrome.                                            every minute for 30 minutes supine and 60 minutes standing were compared with these findings in 15
                                                                                                                          healthy age- and gender-matched control subjects and later during lower body compression with military
                                                                                                                          antishock trousers (MAST). Plasma catecholamines and circulating erythrocyte and plasma volumes were
                                                                                                                          also measured by isotopic dilution methods. RESULTS: Abnormal findings in the patients included
                                                                                                                          excessive orthostatic reductions in systolic (P < 0.001) and diastolic BP (P < 0.001) and excessive
                                                                                                                          orthostatic tachycardia (P < 0.01), together with presyncopal symptoms in 11 of the 15 patients and in none
                                                                                                                          of the control subjects after standing for 60 min. Lower body compression with the MAST restored all
                                                                                                                          orthostatic measurements to normal and overcame presyncopal symptoms within 10 min. Circulating
                                                                                                                          erythrocyte but not plasma volumes were subnormal in the 12 women (P < 0.01) and plasma
                                                                                                                          norepinephrine concentration rose excessively after standing for 10 min. CONCLUSION: Delayed
                                                                                                                          orthostatic hypotension and/or tachycardia caused by excessive gravitational venous pooling, which is
                                                                                                                          correctable with external lower-body compression, together with subnormal circulating erythrocyte volume,
                                                                                                                          are very frequent, although not invariably demonstrable, findings in moderate to severe chronic fatigue
                                                                                                                          syndrome. When present, they may be involved in its pathogenesis.
 Suhadolnik RJ, Peterson                                     Biochemical Dysregulation       Journal of Chronic Fatigue   The aim of the current study was to examine the biochemical defects in KEY components of the 2i,5i-
 DL, Cheney PR, Horvath                                      of the 2-5A                     Syndrome 2000; 5(3/4): 223   oligoadenylate (2-5A) synthetase/RNase L antiviral pathway in an extended cohort of patients with chronic
 SE, Reichenbach NL,                                         Synthetase/RNase L Antiviral                                 fatigue syndrome (CFS) from two sites. CFS patients, who met the CDC criteria for CFS, and matched
 O'Brien K, Lombardi V,                                      Defense Pathway in Chronic                                   controls were assessed with respect to their general health, depression, and pain. Biochemical assays were
 Welsch S, Furr EG,                                          Fatigue Syndrome                                             completed for three blood draws over a period of one year. Analysis of the mean values for bioactive 2-5A,
 Charubala R, Pfleiderer W.                                                                                               RNase L activity, low molecular weight (LMW) RNase L in CFS PBMC extracts confirmed the statistically
                                                                                                                          significant upregulation of the 2-5A synthetase/RNase L pathway compared to control PBMC extracts (p =
                                                                                                                          .001, .002, and .007, respectively). Clinical correlates to the biochemical findings included a negative
                                                                                                                          correlation between Karnofsky Performance Score and bioactive 2-5A (p = .025) or RNase L activity (p =
                                                                                                                          .002) and positive correlation between Metabolic Screening Questionnaire and RNase L activity (p = .01)
                                                                                                                          and between interferon- and LMW RNase L (p = .05). The evidence presented in this study more firmly
                                                                                                                          establishes the dysregulation of the 2-5A synthetase/RNase L pathway in CFS.
 Sweetman BJ.                                                Chronic fatigue syndrome in     J R Soc Med 2000
                                                             mother and child.               Jun;93(6):337-8 Comment
                                                                                             on: J R Soc Med. 2000
 Takahashi Y, Ohta S, Sano    Department of Pediatrics,      Does severe nutcracker          Clin Nephrol 2000            BACKGROUND: In the past five years we experienced 9 fatigued disabled children who were
 A, Kuroda Y, Kaji Y,         Tenri Hospital, Nara, Japan.   phenomenon cause pediatric      Mar;53(3):174-81             intermittently or persistently absent from school. PATIENTS: They had been suspected to be burdened with
 Matsuki M, Matsuo M.                                        chronic fatigue?                                             psychosomatic disorders, having orthostatic hypotension, postural tachycardia, or other autonomic
                                                                                                                          dysfunction symptoms. RESULTS: Investigating the cause of moderate orthostatic proteinuria in some of
                                                                                                                          them, we found by chance severe typical nutcracker phenomenon (NC), which was present in all 9 children
                                                                                                                          complaining of chronic fatigue. CONCLUSION: Their symptoms filled the criteria of chronic fatigue
                                                                                                                          syndrome or idiopathic chronic fatigue (CFS/CF). An association between severe NC and autonomic
                                                                                                                          dysfunction symptoms in children with CFS/CF has been presented.
 Takahashi Y, Sano A,                                        An effective "transluminal      Clin Nephrol 2000
 Matsuo M.                                                   balloon angioplasty" therapy    Jan;53(1):77-8
                                                             for pediatric chronic fatigue
                                                             syndrome with nutcracker
 Taylor RR, Jason LA,         Department of Psychology,      Fatigue rating scales: an       Psychol Med 2000             BACKGROUND: There has been limited research comparing the efficacy of different fatigue rating scales
 Torres A.                    DePaul University, Chicago,    empirical comparison.           Jul;30(4):849-56             for use with individuals with chronic fatigue syndrome (CFS). This investigation explored relationships
                              IL 60614, USA.                                                                              between two commonly-used fatigue rating scales in CFS research, the Fatigue Scale and the Fatigue
                                                                                                                          Severity Scale. Theoretically, these scales have been described as measuring different aspects of the fatigue
ME Research UK — Database of Research Publications 2000

                                                                                                                         construct. The Fatigue Scale was developed as a measure of the severity of specific fatigue-related
                                                                                                                         symptoms, while the Fatigue Severity Scale was designed to assess functional outcomes related to fatigue.
                                                                                                                         METHODS: Associations of these scales with the eight definitional symptoms of CFS and with eight
                                                                                                                         domains of functional disability were examined separately in: (1) an overall sample of individuals with a
                                                                                                                         wide range of fatigue severity and symptomatology; (2) a subsample of individuals with CFS-like
                                                                                                                         symptomatology, and, (3) a subsample of healthy controls. RESULTS: Findings revealed that both scales
                                                                                                                         are appropriate and useful measures of fatigue-related symptomatology and disability within a general
                                                                                                                         population of individuals with varying levels of fatigue. However, the Fatigue Severity Scale appears to
                                                                                                                         represent a more accurate and comprehensive measure of fatigue-related severity, symptomatology, and
                                                                                                                         functional disability for individuals with CFS-like symptomatology.
 Tomoda A, Miike T,          Department of Child            Chronic fatigue syndrome in    Brain Dev 2000                Chronic fatigue occurring in previously healthy children and adolescents is one of the most vexing
 Yamada E, Honda H,          Development, Kumamoto          childhood.                     Jan;22(1):60-4                problems encountered by pediatric practitioners. We report three cases, 11, 12 and 13-year-old children,
 Moroi T, Ogawa M, Ohtani    University School of                                                                        with chronic fatigue syndrome (CFS). They initially developed a low grade fever and generalized fatigue,
 Y, Morishita S.             Medicine, Japan.                                                                            followed by sleep disturbance and psychosomatic symptoms, and their performance ability deteriorated.
                             tomo@kaiju.medic.kumamot                                                                    They were diagnosed as having CFS on the basis of criteria. To investigate the brain function in CFS
                                                                                                      patients, we examined the regional cerebral blood flow by single-photon emission-computed tomography
                                                                                                                         (SPECT) with 111 MBq [123I]-iodoamphetamine (123I-IMP) or xenon-computed tomography (Xe-CT),
                                                                                                                         and brain metabolic levels by MR spectroscopy (MRS). Blood flow, expressed as the corticocerebellar ratio
                                                                                                                         (CCR), in the left temporal and occipital lobes was markedly lower in cases 2 and 3 than that in healthy
                                                                                                                         subjects reported by another investigator. In case 1, however, blood flow in the left basal ganglia and
                                                                                                                         thalamus was markedly higher than in healthy subjects. The MR spectroscopy (MRS) study revealed
                                                                                                                         remarkable elevation of the choline/creatine ratio in the patients with CFS. None of our patients exhibited
                                                                                                                         evidence of focal structural abnormalities on MRI. These findings suggest that the various clinical
                                                                                                                         symptoms in CFS patients may be closely related to an abnormal brain function.
 Treib J, Grauer MT, Haass   Department of Neurology,       Chronic fatigue syndrome in    Eur Neurol 2000;43(2):107-9   Several authors have reported a chronic fatigue-like syndrome in patients that have suffered from Lyme
 A, Langenbach J, Holzer     University Hospital of the     patients with Lyme                                           borreliosis in the past. To further investigate this suspicion of an association without sample bias, we
 G, Woessner R.              Saarland, Homburg,             borreliosis.                                                 carried out a prospective, double-blind study and tested 1, 156 healthy young males for Borrelia antibodies.
                             Germany.                                                                                    Seropositive subjects who had never suffered from clinically manifest Lyme borreliosis or neuroborreliosis
                                                                                                                         showed significantly more often chronic fatigue (p = 0.02) and malaise (p = 0.01) than seronegative
                                                                                                                         recruits. Therefore we believe it is worth examining whether an antibiotic therapy should be considered in
                                                                                                                         patients with chronic fatigue syndrome and positive Borrelia serology. Copyright 2000 S. Karger AG,
 Tuck I, Wallace D,                                         Psychosocial Response of       Journal of Chronic Fatigue    Chronic Fatigue Syndrome (CFS) is a chronic debilitating disease that affects two to five million persons in
 Casalnuova G, May B.                                       Sufferers of Chronic Fatigue   Syndrome 2000; 7(3): 49       the United States. Previous studies examined theories of etiology and have resulted in contradictory
                                                            Syndrome                                                     findings. This study explored the psychosocial factors associated with CFS. Questionnaires were
                                                                                                                         administered to 49 CFS sufferers and a matched sample of non-CFS sufferers. Significant differences were
                                                                                                                         found in the perception of stress and its causes, coping styles, and emotional responses to affective states as
                                                                                                                         measured by the Ways of Coping, Derogatis Stress, Trait Anger, Perceived Stress, and Profile of Moods
                                                                                                                         scales. Groups were not different on the measure of trait anger. The findings indicated that associated
                                                                                                                         psychosocial factors do influence the illness trajectory and the quality of life of CFS sufferers. These
                                                                                                                         findings have implications for nursing practice.
 Tuck I, Wallace D.          School of Nursing, Virginia    Chronic fatigue syndrome: a    Health Care Women Int 2000    Chronic Fatigue Syndrome (CFS) is an illness characterized by fatigue with varying levels of disability.
                             Commonwealth University,       woman's dilemma.               Jul-Aug;21(5):457-66          According to the Centers for Disease Control (CDC) there are 2 to 5 million people in the United States
                             1220 East Broad Street, P.O.                                                                who suffer from CFS and a disproportionate number are women. There are many theories of etiology of the
                             Box 980567, Richmond, VA                                                                    condition and controversy has surrounded recommendations for diagnosis and treatment. CFS can mimic
                             23298-0567, USA.                                                                            other diseases and women are doubly affected since many have comorbid conditions. While diagnoses and
                                                                                              treatment are critical to the health of women, having the disease and coping with the symptoms may have a
                                                                                                                         greater impact on their well-being and quality of life. The authors report qualitative data describing the
                                                                                                                         experience of having CFS (N = 22) and quantitative responses of 42 CFS sufferers reporting psychosocial
                                                                                                                         factors. The psychosocial factors were measured by the Derogatis Stress Profile (DSP), Spielberger Trait-
                                                                                                                         Anger Scale, Ways of Coping Survey, Profile of Moods States (POMS) Survey, and the Perceived Stress
ME Research UK — Database of Research Publications 2000

                                                                                                                          Scale. The findings indicate that CFS changes the lives of women who suffer with the disease and disrupts
                                                                                                                          their relationships, careers, and perceptions of themselves.
 Uter W.                                                     Chronic fatigue syndrome        Contact Dermatitis 2000
                                                             and nickel allergy              Jan;42(1):56-7 Comment on:
                                                                                             Contact Dermatitis. 1999
 Valling RS.                                                 Report on the Second World      Journal of Chronic Fatigue
                                                             Congress on Chronic Fatigue     Syndrome 2000; 6(3/4): 3
                                                             Syndrome and Related
                                                             Disorders: Towards Effective
                                                             Diagnosis and Treatment in
                                                             the 21st Century
 van der Steen WJ.            Faculties of Biology and       Chronic fatigue syndrome: a     Med Hypotheses 2000          The etiology of chronic fatigue syndrome (CFS) remains an enigma. But literature concerning chronic
                              Philosophy, Vrije              matter of enzyme                May;54(5):853-4              fatigue which does not focus on CFS points to all sorts of enzyme deficiencies as possible causes. The
                              Universiteit, Amsterdam, The   deficiencies?                                                deficiencies are probably dismissed as causes of CFS because other characteristic symptoms are lacking in
                              Netherlands.                                                                 CFS patients. But these symptoms are often also lacking in patients with a deficiency. Symptom patterns in
                                                                                                                          enzyme deficiencies are extremely variable. Therefore, patients with CFS should be screened systematically
                                                                                                                          for enzyme deficiencies. Copyright 2000 Harcourt Publishers Ltd.
 van der Werf SP, Prins JB,   Department of Medical          Abnormal                        Neuropsychiatry              OBJECTIVE: The aim of this study was to assess the potential impact of effort in comparative studies
 Jongen PJ, van der Meer      Psychology, University         neuropsychological findings     Neuropsychol Behav Neurol    assessing neurocognitive dysfunction in patients with and without a neurologic diagnosis.
 JW, Bleijenberg G.           Hospital Nijmegen, The         are not necessarily a sign of   2000 Jul;13(3):199-203       BACKGROUND: It was hypothesized that a subgroup within a group of patients with prominent
                              Netherlands.                   cerebral impairment: a                                       neurocognitive complaints but without a neurologic diagnosis would have impaired performance on a task
                                                             matched comparison between                                   originally designed to detect malingering. METHOD: We compared the neuropsychological performance of
                                                             chronic fatigue syndrome and                                 a group of 40 patients with a definite diagnosis of multiple sclerosis (MS) with that of 67 patients with
                                                             multiple sclerosis.                                          chronic fatigue syndrome (CFS). The Amsterdam Short-Term Memory Test, a forced-choice memory task,
                                                                                                                          served as measure to detect submaximal effort. In addition, we administered a regular neuropsychological
                                                                                                                          task generally considered to be sensitive for cognitive deterioration. RESULTS: Compared with the MS
                                                                                                                          group (13%), a larger proportion of the matched CFS group (30%) obtained scores indicative of reduced
                                                                                                                          effort. In contrast, the proportions of patients scoring below the cutoff value on a conventional
                                                                                                                          neuropsychological test did not differ significantly (17% of MS patients and 16% of CFS patients).
                                                                                                                          CONCLUSIONS: The results obtained raise the question of to what extent abnormal test findings in the
                                                                                                                          absence of documented neurologic impairment should be interpreted as a sign of cerebral impairment. The
                                                                                                                          suggestion has been made to screen more often for biased results in comparative research studies so as to
                                                                                                                          enhance valid interpretation of neuropsychological findings.
 van der Werf SP, Prins JB,   The Netherlands Fatigue        Identifying physical activity   J Psychosom Res 2000         OBJECTIVE: Changes in physical activity are thought to play an important role in maintaining symptoms
 Vercoulen JH, van der        Research Group Nijmegen,       patterns in chronic fatigue     Nov;49(5):373-9              in chronic fatigue syndrome (CFS). The aim of this study was to describe intraindividual physical activity
 Meer JW, Bleijenberg G.      Department of Medical          syndrome using actigraphic                                   patterns in more detail and to identify pervasively passive patients. METHODS: With help of a movement-
                              Psychology and Internal        assessment.                                                  sensing device, physical activity levels were registered continuously over a 12-day period in 277 CFS
                              Medicine, University                                                                        patients. Within this registration period, the 10 largest activity peaks were computed. The intensity and
                              Hospital Nijmegen, Post Box                                                                 duration of these activity peaks and their subsequent rest periods were described and compared to those of
                              9101, 6500 HB, Nijmegen,                                                                    47 healthy controls. In addition, the patients' 12 daily activity scores were used to identify patients who
                              The Netherlands.                                                                            were characterised by low levels of physical activity throughout the registration period. RESULTS: The
                                                                                      CFS sample had less intense and shorter activity peaks, while the average rest periods that followed these
                                                                                                                          peaks lasted longer. Approximately one-fourth of the CFS sample differed distinctly from the control group
                                                                                                                          and was labelled as pervasively passive. CONCLUSION: The measurements and classification of actual
                                                                                                                          physical activity levels were found to reduce heterogeneity in the CFS population and therefore could
                                                                                                                          provide the opportunity to optimise behavioural intervention protocols for CFS.
 Van Houdenhove B,                                           Chronic fatigue syndrome.       Am J Med 2000 Aug
 Vanthuyne S, Neerinckx E                                                                    15;109(3):257-9 Comment
                                                                                             on: Am J Med. 2000
                                                                                             Feb;108(2):99-105 Am J
ME Research UK — Database of Research Publications 2000

                                                                                           Med. 2000 Feb;108(2):169-
                                                                                           71 Am J Med. 2000
 Visser JT, De Kloet ER,   TNO Prevention and Health,      Altered glucocorticoid          Ann N Y Acad Sci             It is increasingly recognized that glucocortiocoids (GCs) can have subtle modulatory effects in
 Nagelkerken L.            Division of Immunological       regulation of the immune        2000;917:868-75              immunoregulation rather than having generalized immunosuppressive effects. GCs suppress Th1 cells and
                           and Infectious Diseases, P.O.   response in the chronic                                      cellular immunity, but may favor Th2 responses and humoral immunity. The chronic fatigue syndrome
                           Box 2215, 2301 CE Leiden,       fatigue syndrome.                                            (CFS) appears to be associated with a disturbed HPA-axis. Moreover, CFS patients show several
                           The Netherlands.                                                                             immunological changes suggestive of decreased cellular immunity. It is postulated herein that in CFS
                                                                                                                        patients a decreased Th1/Th2 balance may be the result of selective effects of GC on the IL-10/IL-12
                                                                                                                        regulatory circuit.
 Vojdani A, Franco R.                                      Muliplex PCR for the            Journal of Chronic Fatigue   A multiplex polymerase chain reaction (PCR) was used to detect mycoplasma infection in human DNA
                                                           Detection of Mycoplasma         Syndrome 2000; 5(3/4): 187   samples of patients with CFS and related illnesses. One set of oligonucleotide primers which are specific
                                                           fermentans, M. hominis, and                                  for a highly conserved region among all members of the genus Mycoplasma along with three other primer
                                                           M. penetrans in Patients with                                sets which are specific for Mycoplasma fermentans, M. hominis, and M. penetrans species were used in
                                                           Chronic Fatigue Syndrome,                                    this assay. The sensitivity of detection was determined by adding known mycoplasma DNA copy numbers
                                                           Fibromyalgia, Rheumatoid                                     to 1 mg of genomic DNA from healthy subjects. Each sample was subjected to 40 cycles of amplification.
                                                           Arthritis, and Gulf War                                      The detection level was determined to be 7, 7, 9, and 15 mycoplasma DNA copies per mg of human
                                                           Syndrome                                                     genomic DNA for M. genus, M. fermentans, M. hominis, and M. penetrans, respectively. The assay was
                                                                                                                        applied to DNA extracted from the PBMCs of individuals suffering from chronic fatigue syndrome (CFS)
                                                                                                                        (n = 100), fibromyalgia (FMS) (n = 40), rheumatoid arthritis (RA) (n = 60), and gulf war syndrome (GWS)
                                                                                                                        (n = 60) and compared to age- and sex-matched healthy individuals (n = 160). The percentage of M. genus
                                                                                                                        infection detected in CFS, FMS, RA, and GWS was 52, 54, 49, and 55%, respectively. M. fermentans was
                                                                                                                        detected in 32, 35, 23, and 36%, M. hominis was detected in 9, 8, 11, and 5%, and M. penetrans was
                                                                                                                        detected in 6, 4, 7, and 3% of CFS, FMS, RA, and GWS patients, respectively. M. genus, M. fermentans,
                                                                                                                        M. hominis, and M. penetrans were detected in 15, 8, 3, and 2% of healthy matched controls. This assay
                                                                                                                        provides a rapid and cost efficient procedure to screen clinical samples for the presence of three potentially
                                                                                                                        pathogenic species of Mycoplasma with a high level of sensitivity and specificity.
 Vojdani A, Lapp CW.                                       The Relationship Between        Journal of Chronic Fatigue   Overlapping symptomatologies between chronic fatigue syndrome (CFS) and chemical sensitivity have
                                                           Chronic Fatigue Syndrome        Syndrome 2000; 5(3/4): 207   been observed by different investigators. Interferon-induced proteins 2-5A synthetase and protein kinase
                                                           and Chemical Exposure                                        RNA (PKR) have been implicated in the viral induction of CFS. The objective of this study was to measure
                                                                                                                        2-5A and PKR activity in patients with CFS and toxic chemical exposure. Based on the CDC definition
                                                                                                                        and criteria, twenty CFS patients who were positive for viral genome(s) (mainly HHV6; HTLV II, EBV,
                                                                                                                        and CMV) and did not have any history of exposure to toxic chemicals were included in this study. As a
                                                                                                                        comparison, the second group of patients consisted of twenty individuals from the same geographical area
                                                                                                                        who were negative for viral genomes but had been exposed to methyl tertiary-butyl ether concentration of
                                                                                                                        up to 70 ppb and benzene concentration up to 14 ppb. All patients complained of fatigue and other
                                                                                                                        symptoms overlapping between the two groups. From all 40 patients, blood was drawn, leukocyte extract
                                                                                                                        was prepared and assayed for 2-5A synthetase and PKR activity. Clinical specimens which were positive
                                                                                                                        for viral genomes showed from 2. 2-38.7 fold increase in 2-5A activity and 1.3-13.5 fold increase in PKR
                                                                                                                        activities over the background of the healthy controls. Similarly, the second group (negative for viral
                                                                                                                        genomes, but exposed to chemicals) showed a 1.1-29.2 fold increase for 2-5A synthetase and a 1.3-11.6
                                                                                                                        fold increase for PKR when they were compared to healthy subjects. To elucidate mechanisms involved in
                                                                                                                        viral versus chemical induction of 2-5A synthetase and PKR, MDBK cell lines were cultured either in the
                                                                                                                        presence or absence of HHV6, MTBE, or benzene. 2-5A and PKR activities were measured in all the above
                                                                                                                        conditions. A clear induction of 2-5A and PKR was observed when MDBK cells were exposed to HHV6,
                                                                                                                        MTBE, and benzene indicating that induction of interferon-induced proteins are not unique to viruses. We
                                                                                                                        conclude that 2-5A and PKR are not only biomarkers for viral induction of CFS, but biomarkers to other
                                                                                                                        stressors that include MTBE and benzene.
 Waxman SG, Ptacek LJ.                                     Chronic fatigue syndrome        Med Hypotheses 2000
                                                           and channelopathies             Nov;55(5):457Comment in:
                                                                                           Med Hypotheses. 2000
ME Research UK — Database of Research Publications 2000

                                                                                             Dec;55(6):524 and Med
                                                                                             Hypotheses. 2000
 Werbach MR.                  UCLA School of Medicine,      Nutritional strategies for       Altern Med Rev 2000     Despite considerable worldwide efforts, no single etiology has been identified to explain the development
                              California, USA.              treating chronic fatigue         Apr;5(2):93-108         of chronic fatigue syndrome (CFS). It is likely that multiple factors promote its development, sometimes
                                                            syndrome.                                                with the same factors both causing and being caused by the syndrome. A detailed review of the literature
                                                                                                                     suggests a number of marginal nutritional deficiencies may have etiologic relevance. These include
                                                                                                                     deficiencies of various B vitamins, vitamin C, magnesium, sodium, zinc, L-tryptophan, L-carnitine,
                                                                                                                     coenzyme Q10, and essential fatty acids. Any of these nutrients could be marginally deficient in CFS
                                                                                                                     patients, a finding that appears to be primarily due to the illness process rather than to inadequate diets. It is
                                                                                                                     likely that marginal deficiencies not only contribute to the clinical manifestations of the syndrome, but also
                                                                                                                     are detrimental to the healing processes. Therefore, when feasible, objective testing should identify them
                                                                                                                     and their resolution should be assured by repeat testing following initiation of treatment. Moreover,
                                                                                                                     because of the rarity of serious adverse reactions, the difficulty in ruling out marginal deficiencies, and
                                                                                                                     because some of the therapeutic benefits of nutritional supplements appear to be due to pharmacologic
                                                                                                                     effects, it seems rational to consider supplementing CFS patients with the nutrients discussed above, along
                                                                                                                     with a general high-potency vitamin/mineral supplement, at least for a trial period.
 White C, Schweitzer R.       Department of Psychology      The role of personality in the   J Psychosom Res 2000    OBJECTIVES: Qualitative evidence suggests that personality may have special relevance to the
                              and Counselling, Queensland   development and                  Jun;48(6):515-24        predisposition, precipitation and perpetuation of chronic fatigue syndrome (CFS). This study compares
                              University of Technology,     perpetuation of chronic                                  three dimensions of personality - perfectionism, self-esteem, and emotional control in the personality
                              Brisbane, Australia.          fatigue syndrome.                                        profiles of CFS patients (N=44) and a control group (N=44) without a history of CFS, matched for age and
                                                                                                                     gender. METHODS: Participants were assessed on the MPS [Frost RO, Marten P, Lahart C, Rosenblate R.
                                                                                                                     The dimensions of perfectionism. Cognit Ther Res 1990;14:449-468.]; the Rosenberg Self-Esteem Scale
                                                                                                                     [Rosenberg M. Society and the Adolescent Self-image. Princeton, NJ: Princeton Univ Press, 1965.]; the
                                                                                                                     Courtauld Emotional Scale [Watson M, Greer S. Development of a questionnaire measure of emotional
                                                                                                                     control. J Psychosom Res 1983;27:299-305.] and the Marlowe-Crowne Social Desirability Scale [Crowne
                                                                                                                     DP, Marlowe D. A new scale of social desirability independent of psychopathology. J Consult Psychol
                                                                                                                     1960;24:349-354.]. RESULTS: Analyses revealed that the CFS group reported higher levels than the
                                                                                                                     control group on the Total Perfectionism score and Doubts about Actions and the Concern over Mistakes
                                                                                                                     subscales. Furthermore, the CFS group also reported lower self-esteem than the control group. No
                                                                                                                     difference between the two groups was found on the dimensions of emotional control and social desirability
                                                                                                                     response bias. CONCLUSION: A developmental model of CFS, which considers the predisposing,
                                                                                                                     precipitating, and perpetuating factors that may account for the course of the disorder irrespective of
                                                                                                                     etiology, is proposed. In the context of the results, recommendations for practice and future research are
 White KP, Speechley M,       Department of Medicine,       Co-existence of chronic          Scand J Rheumatol       OBJECTIVE: To determine the proportion of adults with fibromyalgia syndrome (FMS) in the general
 Harth M, Ostbye T.           University of Western         fatigue syndrome with            2000;29(1):44-51        population who also meet the 1988 Centre for Disease Control (CDC) criteria for chronic fatigue syndrome
                              Ontario, London, Canada.      fibromyalgia syndrome in the                             (CFS). METHODS: Seventy-four FMS cases were compared with 32 non-FMS controls with widespread
                            general population. A                                    pain and 23 with localized pain, all recruited in a general population survey. RESULTS: Among females,
                                                            controlled study.                                        58.0% of fibromyalgia cases met the full criteria for CFS, compared to 26.1% and 12.5% of controls with
                                                                                                                     widespread and localized pain, respectively (p=0.0006). Male percentages were 80.0, 22.2, and zero,
                                                                                                                     respectively (p=0.003). Compared to those with FMS alone, those meeting the case definitions for both
                                                                                                                     FMS and CFS reported a worse course, worse overall health, more dissatisfaction with health, more non-
                                                                                                                     CFS symptoms, and greater disease impact. The number of total symptoms and non-CFS symptoms were
                                                                                                                     the best predictors of co-morbid CFS. CONCLUSIONS: There is significant clinical overlap between CFS
                                                                                                                     and FMS.
 White PD.                                                  The role of physical             J Psychosom Res 2000
                                                            inactivity in the chronic        Nov;49(5):283-4
                                                            fatigue syndrome.
 Wittrup IH, Christensen      Parker Research Institute,    Search for Borna disease         Scand J Rheumatol       OBJECTIVE: The purpose of this study was to look for Borna disease virus (BDV) in 18 patients with
 LS, Jensen B, Danneskiold-   Dept. of Rheumatology,        virus in Danish fibromyalgia     2000;29(6):387-90       acute onset of fibromyalgia (FMS) following a "flu-like" episode. BDV is a neurotropic RNA virus
ME Research UK — Database of Research Publications 2000

 Samsee B, Bliddal H, Wiik   Frederiksberg University       patients.                                                affecting horses and sheep. Infections in animals have been reported to cause immune mediated disease
 A.                          Hospital, Copenhagen,                                                                   characterized by abnormalities in behavior. A possible link between BDV and neuropsychiatric diseases in
                             Denmark.                                                                                man has been described, and lately a connection to chronic fatigue syndrome (CFS) has been suggested.
                                                                                    METHODS: A BDV-specific nested PCR (RT-PCR) was performed on serum and spinal fluid. RESULTS:
                                                                                                                     The BDV genome was not detected in any of the FMS cases. CONCLUSION: Although BDV was not
                                                                                                                     demonstrated in spinal fluid or serum from the tested patients with FMS, we believe that it is important to
                                                                                                                     report our results, since FMS can exhibit many manifestations in common with CFS. Possible reasons for
                                                                                                                     the discrepant findings are discussed.
 Woo SB, Schacterle RS,      Dept of Oral Medicine and      Salivary gland changes in     Oral Surg Oral Med Oral    OBJECTIVE: The purpose of this preliminary study is to compare labial salivary gland changes of 11
 Komaroff AL, Gallagher      Diagnostic Sciences, Harvard   chronic fatigue syndrome: a   Pathol Oral Radiol Endod   patients with chronic fatigue syndrome with control subjects. STUDY DESIGN: Changes in labial salivary
 GT.                         School of Dental Medicine,     case-controlled preliminary   2000 Jul;90(1):82-7        glands were graded from 0 to 3+ for acinar dilatation, ductal dilatation, periductal fibrosis, plasmacytic
                             Brigham and Women's            histologic study.                                        infiltrate, lymphocytic infiltrate, mast cell infiltrate, and lymphocytic aggregates or foci. RESULTS: Four
                             Hospital, USA.                                                                          of the 11 subjects had 2+ to 3+ changes in at least 4 of the 7 parameters examined. Only the presence of
                                                                                                                     mast cells was statistically significant between the 2 groups. Two of these 4 patients had 1 lymphocytic
                                                                                                                     focus per 4 mm(2) of tissue. CONCLUSIONS: The salivary gland changes in patients with chronic fatigue
                                                                                                                     syndrome show varying degrees of ductal and acinar dilatation, periductal fibrosis, lymphoplasmacytic
                                                                                                                     infiltrates, and occasional lymphocytic foci, all suggestive of primary gland damage. The one parameter
                                                                                                                     that showed statistical significance was the presence of mast cells (Fisher exact test, 0.0125).
 Zhang QW, Natelson BH,      Department of                  Chronic fatigue syndrome      Chronobiol Int 2000        The fact that many patients with chronic fatigue syndrome (CFS) have an infectious like sudden onset to
 Ottenweller JE, Servatius   Neurosciences, University of   beginning suddenly occurs     Jan;17(1):95-9             their illness has led to the hypothesis that CFS is a medical illness. If CFS were, on the other hand, a
 RJ, Nelson JJ, De Luca J,   Medicine and Dentistry-New     seasonally over the year.                                psychiatric disorder related to symptom amplification, one would expect illness onset to occur randomly
 Tiersky L, Lange G.         Jersey Medical School,                                                                  over the calendar year. This study tested that hypothesis with 69 CFS patients whose illness was on the
                             Newark, USA.                                                                            more severe side of the illness spectrum; all patients reported sudden illness onset with the full syndrome of
                                                                                                                     sore throat, fatigue/malaise, and diffuse achiness developing over no longer than a 2-day period. Date of
                                                                                                                     illness onset was distinctly nonrandom. It peaked from November through January and was at its lowest
                                                                                                                     from April through May. These data support the hypothesis that an infectious illness can trigger the onset
                                                                                                                     of CFS.

Shared By: