ME Research UK — Database of Research Publications 1999 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 26;112(1084):104-5 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 23;111(1076):410-2 Baschetti R. Hydrocortisone and chronic Lancet 1999 May ME Research UK — Database of Research Publications 1999 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- 30;280(12):1061-6 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 Dec;242(6):465-78 Baschetti R. Investigations of J Clin Endocrinol Metab hydrocortisone and 1999 Jun;84(6):2263-4 fludrocortisone in the treatment of chronic fatigue syndrome. 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 Jan;31(1):18-21 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 26;159(8):777-85. 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 ME Research UK — Database of Research Publications 1999 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 laboratory. 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 ME Research UK — Database of Research Publications 1999 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, email@example.com considerations, and new episodes. Family history is loaded with affective, including bipolar, disorders. The latter finding explains Racagni G, Wessely S. i.it 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 firstname.lastname@example.org 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 fatigue. 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 ME Research UK — Database of Research Publications 1999 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 email@example.com 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 firstname.lastname@example.org 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 ME Research UK — Database of Research Publications 1999 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 email@example.com 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 firstname.lastname@example.org 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. email@example.com 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 ME Research UK — Database of Research Publications 1999 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 profession. 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 firstname.lastname@example.org 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. email@example.com 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 syndrome. 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 ME Research UK — Database of Research Publications 1999 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 ME Research UK — Database of Research Publications 1999 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 group. 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. Swedish] 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. se 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 firstname.lastname@example.org depression and suicide attempts among U.S. women physicians. RESULTS: An estimated 1.5% (N = 61) of ME Research UK — Database of Research Publications 1999 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- 30;280(12):1061-6 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 email@example.com 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 ME Research UK — Database of Research Publications 1999 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 ME Research UK — Database of Research Publications 1999 '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 firstname.lastname@example.org 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 stable. 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. email@example.com [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 German] 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 discussed. 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 firstname.lastname@example.org 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 8;353(9164):1619-20 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. E.Jones@hogarth7.demon.co .uk 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 1;171(1):3-7 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. email@example.com 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 Norwegian] 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 ml.kg-1.min- 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 controls. 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. firstname.lastname@example.org 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 Japanese] 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. email@example.com 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 confusion. 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 Swedish] 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 firstname.lastname@example.org 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 ME Research UK — Database of Research Publications 1999 1):130-2 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 email@example.com 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 German] 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. firstname.lastname@example.org 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 email@example.com 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 firstname.lastname@example.org 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 email@example.com 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 firstname.lastname@example.org 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. Academic 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- ME Research UK — Database of Research Publications 1999 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 6;353(9151):455-8 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 ME Research UK — Database of Research Publications 1999 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. email@example.com 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 ME Research UK — Database of Research Publications 1999 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. firstname.lastname@example.org 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 etiology. 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. ME Research UK — Database of Research Publications 1999 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- 25 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- 30;280(12):1061-6 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 ME Research UK — Database of Research Publications 1999 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 Russian] 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 email@example.com 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 611-3 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 firstname.lastname@example.org 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 exclusions. 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 ME Research UK — Database of Research Publications 1999 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. 11;354(9195):2079-80 Lancet. 1999 Dec 11;354(9195):2080 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 supported. 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, email@example.com- electrochemiluminescence Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera Yashiki S, Waltrip RW u.ac.jp 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.