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  1. 1. ME Research UK — Database of Research Publications 2005 Authors Author Address Title Publication Abstract [No authors listed] Summaries for patients. The health of Gulf War veterans. Original report in: Ann Intern Med. 2005 Jun 7;142(11):881- 90. Ann Intern Med. 2005 Jun 7;142(11):I22. [No authors listed] Increased activity OK for chronic pain. Health News. 2005 May;11(5):6. Armengaud D. Service de pediatrie-medecine neonatale, CHI Poissy-Saint- Germain, 78300 Poissy. darmenga@chi- [Chronic fatigue and sleep disorders in adolescents] [Article in French] Rev Prat. 2005 May 31;55(10):1095-8. To be, or to feel tired, is a frequent complaint at any age, and which does not seem in itself to be specific of the teenager. If it frequently lies within the scope of an organic pathology, acute or chronic, besides while being able to be a revealing element for it, it is often insulated and asks a rigorous step in the evaluation of its various possible components. It is then important to be in an active listening and patient, and not in a hasty regulation of a "cosmetic" treatment of this subjective allegation. It is all the work of the doctor whom to support the emergence of the subjacent complaint whose tensions and stakes of adolescence post there their singularity. Aslangul E, Le Jeunne C. Service de Medecine Interne, Hotel-Dieu, 75004 Paris. claire.le- [Diagnosing asthenia and chronic fatigue syndrome] [Article in French] Rev Prat. 2005 May 15;55(9):1029-33. Axe EK, Satz P, Rasgon NL, Fawzy FI ORIGINAL RESEARCH Major Depressive Disorder in Chronic Fatigue Syndrome: A CDC Surveillance Study Journal of Chronic Fatigue Syndrome 2005 12 (3): 7-23 Background: Controversy continues to exist as to whether Chronic Fatigue Syndrome is a psychological/psychiatric disorder. To further understand this condition the Centers for Disease Control (CDC) conducted a Surveillance Study. The CDC partitioned 565 subjects with fatiguing illnesses into four diagnostic groups, one of which met the 1988 CDC criteria for CFS. The non-CFS groups had either insufficient severity (idiopathic), medical exclusions or prior psychiatric disorders. Objectives: The present study reports on the psychiatric features in that study, estimates the time of onset of Major Depressive Disorder (MDD) and looks for possible relationships between 1988 CDC criteria for Chronic Fatigue Syndrome and psychiatric disorders. Methods: The study design is cross- sectional. The Diagnostic Interview Schedule (DIS) assessed for four Axis I psychiatric disorders. Time of onset ofMDDwas estimated from the DIS and validated by an examination of the medical records. Odds ratios and confidence intervals were calculated as tests of association between 1988 CDC criteria and psychiatric disorders. Results: Subjects classified as CFS and non-CFS had similar rates of psychiatric disorders. A minority of subjects had preexisting MDD. Three 1988 CDC criteria were associated with current MDD whilst no criteria were associated with prior MDD. Conclusions: CFS subjects did not demonstrate any unique patterns of psychiatric disorders. MDD may not be an important predisposing factor for CFS or the other fatiguing illnesses. Some 1988 CDC criteria may be preferentially endorsed by subjects with current MDD. Badawy AA, Morgan CJ, Cardiff & Vale NHS Trust, Heterogeneity of serum tryptophan J Psychopharmacol. We assessed the serotonin status of patients with the chronic fatigue syndrome (CFS). Tryptophan (Trp) availability to the brain, expressed as the ratio of concentration of serum Trp to the sum of those
  2. 2. ME Research UK — Database of Research Publications 2005 Llewelyn MB, Albuquerque SR, Farmer A. Biomedical Research Laboratory, Whitchurch Hospital, Cardiff, Wales, UK. Abdulla.Badawy@ cardiffandvale.wal concentration and availability to the brain in patients with the chronic fatigue syndrome. 2005 Jul;19(4):385-91. of its five competitors (CAA), and other parameters of Trp disposition were compared in 23 patients with the CFS and 42 healthy controls. The serum [free Trp]/[CAA] ratio was 43% higher in CFS patients, due to a 48% higher [free Trp]. [Total Trp] was also significantly higher (by 19%) in CFS patients, and, although the [total Trp]/[CAA] ratio did not differ significantly between the control and patient groups, the difference became significant when the results were co-varied with age and gender. [CAA] was not significantly different between groups, but was significantly lower in females, compared to males, of the CFS patient group. We have established normal ranges for Trp disposition parameters and propose criteria for defining the serotonin-biosynthetic status in humans. We have provisionally identified two subgroups of CFS patients, one with normal serotonin and the other with a high serotonin status. The relevance of our findings to, and their implications for, the pharmacological and other therapies of the chronic fatigue syndrome are discussed. Baraniuk JN, Casado B, Maibach H, Clauw DJ, Pannell LK, Hess S S. Georgetown University Proteomics Laboratory, Division of Rheumatology, Immunology & Allergy, Room B- 105, Lower Level Kober-Cogan Building, Georgetown University, Washington, DC 20007-2197, USA. baraniuj@georgeto A Chronic Fatigue Syndrome - related proteome in human cerebrospinal fluid. BMC Neurol. 2005 Dec 1;5:22. BACKGROUND: Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. METHODS: Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 mul/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 mul/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis. RESULTS: Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS- related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of >or=1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance (logistic model). The proteins were alpha-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described. CONCLUSION: This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared. Baraniuk JN, Petrie KN, Le U, Tai CF, Park YJ, Yuta A, Ali M, Vandenbussche CJ, Nelson B. Division of Rheumatology, Immunology and Allergy, Georgetown University, 3800 Reservoir Road, N.W., Washington, DC 20007-2197, USA. baraniuj@georgeto Neuropathology in rhinosinusitis. Am J Respir Crit Care Med. 2005 Jan 1;171(1):5-11. Epub 2004 Oct 11. Pathophysiologic differences in neural responses to hypertonic saline (HTS) were investigated in subjects with acute sinusitis (n = 25), subjects with chronic fatigue syndrome (CFS) with nonallergic rhinitis (n = 14), subjects with active allergic rhinitis (AR; n = 17), and normal (n = 20) subjects. Increasing strengths of HTS were sprayed into their nostrils at 5-minute intervals. Sensations of nasal pain, blockage, and drip increased with concentration and were significantly elevated above normal. These parallels suggested activation of similar subsets of afferent neurons. Urea and lysozyme secretion were dose dependent in all groups, suggesting that serous cell exocytosis was one source of urea after neural stimulation. Only AR and normal groups had mucin dose responses and correlations between symptoms and lysozyme secretion (R(2) = 0.12-0.23). The lysozyme dose responses may represent axon responses in these groups. The neurogenic stimulus did not alter albumin (vascular) exudation in any group. Albumin and mucin concentrations were correlated in sinusitis, suggesting that nonneurogenic factors predominated in sinusitis mucous hypersecretion. CFS had neural hypersensitivity (pain) but reduced serous cell secretion. HTS nasal provocations identified significant,
  3. 3. ME Research UK — Database of Research Publications 2005 unique patterns of neural and mucosal dysregulation in each rhinosinusitis syndrome. Baschetti R. Chronic fatigue syndrome, exercise, cortisol and lymphadenopathy. J Intern Med. 2005 Sep;258(3):291-2. Letter Bazelmans E, Bleijenberg G, Voeten MJ, van der Meer JW, Folgering H. Department of Medical Psychology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome. J Psychosom Res. 2005 Oct;59(4):201-8. OBJECTIVE: This study examined the effects of exercise on symptoms and activity in chronic fatigue syndrome (CFS). METHODS: Twenty CFS patients and 20 neighborhood controls performed an incremental exercise test until exhaustion. Fatigue, muscle pain, minutes spent resting, and the level of physical activity were assessed with a self-observation list. Physical activity was assessed with an actometer as well. Data were obtained 3 days before the maximal exercise test (MET) up to 5 days thereafter. RESULTS: For CFS patients, daily observed fatigue was increased up to 2 days after the exercise test. For controls, self-observed fatigue returned to baseline after 2 h. Both CFS patients and controls spent more minutes resting on the day before and on the day after the MET. For CFS patients, self-observed minutes resting increased on the day of the exercise test. For neither group, a decrease of actometer recorded or self-observed physical activity after exercise was found. CONCLUSION: Fatigue in CFS patients increased after exercise, but the level of actual physical activity remained unchanged. Bazelmans E, Bleijenberg G, Voeten MJ, van der Meer JW, Folgering H. Department of Medical Psychology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. e.bazelmans@mps. Impact of a maximal exercise test on symptoms and activity in chronic fatigue syndrome. J Psychosom Res. 2005 Oct;59(4):201-8. OBJECTIVE: This study examined the effects of exercise on symptoms and activity in chronic fatigue syndrome (CFS). METHODS: Twenty CFS patients and 20 neighborhood controls performed an incremental exercise test until exhaustion. Fatigue, muscle pain, minutes spent resting, and the level of physical activity were assessed with a self-observation list. Physical activity was assessed with an actometer as well. Data were obtained 3 days before the maximal exercise test (MET) up to 5 days thereafter. RESULTS: For CFS patients, daily observed fatigue was increased up to 2 days after the exercise test. For controls, self-observed fatigue returned to baseline after 2 h. Both CFS patients and controls spent more minutes resting on the day before and on the day after the MET. For CFS patients, self-observed minutes resting increased on the day of the exercise test. For neither group, a decrease of actometer recorded or self-observed physical activity after exercise was found. CONCLUSION: Fatigue in CFS patients increased after exercise, but the level of actual physical activity remained unchanged. Bazelmans E, Prins JB, Lulofs R, van der Meer JW, Bleijenberg G; The Netherlands Fatigue Research Group Nijmegen. Department of Medical Psychology, University Medical Centre Nijmegen, Nijmegen, The Netherlands. E.Bazelmans@cuk Cognitive behaviour group therapy for chronic fatigue syndrome: a non-randomised waiting list controlled study. Psychother Psychosom. 2005;74(4):218- 24. BACKGROUND: It has been demonstrated that individual cognitive behaviour therapy is an effective treatment for chronic fatigue syndrome (CFS). The aim of the present study was to investigate the effectiveness of cognitive behaviour group therapy (CBGT) in an unselected group of CFS patients. Additionally, pretreatment characteristics of CFS patients who improve after CBGT were explored. METHODS: In a non-randomised waiting list controlled design, 31 patients were allocated to CBGT and 36 to the waiting list condition. CBGT consisted of 12 two-hour sessions during 6 months. Main outcome measures were fatigue (Checklist Individual Strength) and functional impairment (Sickness Impact Profile). RESULTS: A moderate effect on fatigue in favour of CBGT was found. For functional impairment, the effect was opposite to what was expected. Patients who improved after CBGT had less complaints at baseline compared to patients who did not improve. CONCLUSIONS: An explanation for the moderate effect might be that during CBGT, rest and relaxation were too much emphasised. Furthermore, an unselected group of CFS patients and therapists inexperienced in CB(G)T for CFS participated. Suggestions to improve CBGT for future research are given. Copyright (c) 2005 S. Karger AG, Basel.
  4. 4. ME Research UK — Database of Research Publications 2005 Bell IR, Brooks AJ, Baldwin CM, Fernandez M, Figueredo AJ, Witten ML. Research Service, Southern Arizona VA Health Care System, USA. ibell@u.arizona.ed u JP-8 jet fuel exposure and divided attention test performance in 1991 Gulf War veterans. Aviat Space Environ Med. 2005 Dec;76(12):1136- 44. INTRODUCTION: Previous research indicates that a large cohort of veterans from the 1991 Gulf War report polysymptomatic conditions. These syndromes often involve neurocognitive complaints, fatigue, and musculoskeletal symptoms, thus overlapping with civilian illnesses from low levels of environmental chemicals, chronic fatigue syndrome, and fibromyalgia. METHODS: To test for time- dependent changes over repeated intermittent exposures, we evaluated objective performance on a computerized visual divided attention test in chronically unhealthy Gulf War veterans (n = 22 ill with low-level chemical intolerance (CI); n = 24 ill without CI), healthy Gulf War veterans (n = 23), and healthy Gulf War era veterans (n = 20). Testing was done before and after each of three weekly, double blind, low-level JP-8 jet fuel or clean air sham exposure laboratory sessions, including acoustic startle stimuli. RESULTS: Unhealthy veterans receiving jet fuel had faster mean peripheral reaction times over sessions compared with unhealthy veterans receiving sham clean air exposures. Unhealthy Gulf veterans with CI exhibited faster post- vs. pre-session mean central reaction times compared with unhealthy Gulf veterans without CI. Findings were controlled for psychological distress variables. DISCUSSION: These data on unhealthy Gulf veterans show an acceleration of divided attention task performance over the course of repeated low-level JP-8 exposures. The present faster reaction times are consistent with rat neurobehavioral studies on environmental toxicant cross-sensitization and nonlinear dose-response patterns with stimulant drugs, as well as some previous civilian studies using other exposure agents. Together with previous research findings, the data suggest involvement of central nervous system dopaminergic pathways in affected Gulf veterans. Bellanti JA, Sabra A, Castro HJ, Chavez JR, Malka- Rais J, de Inocencio JM. Departments of Pediatrics , Georgetown University Medical Center, Washington, D.C. 20057, USA. Are attention deficit hyperactivity disorder and chronic fatigue syndrome allergy related? what is fibromyalgia? Allergy Asthma Proc. 2005 Jan- Feb;26(1):19-28. Despite the progress made in the field of allergy-immunology in recent years, there are a group of diseases that the allergist-immunologist may be called on to manage in which their precise etiologies have not been identified but that appear to be initiated or exacerbated by allergic mechanisms. Attention deficit hyperactivity disorder (ADHD), chronic fatigue syndrome (CFS), and fibromyalgia (FM) fall into this category of disorders. Although the precise etiology of ADHD still remains unknown, the most prevalent theory is that it represents a neurobiologically based developmental disability leading to inadequate production of the neurotransmitter dopamine. In patients with CFS, there appears to be a fundamental dysfunction of the neuroendocrine-immunological system with deficiencies of immunological and neurological function, which, together with chronic viral infection, may lead to a sequence of events responsible for the symptoms of this disorder. FM appears to be a variant of CFS with a predominance of hypothalamic pituitary axis dysfunction. The disorder is characterized by chronic widespread pain and the finding of 11/18 tender points on examination. Now, there is emerging evidence to suggest that adverse reactions to foods or food components also may be associated with behavioral disturbances that may play a role in each of these disorders. An understanding of the interactive responses involved in the neuroendocrine-immunological network is essential for a comprehension of the pathophysiology of ADHD, CFS, and FM and the role of allergies appears to be an important triggering event in each of the disorders. Bentler SE, Hartz AJ, Kuhn EM. Department of Family Medicine, College of Medicine, University of Iowa, Iowa City, IA 52242-1097, USA. Prospective observational study of treatments for unexplained chronic fatigue. J Clin Psychiatry. 2005 May;66(5):625-32. BACKGROUND: Unexplained chronic fatigue is a frequent complaint in primary care. A prospective observational study design was used to evaluate whether certain commonly used therapies for unexplained chronic fatigue may be effective. METHOD: Subjects with unexplained chronic fatigue of unknown etiology for at least 6 months were recruited from the Wisconsin Chronic Fatigue Syndrome Association, primary care clinics, and community chronic fatigue syndrome presentations. The primary outcome measure was change in a 5-question fatigue score from 6 months to 2 years. Self- reported interventions tested included prescribed medications, non-prescribed supplements and herbs, lifestyle changes, alternative therapies, and psychological support. Linear regression analysis was used
  5. 5. ME Research UK — Database of Research Publications 2005 to test the association of each therapy with the outcome measure after adjusting for statistically significant prognostic factors. RESULTS: 155 subjects provided information on fatigue and treatments at baseline and follow-up. Of these subjects, 87% were female and 79% were middle-aged. The median duration of fatigue was 6.7 years. The percentage of users who found a treatment helpful was greatest for coenzyme Q10 (69% of 13 subjects), dehydroepiandrosterone (DHEA) (65% of 17 subjects), and ginseng (56% of 18 subjects). Treatments at 6 months that predicted subsequent fatigue improvement were vitamins (p = .08), vigorous exercise (p = .09), and yoga (p = .002). Magnesium (p = .002) and support groups (p = .06) were strongly associated with fatigue worsening from 6 months to 2 years. Yoga appeared to be most effective for subjects who did not have unclear thinking associated with the fatigue. CONCLUSION: Certain alternative therapies for unexplained chronic fatigue, especially yoga, deserve testing in randomized controlled trials. Black CD, McCully KK. Department of Kinesiology, The University of Georgia, Athens, GA, USA. Time course of exercise induced alterations in daily activity in chronic fatigue syndrome. Dyn Med. 2005 Oct 28;4:10. In a previous study we demonstrated that while people with CFS had lower daily activity levels than control subjects, they were able to increase daily activity via a daily walking program. We reanalyzed our data to determine the time course of activity changes during the walking program. Daily activity assessed via an accelometer worn at the hip was divided into sleep, active, and walking periods. Over the first 4-10 days of walking the subjects with CFS were able to reach the prescribed activity goals each day. After this time, walking and total activity counts decreased. Sedentary controls subjects were able to maintain their daily walking and total activity goals throughout the 4 weeks. Unlike our previous interpretation of the data, we feel this new analysis suggests that CFS patients may develop exercise intolerance as demonstrated by reduced total activity after 4-10 days. The inability to sustain target activity levels, associated with pronounced worsening of symptomology, suggests the subjects with CFS had reached their activity limit. Black CD, O'connor PJ, McCully KK. Department of Exercise Science, The University of Georgia, Athens, GA, USA. kmccully@coe.uga .edu. Increased daily physical activity and fatigue symptoms in chronic fatigue syndrome. Dyn Med. 2005 Mar 3;4(1):3. Individuals with chronic fatigue syndrome (CFS) have been shown to have reduced activity levels associated with heightened feelings of fatigue. Previous research has demonstrated that exercise training has beneficial effects on fatigue-related symptoms in individuals with CFS. PURPOSE: The aim of this study was to sustain an increase in daily physical activity in CFS patients for 4 weeks and assess the effects on fatigue, muscle pain and overall mood. METHODS: Six CFS and seven sedentary controls were studied. Daily activity was assessed by a CSA accelerometer. Following a two week baseline period, CFS subjects were asked to increase their daily physical activity by 30% over baseline by walking a prescribed amount each day for a period of four weeks. Fatigue, muscle pain and overall mood were reported daily using a 0 to 100 visual analog scale and weekly using the Profile of Mood States (Bipolar) questionnaire. RESULTS: CFS patients had significantly lower daily activity counts than controls (162.5 +/- 51.7 x 103 counts/day vs. 267.2 +/- 79.5 x 103 counts/day) during a 2-week baseline period. At baseline, the CFS patients reported significantly (P < 0.01) higher fatigue and muscle pain intensity compared to controls but the groups did not differ in overall mood. CFS subjects increased their daily activity by 28+/-19.7% over a 4 week period. Overall mood and muscle pain worsened in +the CFS patients with increased activity. CONCLUSION: CFS patients were able to increase their daily physical activity for a period of four weeks. In contrast to previous studies fatigue, muscle pain, and overall mood did not improve with increased activity. Increased activity was not presented as a treatment which may account for the differential findings between this and previous studies. The results suggest that a daily "activity limit" may exist in this population. Future studies on the impact of physical activity on the symptoms of CFS patients are needed. Blotman F, Thomas E, Myon Rheumatology Department, Awareness and knowledge of Clin Exp Rheumatol. 2005 OBJECTIVES: Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain and fatigue. Its prevalence is estimated to be at 3.4% in women and 0.5% in men. It is a major cause
  6. 6. ME Research UK — Database of Research Publications 2005 E, Andre E, Caubere JP, Taieb C. Lapeyronie Hospital, Montpellier, France. francis.blotman@ fibromyalgia among french rheumatologists and general practitioners. Sep-Oct;23(5):697- 700. of morbidity. Our objective was to evaluate, using a self-questionnaire sent by mail, the level of knowledge of French physicians, general practitioners, and rheumatologists on fibromyalgia and to analyse their therapeutic approach. METHODS: The demographic characteristics of a sample of general practitioners and rheumatologists were compared to those of the overall data available. This comparison demonstrated the good representativeness of our sample. RESULTS: Fibromyalgia was considered as a disease by 23% of rheumatologists and 33% of general practitioners. While on average, each rheumatologist followed 30 fibromyalgia patients, each general practitioner followed 6.1 patients (i.e., 2 to 5% of their practice's patient base). Among rheumatologists, 6.4% made no distinction between this disease and depression vs. 13.1% of general practitioners. The diagnosis of fibromyalgia was made based on tenderness that occurs in precise, localized areas of the body (trigger points) by 94% of rheumatologists and 79.1% of general practitioners. Of general practitioners and rheumatologists, 93.7% and 73.7% respectively, have not received any medical school training on fibromyalgia or chronic fatigue syndrome. CONCLUSION: Given the lack of medical school training and continuing professional education concerning fibromyalgia (rare use of pain rating scales, confusion in the classification of rheumatic diseases), there is an urgent need to initiate an explicit teaching effort on chronic pain, and on fibromyalgia in particular. Bolk JH. Leids Universitair Medisch Centrum, afd Algemene Interne Geneeskunde, 2300 RC Leiden. [Report from the Health Council of the Netherlands on the chronic fatigue syndrome: moving away from the body-mind dichotomy with a view to effective prevention and treatment] [Article in Dutch] Ned Tijdschr Geneeskd. 2005 Apr 2;149(14):739-41. The Health Council of the Netherlands has issued a report on the chronic fatigue syndrome (CFS). CFS is a real and seriously debilitating condition which imposes limitations on an individual's personal, occupational and social functioning. It is a syndrome of unknown aetiology without physical signs or biological markers. Although there is no disease, patients both feel ill and give the appearance of being ill. There is no consensus on whether CSF patients are able to work or whether they should be entitled to social security benefits. An imbalance between demand and coping is central in CFS, with stress as an important intermediary factor. It is little use concluding that unexplained signs are 'psychological' or that 'I cannot find anything wrong with you so you must be healthy'. The classical view that mind and body are separate systems is outmoded. The bio-psycho-social model of disease may be helpful in describing the interaction between body, mind and circumstance. Putting the CFS patient at ease and explaining the pathophysiology of the symptoms is a useful approach but many patients and patient associations are still very somatically orientated, thereby sustaining the condition. However, in patients who accept that their problems may be stress-induced and are prepared to participate in therapy, some therapies have been proven to be effective, notably cognitive behavioural therapy. Bowen J, Pheby D, Charlett A, McNulty C. Health Protection Agency Primary Care Unit, Gloucester, UK. jill.whiting@hpa.o Chronic Fatigue Syndrome: a survey of GPs' attitudes and knowledge. Fam Pract. 2005 Aug;22(4):389-93. Epub 2005 Apr 1. BACKGROUND: GPs need evidence and guidance to help them diagnose and manage Chronic Fatigue Syndrome (CFS)/ME appropriately. OBJECTIVES: The aim of this survey was to obtain baseline data and identify the factors associated with GPs' attitudes to and knowledge of CFS/ME. The attitude of GPs to the condition is an important indicator of likely prognosis. METHODS: A postal questionnaire was sent to 1054 GPs served by Taunton, Bristol and Gloucester laboratories. GPs' attitudes to nine statements about CFS/ME were assessed and the factors associated with positive or negative responses were determined. Knowledge of the clinical features was also assessed. RESULTS: 811 GPs (77%) returned the questionnaire. 48% of GPs did not feel confident with making a diagnosis of CFS/ME and 41% did not feel confident in treatment. 72% of GPs accepted CFS/ME as a recognisable clinical entity and those GPs had significantly more positive attitudes. Three other key factors that were significantly, positively associated with GPs' attitudes were knowing someone socially with CFS/ME, being male and seeing more patients with the condition in the last year. CONCLUSION: Despite the publication of guidance for GPs on CFS/ME, confidence with making a
  7. 7. ME Research UK — Database of Research Publications 2005 diagnosis and management was found to be low. Educational initiatives and guidance for GPs should stress the importance of accepting CFS/ME as a recognisable clinical entity, as this is linked to having a positive attitude and could lead to improved confidence to make a diagnosis and treat CFS/ME patients. Brimacombe M, Lange G, Bisuchio K, Ciccone DS, Natelson B ORIGINAL RESEARCH Cognitive Function Index for Patients with Chronic Fatigue Syndrome Journal of Chronic Fatigue Syndrome 2005 12 (4): 3 - 23 Background: A comprehensive approach to assessing neuropsychological deficits in CFS patients is developed by assessing cognitive function across a number of domains using a battery of tests, rather than relying on any single instrument. Objective: A factor analytic approach was employed to examine the underlying dimensionality of 15 standard cognitive function related test variables in CFS patients. A cognitive function index (CFI) was then developed using appropriately weighted and interpreted factors. Methods: Factor analysis was applied to an initial sample of 65 CFS patients, identifying eight factors accounting for over 70% of total variation. This factor structure was then independently verified on a separate sample of 124 CFS patients. An overall combined CFS sample of 212 was then used to derive the CFI using an appropriately interpreted and weighted average of the derived factors. Results: After including age and education as separate factors, the CFI consists of nine factors accounting for 70% of total variation in the overall CFS group. The CFI was not affected by the presence of current psychiatric comorbidity. A cut-off score for cognitive dysfunction was established using the lower quartile value of a group of sedentary controls on the same index. Conclusions: The CFI will provide a useful summary measure for researchers investigating cognitive function performance in CFS patients. It does not replace existing individual specialized tests. Buskila D, Neumann L, Press J. Department of Internal Medicine, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84101, Israel. dbuskila@bgumail Genetic factors in neuromuscular pain. CNS Spectr. 2005 Apr;10(4):281-4. Recent evidence suggests that fibromyalgia, a chronic widespread pain condition and related syndromes (chronic fatigue syndrome, irritable bowel syndrome, etc.) may share heritable pathophysiologic features. We review the recent literature on genetic and familial factors found to participate in the pathogenesis of these syndromes, specifically fibromyalgia, including evidence suggesting that serotonin- and dopamine-related genes may play a role in the pathogenesis of these illnesses. The importance of environmental factors triggering these conditions in predisposed individuals is also discussed. Cairns R, Hotopf M. Department of Psychological Medicine, Institute of Psychiatry, London, UK. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond). 2005 Jan;55(1):20-31. AIM: To perform a systematic review of studies describing the prognosis of chronic fatigue (CF) and chronic fatigue syndrome (CFS) and to identify occupational outcomes from such studies. METHOD: A literature search was used to identify all studies describing the clinical follow-up of patients following a diagnosis of CF or CFS. The prognosis is described in terms of the proportion of individuals improved during the period of follow-up. Return to work, other medical illnesses and death as outcomes are also considered, as are variables which may influence prognosis. RESULTS: Twenty-eight articles met the inclusion criteria and, for the 14 studies of subjects meeting operational criteria for CFS, the median full recovery rate was 5% (range 0-31%) and the median proportion of patients who improved during follow-up was 39.5% (range 8-63%). Less fatigue severity at baseline, a sense of control over symptoms and not attributing illness to a physical cause were all associated with a good outcome. Return to work at follow-up ranged from 8 to 30% in the three studies that considered this outcome. CONCLUSIONS: Full recovery from untreated CFS is rare. The prognosis for an improvement in symptoms is less gloomy. This review looks at the course of CF/CFS without systematic intervention. However, there is increasing evidence for the effectiveness of cognitive behavioural and graded exercise therapies. Medical retirement should be postponed until a trial of
  8. 8. ME Research UK — Database of Research Publications 2005 such treatment has been given. Cairns V, Godwin J. Consultant Statistician, Am Rothlauf 9, 61476 Kronberg, Germany. Post-Lyme borreliosis syndrome: a meta- analysis of reported symptoms. Int J Epidemiol. 2005 Jul 22; [Epub ahead of print] BACKGROUND: This meta-analysis compares the prevalence of fatigue, musculoskeletal pain, and neurocognitive difficulties in patients who have had Lyme borreliosis (LB) and control subjects without LB. METHODS: Titles and abstracts in PubMed were reviewed for studies with data on the symptoms listed above that compared patients who had had LB with controls from the general population. Five studies with 504 patients and 530 controls were included in the meta-analysis. RESULTS: The prevalence of symptoms was significantly higher in the LB patients, with P-values between <0.00001 and 0.007 for 8 of the 10 symptoms in the three categories listed above. The higher prevalence of certain neurocognitive symptoms but not others, in the same pattern as reported in the literature, is further confirmation of this syndrome. The pattern of symptoms appears to be different from that seen in fibromyalgia, depression, and chronic fatigue syndrome. CONCLUSIONS: This meta-analysis provides strong evidence that some patients with LB have fatigue, musculoskeletal pain, and neurocognitive difficulties that may last for years despite antibiotic treatment. Cairns V, Godwin J. Clinical Trial Service Unit, University of Oxford, UK. Post-Lyme borreliosis syndrome: a meta- analysis of reported symptoms. Int J Epidemiol. 2005 Dec;34(6):1340-5. Epub 2005 Jul 22. BACKGROUND: This meta-analysis compares the prevalence of fatigue, musculoskeletal pain, and neurocognitive difficulties in patients who have had Lyme borreliosis (LB) and control subjects without LB. METHODS: Titles and abstracts in PubMed were reviewed for studies with data on the symptoms listed above that compared patients who had had LB with controls from the general population. Five studies with 504 patients and 530 controls were included in the meta-analysis. RESULTS: The prevalence of symptoms was significantly higher in the LB patients, with P-values between <0.00001 and 0.007 for 8 of the 10 symptoms in the three categories listed above. The higher prevalence of certain neurocognitive symptoms but not others, in the same pattern as reported in the literature, is further confirmation of this syndrome. The pattern of symptoms appears to be different from that seen in fibromyalgia, depression, and chronic fatigue syndrome. CONCLUSIONS: This meta-analysis provides strong evidence that some patients with LB have fatigue, musculoskeletal pain, and neurocognitive difficulties that may last for years despite antibiotic treatment. Casado B, Zanone C, Annovazzi L, Iadarola P, Whalen G, Baraniuk JN. Department of Biochemistry A. Castellani, University of Pavia, V.le Taramelli 3/B, 27100 Pavia, Italy. bc48@georgetown. edu Urinary electrophoretic profiles from chronic fatigue syndrome and chronic fatigue syndrome/fibromya lgia patients: a pilot study for achieving their normalization. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jan 5;814(1):43-51. Aim of our study was to determine if there were distinct, disease-related patterns of urinary analytes in chronic fatigue syndrome (CFS) and chronic fatigue syndrome/fibromyalgia (CFS/FM) compared to normal controls (NC). Urine was collected from these subjects for two consecutive 24 h periods and aliquots were submitted to micellar electrokinetic chromatography (MEKC). To compensate for the differences in peak migration times, these were normalized from the 35 min duration of run to a 100- point scale, and each peak was assigned its normalized time measure. Peak heights were also normalized by dividing the mAU by that of the internal standard (creatinine) and multiplying by 100. MEKC with normalization for peak height and migration time generated comparable results within each of the patient groups. CFS/FM and CFS had significant differences in peaks compared to NC that may be of significance as biomarkers of illnesses. Cervera C, Alegre J, Ruiz E, Vasquez A, Armadans L, Garcia-Quintana AM, Aleman C, de Sevilla TF Employment Status and Financial Repercussions in 60 Patients with Chronic Fatigue Syndrome in Spain: Utility of Journal of Chronic Fatigue Syndrome 2005 12 (2): 35-45 Chronic fatigue syndrome (CFS) is a disabling disorder with implications in employment status. We enrolled 60 patients who fulfilled the CDC diagnostic criteria of Holmes and those of Fukuda. All patients underwent a protocol involving a structured questionnaire to record diagnostic criteria items, clinical features of fatigue, social features and associated symptoms; application of the Fatigue Impact Scale (FIS); an employment repercussion questionnaire; and information on evolution of the symptoms. Statistical comparisons were performed with the Mann-Whitney U test and correlations with the Spearman test. A close correlation was found between work inactivity and higher scores in the FIS cognitive dimension. Patient age and duration of symptoms also correlated with high cognitive
  9. 9. ME Research UK — Database of Research Publications 2005 the Fatigue Impact Scale scores. Chronic fatigue syndrome patients report a considerable decrease in quality of life, and most of them have work limitations, particularly those with poor overall FIS scores and cognitive function scores. Chalmers RA, Jones MG, Goodwin CS, Amjad S. St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. CFSUM1 and CFSUM2 in urine from patients with chronic fatigue syndrome are methodological artefacts. Clin Chim Acta. 2005 Aug 8; [Epub ahead of print] McGregor et al. reported increased levels of an unidentified urinary compound (CFSUM1) in patients with chronic fatigue syndrome (CFS), with reduced excretion of another unidentified compound (CFSUM2), and suggested the possibility of chemical or metabolic 'markers' for CFS. The identity of CFSUM1 as reported was erroneous and the identities of these compounds have remained unknown until now. Urine samples were obtained from 30 patients with ME/CFS, 30 age- and sex-matched healthy controls, 20 control patients with depression and 22 control patients with rheumatoid arthritis. Samples were prepared using the published methods of McGregor et al. to produce heptafluorobutyryl- isobutyl derivatives of urinary metabolites. Alternative preparations utilised isopropyl, n-butyl and trifluoroacetyl derivatives. These were separated and identified using gas chromatography-mass spectrometry. CFSUM2 was identified as being partially derivatised [isobutyl ester-mono- heptafluorobutyryl (HFB)] serine. CFSUM1 was identified as partially derivatised pyroglutamic acid, being the isobutyl ester without formation of a HFB derivative. Both CFSUM1 and CFSUM2 are artefacts of the sample preparation procedure and previously reported quantitative abnormalities of CFSUM1 and CFSUM2 in urine from patients with ME/CFS are also artefactual. Pyroglutamic acid may be of primarily dietary origin. The methods used cannot provide reliable qualitative or quantitative data on urinary metabolites. No clinical or biochemical significance can be drawn between these compounds in ME/CFS or any other clinical conditions. Chaudhuri A. Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: data are insufficient and conclusion inappropriate. Comment on: BMJ. 2005 Jan 1;330(7481):14. BMJ. 2005 Apr 2;330(7494):789- 90; author reply 790. Letter Chia JK. CEI Research Center, Torrance, CA 90505, USA. The role of enterovirus in chronic fatigue syndrome. J Clin Pathol. 2005 Nov;58(11):1126- 32. Two and a half decades after coining of the term chronic fatigue syndrome (CFS), the diagnosis of this illness is still symptom based and the aetiology remains elusive. Enteroviruses are well known causes of acute respiratory and gastrointestinal infections, with tropism for the central nervous system, muscles, and heart. Initial reports of chronic enteroviral infections causing debilitating symptoms in patients with CFS were met with skeptism, and had been largely forgotten for the past decade. Observations from in vitro experiments and from animal models clearly established a state of chronic persistence through the formation of double stranded RNA, similar to findings reported in muscle biopsies of patients with CFS. Recent evidence not only confirmed the earlier studies, but also clarified the pathogenic role of viral RNA through antiviral treatment. This review summarises the available experimental and clinical evidence that supports the role of enterovirus in chronic fatigue syndrome. Cho HJ, Hotopf M, Wessely S. Section of General Hospital The placebo response in the Psychosom Med. 2005 Mar- OBJECTIVE: The placebo response is conventionally asserted to be high in chronic fatigue syndrome (CFS) because of the latter's subjective nature and obscure pathogenesis, but no systematic review of
  10. 10. ME Research UK — Database of Research Publications 2005 Psychiatry, Institute of Psychiatry, King's College London, United Kingdom. k treatment of chronic fatigue syndrome: a systematic review and meta-analysis. Apr;67(2):301-13. placebo responses has been undertaken. We report such a study. Patient expectation is known to be important in the placebo response. It is also known that CFS patients attending specialist clinics often have strong physical attributions regarding causation and hence skepticism about psychological or psychiatric interventions. If so, the placebo response in CFS may be influenced by the type of intervention according to its perceived rationale. We aimed to estimate the summary placebo response in clinical trials of CFS and to determine whether intervention type influences the placebo response in CFS. METHODS: We searched Medline, Embase, Cochrane Library, PsychInfo, and the references of the identified articles, and contacted experts for controlled trials (randomized or nonrandomized) of any intervention on CFS patients reporting the placebo response as a clinical improvement in physical or general outcomes. Data were extracted from the articles and validity assessment conducted by one reviewer and checked by a second. Meta-analysis and metaregression were performed. RESULTS: The pooled placebo response was 19.6% (95% confidence interval, 15.4-23.7), lower than predicted and lower than in some other medical conditions. The meta-regression revealed that intervention type significantly contributed to the heterogeneity of placebo response (p = .03). CONCLUSION: In contrast with the conventional wisdom, the placebo response in CFS is low. Psychological-psychiatric interventions were shown to have a lower placebo response, perhaps linked to patient expectations. Cho HJ, Wessely S. Chronic fatigue syndrome: an overview. Rev Bras Psiquiatr. 2005 Sep;27(3):174-5. Epub 2005 Oct 4. Editorial Cho HJ, Wessely S. Chronic fatigue syndrome: an overview. Rev Bras Psiquiatr. 2005 Sep;27(3):174-5. Epub 2005 Oct 4. Editorial Christie D, Wilson C. University College and Middlesex Hopsitals, London, UK. deborah.christie@ CBT in paediatric and adolescent health settings: a review of practice- based evidence. Pediatr Rehabil. 2005 Oct- Dec;8(4):241-7. Cognitive Behavioural therapy (CBT) has strong theoretical underpinnings that facilitate the systematic evaluation of outcomes and process of change adults. CBT has been extensively adapted for use with children and young people with session content and method of delivery modified to acknowledge developmental stage and ability. Current approaches emphasise the psychological management of the impact of symptoms of particular types of physical health difficulties and prevention of the development of psychological difficulties, as well as in the alleviation of procedurally related stress. The need for collaboration with families and other parts of a child's network is particularly relevant in the paediatric setting. This review describes what we have found helpful in our work and provides a road map of where to go to find out more about how to do more. General CBT approaches are described as well as examples of how CBT has been used specifically for procedural distress, diabetes, sickle cell disease, chronic pain and chronic fatigue. Chrousos GP, Kaltsas G. Athens University, Athens, Greece and National Institutes of Health, Bethesda, MD, USA. chrousge@med.uo Post-SARS sickness syndrome manifestations and endocrinopathy: how, why, and so what? Clin Endocrinol (Oxf). 2005 Oct;63(4):363-5. Comment on: Clin Endocrinol (Oxf). 2005 Aug;63(2):197- 202. Comment Cleare AJ, Messa Section of Brain 5-HT1A Biol Psychiatry. BACKGROUND: Research from neuroendocrine challenge and other indirect studies has suggested
  11. 11. ME Research UK — Database of Research Publications 2005 C, Rabiner EA, Grasby PM. Neurobiology of Mood Disorders, Division of Psychological Medicine, Institute of Psychiatry and Guy-s, King-s and St. Thomas- School of Medicine, London, United Kingdom. a.cleare@iop.kcl.a receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY- 100635. 2005 Feb 1;57(3):239-46. increased central 5-HT function in chronic fatigue syndrome (CFS) and increased 5-HT1A receptor sensitivity. We assessed brain 5-HT1A receptor binding potential directly using the specific radioligand [11C]WAY-100635 and positron emission tomography (PET). METHODS: We selected 10 patients from a tertiary referral clinic who fulfilled the CDC consensus criteria for CFS. To assemble a homogenous group and avoid confounding effects, we enrolled only subjects who were completely medication-free and did not have current comorbid psychiatric illness. We also scanned 10 healthy control subjects. RESULTS: There was a widespread reduction in 5-HT1A receptor binding potential in CFS relative to control subjects. This was particularly marked in the hippocampus bilaterally, where a 23% reduction was observed. CONCLUSIONS: There is evidence of decreased 5- HT1A receptor number or affinity in CFS. This may be a primary feature of CFS, related to the underlying pathophysiology, or a finding secondary to other processes, such as previous depression, other biological changes or the behavioral consequences of CFS. Cook DB, Nagelkirk PR, Peckerman A, Poluri A, Mores J, Natelson BH. University of Wisconsin- Madison, Department of Kinesiology, USA. cookdb@njneurom Exercise and cognitive performance in chronic fatigue syndrome. Med Sci Sports Exerc. 2005 Sep;37(9):1460-7. PURPOSE: To determine the effect of submaximal steady-state exercise on cognitive performance in patients with chronic fatigue syndrome (CFS) alone, CFS with comorbid fibromyalgia FM (CFS + FM), and sedentary healthy controls (CON). METHODS: Twenty CFS-only patients, 19 CFS + FM, and 26 CON completed a battery of cognitive tests designed to assess speed of information processing, variability, and efficiency. Tests were performed at baseline, immediately before, and twice following 25 min of either cycle ergometry set at 40% of peak oxygen capacity or quiet rest. RESULTS: There were no group differences in average percentage of peak oxygen consumption during exercise (CFS = 45%; CFS + FM = 47%; Control = 43%: P = 0.2). There were no significant effects of acute exercise on cognitive performance for any group. At baseline, one-way ANOVA indicated that CFS patients displayed deficits in speed of processing, performance variability, and task efficiency during several cognitive tests compared with healthy controls. However, the CFS + FM patients were not different than controls. Repeated measures ANOVA indicated that across all tests (pre- and postexercise) CFS, but not CFS + FM, were significantly less consistent (F2,59 = 3.7, P = 0.03) and less efficient (F2,59 = 4.6, P = 0.01) than controls. CONCLUSION: CFS patients without comorbid FM exhibit subtle cognitive deficits in terms of speed, consistency, and efficiency that are not improved or exacerbated by light exercise. Importantly, our data suggest that CFS + FM patients do not exhibit cognitive deficits either pre- or postexercise. These results highlight the importance of disease heterogeneity in studies determining acute exercise and cognitive function in CFS. Covelli V, Passeri ME, Leogrande D, Jirillo E, Amati L. Division of Neurology, Polyclinic Hospital, Bari Italy. Drug targets in stress-related disorders. Curr Med Chem. 2005;12(15):1801- 9. Nervous and immune systems mutually cooperate via release of mediators of both neurological and immunological derivation. Adrenocorticotropin hormone (ACTH) is a product of the hypothalamus- pituitary adrenal axis (HPAA) which stimulates secretion of corticosteroids from adrenals. In turn, corticosteroids modulate the immune response in virtue of their anti-inflammatory activity. On the other hand, catecholamines, products of the sympathetic nervous system (SNS), regulate immune function by acting on specific beta-adrenergic receptors. Conversely, cytokines released by monocytes/macrophages and lymphocytes, upon antigenic stimulation, are able to cross the blood- brain-barrier, thus modulating nervous functions (e.g., thermoregulation, sleep, and appetite). However, cytokines are locally produced in the brain, especially in the hypothalamus, thus contributing to the development of anorexic, pyrogenic, somnogenic and behavioural effects. Besides pathogens and/or their products, the so-called stressors are able to activate both HPAA and SNS, thus influencing immune responses. In this respect, many studies conducted in medical students taking exams have evidenced an array of stress-induced immune alterations. Phobic disorders and migraine
  12. 12. ME Research UK — Database of Research Publications 2005 without aura (MWA) represent examples of stress-related disorders in which phagocytic immune deficits, endotoxemia and exaggerated levels of proinflammatory cytokines [Tumor Necrosis Factor- alpha (TNF- alpha), and interleukin- 1 beta] have been detected. Quite interestingly, administration of a thymic hormone could ameliorate clinical symptoms in phobic patients. In MWA patients, a beta- blocker, propranolol, could mitigate migraine, whose cessation coincided with a drop of TNF-alpha serum concentration. In phobic disorders and in MWA, benzodiazepines are very often administered and, in this respect, some of them, such as diazepam, inhibit immune functions, while others, e.g., alprazolam, enhance immune responses. Alprazolam could improve clinical symptoms in MWA patients. Chronic Fatigue Syndrome (CFS) is a disorder whose etiology and pathogenesis are still unknown. In this syndrome both abnormalities of nervous and immune systems have been reported. Despite many immune parameters evaluated in CFS no specific biomarkers of disease have been found. Our own data are in agreement with current literature in that we found decreased levels of serum (IFN)-gamma in these patients, thus indicating a predominance of T helper (h)1 response in CFS. Also leptin, a hormone which regulates food intake, fluctuates within normal ranges in CFS individuals. Quite interestingly, in depressed patients, used as controls, leptinaemia was more elevated than in CFS. Finally, in a series of recent therapeutic trials several immunomodulating agents have been used, such as staphypan Berna, lactic acid bacteria, kuibitang and intravenous immunoglobulin. In conclusion, it seems that major drug targets in stress-related disorders are immune cells in terms of inhibition of proinflammatory cytokines and modulation of Th responses. In particular, according to recent evidences, antidepressants seem to exert beneficial effects in experimental autoimmune neuritis in rats by decreasing IFN- beta release or augmenting NK activity in depressed patients. Crowhurst G. 25% Severe ME Group, Great Walsingham, Norfolk. gregcrowhurst@ya Supporting people with severe myalgic encephalomyelitis. Nurs Stand. 2005 Feb 2-8;19(21):38- 43. This article aims to raise nurses' awareness of myalgic encephalomyelitis (ME) also known as chronic fatigue syndrome (CFS). Key symptoms are presented along with possible service responses and treatment options. It emphasises that this condition is often misunderstood but that it can be serious and more research is needed to promote better understanding of the physical symptoms. Darbishire L, Seed P, Ridsdale L. Department of General Practice and Primary Care, Guy's, King's and St Thomas' School ol of Medicine, 5 Lambeth Walk, London, SE11 6SP, UK. uk Predictors of outcome following treatment for chronic fatigue. Br J Psychiatry. 2005 Apr;186:350- 1. We explored the role of baseline characteristics of 105 patients who presented with fatigue in primary care in determining outcome following either graded exercise or cognitive-behavioural therapy. Meeting the criteria for chronic fatigue syndrome was the most powerful predictor of poor outcome and this negative effect was enhanced by greater functional impairment or greater perceived negative consequences, but was not further enhanced by both. Davidson J. Department of Geography, Queen's University, Kingston, Ont., K7L 3N6, Canada. Contesting stigma and contested emotions: personal experience and public perception of specific phobias. Soc Sci Med. 2005 Nov;61(10):2155- 64. This paper draws on interviews with members of the United Kingdom National Phobics Society to explore the implications of the contested nature of specific phobias for their experience and perception. In common with other chronic and contested conditions such as Chronic Fatigue Syndrome, phobias are stigmatised and subjected to widespread judgmental attitudes in both medical and lay populations. In contrast, however, phobic experience is rarely characterised by difficulty in describing symptoms and obtaining a diagnosis: core fearful reaction to and avoidance of particular
  13. 13. ME Research UK — Database of Research Publications 2005 joyce.davidson@q objects is usually obvious and uncontested. The crucial difference is that phobias are constituted by emotions and behaviours considered irrational and inconsequential, and it is their (perceived absence of) significance that raises questions and eyebrows. In other words, what does it matter and who cares if you happen to be scared of snakes? Using phobics' own words as far as possible, the paper explores the processes through which phobic emotions are constructed as contested, and examines phobic means of managing experience and perception of these emotions. It reveals that many respondents are resourceful and resistant, continually renegotiating their positioning as irrational, incapable and emotionally weak. de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Meer JW, Toni I. F.C. Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, NL- 6500 HB Nijmegen, The Netherlands. floris.delange@fcd Gray matter volume reduction in the chronic fatigue syndrome. Neuroimage. 2005 Jul 1;26(3):777-81. Epub 2005 Apr 7. The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities. We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high- resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities. We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder. Di Giorgio A, Hudson M, Jerjes W, Cleare AJ. Department of Neurological and Psychiatric Services, University of Bari, Bari, Italy 24-hour pituitary and adrenal hormone profiles in chronic fatigue syndrome. Psychosom Med. 2005 May- Jun;67(3):433-40. OBJECTIVES: Disturbances of neuroendocrine function, particularly the hypothalamo-pituitary- adrenal (HPA) axis, have been implicated in the pathophysiology of chronic fatigue syndrome (CFS). However, few studies have attempted to measure blood levels of pituitary or adrenal hormones across a whole 24-hour period in CFS, and those that did so have used infrequent sampling periods. Our aim was to assess 24-hour pituitary and adrenal function using frequent blood sampling. METHODS: We recruited 15 medication-free patients with CFS without comorbid psychiatric disorder and 10 healthy control subjects. Blood samples were collected over 24 hours and assayed for cortisol, corticotropin (ACTH), growth hormone (GH), and prolactin (PRL) levels on an hourly basis during daytime hours (10 am to 10 pm) and every 15 minutes thereafter (10 pm to 10 am). RESULTS: Repeated-measures analyses of variance were undertaken using hormone levels averaged over 2-hour blocks to smooth curves by reducing the influence of sample timing relative to secretory burst. For ACTH, there was both a main effect of group, suggesting reduced mean ACTH secretion in patients with CFS over the whole monitoring period, and a group-by-time interaction, suggesting a differential pattern of ACTH release. Post hoc analysis showed reduced ACTH levels in CFS during the 8 am to 10 am period. In contrast, there were no significant abnormalities in the levels of cortisol, GH, and PRL in patients with CFS over the full cycle compared with control subjects. Cosinor analysis found no differences in the cortisol circadian rhythm parameters, but the ACTH rhythm did differ, patients with CFS showing an earlier acrophase. CONCLUSIONS: Patients with CFS demonstrated subtle alterations in HPA axis activity characterized by reduced ACTH over a full circadian cycle and reduced levels during the usual morning physiological peak ACTH secretion. This provides further evidence of subtle dysregulation of the HPA axis in CFS. Whether this dysregulation is a primary feature of the illness or instead represents a biologic effect secondary to having the illness itself remains unclear. Doljansky JT, The Institute for Working under Chronobiol Int. A 47-yr-old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe
  14. 14. ME Research UK — Database of Research Publications 2005 Kannety H, Dagan Y. Sleep and Fatigue Medicine, Chaim Sheba Health Center, Tel- Hashomer, Israel. Julia.Tamir@Sheb daylight intensity lamp: an occupational risk for developing circadian rhythm sleep disorder? 2005;22(3):597- 605. fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep-wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part-time position 7 yrs ago, because he was unable to maintain a regular full-time job schedule. A 10-day actigraphic record revealed an irregular sleep-wake pattern with extensive day-to-day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep-wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond-grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep-wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10-day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep-wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep-wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep- wake cycle and melancholy. Driver C. An under-active or over-active internal world? An exploration of parallel dynamics within psyche and soma, and the difficulty of internal regulation, in patients with Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. J Anal Psychol. 2005 Apr;50(2):155-73. This paper explores the dynamics brought into analytic work when there is a symmetric fusion between psyche and soma within the patient. It will consider how such a fusion may emerge from reverberations between physical constitution and a lack of maternal attunement, containment and reflective function. I will describe the work with a patient, Jane, who was diagnosed with Myalgic Encephalomyelitis (ME) during the course of her analysis. The dynamic of her physical symptoms within the analytic work, and the impact of her internal affects and internal 'objects' within the transference and countertransference, indicated a difficulty in finding an homeostatic balance resulting in overactivity and underactivity at both somatic and psychological levels. Using the clinical work with Jane this paper will also examine the interrelationship between mother-infant attachment, an inadequate internalized maternal reflective function, affect dysregulation, unconscious fusion, the lack of psyche-soma differentiation and the impact of the latter in relation to internal regulation systems, or lack of, in patients with Chronic Fatigue Syndrome (CFS) and Myalgic Encephalomyelitis (ME). I will draw on similar work carried out by Holland (1997), Simpson (1997) and Simpson et al. (1997). The paper will also employ the concept of the reflective function (Fonagy 2001; Knox 2003), and consider Matte-Blanco's (1999) concepts of generalization and unconscious symmetry in relation to the patient's internal world. I go on to consider how analysis provides a point outside the 'fusion' that can enable the 'deadlock' to be broken. Dumit J. Program in Science, Technology & Illnesses you have to fight to get: Facts as forces in Soc Sci Med. 2005 Aug 5; [Epub ahead of print] Chronic fatigue syndrome and multiple chemical sensitivity are two clusters of illnesses that are pervaded by medical, social and political uncertainty. This article examines how facts are talked about and experienced in struggles over these emergent, contested illnesses in the US. Based principally on
  15. 15. ME Research UK — Database of Research Publications 2005 Society, Massachusetts Institute of Technology, E51- 296D MIT, Cambridge, MA 02139-4307, USA. uncertain, emergent illnesses. a large archive of internet newsgroup postings, and also on fieldwork and on published debates, it finds that (1) sufferers describe their experiences of being denied healthcare and legitimacy through bureaucratic categories of exclusion as dependent upon their lack of biological facts; (2) institutions manage these exclusions rhetorically through exploiting the open-endedness of science to deny efficacy to new facts; (3) collective patient action responds by archiving the systematic nature of these exclusions and developing counter-tactics. The result is the maintenance of these very expensive struggles for all involved. Durlach J, Pages N, Bac P, Bara M, Guiet-Bara A. SDRM, Universite Pierre et Marie Curie, 75252 Paris Cedex 05, France. jean.durlach@wan Magnesium depletion with hypo- or hyper- function of the biological clock may be involved in chronopathological forms of asthma. Magnes Res. 2005 Mar;18(1):19-34. Asthma is a chronic, inflammatory disorder of the airways leading to airflow limitation. Its worldwide rise, mainly in developed countries, is a matter of concern. Nocturnal asthma (NA) frequently occurs and concerns two thirds of asthmatics. But, it remains controversial whether NA is a distinct entity or is a manifestation of more severe asthma. Generally, it is considered as an exacerbation of the underlying pathology. The pathological mechanisms most likely involve endogenous circadian rhythms with pathological consequences on both respiratory inflammation and hyperresponsiveness. A decrease in blood and tissue magnesium levels is frequently reported in asthma and often testifies to a true magnesium depletion. The link with magnesium status and chronobiology are well established. The quality of magnesium status directly influences the Biological Clock (BC) function, represented by the suprachiasmatic nuclei and the pineal gland. Conversely, BC dysrythmias influence the magnesium status. Two types of magnesium deficits must be clearly distinguished: deficiency corresponding to an insufficient intake which can be corrected through mere nutritional Mg supplementation and depletion due to a dysregulation of the magnesium status which cannot be corrected through nutritional supplementation only, but requires the more or less specific correction of the dysregulation mechanisms. Both in clinical and in animal experiments, the dysregulation mechanisms of magnesium depletion associate a reduced magnesium intake with various types of stress including biological clock dysrhythmias. The differenciation between Mg depletion forms with hyperfunction of BC (HBC) and forms with hypofunction of BC (hBC) is seminal and the main biological marker is melatonin (MT) production alteration. We hypothesize that magnesium depletion with HBC or hBC may be involved in chronopathological forms of asthma. Nocturnal asthma would be linked to HBC, represented by an increase in MT levels. The corresponding clinical forms associate diverse expressions of nervous hypoexcitability such as depression, cluster headaches, dyssomnia, mainly advanced sleep phase syndrome, some clinical forms of chronic fatigue syndrome and of fibromyalgia. The main comorbidities are depression and/or asthenia. They take place during the night or the "bad" seasons (autumn and winter) when sunshine is at a minimum. The corresponding chronopathological therapy relies on bright light phototherapy sometimes with additional psychoanaleptics. Conversely, asthma forms linked to hBC are less frequently studied as a whole and present a decrease in MT levels. They associate various signs of nervous hyperexcitability such as anxiety, diurnal cephalalgia (mainly migraine), dyssomnia, mainly delayed sleep phase syndrome, and some clinical forms of chronic fatigue syndrome and of fibromyalgia. The treatment relies on diverse forms of "darkness therapy", possibly with the help of some psycholeptics. Finally, the treatment of asthma involves the maintenance of a standard dosing schedule of anti-asthma drugs, a balanced magnesium intake and the appropriate treatment of the chronopathological disorders. Ehrlich GE. Silicone breast implants. Comment on: J Rheumatol. 2004 J Rheumatol. 2005 Jun;32(6):1173-4; author reply 1174. Letter
  16. 16. ME Research UK — Database of Research Publications 2005 May;31(5):1015; author reply 1015- 6. Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, Toomey R, Jackson LW, Alpern R, Parks BJ, Klimas N, Hall C, Pak HS, Hunter J, Karlinsky J, Battistone MJ, Lyons MJ; Gulf War Study Participating Investigators. Veterans Affairs Medical Center, Washington University School of Medicine, St. Louis, Missouri 63106, USA. .gov Gulf War veterans' health: medical evaluation of a U.S. cohort. Ann Intern Med. 2005 Jun 7;142(11):881-90. BACKGROUND: United States military personnel reported various symptoms after deployment to the Persian Gulf during the 1991 Gulf War. However, the symptoms' long-term prevalence and association with deployment remain controversial. OBJECTIVE: To assess and compare the prevalence of selected medical conditions in a national cohort of deployed and nondeployed Gulf War veterans who were evaluated by direct medical and teledermatologic examinations. DESIGN: A cross- sectional prevalence study performed 10 years after the 1991 Gulf War. SETTING: Veterans were examined at 1 of 16 Veterans Affairs medical centers. PARTICIPANTS: Deployed (n = 1061) and nondeployed (n = 1128) veterans of the 1991 Gulf War. MEASUREMENTS: Primary outcome measures included fibromyalgia, the chronic fatigue syndrome, dermatologic conditions, dyspepsia, physical health-related quality of life (Short Form-36 [SF-36]), hypertension, obstructive lung disease, arthralgias, and peripheral neuropathy. RESULTS: Of 12 conditions, only 4 conditions were more prevalent among deployed than nondeployed veterans: fibromyalgia (deployed, 2.0%; nondeployed, 1.2%; odds ratio, 2.32 [95% CI, 1.02 to 5.27]); the chronic fatigue syndrome (deployed, 1.6%; nondeployed 0.1%; odds ratio, 40.6 [CI, 10.2 to 161]); dermatologic conditions (deployed, 34.6%; nondeployed, 26.8%; odds ratio, 1.38 [CI, 1.06 to 1.80]), and dyspepsia (deployed, 9.1%; nondeployed, 6.0%; odds ratio, 1.87 [CI, 1.16 to 2.99]). The mean physical component summary score of the SF-36 for deployed and nondeployed veterans was 49.3 and 50.8, respectively. LIMITATIONS: Relatively low participation rates introduce potential participation bias, and deployment-related illnesses that resolved before the research examination could not, by design, be detected. CONCLUSIONS: Ten years after the Gulf War, the physical health of deployed and nondeployed veterans is similar. However, Gulf War deployment is associated with an increased risk for fibromyalgia, the chronic fatigue syndrome, skin conditions, dyspepsia, and a clinically insignificant decrease in the SF-36 physical component score. Elena Garralda M, Chalder T. Imperial College, London, UK. egarralda@imperia Practitioner review: chronic fatigue syndrome in childhood. J Child Psychol Psychiatry. 2005 Nov;46(11):1143- 51. BACKGROUND: Chronic fatigue syndrome (CFS) is being increasingly recognized in children and adolescents. Yet comparatively little attention has been given in the literature to management. METHODS: Description of the main features of the disorder, precipitating and maintaining factors and diagnostic assessment. Outline of different views on the nature and treatment of CFS in childhood. Description of a rehabilitation program based on cognitive behavior therapy and graded activity. RESULTS: Using adult research criteria, CFS can be diagnosed in children and adolescents. In its severe form it is often triggered by infectious illness episodes. It is commonly associated with mood disorders in the child and with mental distress and high levels of emotional involvement in parents. A number of patient support groups hold the view that CFS is a medical disorder, contest a psychiatric contribution and advocate 'pacing' as an approach to rehabilitation which includes avoiding activities. To date there is no empirical evidence for the efficacy of this approach. Research in adults, open and clinical reports in children support the use of graded activity and family cognitive behavior therapy. The main aim is to enable children, with the help of their family, to carry out their own rehabilitation with some support and guidance from a health professional. Engaging the child and family in treatment and forming a therapeutic alliance is a continual process and a crucial aspect of management, as many families view the condition as a medical disorder and are initially ambivalent towards this approach. CONCLUSIONS: There is controversy about the nature and management of CFS in childhood but a rehabilitation program based on family cognitive behavior
  17. 17. ME Research UK — Database of Research Publications 2005 therapy can be implemented and seems to hold most promise in the management of children with CFS. Family engagement is a crucial aspect of management. Evengard B, Jacks A, Pedersen NL, Sullivan PF. Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. The epidemiology of chronic fatigue in the Swedish Twin Registry. Psychol Med. 2005 Sep;35(9):1317-26. BACKGROUND: Chronic fatigue syndrome (CFS) remains an idiopathic and controversial entity. METHOD: We screened 31405 individual members of the Swedish Twin Registry (aged 42-64 years) for the symptoms of fatiguing illness via a telephone questionnaire. We refined self-reported symptoms via data from several national registries and from physician review of all available medical records in order to approximate closely the dominant case definition of CFS. FINDINGS: The 6- month prevalence of CFS-like illness was 2.36% (95% CI 2.19-2.53) and was markedly higher in women than men, odds ratio 3.92 (95% CI 3.24-4.72) with no significant association with age or years of education. There was a highly significant association with occupation that disappeared after accounting for gender. INTERPRETATION: CFS-like illness may be more common that previously acknowledged. There is a marked increase in risk by gender. Previous reports that CFS is more prevalent in individuals in certain occupational categories were not confirmed and may have been due to confounding by gender. Fernandez-Sola J, Lluis Padierna M, Nogue Xarau S, Munne Mas P. Servicio de Medicina Interna. Unidad Multidisciplinar de Fatiga Cronica. Hospital Clinic de Barcelona. IDIBAPS. Universitat de Barcelona. Barcelona. Spain. [Chronic fatigue syndrome and multiple chemical hypersensitivity after insecticide exposition.] [Article in Spanish] Med Clin (Barc). 2005 Apr 2;124(12):451-3. Background and objective: Chronic Fatigue Syndrome (CFS) and Multiple Chemical Sensitivity (MCS) are well-defined illnesses that may appear after some toxic exposures. Patients and method: We report a consecutive series of 26 patients who developed CFS after exposure to insecticide products. It was associated with MCS in a third of cases. RESULTS: Toxic exposure was of labour origin after returning to usual work place after a process of fumigation. In 42% of cases there was no fulfilment of fumigation safety rules. The majority of patients were mean-aged women who developed an acute upper airway inflammatory syndrome, without muscarinic or nicotinic manifestations, followed by digestive syndrome, neurocognitive, fibromyalgic and chronic fatigue manifestations. The course of disease was shorter than 1 year in 5 cases (19%), longer than 1 year in 15(58%), and disabling in 6 cases (23%). CONCLUSIONS: Due to the possible prevention of this toxic exposure, it is very important to carefully follow measures of environment isolation and ventilation after insecticide use in order to avoid the development of these diseases. Ferre Ybarz L, Cardona Dahl V, Cadahia Garcia A, Ruiz E, Vazquez A, Fernandez de Sevilla T, Alegre Martin J. Hospital Vall d'Hebron, Barcelona, Spain. laiafy@vodafone.e s [Prevalence of atopy in chronic fatigue syndrome] [Article in Spanish] Allergol Immunopathol (Madr). 2005 Jan- Feb;33(1):42-7. BACKGROUND: Several hypotheses have been postulated to explain the etiopathogenesis of chronic fatigue syndrome (CFS). Among these, immunologic dysfunction has been proposed. Up to 30 % of these patients have a history of allergic disease. The aim of this study was to investigate whether allergic sensitization is higher in patients with CFS than in the general population. METHODS: Twenty-five patients with CFS and 20 controls were evaluated. A clinical history for allergy was taken and immediate hypersensitivity tests were performed. RESULTS: Twelve patients (48 %) and eight controls (40 %) had a family history of atopy. Personal histories of atopy were as follows: rhinoconjunctivitis: 12 patients (48 %), seven controls (35 %); asthma: five patients (20 %), two controls (10 %); food allergy: three patients (12 %); atopic dermatitis: two patients; contact dermatitis: two patients. No statistically significant differences were found between the groups in any of the variables (p > 0.05). In the CSF group, 3.4 % (15/441) of the inhalant prick tests were positive, and in the control group 3.8 % (16/420) were positive. None of the tests for hypersensitivity to food or latex were positive. CONCLUSIONS: In our study atopy was not more prevalent in patients with CFS than in healthy controls, although the CSF group tended to report more respiratory symptoms and drug allergies. Fowler T, Duthie P, Thapar A, Farmer A. Department of Psychological Medicine, Wales The definition of disabling fatigue in children and BMC Fam Pract. 2005 Aug 9;6:33. BACKGROUND: Disabling fatigue is the main illness related reason for prolonged absence from school. Although there are accepted criteria for diagnosing chronic fatigue in adults, it remains uncertain as to how best to define disabling fatigue and Chronic Fatigue Syndrome (CFS) in children
  18. 18. ME Research UK — Database of Research Publications 2005 College of Medicine, Cardiff University, UK. fowlerta@cardiff.a adolescents. and adolescents. In this population-based study, the aim was to identify children who had experienced an episode of disabling fatigue and examine the clinical and demographic differences between those individuals who fulfilled a narrow definition of disabling fatigue and those who fulfilled broader definitions of disabling fatigue. METHODS: Participants (aged 8-17 years) were identified from a population-based twin register. Parent report was used to identify children who had ever experienced a period of disabling fatigue. Standardised telephone interviews were then conducted with the parents of these affected children. Data on clinical and demographic characteristics, including age of onset, gender, days per week affected, hours per day spent resting, absence from school, comorbidity with depression and a global measure of impairment due to the fatigue, were examined. A narrow definition was defined as a minimum of 6 months disabling fatigue plus at least 4 associated symptoms, which is comparable to the operational criteria for CFS in adults. Broader definitions included those with at least 3 months of disabling fatigue and 4 or more of the associated symptoms and those with simply a minimum of 3 months of disabling fatigue. Groups were mutually exclusive. RESULTS: Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were completed on 99 of the 129 participants (77%) who had experienced fatigue. There were no significant differences in demographic and clinical characteristics or levels of impairment between those who fulfilled the narrower definition and those who fulfilled the broader definitions. The only exception was the reported number of days per week that the child was affected by the fatigue. All groups demonstrated evidence of substantial impairment associated with the fatigue. CONCLUSION: Children and adolescents who do not fulfil the current narrow definition of CFS but do suffer from disabling fatigue show comparable and substantial impairment. In primary care settings, a broader definition of disabling fatigue would improve the identification of impaired children and adolescents who require support. Fremont M, El Bakkouri K, Vaeyens F, Herst CV, De Meirleir K, Englebienne P. RED Laboratories, Pontbeek 61, B- 1731 Zellik, Belgium. 2',5'- Oligoadenylate size is critical to protect RNase L against proteolytic cleavage in chronic fatigue syndrome. Exp Mol Pathol. 2005 Jun;78(3):239-46. Epub 2005 Mar 2. A dysregulation in the 2',5'-oligoadenylate (2-5A)-dependent RNase L antiviral pathway has been detected in peripheral blood mononuclear cells (PBMC) of chronic fatigue syndrome (CFS) patients, which is characterized by upregulated 2-5A synthetase and RNase L activities, as well as by the presence of a low molecular weight (LMW) 2-5A-binding protein of 37-kDa related to RNase L. This truncated protein has been shown to originate from proteolytic cleavage of the native 83-kDa RNase L by m-calpain and human leukocyte elastase (HLE). We investigated the possible role of 2-5A oligomers in the proteolytic action toward the endonuclease and show that incubation of CFS PBMC extracts with 2-5A trimer and tetramer, but not with the dimer, results in a significant protection of the native 83-kDa RNase L against cleavage by endogenous and purified proteases. Similar results are obtained with a purified recombinant RNase L. An analysis of the size of 2-5A oligomers produced by the catalytic activity of the 2-5A synthetase present in PBMC extracts further shows that samples containing the 37-kDa RNase L preferentially produce 2-5A dimers instead of higher oligomers. Taken together, our results indicate that homodimerization of RNase L by 2-5A oligomers higher than the dimer prevents its cleavage by proteolytic enzymes. The presence of the truncated 37-kDa RNase L in PBMC extracts is therefore likely to result, not only from the abnormal activation of inflammatory proteases, but also from a dysregulation in 2-5A synthetase induction or activation towards the preferential production of 2-5A dimers. Fremont M, Vaeyens F, Herst CV, De Meirleir K, Englebienne P, 37-Kilodalton/83- Kilodalton RNase L Isoform Ratio in Peripheral Blood Clin Diagn Lab Immunol. 2005 Oct;12(10):1259- 60.
  19. 19. ME Research UK — Database of Research Publications 2005 Tiev KP, Cabane J, Lebleu B. e. Mononuclear Cells: Analytical Performance and Relevance for Chronic Fatigue Syndrome. Fremont M, Vaeyens F, Herst CV, De Meirleir K, Englebienne P. 37-Kilodalton/83- kilodalton RNase L isoform ratio in peripheral blood mononuclear cells: analytical performance and relevance for chronic fatigue syndrome. Clin Diagn Lab Immunol. 2005 Oct;12(10):1259- 60; author reply 1260. Comment on: Clin Diagn Lab Immunol. 2003 Mar;10(2):315-6. Comment Letter Friedberg F, Leung DW, Quick J. Department of Psychiatry, Stony Brook University, Stony Brook, New York 11794-8790, USA. fred.friedberg@sto Do support groups help people with chronic fatigue syndrome and fibromyalgia? A comparison of active and inactive members. J Rheumatol. 2005 Dec;32(12):2416- 20. OBJECTIVE: To examine the benefits and problems of a chronic fatigue syndrome (CFS) and fibromyalgia (FM) support organization as reported by its participants. METHODS: Active members (n = 32) and inactive members or dropouts (n = 135) of a regional support organization for people with CFS and FM completed a 26 item questionnaire by telephone interview or by self-completion and postal return. RESULTS: The most frequently endorsed benefits of membership were illness legitimization (67.8%), finding out helpful new information (66.4%), and feeling understood by others (62.2%). Lower frequency endorsements were given to: helped to find (35.0%) or deal with (38.5%) doctors, and helped to improve my illness (36.4%). The most frequently reported reasons for dropping out were inconvenient location (37.8%) or time (37.0%), too much negative talk or complaining (33.3%), too sick to attend (28.8%), and illness or coping improvement (29.6% each). The active- member group showed significantly higher (p < 0.04) symptom severity scores and less illness improvement (p < 0.01) in comparison to the inactive/dropout group. CONCLUSION: This cross- sectional study suggests that support groups for CFS are viewed as helpful by participants on a number of illness related issues. On the other hand, active members reported greater symptom severity and less illness improvement than inactive members or dropouts. Fries E, Hesse J, Hellhammer J, Hellhammer DH. Department for Psychobiology, University of Trier, Johanniterufer 15, 54290 Trier, Germany. A new view on hypocortisolism. Psychoneuroendocr inology. 2005 Nov;30(10):1010- 6. Low cortisol levels have been observed in patients with different stress-related disorders such as chronic fatigue syndrome, fibromyalgia, and post-traumatic stress disorder. Data suggest that these disorders are characterized by a symptom triad of enhanced stress sensitivity, pain, and fatigue. This overview will present data on the development, mechanisms and consequences of hypocortisolism on different bodily systems. We propose that the phenomenon of hypocortisolism may occur after a prolonged period of hyperactivity of the hypothalamic-pituitary-adrenal axis due to chronic stress as illustrated in an animal model. Further evidence suggests that despite symptoms such as pain, fatigue and high stress sensitivity, hypocortisolism may also have beneficial effects on the organism. This assumption will be underlined by some studies suggesting protective effects of hypocortisolism for the individual. Frissora CL, Koch KL. Department of Medicine, The Weill Medical Symptom overlap and comorbidity of irritable bowel Curr Gastroenterol Rep. 2005 Aug;7(4):264-71. Irritable bowel syndrome (IBS) is one of several highly prevalent, multi-symptom gastrointestinal motility disorders that have a wide clinical spectrum and are associated with symptoms of gastrointestinal dysmotility and visceral hypersensitivity. Symptom overlap and comorbidity between
  20. 20. ME Research UK — Database of Research Publications 2005 College of Cornell University, 520 E. 70th Street, Suite J-314, New York, NY 10021, USA. cfrissor@med.corn syndrome with other conditions. IBS and other gastrointestinal motility disorders (eg, chronic constipation, functional dyspepsia, gastroesophageal reflux disease), with gastrointestinal disorders that are not related to motility (eg, celiac disease, lactose intolerance), and with somatic conditions (eg, fibromyalgia, chronic fatigue syndrome), are frequent. The clinical associations and pathophysiologic links between IBS and these disorders continue to be explored. This review discusses overlapping symptoms and comorbidity of IBS with select gastrointestinal and non-gastrointestinal disorders and attempts to identify commonalities among these conditions. Furberg H, Olarte M, Afari N, Goldberg J, Buchwald D, Sullivan PF. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA. The prevalence of self-reported chronic fatigue in a U.S. twin registry. J Psychosom Res. 2005 Nov;59(5):283-90. OBJECTIVE: To investigate the prevalence and correlates of various definitions of self-reported lifetime fatiguing illness in a U.S. twin registry. METHODS: Data from 4591 female and male twins from the population-based Mid-Atlantic Twin Registry were available for this study. Variables representing different definitions of lifetime fatiguing illness and personal characteristics were obtained through questionnaires. Odds ratios and 95% confidence intervals were calculated as measures of association between fatigue and gender. Kaplan-Meier curves were produced to examine the age at onset for lifetime fatiguing illnesses. RESULTS: Prevalences for different definitions of self-reported lifetime fatigue ranged from 36.7% for any fatigue to 2.7% for chronic fatigue syndrome- like illness. Females were two to three times more likely to report fatigue than males. Gender differences increased as fatigue definitions grew more restrictive. Ages at onset of chronic fatiguing illness were significantly earlier and the number of ancillary symptoms was greater for females than males. People with lifetime fatigue had significantly more compromised functional status than people without lifetime fatigue. CONCLUSION: The prevalence of self-reported lifetime fatiguing illness varied widely depending upon how it was defined. Given the debilitating consequences of fatiguing illnesses, the reasons for the female predominance and the earlier onset in women should receive increased research priority. Gaab J, Rohleder N, Heitz V, Engert V, Schad T, Schurmeyer TH, Ehlert U. Center for Psychobiological and Psychosomatic Research, University of Trier, Trier, Germany. j.gaab@psychology Stress-induced changes in LPS- induced pro- inflammatory cytokine production in chronic fatigue syndrome. Psychoneuroendocr inology. 2005 Feb;30(2):188-98. OBJECTIVE: It has been suggested that a hypofunctional hypothalamic-pituitary-adrenal (HPA) axis in chronic fatigue syndrome could result in an exaggerated release of pro-inflammatory cytokines during stress. As pro-inflammatory cytokines are involved in the induction of sickness behavior and thus constitute a potential physiological correlate of stress-induced symptom exacerbation in chronic fatigue syndrome, we set out to evaluate the LPS-induced production of pro-inflammatory cytokines during psychosocial stress in CFS and healthy controls. METHOD: Twenty-one CFS patients and 20 healthy controls matched for age and gender underwent a standardized psychosocial stress test (Trier social stress test, TSST). Adrenocorticotropine hormone (ACTH), salivary cortisol and plasma cortisol levels were measured before and repeatedly following exposure to the stressor. Lipopolysaccharide- stimulated production of interleukin-6 and tumor necrosis factor-alpha were assessed at baseline as well as 10 and 60 min after the stress test. RESULTS: CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF- alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels. CONCLUSION: CFS patients do not show an exaggerated secretion of LPS-induced cytokines. Although cortisol responses to stress were normal, pro- inflammatory cytokine levels in CFS patients were significantly attenuated. Possible intracellular
  21. 21. ME Research UK — Database of Research Publications 2005 mechanisms, such as for example an enhanced sensitivity to inhibitory effects of glucocorticoids, a diminished responsivity to catecholaminergic stimulation, and a disruption of intracellular activation are discussed. Basal levels of stimulated pro-inflammatory Il-6 levels are generally related to fatigue scores. However, in CFS patients this association is of greater magnitude and can also be observed for TNF-alpha. Gallagher AM, Coldrick AR, Hedge B, Weir WR, White PD. Centre for Psychiatry, Institute of Community Health Sciences, Queen Mary School of Medicine and Dentistry, St. Bartholomew's Hospital, EC1A 7BE London, UK. Is the chronic fatigue syndrome an exercise phobia? A case control study. J Psychosom Res. 2005 Apr;58(4):367-73. OBJECTIVE: The aim of this study was to test whether patients with chronic fatigue syndrome (CFS) have an exercise phobia, by measuring anxiety-related physiological and psychological reactions to ordinary activity and exercise. METHODS: Patients and healthy but sedentary controls were assessed over 8 h of an ordinary day, and before, during and after an incremental exercise test on a motorised treadmill. To avoid confounding effects, those with a comorbid psychiatric disorder were excluded. Heart rate, galvanic skin resistance (GSR) and the amount of activity undertaken were measured, along with state and trait measures of anxiety. RESULTS: Patients with CFS were more fatigued and sleep disturbed than were the controls and noted greater effort during the exercise test. No statistically significant differences were found in either heart rate or GSR both during a normal day and before, during and after the exercise test. Patients with CFS were more symptomatically anxious at all times, but this did not increase with exercise. CONCLUSION: The data suggest that CFS patients without a comorbid psychiatric disorder do not have an exercise phobia. Garralda ME, Rangel L. Academic Unit of Child and Adolescent Psychiatry, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK. e.garralda@imperi Chronic fatigue syndrome of childhood. Comparative study with emotional disorders. Eur Child Adolesc Psychiatry. 2005 Dec;14(8):424-30. OBJECTIVE: To examine clinical specificity in chronic fatigue syndrome (CFS) of childhood, by comparing clinical features in childhood CFS and in emotional disorders (ED). METHOD SAMPLE: 28 children with CFS; 27 with ED. MEASURES: History of disorder; K-SADS psychiatric interviews; self-esteem and physical symptoms questionnaires; premorbid history, behavioural and personality assessments. RESULTS: There were high levels of comorbid emotional disorders in children with CFS, and the two groups were comparable on self-esteem, but CFS children endorsed more fatigue and other somatic symptoms. The two groups were comparable on age at illness onset, but parents of children with CSF reported more biological illness precipitants, more pre-morbid recurrent medical problems and infections. The CFS group had fewer pre-morbid psychological problems and less psychiatric comorbidity than the ED group. CONCLUSION: There is considerable clinical overlap between CFS and ED of childhood, but there are also differences in clinical presentation between these disorders. Glaser R, Padgett DA, Litsky ML, Baiocchi RA, Yang EV, Chen M, Yeh PE, Klimas NG, Marshall GD, Whiteside T, Herberman R, Kiecolt-Glaser J, Williams MV. Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Medical Center, 333 W. 10th Avenue, Columbus, OH 43210, USA. Stress-associated changes in the steady-state expression of latent Epstein-Barr virus: implications for chronic fatigue syndrome and cancer. Brain Behav Immun. 2005 Mar;19(2):91-103. Antibodies to several Epstein-Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-gamma by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the