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 Authors                      Author Address                 Title                        Publication                    Abstract
 Arpino C, Carrieri MP,       Laboratorio di Epidemiologia   Idiopathic chronic fatigue   Ann Ist Super Sanita           The aim of the study was to compare the signs and symptoms of individuals meeting two different
 Valesini G, Pizzigallo E,    e Biostatistica, Istituto      and chronic fatigue          1999;35(3):435-41              definitions of chronic fatigue syndrome (CFS). Ninety-four patients fitting the eligibility criteria for
 Rovere P, Tirelli U, Conti   Superiore di Sanita, Rome,     syndrome: a comparison of                                   idiopathic fatigue were enrolled into the study. Of the 94 patients, 48 met the 1988 definition of CFS, 20
 F, Dialmi P, Barberio A,     Italy.                         two case-definitions.                                       the 1994 (but not the 1988) definition of CFS, and 26 met neither definition. The 1994 defined cases were
 Rusconi N, Bosco O,                                                                                                     more likely than 1988 defined cases, and non-syndromal individuals to be male, married, and high school
 Lazzarin A, Saracco A,                                                                                                  educated. The 1994 cases were less likely than 1988 cases to present acute onset, self reported sore throat,
 Moro ML, Vlahov D.                                                                                                      mild fever lymphadenopathy, pharyngitis. In conclusion, the 1994 criteria increased the number of patients
                                                                                                                         classified as CFS; however, those who fit only the 1994 criteria were less likely to have an acute
                                                                                                                         symptomatic onset and signs and symptoms suggestive of an infectious process.
 Ax S                                                        Coping Differences Between   Journal of Chronic Fatigue     The main objective of the present study was to describe the extent to which CFS sufferers and their carers
                                                             Chronic Fatigue Syndrome     Syndrome 1999: 5(2): 27 - 62   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 differed 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 indicated no
                                                                                                                         gender differences. There were also no differences between sufferers supported and not supported by a
                                                                                                                         carer. However, the results indicated 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.
 Barsky AJ, Borus JF.         Division of Psychiatry,        Functional somatic           Ann Intern Med 1999 Jun        The term functional somatic syndrome has been applied to several related syndromes characterized more by
                              Brigham and Women's            syndromes.                   1;130(11):910-21Comment        symptoms, suffering, and disability than by consistently demonstrable tissue abnormality. These syndromes
                              Hospital, Boston,                                           in: Ann Intern Med. 2000       include multiple chemical sensitivity, the sick building syndrome, repetition stress injury, the side effects of
                              Massachusetts 02115, USA.                                   Feb 15;132(4):327-8;           silicone breast implants, the Gulf War syndrome, chronic whiplash, the chronic fatigue syndrome, the
                                                                                          discussion 329-30 Ann Intern   irritable bowel syndrome, and fibromyalgia. Patients with functional somatic syndromes have explicit and
                                                                                          Med. 2000 Feb                  highly elaborated self-diagnoses, and their symptoms are often refractory to reassurance, explanation, and
                                                                                          15;132(4):327; discussion      standard treatment of symptoms. They share similar phenomenologies, high rates of co-occurrence, similar
                                                                                          329-30 Ann Intern Med.         epidemiologic characteristics, and higher-than-expected prevalences of psychiatric comorbidity. Although
                                                                                          2000 Feb 15;132(4):328-9;      discrete pathophysiologic causes may ultimately be found in some patients with functional somatic
                                                                                          discussion 329-30 Ann Intern   syndromes, the suffering of these patients is exacerbated by a self-perpetuating, self-validating cycle in
                                                                                          Med. 2000 Feb                  which common, endemic, somatic symptoms are incorrectly attributed to serious abnormality, reinforcing
                                                                                          15;132(4):328; discussion      the patient's belief that he or she has a serious disease. Four psychosocial factors propel this cycle of
                                                                                          329-30 Ann Intern Med.         symptom amplification: the belief that one has a serious disease; the expectation that one's condition is
                                                                                          2000 Feb 15;132(4):329;        likely to worsen; the "sick role," including the effects of litigation and compensation; and the alarming
                                                                                          discussion 329-30              portrayal of the condition as catastrophic and disabling. The climate surrounding functional somatic
                                                                                                                         syndromes includes sensationalized media coverage, profound suspicion of medical expertise and
                                                                                                                         physicians, the mobilization of parties with a vested self-interest in the status of functional somatic
                                                                                                                         syndromes, litigation, and a clinical approach that overemphasizes the biomedical and ignores psychosocial
                                                                                                                         factors. All of these influences exacerbate and perpetuate the somatic distress of patients with functional
                                                                                                                         somatic syndromes, heighten their fears and pessimistic expectations, prolong their disability, and reinforce
                                                                                                                         their sick role. A six-step strategy for helping patients with functional somatic syndromes is presented here.
                                                                                                                         Review, Academic
 Baschetti R.                                                Chronic fatigue syndrome.    N Z Med J 1999 Jun
                                                                                          25;112(1090):242 Comment
                                                                                          on: N Z Med J. 1999 Mar
 Baschetti R.                                                Psychological factors and    N Z Med J 1999 Feb
                                                             chronic fatigue syndrome.    26;112(1082):58-9 Comment
                                                                                          on: N Z Med J. 1998 Oct
 Baschetti R.                                                Hydrocortisone and chronic   Lancet 1999 May
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                                                     fatigue syndrome.               8;353(9164):1618;
                                                                                     discussion 1619-20
                                                                                     Comment on: Lancet. 1999
                                                                                     Feb 6;353(9151):455-8
 Baschetti R.                                        Low-dose hydrocortisone for     JAMA 1999 May
                                                     chronic fatigue syndrome.       26;281(20):1887; discussion
                                                                                     1888-9 Comment on: JAMA.
                                                                                     1998 Sep 23-
 Baschetti R.                                        Cortisol deficiency may         J Intern Med 1999
                                                     account for elevated            Apr;245(4):409-10Comment
                                                     apoptotic cell population in    in: J Intern Med. 1999
                                                     patients with chronic fatigue   Apr;245(4):410-2 Comment
                                                     syndrome.                       on: J Intern Med. 1997
 Baschetti R.                                        Investigations of               J Clin Endocrinol Metab
                                                     hydrocortisone and              1999 Jun;84(6):2263-4
                                                     fludrocortisone in the
                                                     treatment of chronic fatigue
 Baschetti R.                                        Overlap of chronic fatigue      Horm Metab Res 1999
                                                     syndrome with primary           Jul;31(7):439 Comment on:
                                                     adrenocortical insufficiency.   Horm Metab Res. 1999
 Baschetti R.                                        Fibromyalgia, chronic fatigue   Arch Intern Med 1999 Nov
                                                     syndrome, and Addison           8;159(20):2481; discussion
                                                     disease                         2482-3 Comment on: Arch
                                                                                     Intern Med. 1999 Apr
 Bazelmans E, Vercoulen    University Hospital       Chronic Fatigue Syndrome        Fam Pract 1999                BACKGROUND: Prevalence studies on Chronic Fatigue Syndrome (CFS) are rare. Because of the
 JH, Swanink CM, Fennis    Nijmegen, Department of   and Primary Fibromyalgia        Dec;16(6):602-4               similarity in symptoms, the prevalence of Primary Fibromyalgia Syndrome (PFS) was investigated at the
 JF, Galama JM, van Weel   Medical Psychology, The   Syndrome as recognized by                                     same time. OBJECTIVES: To determine the prevalence of CFS and PFS as recognized by GPs in The
 C, van der Meer JW,       Netherlands.              GPs.                                                          Netherlands and to inform them of the existence of CFS. METHODS: A postal questionnaire was sent to all
 Bleijenberg G.                                                                                                    GPs. RESULTS: The questionnaire was returned by 60% of the GPs. Seventy-three per cent reported one or
                                                                                                                   more CFS patients and 83% one or more PFS patients in their practice. CONCLUSION: The estimated
                                                                                                                   prevalence of CFS as recognized by GPs of 112 (PFS 157) patients per 100,000 is a minimum estimate.
 Bell IR, Richard R.                                 Differing Patterns of           Journal of Chronic Fatigue    The purpose of the present study was to compare specific neuropsychological, psychological, and family
 Bootzin, Gary E. R.                                 Cognitive Dysfunction and       Syndrome 1999: 5(2): 3 - 25   history patterns, as well as cardiovascular reactivity of three community-recruited groups of nonsmoking,
 Schwartz, Carol M.                                  Heart Rate Reactivity in                                      nonalcoholic middle-aged individuals with and without the symptom of intolerance to low levels of
 Baldwin RN, Faith                                   Chemically-Intolerant                                         environmental chemicals (CI). CI is a common symptom in chronic fatigue syndrome and fibromyalgia.
 Ballesteros                                         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
                                                                                                                   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
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                                                                                                                        subtypes for future studies.
 Bell IR, Szarek MJ,         Department of Psychology,      Patterns of waking EEG          Int J Neurosci 1999         Previous studies indicate that low level chemical intolerance (CI) is a symptom of several different
 Dicenso DR, Baldwin CM,     The University of Arizona,     spectral power in chemically    Mar;97(1-2):41-59           controversial conditions with neuropsychiatric features, e.g., chronic fatigue syndrome, fibromyalgia,
 Schwartz GE, Bootzin RR.    Tucson 85721, USA.             intolerant individuals during                               multiple chemical sensitivity, and "Persian Gulf Syndrome". Prior studies suggest that limbic and/or
                             IBELL@U.ARIZONA.EDU            repeated chemical exposures.                                mesolimbic sensitization may contribute to development of CI. The purpose of this report was to document
                                                                                                                        the waking electroencephalographic (EEG) patterns of individuals with CI during chemical exposures
                                                                                                                        presented over repeated sessions. Three groups of adult subjects who were recruited from the community
                                                                                                                        participated in the study: self-reported CI who had made associated lifestyle changes due to their
                                                                                                                        intolerance (CI/ LSC), self-reported CI who had not made such changes (CI), and normal controls without
                                                                                                                        self-reported CI. Subjects underwent two sessions involving one-minute EEG recordings during exposures
                                                                                                                        to low level chemical odors (a probe for limbic activation). The CI, but not the CI/ LSC, subjects had
                                                                                                                        increased absolute delta power after the chemical exposures during the second, but not the first, session.
                                                                                                                        The findings support the neural sensitization hypothesis for intolerance to low levels of environmental
                                                                                                                        chemicals in vulnerable individuals. As in human studies of stimulant drug sensitization, those with the
                                                                                                                        strongest past history with sensitizing agents may not show-term sensitization to low level exposures in the
 Berg D, Berg LH, Couvaras   HEMEX Laboratories, Inc.,      Chronic fatigue syndrome        Blood Coagul Fibrinolysis   Chronic Fatigue and/or Fibromyalgia have long been diseases without definition. An explanatory model of
 J, Harrison H.              Phoenix, Arizona 85021,        and/or fibromyalgia as a        1999 Oct;10(7):435-8        coagulation activation has been demonstrated through use of the ISAC panel of five tests, including,
                             USA.                           variation of antiphospholipid                               Fibrinogen, Prothrombin Fragment 1+2, Thrombin/ AntiThrombin Complexes, Soluble Fibrin Monomer,
                                                            antibody syndrome: an                                       and Platelet Activation by flow cytometry. These tests show low level coagulation activation from
                                                            explanatory model and                                       immunoglobulins (Igs) as demonstrated by Anti-B2GPI antibodies, which allows classification of these
                                                            approach to laboratory                                      diseases as a type of antiphospholipid antibody syndrome. The ISAC panel allows testing for diagnosis as
                                                            diagnosis.                                                  well as monitoring for anticoagulation protocols in these patients.
 Bickerton S.                                               How she learned to live with    Nurs Times 1999 Jun 2-
                                                            chronic fatigue syndrome.       8;95(22):39
 Blenkiron P, Edwards R,     Division of Psychiatry and     Associations between            J Nerv Ment Dis 1999        This study investigated possible associations between perfectionistic personality traits, mood, and fatigue in
 Lynch S.                    Behavioural Sciences in        perfectionism, mood, and        Sep;187(9):566-70           chronic fatigue syndrome (CFS). Forty CFS sufferers referred to tertiary care and 31 control healthy
                             Relation to Medicine, St.      fatigue in chronic fatigue                                  subjects completed the Multidimensional Perfectionism Scale (MPS), Chalder Fatigue Questionnaire, and
                             James's University Hospital,   syndrome: a pilot study.                                    Hospital Anxiety and Depression (HAD) scale. Total perfectionism scores did not correlate with fatigue,
                             Leeds, United Kingdom.                                                                     anxiety, or depression in either group. Other-oriented MPS scores were significantly lower among CFS
                                                                                                                        sufferers (p = .0019), especially women, and correlated negatively with physical fatigue levels overall (R = -
                                                                                                                        0.27, p = .02). Total and socially prescribed MPS scores correlated with age for the CFS group alone (p =
                                                                                                                        .05). Possible reasons why this study did not confirm a positive association between perfectionism and CFS
                                                                                                                        are discussed. The finding that CFS sufferers set lower standards and have lower expectations for
                                                                                                                        significant others may have implications for rehabilitation and recovery from this disorder.
 Bounous G, Molson J.        Department of Surgery,         Competition for glutathione     Med Hypotheses 1999         The chronic fatigue syndrome (CFS) is typically associated or follows a recognized or presumed infection.
                             McGill University, and         precursors between the          Oct;53(4):347-9             Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion
                             Medical Research Council of    immune system and the                                       of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen. As an
                             Canada.                        skeletal muscle: pathogenesis                               antioxidant, glutathione (GSH) is essential for allowing the lymphocyte to express its full potential without
                                                            of chronic fatigue syndrome.                                being hampered by oxiradical accumulation. Hence, protracted challenge of the immunocytes may lead to
                                                                                                                        cellular GSH depletion. Because GSH is also essential to aerobic muscular contraction, an undesirable
                                                                                                                        competition for GSH precursors between the immune and muscular systems may develop. It is conceivable
                                                                                                                        that the priority of the immune system for the survival of the host has drawn to this vital area the ever-
                                                                                                                        diminishing GSH precursors, thus depriving the skeletal muscle of adequate GSH precursors to sustain a
                                                                                                                        normal aerobic metabolism resulting in fatigue and eventually myalgia.
 Breau LM, McGrath PJ, Ju    Department of Psychology,      Review of juvenile primary      J Dev Behav Pediatr 1999    This article reviews the current literature on childhood fibromyalgia and chronic fatigue syndrome. In doing
 LH.                         Dalhousie University,          fibromyalgia and chronic        Aug;20(4):278-88            so, it questions assumptions about the presumed nature of the disorders-that they are distinct from each
                             Halifax, Canada.               fatigue syndrome.                                           other and are duplicates of their adult counterparts. It also attempts to synthesize the available data to reach
                                                                                                                        some preliminary judgments about these disorders: that fibromyalgia and chronic fatigue syndrome may be
                                                                                                                        related in children and may not be duplicates of the adult disorders; that psychological and psychosocial
                                                                                                                        factors are unlikely contributors to the etiology of these disorders; and that the evidence is increasingly
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                                                                                                                         pointing to a role for genetic factors in their etiology. A discussion of the research into treatments for
                                                                                                                         childhood fibromyalgia and chronic fatigue syndrome highlights the lack of well-designed, controlled
                                                                                                                         studies. Finally, directions for future research are offered where results of the current literature are unclear.
 Brunello N, Akiskal H,     Center of                      Dysthymia: clinical picture,    J Affect Disord 1999 Jan-     Dysthymia, as defined in the American Psychiatric Association and International Classification of Mental
 Boyer P, Gessa GL,         Neuropharmacology, Institute   extent of overlap with          Mar;52(1-3):275-90            Disorders, refers to a prevalent form of subthreshold depressive pathology with gloominess, anhedonia, low
 Howland RH, Langer SZ,     of Pharmacological Sciences,   chronic fatigue syndrome,                                     drive and energy, low self-esteem and pessimistic outlook. Although comorbidity with panic, social phobic,
 Mendlewicz J, Paes de      University of Milan, Italy.    neuropharmacological                                          and alcohol use disorders has been described, the most significant association is with major depressive
 Souza M, Placidi GF,       brunello@isfunix.farma.unim    considerations, and new                                       episodes. Family history is loaded with affective, including bipolar, disorders. The latter finding explains
 Racagni G, Wessely S.                           therapeutic vistas.                                           why dysthymia, especially when onset is in childhood, can lead to hypomanic switches, both spontaneously
                                                                                                                         and upon pharmacologic challenge in as many as 30%. Indeed, antidepressants from different classes -
                                                                                                                         tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), reversible inhibitors of
                                                                                                                         monoamine oxidase A (RIMAs), selective serotonin-reuptake inhibitors (SSRIs) and, more recently,
                                                                                                                         amisulpride, and spanning noradrenergic, serotonergic as well as dopaminergic mechanisms of action -
                                                                                                                         have been shown to be effective against dysthymia in an average of 65% of cases. This is a promising
                                                                                                                         development because social and characterologic disturbances so pervasive in dysthymia often, though not
                                                                                                                         always, recede with continued pharmacotherapy beyond acute treatment. Despite symptomatic overlap of
                                                                                                                         dysthymia with chronic fatigue syndrome - especially with respect to the cluster of symptoms consisting of
                                                                                                                         low drive, lethargy, lassitude and poor concentration - neither the psychopathologic status, nor the
                                                                                                                         pharmacologic response profile of the latter syndrome is presently understood. Chronic fatigue today is
                                                                                                                         where dysthymia was two decades ago. We? submit that the basic science - clinical paradigm that has
                                                                                                                         proven so successful in dysthymia could, before too long, crack down the conundrum of chronic fatigue as
                                                                                                                         well. At a more practical level, we raise the possibility that a subgroup within the chronic fatigue group
                                                                                                                         represents a variant of dysthymia.
 Buchwald D, Herrell R,     Department of Medicine,        The Chronic Fatigue Twin        Twin Res 1999 Sep;2(3):203-   Chronic fatigue syndrome (CFS) and the symptom of chronic fatigue are conditions of unknown etiology.
 Ashton S, Belcourt M,      University of Washington,      Registry: method of             11                            The Centers for Disease Control and Prevention (CDC) define CFS as an illness characterized by > or = 6
 Schmaling K, Goldberg J.   Seattle, USA.                  construction, composition,                                    months of disabling fatigue associated with muscle pain, pharyngitis, and alterations in mood, sleep and
                           and zygosity assignment.                                      neurocognition. We constructed a registry of twins with chronic fatigue to facilitate research on the impact
                                                                                                                         of illness, the associated medical and psychosocial factors, and the heterogeneous proposed mechanisms for
                                                                                                                         these conditions. We have recruited 204 twin pairs in which one or both members reported persistent
                                                                                                                         fatigue through patient support group newsletters (60%), clinicians/researchers familiar with CFS (12%),
                                                                                                                         notices placed on electronic bulletin boards for CFS (11%), twin organizations and researchers (6%),
                                                                                                                         relatives and friends (3%) and other sources (8%). Complete data are available for 177 pairs (87%). Twins
                                                                                                                         completed an extensive questionnaire booklet that included measures of physical and mental health,
                                                                                                                         functional status, and psychosocial factors; a structured psychiatric interview was also conducted by
                                                                                                                         telephone. Twins were classified using three increasingly more stringent diagnostic criteria for chronic
                                                                                                                         fatigue: 1) > or = 6 months of fatigue (115 discordant and 61 concordant pairs); 2) chronic fatigue with
                                                                                                                         additional symptoms and application of the medial exclusions of the CDC CFS case definition as obtained
                                                                                                                         by self-report (92 discordant and 41 concordant pairs) and; 3) chronic fatigue with additional symptoms
                                                                                                                         unexplained by self-reported medical conditions and psychiatric diagnoses as determined by the structured
                                                                                                                         interview (69 discordant pairs and 25 concordant pairs). Despite the limitations of a volunteer registry, the
                                                                                                                         Chronic Fatigue Twin Registry promises to be an important resource for research on CFS and chronic
 Buckley L, MacHale SM,     Department of Psychiatry,      Personality dimensions in       J Psychosom Res 1999          Chronic fatigue syndrome (CFS) is a poorly understood condition. Possible etiological factors include
 Cavanagh JT, Sharpe M,     University of Edinburgh and    chronic fatigue syndrome and    Apr;46(4):395-400             infectious agents, psychiatric disorders, and personality characteristics. We examined personality
 Deary IJ, Lawrie SM.       Royal Edinburgh Hospital,      depression.                                                   dimensions in 30 nondepressed patients with CFS, 20 patients with major depressive disorder (MDD), and
                            UK.                                                                                          15 healthy controls. On the NEO-FFI, patients with CFS scored significantly lower than healthy controls on
                                                                                                                         the extroversion subscale. On the neuroticism dimension of the Eysenck Personality Questionnaire (EPQ),
                                                                                                                         patients with MDD scored higher than those with CFS, who in turn scored significantly higher than the
                                                                                                                         healthy controls. CFS patients rated themselves as higher on neuroticism and less extroverted when ill than
                                                                                                                         when they were well. Our results suggest that high scores on neuroticism and low scores on extroversion in
                                                                                                                         CFS could be a reaction to chronic illness. Controlled Clinical Trial
 Buskila D.                 Department of Medicine B,      Fibromyalgia, chronic fatigue   Curr Opin Rheumatol 1999      Fibromyalgia was almost completely absent from an urban affluent population compared with poor urban
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                             Soroka Medical Center, Beer   syndrome, and myofascial        Mar;11(2):119-26      and rural communities. Seventeen percent of Gulf War veterans with soft tissue syndromes had
                             Sheva, Israel.                pain syndrome.                                        fibromyalgia, a much higher rate than was seen in previous studies of rheumatic disease in the military
                                                                                                                 population. A state of central hyperexcitability in the nociceptive system was reported in fibromyalgia.
                                                                                                                 Altered functioning of the stress-response system has been further documented in fibromyalgia and chronic
                                                                                                                 fatigue syndrome. Administration of growth hormone to patients with fibromyalgia who have low levels of
                                                                                                                 insulin-like growth factor 1 resulted in improvement in their symptoms and tenderness. An association
                                                                                                                 between chronic fatigue syndrome and initial infections was demonstrated. A correlation between particular
                                                                                                                 immunologic abnormalities and measures of disease severity was documented in chronic fatigue syndrome.
                                                                                                                 Concomitant fibromyalgia in other rheumatic diseases was a major contributor to poor quality of life. A
                                                                                                                 favorable outcome of fibromyalgia in children was reported; the majority of patients improved over 2 to 3
                                                                                                                 years of follow-up. Treatment of patients with fibromyalgia continues to be of limited success.
 Cannon JG, Angel JB, Ball   Department of Medicine,       Acute phase responses and       J Clin Immunol 1999   This study addresses the hypothesis that clinical manifestations of chronic fatigue syndrome (CFS) are due
 RW, Abad LW, Fagioli L,     New England Medical           cytokine secretion in chronic   Nov;19(6):414-21      in part to abnormal production of or sensitivity to cytokines such as interleukin-1beta (IL-1beta) and IL-6
 Komaroff AL.                Center, Boston,               fatigue syndrome.                                     under basal conditions or in response to a particular physical stress: 15 min of exercise consisting of
                             Massachusetts 02111, USA.                                                           stepping up and down on a platform adjusted to the height of the patella. The study involved 10 CFS
                                                                                           patients and 11 age-, sex-, and activity-matched controls: of these, 6 patients and 4 controls were tested in
                                                                                                                 both the follicular and the luteal phases of the menstrual cycle, and the remainder were tested in only one
                                                                                                                 phase, for a total of 31 experimental sessions. Prior to exercise, plasma concentrations of the acute phase
                                                                                                                 reactant alpha2-macroglobulin were 29% higher in CFS patients (P < 0.008) compared to controls.
                                                                                                                 Secretion of IL-6 was generally higher for CFS patients (approximately 38%), however, this difference was
                                                                                                                 statistically significant only if all values over a 3-day period were analyzed by repeated-measures ANOVA
                                                                                                                 (P = 0.035). IL-6 secretion correlated with plasma alpha2-macroglobulin in control subjects at rest (R =
                                                                                                                 0.767, P = 0.001). Immediately after exercise, the CFS patients reported greater ratings of perceived
                                                                                                                 exertion (P=0.027) compared to the healthy control subjects. Ratings of perceived exertion correlated with
                                                                                                                 IL-1beta secretion by cells from healthy control subjects (R = 0.603, P = 0.022), but not from CFS patients,
                                                                                                                 and IL-1beta secretion was not different between groups. Exercise induced a slight (< 12%) but significant
                                                                                                                 (P = 0.006) increase in IL-6 secretion, but the responses of the CFS patients were not different than
                                                                                                                 controls. Furthermore, no significant exercise-induced changes in body temperature or plasma alpha2-
                                                                                                                 macroglobulin were observed. These data indicate that under basal conditions, CFS is associated with
                                                                                                                 increased IL-6 secretion which is manifested by chronically elevated plasma alpha2-macroglobulin
                                                                                                                 concentrations. These modest differences suggest that cytokine dysregulation is not a singular or dominant
                                                                                                                 factor in the pathogenesis of CFS.
 Castell LM, Yamamoto T,     University Department of      The role of tryptophan in       Adv Exp Med Biol      Tryptophan is the precursor for the neurotransmitter 5-hydroxytryptamine (5-HT), which is involved in
 Phoenix J, Newsholme EA.    Biochemistry, Oxford, UK.     fatigue in different            1999;467:697-704      fatigue and sleep. It is present in bound and free from in the blood, where the concentration is controlled by
                               conditions of stress.                                 albumin binding to tryptophan. An increase in plasma free tryptophan leads to an increased rate of entry of
                                                                                                                 tryptophan into the brain. This should lead to a higher level of 5-HT which may cause central fatigue.
                                                                                                                 Central fatigue is implicated in clinical conditions such as chronic fatigue syndrome and post-operative
                                                                                                                 fatigue. Increased plasma free tryptophan leads to an increase in the plasma concentration ratio of free
                                                                                                                 tryptophan to the branched chain amino acids (BCAA) which compete with tryptophan for entry into the
                                                                                                                 brain across the blood-brain barrier. The plasma concentrations of these amino acids were measured in
                                                                                                                 chronic fatigue syndrome patients (CFS) before and after exercise (Castell et al., 1998), and in patients
                                                                                                                 undergoing major surgery (Yamamoto et al., 1997). In the CFS patients, the pre-exercise concentration of
                                                                                                                 plasma free tryptophan was higher than in controls (p < 0.05) but did not change during or after exercise.
                                                                                                                 This might indicate an abnormally high level of brain 5-HT in CFS patients leading to persistent fatigue. In
                                                                                                                 the control group, plasma free tryptophan was increased after maximal exercise (p < 0.001), returning
                                                                                                                 towards baseline levels 60 min later. The apparent failure of the CFS patients to change the plasma free
                                                                                                                 tryptophan concentration or the free tryptophan/BCAA ratio during exercise may indicate increased
                                                                                                                 sensitivity of brain 5-HT receptors, as has been demonstrated in other studies (Cleare et al., 1995). In post-
                                                                                                                 operative recovery after major surgery plasma free tryptophan concentrations were markedly increased
                                                                                                                 compared with baseline levels; the plasma free tryptophan/BCAA concentration ratio was also increased
                                                                                                                 after surgery. Plasma albumin concentrations were decreased after surgery: this may account for the
                                                                                                                 increase in plasma free tryptophan levels. Provision of BCAA has improved mental performance in athletes
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                                                                                                                            after endurance exercise (Blomstrand et al., 1995, 1997). It is suggested that BCAA supplementation may
                                                                                                                            help to counteract the effects of an increase in plasma free tryptophan, and may thus improve the status of
                                                                                                                            patients during or after some clinically stressful conditions.
 Charnock D, Shepperd S,      University of Oxford,           DISCERN: an instrument for       J Epidemiol Community        OBJECTIVE: To develop a short instrument, called DISCERN, which will enable patients and information
 Needham G, Gann R.           Division of Public Health       judging the quality of written   Health 1999 Feb;53(2):105-   providers to judge the quality of written information about treatment choices. DISCERN will also facilitate
                              and Primary Health Care,        consumer health information      11                           the production of new, high quality, evidence-based consumer health information. DESIGN: An expert
                              Institute of Health Sciences.   on treatment choices.                                         panel, representing a range of expertise in consumer health information, generated criteria from a random
                                                                                                                            sample of information for three medical conditions with varying degrees of evidence: myocardial infarction,
                                                                                                                            endometriosis, and chronic fatigue syndrome. A graft instrument, based on this analysis, was tested by the
                                                                                                                            panel on a random sample of new material for the same three conditions. The panel re-drafted the
                                                                                                                            instrument to take account of the results of the test. The DISCERN instrument was finally tested by a
                                                                                                                            national sample of 15 information providers and 13 self help group members on a random sample of
                                                                                                                            leaflets from 19 major national self help organisations. Participants also completed an 8 item questionnaire
                                                                                                                            concerning the face and content validity of the instrument. RESULTS: Chance corrected agreement
                                                                                                                            (weighted kappa) for the overall quality rating was kappa = 0.53 (95% CI kappa = 0.48 to kappa = 0.59)
                                                                                                                            among the expert panel, kappa = 0.40 (95% CI kappa = 0.36 to kappa = 0.43) among information
                                                                                                                            providers, and kappa = 0.23 (95% CI kappa = 0.19 to kappa = 0.27) among self help group members.
                                                                                                                            Higher agreement levels were associated with experience of using the instrument and with professional
                                                                                                                            knowledge of consumer health information. Levels of agreement varied across individual items on the
                                                                                                                            instrument, reflecting the need for subjectivity in rating certain criteria. The trends in levels of agreement
                                                                                                                            were similar among all groups. The final instrument consisted of 15 questions plus an overall quality rating.
                                                                                                                            Responses to the questionnaire after the final testing revealed the instrument to have good face and content
                                                                                                                            validity and to be generally applicable. CONCLUSIONS: DISCERN is a reliable and valid instrument for
                                                                                                                            judging the quality of written consumer health information. While some subjectivity is required for rating
                                                                                                                            certain criteria, the findings demonstrate that the instrument can be applied by experienced users and
                                                                                                                            providers of health information to discriminate between publications of high and low quality. The
                                                                                                                            instrument will also be of benefit to patients, though its use will be improved by training.
 Chia JK, Chia LY.            Torrance Memorial Medical       Chronic Chlamydia                Clin Infect Dis 1999
                              Center, California, USA.        pneumoniae infection: a          Aug;29(2):452-3
                                    treatable cause of chronic
                                                              fatigue syndrome.
 Christodoulou C, Deluca J,   University of Medicine and      Examination of Cloninger's       J Psychosom Res 1999         Relatively few studies have examined the personality characteristics of patients with chronic fatigue
 Johnson SK, Lange G,         Dentistry of New Jersey, New    basic dimensions of              Dec;47(6):597-607            syndrome (CFS). The personality profiles of 38 CFS subjects were compared with 40 healthy controls and
 Gaudino EA, Natelson BH.     Jersey Medical School,          personality in fatiguing                                      40 subjects with multiple sclerosis (MS), a chronic illness that shares many symptoms with CFS (e.g.,
                              Newark, USA.                    illness: chronic fatigue                                      fatigue), but has a known neurological substrate. Subjects were examined within Cloninger's biosocial
                                 syndrome and multiple                                         theory of personality, which delineates basic dimensions of temperament. Both illness groups displayed
                                                              sclerosis.                                                    similarly elevated levels of Harm Avoidance, and lower levels of Reward Dependence as compared with
                                                                                                                            healthy controls. The MS group showed a lower level of Persistence than controls and CFS subjects.
                                                                                                                            Implications for the relationship between chronic illness and personality are discussed.
 Clapp LL, Richardson MT,     Health, Physical Education,     Acute effects of thirty          Phys Ther 1999               BACKGROUND AND PURPOSE: Currently, there is no consensus on exercise prescription for patients
 Smith JF, Wang M, Clapp      and Recreation Department,      minutes of light-intensity,      Aug;79(8):749-56Comment      with chronic fatigue syndrome (CFS). This investigation examined whether light-intensity, intermittent
 AJ, Pieroni RE.              Southwest Texas State           intermittent exercise on         in: Phys Ther. 2000          physical activity exacerbated symptoms in patients with CFS immediately following exercise to 7 days
                              University, San Marcos          patients with chronic fatigue    Jan;80(1):115                following exercise. Subjects. Subjects were 9 women (mean age=44.2 years, SD=8.4, range=29-56; mean
                              78666, USA.        syndrome.                                                     weight=74.2 kg, SD=18.8, range=56.36-110.91; and mean height=1.63 m, SD=0.8, range=1.55-1.78) and 1
                                                                                                                            man (age=48 years, weight=97.1 kg, and height= 1.98 m) who met the Centels for Disease Control and
                                                                                                                            Prevention's criteria fi)r (FS. METHODS: Subjects performed 10 discontinuous 3-minute exercise bouts
                                                                                                                            (separated by 3 minutes of recovery) at a self-selected, comfortable walking pace on a treadmill. Oxygen
                                                                                                                            consumption, minute ventilation, respiratory exchange ratio, and heart rate were measured every minute
                                                                                                                            during the exercise session. To assess degree of disability, general health status, activity level, symptoms,
                                                                                                                            and mood, subjects completed various questionnaires before and after exercise. RESULTS: Results
                                                                                                                            indicated that degree of disability, general health status, symptoms, and mood did not change immediately
                                                                                                                            and up to 7 days following exercise. CONCLUSION AND DISCUSSION: Thirty minutes of intermittent
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                                                                                                                            walking did not exacerbate symptoms in subjects with CFS. The physiological data did not show any
                                                                                                                            abnormal response to exercise. Although this study did not determine whether 30 minutes of continuous
                                                                                                                            versus intermittent exercise would exacerbate symptoms, all 10 subjects felt that they could not exercise
                                                                                                                            continuously for 30 minutes without experiencing symptom exacerbation. Despite this limitation, the
                                                                                                                            results indicate that some individuals with CFS may be able to use low-level, intermittent exercise without
                                                                                                                            exacerbating their symptoms.
 Clarke JN.                  Department of Sociology and     Chronic fatigue syndrome:        Aust N Z J Ment Health Nurs   This study employs qualitative research methods to describe and compare the experiences of men and
                             Anthropology, Wilfrid           gender differences in the        1999 Dec;8(4):123-33          women with chronic fatigue syndrome (CFS), focusing on respondents' self-perceived illness experience
                             Laurier University, Waterloo,   search for legitimacy.                                         and relationship with medical practitioners. Data were collected from 59 respondents (18 male, 41 female)
                             Ontario, Canada.                                                                               in telephone interviews using an open-ended focus interview schedule. While respondents explained the
                                                                                                                            causes of the disease in ways that were largely gender appropriate, they did not experience the disease itself
                                                                                                                            in gender different ways. The evidence of the study points to a clear dichotomy between ways in which men
                                                                                                                            and women experience the disease and differences in the ways in which they are treated by the medical
 Cleare AJ, Heap E, Malhi    Department of Psychological     Low-dose hydrocortisone in       Lancet 1999 Feb               BACKGROUND: Reports of mild hypocortisolism in chronic fatigue syndrome led us to postulate that
 GS, Wessely S, O'Keane V,   Medicine, Guy's King's and      chronic fatigue syndrome: a      6;353(9151):455-8Comment      low-dose hydrocortisone therapy may be an effective treatment. METHODS: In a randomised crossover
 Miell J.                    St Thomas' School of            randomised crossover trial.      in: Lancet. 1999 Feb          trial, we screened 218 patients with chronic fatigue. 32 patients met our strict criteria for chronic fatigue
                             Medicine and the Institute of                                    6;353(9151):424-5 Lancet.     syndrome without co-morbid psychiatric disorder. The eligible patients received consecutive treatment with
                             Psychiatry, London, UK.                                          1999 May                      low-dose hydrocortisone (5 mg or 10 mg daily) for 1 month and placebo for 1 month; the order of treatment
                                                             8;353(9164):1618-9;           was randomly assigned. Analysis was by intention to treat. FINDINGS: None of the patients dropped out.
                                                                                              discussion 1619-20 Lancet.    Compared with the baseline self-reported fatigue scores (mean 25.1 points), the score fell by 7.2 points for
                                                                                              1999 May 8;353(9164):1618;    patients on hydrocortisone and by 3.3 points for those on placebo (paired difference in mean scores 4.5
                                                                                              discussion 1619-20 Lancet.    points [95% CI 1.2-7.7], p=0.009). In nine (28%) of the 32 patients on hydrocortisone, fatigue scores
                                                                                              1999 May                      reached a predefined cut-off value similar to the normal population score, compared with three (9%) of the
                                                                                              8;353(9164):1619-20           32 on placebo (Fisher's exact test p=0.05). The degree of disability was reduced with hydrocortisone
                                                                                                                            treatment, but not with placebo. Insulin stress tests showed that endogenous adrenal function was not
                                                                                                                            suppressed by hydrocortisone. Minor side-effects were reported by three patients after hydrocortisone
                                                                                                                            treatment and by one patient after placebo. INTERPRETATION: In some patients with chronic fatigue
                                                                                                                            syndrome, low-dose hydrocortisone reduces fatigue levels in the short term. Treatment for a longer time and
                                                                                                                            follow-up studies are needed to find out whether this effect could be clinically useful.
 Csef H.                     Medizinischen Poliklinik,       [Similarities of chronic         Dtsch Med Wochenschr
                             Universitat Wurzburg.           fatigue syndrome,                1999 Feb 12;124(6):163-9
                                                             fibromyalgia and multiple
                                                             chemical sensitivity].[article
                                                             in German]
 De Becker P, De Meirleir    Faculty of Medicine and         Dehydroepiandrosterone           Horm Metab Res 1999           Previous studies have demonstrated concentrating neuroendocrinological disturbances in chronic fatigue
 K, Joos E, Campine I, Van   Pharmacy, Vrije Universiteit    (DHEA) response to i.v.          Jan;31(1):18-21Comment in:    syndrome (CFS) patients, concentrating in particular on low cortisol levels and a hypothalamic deficiency.
 Steenberge E, Smitz J,      Brussel, Belgium.               ACTH in patients with            Horm Metab Res. 1999          In order to investigate the dynamic response of the adrenal glands, we measured dehydroepiandrosterone
 Velkeniers B.                chronic fatigue syndrome.        Jul;31(7):439                 (DHEA) in serum after adreno-corticotropic hormone (ACTH) stimulation during 60 minutes in 22 CFS-
                                                                                                                            patients and 14 healthy controls. We found normal basal DHEA levels, but a blunted serum DHEA
                                                                                                                            response curve to i.v. ACTH injection. This observation adds to the large amount of evidence of
                                                                                                                            endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might contribute to the overall
                                                                                                                            clinical picture in CFS, and could explain some of the immunological disturbances observed in this
 Dessein PH, Shipton EA.                                     Hydrocortisone and chronic       Lancet 1999 May
                                                             fatigue syndrome.                8;353(9164):1618;
                                                                                              discussion 1619-20
                                                                                              Comment on: Lancet. 1999
                                                                                              Feb 6;353(9151):455-8
 Doyle JP, Frank E,          Division of General             Domestic violence and sexual     J Womens Health Gend          Physicians have been called on to identify victims of domestic violence (DV) and sexual abuse (SA). Few
 Saltzman LE, McMahon        Medicine, Rollins School of     abuse in women physicians:       Based Med 1999                data exist, however, on the prevalence of DV and SA in physicians themselves or on the personal or
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 PM, Fielding BD.         Public Health, Emory           associated medical,             Sep;8(7):955-65                professional sequelae of such experiences. We determined the reported lifetime prevalence of DV and SA
                          University School of           psychiatric, and professional                                  among women physicians and the personal characteristics, health-related factors, and work-related factors
                          Medicine, Atlanta, Georgia     difficulties.                                                  associated with these forms of abuse. We used data from the Women Physicians' Health Study, a large (n =
                          30303, USA.                                                                                   4501 respondents), nationally distributed questionnaire study that included questions on DV and SA
                                                                                                                        histories, personal characteristics, and psychiatric, medical, and work-related histories. We compared the
                                                                                                                        characteristics of women physicians with and without histories of DV or SA. The logistic models indicate
                                                                                                                        that women physicians reporting DV histories (3.7% of the population) were significantly (p < 0.05) less
                                                                                                                        likely to be single and significantly more likely to report depression histories, suicide attempts, substance
                                                                                                                        abuse, current or past cigarette smoking, severe daily stress at home, chronic fatigue syndrome, and DV
                                                                                                                        experienced by their mothers. Women physicians reporting SA histories (4.7% of the population) were
                                                                                                                        significantly more likely to be younger than 60 years, identify themselves as homosexual or bisexual, to
                                                                                                                        have specialized in psychiatry, obstetrics and gynecology, or emergency medicine, and to report histories of
                                                                                                                        depression, suicide attempts, eating disorders, and fair or poor perceived health status. Although the
                                                                                                                        reported lifetime prevalence of DV and SA among women physicians is below other reported figures, such
                                                                                                                        experiences are associated with medical and psychiatric difficulties that could negatively affect them
                                                                                                                        personally and professionally.
 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 1999: 5(2): 77 - 95   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
                                                                                                                        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
 Elkins LE, Pollina DA,   Department of Neurology,       Psychological states and        Appl Neuropsychol              The neuropsychiatric sequelae of chronic Lyme disease remains unclear. This study sought to characterize
 Scheffer SR, Krupp LB.   State University of New York   neuropsychological              1999;6(1):19-26                the psychological status of a group of participants who met criteria for post-Lyme syndrome (PLS). These
                          at Stony Brook 11794-8121,     performances in chronic                                        measures were then used to examine the influence of psychological status on neuropsychological
                          USA.                           Lyme disease.                                                  performances. Thirty PLS participants completed a structured psychiatric interview, the Positive and
                                                                                                                        Negative Affect Schedule, the Lyme Symptom Checklist, and a battery of neuropsychological tests. As a
                                                                                                                        group, the PLS participants did not appear to have an elevated incidence of psychiatric disorders, and
                                                                                                                        psychiatric history was not useful for understanding neuropsychological performances or symptom reports.
                                                                                                                        The mood of the PLS participants was characterized by lowered levels of positive affect (PA) and typical
                                                                                                                        levels of negative affect. This combination can be distinguished from depression and is consistent with
                                                                                                                        previous findings of affect patterns in individuals with chronic fatigue syndrome. PA was also linked to
                                                                                                                        both total symptom severity and severity of cognitive complaints, but not to duration of illness,
                                                                                                                        neurological manifestations at initial diagnosis, or treatment history. Relative to published normative data,
                                                                                                                        neuropsychological performances were not in the impaired range on any measure. Neither psychological
                                                                                                                        status nor symptom report were useful for understanding any aspect of cognitive functioning. It is
                                                                                                                        concluded that decreased PA is the most useful marker of psychological functioning in PLS.
 Endicott NA.             Department of Research,        Chronic fatigue syndrome in     J Psychosom Res 1999           Forty-five psychiatric patients with chronic fatigue syndrome (CFS) were compared, using the case-control
                          Assessment & Training, New     private practice psychiatry:    Oct;47(4):343-54               method, to two control groups selected from the same practice and matched on age, gender, and psychiatric
                          York State Psychiatric         family history of physical                                     diagnosis. The first control group (C-I, N=90) was selected on the basis of relatively good physical health.
                          Institute, New York, USA.      and mental health.                                             The second control group (C-II, N=45) was selected without regard to physical health. The reported family
                                                                                                                        history of physical health revealed: the CFS mothers died at a younger age than the C-II mothers; both
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                                                                                                                          parents died before age 65 among the CFS parents more frequently than did the C-I parents; and the CFS
                                                                                                                          parents had an increased prevalence of cancer, autoimmune disorders, and CFS-like conditions as
                                                                                                                          compared to the families of one or both control groups. The reported family history of mental disorders
                                                                                                                          revealed no significant differences in any of these conditions between the CFS patients and either control
 Evengard B, Briese T,        Department of Immunology,         Absence of evidence of          J Neurovirol 1999         Chronic Fatigue Syndrome (CFS) is characterized by debilitating fatigue, somatic symptoms and cognitive
 Lindh G, Lee S, Lipkin WI.   Microbiology, Pathology and       Borna disease virus infection   Oct;5(5):495-9            impairment. An infectious basis has been proposed; candidate agents include enteroviruses, herpesviruses,
                              Infectious Diseases, Clinic       in Swedish patients with                                  retroviruses and Borna disease virus (BDV), a novel neurotropic virus associated with neuropsychiatric
                              for Infectious Diseases,          Chronic Fatigue Syndrome.                                 disorders. Sera and peripheral blood mononuclear cells (PBMC) from Swedish CFS patients were assayed
                              Karolinska Institutet at                                                                    for evidence of infection using ELISA and Western immunoblot for detection of antibodies to BDV
                              Huddinge University                                                                         proteins N, P and gp18; and using nested reverse transcriptase polymerase chain reaction (RT-PCR) for
                              Hospital.                                                                                   detection of BDV N- and P-gene transcripts. No specific immunoreactivity to BDV proteins was found in
                                                                                                                          sera from 169 patients or 62 controls. No BDV N- or P-gene transcripts were found through RT-PCR
                                                                                                                          analysis of PBMC from 18 patients with severe CFS. These results do not support a role for BDV in
                                                                                                                          pathogenesis of CFS.
 Evengard B, Komaroff AL.     Infektionskliniken, Huddinge      [Chronic fatigue syndrome       Lakartidningen 1999 Jun   Chronic fatigue syndrome is a debilitating condition characterised by neurocognitive and somatic
                              sjukhus.                          does exist. Changes of          30;96(26-27):3166-9       symptoms. Although many patients report an infectious onset, there is no unequivocal evidence to support
                                                                biological parameters are                                 this. The immune system is activated, and the hypothalamic-pituitary-adrenal axis is involved. The
                                                                measurable].[article in                                   aetiology is complex, and its understanding may require modification of our views on ill-health and disease.
 Evengard B, Schacterle RS,   Division of Infectious            Chronic fatigue syndrome:       J Intern Med 1999         Chronic fatigue syndrome (CFS) is a condition characterized by impairment of neurocognitive functions
 Komaroff AL.                 Diseases, Department of           new insights and old            Nov;246(5):455-69         and quality of sleep and of somatic symptoms such as recurrent sore throat, muscle aches, arthralgias,
                              Immunology, Karolinska            ignorance.                                                headache, and postexertional malaise. A majority of patients describe an infectious onset but the link
                              Institute at Huddinge                                                                       between infections and CFS remains uncertain. Findings show an activation of the immune system,
                              University Hospital,                                                                        abberations in several hypothalamic-pituitary axes and involvement of other parts of the central nervous
                              Huddinge, Sweden.                                                                           system. The origin is bound to be complex and it may well be that the solution will come together with a
                              birgitta.evengardinfect.hs.sll.                                                             more generally altered view about mind-body dualism, and the concept of illness and disease.
 Forsyth LM, Preuss HG,       Department of Pediatrics,         Therapeutic effects of oral     Ann Allergy Asthma        BACKGROUND: Chronic fatigue syndrome (CFS) is a disorder of unknown etiology, consisting of
 MacDowell AL, Chiazze L      Georgetown University             NADH on the symptoms of         Immunol 1999              prolonged, debilitating fatigue, and a multitude of symptoms including neurocognitive dysfunction, flu-like
 Jr, Birkmayer GD, Bellanti   School of Medicine,               patients with chronic fatigue   Feb;82(2):185-91Comment   symptoms, myalgia, weakness, arthralgia, low-grade fever, sore throat, headache, sleep disturbances, and
 JA.                          Washington, D.C., USA.            syndrome.                       in: Ann Allergy Asthma    swelling and tenderness of lymph nodes. No effective treatment for CFS is known. OBJECTIVE: The
                                                                                                Immunol. 2000             purpose of the study was to evaluate the efficacy of the reduced form of nicotinamide adenine dinucleotide
                                                                                                Jun;84(6):639-40          (NADH) i.e., ENADA the stabilized oral absorbable form, in a randomized, double-blind, placebo-
                                                                                                                          controlled crossover study in patients with CFS. Nicotinamide adenine dinucleotide is known to trigger
                                                                                                                          energy production through ATP generation which may form the basis of its potential effects. METHODS:
                                                                                                                          Twenty-six eligible patients who fulfilled the Center for Disease Control and Prevention criteria for CFS
                                                                                                                          completed the study. Medical history, physical examination, laboratory studies, and questionnaire were
                                                                                                                          obtained at baseline, 4, 8, and 12 weeks. Subjects were randomly assigned to receive either 10 mg of
                                                                                                                          NADH or placebo for a 4-week period. Following a 4-week washout period, subjects were crossed to the
                                                                                                                          alternate regimen for a final 4-week period. RESULTS: No severe adverse effects were observed related to
                                                                                                                          the study drug. Within this cohort of 26 patients, 8 of 26 (31%) responded favorably to NADH in contrast
                                                                                                                          to 2 of 26 (8%) to placebo. Based upon these encouraging results we have decided to conduct an open-label
                                                                                                                          study in a larger cohort of patients. CONCLUSION: Collectively, the results of this pilot study indicate that
                                                                                                                          NADH may be a valuable adjunctive therapy in the management of the chronic fatigue syndrome and
                                                                                                                          suggest that further clinical trials be performed to establish its efficacy in this clinically perplexing disorder.
 Frank E, Dingle AD.          Department of Family and          Self-reported depression and    Am J Psychiatry 1999      OBJECTIVE: Studies examining suicide rates for U.S. women physicians and other U.S. women have
                              Preventive Medicine, Emory        suicide attempts among U.S.     Dec;156(12):1887-94       found odds ratios as high as 4 to 1. Although such reports are controversial and are based on small groups
                              University School of              women physicians.                                         (N = 17 to 49 suicides), they are often cited as evidence of a high prevalence of psychopathology among
                              Medicine, Atlanta, GA                                                                       women physicians. METHOD: The authors used the results of the Women Physicians' Health Study (N =
                              30303, USA.                                                                                 4,501), a large, nationally distributed questionnaire, to assess the lifetime prevalence of self-identified
                                                                                            depression and suicide attempts among U.S. women physicians. RESULTS: An estimated 1.5% (N = 61) of
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                                                                                                                       U.S. women physicians have attempted suicide, and 19.5% (N = 808) have a history of depression. Those
                                                                                                                       who were born in the United States, were not Asian, had histories of cigarette smoking, alcohol abuse or
                                                                                                                       dependence, sexual abuse, domestic violence, poor current mental health, more severe harassment, or a
                                                                                                                       family history of psychiatric disorders were significantly more likely to report suicide attempts or
                                                                                                                       depression. Depression was more common among those who were not partnered, were childless, had a
                                                                                                                       household gun, had more stress at home, drank alcohol, had worse health, or had a history of obesity,
                                                                                                                       chronic fatigue syndrome, substance abuse, an eating disorder, or another psychiatric disorder and among
                                                                                                                       those who reported working too much, career dissatisfaction, less control at work, and high job stress.
                                                                                                                       Strata reporting higher rates of depression tended to show higher (although usually nonsignificant) rates of
                                                                                                                       suicide attempts. CONCLUSIONS: Depression is approximately as common among U.S. women
                                                                                                                       physicians as among other U.S. women, but suicide attempts may be fewer. A number of conditions may
                                                                                                                       help identify women physicians at high risk for suicide attempts and depression.
 Friedman TC, Adesanya A,                                 Low-dose hydrocortisone for      JAMA 1999 May
 Poland RE.                                               chronic fatigue syndrome.        26;281(20):1888-9 Comment
                                                                                           on: JAMA. 1998 Sep 23-
 Garralda E, Rangel L,       Academic Unit of Child and   Psychiatric adjustment in        J Am Acad Child Adolesc     OBJECTIVE: To ascertain psychiatric adjustment in youngsters with a history of childhood chronic fatigue
 Levin M, Roberts H,         Adolescent Psychiatry,       adolescents with a history of    Psychiatry 1999             syndrome (CFS). METHOD: Subjects were 25 children and adolescents with CFS who were seen in tertiary
 Ukoumunne O.                Imperial College School of   chronic fatigue syndrome.        Dec;38(12):1515-            pediatric/psychiatric clinics (mean age 15.6 years, seen a mean of 45.5 months after illness onset; 17
                             Medicine, St. Mary's                                          21Comment in: J Am Acad     subjects had recovered and 8 were still ill) and 15 healthy matched controls. Youngsters and their parents
                             Hospital, London, England.                                    Child Adolesc Psychiatry.   (usually mothers) were interviewed and completed questionnaires. Instruments used included the Schedule
                                                              2000 Jul;39(7):808-9        for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), the Child Behavior
                                                                                                                       Checklist (CBCL), and the Harter Self-Esteem Questionnaire. RESULTS: At assessment, psychiatric
                                                                                                                       disorders (mainly anxiety and depressive disorders) were present in half the subjects with a history of CFS,
                                                                                                                       a rate significantly higher than in healthy controls. On the CBCL youngsters with a history of CFS had an
                                                                                                                       excess of psychological symptoms and decreased social competence. On the Harter Self-Esteem
                                                                                                                       Questionnaire they reported reduced self-esteem, especially in social competence. Anxiety disorders were
                                                                                                                       significantly more common in recovered subjects than in those with active CFS illness status.
                                                                                                                       CONCLUSIONS: Psychiatric disorders were found to be increased in adolescents with a history of severe
                                                                                                                       CFS; CFS may enhance the risk for or share common predisposing factors with anxiety disorders.
 Gil'miiarova FN,                                         [Chronic fatigue                 Klin Lab Diagn 1999         Multi-level system of defense mechanisms is studied in 206 normal subjects living in an ecologically
 Radomskaia VM, Kretova                                   syndrome:objective criteria      Feb;(2):9-11                unfavorable region and working at chemical plants. Control group consisted of 24 subjects living in en
 IG, Vinogradova LN,                                      of metabolic defects].[article                               ecologically safe region. The content of total protein and albumin and its effective and binding capacity
 Samykina LN, Sheshunov                                   in Russian]                                                  were decreased, while the content of medium molecular weight peptides increased in the blood of subjects
 IV, Babichev AV,                                                                                                      exposed to technogenic environmental pollution. The detected shifts are regarded as a mechanism of
 Sharafutdinova IM,                                                                                                    development of chronic fatigue syndrome.
 Ponomareva LA.
 Godwin M, Delva D, Miller   Department of Family         Investigating fatigue of less    Can Fam Physician 1999      OBJECTIVE: To develop an evidence-based systematic approach to assessment of adult patients who
 K, Molson J, Hobbs N,       Medicine, Queen's            than 6 months' duration.         Feb;45:373-9Comment in:     present to family physicians complaining of fatigue of less than 6 months' duration. The guidelines present
 MacDonald S, MacLeod C.     University, Kingston, ON.    Guidelines for family            Can Fam Physician. 1999     investigative options, making explicit what should be considered in all cases and what should be considered
                                                          physicians.                      Apr;45:872-3 Can Fam        only in specific situations. They aim to provide physicians with an approach that, to the extent possible, is
                                                                                           Physician. 1999             based on evidence so that time and cost are minimized and detection and management of the cause of the
                                                                                           May;45:1152                 fatigue are optimized. QUALITY OF EVIDENCE: MEDLINE was searched from 1966 to 1997 using the
                                                                                                                       key words "family practice" and "fatigue." Articles about chronic fatigue syndrome were excluded. Articles
                                                                                                                       with level 3 evidence were found, but no randomized trials, cohort studies, or case-control studies were
                                                                                                                       found. Articles looking specifically at the epidemiology, demographics, investigations, and diagnoses of
                                                                                                                       patients with fatigue were chosen. Articles based on studies at referral and specialty centres were given less
                                                                                                                       weight than those based on studies in family physicians' offices. MAIN MESSAGE: Adherence to these
                                                                                                                       guidelines will decrease the cost of investigating the symptom of fatigue and optimize diagnosis and
                                                                                                                       management. This needs to be proved in practice, however, and with research that produces level 1 and 2
                                                                                                                       evidence. CONCLUSIONS: Adults presenting with fatigue of less than 6 months' duration should be
                                                                                                                       assessed for psychosocial causes and should have a focused history and physical examination to determine
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                                                                                                                              whether further investigations should be done. The guidelines outline investigations to be considered. The
                                                                                                                              elderly require special consideration. These guidelines have group validation, but they need to be tested by
                                                                                                                              more physicians in various locations and types of practices.
 Goodnick PJ, Jorge CM.                                       Treatment of chronic fatigue     Am J Psychiatry 1999
                                                              syndrome with nefazodone.        May;156(5):797-8
 Gordon R, Michalewski        Department of Neurology,        Cortical motor potential         Int J Mol Med 1999             Premovement, sensory, and cognitive brain potentials were recorded from patients with Chronic Fatigue
 HJ, Nguyen T, Gupta S,       University of California,       alterations in chronic fatigue   Nov;4(5):493-9                 Syndrome (CFS) in four tasks: i) target detection, ii) short-term memory, iii) self-paced movement, and iv)
 Starr A.                     Irvine, Med. Surge I, Room      syndrome.                                                       expectancy and reaction time (CNV). Accuracy and reaction times (RTs) were recorded for tasks i, ii, and
                              154, Irvine, CA 92697-4290,                                                                     iv. Results from CFS patients were compared to a group of healthy normals. Reaction times were slower for
                              USA.                                                                                            CFS patients in target detection and significantly slower in the short-term memory task compared to
                                                                                                                              normals. In target detection, the amplitude of a premovement readiness potential beginning several hundred
                                                                                                                              milliseconds prior to stimulus onset was reduced in CFS, whereas the poststimulus sensory (N100) and
                                                                                                                              cognitive brain potentials (P300) did not differ in amplitude or latency. In the memory task, a negative
                                                                                                                              potential related to memory load was smaller in CFS than normals. The potentials to self-paced movements
                                                                                                                              and to expectancy and RT (CNV) were not different between groups. The findings in CFS of slowed RTs
                                                                                                                              and reduced premovement-related potentials suggest that central motor mechanisms accompanying motor
                                                                                                                              response preparation were impaired in CFS for some tasks. In contrast, measures of neural processes related
                                                                                                                              to both sensory encoding (N100) and to stimulus classification (P300) were normal in CFS.
 Granzow B.                                                   [Mutual features of chronic      Dtsch Med Wochenschr
                                                              fatigue syndrome,                1999 Oct 15;124(41):1224
                                                              fibromyalgia and multiple
                                                              chemical sensitivity].[article
                                                              in German]
 Gray GC, Kaiser KS,          Emerging Illness Division,      Increased postwar symptoms       Am J Trop Med Hyg 1999         To investigate reports on war-related morbidity, 527 active-duty Gulf War veterans and 970 nondeployed
 Hawksworth AW, Hall FW,      Naval Health Research           and psychological morbidity      May;60(5):758-66               veterans from 14 Seabee commands were studied in 1994 with a questionnaire, sera collection, handgrip
 Barrett-Connor E.            Center, San Diego, California   among U.S. Navy Gulf War                                        strength, and pulmonary function testing. The questionnaire assessed postwar symptoms, war exposures,
                              92186-5122, USA.                veterans.                                                       and screened for chronic fatigue syndrome, post-traumatic stress disorder, and psychological symptoms
                                                                                                                              suggesting neurosis (Hopkins Symptom Checklist). Sera were tested with four nonspecific reactant assays:
                                                                                                                              C-reactive protein, transferrin, ferritin, and haptoglobin. Gulf War veterans reported a higher prevalence for
                                                                                                                              35 of 41 symptoms, scored higher on psychological symptom scales, were more likely to screen for post-
                                                                                                                              traumatic stress disorder, had lower handgrip strength, and had higher serum ferritin assay results.
                                                                                                                              Numerous comparisons of these morbidity outcomes with 30 self-reported exposures demonstrated many
                                                                                                                              associations, but no unique exposure or group of exposures were implicated. Morbidity data are consistent
                                                                                                                              with other postwar observations, but the etiology for morbidity findings remains uncertain.
 Green JL, Jennifer Romei,                                    Stigma and Chronic Fatigue       Journal of Chronic Fatigue     We predicted that the largely female population seeking relief from the incapacitating symptoms of chronic
 Benjamin Natelson                                            Syndrome                         Syndrome 1999: 5(2): 63 - 75   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 MD's) may influence attempts of CFS patients to legitimize their symptoms by disclosure and lead
                                                                                                                              to high rates of health care system use
 Gupta S, Aggarwal S, Starr   Department of Medicine,         Increased production of          Int J Mol Med 1999             In an investigator-blinded study, adherent (monocytes) and non-adherent cells (lymphocytes) from patients
 A.                           University of California,       interleukin-6 by adherent and    Feb;3(2):209-13                with chronic fatigue syndrome (CFS) were examined on two separate occasions (when feeling 'fatigued' and
                              Irvine, CA 92697, USA.          non-adherent mononuclear                                        when feeling 'rested') for in vitro spontaneous, phytohemagglutinin- (PHA, for lymphocytes), and
                                                              cells during 'natural fatigue'                                  lipopolysaccharide- (LPS, for monocytes) induced production of IL-6 by ELISA assay. A group of CFS
                                                              but not following                                               patients and controls were also subjected to exercise-induced fatigue ('experimental fatigue') and IL-6
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                                                         'experimental fatigue' in                                     production was compared, in a double-blinded manner, prior to and following induction of fatigue. A
                                                         patients with chronic fatigue                                 significant increase in spontaneous, PHA- and LPS-induced IL-6 secretion by both lymphocytes and
                                                         syndrome.                                                     monocytes was observed in CFS patients during 'natural fatigue' as compared to during state. However, no
                                                                                                                       such changes in IL-6 production were observed during 'experimental fatigue'. These data suggest a role of
                                                                                                                       IL-6 in natural symptomatology and perhaps in the pathogenesis of CFS. In addition, the data demonstrate
                                                                                                                       that laboratory-induced fatigue (experimental fatigue) may not be a good model to study immunological
                                                                                                                       changes in CFS; immunological parameters should be studied in a longitudinal manner during the natural
                                                                                                                       course of the disease.
 Hartz AJ, Kuhn EM,       Department of Family           Prognostic factors for persons   Arch Fam Med 1999 Nov-       BACKGROUND: The simultaneous examination of a large number of patient characteristics in a
 Bentler SE, Levine PH,   Medicine, University of Iowa   with idiopathic chronic          Dec;8(6):495-501             prospective study of patients with chronic fatigue. OBJECTIVE: To compare the relative importance of
 London R.                College of Medicine, Iowa      fatigue.                                                      these characteristics as prognostic factors. METHODS: The data analyzed were from 199 subjects in a
                          City, USA.                                                                                   registry of persons who were aged 18 years or older and had idiopathic fatigue for at least 6 months. All
                                                                                                                       subjects completed an extensive baseline questionnaire that provided information about fatigue,
                                                                                                                       demographic characteristics, medical conditions, lifestyle, sleeping habits, psychological characteristics,
                                                                                                                       and the presence of criteria for chronic fatigue syndrome. Changes in fatigue severity from baseline to 2-
                                                                                                                       year follow-up were tested for an association with risk factors at baseline and with changes in symptoms
                                                                                                                       other than fatigue during the follow-up period. RESULTS: The following characteristics at baseline
                                                                                                                       significantly and independently predicted greater fatigue improvement: less unclear thinking, fewer
                                                                                                                       somatoform symptoms not used to define chronic fatigue syndrome, infrequent awakening, fewer hours
                                                                                                                       sleeping, and being married. Of 29 subjects who at baseline reported no somatoform symptoms unrelated to
                                                                                                                       chronic fatigue syndrome and who thought clearly most of the time, 8 substantially improved, compared
                                                                                                                       with 1 of 29 subjects who had more than 2 somatoform symptoms and never thought clearly (P = .01).
                                                                                                                       Improvements in the following symptoms were significantly and independently associated with
                                                                                                                       improvements in fatigue: unclear thinking, depression, muscle aches, and trouble falling asleep.
                                                                                                                       CONCLUSIONS: This study identified characteristics of subjects that seem to be of prognostic importance
                                                                                                                       for idiopathic chronic fatigue. Symptoms that change concomitantly with changes in fatigue may be
                                                                                                                       intrinsically linked to fatigue.
 Heap LC, Peters TJ,      Department of Clinical         Vitamin B status in patients     J R Soc Med 1999             Some patients with chronic fatigue syndrome say they benefit from taking vitamin supplements. We
 Wessely S.               Biochemistry, King's College   with chronic fatigue             Apr;92(4):183-5              assessed functional status for the B vitamins pyridoxine, riboflavin and thiamine in 12 vitamin-untreated
                          School of Medicine, London,    syndrome.                                                     CFS patients and in 18 healthy controls matched for age and sex. Vitamin-dependent activities--aspartate
                          UK.                                                                                          aminotransferase (AST) for pyridoxine, glutathione reductase (GTR) for riboflavin, transketolase (TK) for
                                                                                                                       thiamine--were measured in erythrocyte haemolysates before and after in-vitro addition of the relevant
                                                                                                                       vitamin. For all three enzymes basal activity (U/g Hb) was lower in CFS patients than in controls: AST 2.84
                                                                                                                       (SD 0.62) vs 4.61 (1.43), P < 0.001; GTR 6.13 (1.89) vs 7.42 (1.25), P < 0.04; TK 0.50 (0.13) vs 0.60
                                                                                                                       (0.07), P < 0.04. This was also true of activated values: AST 4.91 (0.54) vs 7.89 (2.11), P < 0.001; GTR
                                                                                                                       8.29 (1.60) vs 10.0 (1.80), P < 0.001; TK 0.56 (0.19) vs 0.66 (0.08), P < 0.07. The activation ratios,
                                                                                                                       however, did not differ between the groups. These data provide preliminary evidence of reduced functional
                                                                                                                       B vitamin status, particularly of pyridoxine, in CFS patients.
 Hickie I.                St George Hospital and         Nefazodone for patients with     Aust N Z J Psychiatry 1999   OBJECTIVE: Patients with chronic fatigue syndrome (CFS) present with a variety of musculoskeletal,
                          Community Service,             chronic fatigue syndrome.        Apr;33(2):278-80             neurocognitive, sleep disturbance and mood symptoms. An open evaluation of the clinical utility of the
                          Kogarah, New South Wales,                                                                    novel antidepressant compound, nefazodone, was completed. METHOD: Ten patients with CFS presenting
                          Australia.                                                                                   for assessment by a specialist psychiatrist were treated with nefazodone. Patients treated within this
                                                                                         specialist service are also advised to engage in appropriate behavioural and sleep-wake cycle strategies to
                                                                                                                       improve their level of functioning. RESULTS: Of the 10 patients, eight (80%) reported at least some
                                                                                                                       improvement in the key symptom of fatigue, with four (40%) reporting moderate or marked symptom relief.
                                                                                                                       Additionally, sleep disturbance and mood were both moderately or markedly improved in seven (70%) and
                                                                                                                       eight (80%) of the patients, respectively. Five of the patients (50%) achieved at least a moderate
                                                                                                                       improvement in overall functional outcome and were able to return to work or their previous level of role
                                                                                                                       function. The mean dose of nefazodone was 370 mg/day (range = 200-800 mg), with a strong preference
                                                                                                                       for nocturnal dosing. Seven of the patients had previously failed to respond to moclobemide, while seven
                                                                                                                       had previously failed to respond to conventional antidepressant therapy. CONCLUSION: Nefazodone
                                                                                                                       appears to be worthy of further systematic investigation in patients with CFS. Given its effects on sleep,
ME Research UK — Database of Research Publications 1999

                                                                                                                         mood and anxiety symptoms, it may have particular advantages in patients with this disorder.
 Hill NF, Tiersky LA,       Chronic Fatigue Syndrome        Natural history of severe       Arch Phys Med Rehabil 1999   OBJECTIVE: To evaluate the natural history of chronic fatigue syndrome (CFS) in a severely ill group of
 Scavalla VR, Lavietes M,   Center, Department of           chronic fatigue syndrome.       Sep;80(9):1090-4             patients at three points in time. DESIGN: Patients were enrolled from April 1992 to February 1994 and
 Natelson BH.               Neurosciences, University of                                                                 were evaluated three times. Time 1 (at enrollment): history, physical evaluation, and psychiatric evaluation;
                            Medicine and Dentistry-New                                                                   Time 2 (median = 1.6yrs after initial evaluation): postal questionnaire to assess current condition; Time 3
                            Jersey Medical School,                                                                       (median = 1.8 yrs after Time 2): medical and psychiatric evaluations. SETTING: The New Jersey CFS
                            Newark, USA.                                                                                 Cooperative Research Center, an ambulatory setting. PATIENTS: Twenty-three patients fulfilled the 1988
                                                                                                                         case definition for CFS and had symptom complaints that were substantial or worse in severity. All patients
                                                                                                                         were ill less than 4.5 years; and none had a DSM-III-R psychiatric disorder in the 5 years before illness
                                                                                                                         onset; none had substance abuse in the 10 years before enrollment. MAIN OUTCOME MEASURES:
                                                                                                                         Severity of CFS symptoms was assessed by self-report questionnaires, laboratory tests, and medical
                                                                                                                         examination. Psychological status was assessed using the Q-D15 and the Centers for Epidemiological
                                                                                                                         Study-Depression Scale. At each time of evaluation, patients were categorized as severe, slightly improved,
                                                                                                                         improved, and recovered. RESULTS: Over the 4 years of the study, 13 patients remained severely ill, 9
                                                                                                                         improved but still fulfilled the 1994 case definition for CFS, and 1 recovered. Illness duration, mode of
                                                                                                                         onset, psychiatric status or depressed mood at intake, or chemical sensitivity did not predict illness
                                                                                                                         outcome. One patient was diagnosed with an alternate illness, but it probably did not explain her CFS
                                                                                                                         symptoms. Mood improved for those patients whose illness lessened. CONCLUSIONS: The prognosis for
                                                                                                                         recovery was extremely poor for the severely ill subset of CFS patients. The majority showed no symptom
                                                                                                                         improvement and only 4% of the patients recovered. Illness severity between Times 2 and 3 remained
 Hodgson MJ, Kipen HM.      Department of Medicine,         Gulf War illnesses: causation   J Occup Environ Med 1999     Soldiers returning from the Gulf War in 1991 described a range of symptoms, including some consistent
                            University of Connecticut       and treatment.                  Jun;41(6):443-52             with the chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Well-defined adverse
                            Health Center, Farmington,                                                                   health events attributable to service in the Gulf occurred. However, controlled epidemiological studies in
                            USA.                                                                                         Gulf War veterans and controls describe significant excesses of symptoms that were not clearly associated
                                                                                                                         with pathologic disease. At least 12% of veterans currently receive some form of disability from the
                                                                                                                         Department of Veterans Affairs. A number of reports outline theories proposed to explain the excess, but
                                                                                                                         few are scientifically supported. Management guidelines for this spectrum of disorders resembles that of
                                                                                                                         many of "emerging overlap syndromes," including multiple chemical sensitivity, chronic fatigue syndrome,
                                                                                                                         and fibromyalgia. They include the establishment of a trusting doctor-patient relationship, negotiations
                                                                                                                         around a common ground of scientific and etiologic beliefs, non-labeling of the disorder, and work toward
                                                                                                                         recovery in the absence of clear etiologic answers.
 Hotopf M, Wessely S.                                       Chronic fatigue syndrome--      Psychol Med 1999
                                                            mapping the interior.           Mar;29(2):255-8
 Hudson M, Cleare AJ.       Department of Psychological     The 1microg short Synacthen     Clin Endocrinol (Oxf) 1999   OBJECTIVE: Many studies suggest mild hypocortisolism in chronic fatigue syndrome (CFS), usually
                            Medicine, Guy's King's and      test in chronic fatigue         Nov;51(5):625-30 Comment     assumed to be due to reduced suprahypothalamic drive to the hypothalamo-pituitary-adrenal (HPA) axis.
                            St Thomas' School of            syndrome.                       in: Clin Endocrinol (Oxf).   We wished to explore further the state of the HPA axis in CFS using the 1 microg low dose short Synacthen
                            Medicine and the Institute of                                   2000 Jun;52(6):797-9         test. DESIGN: Subjects received an intravenous bolus of 1 microg Synacthen; samples for cortisol
                            Psychiatry, London, UK.                                                                      estimation were taken at baseline and 2, 10, 20, 30, 40 and 60 minutes after injection. PATIENTS: We
                                                                                                                         tested 20 subjects suffering from CFS according to the criteria of the Center for Diseases Control without
                                                                                                                         psychiatric comorbidity and 20 matched healthy controls. All subjects were drug free for at least 1 month.
                                                                                                                         MEASUREMENTS: We calculated the cortisol responses to the test as the maximum cortisol attained, the
                                                                                                                         incremental rise in cortisol over baseline (Deltavalue) and as the integrated area under the curve.
                                                                                                                         RESULTS: There were no significant differences in baseline cortisol or cortisol responses between patients
                                                                                                                         and controls. However, responses generally were low, and many subjects' peak responses were prior to the
                                                                                                                         standard 30 minute sampling time., CONCLUSIONS These results do not lend support to the theory that
                                                                                                                         patients with chronic fatigue syndrome have a low adrenal reserve. However, results from studies assessing
                                                                                                                         the HPA axis are proving to be inconsistent. We suggest that many other factors may be contributing to
                                                                                                                         HPA axis alterations in chronic fatigue syndrome, including sleep disturbance, inactivity, altered circadian
                                                                                                                         rhythmicity, illness chronicity, concomitant medication and comorbid psychiatric disturbance. These
                                                                                                                         sources of heterogeneity need to be considered in future studies, and may explain the inconsistent findings
                                                                                                                         to date.
ME Research UK — Database of Research Publications 1999

 Itoh Y, Igarashi T,       Department of Pediatrics,     [Autoimmune fatigue             Nippon Ika Daigaku Zasshi   We have encounted two patients with fibromyalgia (FM) initially diagnosed as having autoimmune fatigue
 Tatsuma N, Imai T,        Nippon Medical School,        syndrome and fibromyalgia       1999 Aug;66(4):239-44       syndrome (AIFS). To investigate the relationship between AIFS and FM, the distribution of the tender
 Yoshida J, Tsuchiya M,    Tokyo, Japan.                 syndrome].[article in                                       points in patients with AIFS was assessed according to the ACR criteria for FM. It was revealed that AIFS
 Murakami M, Fukunaga Y.                                 Japanese]                                                   patients had 5.6 tender points on averages. Patients with headaches, digestive problems, or difficulty going
                                                                                                                     to school had more tender points than patients without. Patients with ANA titers < 1: 160 had more tender
                                                                                                                     points than patients with ANA > or = 1: 160. Anti-Sa negative patients had more tender points than
                                                                                                                     positive patients. These results suggest a relationship between AIFS and FM in terms of the
                                                                                                                     pathophysiologic mechanisms of the numerous tender points. In other words, ANA-positive FM patients
                                                                                                                     could be one form of AIFS, as well as ANA-positive chronic fatigue syndrome patients. Thus,
                                                                                                                     autoimmunity could explain the controversial disease entities of FM and/or CFS.
 Jackson EL.                                             The effects on siblings in      J Child Health Care 1999    Paediatric CFS/ME is a stressor, which affects not only the sufferer but also the whole family. The sibling
                                                         families with a child with      Summer;3(2):27-32           bond exerts a great influence on all the children in the family. Healthy siblings are often overlooked as
                                                         chronic fatigue syndrome.                                   attention is focused on the child with CFS/ME or other chronic illness. Individual children react in different
                                                                                                                     ways to serious illness in another sibling by adopting a variety of coping mechanisms. There is a need for
                                                                                                                     health and education professionals to consider the whole family when caring for and working with a child
                                                                                                                     with CFS/ME.
 Jahn K, Klenke T.             [Web sites on tinnitus,         MMW Fortschr Med 1999
                                                         fibromyalgia, chronic fatigue   Dec 16;141(51-52):14
                                                         syndrome, etc. Here your
                                                         patients seek
                                                         information].[article in
 Jason LA, King CP,        Department of Psychology,     Chronic fatigue syndrome:       J Clin Psychol 1999         Current approaches to the diagnosis and assessment of Chronic Fatigue Syndrome (CFS) rely primarily on
 Frankenberry EL, Jordan   DePaul University, Chicago,   assessing symptoms and          Apr;55(4):411-24            scales that measure only the occurrence of various symptoms related to CFS. Such approaches do not
 KM, Tryon WW,             IL 60613, USA.                activity level.                                             provide information on either the severity of symptoms or on fluctuations in symptom severity and activity
 Rademaker F, Huang CF.                                                                                              level that occur over time. As a result, these measures do not reflect the complexities and the interrelations
                                                                                                                     among symptoms. By obscuring the fluctuating nature of CFS and its high variability, current assessment
                                                                                                                     procedures may prevent health care professionals from understanding the complexities of this disease. The
                                                                                                                     present study provides two CFS case studies to illustrate the advantages of using self-reporting rating scales
                                                                                                                     in combination with a device used to measure the frequency and intensity of activity. The implications of
                                                                                                                     this assessment system, which captures the symptom dynamics and variability involved in CFS, are
 Jason LA, Melrose H,      DePaul University, Chicago,   Managing chronic fatigue        AAOHN J 1999                1. The basic principles of envelope theory are explained. By not overexerting themselves, people with CFS
 Lerman A, Burroughs V,    IL, USA.                      syndrome: overview and case     Jan;47(1):17-21             can avoid the setbacks and relapses that commonly occur in response to overexertion while increasing their
 Lewis K, King CP,                                       study.                                                      tolerance to activity. 2. By collecting time series data on fluctuations in energy levels, important clinical
 Frankenberry EL.                                                                                                    observations can be made in respect to a client's unique condition and experience with CFS.
 Jason LA, Richman JA,     Department of Psychology,     A community-based study of      Arch Intern Med 1999 Oct    BACKGROUND: Most previous estimates of the prevalence of chronic fatigue syndrome (CFS) have
 Rademaker AW, Jordan      DePaul University, Chicago,   chronic fatigue syndrome.       11;159(18):2129-37          derived largely from treated populations, and have been biased by differential access to health care
 KM, Plioplys AV, Taylor   IL 60614, USA.                                                                            treatment linked with sex, ethnic identification, and socioeconomic status. OBJECTIVE: To assess the
 RR, McCready W, Huang                                                                  point prevalence of CFS in an ethnically diverse random community sample. DESIGN AND
 CF, Plioplys S.                                                                                                     PARTICIPANTS: A sample of 28,673 adults in Chicago, Ill, was screened by telephone, and those with
                                                                                                                     CFS-like symptoms were medically evaluated. MAIN OUTCOME MEASURES AND ANALYSES: Self-
                                                                                                                     report questionnaires, psychiatric evaluations, and complete medical examinations with laboratory testing
                                                                                                                     were used to diagnose patients with CFS. Univariate and multivariate statistical techniques were used to
                                                                                                                     delineate the overall rate of CFS in this population, and its relative prevalence was subcategorized by sex,
                                                                                                                     ethnic identification, age, and socioeconomic status. RESULTS: There was a 65.1% completion rate for the
                                                                                                                     telephone interviews during the first phase of the study. Findings indicated that CFS occurs in about 0.42%
                                                                                                                     (95% confidence interval, 0.29%-0.56%) of this random community-based sample. The highest levels of
                                                                                                                     CFS were consistently found among women, minority groups, and persons with lower levels of education
                                                                                                                     and occupational status. CONCLUSIONS: Chronic fatigue syndrome is a common chronic health
                                                                                                                     condition, especially for women, occurring across ethnic groups. Earlier findings suggesting that CFS is a
                                                                                                                     syndrome primarily affecting white, middle-class patients were not supported by our findings.
ME Research UK — Database of Research Publications 1999

 Jason LA, Tryon WW,       Department of Psychology,       Monitoring and assessing         Psychol Rep 1999             Chronic Fatigue Syndrome's principal symptoms are severe and include prolonged fatigue and a number of
 Taylor RR, King C,        DePaul University, Chicago,     symptoms of chronic fatigue      Aug;85(1):121-30             other minor symptoms. Behavioral data collection methods were used in a case study to show some of the
 Frankenberry EL, Jordan   IL 60614, USA.                  syndrome: use of time series                                  benefits that can be derived from monitoring symptoms hourly and daily. Using time series regression,
 KM.                                                       regression.                                                   several statistically significant correlates of fatigue were found both within days and between days.
                                                                                                                         Perceived energy, physical exertion, and mental exertion were significantly related to fatigue in both
                                                                                                                         analyses. Collection of such data may help resolve a number of theoretical and methodological problems in
                                                                                                                         research on the Chronic Fatigue Syndrome.
 Jeffcoate WJ.             Department of Diabetes and      Chronic fatigue syndrome         Lancet 1999 Feb
                           Endocrinology, City             and functional hypoadrenia--     6;353(9151):424-5Comment
                           Hospital, Nottingham, UK.       fighting vainly the old ennui.   in: Lancet. 1999 Feb
                                                                                            6;353(9151):445-8 Lancet.
                                                                                            1999 May
 Johnson SK, DeLuca J,     Department of Psychology,       Chronic fatigue syndrome:        Ann Behav Med 1999           This article reviews the current state of research in chronic fatigue syndrome (CFS). The evolving
 Natelson BH.              University of North Carolina,   reviewing the research           Summer;21(3):258-71          definition, prevalence, and prognosis of this controversial illness are presented. We review studies
                           Charlotte 28223, USA.           findings.                                                     examining psychiatric, personality, and psychosocial etiology for CFS. The evidence for pathophysiology in
                                                                                                                         CFS is also presented, and studies investigating viral, immune, neuroimaging, neuroendocrine, and central
                                                                                                                         and autonomic nervous system abnormalities in CFS are assessed. Current evidence indicates that CFS is
                                                                                                                         multi-determined and heterogeneous and that subgrouping patients according to factors such as psychiatric
                                                                                                                         state and symptom onset may be fruitful. The current state of treatment for CFS is reviewed, and the
                                                                                                                         challenges for research aimed at resolving this prototypical mind/body problem are discussed.
 Jones E, Wessely S.       Department of Psychological     Case of chronic fatigue          BMJ 1999 Dec 18-
                           Medicine, Guy's, King's, and    syndrome after Crimean war       25;319(7225):1645-7
                           St Thomas's School of           and Indian mutiny.
                           Medicine, London SE5 8AZ.
 Kakumanu S, Yeager M,     Pennsylvania State              Chronic fatigue syndrome.        J Am Osteopath Assoc 1999    The chronic fatigue syndrome is an illness of unknown etiology characterized by severe fatigue, myalgias,
 Craig TJ.                 University, College of                                           Oct;99(10 Su Pt 1):S1-5      lymphadenopathy, arthralgias, chills, fevers, and postexertional malaise. Recognizing chronic fatigue
                           Medicine, Hershey, USA.                                                                       syndrome is primarily a method of exclusion with no definitive diagnostic test or physical findings. As
                                                                                                                         research continues to delve into the many possible etiologic agents for chronic fatigue syndrome--
                                                                                                                         infectious, immunologic, neurologic, or psychiatric alone or in combination--the answer remains elusive.
                                                                                                                         What is known is that chronic fatigue syndrome is a heterogeneous disorder very possibly involving an
                                                                                                                         interaction of biological systems. Therefore, chronic fatigue syndrome may describe a large subset of
                                                                                                                         patients, each exhibiting unique symptoms and serologic profiles dependent on the nature of the onset of
                                                                                                                         illness and the genetic profile of individual patients.
 Keenan PA. Editorial                                      Brain MRI abnormalities          J Neurol Sci 1999 Dec
                                                           exist in chronic fatigue         1;171(1):1-2 Comment on: J
                                                           syndrome.                        Neurol Sci. 1999 Dec
 Kenter EG, Okkes IM.      Academisch Medisch              [Patients with fatigue in        Ned Tijdschr Geneeskd 1999   OBJECTIVE: To gain insight into the prevalence and treatment of severe fatigue in general practice.
                           Centrum/Universiteit van        family practice: prevalence      Apr 10;143(15):796-801       DESIGN: Secondary data analysis. METHOD: By means of an episode-oriented morbidity registration by
                           Amsterdam, afd.                 and treatment].[article in                                    54 GPs throughout the Netherlands over the period 1985-1994 it was established how often in the course of
                           Huisartsgeneeskunde.            Dutch]                                                        one year 'fatigue' was listed as the reason for consultation, what diagnoses were then made, how long
                                                                                                                         episodes of care because of 'fatigue' lasted and what interventions took place (n = 93,297). Of the patients
                                                                                                                         with a care episode because of 'fatigue' lasting at least 6 months, age, sex, comorbidity and consumption of
                                                                                                                         care were established; for this purpose use was also made of a file containing data on 4 years in succession
                                                                                                                         (n = 9630). RESULTS: Per annum, 92 per 1000 listed patients consulted the GP because of fatigue.
                                                                                                                         Somatic or psychic diagnoses were made in 27.7 per 1000 patients listed. The episode of care lasted 4
                                                                                                                         weeks at most in 86% and at least 6 months in approximately 4%. The GPs' management of patients with
                                                                                                                         'fatigue' included physical examination in 63% and blood testing in 34%, conversation in 35%, prescription
ME Research UK — Database of Research Publications 1999

                                                                                                                        of medication in 24% and referral to a specialist in 3%. Of the 97 patients with fatigue lasting longer than 6
                                                                                                                        months, 61% had a chronic disease or psychic problems. CONCLUSION: Fatigue is frequently encountered
                                                                                                                        in general practice, but the estimate that one per 1000 listed patients meets the criteria of the chronic
                                                                                                                        fatigue syndrome looks a little high. It appears that GPs, in accordance with recommendations, mostly
                                                                                                                        adopt a policy of wait and see.
 Kipen HM, Hallman W,       New Jersey Center for         Prevalence of chronic fatigue   Arch Environ Health 1999      More than 68000 of the 700000 veterans of the Gulf War have become members of the Veteran Affairs'
 Kang H, Fiedler N,         Environmental Hazards         and chemical sensitivities in   Sep-Oct;54(5):313-            Gulf War Registry. In 1995, we undertook a questionnaire study of the symptoms and medical histories
 Natelson BH.               Research, East Orange, USA.   Gulf Registry Veterans.         8Comment in: Arch Environ     reported by a randomly selected subsample of 1935 of these veterans to characterize their complaints. All
                                                                                          Health. 1999 Sep-             results reported were based on questionnaire responses without face-to-face evaluation or physical
                                                                                          Oct;54(5):309-11              examinations. Inasmuch as initial registry symptoms overlapped those of Chronic Fatigue Syndrome and
                                                                                                                        Multiple Chemical Sensitivities, we also included standard questions for these syndromes in the
                                                                                                                        questionnaire. A total of 1161 (60%) individuals responded, and there were no major demographic biases;
                                                                                                                        therefore, 15.7% of registry veterans qualified for Chronic Fatigue Syndrome in accordance with the 1994
                                                                                                                        Centers for Disease Control definition. In addition, 13.1% qualified for multiple chemical sensitivities in
                                                                                                                        accordance with a widely used definition, and 3.3% of the respondents had both conditions. There were no
                                                                                                                        effects of gender, race, branch, duty status (active or reserve), or rank, although Multiple Chemical
                                                                                                                        Sensitivities was somewhat more prevalent in women and African Americans. The data gleaned in this
                                                                                                                        study suggested that the unexplained symptom syndromes of Chronic Fatigue and Multiple Chemical
                                                                                                                        Sensitivities may characterize an appreciable portion of the complaints of those who volunteered for the
                                                                                                                        Veterans Affairs' Gulf War Registry, and further investigation is warranted.
 Knobeloch L, Jackson R.    Bureau of Environmental       Recognition of chronic          WMJ 1999 Sep-                 Chronic exposure to low levels of carbon monoxide can cause vague symptoms that are easily mistaken for
                            Health, Wisconsin Division    carbon monoxide poisoning.      Oct;98(6):26-9                other common illnesses. During the past 5 years, three families have contacted the Wisconsin Division of
                            of Public Health, Madison                                                                   Public Health to report illnesses that may have been caused by chronic exposure to carbon monoxide.
                            53703-3043, USA.                                                                            Members of these families were diagnosed with a variety of conditions including chronic fatigue syndrome,
                                                                                                                        depression and influenza. Carbon monoxide exposure was not suspected as a cause of these illnesses until
                                                                                                                        heating contractors discovered that gas appliances in these families' homes were not properly vented. These
                                                                                                                        cases serve as reminders that carbon monoxide exposure should be considered in the differential diagnosis
                                                                                                                        of patients who present with chronic symptoms of headache, fatigue, dizziness, nausea and mental
                                                                                                                        confusion--especially when these symptoms onset during the winter heating season.
 Korszun A, Sackett-        Department of Psychiatry,     Melatonin levels in women       J Rheumatol 1999              OBJECTIVE: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) are stress associated disorders
 Lundeen L, Papadopoulos    University of Michigan        with fibromyalgia and           Dec;26(12):2675-80            mainly affecting women. FM is characterized primarily by widespread musculoskeletal pain, and CFS by
 E, Brucksch C, Masterson   Medical Center, Ann Arbor,    chronic fatigue syndrome.                                     profound debilitating fatigue, but there is considerable overlap of clinical symptoms between these 2
 L, Engelberg NC, Haus E,   USA.                                                                     syndromes. Neuroendocrine abnormalities have been noted in both FM and CFS and desynchronization of
 Demitrack MA, Crofford                                                                                                 circadian systems has been postulated in their etiology. The pineal hormone melatonin is involved in
 L.                                                                                                                     synchronizing circadian systems and the use of exogenous melatonin has become widespread in patients
                                                                                                                        with FM and CFS. METHODS: We examined the characteristics and relationship of melatonin and cortisol
                                                                                                                        levels in premenopausal women with FM (n = 9) or CFS (n = 8), compared to age and menstrual cycle
                                                                                                                        phase matched controls. Blood was collected from an indwelling intravenous catheter every 10 min over 24
                                                                                                                        h, and plasma melatonin and cortisol were determined by radioimmunoassay at 60 and 10 min intervals,
                                                                                                                        respectively. RESULTS: Night time (23:00-06:50) plasma melatonin levels were significantly higher in FM
                                                                                                                        patients compared to controls (p<0.05), but there was no significant difference in melatonin levels between
                                                                                                                        CFS patients and controls. No differences in the timing of cortisol and melatonin secretory patterns and no
                                                                                                                        internal desynchronization of the 2 rhythms were found in either patient group, compared to controls.
                                                                                                                        CONCLUSION: Raised plasma melatonin concentrations have been documented in several other
                                                                                                                        conditions that are associated with dysregulation of neuroendocrine axes. Increased melatonin levels may
                                                                                                                        represent a marker of increased susceptibility to stress induced hypothalamic disruptions. These data
                                                                                                                        indicate that there is no rationale for melatonin replacement therapy in patients with FM and CFS.
 Kreyberg S.                                              [A close meeting with           Tidsskr Nor Laegeforen 1999
                                                          chronic fatigue                 Jun 10;119(15):2229-31
                                                          syndrome].[article in
 Kreyberg S.                                              [Management of chronic          Lakartidningen 1999 Dec
ME Research UK — Database of Research Publications 1999

                                                             fatigue syndrome reflects the    1;96(48):5342
                                                             physician's "illness belief"
                                                             letter)]. [Article in Swedish]
 LaManca JJ, Peckerman A,     CFS Cooperative Research       Cardiovascular response          Clin Physiol 1999           This study examined the cardiovascular response to orthostatic challenge, and incidence and mechanisms
 Walker J, Kesil W, Cook S,   Center, University of          during head-up tilt in chronic   Mar;19(2):111-20            of neurally mediated hypotension in chronic fatigue syndrome (CFS) during a head-up tilt test. Stoke
 Taylor A, Natelson BH.       Medicine and Dentistry of      fatigue syndrome.                                            volume was obtained by a thoracic impedance cardiograph, and continuous heart rate and blood pressure
                              New Jersey-New Jersey                                                                       were recorded during a 45-min 70 degrees head-up tilt test. Thirty-nine CFS patients and 31 healthy
                              Medical School, Newark,                                                                     physically inactive control subjects were studied. A positive tilt, i.e. a drop in systolic blood pressure of >
                              USA.                                                                                        25 mmHg, no concurrent increase in heart rate and/or development of presyncopal symptoms, was seen in
                                                                                                                          11 CFS patients and 12 control subjects (P > 0.05). During baseline and the first 5 min of head-up tilt, CFS
                                                                                                                          patients had higher heart rate and smaller pulsatile-systolic area than control subjects (P < 0.05). Among
                                                                                                                          subjects who completed the test, those with CFS had higher heart rate and smaller stroke volume (P < 0.05)
                                                                                                                          than corresponding control subjects. When comparing those who had a positive test outcome in each group,
                                                                                                                          CFS patients had higher heart rates and lower pulse pressure and pulsatile-systolic areas during the last 4
                                                                                                                          min before being returned to supine (P < 0.05). These data show that there are baseline differences in the
                                                                                                                          cardiovascular profiles of CFS patients when compared with control subjects and that this profile is
                                                                                                                          maintained during head-up tilt. However, the frequency of positive tilts and the haemodynamic adjustments
                                                                                                                          made to this orthostatic challenge are not different between groups.
 LaManca JJ, Sisto SA,        NJ CFS Cooperative             Immunological response in        J Clin Immunol 1999         This study was conducted to evaluate the immunological response to an exhaustive treadmill exercise test
 Zhou XD, Ottenweller JE,     Research Center, UMDNJ-        chronic fatigue syndrome         Mar;19(2):135-42            in 20 female chronic fatigue syndrome patients compared to 14 matched sedentary controls. Venipuncture
 Cook S, Peckerman A,         New Jersey Medical School,     following a graded exercise                                  was performed at baseline and 4 min, 1 hr, and 24 hr postexercise. White blood cells were labeled for
 Zhang Q, Denny TN, Gause     Newark 07103, USA.             test to exhaustion.                                          monoclonal antibody combinations and were quantified by FACsan. Cytokines were assayed utilizing
 WC, Natelson BH.                                                                                                         quantitative RT/PCR. No group difference was seen in VO2peak (28.6 +/- 1.6 vs 30.9 +/- 1.2
                                                                                                                          1; P > 0.05). However, 24 hr after exercise the patients' fatigue levels were significantly increased (P <
                                                                                                                          0.05). The counts of WBC, CD3+ CD8+ cells, CD3+ CD4+ cells, T cells, B cells, natural killer cells, and
                                                                                                                          IFN-gamma changed across time (P's < 0.01). No group differences were seen for any of the immune
                                                                                                                          variables at baseline or after exercise (P's > 0.05). The immune response of chronic fatigue syndrome
                                                                                                                          patients to exhaustive exercise is not significantly different from that of healthy nonphysically active
 Lange G, DeLuca J,           Department of Psychiatry,      Brain MRI abnormalities          J Neurol Sci 1999 Dec       Presence of MRI brain abnormalities in patients with Chronic Fatigue Syndrome (CFS) was determined and
 Maldjian JA, Lee H,          UMDNJ-New Jersey Medical       exist in a subset of patients    1;171(1):3-7Comment in: J   the profile of MRI abnormalities was compared between 39 CFS patients, 18 with (CFS-Psych) and 21
 Tiersky LA, Natelson BH.     School, MSB E-561, 185 S.      with chronic fatigue             Neurol Sci. 1999 Dec        without (CFS-No Psych) a DSM-III-R Axis I psychiatric diagnosis since illness onset, and 19 healthy,
                              Orange Avenue, Newark, NJ      syndrome.                        1;171(1):1-2                sedentary controls (HC). Two neuroradiologists, blind to group membership, separately read the MR films
                              07103-2714, USA.                                                                            using a detailed protocol for rating and categorizing abnormal signal changes. When findings were
                                                                                                                          incongruent, the two neuroradiologists met to try to reach consensus, otherwise a third neuroradiologist
                                                                                                                          evaluated the MR images and served as a tie-breaker. The CFS-No Psych group showed a significantly
                                                                                                                          larger number of brain abnormalities on T2 weighted images than the CFS-Psych and HC groups. Cerebral
                                                                                                                          changes in the CFS-No Psych group consisted mostly of small, punctate, subcortical white matter
                                                                                                                          hyperintensities, found predominantly in the frontal lobes. No significant difference was found when both
                                                                                                                          CFS groups were combined and compared to the HC group. The use of stratification techniques is an
                                                                                                                          important strategy in understanding the pathophysiology of CFS. This frontal lobe pathology could explain
                                                                                                                          the more severe cognitive impairment previously reported in this subset of CFS patients.
 Lange G, Tiersky L,          Center for Environmental       Psychiatric diagnoses in Gulf    Psychiatry Res 1999 Dec     The purpose of this study was to determine whether Gulf War Illness (GWI) can be explained by the
 DeLuca J, Peckerman A,       Hazards Research, VA           War veterans with fatiguing      13;89(1):39-48              presence of psychiatric disorders as assessed by DSM-III-R. To reduce the heterogeneity amongst Persian
 Pollet C, Policastro T,      Medical Center, East Orange,   illness.                                                     Gulf War veterans with GWI (PGV-F), only those were studied who presented with severe fatigue as a
 Scharer J, Ottenweller JE,   NJ, USA.                                                                                    major complaint and also fulfilled clinical case definitions for Chronic Fatigue Syndrome, Idiopathic
 Fiedler N, Natelson BH.                                                                           Chronic Fatigue, and/or Multiple Chemical Sensitivity. A total of 95 Registry PGVs were examined; 53
                                                                                                                          presented with GWI and 42 did not report any post-war health problems (PGV-H). All subjects were
                                                                                                                          assessed for the presence of DSM-III-R Axis I psychiatric disorders. Compared to PGV-Hs, 49% of PGV-Fs
                                                                                                                          had similar post-war psychiatric profiles: either no, or only one, psychiatric disorder was diagnosed.
                                                                                                                          Psychiatric profiles of the remaining 51% of PGV-Fs were significantly different from PGV-Hs in that most
                                                                                                                          of these veterans suffered from multiple post-war psychiatric diagnoses. The presence of psychiatric
ME Research UK — Database of Research Publications 1999

                                                                                                                             disorders as assessed by DSM-III-R criteria cannot explain symptoms of Gulf War Illness among all Persian
                                                                                                                             Gulf veterans with severe fatiguing illness.
 Lloyd AR, Hickie I,          School of Pathology,           Chronic fatigue syndrome:        Curr Clin Top Infect Dis
 Peterson PK.                 University of New South        current concepts of              1999;19:135-59
                              Wales, Australia.              pathogenesis and treatment.
 Lovell DM.                   Oxford University Psychiatry   Chronic fatigue syndrome         J Travel Med 1999              BACKGROUND: A relatively high proportion of overseas development workers may develop chronic
                              Department, Warneford          among overseas development       Mar;6(1):16-23                 fatigue syndrome (CFS). A qualitative study was conducted in order to investigate how such people
                              Hospital, Oxford, England.     workers: A qualitative study.                                   perceived their condition. METHODS: Twelve people who had developed CFS while working overseas
                                                                                                                             with development organizations, or shortly after visiting development projects, were interviewed about their
                                                                                                                             experiences. Their responses were analyzed using a grounded theory approach. RESULTS: Most of the
                                                                                                                             participants considered themselves to have been extremely healthy before they developed CFS. The
                                                                                                                             syndrome did not appear to have been caused by depression. The symptoms which were reported covered
                                                                                                                             the range of symptoms typically found in studies of CFS. Respondents described difficulty in receiving, and
                                                                                                                             accepting, a diagnosis. All of the participants attributed the CFS to multiple causes, the principal causes
                                                                                                                             being overwork, stress and infections. Among the consequences of CFS reported to be the most difficult
                                                                                                                             were having to leave the development project prematurely; pain; powerlessness; loss of independence, and
                                                                                                                             the unpredictability of CFS. Factors which had helped respondents cope with these difficulties included
                                                                                                                             religious beliefs; comparisons with people who were worse off than they were; thinking about positive
                                                                                                                             consequences of the condition, and talking with supportive people. CONCLUSIONS: Some theories have
                                                                                                                             suggested that CFS symptoms arise as a result of depression or other emotional difficulties, which the
                                                                                                                             individual is not able to acknowledge. The results indicated that such theories may not apply to this
                                                                                                                             subgroup of people with CFS. Further research on the etiology of CFS is warranted. Respondents described
                                                                                                                             high levels of work-related stress as common to the experience of development work. It might be beneficial
                                                                                                                             to train development workers in stress management techniques. Development organizations should be
                                                                                                                             encouraged to ensure that their workers take sufficient time to rest, and attempts should be made to reduce
                                                                                                                             work pressures.
 Lundin A.                                                   [Chronic fatigue syndrome is     Lakartidningen 1999 Oct
                                                             not medically explained.         6;96(40):4350-52
                                                             Biomedical explanation is
                                                             confusing for the
                                                             patient].[article in Swedish]
 Magdic B, Ilic T, Jovankic                                  [The chronic fatigue             Vojnosanit Pregl 1999 Mar-
 O, Cedic V.                                                 syndrome--a clinical entity or   Apr;56(2):167-71
                                                             a complex of symptoms of
                                                             various pathologic
                                                             conditions].[article in Serbo-
                                                             Croatian (Cyrillic)]
 Marcusson JA, Lindh G,       Department of Dermatology,     Chronic fatigue syndrome         Contact Dermatitis 1999        50 patients with chronic fatigue syndrome (CFS) and 73 controls were patch tested with 8 metal allergens.
 Evengard B.                  Huddinge University            and nickel allergy.              May;40(5):269-72Comment        We found an overrepresentation of allergies among the CFS patients, which was not significant. However,
                              Hospital, Sweden.                                               in: Contact Dermatitis. 2000   allergy to nickel occurred in 36% of patients in the CFS group and in 19% of subjects in the control group
                                                                                              Jan;42(1):56-7                 (p<0.05). The high frequency of nickel allergy was more noteworthy in females in the CFS group than
                                                                                                                             among female controls (52% and 24%, respectively, p<0.05). Similarly, in the males the figures were 14%
                                                                                                                             and 9%. We suggest that in vivo immunoactivation by ions of nickel, or metal cross-reacting with nickel,
                                                                                                                             could be an etiological factor in CFS.
 Marcusson JA.                                               The frequency of mercury         Contact Dermatitis 1999
                                                             intolerance in patients with     Jul;41(1):60-1
                                                             chronic fatigue syndrome and
                                                             healthy controls.
 Marshall GS.                 Department of Pediatrics,      Report of a workshop on the      J Pediatr 1999
                              University of Louisville       epidemiology, natural            Apr;134(4):395-405
                              School of Medicine,            history, and pathogenesis of
ME Research UK — Database of Research Publications 1999

                            Louisville, Kentucky, USA.    chronic fatigue syndrome in
                            Review Review, Multicase      adolescents.
 Martin WJ.                 Center for Complex            Stealth adaptation of an        Exp Mol Pathol 1999            DNA extracted from cultures of a cytopathic virus isolated from a patient with chronic fatigue syndrome
                            Infectious Diseases,          African green monkey simian     Apr;66(1):3-7                  was cloned into pBluescript plasmid. The nucleotide sequences of the plasmid inserts were analyzed using
                            Rosemead, California 91770,   cytomegalovirus.                                               the BlastN and BlastX programs of the National Center for Biotechnology Information. In confirmation of
                            USA.                                                                                         earlier studies, many of the sequences show partial homology to various regions within the genome of
                                                                                                                         human cytomegalovirus (HCMV). The matching regions were unevenly distributed throughout the HCMV
                                                                                                                         genome. No matches were seen with either the UL55 or the UL83 genes, which provide the major antigenic
                                                                                                                         targets for anti-HCMV cytotoxic T-cell-mediated immunity. This finding is consistent with the notion that
                                                                                                                         certain viruses can avoid immune elimination by deleting genes required for effective antigenic recognition
                                                                                                                         by the cellular immune system. The term "stealth" has been applied to such viruses. Comparisons were also
                                                                                                                         made between the sequences of the stealth virus and the limited sequence data available on
                                                                                                                         cytomegaloviruses from rhesus monkeys and from African green monkeys. These comparisons
                                                                                                                         unequivocally establish that the virus was derived from an African green monkey simian cytomegalovirus.
                                                                                                                         Copyright 1999 Academic Press.
 Matsuda J, Gohchi K.       Department of Clinical        [Chronic fatigue                Ryoikibetsu Shokogun
                            Biochemistry, Faculty of      syndrome].[article in           Shirizu 1999;(24 Pt 2):161-5
                            Pharmaceutical Sciences,      Japanese]
                            Teikyo University.
 Matsumoto Y.               Center of Rheumatic           [Fibromyalgia                   Nippon Rinsho 1999             Fibromyalgia syndrome (FMS) is recognizable syndrome characterized by chronic, diffuse pain, an absence
                            Diseases, Toyokawa City       syndrome].[article in           Feb;57(2):364-9                of inflammatory or structural muscloskeletal abnormalities, and a range of symptoms that include fatigue,
                            Hospital.                     Japanese]                                                      and sleep and mood disturbances. Physical examination and laboratory testing are unrevealing, except for
                                                                                                                         the presence of pain on palpation of characteristic soft-tissue sites, the tender points. Despite the
                                                                                                                         recognition of FMS by the World Health Organization, it remains a controversial condition and its
                                                                                                                         existence as a distinct entity remains uncertain. However, the concept of FMS is a useful one, allowing
                                                                                                                         many investigations to be avoided and appropriate advice on treatment to be given. FMS may overlap with
                                                                                                                         symptoms of, and the patient further impaired by, anxiety and depression. The term FMS dose not imply
                                                                                                                         causation and merely describes the most common symptoms. Many patients with chronic fatigue
                                                                                                                         syndrome(CFS) fulfill the criteria of FMS and represent one end of a spectrum of presentation. Evidence
                                                                                                                         for triggering viral infection and the lower level of serum acylcarnitine, observed in CFS patients, is lacking
                                                                                                                         in the majority of patients with FMS. These findings are suggestive to be distinctively another disorders
                                                                                                                         between FMS and CFS.
 Matsumoto Y.                                             [Immunological aspects of       Nihon Rinsho Meneki
                                                          pathophysiology of chronic      Gakkai Kaishi 1999
                                                          fatigue syndrome].[article in   Jun;22(3):111-22
 McCully KK, Natelson BH.   Department of Medicine,       Impaired oxygen delivery to     Clin Sci (Colch) 1999          The purpose of this study was to determine if chronic fatigue syndrome (CFS) is associated with reduced
                            Medical College of            muscle in chronic fatigue       Nov;97(5):603-8; discussion    oxygen delivery to muscles. Patients with CFS according to CDC (Center for Disease Control) criteria
                            Pennsylvania and              syndrome.                       611-3Comment in: Clin Sci      (n=20) were compared with normal sedentary subjects (n=12). Muscle oxygen delivery was measured as the
                            Hahnemann University,                                         (Colch). 1999                  rate of post-exercise and post-ischaemia oxygen-haem resaturation. Oxygen-haem resaturation was
                            Philadelphia, PA 19129,                                       Nov;97(5):611-3                measured in the medial gastrocnemius muscle using continuous-wavelength near-IR spectroscopy.
                            USA.                                                                    Phosphocreatine resynthesis was measured simultaneously using (31)P magnetic resonance spectroscopy.
                                                                                                                         The time constant of oxygen delivery was significantly reduced in CFS patients after exercise (46.5+/-16 s;
                                                                                                                         mean+/-S.D.) compared with that in controls (29.4+/-6.9 s). The time constant of oxygen delivery was also
                                                                                                                         reduced (20.0+/-12 s) compared with controls (12.0+/-2.8 s) after cuff ischaemia. Oxidative metabolism
                                                                                                                         was also reduced by 20% in CFS patients, and a significant correlation was found between oxidative
                                                                                                                         metabolism and recovery of oxygen delivery. In conclusion, oxygen delivery was reduced in CFS patients
                                                                                                                         compared with that in sedentary controls. This result is consistent with previous studies showing abnormal
                                                                                                                         autonomic control of blood flow. Reduced oxidative delivery in CFS patients could be specifically related
                                                                                                                         to CFS, or could be a non-specific effect of reduced activity levels in these patients. While these results
                                                                                                                         suggest that reduced oxygen delivery could result in reduced oxidative metabolism and muscle fatigue,
                                                                                                                         further studies will be needed to address this issue.
ME Research UK — Database of Research Publications 1999

 Meggs WJ. Editorial                                       Gulf War Syndrome, Chronic      Arch Environ Health 1999
                                                           Fatigue Syndrome, and the       Sep-Oct;54(5):309-11
                                                           Multiple Chemical               Comment on: Arch Environ
                                                           Sensitivity Syndrome:           Health. 1999 Sep-
                                                           stirring the cauldron of        Oct;54(5):313-8
 Merz S.                                                   Lakartidningen. 1999 Nov        Lakartidningen 1999 Oct
                                                           10;96(45):4904 [Treatment       13;96(41):4409 Comment in:
                                                           of chronic fatigue              Lakartidningen. 1999 Dec
                                                           syndrome].[article in           15;96(50):5610
 Michiels V, de Gucht V,    Free University of Brussels    Attention and information       J Clin Exp Neuropsychol      In this study a battery of attentional tests and a verbal memory task were administered to outpatients with
 Cluydts R, Fischler B.     (VUB), Belgium.                processing efficiency in        1999 Oct;21(5):709-29        Chronic Fatigue Syndrome (CFS) in order to evaluate aspects of attention that have not been explored in
                                                           patients with Chronic Fatigue                                this group to date. In addition, this study was designed to further examine memory function and to extend
                                                           Syndrome.                                                    the few reports investigating the rate of cognitive processing independent of motor speed and the possibility
                                                                                                                        of a modality-specific impairment of information processing. Twenty-nine patients with CFS and 22
                                                                                                                        healthy controls matched for age, gender, intelligence, and education were included in this study. The
                                                                                                                        results show that patients with CFS do not seem to be impaired for modification of phasic arousal level, nor
                                                                                                                        for visual selective attention requiring shifting of attention in the visuospatial field. The results further
                                                                                                                        support the presence of reduced information processing speed and efficiency, and strengthen the evidence
                                                                                                                        of a global non-modality-specific attentional dysfunction in patients with CFS. In this study the poor
                                                                                                                        performance of patients with CFS on recall of verbal information was due to poor initial storage rather than
                                                                                                                        to a retrieval failure.
 Mojarro Praxedes MD,       Servicio de                    [The chronic fatigue and        Actas Esp Psiquiatr 1999     INTRODUCTION: Fatigue is one of the most common symptoms in community studies, primary care and
 Benjumea Pino P.           Psiquiatria,Hospital Clinico   neurasthenia in the student     Jan-Feb;27(1):14-21          other medical setting. In spite of a high frequency of fatigue, the incidence of chronic fatigue syndrome is
                            Universitario, Sevilla,        population].[article in                                      very low. In this paper, we want to know the frequency of chronic fatigue syndrome and neurasthenia; we
                            Sevilla, 41009,Espana.         Spanish]                                                     want to know the association between fatigue and depressive symptoms in students. METHODS: We
                                                                                                                        studied 277 medical student, administering: 1. a center for disease control questionnaire to assess major
                                                                                                                        criteria and minor criteria of chronic fatigue syndrome, 2. ICD 10 criteria for the diagnoses of neurasthenia
                                                                                                                        and 3. Beck depression inventory. RESULTS AND CONCLUSIONS: We found that the 37,55% of the
                                                                                                                        subjects suffer fatigue. 9 subjects (3,25% of the total) meet the criteria of neurasthenia. 2 subjects (0,72%
                                                                                                                        of the total) meet the chronic fatigue syndrome criteria. The depressive symptoms are most frequent in the
                                                                                                                        subjects with fatigue, but we don't know if they are the cause or the consequence of the fatigue. With the
                                                                                                                        factorial analyses, we find that symtoms of physical fatigue, mental fatigue and cognitive difficulties are
                                                                                                                        factor independent of each other.
 Morriss RK, Ahmed M,       Department of Community        The role of depression in       J Affect Disord 1999         BACKGROUND: The association between depression and pain, function, medically unexplained
 Wearden AJ, Mullis R,      Psychiatry, Royal Preston      pain, psychophysiological       Oct;55(2-3):143-8            symptoms and psychophysiological syndromes such as irritable bowel syndrome has not been explored
 Strickland P, Appleby L,   Hospital, University of        syndromes and medically                                      before in chronic fatigue syndrome. METHODS: Cross-sectional controlled study of the current prevalence
 Campbell IT, Pearson D.    Manchester, UK.                unexplained symptoms                                         of psychophysiological syndromes, pain, function and lifetime prevalence of medically unexplained
                                                           associated with chronic                                      symptoms in 77 out-patients with chronic fatigue syndrome (CFS) without DSM-III-R depression, 42 CFS
                                                           fatigue syndrome.                                            out-patients with DSM-III-R depression and 26 out-patient with primary DSM-III-R depression. RESULTS:
                                                                                                                        Both CFS groups differed significantly from the primary depression group but not each other in the
                                                                                                                        prevalence of tension headaches (P < 0.001), reporting of widespread bodily pain (P < 0.001) and the
                                                                                                                        number of lifetime medically unexplained symptoms (P < 0.001). The three groups did not significantly
                                                                                                                        differ in the prevalence of irritable bowel syndrome or fibromyalgia. CFS patients with depression were
                                                                                                                        more impaired in social function than other CFS patients. CONCLUSION: Depression is not associated
                                                                                                                        with the reporting of pain, psychophysiological syndromes and medically unexplained symptoms in CFS
                                                                                                                        patients. Depression is associated with decreased social function in CFS patients. LIMITATIONS: Study
                                                                                                                        depended on recall of symptoms, not confirmed by medical records and current investigations. Patients
                                                                                                                        with depression were taking antidepressants. CLINICAL RELEVANCE: Treating depression in chronic
                                                                                                                        fatigue syndrome is unlikely to diminish reporting of pain and medically unexplained symptoms but may
                                                                                                                        improve social function.
ME Research UK — Database of Research Publications 1999

 Moss RB, Mercandetti A,   The Immune Response              TNF-alpha and chronic           J Clin Immunol 1999            Based upon the clinical presentation of chronic fatigue syndrome (CFS), we hypothesized that
 Vojdani A.                Corporation, Carlsbad,           fatigue syndrome.               Sep;19(5):314-6                proinflammatory cytokines may play a role in the pathogenesis of the disease. We therefore undertook a
                           California 92008, USA.                                                                          retrospective cross-sectional study to examine the role of TNF-alpha in patients with CFS. Our results
                                                                                                 suggest a significant increase serum TNF-alpha in patients with CFS (P<0.0001) compared to non-CFS
                                                                                                                           controls. This study supports the further examination of the role of proinflammatory mediators in CFS.
                                                                                                                           Furthermore, the clinical testing of TNF-alpha blockers and other antiinflammatory agents for the treatment
                                                                                                                           of this disease is warranted.
 Mullis R, Campbell IT,    Department of Physiotherapy      Prediction of peak oxygen       Br J Sports Med 1999           OBJECTIVES: To establish a simple, valid, and acceptable method of predicting peak oxygen uptake
 Wearden AJ, Morriss RK,   Studies, University of Keele,    uptake in chronic fatigue       Oct;33(5):352-6                (VO2peak) in patients with chronic fatigue syndrome (CFS), which could provide a basis for subsequent
 Pearson DJ.               Staffordshire, United            syndrome.                                                      exercise prescription at an appropriate intensity as part of a clinical rehabilitation programme. METHODS:
                           Kingdom.                                                                                        A total of 130 patients who met UK research criteria for CFS were taken from consecutive referrals for
                                                                                                                           chronic fatigue to the University Department of Medicine at Withington Hospital, Manchester. VO2peak
                                                                                                                           was determined using an incremental graded exercise test to exhaustion. Respiratory gas exchange, work
                                                                                                                           rate, and heart rate were monitored throughout. RESULTS: In all patients, VO2peak was found to correlate
                                                                                                                           strongly and significantly with peak work rate (WRpeak) during testing (r2 = 0.88, p<0.001). In patients
                                                                                                                           who exercised for longer than two minutes (n = 119), regression analysis established the relation as
                                                                                                                           Vo2peak = 13.1 x WRPpeak + 284, where VO2 is given in ml/min and WR in W. The mean error between
                                                                                                                           the measured VO2peak and the predicted value was 10.7%. The relation between increase in work rate and
                                                                                                                           oxygen uptake across the group was highly significant (r2 = 0.87, p<0.001), and given as VO2increase =
                                                                                                                           12.0 x WRincrease, this value being similar to that expected for healthy individuals. Almost all (97%)
                                                                                                                           subjects reported no exacerbation of symptoms after maximal exercise testing. CONCLUSIONS: Using a
                                                                                                                           simple to administer maximal exercise test on a cycle ergometer, it is possible to predict accurately the
                                                                                                                           VO2peak of a patient with CFS from peak work rate alone. This value can then be used as an aid to setting
                                                                                                                           appropriate exercise intensity for a rehabilitation programme. The increase in VO2 per unit increase in
                                                                                                                           workload was consistent with that expected in healthy individuals, suggesting that the physiological
                                                                                                                           response of the patients measured here was not abnormal. Contrary to the belief of many patients, maximal
                                                                                                                           exercise testing to the point of subjective exhaustion proved to be harmless, with no subjects suffering any
                                                                                                                           lasting deterioration in their condition after assessment.
 Myers C, Wilks D.         Regional Infectious Diseases     Comparison of Euroqol EQ-       Qual Life Res 1999;8(1-2):9-   The objective of the study was to compare the Euroqol EQ-5D (Euroqol) and short-form 36 (SF-36) health
                           Unit, Western General            5D and SF-36 in patients        16                             questionnaires in patients with chronic fatigue syndrome (CFS). One hundred and twenty-seven outpatients
                           Hospital, Edinburgh, UK.         with chronic fatigue                                           referred to a hospital-based infectious disease clinic with a diagnosis of CFS were contacted by post and
                                                            syndrome.                                                      asked to complete both questionnaires. Additional data were determined from hospital casenotes. Eighty-
                                                                                                                           five patients returned correctly completed questionnaires. Euroqol health values and visual analogue scale
                                                                                                                           (VAS) scores were strongly and significantly correlated with all dimensions of the SF-36, with the
                                                                                                                           exception of physical limitation of role. SF-36 dimensions were in turn strongly and significantly correlated
                                                                                                                           with each other, with the same exception. Patients reported a high degree of physical disability and a
                                                                                                                           moderate degree of emotional or psychological ill-health. The Euroqol elements dealing with mobility and
                                                                                                                           self-care referred to inappropriately severe degrees of disability for these patients with CFS. Similarly some
                                                                                                                           dimensions in the SF-36 were oversensitive and did not discriminate between patients with moderate or
                                                                                                                           severe disability. It was concluded that Euroqol scores correlated strongly with SF-36 scores and provided
                                                                                                                           useful information about patients with CFS and that Euroqol would be a useful tool for the rapid
                                                                                                                           assessment of health status in CFS. The current Euroqol instrument refers to inappropriately severe degrees
                                                                                                                           of disability for patients with CFS and would need to be modified to be maximally useful in this situation.
 Nakaya T, Takahashi H,    Section of Serology, Institute   Borna disease virus infection   Microbiol Immunol              A high rate of Borna disease virus (BDV) infection has been demonstrated in patients with chronic fatigue
 Nakamur Y, Kuratsune H,   of Immunological Science,        in two family clusters of       1999;43(7):679-89              syndrome (CFS). Herein, we focused on BDV infection in two family clusters of patients with CFS: a
 Kitani T, Machii T,       Hokkaido University,             patients with chronic fatigue                                  father, mother, two sons and one daughter (family #1); and a father, mother, two daughters and one son
 Yamanishi K, Ikuta K.     Sapporo, Japan.                  syndrome.                                                      (family #2). All members, except for the elder son in family #1 and the father and son in family #2, were
                                                                                                                           diagnosed with CFS. The results supported that all the family members with CFS were infected with BDV,
                                                                                                                           as evidenced by the presence of antibodies to viral p40, p24 and/or gp18 and BDV p24 RNA in peripheral
                                                                                                                           blood mononuclear cells. The healthy members, except for the father of family #2 who was positive for
                                                                                                                           antibody to p24, were all negative by both assays. Follow-up studies in family #1 continued to reveal BDV
                                                                                                                           antibodies and BDV RNA, except in the mother, who lost the RNA upon slight recovery from the disease.
ME Research UK — Database of Research Publications 1999

 Nasralla M, Haier J,         The Institute for Molecular   Multiple mycoplasmal             Eur J Clin Microbiol Infect   The aim of this study was to investigate the presence of different mycoplasmal species in blood samples
 Nicolson GL.                 Medicine, Huntington Beach,   infections detected in blood     Dis 1999 Dec;18(12):859-65    from patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Previously, more than 60% of
                              CA 92649-1041, USA.           of patients with chronic                                       patients with chronic fatigue syndrome/fibromyalgia syndrome were found to have mycoplasmal blood
                                                            fatigue syndrome and/or                                        infections, such as Mycoplasma fermentans infection. In this study, patients with chronic fatigue
                                                            fibromyalgia syndrome.                                         syndrome/fibromyalgia syndrome were examined for multiple mycoplasmal infections in their blood. A
                                                                                                                           total of 91 patients diagnosed with chronic fatigue syndrome/fibromyalgia syndrome and with a positive
                                                                                                                           test for any mycoplasmal infection were investigated for the presence of Mycoplasma fermentans,
                                                                                                                           Mycoplasma pneumoniae, Mycoplasma hominis and Mycoplasma penetrans in blood using forensic
                                                                                                                           polymerase chain reaction. Among these mycoplasma-positive patients, infections were detected with
                                                                                                                           Mycoplasma pneumoniae (54/91), Mycoplasma fermentans (44/91), Mycoplasma hominis (28/91) and
                                                                                                                           Mycoplasma penetrans (18/91). Multiple mycoplasmal infections were found in 48 of 91 patients, with
                                                                                                                           double infections being detected in 30.8% and triple infections in 22%, but only when one of the species
                                                                                                                           was Mycoplasma pneumoniae or Mycoplasma fermentans. Patients infected with more than one
                                                                                                                           mycoplasmal species generally had a longer history of illness, suggesting that they may have contracted
                                                                                                                           additional mycoplasmal infections with time.
 Natelson BH, Denny T,        Department of Neuroscience,   Is depression associated with    J Affect Disord 1999          BACKGROUND: Some research immunologists have suggested that major depression amd chronic fatigue
 Zhou XD, LaManca JJ,         UMDNJ-New Jersey Medical      immune activation?               May;53(2):179-84              syndrome (CFS) are characterized by immune activation. To test this hypothesis, we compared
 Ottenweller JE, Tiersky L,   School, East Orange, Newark                                                                  immunological function in patients with major depression and in patients with CFS who developed major
 DeLuca J, Gause WC.          07103, USA.                                                                                  depression after the onset of CFS to that of sedentary healthy controls. METHODS: Subjects completed the
                                                                                                                           Centers for Epidemiological Study-Depression (CES-D) questionnaire and allowed venisection. We
                                                                                                                           performed flow cytometric analysis on 13 groups of white blood cells and used a reverse transcriptase PCR
                                                                                                                           method to assay m-RNA of eight cytokines. RESULTS: CES-D scores were high in both patient groups and
                                                                                                                           did not differ significantly. We found no evidence for immune activation in either patient group. Instead the
                                                                                                                           data suggested immunological downregulation in depression. LIMITATIONS: Not all the subjects in the
                                                                                                                           two patient groups were off antidepressants. CONCLUSIONS: The data indicate that immune activation is
                                                                                                                           not necessary in depression--either alone or with CFS.
 Nores JM                                                   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 1999: 5(2): 99 -     ethics. The first question posing a problem is: should pain be added to or included in the list of the five
                                                                                             105                           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.
 Onouchi H, Muro Y,           Department of Dermatology,    Clinical features and IgG        J Autoimmun 1999              We examined the clinical features of patients presenting antinuclear autoantibodies against p80-coilin and
 Tomita Y.                    Nagoya University School of   subclass distribution of anti-   Sep;13(2):225-32              the IgG subclass distribution of anti- p80-coilin antibodies. Sera from 365 Japanese patients were analysed.
                              Medicine, Nagoya, Japan.      p80 coilin antibodies.                                         Immunoblotting and indirect immunofluorescence microscopy techniques were used with a polyclonal
                                                                                                                           rabbit antiserum against p80-coilin. Eleven patients with anti-p80-coilin antibodies were found. All the
                                                                                                                           patients were female and nine were in their twenties. None could be diagnosed with differentiated
                                                                                                                           rheumatic disease except for one case of systemic scleroderma and another of Sjogren's syndrome. Most
                                                                                                                           patients had general fatigue, arthralgia, headaches, dysmenorrhea, lymph node swelling and/or low grade
                                                                                                                           fever such as chronic fatigue syndrome (CFS), and showed low complement. One patient fulfilled the
                                                                                                                           criteria for CFS. All were younger females than those often diagnosed with rheumatic disease in previous
                                                                                                                           reports. Patients' sera had a predominant distribution of subclass IgG(1)anti-p80-coilin antibodies and five
                                                                                                                           sera had concomitant subclass IgG(2). Two rheumatic disease patients had a relatively high titer of
                                                                                                                           IgG(2)anti-p80-coilin antibodies. The IgG(2)subclass of anti-p80-coilin antibodies may be a specific
                                                                                                                           marker for systemic autoimmune disease. Copyright 1999 Academic Press.
 Pagani M, Lucini D.          Centro Ricerca Terapia        Chronic fatigue syndrome: a      Clin Sci (Colch) 1999         Chronic fatigue syndrome is a debilitating illness of unknown aetiology, with estimated levels of prevalence
ME Research UK — Database of Research Publications 1999

                         Neurovegetativa, Ospedale L.   hypothesis focusing on the    Jan;96(1):117-25Comment        of up to about 8. 7/100 000 in the U.S.A. Like pain fatigue it is a personal, emotionally rich experience,
                         Sacco, University of Milan,    autonomic nervous system.     in: Clin Sci (Colch). 1999     which may originate from peripheral or central sites (or both). The nature of the symptoms is complex and
                         Via G.B. Grassi, 74, 20157                                   Sep;97(3):319-22               reflects the interaction of the patient with the environment and cultural milieu. Accordingly the common
                         Milan, Italy.                                                                               use of the same terminology for different types of fatigue may be misleading. Autonomic activation is a key
                                                                                                                     component of both real and simulated physical exercise. Alterations in autonomic nervous system activity
                                                                                                                     are a key component of several physiopathological conditions. In chronic fatigue syndrome disturbances in
                                                                                                                     autonomic activity, and in other homoeostatic mechanisms, such as the hormonal and immune systems,
                                                                                                                     have been reported recently. In this review we followed the hypothesis that in chronic fatigue syndrome the
                                                                                                                     paradoxical condition of disturbing somatic symptoms in the absence of organic evidence of disease might
                                                                                                                     be addressed by focusing on attending functional correlates. In particular we addressed possible alterations
                                                                                                                     in cardiovascular autonomic control, as can be assessed by spectral analysis of R-R interval and systolic
                                                                                                                     arterial pressure variability. With this approach, in subjects complaining of unexplained fatigue, we
                                                                                                                     obtained data suggesting a condition of prevailing sympathetic modulation of the sino-atrial node at rest,
                                                                                                                     and reduced responsiveness to excitatory stimuli. Far from considering the issue resolved, we propose that
                                                                                                                     in the context of the multiple physiological and psychological interactions involved in the perception and
                                                                                                                     self-reporting of symptoms, attendant changes in physiological equivalents might furnish a convenient
                                                                                                                     assessment independent from subjective components. Indices of sympathetic modulation could,
                                                                                                                     accordingly, provide quantifiable signs of the interaction between subject's efforts and environmental
                                                                                                                     demands, independently of self descriptions, which could provide convenient measurable outcomes, both
                                                                                                                     for diagnosis and treatment titration in chronic fatigue syndrome.
 Paul L, Wood L, Behan   Department of                  Demonstration of delayed      Eur J Neurol 1999              Patients with the chronic fatigue syndrome (CFS) complain consistently of delay in recovery of peripheral
 WM, Maclaren WM.        Physiotherapy, Glasgow         recovery from fatiguing       Jan;6(1):63-9                  muscle function after exercise. The purpose of this study was to try to confirm this observation. A fatiguing
                         Caledonian University,         exercise in chronic fatigue                                  exercise test was carried out on the quadriceps muscle group of ten patients and ten control subjects. The
                         Glasgow, Scotland.             syndrome.                                                    test consisted of 18 maximum voluntary contractions (MVCs) with a 50% duty cycle (10 s contraction, 10 s
                                                                                                                     rest), and the force generated by each contraction was recorded using a KinCom dynamometer. This was
                                                                                                                     followed by a recovery phase lasting 200 min in which quadriceps strength was evaluated at increasing
                                                                                                                     intervals, and a follow-up session at 24 h post-exercise involving three 10 s MVCs. Throughout the exercise
                                                                                                                     period, the MVCs obtained from the control group were significantly higher than those of the patient group
                                                                                                                     (P = 0.006), but both groups showed a parallel decline in force over the 18 contractions, in keeping with a
                                                                                                                     similar endurance capacity. Recovery was prolonged in the patient group, however, with a significant
                                                                                                                     difference compared to initial MVCs being evident during the recovery phase after exercise (P = 0.001) and
                                                                                                                     also at 24 h (P < 0.001). In contrast, the control group achieved MVCs which were not significantly
                                                                                                                     different from initial values during the recovery phase, and maintained these at 24 h. These findings
                                                                                                                     support the clinical complaint of delayed recovery after exercise in patients with CFS. Copyright 1999
                                                                                                                     Lippincott Williams & Wilkins
 Perry LD.                                              Chronic fatigue syndrome?     Pediatrics 1999 Jul;104(1 Pt
                                                                                      1):130, discussion 131-2
 Pheley AM, Melby D,     Ohio University College of     Can we predict recovery in    Minn Med 1999                  PURPOSE: To determine if selected demographic or clinical features of chronic fatigue syndrome (CFS)
 Schenck C, Mandel J,    Osteopathic Medicine,          chronic fatigue syndrome?     Nov;82(11):52-6                are associated with recovery. PATIENTS AND METHODS: A follow-up questionnaire was mailed to 341
 Peterson PK.            Athens, USA.                                                                                patients who had been ill on average for nine years to ascertain "recovery" rate (defined as self-reported
                                                                                                                     recovery on a visual analog scale). Baseline demographic and clinical features (functional status and
                                                                                                                     psychological status) recorded at the time of the initial (baseline) clinical visit were analyzed for their
                                                                                                                     association with recovery at the time of follow-up. RESULTS: Of the 177 patients who responded to the
                                                                                                                     follow-up questionnaire, only 21 (12%) reported "recovery." Patients with higher levels of physical and
                                                                                                                     social functioning and lower levels of anxiety and obsessive-compulsiveness at baseline were more likely to
                                                                                                                     report recovery at follow-up (p < 0.05). No specific demographic characteristics were associated with
                                                                                                                     recovery. CONCLUSION: These findings support previous research that complete recovery from CFS is
                                                                                                                     rare and that patients with less severe illness at the initial clinic visit are more likely to have a positive
                                                                                                                     prognosis for recovery. However, considerable overlap in illness severity was observed between the
                                                                                                                     recovered and nonrecovered groups, suggesting that accurate prediction of recovery in individual CFS
                                                                                                                     patients is not currently feasible.
 Plioplys AV.                                           Chronic fatigue syndrome?     Pediatrics 1999 Jul;104(1 Pt
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 Prins JB, Bleijenberg G.   Department of Medical            Cognitive behavior therapy      J Behav Ther Exp Psychiatry   The case of a 26-year old woman with Chronic Fatigue Syndrome (CFS) is presented. Multidimensional
                            Psychology, Hospital             for chronic fatigue syndrome:   1999 Dec;30(4):325-39         assessment showing severe debilitating fatigue and considerable psychological, social and occupational
                            Nijmegen, The Netherlands.       a case study.                                                 impairment confirmed the diagnosis. Cognitive behavior therapy (CBT) was based on a tested causal model
                                                                                             of CFS and individual behavioral analyses. Key elements in CBT were process variables from the CFS
                                                                                                                           model, like sense of control, causal attributions, physical activity and focusing on bodily functions. Goals
                                                                                                                           were recovery from fatigue, returning to work and relapse prevention. The course of therapy is described in
                                                                                                                           detail to illustrate difficulties in treating CFS. Assessments were made five times, at baseline and at 8, 14,
                                                                                                                           21 and 33 months. Comparison of the pretest, post-test and follow-up scores of the outcome variables,
                                                                                                                           fatigue and functional impairment and of the process variables showed clinically significant improvement
                                                                                                                           from the range of CFS patients to the range of healthy controls.
 Propsner NM.               The classic profile of the       Fatigue that doesn't go away.   N J Med 1999 Jun;96(6):29-
                            chronic fatigue syndrome                                         31
                            (CFS) patient is a white,
                            middle-age female.
                            Characterized by profound
                            fatigue, CFS often starts with
                            an acute viral infection.
                            While today's medicine
                            provides symptomatic relief,
                            research is offering in
 Rea T, Buchwald D.                                          Hydrocortisone and chronic      Lancet 1999 May
                                                             fatigue syndrome.               8;353(9164):1618-9;
                                                                                             discussion 1619-20
                                                                                             Comment on: Lancet. 1999
                                                                                             Feb 6;353(9151):455-8
 Riem L.                                                     [Etiology and therapy of        MMW Fortschr Med 1999
                                                             chronic fatigue syndrome.       Nov 11;141(45):16-8
                                                             Too tired for life. Press
                                                             Conference: Fatigue--
                                                             Paralyzing Symptom in
                                                             Cancer Patients, Cologne, 17
                                                             September 1999].[article in
 Robertson TJ.                                               Misunderstood illnesses:        Alta RN 1999 May-
                                                             fibromyalgia and chronic        Jun;55(3):6-7
                                                             fatigue syndrome.
 Rowe PC, Barron DF,        Department of Pediatrics,        Orthostatic intolerance and     J Pediatr 1999                OBJECTIVE: To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome
 Calkins H, Maumenee IH,    Center for Hereditary Eye        chronic fatigue syndrome        Oct;135(4):494-9              (EDS) and orthostatic intolerance. STUDY DESIGN: Case series of adolescents referred to a tertiary clinic
 Tong PY, Geraghty MT.      Diseases, Wilmer Eye             associated with Ehlers-                                       for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance,
                            Institute, Johns Hopkins         Danlos syndrome.                                              and examinations by both a geneticist and an ophthalmologist. RESULTS: Twelve patients (11 female),
                            University School of                                                                           median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or
                            Medicine, Baltimore,                                                                           neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had
                            Maryland, USA.                                                                                 hypermobile-type EDS. CONCLUSIONS: Among patients with CFS and orthostatic intolerance, a subset
                                                                                                                           also has EDS. We propose that the occurrence of these syndromes together can be attributed to the
                                                                                                                           abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend
                                                                                                                           excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling
                                                                                                                           and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for
                                                                                                                           hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS
                                                                                                                           and orthostatic intolerance syndromes.
 Russell IJ, Vipraio GA,    Department of Medicine,          Lymphocyte markers and          J Interferon Cytokine Res     A clinical study was designed to utilize flow cytometric immunophenotyping and chromium release from
ME Research UK — Database of Research Publications 1999

 Michalek JE, Craig FE,   University Clinical Research   natural killer cell activity in   1999 Aug;19(8):969-78        cultured tumor target cells to characterize peripheral blood mononuclear leukocyte (PBML) subpopulations
 Kang YK, Richards AB.    Center, The University of      fibromyalgia syndrome:                                         and natural killer activity in healthy normal controls (n = 18) and in patients with fibromyalgia syndrome
                          Texas Health Science Center,   effects of low-dose,                                           (FMS) at baseline (n = 124) and again after 6 weeks of treatment with low-doses of orally administered
                          San Antonio 78284-7868,        sublingual use of human                                        human interferon-alpha (IFN-alpha). Volunteer subjects discontinued all analgesic and sedative hypnotic
                          USA.       interferon-alpha.                                              medications for 2 weeks prior to the baseline phlebotomy. Laboratory measures included a complete blood
                                                                                                                        count; a phenotypic analysis of PBML by flow cytometry; and in vitro natural killer (NK) cell activity.
                                                                                                                        After baseline blood sample collection, the FMS patients were randomized to one of four parallel treatment
                                                                                                                        groups (n = 28/group) to receive sublingual IFN-alpha (15 IU, 50 IU, 150 IU), or placebo every morning for
                                                                                                                        6 weeks. The tests were repeated at week 6 to evaluate treatment effects. At baseline, FMS patients
                                                                                                                        exhibited fewer lymphocytes and more CD25+ T lymphocytes than did normal controls. By week 6, the
                                                                                                                        main significant and consistent change was a decrease in the HLA-DR+ CD4+ subpopulation in the 15 IU
                                                                                                                        and 150 IU treatment groups. These data do not support an immunologically dysfunctional PBML
                                                                                                                        phenotype among patients with FMS as has been observed in the chronic fatigue syndrome.
 Sacco P, Hope PA,        Australian Neuromuscular       Corticomotor excitability and     Clin Neurophysiol 1999       OBJECTIVE: We have investigated the possibility of a central basis for the complaints of fatigue and poor
 Thickbroom GW, Byrnes    Research Institute, QE II      perception of effort during       Nov;110(11):1883-91          exercise tolerance in subjects with chronic fatigue syndrome (CFS). METHODS: Transcranial magnetic
 ML, Mastaglia FL.        Medical Centre, Nedlands,      sustained exercise in the                                      stimulation of the motor cortex was used to measure sequential changes in motor evoked potential (MEP)
                          WA, Australia.                 chronic fatigue syndrome.                                      amplitude, post-excitatory silent period (SP) duration and twitch force of the biceps brachii muscle during a
                                                                                     20% maximum isometric elbow flexor contraction maintained to the point of exhaustion. Ten patients with
                                                                                                                        post-infectious CFS and 10 age- and sex-matched control subjects were studied. Results were analysed
                                                                                                                        using non-parametric repeated measures analysis of variance (Friedman's test) and Mann-Whitney U-tests
                                                                                                                        for intra- and inter-group comparisons respectively. RESULTS: Mean endurance time for the CFS group
                                                                                                                        was lower (13.1+/-3.2 min, mean +/- SEM) than controls (18.6+/-2.6 min, P < 0.05) and CFS subjects
                                                                                                                        reported higher ratings of perceived exertion. During the exercise period MEP amplitude and SP duration
                                                                                                                        increased in both groups but to a lesser extent in CFS subjects. Interpolated twitch force amplitude also
                                                                                                                        increased during exercise, being more pronounced in CFS subjects. CONCLUSION: The findings are in
                                                                                                                        keeping with an exercise-related diminution in central motor drive in association with an increased
                                                                                                                        perception of effort in CFS.
 Saheki T.                Department of Biochemistry,    [Carnitine as a vitamin-like      Nippon Rinsho 1999           Carnitine is a well-known cofactor for the beta-oxidation of long-chain fatty acid. It also plays a role in
                          Faculty of Medicine,           biofactor].[article in            Oct;57(10):2270-5            transport of acetyl moity for fatty acid and cholesterol synthesis, excretion of organic acid and xenobiotic
                          Kagoshima University.          Japanese]                                                      acid as carnitine ester, and control of ratio of acetylCoA to CoA. Therapeutic effect of acetylcarnitine on
                                                                                                                        Alzheimer disease and HIV-infection, and aberrant incorporation acetylcarnitine into brain under chronic
                                                                                                                        fatigue syndrome have been reported. Carnitine deficiency causes hyperammonemia through suppression of
                                                                                                                        gene expression of urea cycle enzymes. On the other hand, a large amount of carnitine has a therapeutic
                                                                                                                        effect on hyperammonemia by still unclear mechanism. These suggest carnitine as a multifunctional
                                                                                                                        biofactor. Review Literature
 Saul JP.                 MUSC, Charleston 29425,        Syncope: etiology,                J S C Med Assoc 1999         An abnormality of blood pressure control is by far the most likely cause of syncope in children; however,
                          USA.                           management, and when to           Oct;95(10):385-7             syncope in children may be due to primary cardiac dysrhythmias, particularly in the presence of structural
                                                         refer.                                                         heart disease. An appropriate work-up should include an ECG with a 60-second rhythm strip at first
                                                                                                                        presentation. Tilt testing can usually wait until after a second occurrence on non-pharmacologic therapy.
                                                                                                                        Patients who require more than a history and ECG by the algorithm in the Figure should probably be
                                                                                                                        referred to a cardiologist familiar with the evaluation of syncope. The common form of neurally mediated
                                                                                                                        syncope is also probably related to both breath-holding spells in toddlers, and to many of the cases of
                                                                                                                        chronic fatigue syndrome.
 Schondorf R, Benoit J,   Department of Neurology,       Orthostatic intolerance in the    J Auton Nerv Syst 1999 Feb   This study aims to investigate the prevalence and pathophysiology of orthostatic intolerance (OI) and its
 Wein T, Phaneuf D.       McGill University, Sir         chronic fatigue syndrome.         15;75(2-3):192-201           potential contribution to symptoms of a group of unselected patients with chronic fatigue syndrome (CFS).
                          Mortimer B. Davis Jewish                                                                      Seventy five patients (65 women, 10 men) with CFS were evaluated. During an initial visit, a clinical
                          General Hospital, Montreal,                                                                   suspicion as to the likelihood of observing laboratory evidence of OI was assigned. Laboratory investigation
                          Quebec, Canada.                                                                               consisted of beat-to-beat recordings of heart rate, blood pressure (Finapres), and stroke volume (impedance
                                                                                         cardiograph) while supine and during 80 degrees head-up tilt (HUT), during rhythmic deep breathing (6
                                                                                                                        breaths/min) and during the Valsalva maneuver. The responses of 48 age-matched healthy controls who had
                                                                                                                        no history of OI were used to define the range of normal responses to these three maneuvers. Forty percent
                                                                                                                        of patients with CFS had OI during head-up tilt. Sixteen exhibited neurally-mediated syncope alone, seven
ME Research UK — Database of Research Publications 1999

                                                                                                                        tachycardia (> 35 bpm averaged over the whole of the head-up tilt) and six a mixture of tachycardia and
                                                                                                                        syncope. Eight of 48 controls exhibited neurally-mediated syncope. The responses to the Valsalva
                                                                                                                        maneuver and to deep breathing were similar in controls and patients. On average, the duration of disease
                                                                                                                        and patient age were significantly less and the onset of symptoms was more often subacute in patients with
                                                                                                                        OI than in those without OI. We conclude that there exists a clinically identifiable subgroup of patients with
                                                                                                                        CFS and OI that differs from control subjects and from those with CFS without OI for whom treatment
                                                                                                                        specifically aimed at improving orthostatic tolerance may be indicated.
 Schondorf R, Freeman R.     Dept. of Neurology, McGill     The importance of orthostatic    Am J Med Sci 1999          Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis is a clinically defined syndrome
                             University, Sir Mortimer B.    intolerance in the chronic       Feb;317(2):117-23          characterized by persistent or relapsing debilitating fatigue for longer than 6 months in the absence of any
                             Davis Jewish General           fatigue syndrome.                                           definable medical diagnosis. The cause of this syndrome is unknown. Symptoms of orthostatic intolerance,
                             Hospital, Montreal, Quebec,                                                                such as disabling fatigue, dizziness, diminished concentration, tremulousness, and nausea, are often found
                             Canada.                                                                                    in patients with CFS. In this review, we critically evaluate the relationship between orthostatic intolerance
                                                                                         and CFS. Particular emphasis is placed on clinical diagnosis, laboratory testing, pathophysiology, and
                                                                                                                        therapeutic management. It is hoped that this review will provide a stimulus for further study of this
                                                                                                                        complex and disabling condition.
 Schutzer SE, Natelson BH.   Department of Medicine,        Absence of Borrelia              Neurology 1999 Oct         Chronic fatigue syndrome (CFS) and Lyme disease often share clinical features, especially fatigue,
                             University of Medicine and     burgdorferi-specific immune      12;53(6):1340-1            contributing to concern that Borrelia burgdorferi (Bb), the cause of Lyme disease, may underlie CFS
                             Dentistry, New Jersey          complexes in chronic fatigue                                symptoms. We examined 39 CFS patients and 40 healthy controls with a Bb immune complex test. Patients
                             Medical School, Newark         syndrome.                                                   and controls were nonreactive. Centers for Disease Control and Prevention-defined CFS patients lacking
                             07103, USA.                                                                                antecedent signs of Lyme disease--erythema migrans, Bell's palsy, or large joint arthritis--are not likely to
                                                                                            have laboratory evidence of Bb infection.
 Scott LV, Dinan TG.         Department of Psychiatry,      The neuroendocrinology of        Funct Neurol 1999 Jan-
                             Trinity College Medical        chronic fatigue syndrome:        Mar;14(1):3-11
                             School, St James' Hospital,    focus on the hypothalamic-
                             Dublin, Ireland. Review,       pituitary-adrenal axis.
 Scott LV, Medbak S, Dinan   Department of Psychiatry,      Desmopressin augments            Biol Psychiatry 1999 Jun   BACKGROUND: Corticotropin-releasing hormone (CRH) and vasopressin (VP) are the two principal
 TG.                         Trinity College Medical        pituitary-adrenal responsivity   1;45(11):1447-54           neuropeptide regulators of the hypothalamic-pituitary-adrenal axis in man, with VP serving to augment
                             School, St. James' Hospital,   to corticotropin-releasing                                  CRH-induced adrenocorticotropic hormone (ACTH) release. Unlike VP, desmopressin (DDAVP), which is
                             Dublin, Ireland.               hormone in subjects with                                    a synthetic analogue of VP, when administered alone, has not been shown in healthy subjects to have
                                                            chronic fatigue syndrome and                                consistent ACTH-releasing properties. It has been suggested that chronic fatigue syndrome (CFS),
                                                            in healthy volunteers.                                      characterized by profound fatigue and a constellation of other symptoms, may be caused by a central
                                                                                                                        deficiency of CRH. METHODS: We administered 100 micrograms ovine CRH (oCRH) and 10 micrograms
                                                                                                                        DDAVP, both alone and in combination, to a group of subjects with CFS, and to a group of healthy
                                                                                                                        volunteers. Our aim was to establish the effect of DDAVP on CRH-induced ACTH release in these two
                                                                                                                        groups. RESULTS: The delta-ACTH responses to oCRH were attenuated in the CFS (21.0 +/- 4.5 ng/L)
                                                                                                                        compared to the control subjects (57.8 +/- 11.0 ng/L; t = 3.2, df = 21, p < .005). The delta-cortisol
                                                                                                                        responses were also reduced in the CFS (157.6 +/- 40.7 nmol/L) compared to the healthy subjects (303.5
                                                                                                                        +/- 20.9 nmol/L; t = 3.1, df = 21, p < .01). The delta-ACTH and delta-cortisol responses to DDAVP alone
                                                                                                                        did not differ between the two groups. On administration of both CRH and DDAVP no response
                                                                                                                        differences between the two groups for either ACTH (p = .3) or cortisol output (p = .87) were established.
                                                                                                                        Comparing the ACTH and cortisol responses to CRH and CRH/DDAVP in only those individuals from
                                                                                                                        each group who had both tests, the cortisol output to the combination was significantly greater in the CFS
                                                                                                                        compared to the healthy group. The ACTH output was also increased in the former group, though this was
                                                                                                                        not significant. CONCLUSIONS: DDAVP augments CRH-mediated pituitary-adrenal responsivity in
                                                                                                                        healthy subjects and in patients with CFS. That DDAVP was capable of normalizing the pituitary-adrenal
                                                                                                                        response to oCRH in the CFS group suggests there may be increased vasopressinergic responsivity of the
                                                                                                                        anterior pituitary in CFS and/or that DDAVP may be exerting an effect at an adrenal level.
 Scott LV, Salahuddin F,     Department of Psychiatry,      Differences in adrenal steroid   J Affect Disord 1999       BACKGROUND: Hyperactivity and hypoactivity of the HPA have been forwarded as of
 Cooney J, Svec F, Dinan     Trinity College Medical        profile in chronic fatigue       Jul;54(1-2):129-37         pathophysiological relevance in major depressive disorder and chronic fatigue syndrome (CFS),
 TG.                         School, Dublin, Ireland.       syndrome, in depression and                                 respectively. METHODS: This study examines cortisol levels in the two disorders, and also assesses levels
                                                            in health.                                                  of the adrenal androgens, dehydroepiandrosterone (DHEA) and its sulphate derivative (DHEA-S), and 17-
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                                                                                                                      alpha-hydroxyprogesterone; 15 subjects with CFS diagnosed according to CDC criteria, 15 subjects with
                                                                                                                      DSM III-R major depression and 11 healthy subjects were compared. RESULTS: DHEA and DHEA-S
                                                                                                                      levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA,
                                                                                                                      were lower in the depressives; cortisol and 17-alpha-hydroxyprogesterone did not differ between the three
                                                                                                                      groups. CONCLUSIONS: A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS,
                                                                                                                      is suggested.
 Scott LV, Teh J, Reznek R,   Department of Psychiatry,      Small adrenal glands in       Psychoneuroendocrinology   No inclusive or satisfactory biomedical explanation for chronic fatigue syndrome (CFS) has as yet been
 Martin A, Sohaib A, Dinan    Trinity College Dublin         chronic fatigue syndrome: a   1999 Oct;24(7):759-68      forwarded. Recent research suggests that a dysregulated hypothalamic-pituitary-adrenal axis (HPA) may be
 TG.                          Medical School, St. James's,   preliminary computer                                     contributory, and in particular that there may be diminished forward drive and adrenal under-stimulation. In
                              Hospital, Ireland.             tomography study.                                        this preliminary study we wished to examine a cohort of CFS patients in whom evidence for such
                                                                                                                      hypofunctioning was found. Our aim was to establish whether these patients had altered adrenal gland size.
                                                                                                                      Patients were recruited from a fatigue clinic. Those who fulfilled the Centre for Disease Control and
                                                                                                                      Prevention (CDC) criteria underwent a 1 microgram adrenocorticotropin (ACTH) stimulation test, a test of
                                                                                                                      adrenal gland functioning. Eight subjects (five females, three males) with a subnormal response to this test
                                                                                                                      underwent a computer tomography (CT) adrenal gland assessment. Measurements were compared with
                                                                                                                      those from a group of 55 healthy subjects. The right and left adrenal gland bodies were reduced by over
                                                                                                                      50% in the CFS subjects indicative of significant adrenal atrophy in a group of CFS patients with abnormal
                                                                                                                      endocrine parameters. This is the first study to use imaging methods to measure adrenal gland size in CFS.
                                                                                                                      It is a limitation of this study that a selected CFS sample was employed. A future larger study would
                                                                                                                      optimally employ an unselected cohort of CFS patients. This study has implications not only for the
                                                                                                                      elucidation of CFS pathophysiology, but also for possible therapeutic strategies.
 Shepherd C.                                                 Hydrocortisone and chronic    Lancet 1999 May
                                                             fatigue syndrome.             8;353(9164):1619-20
                                                                                           Comment on: Lancet. 1999
                                                                                           Feb 6;353(9151):424-5
                                                                                           Lancet. 1999 Feb
 Shlaes JL, Jason LA,         DePaul University,             The development of the        Eval Health Prof 1999      Chronic Fatigue Syndrome (CFS) is characterized by debilitating symptoms including persistent or
 Ferrari JR.                  Department of Psychology,      Chronic Fatigue Syndrome      Dec;22(4):442-65           relapsing fatigue. As a result of CFS, some individuals experience significant stigma that is attached to this
                              Chicago, IL 60614, USA.        Attitudes Test. A                                        illness. Many medical professionals are skeptical of the validity of the illness, and employers often fail to
                                                             psychometric analysis.                                   appreciate the seriousness of the symptoms. Although negative attitudes greatly affect the lives of
                                                                                                                      individuals with CFS, there is presently no measurement of attitudes toward this illness and people who
                                                                                                                      have CFS. The purpose of the present studies was to create a scale that measures attitudes toward
                                                                                                                      individuals with CFS--the Chronic Fatigue Attitudes Test (CAT)--and to assess the scale's reliability and
                                                                                                                      validity. The 13-item scale was created using several constructs outlined in the literature regarding negative
                                                                                                                      attitudes toward people with CFS, disabilities, and AIDS. Theoretical implications of the findings and the
                                                                                                                      utility of the CAT are discussed.
 Smith AP, Borysiewicz L,     Department of Experimental     Acute fatigue in chronic      Psychol Med 1999           BACKGROUND: Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible
 Pollock J, Thomas M,         Psychology, University of      fatigue syndrome patients.    Mar;29(2):283-90           to acute mental fatigue. It is important to determine whether this is observed using objective tests of
 Perry K, Llewelyn M.         Bristol.                                                                                sustained attention and responding. METHODS: Sixty-seven patients who fulfilled the criteria for CFS
                                                                                                                      proposed by Sharpe et al. (1991) were compared with 126 matched healthy controls. Acute fatigue was
                                                                                                                      assessed by comparing performance at the start and end of a lengthy test session and by examining changes
                                                                                                                      over the course of individual tasks. RESULTS: CFS patients showed impaired performance compared to
                                                                                                                      the controls and these differences increased as the volunteers developed acute fatigue. In addition,
                                                                                                                      differences between the two groups were larger at the end of the test session. CONCLUSIONS: The present
                                                                                                                      results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect
                                                                                                                      motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with
                                                                                                                      previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by
                                                                                                                      considering it as the end point of a continuum of fatigue rather than a distinct disease.
 Social Security              Notice of Social Security      Social Security Ruling, SSR   Fed Regist 1999 Apr        In accordance with 20 CFR 402.35(b)(1), the Commissioner of Social Security gives notice of Social
 Administration.              ruling.                        99-2p.; titles II and XVI;    30;64(83):23380-4          Security Ruling, SSR 99-2p. This Ruling clarifies disability policy for the evaluation and adjudication of
                                                             evaluating cases involving                               disability claims involving Chronic Fatigue Syndrome (CFS). This Ruling explains that, when it is
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                                                          chronic fatigue syndrome                                    accompanied by appropriate medical signs or laboratory findings, CFS is a medically determinable
                                                          (CFS).                                                      impairment that can be the basis for a finding of "disability." This Ruling ensures that all adjudicators will
                                                                                                                      use the same policies and procedures in evaluating disability claims involving CFS, and provides a
                                                                                                                      consolidated statement of these policies and procedures.
 Soetekouw PM, Lenders      Department of Medicine, St.   Autonomic function in           Clin Auton Res 1999         Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with
 JW, Bleijenberg G, Thien   Radboud University            patients with chronic fatigue   Dec;9(6):334-40             chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an
 T, van der Meer JW.        Hospital, Nijmegen, The       syndrome.                                                   unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in
                            Netherlands.                                                                              37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded
                                                                                                                      continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and
                                                                                                                      sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires
                                                                                                                      to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in
                                                                                                                      blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be
                                                                                                                      lower in CFS patients (28.4 +/- 10.5 beats) than in healthy controls (32.2 +/- 9.5) (p = 0.11). The maximal
                                                                                                                      increase in HR during standing up was not significantly different between the CFS group (37.6 +/-8.9
                                                                                                                      beats) and the control group (40.2 +/- 8.9 beats). There were no significant differences between both groups
                                                                                                                      with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly
                                                                                                                      larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva
                                                                                                                      maneuver. The HR response to MA was significantly less in the CFS group (22.6 +/- 9.9) than in the
                                                                                                                      control group (29.5 +/- 16.7) (p < 0.05), suggesting impaired cardiac sympathetic responsiveness to mental
                                                                                                                      stress. The lower HR responses could not be explained by the level of concentration in the CFS group.
                                                                                                                      During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group,
                                                                                                                      but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant
                                                                                                                      differences between CFS patients with and without symptoms of autonomic dysfunction regarding the
                                                                                                                      hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are
                                                                                                                      no gross alterations in cardiovascular autonomic function in patients with CFS.
 Sorenson WG.               Division of Respiratory       Fungal spores: hazardous to     Environ Health Perspect     Fungi have long been known to affect human well being in various ways, including disease of essential
                            Disease Studies, National     health?                         1999 Jun;107 Suppl 3:469-   crop plants, decay of stored foods with possible concomitant production of mycotoxins, superficial and
                            Institute for Occupational                                    72                          systemic infection of human tissues, and disease associated with immune stimulation such as
                            Safety and Health,                                                                        hypersensitivity pneumonitis and toxic pneumonitis. The spores of a large number of important fungi are
                            Morgantown, WV 26505,                                                                     less than 5 microm aerodynamic diameter, and therefore are able to enter the lungs. They also may contain
                            USA.                                                                         significant amounts of mycotoxins. Diseases associated with inhalation of fungal spores include toxic
                                                                                                                      pneumonitis, hypersensitivity pneumonitis, tremors, chronic fatigue syndrome, kidney failure, and cancer.
 Starcevic V.               University of Belgrade        Neurasthenia: cross-cultural    Gen Hosp Psychiatry 1999    The purpose of this study was to examine several conceptual and cross-cultural issues in neurasthenia,
                            School of Medicine,           and conceptual issues in        Jul-Aug;21(4):249-55        particularly in terms of their relationship to chronic fatigue syndrome. A review of this relationship led to
                            Yugoslavia.                   relation to chronic fatigue                                 the conclusion that these conditions are much more alike in Western countries than in countries such as
                                                          syndrome.                                                   China, where neurasthenia could almost be regarded as a "culture-bound syndrome." This may be a
                                                                                                                      consequence of factors such as the heterogeneous nature of neurasthenia and different diagnostic practices
                                                                                                                      in different countries, despite the ICD-10 definition of neurasthenia, intended for worldwide use. Likewise,
                                                                                                                      there is no consensus on what the "core" characteristics of neurasthenia are, because its clinical
                                                                                                                      presentation and key features in different countries are very different. Despite the finding of relatively low
                                                                                                                      comorbidity rates between neurasthenia and other mental disorders, clinical experience suggests that
                                                                                                                      features of neurasthenia frequently overlap with those of depression, chronic anxiety, and somatoform
                                                                                                                      disorders. There is no convincing evidence that in cases of overlap or comorbidity, other diagnoses should
                                                                                                                      automatically have "primacy" over neurasthenia nor should the diagnosis of neurasthenia thereby be
                                                                                                                      excluded. Although some aspects of its validity have improved recently, especially its descriptive validity,
                                                                                                                      the overall validity of the diagnosis of neurasthenia is still not satisfactory. Suggestions for further research,
                                                                                                                      aimed at improving the diagnostic validity of neurasthenia, are offered in this paper.
 Stark FM, Sobetzko HM.     Klinik fur Psychiatrie und    Approaches to coping with       Zentralbl Hyg Umweltmed     The 1994 approach to the definition of Chronic Fatigue Syndrome (CFS) describes a severe disorder with
                            Psychotherapie,               chronic fatigue syndrome        1999 Aug;202(2-4):179-90    unknown etiology and pathophysiology. It results in substantial reduction in previous levels of
                            Universitatskrankenhaus       (CFS).                                                      occupational, educational, social, or personal activities. Most patients cannot continue their usual lifestyle.
                            Eppendorf, Hamburg,                                                                       No causal treatments or other therapies suitable for all patients exist so far. Therefore it was intended to
                            Germany.                                                                                  identify approaches to an effective disease management by the long time escort and observation of a CFS
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                                                                                                                 support group. CFS should be diagnosed according to the actual CDC guidelines. Conditions with similar
                                                                                                                 symptoms explaining chronic fatigue have to be ruled out first. Then an individually shaped disease
                                                                                                                 management comprising of different components plays a central role in the coping process. Medical long
                                                                                                                 time care performed by a general practitioner and the membership in a suitable support group are integrated
                                                                                                                 within this approach.
 Stejskal VD, Danersund A,   Dept Clinical Chemistry,      Metal-specific lymphocytes:    Neuroendocrinol Lett   Many patients attribute their health problems to amalgam and other dental metals. In genetically susceptible
 Lindvall A, Hudecek R,      Danderyd Hospital and         biomarkers of sensitivity in   1999;20(5):289-298     indviduals, mercury and gold may function as haptens and elicit allergic and autoimmune reactions. The
 Nordman V, Yaqob A,         Karolinska Institute,         man.                                                  frequency of metal-induced lymphocyte responses was examined in 3,162 patients in three European
 Mayer W, Bieger W, Lindh    Stockholm, Sweden.                                                                  laboratories using MELISA(R), an optimized lymphocyte proliferation test. The patients suffered from local
 U.                                                                              and systemic symptoms attributed to dental restorations. The effect of dental metal removal was studied in
                                                                                                                 111 patients with metal hypersensitivity and symptoms resembling Chronic Fatigue Syndrome (CFS). After
                                                                                                                 consultation with a dentist the patients decided to replace their metal restorations with non-metallic
                                                                                                                 materials. The changes in health and in vitro lymphocyte reactivity were studied by inquiries and follow-up
                                                                                                                 MELISA(R). Lymphocyte reactivity was also analyzed in 116 healthy subjects with no complaints of metal
                                                                                                                 allergy. A significant number of patients had metal-specific lymphocytes in the blood. Nickel was the most
                                                                                                                 common sensitizer, followed by inorganic mercury, gold, phenylmercury, cadmium and palladium. As
                                                                                                                 compared to lymphocyte responses in healthy subjects, the CFS group had significantly increased responses
                                                                                                                 to several metals, especially to inorganic mercury, phenylmercury and gold. Following dental metal
                                                                                                                 removal, 83 patients (76%) reported long-term health improvement. Twenty-four patients (22%) reported
                                                                                                                 unchanged health and two (2%) reported worsening of symptoms. Following dental metal replacement, the
                                                                                                                 lymphocyte reactivity to metals decreased as well. We propose that an inflammatory process induced by
                                                                                                                 metals may modulate the hypothalamic-pituitary-adrenal axis (HPA axis) and trigger multiple non-specific
                                                                                                                 symptoms characterizing CFS and other chronic conditions like myalgic encephalitis (ME) and multiple
                                                                                                                 chemical sensitivity (MCS).
 Sterzl I, Prochazkova J,    Institute of Endocrinology,   Mercury and nickel allergy:    Neuroendocrinol Lett   This study examined the presence of hypersensitivity to dental and environmental metals in patients with
 Hrda P, Bartova J,          Prague, Czech Republic.       risk factors in fatigue and    1999;20(3-4):221-228   clinical disorders complicated with chronic fatigue syndrome. Three groups of patients were examined
 Matucha P, Stejskal VD.                                   autoimmunity.                                         through medical history, dental examination, and by using a modified test of blast transformation for
                                                                                                                 metals-MELISA(R). The three groups consisted of the following: 22 patients with autoimmune thyroiditis
                                                                                                                 with or without polyglandular autoimmune activation; 28 fatigued patients free from endocrinopathy; and
                                                                                                                 22 fatigued professionals without evidence of autoimmunity. As controls, a population sample or 13
                                                                                                                 healthy subjects without any evidence of metal sensitivity was included. Healthy controls did not complain
                                                                                                                 of marked fatigue and their laboratory tests did not show signs of autoimmunity and endocrinopathy. We
                                                                                                                 have found that fatigue, regardless of the underlying disease, is primarily associated with hypersensitivity to
                                                                                                                 inorganic mercury and nickel. The lymphocyte stimulation by other metals was similar in fatigued and
                                                                                                                 control groups. To evaluate clinical relevance of positive in vitro findings, the replacement of amalgam
                                                                                                                 with metal-free restorations was performed in some of the patients. At a six-month follow-up, patients
                                                                                                                 reported considerably alleviated fatigue and disappearance of many symptoms previously encountered; in
                                                                                                                 parallel, lymphocyte responses to metals decreased as well. We suggest that metal-driven inflammation may
                                                                                                                 affect the hypothalamic-pituitary-adrenal axis (HPA axis) and indirectly trigger psychosomatic
                                                                                                                 multisymptoms characterizing chronic fatigue syndrome, fibromyalgia, and other diseases of unknown
 Stewart JM, Gewitz MH,      Department of Pediatrics,     Orthostatic intolerance in     Pediatrics 1999        OBJECTIVES: To demonstrate the association between orthostatic intolerance and the chronic fatigue
 Weldon A, Arlievsky N, Li   New York Medical College,     adolescent chronic fatigue     Jan;103(1):116-21      syndrome (CFS) in adolescents and to delineate the form that orthostatic intolerance takes in these children.
 K, Munoz J.                 Valhalla, New York, USA.      syndrome.                                             STUDY DESIGN: We investigated the heart rate and blood pressure (BP) responses to head-up tilt (HUT)
                                                                                                                 in 26 adolescents aged 11 to 19 years with CFS compared with responses in adolescents referred for the
                                                                                                                 evaluation of simple faint and to responses in 13 normal healthy control children of similar age. RESULTS:
                                                                                                                 A total of 4/13 of the controls and 18/26 simple faint patients experienced typical faints with an abrupt
                                                                                                                 decrease in BP and heart rate associated with loss of consciousness. One CFS patient had a normal HUT. A
                                                                                                                 total of 25/26 CFS patients experienced severe orthostatic symptoms associated with syncope in 7/25,
                                                                                                                 orthostatic tachycardia with hypotension in 15/25, and orthostatic tachycardia without significant
                                                                                                                 hypotension in 3/25. Acrocyanosis, cool extremities, and edema indicated venous pooling in 18/25. None
                                                                                                                 of the control or simple faint patients experienced comparable acral or tachycardic findings.
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                                                                                                                             CONCLUSIONS: We conclude that chronic fatigue syndrome is highly related to orthostatic intolerance in
                                                                                                                             adolescents. The orthostatic intolerance of CFS often has heart rate and BP responses similar to responses
                                                                                                                             in the syndrome of orthostatic tachycardia suggesting that a partial autonomic defect may contribute to
                                                                                                                             symptomatology in these patients.
 Stewart JM, Gewitz MH,     Department of Pediatrics,       Patterns of orthostatic           J Pediatr 1999 Aug;135(2 Pt    OBJECTIVES: To describe the orthostatic tachycardia syndrome (OTS) in adolescents, similarities to and
 Weldon A, Munoz J.         Division of Cardiology, New     intolerance: the orthostatic      1):218-25                      differences from chronic fatigue syndrome (CFS), and patterns of orthostatic intolerance during head-up tilt
                            York Medical College,           tachycardia syndrome and                                         (HUT). STUDY DESIGN: Using electrocardiography and arterial tonometry, we investigated the heart rate
                            Valhalla 10595, USA.            adolescent chronic fatigue.                                      and blood pressure responses during HUT in 20 adolescents with OTS compared with 25 adolescents with
                                                                                                                             CFS, 13 healthy control subjects, and 20 patients with simple faint. RESULTS: Of the control subjects, 4 of
                                                                                                                             13 experienced typical vasovagal faints with an abrupt fall in blood pressure and heart rate, and 14 of 20
                                                                                                                             patients with simple faint experienced similar HUT responses. All patients with CFS (25/25) experienced
                                                                                                                             severe orthostatic symptoms with syncope in 2 of 25, early orthostatic tachycardia during HUT in 16 of 23
                                                                                                                             (13/16 hypotensive), and delayed orthostatic tachycardia in 7 of 23 (6/7 hypotensive). Acrocyanosis and
                                                                                                                             edema occurred in 18 of 25. Early orthostatic tachycardia occurred in 10 of 20 patients with OTS. Of these,
                                                                                                                             9 of 10 were hypotensive, but hypotension was delayed in 4 of 9. Delayed tachycardia occurred in 10 of 20
                                                                                                                             (all hypotensive). Acrocyanosis and edema occurred in most patients with CFS, fewer patients with OTS,
                                                                                                                             and in one patient with simple faint. Orthostatic symptoms were similar but more severe in patients with
                                                                                                                             CFS compared with patients with OTS. CONCLUSIONS: Symptoms and patterns of orthostatic heart rate
                                                                                                                             and blood pressure change in OTS overlap strongly with those of CFS. Orthostatic intolerance in OTS may
                                                                                                                             represent an attenuated form of chronic fatigue pathophysiology.
 Streeten DH, Bell DS.                                      Long- and short-term blood        Clin Sci (Colch) 1999
                                                            pressure and RR-interval          Sep;97(3):319-22 Comment
                                                            variability and                   on: Clin Sci (Colch). 1998
                                                            psychosomatic distress in         Jan;94(1):57-63 Clin Sci
                                                            chronic fatigue syndrome.         (Colch). 1999 Jan;96(1):117-
 Teitelbaum JE, Bird B,                                     Low-dose hydrocortisone for       JAMA 1999 May
 Weiss A, Gould L.                                          chronic fatigue syndrome.         26;281(20):1887-8;
                                                                                              discussion 1888-9 Comment
                                                                                              on: JAMA. 1998 Sep 23-
 Terra JL.                  Departement d'information et    [Symptomatic and concurrent       Rev Prat 1999 Apr              The symptomatic and concurrent depressions description need to resort to comorbidity and symptomatic
                            d'evaluation medicales,         depressions].[article in          1;49(7):727-31                 co-occurrence concepts. Patients with depressive symptoms or in a major depressive episode may also be
                            Centre hospitalier specialise   French]                                                          suffering from another nonmood psychiatric disorders as alcoholism, anxiety or eating disorders. Many
                            Le Vinatier, Bron.                                                                               general medical conditions which are link with depression are illustrated with the examples of cancer,
                                                                                                                             coronary artery disease, endocrinologic diseases, dementia, stroke and chronic fatigue syndrome. When
                                                                                                                             depression and another psychiatric or medical conditions occur together, it is important to provide to the
                                                                                                                             practitioner guidelines for the decision to treat one of the two disorders. This paper contains an example of
                                                                                                                             decisional algorithm.
 Theorell T, Blomkvist V,   National Institute for          Critical life events,             Psychosom Med 1999 May-        OBJECTIVE: The purpose of this study was to describe the sequence of psychosocial events and infections
 Lindh G, Evengard B.       Psychosocial Factors and        infections, and symptoms          Jun;61(3):304-10               preceding the onset of chronic fatigue syndrome (CFS). This information was related to the temporal
                            Health, Stockholm, Sweden.      during the year preceding                                        development of crucial symptoms in relation to the onset of, namely, fatigue, sadness, irritability, pain, and
                                                            chronic fatigue syndrome                                         feeling of fever. METHODS: A personal interview was conducted in 46 patients (mean age, 39.5 years; SD,
                                                            (CFS): an examination of                                         9 years) who fulfilled international CFS criteria. These patients were matched with regard to age and gender
                                                            CFS patients and subjects                                        to 46 carefully matched control subjects. Twenty-three percent of the study subjects were men, and 77%
                                                            with a nonspecific life crisis.                                  were women. The patient at first identified the month that coincided with the onset of CFS. Similarly, each
                                                                                                                             control subject was asked to identify a "very difficult period" within approximately the same period as the
                                                                                                                             patient with whom the control subject was matched. A list of 14 different life events was perused.
                                                                                                                             Participants were asked to identify for each month whether each of the listed events had occurred.
                                                                                                                             Furthermore, they were asked to rate the importance of the events they had experienced. In addition, for
                                                                                                                             each of the cardinal symptoms (fatigue, sadness, irritability, pain, and feeling of fever) and for each month,
                                                                                                                             the subjects were asked to rate, on a visual analogue scale, the symptom intensity. Also, the number of
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                                                                                                                   infections was noted. RESULTS: A statistically significant group difference in fatigue intensity existed
                                                                                                                   during the period 4 to 10 months before the onset of CFS. During the 3 months preceding the diagnosis for
                                                                                                                   the CFS patients or the peak of the crisis for the control group, there was a dramatic rise in fatigue in both
                                                                                                                   groups. The CFS group reached a much higher fatigue level, which leveled off somewhat during the first
                                                                                                                   year of follow-up but still remained very high in comparison with the control group, which reached
                                                                                                                   precrisis levels 4 months after the peak. Similar patterns were observed for fever and pain. With regard to
                                                                                                                   sadness and irritability, no group difference was observed during the period preceding the crisis. In the
                                                                                                                   patient group, the level stayed high throughout the whole first year of follow-up, whereas a slow return
                                                                                                                   started in the control group; precrisis levels were reached after 1 year in this group. The prevalence ratio
                                                                                                                   (CFS patients/control subjects) for negative events was around 1.0 for the periods 4 to 12 months preceding
                                                                                                                   CFS but 1.9 during the quarter year preceding the onset. For infections, the prevalence ratio increased
                                                                                                                   successively during the four quarters preceding CFS (from 1.4 to 2.3). CONCLUSIONS: According to the
                                                                                                                   retrospective self-reports, there were differences between the groups in fatigue, pain, and feeling of fever
                                                                                                                   during the months preceding the crisis. With regard to depressive and irritable feelings, no preillness
                                                                                                                   differences were reported between the groups. There was a reported excess prevalence of both infections
                                                                                                                   and negative life events during the quarter year preceding the onset of CFS or crisis. Potential sources of
                                                                                                                   error are discussed. These findings must be replicated in longitudinal studies.
 Vermel' AE.                                        [Chronic fatigue                 Klin Med (Mosk)
                                                    syndrome].[article in            1999;77(7):11-5
 Vojdani A, Lapp CW.    Immunosciences Laboratory   Interferon-induced proteins      Immunopharmacol               Overlapping symptomatologies between Chronic Fatigue Syndrome (CFS) and Chemical Sensitivity have
                        Inc., Beverly Hills,        are elevated in blood samples    Immunotoxicol 1999            been observed by different investigators. Therefore, it is of great importance to develop biomarker(s) for
                        California, USA.            of patients with chemically or   May;21(2):175-202             possible differentiation between viral induced CFS (without sensitivity to chemicals) versus chemically
                    virally induced chronic                                        induced CFS. Since interferon induced proteins 2-5A Synthetase and Protein Kinase RNA (PKR) have been
                                                    fatigue syndrome.                                              implicated in the viral induction of CFS, the objective of this study was to utilize 2-5A and PKR activity
                                                                                                                   for differentiation between CFS induced by either viruses or chemicals. Based on the CDC definition and
                                                                                                                   criteria, twenty CFS patients who were positive for viral genome(s) (mainly HHV6; HTLVII, 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, heat shock proteins and interferon-beta. 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. This induction was more significant with
                                                                                                                   HSP90, HSP70, and IFN-beta indicating their involvement in the mechanism of action. However, when
                                                                                                                   MDBK cells were incubated either with MTBE + Benzene or HHV6 in the presence or absence of anti IFN-
                                                                                                                   beta or anti-HSP-70, the activities of both 2-5A and PKR in HHV6 infected cells were inhibited by more
                                                                                                                   than 90% due to addition of anti IFN-beta, and only 20% by addition of anti-HSP70. While in MTBE +
                                                                                                                   Benzene exposed cells anti IFN-beta reduced the activity of these enzymes by 40% and anti-HSP70 by
                                                                                                                   more than 90%. This variation in the induction of 2-5A and PKR by anti-HSP70 or IFN-beta indicates
                                                                                                                   involvement of IFN-beta in viral induction 2-5A and PKR, and HSP involvement in chemical induction of
                                                                                                                   these enzymes. 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.
 Wagenmakers AJ.        Department of Human         Chronic fatigue syndrome:        Clin Sci (Colch) 1999
                        Biology, Maastricht         the physiology of people on      Nov;97(5):611-3 Erratum in:
ME Research UK — Database of Research Publications 1999

                            University, PO Box 616,        the low end of the spectrum       Clin Sci (Colch) 1999
                            6200 MD Maastricht, The        of physical activity?             Dec;97(6):719 Comment on:
                            Netherlands.                                                     Clin Sci (Colch). 1999
                                                                                             Nov;97(5):603-8; discussion
 Wagner-Raphael LI, Jason   Department of Psychology,      Chronic fatigue syndrome,         J Occup Health Psychol 1999      Members of 2 nurses' associations (N = 71) were assessed using 2 mail questionnaires, a telephone
 LA, Ferrari JR.            DePaul University, USA.        chronic fatigue, and              Jan;4(1):63-71                   questionnaire, the Diagnostic Interview Schedule, and medical records. Physicians reviewed participants to
                                  psychiatric disorders:                                             determine whether they met current criteria for chronic fatigue syndrome (CFS). Stepwise multivariate
                                                           predictors of functional                                           regression analyses were conducted to identify predictors of functional status scores. Impairments in
                                                           status in a national nursing                                       physical, role, and social functioning increased as fatigue severity increased. Bodily pain increased as
                                                           sample.                                                            fatigue severity increased, and ratings of overall health increased as severity of fatigue decreased. Nurses
                                                                                                                              with a current psychiatric diagnosis reported more impairments in emotional functioning than nurses with a
                                                                                                                              lifetime diagnosis or no psychiatric diagnosis. Quality of life decreased as fatigue severity increased.
                                                                                                                              Nurses with fatigue not meeting CFS criteria reported better quality of life than those with CFS or medical
 Walker TL.                 Parke-Davis, Ann Arbor, MI,    Chronic fatigue syndrome.         Am J Nurs 1999
                            USA.                           Do you know what it means?        Mar;99(3):70-4, 76
 Wallace HL 2nd, Natelson   Department of Microbiology,    Human herpesviruses in            Clin Diagn Lab Immunol           We have conducted a double-blind study to assess the possible involvement of the human herpesviruses
 B, Gause W, Hay J.         State University of New York   chronic fatigue syndrome.         1999 Mar;6(2):216-23             (HHVs) HHV6, HHV7, Epstein-Barr virus (EBV), and cytomegalovirus in chronic fatigue syndrome (CFS)
                            at Buffalo, Buffalo, New                                                                          patients compared to age-, race-, and gender-matched controls. The CFS patient population was composed
                            York 14214, USA.                                                                                  of rigorously screened civilian and Persian Gulf War veterans meeting the Centers for Disease Control and
                                                                                                                              Prevention's CFS case definition criteria. Healthy control civilian and veteran populations had no evidence
                                                                                                                              of CFS or any other exclusionary medical or psychiatric condition. Patient peripheral blood mononuclear
                                                                                                                              cells were analyzed by PCR for the presence of these HHVs. Using two-tailed Fisher's exact test analyses,
                                                                                                                              we were unable to ascertain any statistically significant differences between the CFS patient and control
                                                                                                                              populations in terms of the detection of one or more of these viruses. This observation was upheld when the
                                                                                                                              CFS populations were further stratified with regard to the presence or absence of major axis I
                                                                                                                              psychopathology and patient self-reported gradual versus acute onset of disease. In tandem, we performed
                                                                                                                              serological analyses of serum anti-EBV and anti-HHV6 antibody titers and found no significant differences
                                                                                                                              between the CFS and control patients.
 Ware NC.                   Department of Social           Toward a model of social          Cult Med Psychiatry 1999         Retrospective, narrative accounts of illness experience in chronic fatigue syndrome provide the empirical
                            Medicine, Harvard Medical      course in chronic illness: the    Sep;23(3):303-31                 basis for a preliminary conceptual model of social course in chronic illness. Qualities of distress interact
                            School, Boston, MA 02115,      example of chronic fatigue                                         with culturally specific expectations for social life and personal conduct to trigger microsocial processes of
                            USA.                           syndrome.                                                          marginalization: role constriction, delegitimation, impoverishment, and social isolation. Marginalizing
                                                                                                                              processes are opposed by acts of resistance initiated by ill individuals and directed toward integration in
                                                                                                                              social worlds. Social distance from the perceived centers of CFS sufferers' interpersonal worlds expands
                                                                                                                              and contracts with the changing predominance of marginalizing and resisting influences over time. Social
                                                                                                                              course thus consists of successive, bi-directional movements along a 'continuum of marginality' by persons
                                                                                                                              living lives with chronic illness.
 Warren G, McKendrick M,    The University of Sheffield,   The role of essential fatty       Acta Neurol Scand 1999           OBJECTIVE: To replicate the treatment study by Behan et al. (1990) using current research criteria for
 Peet M.                    Section of Psychiatry,         acids in chronic fatigue          Feb;99(2):112-6                  Chronic Fatigue Syndrome (CFS). METHOD: Fifty patients who fulfilled the Oxford Criteria for CFS were
                            Northern General Hospital,     syndrome. A case-controlled                                        randomly allocated to treatment with either Efamol Marine or placebo for 3 months. They were seen
                            UK.                            study of red-cell membrane                                         monthly and completed a physical symptoms checklist and the Beck Inventory for Depression and reported
                                                           essential fatty acids (EFA)                                        if they were the same, better or worse at the end of the study. RESULTS: Symptoms generally improved
                                                           and a placebo-controlled                                           with time but not significantly and there were no significant differences between the treatment and placebo
                                                           treatment study with high                                          groups. Pretreatment red-cell membrane (RBC) lipids of patients compared with age-and sex-matched
                                                           dose of EFA.                                                       normal controls showed no significant differences. DISCUSSION: The results of this study contrast sharply
                                                                                                                              with the previous study where 85% of patients had a clinically significant improvement of symptoms with
                                                                                                                              Efamol Marine over a 3-month treatment period.
 Wessely S, Hotopf M.       Academic Department of         Is fibromyalgia a distinct        Baillieres Best Pract Res Clin   Most medical specialities have defined medically unexplained syndromes such as fibromyalgia, to
                            Psychological Medicine,        clinical entity? Historical and   Rheumatol 1999                   categorize patients with prominent but unexplained symptoms. Other such syndromes include irritable
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                                Guy's, King's and St Thomas'   epidemiological evidence.      Sep;13(3):427-36             bowel syndrome, chronic fatigue syndrome and atypical chest pain. In this chapter we present evidence to
                                School of Medicine, London,                                                                suggest that fibromyalgia is not a unique clinical entity, but shares much with these other syndromes. We
                                UK.                                                                                        use historical, clinical and epidemiological evidence to illustrate this idea. The historical data emphasize
                                                                                                                           the essentially arbitrary way in which fibromyalgia developed. The clinical evidence shows the considerable
                                                                                                                           overlap between patients with fibromyalgia and those with other unexplained syndromes. From an
                                                                                                                           epidemiological perspective we emphasize the strong associations between symptoms such as myalgia and
                                                                                                                           fatigue. We conclude by suggesting that fibromyalgia is one of many medically unexplained syndromes
                                                                                                                           which have more similarities than differences between them.
 Wessely S, Nimnuan C,          Department of Psychological    Functional somatic             Lancet 1999 Sep              We review the concept and importance of functional somatic symptoms and syndromes such as irritable
 Sharpe M.                      Medicine, Guy's, King's and    syndromes: one or many?        11;354(9182):936-            bowel syndrome and chronic fatigue syndrome. On the basis of a literature review, we conclude that a
                                St Thomas' School of                                          9Comment in: Lancet. 1999    substantial overlap exists between the individual syndromes and that the similarities between them
                                Medicine, London, UK.                                         Dec 11;354(9195):2078;       outweigh the differences. Similarities are apparent in case definition, reported symptoms, and in non-
                                                                                              discussion 2078-9 Lancet.    symptom association such as patients' sex, outlook, and response to treatment. We conclude that the
                                                                                              1999 Dec 11;354(9195):2079   existing definitions of these syndromes in terms of specific symptoms is of limited value; instead we
                                                                                              Lancet. 1999 Dec             believe a dimensional classification is likely to be more productive.
                                                                                              Lancet. 1999 Dec
 Wood B, Wessely S.             Maudsley Hospital and the      Personality and social         J Psychosom Res 1999         One hundred one chronic fatigue syndrome (CFS) patients attending a specialist CFS clinic were compared
                                Institute of Psychiatry,       attitudes in chronic fatigue   Oct;47(4):385-97             with 45 rheumatoid arthritis (RA) patients on a range of standardized questionnaire measures, to investigate
                                London, UK.                    syndrome.                                                   whether CFS patients are characterized by particular personality traits or social attitudes. No differences
                                                                                                                           were found between CFS and RA patients in measures of perfectionism, attitudes toward mental illness,
                                                                                                                           defensiveness, social desirability, or sensitivity to punishment (a concept related to neuroticism), on either
                                                                                                                           crude or adjusted analyses. Alexithymia scores were greater in the RA patient group (p<0.05). Social
                                                                                                                           adjustment, based on subjective assessment of overall restriction in activities and relationship difficulties,
                                                                                                                           was substantially poorer in the CFS group (p<0.001). This was highly associated with depressive
                                                                                                                           symptoms, but remained significant even after adjusting for depressive symptomatology. There was no
                                                                                                                           evidence from this study of major differences between the personalities of CFS patients and RA patients.
                                                                                                                           The stereotype of CFS sufferers as perfectionists with negative attitudes toward psychiatry was not
 Yamaguchi K, Sawada T,         Blood Transfusion Service      Detection of borna disease     Clin Diagn Lab Immunol       The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders
 Naraki T, Igata-Yi R,          and Internal Medicine,         virus-reactive antibodies      1999 Sep;6(5):696-700        and healthy individuals has varied in several reports using several different serological assay methods. A
 Shiraki H, Horii Y, Ishii T,   Kumamoto University School     from patients with                                          reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological
 Ikeda K, Asou N, Okabe H,      of Medicine, Kumamoto,         psychiatric disorders and                                   significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay
 Mochizuki M, Takahashi         Japan.                         from horses by                                              (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length).
 K, Yamada S, Kubo K,           kyama@gpo.kumamoto-            electrochemiluminescence                                    Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera
 Yashiki S, Waltrip RW                        immunoassay.                                                from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845
 2nd, Carbone KM.                                                                                                          schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV.
                                                                                                                           Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic
                                                                                                                           fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune diseases
                                                                                                                           including rheumatoid arthritis and systemic lupus erythematosis and 17 with leprosy, there was no positive
                                                                                                                           case except one case each with alcohol addiction, AIDS, and dementia. Although 19 (1.36%) of 1,393
                                                                                                                           patients with various ocular diseases, 10 (1.09%) of 917 blood donors, and 3 (4.55%) of 66 multitransfused
                                                                                                                           patients were seropositive for BDV-specific antigen, high levels of seroprevalence in schizophrenia patients
                                                                                                                           and young patients (16 to 59 years old) with mood disorders were statistically significant. The
                                                                                                                           immunoreactivity of seropositive sera could be verified for specificity by blocking with soluble p40 and/or
                                                                                                                           p24 recombinant protein. Anti-p24 antibody was more frequent than p40 antibody in most cases, and in
                                                                                                                           some psychotic patients antibody profiles showed only p40 antibody. Although serum positive for both p40
                                                                                                                           and p24 antibodies was not found in this study, the p40 ECLIA count in schizophrenia patients was higher
                                                                                                                           than that of blood donors. Furthermore, we examined 90 sera from Japanese feral horses. Antibody profiles
                                                                                                                           of control human samples are similar to that of naturally BDV-infected feral horses. We concluded that
                                                                                                                           BDV infection was associated in some way with psychiatric disorders.
ME Research UK — Database of Research Publications 1999

 Zhang Q, Zhou XD, Denny    Center for Environmental     Changes in immune               Clin Diagn Lab Immunol   The purpose of this study was to evaluate immune function through the assessment of lymphocyte
 T, Ottenweller JE, Lange   Hazards Research, DVA        parameters seen in Gulf War     1999 Jan;6(1):6-13       subpopulations (total T cells, major histocompatibility complex [MHC] I- and II-restricted T cells, B cells,
 G, LaManca JJ, Lavietes    Medical Center, E. Orange,   veterans but not in civilians                            NK cells, MHC II-restricted T-cell-derived naive and memory cells, and several MHC I-restricted T-cell
 MH, Pollet C, Gause WC,    New Jersey 07018, USA.       with chronic fatigue                                     activation markers) and the measurement of cytokine gene expression (interleukin 2 [IL-2], IL-4, IL-6, IL-
 Natelson BH.                                            syndrome.                                                10, IL-12, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) from peripheral
                                                                                                                  blood lymphocytes. Subjects included two groups of patients meeting published case definitions for chronic
                                                                                                                  fatigue syndrome (CFS)-a group of veterans who developed their illness following their return home from
                                                                                                                  participating in the Gulf War and a group of nonveterans who developed the illness sporadically. Case
                                                                                                                  control comparison groups were comprised of healthy Gulf War veterans and nonveterans, respectively. We
                                                                                                                  found no significant difference for any of the immune variables in the nonveteran population. In contrast,
                                                                                                                  veterans with CFS had significantly more total T cells and MHC II+ T cells and a significantly higher
                                                                                                                  percentage of these lymphocyte subpopulations, as well as a significantly lower percentage of NK cells,
                                                                                                                  than the respective controls. In addition, veterans with CFS had significantly higher levels of IL-2, IL-10,
                                                                                                                  IFN-gamma, and TNF-alpha than the controls. These data do not support the hypothesis of immune
                                                                                                                  dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf
                                                                                                                  is associated with an altered immune status in veterans who returned with severe fatiguing illness.