Research Publications 2006

ME Research UK — Database of Research Publications 2006
Authors Author Address Title Publication Abstract

Ablin JN, Department of Fibromyalgia, J Autoimmun. As the pathogenesis of fibromyalgia continues to raise debate, multiple putative triggers have been
Shoenfeld Y, Rheumatology, infection and 2006 implicated. The current review summarizes the available data linking fibromyalgia to either infection
Buskila D. Tel-Aviv Sourasky vaccination: Two Nov;27(3):145-52. or vaccination. Multiple infectious agents have been associated with the development of either full-
Medical Center more parts in the Epub 2006 Oct 30. blown fibromyalgia (e.g. hepatits C), or with symptom complexes extensively overlapping with that
and Sackler etiological puzzle. syndrome (e.g. chronic Lyme disease). The cases of Lyme disease, mycoplasma, hepatits C and HIV
Faculty of are detailed. Despite the described associations, no evidence is available demonstrating the utility of
Medicine, Tel- antibiotic or anti-viral treatment in the management of fibromyalgia. Possible mechanistic links
Aviv University, 6 between fibromyalgia and HIV are reviewed. Associations have been described between various
Weizman St., vaccinations and symptom complexes including fibromyalgia and chronic fatigue syndrome. The case
64239 Tel-Aviv, of Gulf War syndrome, a functional multisystem entity sharing many clinical characteristics with
Israel. fibromyalgia is discussed, with emphasis on the possibility of association with administration of
multiple vaccinations during deployment in the Persian Gulf and the interaction with stress and
trauma. Based on this example a model is proposed, wherein vaccinations function as co-triggers for
the development of functional disorders including fibromyalgia, in conjunction with additional
contributing factors.
Arnold Llamosas Inmunologia y [Multiple chemical Med Clin (Barc). The sick building syndrome includes irritation of the eyes and the respiratory tract neurotoxicity
PA, Arrizabalaga Medicina Interna, sensitivity in sick- 2006 May affectation and skin problems, which can occur in individuals under improperly ventilated buildings.
Clemente P, Servicio de building 27;126(20):774-8. Poor air quality, as shown in CO2 atmospheric levels of more than 1,000 ppm, results in a
Bonet Agusti M, Reumatologia, syndrome] [Article pathological exposure to biological and chemical products. We present a work-related case of
de la Fuente Brull Centro in Spanish] multiple chemical hypersensitivity from a dialysis unit that had no air renewal. This person, who was
X. Internacional summitted to continuous exposure despite having taken corrective measures in the ventilation,
Medicina developed chronic fatigue syndrome. An acoustic voice observation alerted of the case which led to
Avanzada (CIMA), the analysis of the environmental conditions which confirmed the relationship between multiple
Servei Acreditat chemical hypersensitivity and chronic fatigue syndrome. This case stresses the neglected fact that all
Cat Salut, health service centres pose a high risk of chemical exposure and that there exists a lack of
Barcelona, Spain. rigoroursness in putting in practice scientific medical knowledge.
Aslakson E, Centers for The validity of an Pharmacogenomic OBJECTIVES: To validate a latent class structure derived empirically from a clinical data set
Vollmer-Conna Disease Control empirical s. 2006 obtained from persons with chronic medically unexplained fatigue. METHODS: The strategies
U, White PD. and Prevention, delineation of Apr;7(3):365-73. utilized in this validation study included: recalculating latent class analysis (LCA) results varying
Division of Viral heterogeneity in random seeds and the number of initial random starting sets; recalculating LCA results by substituting
and Rickettsial chronic alternate variables to demonstrate a robust solution; determining the statistical significance of
Diseases, National unexplained between-class differences on disability, fatigue and demographic measures omitted from the data set
Center for fatigue. used for LCA; cross-classifying class membership using established Centers for Disease Control and
Infectious Prevention (CDC) research criteria for chronic fatigue syndrome (CFS) to compare the relative
Diseases, Atlanta, proportions of subjects designated CFS, chronic fatigue (not CFS) or healthy controls captured by the
GA 30333, USA. latent classes. RESULTS: Recalculation of results and substitution of variables for low-loading
EAslakson@cdc.g variables demonstrated a robust LCA result. Highly significant between-class differences were
ov confirmed between Class 2 (well) and those interpreted as ill/fatigued. Analysis of between-class
differences for the fatigue groups revealed significant differences for all disability and fatigue
variables, but with equivalent levels of reported activity and reduction in motivation. Cross-
classification against established CDC criteria demonstrated that 89% of subjects constituting Class 2
(well) were indeed nonfatigued controls. A general tendency for grouping CFS cases in the multiple
symptomatic classes was noted. CONCLUSION: This study established reasonably good validity for
an empirically-derived latent class solution reflecting considerable heterogeneity among subjects with
medically unexplained chronic fatigue. This work strengthens the growing understanding of CFS as a
heterogeneous entity comprised of several conditions with different underlying pathophysiological
mechanisms.
Authier FJ, Centre de [Muscular Rev Neurol Introduction of highly active antiretroviral therapy (HAART) has dramatically modified the natural
Gherardi RK. Reference pour complications of (Paris). 2006 history of HIV disease, but lengthening the survival of HIV-infected individuals has been associated
Maladies human Jan;162(1):71-81. with an increasing prevalence of iatrogenic conditions. Muscular complications of HIV infection are
Neuromusculaires immunodeficiency classified as follows: (1) HIV-associated myopathies and related conditions including polymyositis,
Garches-Necker- virus (HIV) inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS),
Mondor-Hendaye infection in the era HIV-wasting syndrome, vasculitis, myasthenic syndromes, and chronic fatigue; (2) iatrogenic
(GNMH), Hopital of effective anti- conditions including mitochondrial myopathies, HIV-associated lipodystrophy syndrome, and
Henri-Mondor, retroviral therapy] immune restoration syndrome; (3) opportunistic infections and tumor infiltrations of skeletal muscle;
AP-HP, Creteil. [Article in French] and (4) rhabdomyolysis. These features are described in the present review.
francois-
jerome.authier@h
mn.aphp.fr
Axelrod FB, Dysautonomia Pediatric Pediatrics. 2006 The scope of pediatric autonomic disorders is not well recognized. The goal of this review is to
Chelimsky GG, Treatment and autonomic Jul;118(1):309-21. increase awareness of the expanding spectrum of pediatric autonomic disorders by providing an
Weese-Mayer Evaluation Center, disorders. overview of the autonomic nervous system, including the roles of its various components and its
DE. Department of pervasive influence, as well as its intimate relationship with sensory function. To illustrate further the
Pediatrics and breadth and complexities of autonomic dysfunction, some pediatric disorders are described,
Neurology, New concentrating on those that present at birth or appear in early childhood.
York University
School of
Medicine, 530
First Ave, Suite
9Q, New York,
New York 10016,
USA.
felicia.axelrod@m
ed.nyu.edu
Bailes S, Libman SMBD-Jewish Brief and distinct J Psychosom Res. OBJECTIVE: Sleepiness and fatigue are conceptually distinct but pervasively confounded in
E, Baltzan M, General Hospital, empirical 2006 research, measurement instruments, clinical settings, and everyday spoken language. The purpose of
Amsel R, Montreal, Canada. sleepiness and Jun;60(6):605-13. the present study was to construct two scales that represent unconfounded measures of sleepiness and
Schondorf R, sally.bailes@mail. fatigue scales. fatigue, using widely used questionnaires. METHOD: Four questionnaires purporting to measure
Fichten CS. mcgill.ca sleepiness [Stanford Sleepiness Scale (SSS); Epworth Sleepiness Scale (ESS)] or fatigue [Fatigue
Severity Scale (FSS); Chalder Fatigue Scale (CFS)] were administered, as well as a battery measuring
sleep, psychological, and health functioning variables, to three samples: 19 individuals with chronic
fatigue syndrome, 14 with narcolepsy, and 11 normal control subjects. RESULTS: Analyses revealed
two distinct sets of items (six sleepiness and three fatigue items) that were combined into two scales.
These newly formed scales are only minimally correlated and represent separate constructs that have
reasonably distinctive patterns of association. Findings were replicated and validated in a sample of
128 older individuals complaining of daytime sleepiness and/or fatigue. CONCLUSIONS: We
conclude that (a) it is possible to derive empirically distinct sleepiness and fatigue scales from
existing, commonly used self-report instruments, (b) the Empirical Sleepiness Scale is limited to the
experience of daytime sleep tendency, while (c) the Empirical Fatigue Scale is associated more
broadly with insomnia, psychological maladjustment, and poorer perceived health function. The
important clinical implication of the new Empirical Sleepiness and Fatigue Scales is in the ability to
identify "sleepiness which is not fatigue," a construct closely related to primary sleep disorders, such
as sleep apnea/hypopnea syndrome, for which there is both available and effective treatment.
Barat M, Dehail Unite de Fatigue after spinal Ann Readapt Med OBJECTIVES: To identify variables increasing fatigue following spinal cord injury (SCI) and their
P, de Seze M. Reeducation cord injury. Phys. 2006 functional consequences. METHODS: A search of the Medline and Reedoc databases with the
Neurologique, [Article in English, Jul;49(6):277-82, keywords SCI, fatigue, intrinsic muscular fatigue, chronic fatigue, aging, training, electrostimulation,
Universite Victor- French] 365-9. Epub 2006 quality of life and the same words in French. RESULTS: Two kinds of fatigue are identified
Segalen Bordeaux- Apr 25. following SCI. Intrinsic fatigue in muscles totally or partially paralysed at the level of or below the
II et Federation spinal cord lesion; this peripheral fatigue is due to denervation, total or partial loss of motoneurons, or
des Neurosciences histological and metabolical changes in muscle; it is well-defined by electrophysiological technology;
Cliniques, CHU de spasticity and spasms have little influence on its development; it is reversible in part with long term
Bordeaux, 146, rue electrostimulation, but at this time, electroneuroprosthetic techniques do not reduce the excessive
Leo-Saignat, energetic cost to stand up and walk. Chronic fatigue appears in the long term following SCI; it is
33076 Bordeaux linked with aging, physiological, and psychological deconditioning; some data point to chronic
cedex, France. fatigue after SCI similar to post-polio syndrome and chronic fatigue syndrome, which may explain
michel.barat@chu- the central nature of the fatigue; training programs could be useful in delaying this chronic fatigue
bordeaux.fr and as a consequence, increasing the latent quality of life. CONCLUSION: Muscular intrinsic fatigue
after SCI is always of a peripherical nature in muscles partially or totally paralysed. Chronic fatigue
during aging greatly decreases quality of life. Both intrinsic and chronic fatigue could be anticipated
by electrostimulation technique on the one hand and long term training on the other.
Barbado Servicio de [The chronic An Med Interna.
Hernandez FJ, Medicina Interna, fatigue syndrome 2006
Gomez Cerezo J, Hospital and its diagnosis in May;23(5):238-44.
Lopez Rodriguez Universitario La internal medicine]
M, Vazquez Paz, Universidad [Article in
Rodriguez JJ. Autonoma, Spanish]
Madrid.
Baschetti R. Chronic fatigue. CMAJ. 2006 Aug
Comment on: 15;175(4):386;
CMAJ. 2006 Mar author reply 387-8.
14;174(6):765-7.
Bates MN. Division of Mercury amalgam Int J Hyg Environ Dental amalgam fillings containing approximately 50% mercury have been used for almost 200 years
Environmental dental fillings: an Health. 2006 and have been controversial for almost the same time. Allegations of effects caused by amalgams
Health Sciences, epidemiologic Jul;209(4):309-16. have involved many diseases. Recent evidence that small amounts of mercury are continuously
School of Public assessment. Epub 2006 Jan 30. released from amalgam fillings has fuelled the controversy. This is a comprehensive review of the
Health, 140 epidemiologic evidence for the safety of dental amalgam fillings, with an emphasis on
Warren Hall, methodological issues and identifying gaps in the literature. Studies show little evidence of effects on
University of general chronic disease incidence or mortality. Limited evidence exists for an association with
California, multiple sclerosis, but few studies on either Alzheimer's or Parkinson's diseases. The preponderance
Berkeley, CA of evidence suggests no renal effects and that ill-defined symptom complexes, including chronic
94720-7360, USA. fatigue syndrome, are not caused by amalgams. There is little direct evidence that can be used to
m_bates@berkeley assess reproductive hazards. Overall, few relevant epidemiologic studies are available. Most prior
.edu assessments of possible amalgam health effects have been based on comparisons of dental mercury
exposures with occupational exposures causing harm. However, the amalgam-exposed population
contains a broader, possibly more susceptible, spectrum of people. Common limitations of
population-based studies of dental amalgam effects include inadequate longitudinal exposure
assessment and negative confounding by better access to dental care in higher socioeconomic groups.
Better designed studies are needed, particularly for investigation of neurodegenerative diseases and
effects on infants and children.
Bell SD, Van Guidelines for the Journal of Chronic In this special issue of the Journal of Chronic Fatigue Syndrome, chronic fatigue syndrome (CFS) in
Hoof E. Diagnosis of Fatigue Syndrome children and adolescents is specifically addressed. It is a topic long overdue. It is my sincere hope that
Pediatric Chronic 2006;13(2/3): 79- the criteria presented here will begin a process of rigorous clinical testing and refinement so that
Fatigue Syndrome: 88 pediatricians and other medical providers will come to have a reliable and accepted way of making
Things Parents the diagnosis of ME/CFS in a person under 18 years of age. This short review is meant for parents
Need to Know and other caregivers as a brief summary of the guidelines that may be of value. The primary role of
This these guidelines is to present a strict and rigorous definition that can be tried and tested. This
summary is to make the process of diagnosis somewhat easier for parents and caregivers alike until
the testing process is completed. Therefore, for more detailed symptom description and exclusionary
illness description, I would refer the reader to the primary article. Professional caregivers and
clinicians may offer this article available to inform parents with a child or/ adolescent suffering from
CFS.
Blockmans D, Department of Does Am J Med. 2006 PURPOSE: Chronic fatigue syndrome is a clinical entity consisting of prolonged and debilitating
Persoons P, Van Internal Medicine, methylphenidate Feb;119(2):167.e2 fatigue in which concentration disturbances are very frequent. Until now, no medical treatment has
Houdenhove B, University reduce the 3-30. shown any efficacy. The objectives of this study were to investigate the short-term effects of
Bobbaers H. Hospital symptoms of methylphenidate, an amphetamine derivative, on fatigue, concentration disturbances, and quality of
Gasthuisberg, chronic fatigue life. SUBJECTS AND METHODS: A double-blind randomized placebo-controlled crossover study
Leuven, Belgium. syndrome? was conducted in 60 patients who fulfilled the 1994 Centers for Disease Control criteria for chronic
daniel.blockmans fatigue syndrome and had concentration difficulties. Patients were enrolled between March 2003 and
@uz.kuleuven.ac.b March 2004 at the outpatient department of a university hospital referral center for chronic fatigue
e syndrome patients. Random assignment to 4 weeks treatment with methylphenidate 2 x 10 mg/day,
followed by 4 weeks of placebo treatment, or 4 weeks of placebo treatment, followed by
methylphenidate treatment. Fatigue and concentration were measured with a Checklist Individual
Strength (CIS) and a Visual Analogue Scale (VAS). RESULTS: Fatigue scores fell significantly
during methylphenidate intake in comparison with baseline (mean difference: -0.7, P = .010 for VAS;
mean difference: -11.8, P <.0001 for CIS) and in comparison with placebo (mean difference: -1.0, P =
.001 for VAS; mean difference: -9.7, P <.0001 for CIS). Concentration disturbances, measured with a
VAS improved significantly under methylphenidate treatment compared with baseline (mean
difference: -1.3, P <.0001) and compared with placebo (mean difference: -1.1, P <.0001). A clinical
significant effect (> or =33% improvement or CIS < or =76) on fatigue was achieved in 17% of
patients, who were considered responders; on concentration in 22% of patients. CONCLUSIONS:
Methylphenidate at a dose of 2 x 10 mg/day is significantly better than placebo in relieving fatigue
and concentration disturbances in a minority of chronic fatigue syndrome patients. Further studies are
needed to investigate the long-term effects of this treatment.
Bond PA, Dinan Antibodies to Journal of Chronic Background. It has been suggested that Herpes simplex virus (HSV) could play a role in the aetiology
TG. Herpes Simplex Fatigue Syndrome of chronic fatigue syndrome (CFS). An immune system that has been compromised, could account for
Types 1 and 2 in 2006;13(1): 35-40 HSV reactivating or infecting for the first time, and also being insufficiently under control in the
Chronic Fatigue body. Another consequence of inadequate control could be that several strains of HSV could
Syndrome simultaneously infect the body. Objectives. To look for the presence of antibodies to HSV-1 and
HSV-2 in patients with CSF and in controls. The presence of antibodies to both types of HSV could
reflect infection by multiple strains of HSV. Methods. Antibodies to HSV-1 and HSV-2 were
measured in sera from 27 CSF patients and 26 ageand sex-matched controls. CFS was diagnosed
using the CDC criteria. Results. More CFS patients had antibodies to HSV-1, HSV-2 and both types
simultaneously, than did the controls (all p < .019). Conclusions. More CFS patients have antibodies
to both HSV-1 and HSV-2 than do controls. The possibility that multiple strains could
Broderick G, University of Identifying illness Pharmacogenomic OBJECTIVES: To examine the potential of multivariate projection methods in identifying common
Craddock RC, Alberta, Institute parameters in s. 2006 patterns of change in clinical and gene expression data that capture the illness state of subjects with
Whistler T, for Biomolecular fatiguing Apr;7(3):407-19. unexplained fatigue and nonfatigued control participants. METHODS: Data for 111 female subjects
Taylor R, Klimas Design, Edmonton, syndromes using was examined. A total of 59 indicators, including multidimensional fatigue inventory (MFI), medical
N, Unger ER. Alberta, T6G 2H7, classical projection outcome Short Form 36 (SF-36), Centers for Disease Control and Prevention (CDC) symptom
Canada. methods. inventory and cognitive response described illness. Partial least squares (PLS) was used to construct
gordon.broderick two feature spaces: one describing the symptom space from gene expression in peripheral blood
@ualberta.ca mononuclear cells (PBMC) and one based on 117 clinical variables. Multiplicative scatter correction
followed by quantile normalization was applied for trend removal and range adjustment of microarray
data. Microarray quality was assessed using mean Pearson correlation between samples. Benjamini-
Hochberg multiple testing criteria served to identify significantly expressed probes. RESULTS: A
single common trend in 59 symptom constructs isolates of nonfatigued subjects from the overall
group. This segregation is supported by two co-regulation patterns representing 10% of the overall
microarray variation. Of the 39 principal contributors, the 17 probes annotated related to basic
cellular processes involved in cell signaling, ion transport and immune system function. The single
most influential gene was sestrin 1 (SESN1), supporting recent evidence of oxidative stress
involvement in chronic fatigue syndrome (CFS). Dominant variables in the clinical feature space
described heart rate variability (HRV) during sleep. Potassium and free thyroxine (T4) also figure
prominently. CONCLUSION: Combining multiple symptom, gene or clinical variables into
composite features provides better discrimination of the illness state than even the most influential
variable used alone. Although the exact mechanism is unclear, results suggest a common link
between oxidative stress, immune system dysfunction and potassium imbalance in CFS patients
leading to impaired sympatho-vagal balance strongly reflected in abnormal HRV.
Brooks JK, Department of Postural orthostatic J Am Dent Assoc. BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a chronic, relatively common
Francis LA. Diagnostic tachycardia 2006 autonomic disorder typically affecting younger females. It is distinguished by a dramatic increase in
Sciences and syndrome: Dental Apr;137(4):488- heart rate on the assumption of an upright posture from the supine position. METHODS: The authors
Pathology, treatment 93. provide an overview of the demographics, clinical assessment, diagnostic features, differential
Baltimore College considerations. diagnoses, pathogeneses and medical treatment of patients with POTS, with an emphasis on the
of Dental Surgery, clinical treatment of the dental patient affected by the syndrome. CONCLUSION: Patients frequently
Dental School, exhibit symptoms of lightheadedness, fatigue, palpitations and syncope. Patients with POTS may
University of have Ehlers-Danlos syndrome, mitral valve prolapse, chronic fatigue syndrome or, rarely, the
Maryland, Brugada syndrome. Despite widespread dissemination of information regarding POTS in the medical
Baltimore, MD literature, scant information on it has appeared in dental publications. PRACTICE IMPLICATIONS:
21201, USA. Dentists need to be familiar with the clinical features of POTS and be prepared to treat patients at risk
Oralpath5@aol.co of developing syncope.
m
Bruusgaard D. Institutt for [With the back to Tidsskr Nor
allmenn- og the future] [Article Laegeforen. 2006
samfunnsmedisin, in Norwegian] Oct
Universitetet i 19;126(20):2686.
Oslo, Postboks
1130 Blindern
O318, Oslo,
Norway.
dag.bruusgaard@
medisin.uio.no
Capuron L, Department of Cognitive Neuropsychophar Patients with chronic fatigue syndrome (CFS) frequently complain of cognitive dysfunction.
Welberg L, Heim Psychiatry and dysfunction relates macology. 2006 However, evidence of cognitive impairment in CFS patients has been found in some, but not other,
C, Wagner D, Behavioral to subjective report Aug;31(8):1777- studies. This heterogeneity in findings may stem from the relative presence of mental fatigue in the
Solomon L, Sciences, Emory of mental fatigue 84. Epub 2006 Jan patient populations examined. The present study assessed this possibility in a population-based
Papanicolaou DA, University School in patients with 4. sample of CFS patients. In all, 43 patients with CFS defined by the criteria of the 1994 research case
Craddock RC, of Medicine, chronic fatigue definition using measurements recommended by the 2003 International CFS Study Group, and 53
Miller AH, Atlanta, GA, USA. syndrome. age-, sex-, and race/ethnicity-matched nonfatigued subjects were included in the study. Mental
Reeves WC. fatigue was assessed using the mental fatigue subscale of the multidimensional fatigue inventory.
Cognitive function was evaluated using an automated battery of computerized tests (Cambridge
neuropsychological test automated battery (CANTAB)) that assessed psychomotor function, planning
and problem-solving abilities, and memory and attentional performance. CFS patients with significant
complaints of mental fatigue (score of mental fatigue 2 standard deviations above the mean of
nonfatigued subjects) exhibited significant impairment in the spatial working memory and sustained
attention (rapid visual information processing) tasks when compared to CFS patients with low
complaints of mental fatigue and nonfatigued subjects. In CFS patients with significant mental
fatigue, sustained attention performance was impaired only in the final stages of the test, indicating
greater cognitive fatigability in these patients. CFS patients with low mental fatigue displayed
performance comparable to nonfatigued subjects on all tests of the CANTAB battery. These findings
show strong concordance between subjective complaints of mental fatigue and objective
measurement of cognitive impairment in CFS patients and suggest that mental fatigue is an important
component of CFS-related cognitive dysfunction.
Carlo-Stella N, Immunogenetics A first study of Clin Exp OBJECTIVE: In the past two years we have developed a biological bank of genomic DNA, cDNA,
Badulli C, De Laboratory, Dept. cytokine genomic Rheumatol. 2006 serum and red blood cells of Italian patients with certified CFS from the two Italian referral centers
Silvestri A, of Genetics and polymorphisms in Mar- for the syndrome. Recent studies have shown an imbalance in cytokine production in disease states
Bazzichi L, Microbiology, CFS: Positive Apr;24(2):179-82. similar to Chronic Fatigue Syndrome (CFS), such as sickness behavior, both in animals and in
Martinetti M, University of association of humans. However we notice that serum cytokine concentrations are often inconstant and degrade
Lorusso L, Pavia, Italy. TNF-857 and rapidly. With this in mind, we investigated cytokine gene polymorphisms in 80 Italian patients with
Bombardieri S, nickics@ipvgen.un IFNgamma 874 CFS in order to ascertain whether in this group of patients it is possible to describe a genetic
Salvaneschi L, ipv.it rare alleles. predisposition to an inflammatory response. METHODS: We analyzed the promoter polymorphisms
Cuccia M. of IL-10, IL-6 and the IFNgamma 874 T/A polymorphism in intron 1 with a PCR-SSP method
(Cytogen One Lambda Inc. Canoga Park, CA, U.S.A) in 54 patients and TNF-308 G/A and -857 C/T
promoter polymorphisms with a PCR-RFLP method (in 54 and 80 patients respectively). RESULTS:
There is a highly significant increase of TNF -857 TT and CT genotypes (p = 0.002) among patients
with respect to controls and a significant decrease of IFN gamma low producers (A/A) (p = 0.04)
among patients with respect to controls. CONCLUSIONS: We hypothesize that CFS patients can
have a genetic predisposition to an immunomodulatory response of an inflammatory nature probably
secondary to one or more environmental insults of unknown nature.
Carmel L, Efroni National Center Gene expression Pharmacogenomic OBJECTIVES: To identify the underlying gene expression profiles of unexplained chronic fatigue
S, White PD, for Biotechnology profile of s. 2006 subjects classified into five or six class solutions by principal component (PCA) and latent class
Aslakson E, Information, empirically Apr;7(3):375-86. analyses (LCA). METHODS: Microarray expression data were available for 15,315 genes and 111
Vollmer-Conna National Library delineated classes female subjects enrolled from a population-based study on chronic fatigue syndrome. Algorithms
U, Rajeevan MS. of Medicine, of unexplained were developed to assign gene scores and threshold values that signified the contribution of each gene
National Institutes chronic fatigue. to discriminate the multiclasses in each LCA solution. Unsupervised dimensionality reduction was
of Health, first used to remove noise or otherwise uninformative gene combinations, followed by supervised
Bethesda, dimensionality reduction to isolate gene combinations that best separate the classes. RESULTS: The
Maryland, USA. authors' gene score and threshold algorithms identified 32 and 26 genes capable of discriminating the
five and six multiclass solutions, respectively. Pair-wise comparisons suggested that some genes (zinc
finger protein 350 [ZNF350], solute carrier family 1, member 6 [SLC1A6], F-box protein 7 [FBX07]
and vacuole 14 protein homolog [VAC14]) distinguished most classes of fatigued subjects from
healthy subjects, whereas others (patched homolog 2 [PTCH2] and T-cell leukemia/lymphoma
[TCL1A]) differentiated specific fatigue classes. CONCLUSION: A computational approach was
developed for general use to identify discriminatory genes in any multiclass problem. Using this
approach, differences in gene expression were found to discriminate some classes of unexplained
chronic fatigue, particularly one termed interoception.
Caseras X, Unitat de Probing the Psychosom Med. OBJECTIVE: Up to 90% of patients with chronic fatigue syndrome (CFS) report substantial cognitive
Mataix-Cols D, Psicologia Medica, working memory 2006 Nov- difficulties. However, objective evidence supporting these claims is inconsistent. The present
Giampietro V, Institut de system in chronic Dec;68(6):947-55. functional magnetic resonance imaging study examined the neural correlates of working memory in
Rimes KA, Neurociencies, fatigue syndrome: Epub 2006 Nov 1. patients with CFS compared with controls. METHODS: Seventeen patients with CFS and 12 healthy
Brammer M, Universitat a functional control subjects were scanned while performing a parametric version of the n-back task (0-, 1-, 2-,
Zelaya F, Chalder Autonoma de magnetic and 3-back). RESULTS: Both groups performed comparably well and activated the verbal working
T, Godfrey EL. Barcelona, resonance imaging memory network during all task levels. However, during the 1-back condition, patients with CFS
Barcelona, Spain. study using the n- showed greater activation than control subjects in medial prefrontal regions, including the anterior
x.caseras@iop.kcl. back task. cingulate gyrus. Conversely, on the more challenging conditions, patients with CFS demonstrated
ac.uk reduced activation in dorsolateral prefrontal and parietal cortices. Furthermore, on the 2- and 3-back
conditions, patients but not control subjects significantly activated a large cluster in the right
inferior/medial temporal cortex. Trend analyses of task load demonstrated statistically significant
differences in brain activation between the two groups as the demands of the task increased.
CONCLUSIONS: These results suggest that patients with CFS show both quantitative and qualitative
differences in activation of the working memory network compared with healthy control subjects. It
remains to be determined whether these findings stay stable after successful treatment.
Chalmers RA, St George's CFSUM1 and Clin Chim Acta. McGregor et al. reported increased levels of an unidentified urinary compound (CFSUM1) in patients
Jones MG, Hospital Medical CFSUM2 in urine 2006 Feb;364(1- with chronic fatigue syndrome (CFS), with reduced excretion of another unidentified compound
Goodwin CS, School, Cranmer from patients with 2):148-58. Epub (CFSUM2), and suggested the possibility of chemical or metabolic 'markers' for CFS. The identity of
Amjad S. Terrace, London chronic fatigue 2005 Aug 10. CFSUM1 as reported was erroneous and the identities of these compounds have remained unknown
SW17 0RE, UK. syndrome are until now. Urine samples were obtained from 30 patients with ME/CFS, 30 age- and sex-matched
rachalmers@cimo methodological healthy controls, 20 control patients with depression and 22 control patients with rheumatoid arthritis.
a.org.uk artefacts. 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.
Chambers D, Centre for Interventions for J R Soc Med. 2006 OBJECTIVES: To determine whether any particular intervention or combination of interventions is
Bagnall AM, Reviews and the treatment, Oct;99(10):506-20. effective in the treatment, management and rehabilitation of adults and children with a diagnosis of
Hempel S, Forbes Dissemination, management and chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME). DESIGN: Substantive update of a
C. University of rehabilitation of systematic review published in 2002. Randomized (RCTs) and non-randomized controlled trials of
York, York YO10 patients with any intervention or combination of interventions were eligible for inclusion. Study participants could
5DD, UK. chronic fatigue be adults or children with a diagnosis of CFS/ME based on any criteria. We searched eleven
dc510@york.ac.uk syndrome/myalgic electronic databases, reference lists of articles and reviews, and textbooks on CFS/ME. Additional
encephalomyelitis: references were sought by contact with experts. RESULTS: Seventy studies met the inclusion criteria.
an updated Studies on behavioural, immunological, pharmacological and complementary therapies, nutritional
systematic review. supplements and miscellaneous other interventions were identified. Graded exercise therapy and
cognitive behaviour therapy appeared to reduce symptoms and improve function based on evidence
from RCTs. For most other interventions, evidence of effectiveness was inconclusive and some
interventions were associated with significant adverse effects. CONCLUSIONS: Over the last five
years, there has been a marked increase in the size and quality of the evidence base on interventions
for CFS/ME. Some behavioural interventions have shown promising results in reducing the symptoms
of CFS/ME and improving physical functioning. There is a need for research to define the
characteristics of patients who would benefit from specific interventions and to develop clinically
relevant objective outcome measures.
Chapenko S, August Activation of J Clin Virol. 2006 BACKGROUND: Human herpesvirus 6 (HHV-6) and 7 (HHV-7) have been suggested as possible
Krumina A, Kirchenstein human Dec;37 Suppl triggering agents for chronic fatigue syndrome (CFS). OBJECTIVES: To determine the possible
Kozireva S, Nora Institute of herpesviruses 6 1:S47-51. association of HHV-6 and HHV-7 infections with CFS. STUDY DESIGN: The prevalence of
Z, Sultanova A, Microbiology and and 7 in patients latent/persistent and active viral infections by nPCR, characteristic of HHV-6 variants using
Viksna L, Virology, Riga with chronic restriction endonuclease analysis and changes of lymphocyte subsets in peripheral blood by laser
Murovska M. Stradins fatigue syndrome. flow-cytometry in 17 CFS patients was examined. In addition, 12 patients with unexplained chronic
University, fatigue and 20 blood donors (BD) were studied. RESULTS: No difference in prevalence of
Ratsupites St.1, latent/persistent single viral infections between the patients and BD was found but dual infection rate
Riga, LV-1067, was significantly higher in CFS patients. Active HHV-6 and dual (HHV-6 + HHV-7) infections were
Latvia. detected in CFS patients only and frequency of HHV-7 reactivation was also significantly higher in
these patients. HHV-6 variant B was predominant in CFS patients (12/13). The changes of
immunological parameters in CFS patients with active dual infection were characterized by
significant decrease of CD3+ and CD4+ T cells, significant increase of CD95+ cells and decrease of
CD4+/CD8+ ratio. CONCLUSIONS: HHV-6 and HHV-7 may be involved in the pathogenesis of
CFS and reactivation of both viruses may provoke changes in the phenotype of circulating
lymphocytes.
Chaudhuri A. Essex Centre for Diagnosing Practitioner. 2006 Review

Neurological chronic fatigue. Oct;250(1687):33-
Sciences, 4, 37.
Oldchurch
Hospital, Romford,
Essex.
Cho HJ, Skowera Department of Chronic fatigue Curr Opin PURPOSE OF REVIEW: Chronic fatigue syndrome is a controversial condition especially
A, Cleare A, Psychological syndrome: an Psychiatry. 2006 concerning its clinical definition and aetiopathogenesis. Most recent research progress has been made
Wessely S. Medicine, Institute update focusing on Jan;19(1):67-73. in phenomenology and pathophysiology and we focused our review on these two areas. RECENT
of Psychiatry, phenomenology FINDINGS: The phenomenology research supports the notion of a discrete fatigue syndrome which
King's College and can be distinguished from depression and anxiety. The current case definition, however, may need an
London, London, pathophysiology. improvement based on empirical data. Recent advances in understanding the pathophysiology of
UK. chronic fatigue syndrome continue to demonstrate the involvement of the central nervous system.
h.cho@iop.kcl.ac. Hyperserotonergic state and hypoactivity of the hypothalamic-pituitary-adrenal axis constitute other
uk findings, but the question of whether these alterations are a cause or consequence of chronic fatigue
syndrome still remains unanswered. Immune system involvement in the pathogenesis seems certain
but the findings on the specific mechanisms are still inconsistent. Genetic studies provide some
evidence of the syndrome being a partly genetic condition, but environmental effects seem to be still
predominant and identification of specific genes is still at a very early stage. SUMMARY: The recent
findings suggest that further research is needed in improving the current case definition; investigating
overlaps and boundaries among various functional somatic syndromes; answering the question of
whether the pathophysiologic findings are a cause or consequence; and elucidating the involvement of
the central nervous system, immune system and genetic factors.
Cook DB, University of The influence of Arthritis Rheum. OBJECTIVE: To investigate cardiorespiratory and perceptual responses to exercise in patients with
Nagelkirk PR, Wisconsin, aerobic fitness and 2006 chronic fatigue syndrome (CFS), accounting for comorbid fibromyalgia (FM) and controlling for
Poluri A, Mores Madison, WI fibromyalgia on Oct;54(10):3351- aerobic fitness. METHODS: Twenty-nine patients with CFS only, 23 patients with CFS plus FM, and
J, Natelson BH. 53706, USA. cardiorespiratory 62. 32 controls completed an incremental bicycle test to exhaustion. Cardiorespiratory and perceptual
dcook@education. and perceptual responses were measured. Results were determined for the entire sample and for 18 subjects from
wisc.edu responses to each group matched for peak oxygen consumption. RESULTS: In the overall sample, there were no
exercise in patients significant differences in cardiorespiratory parameters between the CFS only group and the controls.
with chronic However, the CFS plus FM group exhibited lower ventilation, lower end-tidal CO2, and higher
fatigue syndrome. ventilatory equivalent of carbon dioxide compared with controls, and slower increases in heart rate
compared with both patients with CFS only and controls. Peak oxygen consumption, ventilation, and
workload were lower in the CFS plus FM group. Subjects in both the CFS only group and the CFS
plus FM group rated exercise as more effortful than did controls. Patients with CFS plus FM rated
exercise as significantly more painful than did patients with CFS only or controls. In the subgroups
matched for aerobic fitness, there were no significant differences among the groups for any measured
cardiorespiratory response, but perceptual differences in the CFS plus FM group remained.
CONCLUSION: With matching for aerobic fitness, cardiorespiratory responses to exercise in patients
with CFS only and CFS plus FM are not different from those in sedentary healthy subjects. While
CFS patients with comorbid FM perceive exercise as more effortful and painful than do controls,
those with CFS alone do not. These results suggest that aerobic fitness and a concurrent diagnosis of
FM are likely explanations for currently conflicting data and challenge ideas implicating metabolic
disease in the pathogenesis of CFS.
Craddock RC, Centers for Exploration of Pharmacogenomic The entropy correlation coefficient (ECC) is a useful tool for measuring statistical dependence
Taylor R, Disease Control statistical s. 2006 between variables. We employed this tool to search for pairs of variables that correlated in the
Broderick G, and Prevention, dependence Apr;7(3):421-8. chronic fatigue syndrome (CFS) Computational Challenge dataset. Highly related variables are
Whistler T, Viral Exanthems between illness candidates for data reduction, and novel relationships could lead to hypotheses regarding the
Klimas N, Unger and Herpesvirus parameters using pathogenesis of CFS. METHODS: Data for 130 female participants in the Wichita (KS, USA) clinical
ER. Branch, Atlanta, the entropy study [1] was coded into numerical values. Metric data was grouped using Gaussian mixture models;
GA 30333, USA. correlation the number of groups was chosen using Bayesian information content. The pair-wise correlation
cmi5@cdc.gov coefficient. between all variables was computed using the ECC. Significance was estimated from 1000 iterations
of a permutation test and a threshold of 0.01 was used to identify significantly correlated variables.
RESULTS: The five dimensions of multidimensional fatigue inventory (MFI) were all highly
correlated with each other. Seven Short Form (SF)-36 measures, four CFS case-defining symptoms
and the Zung self-rating depression scale all correlated with all MFI dimensions. No physiological
variables correlate with more than one MFI dimension. MFI, SF-36, CDC symptom inventory, the
Zung self-rating depression scale and three Cambridge Neuropsychological Test Automated Battery
(CANTAB) measures are highly correlated with CFS disease status. DISCUSSION: Correlations
between the five dimensions of MFI are expected since they are measured from the same instrument.
The relationship between MFI and Zung depression index has been previously reported. MFI, SF-36,
and Centers for Disease Control and Prevention (CDC) symptom inventory are used to classify CFS;
it is not surprising that they are correlated with disease status. Only one of the three CANTAB
measures that correlate with disease status has been previously found, indicating the ECC identifies
relationships not found with other statistical tools. CONCLUSION: The ECC is a useful tool for
measuring statistical dependence between variables in clinical and laboratory datasets. The ECC
needs to be further studied to gain a better understanding of its meaning for clinical data.
Crawley E. Chronic fatigue Br J Hosp Med Editorial
syndrome in young (Lond). 2006
people: the Sep;67(9):452-3.
spectrum and the
myths.
Demitrack MA. Neuronetics, Inc., Clinical Pharmacogenomic Chronic fatigue syndrome (CFS) is a complex, multisymptom illness of unknown etiology. A variety
One Great Valley methodology and s. 2006 of operational case definitions based on symptom report have been developed that share some
Parkway, Suite 2, its implications for Apr;7(3):521-8. common clinical features. Patients often come to clinical presentation after months or, more typically,
Malvern, the study of years of symptomatic distress. Comorbid presentation with psychiatric illnesses has been noted. Due
Pennsylvania therapeutic to these fundamental issues, the impact of patient selection and the specification of the methods of
19355, USA. interventions for outcome assessment loom large in therapeutic studies of CFS. While a substantial body of research
mdemitrack@neur chronic fatigue has focused on increasing our understanding of the basic pathobiology of CFS, there have been
onetics.com syndrome: a comparatively fewer studies that have addressed the problems of patient characterization and outcome
commentary. assessment. The role of clinical methodology in the study of the therapeutics of CFS is not trivial, and
may confound our understanding of pragmatic recommendations for treatment.
Devanur LD, Chronic Fatigue Chronic fatigue J Clin Virol. 2006 Chronic fatigue syndrome (CFS) is thought to have a worldwide prevalence of 0.4-1% with
Kerr JR. Syndrome (CFS) syndrome. Nov;37(3):139-50. approximately 240,000 patients in the UK. Diagnosis is based on clinical criteria and critically
Group, Epub 2006 Sep 15. depends on exclusion of other physical and psychiatric diseases. Studies of pathogenesis have
Department of revealed immune system abnormalities and chronic immune activation, dysfunction of the
Cellular & hypothalamic-pituitary-adrenal (HPA) axis, brain abnormalities, evidence of emotional stress
Molecular (comprising host aspects) and evidence of exogenous insults, for example, various microbial
Medicine, St. infections (Epstein-Barr virus, enteroviruses, parvovirus B19, Coxiella burnetii and Chlamydia
George's pneumoniae), vaccinations and exposure to organophosphate chemicals and other toxins (comprising
University of environmental aspects). Emotional stress appears to be very important as it reduces the ability of the
London, Cranmer immune system to clear infections, it's presence has been shown to determine whether or not an
Terrace, London individual develops symptoms upon virus infection, and it leads to activation of the HPA axis. But,
SW17 0RE, United emotional stress is distinct from depression, the presence of which precludes a diagnosis of CFS.
Kingdom. There is no specific treatment for CFS other than the much underutilised approach of specific
treatment of virus infections. Current priorities are to understand the molecular pathogenesis of
disease in terms of human and virus gene expression, to develop a diagnostic test based on protein
biomarkers, and to develop specific curative treatments.
Dumit J. Program in Illnesses you have Soc Sci Med. 2006 Chronic fatigue syndrome and multiple chemical sensitivity are two clusters of illnesses that are
Science, to fight to get: Feb;62(3):577-90. pervaded by medical, social and political uncertainty. This article examines how facts are talked
Technology & facts as forces in Epub 2005 Aug 8. about and experienced in struggles over these emergent, contested illnesses in the US. Based
Society, uncertain, principally on a large archive of internet newsgroup postings, and also on fieldwork and on published
Massachusetts emergent illnesses. debates, it finds that (1) sufferers describe their experiences of being denied healthcare and legitimacy
Institute of through bureaucratic categories of exclusion as dependent upon their lack of biological facts; (2)
Technology, E51- institutions manage these exclusions rhetorically through exploiting the open-endedness of science to
296D MIT, deny efficacy to new facts; (3) collective patient action responds by archiving the systematic nature of
Cambridge, MA these exclusions and developing counter-tactics. The result is the maintenance of these very
02139-4307, USA. expensive struggles for all involved.
dumit@mit.edu
Dyer C. GMC must BMJ. 2006 May
consider case 13;332(7550):1110
against .
paediatricians who
suspected parents
of fabricating
child's illness.
Engel CC. Department of Explanatory and CNS Spectr. 2006 In recent years, research-methods literature mainly addressing controlled clinical trials has arisen
Psychiatry, F. pragmatic Mar;11(3):225-32. regarding explanatory and pragmatic treatment trials. Explanatory trials tend to examine causal
Edward Hebert perspectives mechanisms and questions of efficacy and value internal validity (creating optimal study conditions)
School of regarding over generalizability (using study results to understand treatment effects in real-life patient
Medicine of idiopathic physical populations). In contrast, pragmatic trials value "external relevance" (generalizability) of study results
Uniformed symptoms and over "internal elegance" so that clinicians and health policymakers can better understand how
Services related syndromes. treatments might impact their patients and policies. This review draws inspiration from these
University of contrasting explanatory and pragmatic perspectives and develops them for clinical and research
Health Sciences, pertaining to idiopathic physical symptoms and related syndromes (eg, somatization disorder, chronic
Bethesda, MD fatigue syndrome, multiple chemical sensitivities, irritable bowel syndrome). Explanatory and
20814-4799, USA. pragmatic perspectives are used to examine these idiopathies with regard to causation, case definition,
cengel@usuhs.mil labels, and treatment. It is concluded that idiopathic symptom syndromes are fundamentally
pragmatic clinical and research challenges. For epidemiologic and methodologic reasons, the
complex explanations for these syndromes remain largely elusive. Even so, scientific and clinical
pragmatism offers the opportunity to reduce disagreement between competing medical disciplines and
between clinicians and affected patients with regard to irreconcilable etiologic questions and to
remain evidence-based in the care of patients.

Fang H, Xie Q, Z-Tech Gene expression Pharmacogenomic OBJECTIVE: To gain understanding of the molecular basis of chronic fatigue syndrome (CFS)
Boneva R, Fostel Corporation at profile exploration s. 2006 through gene expression analysis using a large microarray data set in conjunction with clinically
J, Perkins R, NCTR, Division of of a large dataset Apr;7(3):429-40. administrated questionnaires. METHOD: Data from the Wichita (KS, USA) CFS Surveillance Study
Tong W. Bioinformatics, on chronic fatigue was used, comprising 167 participants with two self-report questionnaires (multidimensional fatigue
3900 NCTR Road, syndrome. inventory [MFI] and Zung depression scale [Zung]), microarray data, empiric classification, and
Jefferson, AR others. Microarray data was analyzed using bioinformatics tools from ArrayTrack. RESULTS:
72079, USA. Correspondence analysis was applied to the MFI questionnaire to select the 23 samples having either
the most or the least fatigue, and to the Zung questionnaire to select the 26 samples having either the
most or least depression; ten samples were common, resulting in a total of 39 samples. The MFI and
Zung-based CFS/non-CFS (NF) classifications on the 39 samples were consistent with the empiric
classification. Two differentially-expressed gene lists were determined, 188 fatigue-related genes and
164 depression-related genes, which shared 24 common genes and involved 11 common pathways.
Principal component analysis based on 24 genes clearly separates 39 samples with respect to their
likelihood to be CFS. Most of the 24 genes are not previously reported for CFS, yet their functions are
consistent with the prevailing model of CFS, such as immune response, apoptosis, ion channel
activity, signal transduction, cell-cell signaling, regulation of cell growth and neuronal activity.
Hierarchical cluster analysis was performed based on 24 genes to classify 128 (=167-39) unassigned
samples. Several of the 11 identified common pathways are supported by earlier findings for CFS,
such as cytokine-cytokine receptor interaction and neuroactive ligand-receptor interaction.
Importantly, most of the 11 common pathways are interrelated, suggesting complex biological
mechanisms associated with CFS. CONCLUSION: Bioinformatics is critical in this study to select
definitive sample groups, analyze gene expression data and gain insight into biological mechanisms.
The 24 identified common genes and 11 common pathways could be important in future studies of
CFS at the molecular level.
Fenske M. Comment on J Psychosom Res.
"diurnal excretion 2006
of urinary cortisol, Jun;60(6):627-8;
cortisone, and author reply 629.
cortisol
metabolites in
chronic fatigue
syndrome".
Fostel J, Boneva National Center Exploration of the Pharmacogenomic OBJECTIVE: To identify biomarkers of chronic fatigue syndrome (CFS) and related disorders
R, Lloyd A. for gene expression s. 2006 through analysis of microarray data, pathology test results and self-report symptom profiles.
Toxicogenomics, correlates of Apr;7(3):441-54. METHOD: To empirically derive the symptom domains of the illnesses, factor analysis was
NIEHS MD F1-05, chronic performed on responses to self-report questionnaires (multidimensional fatigue inventory, Centers for
111 Alexander unexplained Disease Control and Prevention (CDC) symptom inventory and Zung depression scale) before
Drive, PO Box fatigue using validation with independent datasets. Gene expression patterns that distinguished subjects across each
12233, Research factor analysis. factor dimension were then sought. RESULTS: A four-factor solution was favored, featuring 'fatigue'
Triangle Park, NC and 'mood disturbance' factors. Scores on these factors correlated with measures of disability on the
27709-2233, USA. Short Form (SF)-36. A total of 57 genes that distinguished subjects along each factor dimension were
fostel@niehs.nih.g identified, although the separation was significant only for subjects beyond the extreme (15th and
ov 85th) percentiles of severity. Clustering of laboratory parameters with expression of these genes
revealed associations with serum measurements of pH, electrolytes, glucose, urea, creatinine, and
liver enzymes (aspartate amino transferase [AST] and alanine amino transferase [AST]); as well as
hematocrit and white cell count. CONCLUSION: CFS is a complex syndrome that cannot simply be
associated with changes in individual laboratory tests or expression levels of individual genes. No
clear association with gene expression and individual symptom domains was found. However,
analysis of such multifacetted datasets is likely to be an important means to elucidate the
pathogenesis of CFS.
Frémont M, Antiviral Pathway Journal of Chronic Chronic fatigue syndrome (CFS) is a poorly defined medical condition diagnosed by exclusion,
Freya Vaeyens, Deregulation of Fatigue Syndrome which, besides severe chronic fatigue as the hallmark symptom, involves inflammatory and immune
C. Vincent Herst, Chronic Fatigue 2006; 13(4): 19-30 activation stigma. Although viral infections are not systematically found in CFS patients, the type I
Kenny De Syndrome Induces interferon antiviral pathway has been repeatedly shown to be activated in peripheral blood
Meirleir, Patrick Nitric Oxide mononuclear cells (PBMC) of the most afflicted patients. An abnormal truncated form of
Englebienne Production in ribonuclease L (37-kDa RNase L) is also found in the PBMC of CFS patients and this protein has
Immune Cells that been proposed as a biological marker for CFS. Recently, the levels of this abnormal protein have been
Precludes a significantly correlated to the extent of inflammatory symptoms displayed by CFS patients. We report
Resolution of the here that active double-stranded RNA-dependent kinase (PKR) is expressed and activated in parallel
Inflammatory to the presence of the 37-kDa RNase L and to an increase in nitric oxide production by immune cells.
Response However, PKR upregulation results also in a significant increase followed by a decrease in caspase 3
activity for the samples containing the highest levels of 37-kDa RNase L. This caspase 3
downregulation does not result from increased expression of the anti-apoptotic proteins Bcl-2 and
Bcl-XL. These results therefore suggest that chronic inflammation due to excess nitric oxide
production plays a role in CFS and that the normal resolution of the inflammatory process by NF-ΚB
activation and apoptotic induction is impaired. These observations draw new directions for the
therapeutic approach of CFS.
Fremont M, Antiviral Pathway Journal of Chronic No abstract available at September 2006
Vaeyens F, Herst Deregulation of Fatigue Syndrome
CV, De Meirleir Chronic Fatigue 2006;13(4):
K, Englebienne P. Syndrome Induces
Nitric Oxide
Production in
Immune Cells That
Precludes a
Resolution of the
Inflammatory
Response
Garcia-Campayo Department of The Spanish Gen Hosp OBJECTIVE: To examine some of the psychometric properties of the Spanish version of the
J, Pascual A, Psychiatry, Miguel version of the Psychiatry. 2006 FibroFatigue Scale (FFS). METHODS: FFS was administered to 120 patients diagnosed with
Alda M, Marzo J, Servet University FibroFatigue Mar- fibromyalgia and chronic fatigue syndrome. Internal consistency was evaluated by using Cronbach's
Magallon R, Hospital and Scale: validation Apr;28(2):154-60. alpha, test-retest reliability with weighted kappa and construct validity by correlations among FFS,
Fortes S. University of of a questionnaire the Fibromyalgia Impact Questionnaire (FIQ), the EuroQol 5D (EQ-5D) and the Hospital Anxiety and
Zaragoza Faculty for the observer's Depression Scale (HADS). The interrater reliability was tested using analysis of variance with
of Medicine, assessment of patients and raters as independent factors. RESULTS: Internal consistency (alpha) was .88, test-retest
Avenida Isabel La fibromyalgia and reliability was .91, and interrater reliability was .93. Significant correlations were obtained between
Catolica, s/n chronic fatigue overall FFS and the FIQ (.55, P<.01), the EQ-5D (-.48, P<.01) and the HADS depression subscale
50.009 Zaragoza, syndrome. (.25, P<.01), but not with the HADS anxiety subscale. CONCLUSION: These results support the
Spain. reliability and validity of the data obtained with the Spanish version of the FSS.
jgarcamp@arrakis.
es
Geisser ME, Chronic Pain and The association Eur J Pain. 2006 Evoked or experimental pain is often used as a model for the study of clinical pain, yet there are little
Gracely RH, Fatigue Research between Mar 16; [Epub data regarding the relationship between the two. In addition, there are few data regarding the types of
Giesecke T, Center, experimental and ahead of print] stimuli and stimulus intensities that are most closely related to clinical pain. In this study, 36 subjects
Petzke FW, Department of clinical pain with fibromyalgia (FM), chronic fatigue syndrome (CFS), or both syndromes were administered
Williams DA, Internal Medicine, measures among measures of clinical pain and underwent a dolorimetry evaluation. Subjects also underwent
Clauw DJ. Division of persons with experimental pain testing utilizing heat and pressure stimulation. Stimulation levels evoking low,
Rheumatology, fibromyalgia and moderate and high sensory intensity, and comparable levels of unpleasantness, were determined for
University of chronic fatigue both types of stimuli using random staircase methods. Clinical pain was assessed using visual
Michigan, Ann syndrome. analogue ratings and the short form of the McGill Pain Questionnaire (MPQ). Ratings of heat pain
Arbor, MI, United sensation were not significantly associated with clinical pain ratings, with the exception of
States; Department unpleasantness ratings at high stimulus intensities. Pain threshold and tolerance as assessed by
of Physical dolorimetry were significantly associated with average measures of clinical pain. Both intensity and
Medicine and unpleasantness ratings of pressure delivered using random staircase methods were significantly
Rehabilitation, associated with clinical pain at low, moderate and high levels, and the strength of the association was
University of greater at increasingly noxious stimulus intensities. These findings suggest that random pressure
Michigan Health stimulation as an experimental pain model in these populations more closely reflects the clinical pain
System, 325 E. for these conditions. These findings merit consideration when designing experimental studies of
Eisenhower clinical pain associated with FM and CFS.
Parkway, Ann
Arbor, MI 48108,
United States.
Gharibzadeh S, Is there any Med Hypotheses.
Hoseini SS. relation between 2006;66(6):1243-
moldy building 4. Epub 2006 Mar
exposure and 9.
chronic fatigue
syndrome?
Gharibzadeh S, The potential role Med Hypotheses.
Hoseini SS. of nitric oxide 2006;67(1):197-8.
metabolites in Epub 2006 Mar
diagnosing chronic 15.
fatigue syndrome.
Gibson I. House of A new look at J Clin Pathol. 2006 It has been three years since the Chief Medical Office reported on CFS/ME and the time has come for
Commons, United Chronic Fatigue Aug 25; [Epub a thorough investigation by an All Party Group drawn from the House of Commons and the House of
Kingdom. Syndrome / ahead of print] Lords. We have received many written submissions and are engaged in taking oral evidence in 2-hour
Myalgic sessions, which we open to the public as well as interested groups. The group has received a fantastic
Encephalomyelitis response to its requests for written evidence over the last few months. Questions that arise for a
(CFS/ME). government response are the lack of provision and support for CFS/ME patients, the issue of the
clinical definition of CFS/ME, the need for a diagnostic test for CFS/ME, effectiveness of the NICE
guidelines, and criteria used to decide which treatments are best for patients with CFS/ME.
Glass JM. University of Cognitive Curr Rheumatol Fibromyalgia (FM) and chronic fatigue syndrome (CFS) patients often have memory and cognitive
Michigan, Institute dysfunction in Rep. 2006 complaints. Objective cognitive testing demonstrates long-term and working memory impairments. In
for Social fibromyalgia and Dec;8(6):425-9. addition, CFS patients have slow information-processing, and FM patients have impaired control of
Research and chronic fatigue attention, perhaps due to chronic pain. Neuroimaging studies demonstrate cerebral abnormalities and
Department of syndrome: new a pattern of increased neural recruitment during cognitive tasks. Future work should focus on the
Psychiatry, 426 trends and future specific neurocognitive systems involved in cognitive dysfunction in each syndrome.
Thompson Street, directions.
Room 5256, Ann
Arbor, MI 48106-
1248, USA.
jglass@umich.edu
Goertzel BN, Virginia Tech, Combinations of Pharmacogenomic OBJECTIVE: This paper asks whether the presence of chronic fatigue syndrome (CFS) can be more
Pennachin C, de National Capital single nucleotide s. 2006 accurately predicted from single nucleotide polymorphism (SNP) profiles than would occur by
Souza Coelho L, Region, Arlington, polymorphisms in Apr;7(3):475-83. chance. METHODS: Specifically, given SNP profiles for 43 CFS patients, together with 58 controls,
Gurbaxani B, VA, USA. neuroendocrine we used an enumerative search to identify an ensemble of conjunctive rules that predict whether a
Maloney EM, ben@goertzel.org effector and patient has CFS. RESULTS: The accuracy of the rules reached 76.3%, with the highest accuracy rules
Jones JF. receptor genes yielding 49 true negatives, 15 false negatives, 28 true positives and nine false positives (odds ratio
predict chronic [OR] 8.94, p < 0.0001). Analysis of the SNPs used most frequently in the overall ensemble of rules
fatigue syndrome. gave rise to a list of 'most important SNPs', which was not identical to the list of 'most differentiating
SNPs' that one would calculate via studying each SNP independently. The top three genes containing
the SNPs accounting for the highest accumulated importances were neuronal tryptophan hydroxylase
(TPH2), catechol-O-methyltransferase (COMT) and nuclear receptor subfamily 3, group C, member 1
glucocorticoid receptor (NR3C1). CONCLUSION: The fact that only 28 out of several million
possible SNPs predict whether a person has CFS with 76% accuracy indicates that CFS has a genetic
component that may help to explain some aspects of the illness.
Goertzel BN, Virginia Tech, Allostatic load is Pharmacogenomic OBJECTIVES: To further explore the relationship between chronic fatigue syndrome (CFS) and
Pennachin C, de National Capital associated with s. 2006 allostatic load (AL), we conducted a computational analysis involving 43 patients with CFS and 60
Souza Coelho L, Region, Arlington, symptoms in Apr;7(3):485-94. nonfatigued, healthy controls (NF) enrolled in a population-based case-control study in Wichita (KS,
Maloney EM, Virginia, USA. chronic fatigue USA). We used traditional biostatistical methods to measure the association of high AL to
Jones JF, ben@goertzel.org syndrome patients. standardized measures of physical and mental functioning, disability, fatigue and general symptom
Gurbaxani B. severity. We also used nonlinear regression technology embedded in machine learning algorithms to
learn equations predicting various CFS symptoms based on the individual components of the
allostatic load index (ALI). METHODS: An ALI was computed for all study participants using
available laboratory and clinical data on metabolic, cardiovascular and hypothalamic-pituitary-
adrenal (HPA) axis factors. Physical and mental functioning/impairment was measured using the
Medical Outcomes Study 36-item Short Form Health Survey (SF-36); current fatigue was measured
using the 20-item multidimensional fatigue inventory (MFI); frequency and intensity of symptoms
was measured using the 19-item symptom inventory (SI). Genetic programming, a nonlinear
regression technique, was used to learn an ensemble of different predictive equations rather just than
a single one. Statistical analysis was based on the calculation of the percentage of equations in the
ensemble that utilized each input variable, producing a measure of the 'utility' of the variable for the
predictive problem at hand. Traditional biostatistics methods include the median and Wilcoxon tests
for comparing the median levels of subscale scores obtained on the SF-36, the MFI and the SI
summary score. RESULTS: Among CFS patients, but not controls, a high level of AL was
significantly associated with lower median values (indicating worse health) of bodily pain, physical
functioning and general symptom frequency/intensity. Using genetic programming, the ALI was
determined to be a better predictor of these three health measures than any subcombination of ALI
components among cases, but not controls.
Goodwin GM. Oxford University, Depression and Dialogues Clin Depression can occur in association with virtually all the other psychiatric and physical diagnoses.
Warneford associated physical Neurosci. Physical illness increases the risk of developing severe depressive illness. There are two broadly
Hospital, United diseases and 2006;8(2):259-65. different mechanisms. The most obvious has a psychological or cognitive mechanism. Thus, the
Kingdom. symptoms. illness may provide the life event or chronic difficulty that triggers a depressive episode in a
guy.goodwin@psy vulnerable individual. Secondly, more specific associations appear to exist between depression and
chiatry.oxford.ac.u particular physical disorders. These may turn out to be of particular etiological interest. The best
k examples are probably stroke and cardiovascular disease. Finally, major depression, but especially
minor depression, dysthymia, and depressive symptoms merge with other manifestations of human
distress with which patients present to their doctors. Such somatic presentations test the conventional
distinction between physical and mental disorder and are a perennial source of controversy.
Gottfries CG, Long-Term Journal of Chronic No abstract available at September 2006
Hager O, Regland Treatment with a Fatigue Syndrome
B, Zachrisson O. Staphylococcus 2006;13(4):
Toxoid Vaccine in
Patients with
Fibromyalgia and
Chronic Fatigue
Syndrome
Gottfries CG, Long-Term Journal of Chronic One hundred and sixty patients with fibromyalgia and chronic fatigue syndrome, who were on a
Ove Häger, Björn Treatment with a Fatigue Syndrome continuous treatment with a Staphylococcus vaccine, were followed during one year with repeated
Regland, Olof Staphylococcus 2006; 13(4): 31-43 consultation visits. The patients had participated in controlled studies and been on continuous
Zachrisson Toxoid Vaccine in treatment with the vaccine for 22 ±10 months before inclusion into this follow-up study. They were
Patients with treated with 1 mL of the vaccine subcutaneously every third to fourth week. Adverse events were
Fibromyalgia and few. The adherence to the treatment was very good. Over a period of one year, 8% withdrew, and in
Chronic Fatigue only 5%, the withdrawal was due to insufficient clinical effect. Only in two cases where the patients
Syndrome were allergic to the preservative of the vaccine, the side effects caused the withdrawal of the
treatment. Ratings with scales (CPRS-15 and FibroFatigue) showed improvement from start of
treatment and also further improvement during the follow-up year. In view of the natural history for
these disorders the result is of interest.
Grans H, Nilsson Karolinska Reduced levels of J Clin Pathol. 2006 BACKGROUND: Chronic fatigue syndrome (CFS) is an illness with unknown aetiology and
M, Dahlman- Institutet, Sweden. oestrogen receptor May 26; [Epub pathophysiology. The sex difference observed for CFS indicates a role for oestrogen and oestrogen
Wright K, {beta} mRNA in ahead of print] receptors (ERs) for disease development. Furthermore, an immuno-mediated pathogenesis has been
Evengard B. Swedish patients suggested for CFS which provides an additional connection to oestrogen, which display
with chronic immunomodular functions. AIMS: The aim of this study was to investigate a possible association of
fatigue syndrome. ER mRNAs and two ERbeta single nucleotide polymorphisms (SNPs) with CFS. METHODS:
Messenger RNA levels of ERalpha, ERbetawt and ERbetacx were investigated in peripheral blood
mononuclear cells (PBMCs) from 30 CFS patients and 36 healthy controls by quantitative real-time
PCR. Two ERbeta SNPs were scored in the same material. RESULTS: The CFS patient group
showed significantly lower mRNA expression levels of ERbetawt compared with the healthy control
group. No differences were observed for ERalpha or ERbetacx between patients and controls. There
were no significant differences in frequency for the investigated ERbeta SNPs between cases and
controls. CONCLUSIONS: The reduced ERbetawt expression levels observed in this study is
consistent with an immune-mediated pathogenesis of CFS. Additionally, the observation that
ERbetawt expression is decreased in CFS could provide an entry point to identify interesting,
potentially disease causing, candidate molecules for further study. A possible connection between
oestrogen, ERs and CFS should be further evaluated.
Greenberg S, Cardiac [Chronic fatigue Harefuah. 2006 One of the major symptoms of chronic fatigue syndrome (CFS) is reduced exercise and functional
Frid M. Rehabilitation and syndrome-- Apr;145(4):276- capacity and increased fatigue symptoms following physical effort. A review of the literature
Prevention Unit, exercise and 80, 318. indicates that patients that suffer from CFS are characterized by: low aerobic capacity, higher heart
Tel Aviv Medical physical activity] rate during sub-maximal exercise, higher subjective effort prescription, reduced muscle strength, and
Center, Israel. [Article in prolonged recovery period. Although several symptoms are a result of lack of physical activity,
shaigr@zahav.net.i Hebrew] several mechanisms were suggested to explain those symptoms: pathological heart rate control,
l reduced aerobic metabolic capacity, reduced blood supply to the working muscles and nerve system
dysfunction. Participating in guided exercise programs was found to be the most effective treatment
in improving exercise and functional capacity, reducing fatigue syndromes and improving patients'
daily function.
Greenfield JR, Department of Evaluation of 38: Eur J OBJECTIVE: The aim of this study was to review the results of dynamic pituitary testing in patients
Samaras K. Endocrinology, St pituitary function Endocrinol. 2006 presenting with fatigue. METHODS: We reviewed clinical histories and insulin tolerance test (ITT)
Vincent's Hospital in the fatigued Jan;154(1):147-57. results of 59 patients who presented with fatigue and other symptoms of glucocorticoid insufficiency
and St Vincent's patient: a review over a 4-year period. All patients referred for ITT had an early-morning cortisol level of <400 nM and
Clinic and the of 59 cases. a low or normal ACTH level. RESULTS: Peak cortisol and GH responses following insulin-induced
Garvan Institute of hypoglycaemia were normal in only seven patients (12%). Median age of the remaining 52 patients
Medical Research, was 47 years (range, 17-67 years); all but five were female. Common presenting symptoms were
Sydney, Australia. neuroglycopaenia (n = 47), depression (n = 37), arthralgia and myalgia (n = 28), weight gain (n = 25),
weight loss (n = 9), postural dizziness (n = 15) and headaches (n = 13). Other medical history
included autoimmune disease (n = 20; particularly Hashimoto's thyroiditis, Graves' disease and
coeliac disease), postpartum (n = 8) and gastrointestinal (n = 2) haemorrhage and
hyperprolactinaemia (n = 13). 31 subjects had peak cortisol levels of <500 nM (suggestive of ACTH
deficiency; 18 of whom had levels < 400 nM) and a further six had indeterminate results (500-550
nM). The remaining 15 subjects had normal cortisol responses (median 654 nM; range, 553-1062 nM)
but had low GH levels following hypoglycaemic stimulation (5.9 mU/l; 3-11.6 mU/l).
CONCLUSION: Our results suggest that patients presenting with fatigue and symptoms suggestive of
hypocortisolism should be considered for screening for secondary adrenal insufficiency, particularly
in the presence of autoimmune disease or a history of postpartum or gastrointestinal haemorrhage.
Whether physiological glucocorticoid replacement improves symptoms in this patient group is yet to
be established.
Guilleminault C, Stanford Chronic fatigue, Sleep Med. 2006 BACKGROUND AND PURPOSE: To investigate the complaint of unrefreshing sleep with study of
Poyares D, Rosa University Sleep unrefreshing sleep Sep;7(6):513-20. sleep electroencephalogram (EEG) in patients with chronic fatigue. PATIENTS AND METHODS:
A, Kirisoglu C, Disorders Clinic, and nocturnal Epub 2006 Aug Fourteen successively seen patients (mean age: 41.1 9.8) who complained of chronic fatigue but
Almeida T, Lopes 401 Quarry road, polysomnography. 24. denied sleepiness and agreed to participate were compared to 14 controls (33.6+/-10.2 years) who
MC. suite 3301, were monitored during sleep recorded in parallel. After performing conventional sleep scoring we
Stanford, CA applied Fast Fourier Transformation (FFT) for the delta 1, delta 2, theta, alpha, sigma 1, sigma 2, beta
94305, USA. EEG frequency bands. The presence of non-rapid eye movement (NREM) sleep instability was
cguil@stanford.ed studied with calculation of cyclic alternating pattern (CAP) rate. Two-way analysis of variance
u (ANOVA) was performed to analyze FFT results and Mann-Whitney U-test to compare CAP rate in
both groups of subjects. RESULTS: Slow wave sleep (SWS) percentage and sleep efficiency were
lower, but there was a significant increase in delta 1 (slow delta) relative power in the chronic fatigue
group when compared to normals (P<0.01). All the other frequency bands were proportionally and
significantly decreased compared to controls. CAP rate was also significantly greater in subjects with
chronic fatigue than in normals (P=0.04). An increase in respiratory effort and nasal flow limitation
were noted with chronic fatigue. CONCLUSIONS: The complaints of chronic fatigue and
unrefreshing sleep were associated with an abnormal CAP rate, with increase in slow delta power
spectrum, affirming the presence of an abnormal sleep progression and NREM sleep instability.
These specific patterns were related to subtle, undiagnosed sleep-disordered breathing.
Gurbaxani BM, 1Centers for Linear data mining Pharmacogenomic OBJECTIVES: To provide a mathematical introduction to the Wichita (KS, USA) clinical dataset,
Jones JF, Disease Control the Wichita s. 2006 which is all of the nongenetic data (no microarray or single nucleotide polymorphism data) from the
Goertzel BN, and Prevention, clinical matrix Apr;7(3):455-65. 2-day clinical evaluation, and show the preliminary findings and limitations, of popular, matrix
Maloney EM. 600 Clifton Road, suggests sleep and algebra-based data mining techniques. METHODS: An initial matrix of 440 variables by 227 human
MS A-15, Atlanta, allostatic load subjects was reduced to 183 variables by 164 subjects. Variables were excluded that strongly
GA 30333, USA. involvement in correlated with chronic fatigue syndrome (CFS) case classification by design (for example, the
buw8@cdc.gov chronic fatigue multidimensional fatigue inventory [MFI] data), that were otherwise self reporting in nature and also
syndrome. tended to correlate strongly with CFS classification, or were sparse or nonvarying between case and
control. Subjects were excluded if they did not clearly fall into well-defined CFS classifications, had
comorbid depression with melancholic features, or other medical or psychiatric exclusions. The
popular data mining techniques, principle components analysis (PCA) and linear discriminant
analysis (LDA), were used to determine how well the data separated into groups. Two different
feature selection methods helped identify the most discriminating parameters. RESULTS: Although
purely biological features (variables) were found to separate CFS cases from controls, including many
allostatic load and sleep-related variables, most parameters were not statistically significant
individually. However, biological correlates of CFS, such as heart rate and heart rate variability,
require further investigation. CONCLUSIONS: Feature selection of a limited number of variables
from the purely biological dataset produced better separation between groups than a PCA of the entire
dataset. Feature selection highlighted the importance of many of the allostatic load variables studied
in more detail by Maloney and colleagues in this issue [1] , as well as some sleep-related variables.
Nonetheless, matrix linear algebra-based data mining approaches appeared to be of limited utility
when compared with more sophisticated nonlinear analyses on richer data types, such as those found
in Maloney and colleagues [1] and Goertzel and colleagues [2] in this issue.
Hampton T. Chronic fatigue JAMA. 2006 Dec News
syndrome answers 27;296(24):2915.
sought.
Hampton T. Researchers find JAMA. 2006 Jun
genetic clues to 7;295(21):2466-7.
chronic fatigue
syndrome.
Hanna EZ. Comments on J Clin Letter
guest editorial, Psychopharmacol.
"Chronic fatigue 2006
syndrome, mast Dec;26(6):690;
cells, and tricyclic author reply 690-1.

antidepressants". J
Clin
Psychopharmacol.
2005
Dec;25(6):515-20
Hannestad U, Faculty of Health beta-Alanine and Clin Chim Acta. BACKGROUND: Due to the occurrence of sleep disturbances and fatigue in chronic fatigue
Theodorsson E, Science, Division gamma- 2006 Jul 14; [Epub syndrome (CFS), an investigation was performed to examine if there is an abnormal excretion of
Evengard B. of Clinical aminobutyric acid ahead of print] gamma-aminobutyric acid (GABA) and/or its structural analogue beta-alanine in the urine from CFS
Chemistry, in chronic fatigue patients. Both GABA and beta-alanine are inhibitory neurotransmitters in the mammalian central
Linkoping syndrome. nervous system. METHODS: The 24 h urine excretion of GABA and beta-alanine was determined by
University, SE-581 isotope dilution gas chromatography mass spectrometry in 33 CFS patients and 43 healthy controls.
85 Linkoping, The degree of symptoms in both patients and controls was measured by grading of three typical CFS
Sweden. symptoms using a Visual Analogue Scale. RESULTS: Men had a significantly higher excretion of
both beta-alanine and GABA than women. Comparing CFS patients with healthy controls showed no
significant difference in excretion of neither beta-alanine nor GABA. No correlation was found
between the excretion of beta-alanine or GABA and any of the three characteristic CFS symptoms
measured. However, two female and two male CFS patients excreted considerably higher amounts of
beta-alanine in their 24 h urine samples than control subjects. CONCLUSIONS: Increased excretion
of beta-alanine was found in a subgroup of CFS patients, indicating that there may be a link between
CFS and beta-alanine in some CFS patients.
Hawk C, Jason Reliability of a Journal of Chronic No abstract available at September 2006
LA, Torres- Chronic Fatigue Fatigue Syndrome
Harding SR. Syndrome 2006;13(4):
Questionnaire
Heesen C, Department of Fatigue in multiple J Neurol BACKGROUND: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is
Nawrath L, Reich Neurology, sclerosis: an Neurosurg known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and
C, Bauer N, University example of Psychiatry. 2006 studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative
Schulz KH, Gold Hospital cytokine mediated Jan;77(1):34-9. role in the development of fatigue. METHODS: We compared whole blood stimulatory capacity for
SM. Eppendorf, sickness Comment in: J pro- (TNFalpha, IFNgamma) and anti-inflammatory cytokines (IL-10) as well as hypothalamo-
Martinistrasse 52, behaviour? Neurol Neurosurg pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without
D-20246 Psychiatry. 2006 fatigue as determined by the Fatigue Severity Scale (FSS). RESULTS: Proinflammatory cytokines
Hamburg, Jan;77(1):2-3. were significantly higher (TNFalpha: 478.9 v 228.2 pg/ml, p = 0.01; IFNgamma: 57.6 v 27.8 pg/ml; p
Germany. = 0.01) in MS patients with fatigue. Furthermore, TNFalpha values significantly correlated with
heesen@uke.uni- daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for
hamburg.de disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration,
Expanded Disability Status Scale, and depression further increased the correlation of cytokine
production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with
cognitive impairment. CONCLUSION: Our data suggest that fatigue in MS is at least partially
mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis
dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive
impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in
MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis
in MS.
Heim C, Wagner Viral Exanthems Early adverse Arch Gen CONTEXT: Chronic fatigue syndrome (CFS) is an important public health problem. The causes of
D, Maloney E, and Herpesvirus experience and Psychiatry. 2006 CFS are unknown and effective prevention strategies remain elusive. A growing literature suggests
Papanicolaou DA, Branch, Division risk for chronic Nov;63(11):1258- that early adverse experience increases the risk for a range of negative health outcomes, including
Solomon L, Jones of Viral and fatigue syndrome: 66. fatiguing illnesses. Identification of developmental risk factors for CFS is critical to inform
JF, Unger ER, Rickettsial results from a pathophysiological research and devise targets for primary prevention. OBJECTIVE: To examine the
Reeves WC. Diseases, National population-based relationship between early adverse experience and risk for CFS in a population-based sample of
Center for study. clinically confirmed CFS cases and nonfatigued control subjects. DESIGN, SETTING, AND
Infectious PARTICIPANTS: A case-control study of 43 cases with current CFS and 60 nonfatigued controls
Diseases, Centers identified from a general population sample of 56 146 adult residents from Wichita, Kan. MAIN
for Disease OUTCOME MEASURES: Self-reported childhood trauma (sexual, physical, and emotional abuse and
Control and emotional and physical neglect) and psychopathology (depression, anxiety, and posttraumatic stress
Prevention, disorder) by CFS status. RESULTS: The CFS cases reported significantly higher levels of childhood
Atlanta, GA trauma and psychopathology compared with the controls. Exposure to childhood trauma was
30322, USA. associated with a 3- to 8-fold increased risk for CFS across different trauma types. There was a
cmheim@emory.e graded relationship between the degree of trauma exposure and CFS risk. Childhood trauma was
du associated with greater CFS symptom severity and with symptoms of depression, anxiety, and
posttraumatic stress disorder. The risk for CFS conveyed by childhood trauma increased with the
presence of concurrent psychopathology. CONCLUSIONS: This study provides evidence of increased
levels of multiple types of childhood trauma in a population-based sample of clinically confirmed
CFS cases compared with nonfatigued controls. Our results suggest that childhood trauma is an
important risk factor for CFS. This risk was in part associated with altered emotional state. Studies
scrutinizing the psychological and neurobiological mechanisms that translate childhood adversity into
CFS risk may provide direct targets for the early prevention of CFS.
Hickie I, Brain and Mind Post-infective and BMJ. 2006 Sep OBJECTIVE: To delineate the risk factors, symptom patterns, and longitudinal course of prolonged
Davenport T, Research Institute, chronic fatigue 16;333(7568):575. illnesses after a variety of acute infections. DESIGN: Prospective cohort study following patients
Wakefield D, Sydney University, syndromes Epub 2006 Sep 1. from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever),
Vollmer-Conna Sydney, NSW precipitated by or Ross River virus (epidemic polyarthritis). SETTING: The region surrounding the township of
U, Cameron B, 2050, Australia. viral and non-viral Dubbo in rural Australia, encompassing a 200 km geographical radius and 104,400 residents.
Vernon SD, pathogens: PARTICIPANTS: 253 patients enrolled and followed at regular intervals over 12 months by self
Reeves WC, prospective cohort report, structured interview, and clinical assessment. OUTCOME MEASURES: Detailed medical,
Lloyd A; Dubbo study. psychiatric, and laboratory evaluations at six months to apply diagnostic criteria for chronic fatigue
Infection syndrome. Premorbid and intercurrent illness characteristics recorded to define risk factors for
Outcomes Study chronic fatigue syndrome. Self reported illness phenotypes compared between infective groups.
Group. RESULTS: Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive
difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of
whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue
syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The
syndrome was predicted largely by the severity of the acute illness rather than by demographic,
psychological, or microbiological factors. CONCLUSIONS: A relatively uniform post-infective
fatigue syndrome persists in a significant minority of patients for six months or more after clinical
infection with several different viral and non-viral micro-organisms. Post-infective fatigue syndrome
is a valid illness model for investigating one pathophysiological pathway to chronic fatigue
syndrome.
Hines CH, Reliability of a Journal of Chronic Background: A diagnostic instrument, the CFS Questionnaire, was developed for clinicians and
Leonard A. Chronic Fatigue Fatigue Syndrome researchers to administer to their patients as a screening instrument for CFS. The CFS Questionnaire
Jason, Susan R. Syndrome 2006; 13(4): 45-71 is comprehensive, covering the inclusionary and exclusionary self-report criteria of the current U.S.
Torres-Harding Questionnaire case definition (Fukuda et al. 199). The instrument also assesses past and current activity levels, and
symptoms of post-exertional malaise to ensure these items are adequately assessed. Objectives: The
goal of the present study was to evaluate the diagnostic reliability of an experimental measure for
assessing chronic fatigue syndrome (CFS). Methods: This instrument was administered to 15 persons
with CFS, 15 persons with major depressive disorder (MDD), and 15 controls. Using the Fukuda et al.
(1994) diagnostic criteria, raters independently reviewed participants' CFS Questionnaire responses
and rated whether each study participant met criteria for chronic fatigue syndrome. Results: This
instrument demonstrated good inter-rater reliability. Further, this instrument demonstrated adequate
classification accuracy, with a 9.3 positive likelihood ratio and a .08 negative likelihood ratio.
Overall, the CFS Questionnaire demonstrated good test-retest reliability, with intra-class correlation
coefficients and kappa coefficients at .70 or higher for most items. Lower test-retest reliability
coefficients were found for some items assessing temporal symptoms or items requiring an estimate
of time. Conclusion: The present study suggests that the CFS Questionnaire is a reliable diagnostic
tool. Use of the CFS Questionnaire should promote higher levels of diagnostic reliability because it
allows for accurate classification of individuals with CFS
Horng-Shiuann Unexplained Journal of Chronic Background: Unexplained prolonged fatigue (UPF) is one of the most common complaints in primary
Wu HS, Mengel Prolonged Fatigue Fatigue Syndrome care. UPF is difficult to manage because of its nonspecific nature and unknown mechanism. UPF
MB. in Primary Care 2006;13(1): 15-34 frequently frustrates health care professionals and has negative impacts on the physician-patient
relationship. Although it is nonfatal, fatigueassociated functional impairments and economic
consequences are substantial, negatively impacting patients' quality of life. Objectives: To evaluate
current knowledge development of UPF and to help focus the direction of future investigations.
Methods: A literature review was undertaken with the MEDLINE databases chosen as the primary
electronic resources to retrieve the literature. Results: Current understanding of UPF is limited. Lack
of consistent scientific language is a major problem. There is no consensus about the case definition
of UPF even for the most widely studied chronic fatigue syndrome (CFS). Various sets of
classification have been developed, each with similar but not identical criteria. Clinicians are dubious
about perceiving fatigue as a clinical entity and ignore the diagnosis criteria. Many more patients are
excluded than included from the current classifications and lack appropriate evaluation and treatment.
The predisposing factors are not well established with the exception of being female and relatively
young. Laboratory testing and immune and endocrine abnormalities are inconsistent in determining
the causes. Psychological and social factors play an important but inconclusive role in mediating
fatigue status. Conclusions: The high prevalence, persistence, and disability-associated consequences
of UPF warrant more attention. Further investigations of the symptoms, psychosocial-based symptom
experiences, and a search for effective management are needed.
Keywords: Unexplained fatigue, prolonged fatigue, primary care
Hoseini SS, Anakinra: a Med Hypotheses.
Gharibzadeh S. potential treatment 2006;67(1):196-7.
for chronic fatigue Epub 2006 Mar
syndrome. 13.
Huibers MJ, Department of Chronic fatigue Occup Environ OBJECTIVE: To assess whether CFS-like caseness (meeting the criteria for chronic fatigue syndrome
Leone SS, Kant Medical, Clinical syndrome-like Med. 2006 (CFS)) predicts work status in the long term. METHODS: Prospective study in a sample of fatigued
IJ, Knottnerus and Experimental caseness as a Aug;63(8):570-2. employees absent from work. Data were collected at baseline and four years later, and included CFS-
JA. Psychology, predictor of work Epub 2006 May like caseness and work status (inactive work status and full work incapacity). RESULTS: CFS-like
Maastricht status in fatigued 12. cases at baseline were three times more likely to be unable to work at follow up than fatigued
University, employees on sick employees who did not meet CFS criteria at baseline (ORs 3-3.3). These associations grew even
Maastricht, leave: four year stronger when demographic and clinical confounders were controlled for (ORs 3.4-4.4).
Netherlands. follow up study. CONCLUSION: A CFS-like status (compared to non-CFS fatigue) proved to be a strong predictor of
m.huibers@dmkep an inactive work status and full work incapacity in the long term. Since little is known about effective
.unimaas.nl interventions that prevent absenteeism and work incapacity or facilitate return to work in subjects
with chronic fatigue, there is a great need for powerful early interventions that restore or preserve the
ability to work, especially for workers who meet criteria for CFS.
Huibers MJ, Department of The act of Psychol Med. 2006 BACKGROUND: One of the many controversies surrounding chronic fatigue syndrome (CFS) is the
Wessely S. Medical, Clinical diagnosis: pros and Jul;36(7):895-900. possible impact of the diagnostic label: is it disabling or enabling? In this paper, we discuss the pros
& Experimental cons of labelling Epub 2006 Jan 10. and cons of labelling CFS. METHOD: A narrative synthesis of the literature. RESULTS: Diagnosed
Psychology, chronic fatigue CFS patients have a worse prognosis than fatigue syndrome patients without such a label. The ways in
Maastricht syndrome. which CFS patients perceive themselves, label their symptoms and appraise stressors may perpetuate
University, The or exacerbate their symptoms, a process that involves psychological, psychosocial and cultural
Netherlands. factors. Labels can also lead to conflicts with doctors who fear diagnosis might lead to worse
m.huibers@dmkep outcomes. However, on the other hand, finding a label that fits one's condition can provide meaning,
.unimaas.nl emotional relief and recognition, whilst the denial of the diagnosis of CFS in those who have already
reached their own conclusion can be very counter productive. The act of diagnosis therefore seems to
be a trade-off between empowerment, illness validation and group support, contrasted with the risk of
diagnosis as self-fulfilling prophecy of non-recovery. CONCLUSIONS: The answer to the question of
'to label or not to label' may turn out to depend not on the label, but on what that label implies. It is
acceptable and often beneficial to make diagnoses such as CFS, provided that this is the beginning,
and not the end, of the therapeutic encounter.
Hunsaker DH, Department of Snoring Otolaryngol Head OBJECTIVE: To analyze the impact of snoring, independent of obstructive sleep apnea syndrome on
Riffenburgh RH. Otolaryngology, significance in Neck Surg. 2006 patients referred for home sleep studies and to report a new technology for the reporting of snoring,
Naval Medical patients May;134(5):756- using sophisticated sound collection and noise-canceling technology. STUDY DESIGN AND
Center San Diego, undergoing home 60. SETTING: A retrospective statistical review of consecutive anonymous data compiled from
San Diego, sleep studies. questionnaires and digital data of snoring loudness and duration measured at the upper lip during
California 92109, unattended home sleep studies in 4,860 patients referred for snoring and sleep-disturbed breathing.
USA. RESULTS: A strong relationship exists between a history of snoring and complaints of daytime
tripwest@earthlink sleepiness (80%), obesity (73%), and chronic fatigue (78%) (all yield P<0.001). By contrast, only
.net 42% to 48% of patients without these symptoms complain of snoring. In 3 multiple-regression
analyses, the percent of time snoring, average loudness, and peak loudness are all significantly
predicted by the apnea hypopnea index (all P<0.003), body mass index (all P<0.001), and age
(P=0.014). Daytime sleepiness was strongly predicted by percent time snoring (P=0.014), weakly by
average loudness (P=0.046), and not at all by peak loudness (P=0.303). CONCLUSION: By using a
pair of microphones placed at the upper lip, one that samples breath sounds and the other ambient
sound and artifact noise, the NovaSOM QSG measures snoring while canceling ambient noise. The
clinical impact of snoring on the patient as well as the bed partner, independent of obstructive sleep
apnea syndrome, is an unrecognized factor in sleep-disturbed breathing. SIGNIFICANCE:
Measurable criteria to define snoring are suggested. Snoring loudness is not measured in most
laboratory Polysomnograms. EBM rating: B-3b.
Hyland ME, School of Chronic fatigue J Health Psychol. Fifty-three chronic fatigue syndrome patients treated at a complementary medical centre were
Sodergren SC, Psychology, syndrome: the role 2006 assessed over 12 months. Measures included the Chalder Fatigue scale, the General Health
Lewith GT. University of of positivity to Sep;11(5):731-41. Questionnaire (GHQ) and positivity in illness (Silver Lining Questionnaire, SLQ). The SLQ measured
Plymouth, illness in chronic at 6 and 9 months predicted (p < .01) mental (but not physical) fatigue at 12 months independently of
Plymouth, UK. fatigue syndrome current mental fatigue, initial mental fatigue, duration since diagnosis and time between start of
mhyland@plymout patients. treatment and entry to the study. The GHQ did not predict fatigue at any time point. The results
h.ac.uk suggest that a caring therapeutic intervention increases positive interpretations of illness prior to
improvements in mental fatigue, but that positivity does not play a causal role in the reduction of
fatigue.
Hyland ME, University of Chronic fatigue J Health Psychol. Fifty-three chronic fatigue syndrome patients treated at a complementary medical centre were
Sodergren SC, Plymouth, UK. syndrome: the role 2006 assessed over 12 months. Measures included the Chalder Fatigue scale, the General Health
Lewith GT. mhyland@plymout of positivity to Sep;11(5):731-41. Questionnaire (GHQ) and positivity in illness (Silver Lining Questionnaire, SLQ). The SLQ measured
h.ac.uk. illness in chronic at 6 and 9 months predicted (p < .01) mental (but not physical) fatigue at 12 months independently of
fatigue syndrome current mental fatigue, initial mental fatigue, duration since diagnosis and time between start of
patients. treatment and entry to the study. The GHQ did not predict fatigue at any time point. The results
suggest that a caring therapeutic intervention increases positive interpretations of illness prior to
improvements in mental fatigue, but that positivity does not play a causal role in the reduction of
fatigue.
Hyland ME, Whalley Chronic fatigue Comment on:
B.
syndrome. Lancet. 2006 Jan
28;367(9507):346-
55.
Lancet. 2006 May
13;367(9522):1573
-4; author reply
1575.
Iasiukiavichene [Chronic fatigue Kardiologiia. Chronic fatigue markedly worsens quality of life of cardiological patients. Chronic fatigue and
L, Vasiliauskas D. syndrome in 2006;46(1):58-64. chronic fatigue syndrome are neuro-immuno-endocrine disorders which manifest as moderate and
cardiology severe even invalidizing fatigue with psychosomatic symptoms. External and internal stress such as
neurohumoral psychological stress, stress after major surgery and trauma, depressive states, inadequate physical
changes] [Article exercise, chronic heart failure, chronic viral infection, oncologic diseases, -- can promote
in Russian] development of chronic fatigue. Immune and hypothalamic-pituitary-adrenal (HPA) axis
abnormalities were found to be associated with this condition. Measurement of plasma cortisol
concentration is used as basic characteristic of HPA axis function. Measures aimed at detection of
chronic fatigue in cardiological patients and its appropriate management should supplement programs
of integrated rehabilitation in order to improve quality of life and facilitate return to work.
Ismail K, Lewis Department of Multi-symptom Philos Trans R Soc Explanatory models for the increased prevalence of ill health in Gulf veterans compared to those not
G. Psychological illnesses, Lond B Biol Sci. deployed to the Gulf War 1990-1991 remain elusive. This article addresses whether multi-symptom
Medicine, Institute unexplained illness 2006 Apr reporting in Gulf veterans are types of medically unexplained symptoms and whether the alleged Gulf
of Psychiatry, and Gulf War 29;361(1468):543- War Syndrome is best understood as a medically unexplained syndrome. A review of the
King's College Syndrome. 51. epidemiological studies, overwhelmingly cross-sectional, describing ill health was conducted
London, Weston including those that used factor analysis to search for underlying or latent clinical constructs. The
Education Centre, overwhelming evidence was that symptoms in Gulf veterans were either in keeping with currently
UK. defined psychiatric disorders such as depression and anxiety or were medically unexplained. The
k.ismail@iop.kcl.a application of factor analysis methods had varied widely with a risk of over interpretation in some
c.uk studies and limiting the validity of their findings. We concluded that ill health in Gulf veterans and
the alleged Gulf War Syndrome is best understood within the medically unexplained symptoms and
syndromes constructs. The cause of increased reporting in Gulf veterans are still not clear and
requires further inquiry into the interaction between sociological factors and symptomatic distress.
Ito N, Nagai T, Kitasato Institute Antidepressant- Phytomedicine. Koso-san (Xiang-Su-San in Chinese), a Kampo (Japanese herbal) medicine, is used clinically in East
Yabe T, Nunome for Life Sciences, like activity of a 2006 Nov;13(9- Asia for the treatment of depression-like symptoms associated with the initial stage of the common
S, Hanawa T, Kitasato Kampo (Japanese 10):658-67. Epub cold, allergic urticaria due to food ingestion, irritable bowel syndrome, chronic fatigue syndrome,
Yamada H. University, 5-9-1 herbal) medicine, 2006 Mar 3. insomnia, and autonomic imbalance. However, the antidepressant-like activity of Koso-san has never
Shirokane, Koso-san (Xiang- been evaluated scientifically. In this study, ddY mice subjected to a combination of forced swimming
Minato-ku, Tokyo Su-San), and its and chronic mild stresses were termed depression-like model mice. The degree of the depression-like
108-8641, Japan. mode of action via state was measured by the animal's duration of immobility using the forced swimming test (FST).
the hypothalamic- Oral administration of Koso-san (1.0 g/kg/body wt./day, 9 days) significantly shortened the duration
pituitary-adrenal of immobility of the depression-like model mice in the FST; however, locomotor activity was not
axis. affected. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in
the pathophysiology of depression. Levels of corticotropin-releasing hormone mRNA expression in
the hypothalamus and proopiomelanocortin mRNA expression in the pituitary were significantly
increased, and glucocorticoid receptor protein expression in the hypothalamus paraventricular nucleus
was downregulated in the depression-like model mice. However, Koso-san ameliorated these
alterations to the normal conditions. The results of this study suggest that Koso-san shows the
antidepressant-like effect through suppressing the hyperactivity of the HPA axis in depression-like
model mice.
Jackson JL, Department of Antidepressants CNS Spectr. 2006 Somatic symptoms are common in primary care and clinicians often prescribe antidepressants as
O'Malley PG, Medicine, and cognitive- Mar;11(3):212-22. adjunctive therapy. There are many possible reasons why this may work, including treating comorbid
Kroenke K. Uniformed behavioral therapy depression or anxiety, inhibition of ascending pain pathways, inhibition of prefrontal cortical areas
Services for symptom that are responsible for "attention" to noxious stimuli, and the direct effects of the medications on the
University of syndromes. syndrome. There are good theoretical reasons why antidepressants with balanced norepinephrine and
Health Sciences, serotonin effects may be more effective than those that act predominantly on one pathway, though
Bethesda, MD head-to-head comparisons are lacking. For the 11 painful syndromes review in this article, cognitive-
20814, USA. behavioral therapy is most consistently demonstrated to be effective, with various antidepressants
jejackson@usuhs. having more or less randomized controlled data supporting or refuting effectiveness. This article
mil reviews the randomized controlled trial data for the use of antidepressant and cognitive-behavior
therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain, headache,
fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms, chronic facial pain,
noncardiac chest pain, interstitial cystitis, and chronic pelvic pain. For some syndromes, the data for
or against treatment effectiveness is relatively robust, for many, however, the data, one way or the
other is scanty.
Janal MN, Fatigue Research Sub-typing CFS Biol Psychol. 2006 The diagnosis of chronic fatigue syndrome (CFS), an illness characterized by medically unexplained
Ciccone DS, Center and patients on the Aug;73(2):124-31. fatigue, depends on a clinical case definition representing one or more pathophysiological
Natelson BH. Department of basis of 'minor' Epub 2006 Feb 10. mechanisms. To prepare for studies of these mechanisms, this study sought to identify subtypes of
Psychiatry, New symptoms. CFS. In 161 women meeting 1994 criteria for CFS, principal components analysis of the 10 'minor'
Jersey Medical symptoms of CFS produced three factors interpreted to indicate musculoskeletal, infectious and
School, BHSB- neurological subtypes. Extreme scores on one or more of these factors characterized about 2/3 of the
F1522, Box 1709, sample. Those characterized by the neurological factor were at increased risk of reduced scores on
University of cognitive tests requiring attention, working memory, long-term memory or rapid performance. In
Medicine and addition, the neurological subtype was associated with reduced levels of function. Those
Dentistry of New characterized by the musculoskeletal factor were at increased risk for the diagnosis of fibromyalgia
Jersey, Newark, NJ (chronic widespread pain and mechanical allodynia) and reduced physical function. Those
07101, United characterized by the infectious factor were less likely to evidence co-occurring fibromyalgia, and
States. showed lesser risk of functional impairment. The prevalence of disability was increased in those with
the highest scores on any of the subtypes, as well as in those with high scores on multiple factors.
Depression and anxiety, while frequently present, were not more prevalent in any particular subtype,
and did not increase with the severity of specific symptom reports. Results suggest that subtypes of
CFS may be identified from reports of the minor diagnostic symptoms, and that these subtypes
demonstrate construct validity.
Jason LA, Bell A Pediatric Case Journal of Chronic For a diagnosis chronic fatigue syndrome (CFS), most researchers use criteria that were developed by
DS, Row J, Van Definition for Fatigue Syndrome Fukuda et al. (1994), with modifications suggested by Reeves et al. (2003). However, this case
Hoof EL, Jordan Myalgic 2006;13(2/3): 1-44 definition was established for adults rather than children. A Canadian Case Definition (ME/CFS;
K, Lapp C, Encephalomyelitis Myalgic Encephalomyelitis/CFS) has recently been developed, with more specific inclusion criteria
Gurwitt A, Miike and Chronic (Carruthers et al., 2003). Again, the primary aim of this case definition is to diagnose adult CFS. A
T, Torres- Fatigue Syndrome significant problem in the literature is the lack of both a pediatric definition of ME/CFS and a reliable
Harding S, De instrument to assess it. These deficiencies can lead to criterion variance problems resulting in studies
Meirleir K. labeling children with a wide variety of symptoms as having ME/CFS. Subsequently, comparisons
between articles become more difficult, decreasing the possibility of conducting a meta-analysis. This
article presents recommendations developed by the International Association of Chronic Fatigue
Syndrome Pediatric Case Definition Working group for a ME/CFS pediatric case definition. It is
hoped that this pediatric case definition will lead to more appropriate identification of children and
adolescents with ME/CFS.
Jason LA, DePaul University, Causes of death Health Care Chronic fatigue syndrome (CFS) is a debilitating illness affecting thousands of individuals. At the
Corradi K, Gress Chicago, IL among patients Women Int. 2006 present time, there are few studies that have investigated causes of death for those with this
S, Williams S, 60614, USA. with chronic Aug;27(7):615-26. syndrome. The authors analyzed a memorial list tabulated by the National CFIDS Foundation of 166
Torres-Harding Ljason@depaul.ed fatigue syndrome. deceased individuals who had had CFS. There were approximately three times more women than men
S. u on the list. The three most prevalent causes of death were heart failure, suicide, and cancer, which
accounted for 59.6% of all deaths. The mean age of those who died from cancer and suicide was 47.8
and 39.3 years, respectively, which is considerably younger than those who died from cancer and
suicide in the general population. The implications of these findings are discussed.
Jerjes WK, Department of Diurnal excretion J Psychosom Res. OBJECTIVE: The aim of this study was to obtain comprehensive information on basal hypothalamic-
Peters TJ, Taylor Clinical of urinary cortisol, 2006 pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not
NF, Wood PJ, Biochemistry, cortisone, and Feb;60(2):145-53. affected by medication or comorbid psychiatric disorder likely to influence the HPA axis. METHOD:
Wessely S, Cleare Guy's, King's and cortisol Comment in: J Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in
AJ. St Thomas' School metabolites in Psychosom Res. controls. RESULTS: Urinary free cortisol and cortisone concentrations showed a significant normal
of Medicine, chronic fatigue 2006 diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol
Bessemer Road, syndrome. Jun;60(6):627-8; metabolites also showed a normal diurnal rhythm, levels were not significantly different between the
SE5 9RS London, author reply 629. CFS and controls at any time. Derived metabolite ratios were similar in both groups. CONCLUSION:
UK. This study provides further evidence for reduced basal HPA axis function in patients with CFS, based
jerjes@kcl.ac.uk on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data.
The difference between these measures cannot be explained by an altered timing of the diurnal
rhythm.
Jerjes WK, Department of Urinary cortisol Psychosom Med. OBJECTIVES: Reduced basal hypothalamic-pituitary-adrenal (HPA) axis output in chronic fatigue
Taylor NF, Peters Clinical and cortisol 2006 Jul- syndrome (CFS) has been inferred from low cortisol levels in blood, saliva, and urine in some studies.
TJ, Wessely S, Biochemistry, metabolite Aug;68(4):578-82. Because > 95% of cortisol is metabolized before excretion, we assessed cortisol output by assay of
Cleare AJ. Guy's, King's and excretion in both cortisol metabolites and free cortisol in 24-hour urine collections and also investigated sex
St. Thomas' chronic fatigue differences in these between CFS and control groups. METHOD: We calculated total urinary cortisol
School of syndrome. metabolites (TCM) and cortisol metabolite ratios from individual steroid data in 40 patients (20 males
Medicine, King's and 20 females) with CFS who were free of medication or comorbid psychiatric disorder likely to
College London, influence the HPA axis. Results were compared with those of 40 healthy volunteers (20 males and 20
UK. females) well matched for age and body mass index. Data for free cortisol was obtained on 28 of the
walid.jerjes@kcl.a patients and 27 of the controls. RESULTS: The mean of TCM and cortisol metabolite ratios was not
c.uk significantly different between patients and controls for either sex (p > .05 for all parameters).
Previously established sex differences were confirmed in our controls and were found to be similar in
CFS for TCM and the ratios 11OH/11OXO, 5alpha/5beta THF, and 20OH/20OXO (see text) (p < .
005, p < .05, p < .05, and p < .005, respectively). Urinary free cortisol values were numerically (but
not statistically) lower in patients with CFS than controls, and correlated inversely with fatigue levels
in patients. CONCLUSION: The finding of normal urinary cortisol metabolite excretion in patients
with CFS is at variance with earlier reports that CFS is a hypocortisolemic state. If serum and saliva
cortisol levels are lower in CFS, this would suggest that metabolic clearance of cortisol is faster in
patients with CFS than controls. This study also demonstrates that sex differences must be taken into
account when interpreting results in patients with CFS.
Jones G, Godlee Chronic Fatigue Journal of Chronic
F. Syndrome: Fatigue Syndrome
Editorial Bias in 2006;13(1): 69-70
the British Medical
Journal. Letter
Jonker K, van Parnassiagroep- [Treatment of Ned Tijdschr In the last few years, the chronic-fatigue syndrome has been recognised as an important health
Hemert AM. PsyQ, afd patients with the Geneeskd. 2006 problem. In a recent report, the Health Council of the Netherlands suggested that the capacity for
Somatiek en chronic-fatigue Sep treatment be increased. Cognitive behavioural therapy and graded exercise training are treatment
Psyche, Den Haag. syndrome] [Article 23;150(38):2067- options of first choice. A recently published, uncontrolled evaluation of a Dutch clinical rehabilitation
in Dutch] 8. Comment on: programme based partly on these methods proved to be successful. Unfortunately, due to the
Ned Tijdschr uncontrolled character of the study, it remains unclear which elements in the treatment were
Geneeskd. 2006 responsible for the success. Which patients should be included in a costly clinical rehabilitation
Sep programme also remains unclear. More in general, there is room for empirical studies of treatment
23;150(38):2088- allocation, not in the least because of the frequently occurring comorbidity. Good progress has been
94. made in the treatment of the chronic-fatigue syndrome, but we are still far removed from evidence-
based, stepped care, treatment programmes.
Jordan KM, Prevalence of Journal of Chronic No abstract available
Jason LA, Mears Pediatric Chronic Fatigue Syndrome
CJ, Katz BZ, Fatigue Syndrome 2006;13(2/3): 75-
Rademaker A, in a Community- 77
Huang CF, Based Sample
Richman J,
McCready W,
Ayers PM, Taylor
KK
Kaiser J. Biomedicine. Science. 2006 May

Genes and chronic 5;312(5774):669-
fatigue: how 71.
strong is the
evidence?
Katafuchi T, Department of Brain cytokines Ann N Y Acad Fatigue is evoked not only by peripheral factors, such as muscle fatigue, but also by the central
Kondo T, Take S, Integrative and the 5-HT Sci. 2006 nervous system (CNS). For example, it is generally known that the feeling of fatigue is greatly
Yoshimura M. Physiology, system during poly Nov;1088:230-7. influenced by psychological aspects, such as motivation. However, little is known about the central
Graduate School I:C-induced mechanisms of fatigue. The clinical symptoms of chronic fatigue syndrome (CFS) are shown to
of Medical fatigue. include disorders in neuroendocrine, autonomic, and immune systems. On the other hand, it has been
Sciences, Kyushu demonstrated that cytokines produced in the brain play significant roles in neural-immune
University, interactions through their various central actions, including hypothalamo-pituitary and sympathetic
Fukuoka, 812- activation, as well as immunosuppression. In this article, using the immunologically induced fatigue
8582, Japan. model, which was achieved by intraperitoneal (i.p.) injection of synthetic double-stranded RNAs,
kataf@physiol.me polyriboinosinic: polyribocytidylic acid (poly I:C) in rats, we show an involvement of brain
d.kyushu-u.ac.jp interferon-alpha (IFN-alpha) and serotonin (5-HT) transporter (5-HTT) in the central mechanisms of
fatigue. In the poly I:C-induced fatigue rats, expression of IFN-alpha and 5-HTT increased, while
extracellular concentration of 5-HT in the medial prefrontal cortex decreased, probably on account of
the enhanced expression of 5-HTT. Since the poly I:C-induced reduction of the running wheel
activity was attenuated by a 5-HT(1A) receptor agonist, but not by 5-HT(2), 5-HT(3), or dopamine
D(3) receptor agonists, it is suggested that the decrease in 5-HT actions on 5-HT(1A) receptors may
at least partly contribute to the poly I:C-induced fatigue.
Kato K, Sullivan Department of Premorbid Arch Gen CONTEXT: Chronic fatigue syndrome is a disabling problem characterized by persistent fatigue
PF, Evengard B, Medical predictors of Psychiatry. 2006 lasting at least 6 months with a number of ancillary symptoms. Although the etiology of chronic
Pedersen NL. Epidemiology and chronic fatigue. Nov;63(11):1267- fatiguing illness is unknown, some evidence suggests that stress may confer increased risk for
Biostatistics, 72. development of the disorder. Moreover, subjects with chronic fatiguing illness may have distinctive
Karolinska personality traits, although this finding could reflect confounding by other mechanisms. OBJECTIVE:
University To assess the prospective association of premorbid self-reported stress and personality with chronic
Hospital fatigue-like illness. DESIGN: Prospective nested case-control study in a population-based sample.
Huddinge, SETTING: General community. PARTICIPANTS: From the Swedish Twin Registry, 19,192 twins
Karolinska born between January 1, 1935, and December 31, 1958. MAIN OUTCOME MEASURES:
Institutet, Information about current chronic fatiguing illnesses was obtained from computer-assisted telephone
Stockholm, interviews conducted between 1998 and 2002. Self-reported stress (based on a single question) and
Sweden. personality scales (emotional instability and extraversion in the Eysenck Personality Inventory) were
measured from 1972 to 1973 by a mailed questionnaire. Relative risks were estimated with case-
control analyses (matched for age and sex) and co-twin control analyses (comparing discordant pairs).
RESULTS: Higher emotional instability and self-reported stress in the premorbid period were
associated with higher risk for chronic fatigue-like illness in matched case-control analyses (odds
ratios, 1.72 and 1.64, respectively). In co-twin control analyses, relative risk of emotional instability
decreased to 1.02 whereas that of stress increased considerably to 5.81. There was no association
between extraversion and fatigue. CONCLUSIONS: Elevated premorbid stress is a significant risk
factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences.
Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic
mechanisms contributing to both personality style and expression of the disorder. These findings
suggest plausible mechanisms for chronic fatiguing illness.

Kato K, Sullivan Department of Chronic Arch Intern Med. BACKGROUND: Chronic widespread pain (CWP), the cardinal symptom of fibromyalgia, is
PF, Evengard B, Medical widespread pain 2006 Aug 14- prevalent and co-occurs with numerous symptom-based conditions such as chronic fatigue syndrome,
Pedersen NL. Epidemiology and and its 28;166(15):1649- joint pain, headache, irritable bowel syndrome, and psychiatric disorders. Few studies have examined
Biostatistics, comorbidities: a 54. the comorbidities of CWP in the general population. Furthermore, little is known about the
Karolinska population-based importance of familial (genetic and family environmental) factors in the etiology of co-occurrence.
Institutet, SE-171 study. METHODS: Data were obtained from 44 897 individuals in the Swedish Twin Registry via computer-
77 Stockholm, assisted telephone interview from 1998 through 2002 (age >/=42 years; 73.2% response rate).
Sweden. Screening for CWP was based on the American College of Rheumatology criteria without clinical
Kenji.Kato@ki.se evaluation. Measures for comorbidities were based on standard criteria when available. Odds ratios
(ORs) were calculated in case-control and co-twin control designs to assess the effect of familial
confounding in the associations. RESULTS: Considerable co-occurrences were found in CWP cases
for chronic fatigue (OR, 23.53; 95% confidence interval [CI], 19.67-28.16), joint pain (OR, 7.41;
95% CI, 6.70-8.21), depressive symptoms (OR, 5.26; 95% CI, 4.75-5.82), and irritable bowel
syndrome (OR, 5.17; 95% CI, 4.55-5.88). In co-twin control analyses, ORs were no longer significant
for psychiatric disorders, whereas they decreased but remained significant for most other
comorbidities. No changes in ORs were observed for headache. CONCLUSIONS: Associations
between CWP and most comorbidities are mediated by unmeasured genetic and family environmental
factors in the general population. The extent of mediation via familial factors is likely to be disorder
specific.
Kaufman FR, Depression, Journal of Chronic Centers for Disease Control criteria for chronic fatigue syndrome (CFS) specifically recognize that
Goodnick PJ Chronic Fatigue Fatigue Syndrome patients can have both CFS and depression. The clinician's challenge is to judge for each individual
Syndrome, and 2006; 13(4): 83- patient whether the complaint of fatigue is primarily depression, physical illness, such as CFS, or a
Fibromyalgia: An 112 combination of both. This review differentiates CFS and fibromyalgia, discussed as "chronic fatigue
Update syndrome and related immune deficiency syndromes" (CFIDS), from depression in terms of physical
signs, symptoms, biological parameters, brain imaging, immunology, and treatment. The review
focuses on practical applications of research findings with a further focus on future ability to show
clear biologic separation and specific treatment. When depressive symptoms exist with those of CFS,
accurate differentiation can usually be accomplished by focusing on diagnostic criteria. Presence of
multiple physical signs and symptoms of CFIDS may be of great value. In terms of laboratory testing,
a single helpful test may be measuring the plasma cortisol, which is usually high in depression and
low in CFS. Future research should focus on the combination of plasma cortisol with an index of
serotonin function, which is high in CFIDS and low in depression. Additional research should focus
on neuroimaging and immune differentiation. Combination of multiple tests should result in a
significant and clinically useful separation between CFIDS and major depressive disorder (MDD). In
treating patients with significant depression or MDD with CFIDS, one should think of the
noradrenergic approach using bupropion or low-dose tricyclic antidepressants in combination with a
selective serotonin reuptake inhibitor, especially sertraline, to aid improvement of global, pain, and
immunologic parameters. Alternatively, serotonin norepinephrine reuptake inhibitors (venlafaxine
and duloxetine) should be considered. Future treatment research should focus on larger placebo-
controlled, double-blind trials of these and other antidepressants as well as the evaluation of
psychostimulants, electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation
(rTMS).
Kaufman KR, Depression, Journal of Chronic No abstract available at September 2006
Goodnick PJ. Chronic Fatigue Fatigue Syndrome

Syndrome and 2006;13(4):
Fibromyalgia An
Update
Kelsall H, Sim M, Department of Medically J Psychosom Res. OBJECTIVE: The aim of this study was to evaluate fatigue in Australian Gulf War veterans and a
McKenzie D, Epidemiology and evaluated 2006 military comparison group according to the 1994 chronic fatigue syndrome (CFS) definition and
Forbes A, Leder Preventive psychological and Jun;60(6):575-84. investigate the relation with exposures. METHODS: Comprehensive medical, psychological and
K, Glass D, Ikin Medicine, Monash physical health of reported exposure assessments of 1,456 veterans and 1,588 comparison group in a cross-sectional
J, McFarlane A. University, Australian Gulf study. RESULTS: More Gulf War veterans had fatigue at all levels than did the military comparison
Melbourne, War veterans with group. The findings may be at least partly explained as an "active-deployment effect." The odds ratios
Victoria, Australia. chronic fatigue. increased with increasing clinical evaluation of the nature of the fatigue, even after adjustment for
helen.kelsall@med current psychiatric disorders in addition to other possible confounding factors. CONCLUSION:
.monash.edu.au Medically unexplained chronic fatigue was more common, but not more disabling, in veterans than in
the comparison group, but veterans with unexplained chronic fatigue had poorer health than veterans
without. Within both populations, CFS is uncommon and at a similar level to the general community.
Kennedy G, Vascular Diseases Is chronic fatigue Blood Coagul Chronic fatigue syndrome (CFS) is a debilitating condition that has no known aetiology or
Norris G, Spence Research Unit, syndrome Fibrinolysis. 2006 pathophysiology. Recent investigations by other workers have suggested that individuals with CFS
V, McLaren M, University associated with Mar;17(2):89-92. may have a hypercoagulable state. This study investigated various aspects of platelet activation and
Belch JJ. Department of platelet activation? function in 17 patients with CFS and in 16 age-matched and sex-matched healthy controls. Platelet
Medicine, aggregation, platelet volume and coagulation tests were performed. Platelet aggregation was
Ninewells Hospital investigated by means of the photometric changes using citrated platelet-rich plasma, whole blood
& Medical School, aggregation was calculated as the percentage fall in single platelet counts and the coagulation tests
Dundee, UK. were performed on an automatic microcentrifugal analyser.A trend was observed for the patients to
g.y.kennedy@dun have lower aggregation results and a reduced mean platelet volume. However, this only reached
dee.ac.uk statistical significance for one result; the rate of the aggregation slope by 1.0 microg/ml collagen
[CFS patients, 18 (9-28) versus controls, 32.5 (19-36); Mann-Whitney U test, P = 0.029]. No
significant differences were found for any of the measurements of coagulation.These results are in
contrast to previously reported findings. However, due to the heterogeneous nature of the disease, and
the resulting lifestyles of the patients, caution should be taken when comparing one group of patients
with another. Nevertheless, we certainly found no evidence of increased platelet activation or of a
hypercoagulable state in patients with CFS and, on the basis of these results, anti-platelet or anti-
coagulant therapy is not warranted.
Kerr JR, St George's Current research J Clin Pathol. 2006 Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of at least 6 months
Christian P, University of priorities in Aug 25; [Epub duration which is accompanied by various rheumatological, infectious and neuropsychiatric
Hodgetts A, London, United Chronic Fatigue ahead of print] symptoms. A collaborative study group has been formed in order to address the current areas for
Langford PR, Kingdom. Syndrome / development in CFS research, namely, to develop an understanding of the molecular pathogenesis of
Devanur LD, Myalgic CFS, to develop a diagnostic test, and to develop specific and curative treatments. Various groups
Petty R, Burke B, Encephalomyelitis have studied the gene expression in peripheral blood of CFS patients and of those studies which have
Sinclair LI, (CFS/ME): disease been confirmed using polymerase chain reaction (PCR), it is clear that the most predominant
Richards SC, mechanisms, a functional theme is that of immunity and defense. However, we do not yet know the precise gene
Montgomery J, diagnostic test and signature and metabolic pathways involved. Currently, this is being addressed using a microarray
McDermott C, specific representing 47,000 human genes and variants, massive parallel signature sequencing (MPSS) and
Harrison TJ, treatments. real-time PCR. It will be important to ensure that once a gene signature has been identified, that it is
Kellam P, Nutt specific to CFS and does not occur in other diseases and infections. A diagnostic test is being
DJ, Holgate ST. developed using Surface-Enhanced, Laser-Desorption and Ionisation - Time of Flight (SELDI-TOF)
mass spectrometry following a pilot study in which putative biomarkers were identified. And, finally,
clinical trials are being planned; novel treatments which we believe are important to trial in CFS
patients are interferon-a and one of the anti-tumour necrosis factor-a drugs.
Kodama M, Kodama Research Four problems In Vivo. 2006 Since 1996 in our clinic, the regular practice of megadose vitamin C infusion with
Kodama T. Institute of with the clinical Mar- dehydroepiandrosterone-cortisol annex and the continuous intake of erythromycin and
Preventive control of Apr;20(2):285-91. chloramphenicol have been found useful for the clinical control of the autoimmune disease interstitial
Medicine, 50-5 interstitial pneumonia, also known as chronic fatigue syndrome. The long-term use of these two systems for the
Chiyogaoka, pneumonia, or treatment of the autoimmune disease has led to the emergence of four problems of theoretical or
Chikusaku, chronic fatigue practical importance, as described below: i) Should maintenance of the above core treatments be
Nagoya 464-0005, syndrome, using continued for prophylactic purposes in the absence of acute signs of pneumonia? Evidence indicated
Japan. the megadose that their use was essential to arrest the dynamic activity of an intrapulmonary bacterial colony in the
vitamin C infusion immunodeficient host, and that the 5-year survival rate of interstitial pneumonia patients would have
system with been worse without the prophylactic practice of the 2 treatments. ii) Evidence was presented to
dehydroepiandrost suggest that the activity of the intrapulmonary bacterial colony was becoming less responsive because
erone-cortisol of the emergence of a drug-resistent mutant bacterium. The introduction of new antibiotics
annex. (kanamycin) was found to improve the acute signs of pneumonia. iii) The bone marrow function of
one male patient with interstitial pneumonia was found to decline during the observation period of 9
years. It was speculated that his bone marrow, like his lungs, was in the course of fibrosis. iv) One
female patient was diagnosed with breast cancer in the course of interstitial pneumonia treatment--an
example indicating that the persistence of an autoimmune disease in an elderly subject might be
associated with the emergence of malignancy. Dehydroepiandrosterone was shown to promote the
recovery of hepatic function in the course of cancer chemotherapy with cyclophosphamide. The
beneficial effect of the adrenal androgen was dose-dependent. The significance of this finding is
discussed in the light of the steroid carcinogenesis concept. The reasoning behind the view that
interstitial pneumonia and chronic fatigue syndrome are one disease is also discussed.
Komaroff AL, Harvard Medical Highlights from Herpes. 2006 This article reports on key presentations at the 5th International Conference on Human Herpesvirus
Jacobson S, School, Boston, 5th International Nov;13(3):81-2. (HHV)-6 and -7, organized by the HHV-6 Foundation. New assays for HHV-6 and -7 promise to be
Ablashi DV, MA, USA. Conference on more accurate and better able to distinguish between HHV-6A and B or differentiate active from
Yamanishi K. HHV-6 and -7. latent infection. Nevertheless, more research is needed to enhance the sensitivity and specificity of
these assays. Cellular receptors for both HHV-6 and -7 have been identified. Both viruses have in
vitro tropism for neurons and dendritic cells of the central nervous system (CNS), and their role in
producing CNS disease in the immunocompromised (particularly transplant recipients and the HIV-
infected) is well established. HHV-6 may enhance the progression of simian immunodeficiency virus
in monkeys, as suggested by in vivo data. In immunocompetent children and adults, HHV-6 and/or -7
may play a role in triggering and perpetuating several diseases of the nervous system, namely
encephalitis, multiple sclerosis, chronic fatigue syndrome and epilepsy.
Komaroff AL. Division of Is human J Clin Virol. 2006 Chronic fatigue syndrome (CFS) is an illness currently defined entirely by a combination of non-
General Medicine, herpesvirus-6 a Dec;37 Suppl specific symptoms. Despite this subjective definition, CFS is associated with objective underlying
Department of trigger for chronic 1:S39-46. biological abnormalities, particularly involving the nervous system and immune system. Most studies
Medicine, fatigue syndrome? have found that active infection with human herpesvirus-6 (HHV-6) - a neurotropic, gliotropic and
Brigham and immunotropic virus - is present more often in patients with CFS than in healthy control and disease
Women's Hospital, comparison subjects, yet it is not found in all patients at the time of testing. Moreover, HHV-6 has
Harvard Medical been associated with many of the neurological and immunological findings in patients with CFS.
School, 10 Finally, CFS, multiple sclerosis and seizure disorders share some clinical and laboratory features and,
Shattuck Street, like CFS, the latter two disorders also are being associated increasingly with active HHV-6 infection.
Suite 602, Boston, Therefore, it is plausible that active infection with HHV-6 may trigger and perpetuate CFS in a subset
MA 02115, USA. of patients.
Komaroff AL. By the way, Harv Health Lett.
doctor. I would be 2006
most grateful for Aug;31(10):8.
information
concerning chronic
fatigue syndrome,
a disorder from
which I have
suffered for the
past 10 years. Do
you see any help
on the horizon?
Kondo K. Department of [Chronic fatigue Nippon Rinsho.
Microbiology, The syndrome] [Article 2006 Mar;64 Suppl
Jikei University in Japanese] 3:490-5.
School of
Medicine.
Lapp CW Recognizing Journal of Chronic Pediatricians and primary care physicians may be uncomfortable diagnosing Chronic Fatigue
Pediatric CFS in Fatigue Syndrome Syndrome in children because a good diagnostic tool has not been available. Deferring a diagnosis,
the Primary Care 2006;13(2/3): 89- however, may lead to apprehension, over-utilization of medical resources in a search for validity, a
Practice: A 96 delay in treatment, and possibly inappropriate coping techniques. This case-based article discusses
Practicing symptoms and signs seen in adolescent patients with CFS, evaluation of suspect cases, and both
Clinician's current and future diagnostic case definitions
Approach This
Article is
Le Bon O. Unite du sommeil, [Chronic fatigue Rev Med Brux.
Service de syndrome] [Article 2006 Mar-
Psychiatrie, in French] Apr;27(2):S115-7.
C.H.U. Brugmann.
Leone SS, Department of Long-term J Psychosom Res. OBJECTIVE: In an earlier study, we found that cognitive-behavioral therapy (CBT) delivered by
Huibers MJ, Epidemiology, efficacy of 2006 general practitioners (GPs) for fatigue among employees on sick leave was not effective after 12
Kant I, van Maastricht cognitive- Nov;61(5):601-7. months. In this study we aim to assess the long-term efficacy of CBT by GPs for fatigue. It was
Amelsvoort LG, University, behavioral therapy hypothesized that the intervention could prevent deterioration as well as relapse of fatigue complaints
van Schayck CP, Maastricht, The by general and relapse into absenteeism in the long term. METHODS: Patients who participated in the original
Bleijenberg G, Netherlands. practitioners for randomized controlled trial were followed up 4 years later. Fatigue and absenteeism were the main
Knottnerus JA. stephanie.leone@e fatigue: a 4-year outcomes. RESULTS: Fatigue and absenteeism were high in the intervention and control groups at
pid.unimaas.nl follow-up study. the 4-year follow-up. There was no significant difference between the intervention group and the
control group on fatigue and absenteeism. The intervention group however tended toward less-
favorable outcomes as compared with the control group. CONCLUSIONS: Like that of chronic
fatigue syndrome, the prognosis of less-advanced fatigue is rather poor. CBT delivered by GPs is not
effective in the long term.

Leone SS, Department of Long-term Psychol Med. 2006 BACKGROUND: Persistent fatigue is strongly associated with functional status and can lead to
Huibers MJ, Epidemiology, predictors of Sep;36(9):1293- absenteeism and work disability. Despite several prognostic studies on chronic fatigue, little attention
Kant I, Van Maastricht outcome in 300. Epub 2006 has been paid to occupational outcomes. METHOD: A total of 127 fatigued employees on sick leave
Schayck CP, University, The fatigued Jun 6. were followed-up after 4 years to determine long-term predictors of work disability, fatigue caseness
Bleijenberg G, Netherlands. employees on sick and chronic fatigue syndrome (CFS)-like caseness. Measures included fatigue, physical functioning,
Andre Stephanie.Leone@ leave: a 4-year illness attributions, psychological problems and emotional exhaustion. RESULTS: Thirty-three
Knottnerus J. epid.unimaas.nl follow-up study. participants (26%) were receiving work disability benefits at the 4-year follow-up. Older age and
lower levels of physical functioning predicted work disability. Weaker psychological attributions and
lower levels of physical functioning were predictors of fatigue caseness. CFS-like caseness was
predicted by female gender and lower levels of physical functioning. Self-reported physical
functioning remained a strong and statistically significant determinant of work disability [odds ratio
(OR) 0.45, 95% confidence interval (CI) 0.24-0.87] and CFS-like caseness (OR 0.20, 95% CI 0.09-
0.43) after controlling for confounders. CONCLUSIONS: This study suggests that physical
functioning plays an important role in the persistence of fatigue complaints and work disability in
employees on sick leave. The course of fatigue is a complex process, and exploring temporal
relationships between fatigue, functional status and work status in future research could provide
valuable information for the improvement of fatigue management.
Leppavuori A. HYKS Psykiatrian [Chronic fatigue Duodecim.
klinikka, HUS. syndrome] [Article 2006;122(5):545-
antero.leppavuori in Finnish] 53.
@hus.fi
Lin SM, Northwestern Improved Pharmacogenomic A desired application for microarrays in the clinic is to predict treatment response from an often
Devakumar J, University, Robert prediction of s. 2006 diverse patient population. We present a method for analyzing microarray data that is predicated on
Kibbe WA. H Lurie Cancer treatment response Apr;7(3):495-501. biological pathway and function knowledge as opposed to a purely data-driven initial analysis. From
Center, Chicago, using microarrays an analysis perspective, this methodology takes advantage of information that is available across
IL 60611, USA. S- and existing genes on a single array, as well as differences in those patterns across measurements. By using
Lin2@northwester biological biological knowledge in the initial analysis, the accuracy and robustness of microarray profile
n.edu knowledge. classification is enhanced, especially when low numbers of samples are available. For clinical studies,
particularly Phase I or I/II studies, this technique is exceptionally advantageous.
Lincoln AE, War-Related The war-related Mil Med. 2006 Combat veterans often return from deployment having experienced a wide range of exposures,
Helmer DA, Illness and Injury illness and injury Jul;171(7):577-85. symptoms, and medical conditions. The Department of Veterans Affairs established war-related
Schneiderman AI, Study Center, study centers: a illness and injury study centers to serve combat veterans with unexplained illnesses. We report the
Li M, Copeland Washington DC resource for exposures, clinical status, and utilization of 53 combat veterans who participated in the National
HL, Prisco MK, Veterans Affairs deployment- Referral Program (NRP) from January 2002 until March 2004. Participants were primarily male
Wallin MT, Kang Medical Center, 50 related health (81%) and served in the Persian Gulf War (79%). Common diagnoses were chronic fatigue syndrome
HK, Natelson BH. Irving Street, NW, concerns. (n = 23, 43%), neurotic depression (n = 21, 40%), and post-traumatic stress disorder (n = 20, 38%).
Washington, DC Self-reported exposures related to weaponry, disease prophylaxis, environmental hazards, stress, and
20422, USA. poor hygiene. A small increase in mean SF-36V mental component scores (2.8 points, p = 0.009) and
use of rehabilitation therapies (1.6 additional visits, p = 0.018) followed the NRP referral. The small
gain in mental function suggests that the NRP may benefit combat veterans with long and complex
medical histories.
Lindal E, The prevalence of Nord J Psychiatry.
Stefansson JG, chronic fatigue 2006;60(2):183.
Bergmann S. syndrome in
Iceland--a national
comparison by
gender drawing on
four different
criteria.
Lundell K, Qazi Parker Hughes Clinical activity of Arzneimittelforsch A high incidence of severe B-cell immunodeficiency and chronic reactivated Epstein-Barr virus
S, Eddy L, Uckun Institute and folinic acid in ung. (EBV) infection in patients with chronic fatigue syndrome (CFS) is reported herein. Of the 58 patients
FM. Parker Hughes patients with 2006;56(6):399- evaluated, 100% had evidence of prior EBV exposure and 72% had evidence for reactivated EBV
Clinics, St. Paul, chronic fatigue 404. infection. Notably, 94% of CFS patients had B-cell immunodeficiency with a marked depletion of
MN 55113, USA. syndrome. their CD19+IgM+ mature B-lymphocyte population. A remarkable 81% of CFS patients experienced
subjective improvement of their symptoms after treatment with folinic acid (CAS 58-05-9,
leucovorin). The findings provide unprecedented evidence that CFS frequently is a folinic acid
responsive clinical entity accompanied by B-cell immunodeficiency and inappropriate antibody
responses to EBV.
Madhavan G, Department of Cardiovascular Biomed Instrum The decreased blood pressure and flow rates associated with orthostasis have been implicated in the
Stewart JM, Orthopaedics, systemic Technol. 2006 Jan- etiology of numerous clinical conditions, including deep vein thrombosis, chronic fatigue syndrome,
McLeod KJ. School of regulation by Feb;40(1):78-84. and more recently osteoporosis. Here, we investigate the potential of low-magnitude vibration,
Medicine, Health plantar surface applied at the plantar surface, to inhibit the cardiovascular responses of adult women to the
Sciences Center, stimulation. orthostatic stress associated with quiet sitting. METHODS: Thirty healthy women, aged 22-82 years,
State University of were exposed to a plantar-based vibration immediately after taking a seated position. Seven stimulus
New York, Stony frequencies (0, 15, 22, 44, 60, 90, and 120 Hz, all at 0.2g) were tested on each subject, and
Brook, USA. cardiovascular responses were followed for 20 minutes. Each subject experienced only a single test
guru@binghamton frequency on any day. Pre- and poststimulus blood pressures and continuous electrocardiogram results
.edu were obtained, from which mean arterial pressure (MAP) and heart rate variability (HRV) were
calculated. RESULTS: In the per-protocol study population (n = 25), 20 minutes of quiet sitting was
associated with an average depression of 8.95 mm Hg in systolic pressure and of 1.9 mm Hg in
diastolic blood pressure, corresponding to an average decrease in MAP of 5.15 mm Hg. These
orthostasis-based changes in blood pressure were significantly reduced by exposure to plantar
vibration, in a frequency-dependent manner, with essentially complete suppression of the drop in
MAP achieved with plantar stimulation at 44 Hz (P < or = . 01). In the orthostatically hypotensive
subpopulation (n = 15), both the 9.3-mm Hg depression in MAP and the decline in HRV were
eliminated by exposure to plantar vibrations in the 40- to 60-Hz range (P = .01 and P = .03,
respectively). These results are consistent with the hypothesis that the plantar vibration may be
stimulating type IIA muscle fiber activity in the leg, which is critical for effective skeletal muscle
pumping in the absence of locomotion. CONCLUSIONS: Our findings lead us to suggest that
noninvasive, low-level, plantar-based vibration in the regime of 30-60 Hz can significantly inhibit the
effects of the orthostatic stress of quiet sitting on the cardiovascular system.
Maes M, M-Care4U Lower serum zinc J Affect Disord. The present study examines serum zinc concentrations in patients with chronic fatigue syndrome
Mihaylova I, De Outpatient Clinics, in Chronic Fatigue 2006 Feb;90(2- (CFS) versus normal volunteers. Serum zinc levels were determined by means of an atomic
Ruyter M. Olmenlaan 9, 2610 Syndrome (CFS): 3):141-7. Epub absorption method. We found that serum zinc was significantly lower in the CFS patients than in the
Antwerp-Wilrijk, relationships to 2005 Dec 9. normal controls. There was a trend toward a significant negative correlation between serum zinc and
Belgium. immune the severity of CFS and there was a significant and negative correlation between serum zinc and the
crc.mh@telenet.be dysfunctions and subjective experience of infection. We found that serum zinc was significantly and negatively
relevance for the correlated to the increase in the alpha2 protein fraction and positively correlated to decreases in the
oxidative stress expression of mitogen-induced CD69+ (a T cell activation marker) on CD3+ as well as CD3+CD8+ T
status in CFS. cells. These results show that CFS is accompanied by a low serum zinc status and that the latter is
related to signs of inflammation and defects in early T cell activation pathways. Since zinc is a strong
anti-oxidant, the present results further support the findings that CFS is accompanied by increased
oxidative stress. The results of these reports suggest that some patients with CFS should be treated
with specific antioxidants, including zinc supplements.
Maes M, MCare4U Chronic fatigue Neuro Endocrinol There is now some evidence that chronic fatigue syndrome (CFS) is accompanied by signs of
Mihaylova I, Outpatient Clinics, syndrome is Lett. 2006 oxidative stress and by a decreased antioxidant status. The aim of the present study was to examine
Leunis JC. Antwerp, Belgium. accompanied by an Oct;27(5):615-21. whether CFS is accompanied by an immune response to neoepitopes of a variety of modified lipids
IgM-related and proteins indicating damage caused by oxidative and nitrosative stress. Toward this end we
immune response examined serum antibodies to fatty acids (oleic, palmitic and myristic acid), by-products of lipid
directed against peroxidation, i.e. azelaic acid and malondialdehyde (MDA), acetylcholine, S-farnesyl-L-cysteine, and
neopitopes formed N-oxide modified amino-acids in 14 patients with CFS, 14 subjects with partial CFS and 11 normal
by oxidative or controls. We found that the prevalences and mean values for the serum IgM levels directed against
nitrosative damage oleic, palmitic and myristic acid, MDA, azelaic acid, S-farnesyl-L-cysteine, and the N-oxide
to lipids and derivates, nitro-tyrosine, nitro-phenylalanine, nitro-arginine, nitro-tryptophan, and nitro-cysteinyl
proteins. were significantly greater in CFS patients than in normal controls, whereas patients with partial CFS
took up an intermediate position. There were significant and positive correlations between the serum
IgM levels directed against fatty acids, MDA and azelaic acid and the above N-oxide-derivates and
the severity of illness (as measured by the FibroFatigue scale) and symptoms, such as aches and pain,
muscular tension and fatigue. The results show that CFS is characterized by an IgM-related immune
response directed against disrupted lipid membrane components, by-products of lipid peroxidation, S-
farnesyl-L-cysteine, and NO-modified amino-acids, which are normally not detected by the immune
system but due to oxidative and nitrosative damage have become immunogenic.
Malaguarnera M, L-carnitine South Med J. 2006
Di Mauro A, reduces severity of Mar;99(3):315-6.
Gargante PM, physical and
Rampello L. mental fatigue and
improves daily
activities in the
elderly.
Maloney EM, Centers for Chronic fatigue Pharmacogenomic STUDY POPULATION: We examined the relationship between chronic fatigue syndrome (CFS) and
Gurbaxani BM, Disease Control syndrome and high s. 2006 allostatic load in a population-based, case-control study of 43 CFS patients and 60 nonfatigued,
Jones JF, de and Prevention, allostatic load. Apr;7(3):467-73. healthy controls from Wichita, KS, USA. METHODS: An allostatic load index was computed for all
Souza Coelho L, 1600 Clifton Road, study participants using available laboratory and clinical data, according to a standard algorithm for
Pennachin C, MS A-15, Atlanta, allostatic load. Logistic regression analysis was used to compute odds ratios (ORs) as estimates of
Goertzel BN. GA 30333, USA. relative risk in models that included adjustment for matching factors and education; 95% confidence
evm3@cdc.gov intervals (CIs) were computed to estimate the precision of the ORs. RESULTS: CFS patients were
1.9-times more likely to have a high allostatic load index than controls (95% CI = 0.75, 4.75) after
adjusting for education level, in addition to matching factors. The strength of this association
increased in a linear trend across categories of low, medium and high levels of allostatic load (p =
0.06). CONCLUSION: CFS was associated with a high level of allostatic load. The three allostatic
load components that best discriminated cases from controls were waist:hip ratio, aldosterone and
urinary cortisol.
Maoz D, [Chronic fatigue Harefuah. 2006 BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by severe fatigue and other non-
Shoenfeld Y. syndrome] [Article Apr;145(4):272-5, specific symptoms. It causes disturbance of normal function. Uncertainty about etiology and the
in Hebrew] 319, 318. appropriate treatment, combined with high prevalence of psychiatric comorbidity, cause a problem in
the perception of the disease by the patient, physician and society. OBJECTIVES: This review
recapitulates the updated information regarding CFS. It addresses the following aspects: definitions,
diagnosis, demographic figures, etiology and treatment options. Since much about CFS is yet to be
known, a large amount of work has recently been performed on this subject. Current perceptions, as
recognized today, are also presented. METHODS: A literature search was performed using Medline.
RESULTS: Accurate diagnosis of CFS patients is low despite the disabling fatigue. CFS patients
present certain demographic characteristics and the illness etiology is as yet unclear. Nonetheless,
many possible directions exist with inconclusive evidence about certain suspected causes. There are
no treatment guidelines available. Different treatment approaches were investigated without
consensus on the results. CONCLUSIONS: CFS is an illness that should be taken seriously by the
medical establishment. Conscious awareness of the malady might reduce rates of undiagnosed
patients. The different etiologic factors showing some degree of involvement in CFS, might suggest
that this syndrome is a multi-factorial condition. Despite the fact that there is no distinct undisputed
treatment, there are 2 treatments (cognitive behavioral therapy and graded exercise therapy) that
might be effective.
Maquet D, Departement des Chronic fatigue Ann Readapt Med OBJECTIVE: A systematic review of the literature about chronic fatigue syndrome (CFS).
Demoulin C, Sciences de la syndrome: a Phys. 2006 METHODS: A search of the Medline database (via Ovid and PubMed) with the key words chronic
Crielaard JM. Motricite, Unite de systematic review. Jul;49(6):337-47, fatigue syndrome, diagnosis, classification, epidemiology, etiology, physiopathology, metabolism,
Medecine [Article in English, 418-27. Epub 2006 microbiology, immunology, virology, psychology, drug therapy, rehabilitation, and therapy. The
Physique et French] Apr 19. reference lists of each article were examined for additional related articles. RESULTS: CFS was
Kinesitherapie- defined in 1988 by the US Centes for Disease Control and Prevention. The prevalence of chronic
Readaptation, fatigue syndrome has ranged from 0.2% to 0.7% in the general population. In 1994, the definition of
Universite de CFS was revised by Fukuda et al. Despite various research in several topics (e.g. infection, immune
Liege, CHU Sart- systems, neuroendocrinology, autonomic activity, neuromuscular involvement), the pathophysiology
Tilman, ISEPK, remains unknown. CONCLUSION: CFS, with its various major clinical and functional impacts,
Belgique. should be associated with a "biopsychosocial model". Progressive muscular rehabilitation, combined
D.Maquet@ulg.ac. with behavioral and cognitive treatment, is an essential part of therapy.
be
Margutti P, Dipartimento di Autoantibodies Curr Neurovasc Growing evidence suggests that autoantibodies to neuronal or endothelial targets in psychiatric
Delunardo F, Malattie Infettive, associated with Res. 2006 disorders exist and may be pathogenic. This review describes and discusses the possible role of
Ortona E. Parassitarie e psychiatric May;3(2):149-57. autoantibodies related to the psychiatric manifestations in autoimmune diseases, autoantibodies
Immunomediate, disorders. related to the psychiatric disorders present in post-streptococcal diseases, celiac disease, chronic
Istituto Superiore fatigue syndrome and substance abuse, and autoantibodies related to schizophrenia and autism,
di Sanita, Rome, disorders now considered of autoimmune origin.
Italy.
ortona@iss.it.
McCue P, Department of Screening for Br J Clin Psychol. OBJECTIVES: To investigate the factor structure and internal consistency of the Hospital Anxiety
Buchanan T, Psychology, psychological 2006 Nov;45(Pt and Depression Scale (HADS) in individuals with Chronic Fatigue Syndrome (CFS) using an Internet
Martin CR. Northumbria distress using 4):483-98. administered version of the instrument. DESIGN: Between subjects. METHOD: Confirmatory factor
University, UK. internet analysis (CFA) and internal consistency analysis of the HADS was used to determine the
administration of psychometric characteristics of the instrument in individuals with CFS and a control group with data
the Hospital captured via an Internet data collection protocol. RESULTS: CFA revealed that a 3-factor solution
Anxiety and offered the most parsimonious account of the data. Internal consistency estimations of the anxiety and
Depression Scale depression subscales were found to be acceptable for both groups. The CFS group was found to have
(HADS) in significantly higher HADS-assessed anxiety and depression scores compared with controls, however,
individuals with there was also evidence found that Internet administration of the instrument may inflate HADS
chronic fatigue subscale scores as an artifact of testing medium. CONCLUSIONS: The HADS is suitable for use for
syndrome. screening individuals with CFS in terms of the factor structure of the instrument, however, clinicians
should be aware that this instrument assesses 3 domains of affective disturbance rather than 2 as is
interpreted within the current HADS anxiety and depression subscale scoring system. Researchers
need also be aware that Internet administration of negative affective state measures such as the HADS
is likely to inflate scores and need to ensure that comparisons between clinical groups are made with
control group data gathered using the same collection methodology.
McCully KK, Department of Increase of free Dyn Med. 2006 ABSTRACT : In a previous study we evaluated muscle blood flow and muscle metabolism in patients
Malucelli E, Iotti Kinesiology, Mg2+ in the Jan 11;5:1. diagnosed with chronic fatigue syndrome (CFS). To better understand muscle metabolism in CFS, we
S. University of skeletal muscle of re-evaluated our data to calculate free Magnesium levels in skeletal muscle. Magnesium is an
Georgia, Athens chronic fatigue essential cofactor in a number of cell processes. A total of 20 CFS patients and 11 controls were
GA 30602. syndrome patients. evaluated. Phosphorus magnetic resonance spectroscopy from the medial gastrocnemius muscle was
mccully@uga.edu. used to calculate free Mg2+ from the concentrations and chemical shifts of Pi, PCr, and beta ATP
peaks. CFS patients had higher magnesium levels in their muscles relative to controls (0.47 + 0.07 vs
0.36 + 0.06 mM, P < 0.01), although there was no difference in the rate of phosphocreatine recovery
in these subjects, as reported earlier. This finding was not associated with abnormal oxidative
metabolism as measured by the rate of recovery of phosphocreatine after exercise. In summary,
calculation of free Mg2+ levels from previous data showed CFS patients had higher resting free
Mg2+ levels compared to sedentary controls.
McDermott C, University of A placebo- QJM. 2006 BACKGROUND: Previous research has suggested that natural killer (NK) cell activity may be
Richards SC, Southampton, UK. controlled, double- Jul;99(7):461-8. reduced in patients with chronic fatigue syndrome (CFS). AIM: To evaluate the effectiveness of a
Thomas PW, crm202@soton.ac. blind, randomized Epub 2006 Jun 29. putative NK cell stimulant, BioBran MGN-3, in reducing fatigue in CFS patients. DESIGN:
Montgomery J, uk controlled trial of a Randomized, double-blind, placebo-controlled trial. METHODS: We recruited 71 patients with CFS
Lewith G. natural killer cell (according to the Centers for Disease Control 1994 criteria) attending an out-patient specialist CFS
stimulant (BioBran service. Participants were given oral BioBran MGN-3 for 8 weeks (2 g three times per day) or
MGN-3) in chronic placebo equivalent. The primary outcome measure was the Chalder physical fatigue score. Self-
fatigue syndrome. reported fatigue measures, self-assessment of improvement, change in key symptoms, quality of life,
anxiety and depression measures were also included. RESULTS: Data were complete in 64/71
patients. Both groups showed marked improvement over the study duration, but without significant
differences. Mean improvement in the Chalder fatigue score (physical scale) was 0.3 (95%CI -2.6 to
3.2) lower in the BioBran group. DISCUSSION: The findings do not support a specific therapeutic
effect for BioBran in CFS. The improvement showed by both groups over time highlights the
importance of placebo controls when evaluating interventions in CFS.
McIntyre RS, Department of Medical Psychiatr Serv. OBJECTIVE: This is the first cross-national population-based investigation exploring the prevalence
Konarski JZ, Psychiatry, comorbidity in 2006 and functional implications of comorbid general medical disorders in bipolar disorder. METHODS:
Soczynska JK, University of bipolar disorder: Aug;57(8):1140-4. Data were extracted from the Canadian Community Health Survey (N = 36,984). Analyses were
Wilkins K, Toronto, Ontario, implications for conducted to ascertain the prevalence and prognostic implications of predetermined comorbid general
Panjwani G, Canada. functional medical disorders among persons who screened positive for a lifetime manic episode (indicative of a
Bouffard B, roger.mcintyre@u outcomes and diagnosis of bipolar disorder). Within the subpopulation of people who screened positive for a manic
Bottas A, hn.on.ca health service episode, the effect of medical comorbidity on employment, functional role, psychiatric care, and
Kennedy SH. utilization. medication use was examined. RESULTS: When the data were weighted to be representative of the
household population of the ten provinces in 2002, an estimated 2.4 percent of respondents screened
positive for a lifetime manic episode. Rates of chronic fatigue syndrome, migraine, asthma, chronic
bronchitis, multiple chemical sensitivities, hypertension, and gastric ulcer were significantly higher in
the bipolar disorder group (all p < .05). Chronic medical disorders were associated with a more severe
course of bipolar disorder, increased household and work maladjustment, receipt of disability
payments, reduced employment, and more frequent medical service utilization. CONCLUSIONS:
Comorbid medical disorders in bipolar disorder are associated with several indices of harmful
dysfunction, decrements in functional outcomes, and increased utilization of medical services.
McLean SA, Department of Cerebrospinal fluid Neuropsychophar Previous studies have identified stress system dysregulation in fibromyalgia (FM) patients; such
Williams DA, Emergency corticotropin- macology. 2006 dysregulation may be involved in the generation and/or maintenance of pain and other symptoms.
Stein PK, Harris Medicine, releasing factor Dec;31(12):2776- Corticotropin-releasing factor (CRF) is the principal known central nervous system mediator of the
RE, Lyden AK, University of concentration is 82. Epub 2006 stress response; however, to date no studies have examined cerebrospinal fluid (CSF) CRF levels in
Whalen G, Park Michigan Medical associated with Aug 23. patients with FM. The relationship between CSF CRF level, heart rate variability (HRV), and pain,
KM, Liberzon I, Center, Ann pain but not fatigue, and depressive symptoms was examined in patients with FM. Among participants (n=26),
Sen A, Gracely Arbor, MI, USA. fatigue symptoms CSF CRF levels were associated with sensory pain symptoms (r=0.574, p=0.003) and affective pain
RH, Baraniuk JN, samclean@umich. in patients with symptoms (r=0.497, p=0.011), but not fatigue symptoms. Increased HRV was also strongly associated
Clauw DJ. edu fibromyalgia. with increased CSF CRF and FM pain. In multivariate analyses adjusting for age, sex, and depressive
symptoms, the association between CSF CRF and sensory pain symptoms (t=2.54, p=0.027) persisted.
Women with FM who reported a history of physical or sexual abuse had lower CSF CRF levels than
women who did not report such a history. CSF CRF levels are associated with both pain symptoms
and variation in autonomic function in FM. Differences in CSF CRF levels among women with and
without a self-reported history of physical or sexual abuse suggest that subgroups of FM patients may
exist with different neurobiological characteristics. Further studies are needed to better understand the
nature of the association between CSF CRF and pain symptoms in FM.
Meeus M, Nijs J, Division of Chronic Eur J Pain. 2006 BACKGROUND: In addition to debilitating fatigue the majority of patients with chronic fatigue
Meirleir KD. Musculoskeletal musculoskeletal Jul 12; [Epub syndrome (CFS) experience chronic widespread pain. AIMS: Conducting a systematic review to
Physiotherapy, pain in patients ahead of print] critically assess the existing knowledge on chronic pain in CFS. We focussed on the definition, the
Higher Institute of with the chronic prevalence and incidence, the aetiology, the relevance and the therapy strategy for chronic
Physiotherapy, fatigue syndrome: musculoskeletal pain and post-exertional pain in CFS. METHODS: To identify relevant articles, we
Department of A systematic searched eight medical search engines. The search terms "chronic fatigue syndrome" AND "pain",
Health Care review. "nociception", "arthralgia" and "myalgia", were used to identify articles concerning pain in CFS.
Sciences, Included articles were reviewed by two blinded researchers. RESULTS: Twenty-five articles and two
Hogeschool abstract were identified and selected for further appraisal. Only 11 search results focussed on
Antwerpen (HA), musculoskeletal pain in CFS patients. Regarding the standardized review of the articles, a 96%
Van agreement between the researchers was observed. There is no consensus in defining chronic
Aertselaerstraat widespread pain in CFS, and although there is little or no strong proof for the exact prevalence,
31, 2170 chronic pain is strongly disabling in CFS. Aetiological theories are proposed (sleep abnormalities,
Merksem, tryptophan, parovirus-B, hormonal and brain abnormalities and central sensitisation) and a reduction
Belgium; of pain threshold after exercise has been shown. Furthermore depression seemed not related to pain in
Department of CFS and a staphylococcus toxoid vaccine caused no significant pain reduction. CONCLUSIONS: The
Human results from the systematic review highlight the clinical importance of chronic pain in CFS, but only
Physiology, few studies addressing the aetiology or treatment of chronic pain in CFS are currently available.
Faculty of Physical
Education and
Physiotherapy,
Vrije Universiteit
Brussel (VUB),
Belgium.
Meeus M, Nijs J. Department of Central Clin Rheumatol. In addition to the debilitating fatigue, the majority of patients with chronic fatigue syndrome (CFS)
Human sensitization: a 2006 Nov 18; experience chronic widespread pain. These pain complaints show the greatest overlap between CFS
Physiology, biopsychosocial [Epub ahead of and fibromyalgia (FM). Although the literature provides evidence for central sensitization as cause
Faculty of Physical explanation for print] for the musculoskeletal pain in FM, in CFS this evidence is currently lacking, despite the observed
Education and chronic similarities in both diseases. The knowledge concerning the physiological mechanism of central
Physiotherapy, widespread pain in sensitization, the pathophysiology and the pain processing in FM, and the knowledge on the
Vrije Universiteit patients with pathophysiology of CFS lead to the hypothesis that central sensitization is also responsible for the
Brussel (VUB), fibromyalgia and sustaining pain complaints in CFS. This hypothesis is based on the hyperalgesia and allodynia
Brussel, Belgium. chronic fatigue reported in CFS, on the elevated concentrations of nitric oxide presented in the blood of CFS patients,
syndrome. on the typical personality styles seen in CFS and on the brain abnormalities shown on brain images.
To examine the present hypothesis more research is required. Further investigations could use similar
protocols to those already used in studies on pain in FM like, for example, studies on temporal
summation, spatial summation, the role of psychosocial aspects in chronic pain, etc.
Michielsen HJ, Department of Depression, Clin Rheumatol. The aims of the present study were to compare a single diagnosis (chronic fatigue syndrome, CFS)
Van Houdenhove Psychology and attribution style 2006 and a double diagnosis (CFS + fibromyalgia, CFS+FM) group regarding depression, attribution style
B, Leirs I, Health, Tilburg and self-esteem in Mar;25(2):183-8. and self-esteem as well as to examine whether attribution style is a mediator in the relationship
Vandenbroeck A, University, chronic fatigue Epub 2005 Jul 12. between self-esteem and depression. Eighty-five patients (CFS: 47, CFS+FM: 38) completed
Onghena P. Tilburg, The syndrome and questionnaires on attribution style, self-esteem and depression. The single and double diagnosis
Netherlands. fibromyalgia groups tended to differ slightly, but the differences were never statistically significant. In addition,
patients: is there a only one condition was met of the four conditions mentioned by Baron and Kenny to establish that
link? mediation exists between two variables. In conclusion, an external attribution style does not protect
the CFS or CFS+FM patients with a low self-esteem from depression. The prevalence rate of
depression was high in both patient samples, of which clinicians should be aware.
Miike T. miketeru@kaiju.m [Brain science, No To Hattatsu.
edic.kumamoto- education and 2006
u.ac.jp living Mar;38(2):85-91.
environment]
[Article in
Japanese]
Mommersteeg Department of Clinical burnout is Psychoneuroendoc Burnout is presumed to be the result of chronic stress, and chronic stress is known to affect the HPA-
PM, Heijnen CJ, Health not reflected in the rinology. 2006 axis. To date, studies on HPA-axis functioning in burnout have showed inconsistent results. In the
Verbraak MJ, Psychology, cortisol awakening Feb;31(2):216-25. present study, a large sample (n=74) of clinically diagnosed burnout individuals, mostly on sick-
van Doornen LJ. Utrecht University, response, the day- Epub 2005 Sep 16. leave, were included and compared with 35 healthy controls. Salivary cortisol was sampled on 2 days
P.O. Box 80.140, curve or the to determine the cortisol awakening response (CAR) and the day-curve. In addition, the
3508 TC Utrecht, response to a low- dexamethasone suppression test (DST) was applied to assess the feedback efficacy of the HPA-axis.
The Netherlands. dose There were no differences observed in the CAR, day-curve or CAR after DST in the burnout group as
p.mommersteeg@f dexamethasone compared to a healthy control group. Burnout shows overlap in symptoms with chronic fatigue
ss.uu.nl suppression test. syndrome (CFS) and depression. Therefore, differential changes in HPA-axis functioning that
resemble the hypo-functioning of the HPA-axis in CFS, or rather the hyper-functioning of the HPA-
axis in depression, might have obscured the findings. However, no effect of fatigue or depressive
mood on HPA-axis functioning was found in the burnout group. We concluded that HPA-axis
functioning in clinically diagnosed burnout participants as tested in the present study, seems to be
normal.
Moss-Morris R, School of To "lump" or to Psychosom Med. OBJECTIVES: Recent academic debate has centered on whether functional somatic syndromes
Spence M. Psychology, "split" the 2006 May- should be defined as separate entities or as one syndrome. The aim of this study was to investigate
University of functional somatic Jun;68(3):463-9. whether there may be significant differences in the etiology or precipitating factors associated with
Southampton, syndromes: can two common functional syndromes, irritable bowel syndrome (IBS) and chronic fatigue syndrome
Highfield, infectious and (CFS). METHODS: We prospectively studied 592 patients with an acute episode of Campylobacter
Southampton, emotional risk gastroenteritis and 243 with an acute episode of infectious mononucleosis who had no previous
SO17 1BJ, United factors history of CFS or IBS. At the time of infection, patients completed a baseline questionnaire that
Kingdom. differentiate measured their levels of distress using the Hospital Anxiety and Depression scale. At 3- and 6-month
R.E.Moss- between the onset follow-up, they completed questionnaires to determine whether they met published diagnostic criteria
Morris@soton.ac.u of chronic fatigue for chronic fatigue (CF), CFS, and/or IBS. RESULTS: The odds of developing IBS were significantly
k syndrome and greater post-Campylobacter than post-infectious mononucleosis at both 3- (odds ratio, 3.45 [95%
irritable bowel confidence interval (CI), 1.75-6.67]) and 6- (2.22 [95% CI, 1.11-6.67]) month follow-up. In contrast,
syndrome? the odds for developing CF/CFS were significantly greater after infectious mononucleosis than after
Campylobacter at 3 (2.77 [95% CI, 1.08-7.11]) but not 6 (1.48 [95% CI, 0.62-3.55]) months
postinfection. Anxiety and depression were the strongest predictors of CF/CFS, whereas the nature of
the infection was the strongest predictor of IBS. CONCLUSIONS: These results support the argument
to distinguish between postinfectious IBS and CFS. The nature of the precipitating infection appears
to be important, and premorbid levels of distress appear to be more strongly associated with CFS than
IBS, particularly levels of depression.
Naschitz J, Fields Department of Shortened QT J Electrocardiol. PURPOSE: Because autonomic nervous functioning is frequently abnormal in chronic fatigue
M, Isseroff H, Internal Medicine interval: a 2006 syndrome (CFS), we examined whether the corrected QT interval (QTc) in CFS differs from QTc in
Sharif D, Sabo E, A, Bnai Zion distinctive feature Oct;39(4):389-94. other populations. METHODS: The QTc was calculated at the end of 10 minutes of recumbence and
Rosner I. Medical Center of the Epub 2006 Feb 28. the end of 10 minutes of head-up tilt. In a pilot study, groups of 15 subjects, CFS, and controls,
and Rappaport dysautonomia of matched for age and sex, were investigated. In a second phase of the study, the QTc was measured in
Family Faculty of chronic fatigue larger groups of CFS (n = 30) and control patients (n = 96) not matched for demographic features.
Medicine, syndrome. RESULTS: In the pilot study, the average supine QTc in CFS was 0.371 +/- 0.02 seconds and QTc on
Technion-Israel tilt, 0.385 +/- 0.02 seconds, significantly shorter than in controls (P = .0002 and .0003, respectively).
Institute of Results of phase II confirmed this data. CONCLUSIONS: Relative short QTc intervals are features of
Technology, P.O. the CFS-related dysautonomia. The significance of this finding is discussed.
Box 4940, Haifa
31048, Israel.
naschitz@tx.techni
on.ac.il
Naschitz JE, Department of Patterns of Am J Med Sci. OBJECTIVES: To assess whether head-up tilt-induced hyperventilation is seen more often in patients
Mussafia-Priselac Internal Medicine hypocapnia on tilt 2006 with chronic fatigue syndrome (CFS), fibromyalgia, dizziness, or neurally mediated syncope (NMS)
R, Kovalev Y, A, the Bnai-Zion in patients with Jun;331(6):295- as compared to healthy subjects or those with familial Mediterranean fever (FMF). PATIENTS AND
Zaigraykin N, Medical Center fibromyalgia, 303. METHODS: A total of 585 patients were assessed with a 10-minute supine, 30-minute head-up tilt
Slobodin G, Elias and Bruce chronic fatigue test combined with capnography. Experimental groups included CFS (n = 90), non-CFS fatigue (n =
N, Rosner I. Rappaport Faculty syndrome, 50), fibromyalgia (n = 70), nonspecific dizziness (n = 75), and NMS (n =160); control groups were
of Medicine, nonspecific FMF (n = 90) and healthy (n = 50). Hypocapnia, the objective measure of hyperventilation, was
Technion-Israel dizziness, and diagnosed when end-tidal pressure of CO2 (PETCO2) less than 30 mm Hg was recorded
Institute of neurally mediated consecutively for 10 minutes or longer. When tilting was discontinued because of syncope, one
Technology, syncope. PETCO2 measurement of 25 or less was accepted as hyperventilation. RESULTS: Hypocapnia was
Haifa, Israel. diagnosed on tilt test in 9% to 27% of patients with fibromyalgia, CFS, dizziness, and NMS versus
Naschitz@tx.techn 0% to 2% of control subjects. Three patterns of hypocapnia were recognized: supine hypocapnia (n =
ion.ac.il 14), sustained hypocapnia on tilt (n = 76), and mixed hypotensive-hypocapnic events (n = 80).
Hypocapnia associated with postural tachycardia syndrome (POTS) occurred in 8 of 41 patients.
CONCLUSIONS: Hyperventilation appears to be the major abnormal response to postural challenge
in sustained hypocapnia but possibly merely an epiphenomenon in hypotensive-hypocapnic events.
Our study does not support an essential role for hypocapnia in NMS or in postural symptoms
associated with POTS. Because unrecognized hypocapnia is common in CFS, fibromyalgia, and
nonspecific dizziness, capnography should be a part of the evaluation of patients with such
conditions.
Nater UM, Viral Exanthems Coping styles in J Psychosom Res. OBJECTIVE: Studies of primary and tertiary care patients suggest that maladaptive coping styles
Wagner D, and Herpesvirus people with 2006 contribute to the pathogenesis and maintenance of chronic fatigue syndrome (CFS). We assessed
Solomon L, Jones Branch, Division chronic fatigue Jun;60(6):567-73. coping styles in persons with unexplained fatigue and nonfatigued controls in a population-based
JF, Unger ER, of Viral and syndrome study. METHODS: We enrolled 43 subjects meeting the 1994 Research Case Definition of CFS,
Papanicolaou DA, Rickettsial identified from the matching them with 61 subjects with chronic unexplained fatigue who did not meet criteria for CFS
Reeves WC, Heim Diseases, National general population [we term them insufficient symptoms or fatigue (ISF)] and 60 non-ill (NI) controls. Coping styles and
C. Center for of Wichita, KS. clinical features of CFS were assessed using standard rating scales. RESULTS: Subjects with CFS
Infectious and ISF reported significantly more escape-avoiding behavior than NI controls. There were no
Diseases, Centers differences between the CFS and ISF subjects. Among participants with CFS, escape-avoiding
for Disease behavior was associated with fatigue severity, pain, and disability. CONCLUSIONS: We demonstrate
Control and significantly higher reporting of maladaptive coping in a population-based sample of people with CFS
Prevention, and other unexplained fatiguing illnesses defined by reproducible standardized clinical empirical
Atlanta, GA, USA. means in comparison to NI controls.
Nicolson GL, Lipid Replacement Journal of Chronic Evidence in the literature indicates that diminished mitochondrial function through loss of efficiency
Ellithorpe R. and Antioxidant Fatigue Syndrome in the electron transport chain caused by oxidation occurs during aging and in fatiguing illnesses.
Nutritional 2006;13(1): 57-68 Lipid Replacement Therapy (LRT) administered as a nutritional supplement with antioxidants can
Therapy for prevent oxidative membrane damage, and LRT can be used to restore mitochondrial and other
Restoring cellular membrane functions via delivery of undamaged replacement lipids to cellular organelles.
Mitochondrial Recent clinical trials using patients with chronic fatigue have shown the benefit of LRT plus
Function and antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe
Reducing Fatigue chronic fatigue. These studies indicate the benefits of LRT plus antioxidants in reducing fatigue and
in Chronic Fatigue preventing loss of mitochondrial function, most likely by protecting mitochondrial and other cellular
Syndrome and membranes from oxidative and other damage and removing damaged lipids by lipid replacement. In
Other Fatiguing one clinical study we determined if mitochondrial function is reduced in subjects with mild to severe
Illnesses chronic fatigue, and if this can be reversed with NT Factor(r), a nutritional supplement that replaces
damaged cellular lipids. With the use of the Piper Fatigue Scale, there was a significant time-
dependent reduction in overall fatigue in moderately or severely fatigued subjects while on the
dietary supplement for 4-8 weeks. Analysis of mitochrondrial function indicated that four and eight
weeks of the dietary supplement in moderately or severely fatigued subjects significantly increased
mitochondrial function. Similarly, chronic fatigue syndrome patients administered antioxidants plus
LRT also show reductions in fatigue. The results indicate that LRT plus antioxidants can significantly
reduce moderate to severe chronic fatigue and restore mitochondrial function. Dietary use of
unoxidized membrane lipids plus antioxidants is recommended for patients with moderate to severe
chronic fatigue.
Nijs J, Aerts A, Department of Generalized joint J Manipulative OBJECTIVES: This study aimed at (1) comparing the prevalence of generalized hypermobility in
De Meirleir K. Human hypermobility is Physiol Ther. 2006 patients with chronic fatigue syndrome (CFS) and healthy volunteers, (2) examining the clinical
Physiology- more common in Jan;29(1):32-9. importance of generalized hypermobility in patients with CFS, and (3) examining whether knee
Faculty of Physical chronic fatigue proprioception is associated with hypermobility in patients with CFS. METHODS: Sixty-eight
Education and syndrome than in patients with CFS filled out two self-reported measures (for the assessment of symptom severity and
Physiotherapy healthy control disability), were questioned about muscle and joint pain, and were screened for generalized
Vrije Universiteit subjects. hypermobility. Afterward, the patients performed a knee repositioning test (assessment of knee
Brussel (VUB), proprioception), and it was examined whether or not they fulfilled the criteria for benign joint
Belgium. hypermobility syndrome (BJHS). Sixty-nine age- and sex-matched healthy volunteers were screened
jo.Nijs@vub.ac.be for generalized joint hypermobility and performed the same knee repositioning test. RESULTS:
Compared with the healthy volunteers (4.3%, 3/68), significantly more patients with CFS (20.6%,
14/69) fulfilled the criteria for generalized joint hypermobility (Fisher exact test, P < .004). No
associations were found between generalized joint hypermobility and the self-reported measures
(including pain severity) or knee proprioception (Spearman correlation analysis). Knee proprioception
was similar in both groups (Mann-Whitney U = 1961, z = -1.745, P = .81). Forty patients with CFS
(58.8%) fulfilled the criteria for BJHS. CONCLUSIONS: These data indicate that a subgroup of
patients with CFS present with generalized joint hypermobility and most patients with of CFS fulfill
the diagnostic criteria for BJHS. There appears to be no association between musculoskeletal pain and
joint hypermobility in patients with CFS.
Nijs J, De Nitric oxide and Med Hypotheses.
Meirleir K. chronic fatigue 2006;66(2):449-
syndrome: Are we 50. Epub 2005 Oct
caring for our 10. Comment on:
patients or are we Med Hypotheses.
practicing 2005;65(3):631-3.
selfcare?
Nijs J, Meeus M, Department of Chronic Man Ther. 2006 Patients with chronic fatigue syndrome (CFS) experience chronic musculoskeletal pain which is even
De Meirleir K. Human musculoskeletal Aug;11(3):187- more debilitating than fatigue. Scientific research data gathered around the world enables clinicians to
Physiology, pain in chronic 191. Epub 2006 understand, at least in part, chronic musculoskeletal pain in CFS patients. Generalized joint
Faculty of Physical fatigue syndrome: Jun 14. hypermobility and benign joint hypermobility syndrome appear to be highly prevalent among CFS
Education and Recent sufferers, but they do not seem to be of any clinical importance. On the other hand, pain
Physiotherapy, developments and catastrophizing accounts for a substantial portion of musculoskeletal pain and is a predictor of
Vrije Universiteit therapeutic exercise performance in CFS patients. The evidence concerning pain catastrophizing is supportive of
Brussel, Belgium; implications. the indirect evidence of a dysfunctional pain processing system in CFS patients with musculoskeletal
Department of pain. CFS sufferers respond to incremental exercise with a lengthened and accentuated oxidative
Health Sciences, stress response, explaining muscle pain, postexertional malaise, and the decrease in pain threshold
Division of following graded exercise in CFS patients. Applying the scientific evidence to the manual
Musculoskeletal physiotherapy profession, pacing self-management techniques and pain neurophysiology education
Physiotherapy, are indicated for the treatment of musculoskeletal pain in CFS patients. Studies examining the
Higher Institute of effectiveness of these strategies for CFS patients are warranted.
Physiotherapy,
Hogeschool
Antwerpen,
Belgium.
O'Dowd H, Pain Management Cognitive Health Technol OBJECTIVES: To test the hypothesis that group cognitive behavioural therapy (CBT) will produce
Gladwell P, Centre, Frenchay behavioural Assess. 2006 an effective and cost-effective management strategy for patients in primary care with chronic fatigue
Rogers CA, Hospital, Bristol, therapy in chronic Oct;10(37):iii-iv, syndrome/myalgic encephalopathy (CFS/ME). DESIGN: A double-blind, randomised controlled trial
Hollinghurst S, UK. fatigue syndrome: ix-x, 1-121. was adopted with three arms. Outcomes were assessed at baseline and 6 and 12 months after first
Gregory A. a randomised assessment and results were analysed on an intention-to-treat basis. SETTING: A health psychology
controlled trial of department for the management of chronic illness in a general hospital in Bristol, UK.
an outpatient PARTICIPANTS: Adults with a diagnosis of CFS/ME referred by their GP. INTERVENTIONS: The
group programme. three interventions were group CBT incorporating graded activity scheduling, education and support
group (EAS) and standard medical care (SMC). OUTCOME MEASURES: The primary outcome
measure was the Short Form with 36 Items (SF-36) physical and mental health summary scales. Other
outcome measures included the Chalder fatigue scale, Hospital Anxiety and Depression Scale,
General Health Questionnaire, physical function (shuttles walked, walking speed and perceived
fatigue), health utilities index and cognitive function (mood, recall and reaction times). RESULTS: A
total of 153 patients were recruited to the trial and 52 were randomised to receive CBT, 50 to EAS
and 51 to SMC. Twelve patients failed to attend for the 12-month follow-up and 19 patients attended
one follow-up, but not both. The sample was found to be representative of the patient group and the
characteristics of the three groups were similar at baseline. Three outcome measures, SF-36 mental
health score, Chalder fatigue scale and walking speed, showed statistically significant differences
between the groups. Patients in the CBT group had significantly higher mental health scores
[difference +4.35, 95% confidence interval (CI) +0.72 to +7.97, p = 0.019], less fatigue (difference
-2.61, 95% CI -4.92 to -0.30, p = 0.027) and were able to walk faster (difference +2.83 shuttles, 95%
CI +1.12 to +5.53, p = 0.0013) than patients in the SMC group. CBT patients also walked faster and
were less fatigued than those randomised to EAS (walking speed: difference +1.77, 95% CI +0.025 to
+3.51, p = 0.047; fatigue: difference -3.16, 95% CI -5.59 to -0.74, p = 0.011). Overall, no other
statistically significant difference across the groups was found, although for many measures a trend
towards an improved outcome with CBT was seen. Except for walking speed, which, on average,
increased by +0.87 shuttles (95% CI +0.09 to +1.65, p = 0.029) between the 6- and 12-month follow-
ups, the scores were similar at 6 and 12 months. At baseline, 30% of patients had an SF-36 physical
score within the normal range and 52% had an SF-36 mental health score in the normal range. At 12
months, the physical score was in the normal range for 46% of the CBT group, 26% of the EAS group
and 44% of SMC patients. For mental health score the percentages were CBT 74%, EAS 67% and
SMC 70%. Of the CBT group, 32% showed at least a 15% increase in physical function and 64%
achieved a similar improvement in their mental health. For the EAS and SMC groups, this
improvement in physical and mental health was achieved for 40 and 60% (EAS) and 49 and 53%
(SMC), respectively. The cost-effectiveness of the intervention proved very difficult to assess and did
not yield reliable conclusions. CONCLUSIONS: Group CBT did not achieve the expected change in
the primary outcome measure as a significant number did not achieve scores within the normal range
post-intervention. The treatment did not return a significant number of subjects to within the normal
range on this domain; however, significant improvements were evident in some areas. Group CBT
was effective in treating symptoms of fatigue, mood and physical fitness in CFS/ME. It was found to
be as effective as trials using individual therapy in these domains. However, it did not bring about
improvement in cognitive function or quality of life. There was also evidence of improvement in the
EAS group, which indicates that there is limited value in the non-specific effects of therapy. Further
research is needed to develop better outcome measures, assessments of the broader costs of the illness
and a clearer picture of the characteristics best fitted to this type of intervention.
Oleske JM, REVIEW Chronic Journal of Chronic Objective: An overview of the unique aspects of Chronic Fatigue Syndrome in children and
Friedman KJ, Fatigue Syndrome Fatigue Syndrome adolescents (CACFS) is herein provided for healthcare professionals who may be called upon to
Kaufman KK, in Children and 2006;13(2/3): 97- diagnose and/or treat this illness. Young age of onset, puberty, and interactions with peers and the
Palumbo D, Adolescents 115 educational system provide greater diagnostic and treatment challenges than found with adult onset
Sterling J, Evans CFS. Method: A review of diagnostic procedures and treatment protocols found in the contemporary
TL literature is coupled with the professional experiences of the authors in treating CACFS to delineate
the roles and responsibilities of family, healthcare providers and educators in diagnosing, treating and
supporting the CACFS patient. Results: Areas discussed include: pathogenesis, patient evaluation,
clinical evaluation, laboratory evaluation, treatment options, psychological issues, role of schools,
and the roles of primary and tertiary care providers. Conclusion: CACFS can be diagnosed and treated
with varying levels of success if all the professionals involved in the treatment program have a clear
understanding of their roles and responsibilities. Primary care physicians, pediatricians, other
subspecialists, family members, social workers and educators, may all be called upon to participate in
the treatment program of CACFS. While it is best to have one, compassionate physician in charge of
care, the CACFS may benefit from the inclusion of specialized treatment options available from or
through a tertiary care provider. To the extent possible, socialization, education and psychological
support of the CACFS should be provided.
Ouyang A, Wrzos Division of Contribution of Am J The irritable bowel syndrome (IBS) is found more commonly in women than men. It is more
HF. Gastroenterology Gender to Gastroenterol. prevalent in patients with chronic fatigue syndrome, fibromyalgia, and chronic pelvic pain, all
and Hepatology, Pathophysiology 2006 Dec;101 syndromes characterized by pain and found predominantly in women. This article reviews evidence
The Milton S. and Clinical Suppl 3:S602-9. for a role of biological sex factors and gender on the pathways mediating visceral pain. The effect of
Hershey Medical Presentation of gonadal hormones on gastrointestinal motility and the sensory afferent pathway and central
Center, College of IBS: Should processing of visceral stimuli and the contribution of gender role to the clinical presentation are
Medicine, Management Be discussed. Although differences in responses to treatment modalities between genders exist, the
Pennsylvania State Different in approach to IBS patients in both genders is quite similar. Nevertheless, a special attention to gender
University, Women? role and stress-related factors should be addressed. New developments in research, outlined in the
Hershey, paper, might bring more gender-specific treatments in the future.
Pennsylvania.
Padhan P. Chronic fatigue. CMAJ. 2006 Aug
15;175(4):386-7;
author reply 387-8.
Comment on:
CMAJ. 2006 Mar
14;174(6):765-7.
Page WF. Medical Follow-up Update on the Twin Res Hum The National Academy of Sciences-National Research Council (NAS-NRC) Twin Registry is one of
Agency, Institute NAS-NRC Twin Genet. 2006 the oldest, national population-based twin registries in the United States. It consists of 15,924 white
of Medicine, 500 Registry. Dec;9(6):985-7. male twin pairs born in the years 1917 to 1927 (inclusive), both of whom served in the armed forces,
Fifth Street NW, mostly during World War II. This article updates activity in this registry since the earlier 2002 article
Washington, DC in Twin Research. The results of clinically based studies on dementia, Parkinson's disease, age-related
20001, USA. macular degeneration, and primary osteoarthritis were published, as well as articles based on
wpage@nas.edu previously collected questionnaire data on chronic fatigue syndrome, functional limitations, and
healthy aging. In addition, risk factor studies are being planned to merge clinical data with earlier
collected risk factor data from questionnaires. Examination data from the subset of National Heart,
Lung, and Blood Institute (NHLBI) twins resulted in a number of articles, including the relationship
of endogenous sex hormones to coronary heart disease and morphological changes in aging brain
structures. The NEO Five-Factor Personality Inventory (a paper-and-pencil self-administered
questionnaire) has been fielded for the first time. A push to consolidate the various data holdings of
the registry is being made.
Pardaens K, Chronic Fatigue How relevant are Clin Rehabil. 2006 OBJECTIVE: To evaluate the outcome of a multidisciplinary treatment programme for patients with
Haagdorens L, Reference Centre, exercise capacity Jan;20(1):56-66. chronic fatigue syndrome, including health-related quality of life (HRQoL) and psychosocial
Van Wambeke P, University measures for variables, and exercise capacity measures. DESIGN: A six-month prospective outcome study.
Van den Broeck Hospitals and evaluating SETTING: University outpatient rehabilitation clinic; group setting. SUBJECTS: One hundred and
A, Van Department of treatment effects sixteen women fulfilling chronic fatigue syndrome criteria. INTERVENTIONS: Cognitive
Houdenhove B. Rehabilitation in chronic fatigue behaviourally and graded exercise-based strategies; emphasis on adaptive lifestyle changes.
Sciences, KU syndrome? Results MEASURES: Short Form General Health Survey (SF-36); Symptom Checklist (SCL-90); Causal
Leuven, Belgium. from a Attribution List (CAL); Self-Efficacy Scale (SE); maximum progressive bicycle ergometer test with
prospective, respiratory gas analysis; and isokinetic leg strength test, before and after treatment. RESULTS: The
multidisciplinary total group significantly improved on nearly all reported HRQoL/psychosocial variables. Changes in
outcome study. exercise capacity measures were rather modest and did not correlate or only weakly correlated with
HRQoL/psychosocial variables. Subgroup analyses indicated that less fit patients improved
significantly more on exercise capacity measures than their more fit counterparts. Patients who were
fitter at baseline scored better on pretreatment HRQoL/psychosocial variables, but both subgroups
improved similarly on these variables. CONCLUSIONS: Health-related quality of life and
psychosocial functioning in patients with chronic fatigue syndrome improves after a six-month
cognitive behaviourally and graded exercise-based multidisciplinary treatment programme. Increase
in exercise capacity measures is not a necessary condition for reported improvements, except for less
fit patients.
Parker NR, Darling Downs Q fever. Lancet. 2006 Feb Q fever is a zoonosis with many manifestations. The most common clinical presentation is an
Barralet JH, Bell Public Health 25;367(9511):679- influenza-like illness with varying degrees of pneumonia and hepatitis. Although acute disease is
AM. Unit, Queensland 88. usually self-limiting, people do occasionally die from this condition. Endocarditis is the most frequent
Health, Australia. chronic presentation. Although Q fever is widespread, practitioner awareness and clinical
neil_parker@healt manifestations vary from region to region. Geographically limited studies suggest that chronic fatigue
h.qld.gov.au syndrome and cardiovascular disease are long-term sequelae. An effective whole-cell vaccine is
licensed in Australia. Live and acellular vaccines have also been studied, but are not currently
licensed.
Peakman M, Department of Immunological Philos Trans R Soc One candidate cause of Gulf War illness is vaccination against infectious diseases including medical
Skowera A, Immunobiology, dysfunction, Lond B Biol Sci. counter-measures against biological weapons. One influential theory has suggested that such mass-
Hotopf M. King's College vaccination and 2006 Apr vaccination caused a shift in immune response to a Type 2 cytokine pattern (Th2), which it was
London, School of Gulf War illness. 29;361(1468):681- suggested was accompanied by a chronic fatigue syndrome-like illness. This article critically
Medicine at Guy's, 7. appraises this theory. We start by examining epidemiological evidence, which indicates that single
UK. vaccines are unlikely to be a substantial cause of Gulf War illness, but that there was a modest
relationship with multiple vaccines, which was strongest in those vaccinated while deployed to the
Gulf. These relationships may be affected by recall bias. We conclude by examining the results of
immunological studies carried out in veterans or in a relevant setting in vitro. The balance of
evidence from immunological studies on veterans returning from the War, including those developing
multi-symptom illness, is that the immune response has not become polarized towards Th2. In
summary, the epidemiological evidence for a multiple vaccine effect on Gulf War-related illness
remains a potentially important aetiological lead, but mechanistic studies available at this stage do
not identify any immunological basis for it.
Pedersen BK, The Centre of Evidence for Scand J Med Sci Considerable knowledge has accumulated in recent decades concerning the significance of physical
Saltin B. Inflammation and prescribing Sports. 2006 activity in the treatment of a number of diseases, including diseases that do not primarily manifest as
Metabolism, exercise as therapy Feb;16 Suppl 1:3- disorders of the locomotive apparatus. In this review we present the evidence for prescribing exercise
Department of in chronic disease. 63. therapy in the treatment of metabolic syndrome-related disorders (insulin resistance, type 2 diabetes,
Infectious dyslipidemia, hypertension, obesity), heart and pulmonary diseases (chronic obstructive pulmonary
Diseases, disease, coronary heart disease, chronic heart failure, intermittent claudication), muscle, bone and
Copenhagen, joint diseases (osteoarthritis, rheumatoid arthritis, osteoporosis, fibromyalgia, chronic fatigue
Denmark. syndrome) and cancer, depression, asthma and type 1 diabetes. For each disease, we review the effect
bkp@rh.dk of exercise therapy on disease pathogenesis, on symptoms specific to the diagnosis, on physical
fitness or strength and on quality of life. The possible mechanisms of action are briefly examined and
the principles for prescribing exercise therapy are discussed, focusing on the type and amount of
exercise and possible contraindications.
Petersen I, Centre for Risk and QJM. 2006 BACKGROUND: Fatigue has been found to complicate infectious mononucleosis (IM) when patients
Thomas JM, Psychiatry, Barts predictors of Jan;99(1):49-55. are directly asked about it. We do not know whether such fatigue is clinically significant, nor whether
Hamilton WT, and The London, fatigue after Epub 2005 Dec 5. IM is a specific risk for fatigue (or whether it can follow other common infections). Various risk
White PD. Queen Mary's infectious markers for post-infectious fatigue have been identified, but findings are inconsistent. AIM: To
School of mononucleosis in a determine the risk of clinically reported fatigue (compared with depression) after IM (compared with
Medicine and large primary-care both influenza and tonsillitis) in patients attending primary care, and to examine risk markers for
Dentistry, UK. cohort. post-IM fatigue. DESIGN: Comparison of matched primary-care cohorts. METHODS: We identified
1438 adult patients with a positive heterophil antibody test for IM from the UK General Practice
Research Database. These patients were individually matched on age, sex and practice to two
comparison groups; one with a clinical diagnosis of influenza and the other of tonsillitis. RESULTS:
The odds ratios (ORs) (95%CI) for reported fatigue after IM vs. influenza and tonsillitis were 4.4
(2.9-6.9) and 6.6 (4.2-10.4), respectively. Risk markers for post-IM fatigue included female sex and
premorbid mood disorder. By comparison, the ORs for depression after IM vs. influenza and
tonsillitis were 1.6 (0.9-2.6) and 2.3 (1.4-3.9), respectively. DISCUSSION: IM is a specific and
significant risk for clinically reported fatigue, which is both separate from, and more common than,
depression. Female sex and premorbid mood disorder are risk markers for fatigue. These can be used
both to target prevention strategies and to explore aetiological mechanisms.
Pittion- Department of Fatigue in multiple J Neurol Sci. 2006 Fatigue in multiple sclerosis is a frequent and disabling symptom that can interfere in daily
Vouyovitch S, Neurology, Central sclerosis is related Apr 15;243(1- functioning. The aim of this study is to demonstrate the relationship between fatigue and disability,
Debouverie M, Hospital, 54000 to disability, 2):39-45. Epub disease course, depression and quality of life. We administered French valid versions of the Fatigue
Guillemin F, Nancy, France. depression and 2006 Jan 24. Impact Scale (EMIF-SEP), the short form of the Beck depression inventory (13 items) and the SF-36
Vandenberghe N, sophie- quality of life. to 237 out of 312 patients with clinically definite multiple sclerosis with EDSS<or=6.5. The EMIF-
Anxionnat R, pittion@wanadoo.f SEP is composed of four dimensions (cognitive, physical, social role and psychological) and allows a
Vespignani H. r multidimensional evaluation. Using a multivariate analysis, EMIF-SEP total scores with physical and
social role subscales were highly correlated with EDSS (p < 0.0001). Cognitive and psychological
dimensions of the EMIF-SEP were not linked to EDSS. EMIF-SEP was not correlated with disease
course after adjusting for EDSS. EMIF-SEP scores were significantly associated with depression
scores (r = 0.74, p < 0.0001). The multivariate analysis also showed a significant impact of fatigue on
each scale of quality of life of the SF-36. These data confirm that fatigue is correlated with disability,
but cognitive and psychological dimensions of fatigue remain independent. Fatigue is also associated
with depression and quality of life.
Prins JB, van der Department of Chronic fatigue Lancet. 2006 Jan During the past two decades, there has been heated debate about chronic fatigue syndrome (CFS)
Meer JW, Medical syndrome. 28;367(9507):346- among researchers, practitioners, and patients. Few illnesses have been discussed so extensively. The
Bleijenberg G. Psychology, 55. Comment in: existence of the disorder has been questioned, its underlying pathophysiology debated, and an
Radboud Lancet. 2006 May effective treatment opposed; patients' organisations have participated in scientific discussions. In this
University 13;367(9522):1573 review, we look back on several controversies over CFS with respect to its definition, diagnosis,
Nijmegen Medical -4; author reply pathophysiology, and treatment. We review issues of epidemiology and clinical manifestations,
Centre, Nijmegen, 1575. Lancet. 2006 focusing on the scientific status of CFS. Modern neuroscience and genetics research offer interesting
Netherlands. May findings for new hypotheses on the aetiology and pathogenesis of the illness. We also discuss
j.prins@mps.umcn 13;367(9522):1574 promising future issues, such as psychopathophysiology and mechanisms of improvement, and
.nl ; author reply 1575 suggest multidisciplinary prospective studies of CFS and fatigue in the general population. These
studies should pay particular attention to similarities to and differences from functional somatic
syndromes and other fatiguing conditions.
Puri BK. MRC Clinical Proton and 31- Int Rev Psychiatry. Neurospectroscopy allows biochemical processes in the brain to be studied non-invasively. At
Sciences Centre, phosphorus 2006 magnetic field strengths of 1.5 T or higher, cerebral proton neurospectroscopy allows the
Imperial College, neurospectroscopy Apr;18(2):145-7. ascertainment of values of myo-inositol, choline-containing compounds, creatine, glutamate,
Hammersmith in the study of glutamine, and N-acetyl aspartate. At similar field strengths, cerebral 31-phosphorus
Hospital, London, membrane neurospectroscopy allows the ascertainment of values of phosphomonoesters, inorganic phosphate,
UK. phospholipids and phosphodiesters, phosphocreatine, and the gamma, alpha and beta nucleotide triphosphate (mainly
basant.puri@csc.m fatty acid adenosine triphosphate) resonances. Since choline is a common polar head group at the Sn3 position
rc.ac.uk intervention in of membrane phospholipid molecules, a raised level of free choline, as indexed by proton
schizophrenia, neurospectroscopy, can indicate relatively low anabolism of membrane phospholipid molecules.
depression, Furthermore, the choline peak includes phosphorylcholine and glycerophosphorylcholine and even
chronic fatigue ethanolamine. The phosphomonoesters peak measured using 31-phosphorus spectroscopy includes
syndrome (myalgic major contributions from phosphocholine, phosphoethanolamine and L-phosphoserine, which are
encephalomyelitis) important precursors of membrane phospholipids, while the phosphodiesters peak includes
and dyslexia. contributions from glycerophosphocholine and glycerophosphoethanolamine, which are important
products of membrane phospholipid catabolism. Hence proton neurospectroscopy and 31-phosphorus
neurospectroscopy can yield important information relating to the metabolism of cerebral membrane
phospholipids. The application of these techniques to the investigation of membrane phospholipid
metabolism in schizophrenia, depression, chronic fatigue syndrome (myalgic encephalomyelitis or
M.E.) and dyslexia is described.
Puri BK. MRC Clinical High-resolution Int Rev Psychiatry. Serial high-resolution structural magnetic resonance imaging scans of the brain can now be precisely
Sciences Centre, magnetic 2006 aligned, with six degrees of freedom (three mutually orthogonal translational and three rotational
Imperial College, resonance imaging Apr;18(2):149-54. degrees of freedom around three mutually orthogonal axes), using a rigid-body subvoxel registration
Hammersmith sinc-interpolation- technique. This is driven by the in-plane point spread function for images acquired in the Fourier
Hospital, London, based subvoxel domain with data obtained over a bounded region of k-space, namely the sinc interpolation function,
UK. registration and where sinc z = (sin z)/z, with z being any complex number (including zero). Computational
basant.puri@csc.m semi-automated subtraction of the three-dimensional Cartesian spatial representation matrices of serially acquired
rc.ac.uk quantitative lateral scan data allows for the determination of structural cerebral changes with great precision, since voxel
ventricular signals from unchanged structures are almost completely cancelled. Thus changes readily show up
morphology against a background of noise. Furthermore, lateral ventricular changes can now be accurately
employing quantified using a semi-automated method involving contour production, threshold computation,
threshold binary image creation and ventricular extraction. These techniques have been applied to the
computation and investigation of the effects on cerebral structure of intervention with fatty acids, particularly the long-
binary image chain polyunsaturated n-3 fatty acid eicosapentaenoic acid (EPA), in disorders such as schizophrenia,
creation in the treatment-resistant depression, chronic fatigue syndrome (myalgic encephalomyelitis or ME), and
study of fatty acid Huntington's disease.
interventions in
schizophrenia,
depression,
chronic fatigue
syndrome and
Huntington's
disease.
Puri BK. Hammersmith Long-chain J Clin Pathol. 2006 Evidence is put forward to suggest that myalgic encephalomyelitis, also known as chronic fatigue
Hospital, United polyunsaturated Aug 25; [Epub syndrome, may be associated with persistent viral infection. In turn, such infections are likely to
Kingdom. fatty acids and the ahead of print] impair the ability of the body to biosynthesize n-3 and n-6 long-chain polyunsaturated fatty acids by
pathophysiology of inhibiting the delta-6 desaturation of the precursor essential fatty acids alpha-linolenic acid and
myalgic linoleic acid. In turn, this would impair the proper functioning of cell membranes, including cell
encephalomyelitis signalling, and have an adverse effect of the biosynthesis of eicosanoids from the long-chain
(chronic fatigue polyunsaturated fatty acids dihomo-a-linolenic acid, arachidonic acid and eicosapentaenoic acid.
syndrome). These actions might offer an explanation for some of the symptoms and signs of myalgic
encephalomyelitis. A potential therapeutic avenue may be offered by bypassing the inhibition of the
enzyme delta-6-desaturase by administering both virgin cold-pressed non-raffinated evening primrose
oil and eicosapentaenoic acid. The former would supply gamma-linolenic acid and lipophilic
pentacyclic triterpenes. The gamma-linolenic acid can readily be converted into dihomo-a-linolenic
acid and thence arachidonic acid, while triterpenes have important free radical scavenging,
cyclooxygenase and neutrophil elastase inhibitory activities. Furthermore, both arachidonic acid and
eicosapentaenoic acid are, at relatively low concentrations, directly virucidal.
Quarmby L, King's College Cognitive- Behav Res Ther. Outcomes for cognitive-behaviour therapy (CBT) in randomised controlled trials (RCTs) have rarely
Rimes KA, Deale London, Academic behaviour therapy 2006 Oct 27; been compared to those in routine clinical practice. Taking the case of CBT for chronic fatigue
A, Wessely S, Department of for chronic fatigue [Epub ahead of syndrome (CFS), we evaluated the results of a successful RCT against those of the same treatment
Chalder T. Psychological syndrome: print] given in the same setting as part of routine practice. Fatigue and social adjustment scores were
Medicine, Weston Comparison of compared for patients who received CBT for CFS as part of a RCT (N=30) and patients who received
Education Centre, outcomes within CBT as part of everyday clinical practice (N=384). The results in the RCT were superior to those in
Cutcombe Road, and outside the routine clinical practice. Between pre-treatment and 6-month follow-up, the RCT showed a larger
London SE5 9RJ, confines of a reduction in fatigue and greater improvement in social adjustment than those in routine treatment.
UK. randomised The changes in fatigue scores were similar for both groups during treatment but were greater in the
controlled trial. RCT between post-treatment and follow-up. Potential reasons for the superior results of the RCT
include patient selection, therapist factors and the use of a manualised treatment protocol.
Practitioners need to pay particular attention to relapse prevention and ensuring adequate follow-up in
addition to encouraging patients to continue with cognitive-behavioural strategies once treatment has
ended.
Rajeevan MS, Division of Viral Glucocorticoid Genes Brain Chronic fatigue syndrome (CFS) is a significant public health problem of unknown etiology, the
Smith AK, and Rickettsial receptor Behav. 2006 Jun 1; pathophysiology has not been elucidated, and there are no characteristic physical signs or laboratory
Dimulescu I, Diseases, National polymorphisms [Epub ahead of abnormalities. Some studies have indicated an association of CFS with deregulation of immune
Unger ER, Center for and haplotypes print] functions and hypothalamic-pituitary-adrenal (HPA) axis activity. In this study, we examined the
Vernon SD, Heim Infectious associated with association of sequence variations in the glucocorticoid receptor gene (NR3C1) with CFS because
C, Reeves WC. Diseases, Centers chronic fatigue NR3C1 is a major effector of the HPA axis. There were 137 study participants (40 with CFS, 55 with
for Disease syndrome. insufficient symptoms or fatigue, termed as ISF, and 42 non-fatigued controls) who were clinically
Control and evaluated and identified from the general population of Wichita, KS. Nine single nucleotide
Prevention, polymorphisms (SNPs) in NR3C1 were tested for association of polymorphisms and haplotypes with
Atlanta, GA, USA. CFS. We observed an association of multiple SNPs with chronic fatigue compared to non-fatigued
(NF) subjects (P < 0.05) and found similar associations with quantitative assessments of functional
impairment (by the SF-36), with fatigue (by the Multidimensional Fatigue Inventory) and with
symptoms (assessed by the Centers for Disease Control Symptom Inventory). Subjects homozygous
for the major allele of all associated SNPs were at increased risk for CFS with odds ratios ranging
from 2.61 (CI 1.05-6.45) to 3.00 (CI 1.12-8.05). Five SNPs, covering a region of approximately 80
kb, demonstrated high linkage disequilibrium (LD) in CFS, but LD gradually declined in ISF to NF
subjects. Furthermore, haplotype analysis of the region in LD identified two associated haplotypes
with opposite alleles: one protective and the other conferring risk of CFS. These results demonstrate
NR3C1 as a potential mediator of chronic fatigue, and implicate variations in the 5' region of NR3C1
as a possible mechanism through which the alterations in HPA axis regulation and behavioural
characteristics of CFS may manifest.
Reeves WC, Heim Viral Exanthems Sleep BMC Neurol. 2006 BACKGROUND: The etiology and pathophysiology of chronic fatigue syndrome (CFS) remain
C, Maloney EM, & Herpesvirus characteristics of Nov 16;6:41. inchoate. Attempts to elucidate the pathophysiology must consider sleep physiology, as unrefreshing
Youngblood LS, Branch, Division persons with sleep is the most commonly reported of the 8 case-defining symptoms of CFS. Although published
Unger ER, of Viral & chronic fatigue studies have consistently reported inefficient sleep and documented a variable occurrence of
Decker MJ, Jones Rickettsial syndrome and non- previously undiagnosed primary sleep disorders, they have not identified characteristic disturbances
JF, Rye DB. Diseases, National fatigued controls: in sleep architecture or a distinctive pattern of polysomnographic abnormalities associated with CFS.
Center for results from a METHODS: This study recruited CFS cases and non-fatigued controls from a population based study
Infectious population-based of CFS in Wichita, Kansas. Participants spent two nights in the research unit of a local hospital and
Diseases, Centers study. underwent overnight polysomnographic and daytime multiple sleep latency testing in order to
for Disease characterize sleep architecture. RESULTS: Approximately 18% of persons with CFS and 7% of
Control & asymptomatic controls were diagnosed with severe primary sleep disorders and were excluded from
Prevention, further analysis. These rates were not significantly different. Persons with CFS had a significantly
Atlanta, GA, USA. higher mean frequency of obstructive apnea per hour (p = .003); however, the difference was not
wcr1@cdc.gov clinically meaningful. Other characteristics of sleep architecture did not differ between persons with
CFS and controls. CONCLUSION: Although disordered breathing during sleep may be associated
with CFS, this study generally did not provide evidence that altered sleep architecture is a critical
factor in CFS. Future studies should further scrutinize the relationship between subjective sleep
quality relative to objective polysomnographic measures.
Ryall C, Coggon MRC A case-control Occup Med OBJECTIVES: To investigate the association of occupational activities, mental health and
D, Peveler R, Epidemiology study of risk (Lond). 2006 comorbidity with care seeking for arm pain, and to test the hypothesis that specific disorders arise
Reading I, Resource Centre, factors for arm Mar;56(2):137-43. from physical risk factors and non-specific pain from psychological ones. METHODS: Patients with a
Palmer KT. University of pain presenting to Epub 2006 Feb 1. new episode of arm pain and matched controls were recruited from eight general practices. A
Southampton, primary care questionnaire about risk factors was completed and cases were classified using a validated
Southampton services. examination schedule. Questions were asked about occupational activities and psychosocial stressors.
General Hospital, Mental health was assessed using the Hospital Anxiety Depression Scale, elements of the Brief
Tremona Road, Symptom Inventory (somatizing tendency) and the Whiteley Index (health anxiety); comorbidity
Southampton from chronic fatigue syndrome (CFS) and chronic widespread pain (CWP) was ascertained using
SO16 6YD, UK. standard definitions. Associations were explored using logistic regression and summarized as odds
ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Altogether, 132 cases and 127
controls were studied. Consulting with arm pain was strongly associated with all of the mental health
variables and with CFS and CWP, irrespective of the site of arm pain or diagnosis. The OR in those
with >3 versus <3 distressing somatic symptoms was 3.9 (95% CI 1.7-9.0). There were several
significant associations with physical activity, but none with occupational psychosocial stressors.
Repeated wrist/finger movements and carrying weights were more strongly associated with specific
diagnoses than with non-specific pain. CONCLUSIONS: Somatizing tendency, health anxiety, low
mood, CFS and CWP are more common in arm pain consulters. Certain mechanical activities are also
overrepresented, particularly in those with specific pathology.
Saggini R, Physical Therapy Submaximal Eura Medicophys. AIM: Chronic fatigue syndrome (CFS) is an illness characterised by disabling fatigue of uncertain
Vecchiet J, Iezzi Institute, aerobic exercise 2006 Jun;42(2):97- aetiology and other nonspecific symptoms. Typically CFS patients complain of a severe fatigue made
S, Racciatti D, Department of with mechanical 102. worse by exercise, with a consistent reduction of working activity. A physical deconditioning could
Affaitati G, Medicine and vibrations explain CFS features as well as a neuromuscular dysfunction, of central or peripheric origin.
Bellomo RG, Aging, G. improves the METHODS: Ten CFS patients were enrolled in a protocol of a rehabilitative treatment over a six-
Pizzigallo E. D'Annunzio functional status of month period: they underwent a submaximal and predominantly aerobic exercise with a reduced O2
University, Chieti, patients with consumption using a Galileo 2000 system that provides mechanical vibrations characterised by
Italy. chronic fatigue sinusoid vertical sollecitations. Before and after such treatment, all patients underwent a pressure pain
syndrome. thresholds profile, an evaluation of physical and psychosocial parameters using the visual analogue
scale (VAS) of Scott-Huskisson, and a muscle performance analysis by the CIBEX 6000
dynamometer. RESULTS: After the six-month period of study there was an overall improvement of
the above described parameters as compared to the basal determinations. CONCLUSION: We
conclude that the rehabilitative exertion provides an useful treatment for CFS patients particularly to
realize an effective training of the explosive strength.
Saidi G, Haines Research Division, The management Br J Gen Pract. BACKGROUND: Most studies on children with chronic fatigue syndrome (CFS)/myalgic
L. Royal College of of children with 2006 encephalomyelitis (ME) have been undertaken in tertiary care and little is known about their
Paediatrics and chronic fatigue Jan;56(522):43-7. management in primary care. AIM: To describe the characteristics of patients aged 5-19 years with
Child Health, 50 syndrome-like CFS-like illness in primary care and to examine how GPs investigate and manage patients. DESIGN
Hallam Street, illness in primary OF STUDY: Descriptive retrospective questionnaire study. SETTING: Sixty-two UK GP practices in
London W1W care: a cross- the MRC General Practice Research Framework (GPRF). METHOD: One hundred and twenty-two
6DE, UK. sectional study. practices were approached; 62 identified 116 patients consulting a GP with severe fatigue lasting over
3 months. Practice nurses and GPs completed questionnaires from medical notes and patients
completed postal questionnaires. RESULTS: Ninety-four patients were considered by a clinical panel,
blind to diagnosis, to meet the Oxford CFS criteria with a fatigue duration of 3 months. Seventy-three
per cent were girls, 94% white, mean age was 12.9 years and median illness duration 3.3 years. GPs
had principal responsibility for 62%. A diagnosis of CFS/ME was made in 55%, 30% of these within
6 months. Fifty per cent had a moderate illness severity. Paediatric referrals were made in 82% and
psychiatric referrals in 46% (median time of 2 and 13 months respectively). Advice given included
setting activity goals, pacing, rest and graded exercise. CONCLUSIONS: Patient characteristics are
comparable to those reported in tertiary care, although fewer are severe cases. GPs have responsibility
for the majority of patients, are diagnosing CFS/ME within a short time and applying a range of
referral and advice strategies.
Sakudo A, Department of Spectroscopic Biochem Biophys To investigate visible and near-infrared (Vis-NIR) spectroscopy enabling chronic fatigue syndrome
Kuratsune H, Virology, Center diagnosis of Res Commun. (CFS) diagnosis, we subjected sera from CFS patients as well as healthy donors to Vis-NIR
Kobayashi T, for Infectious chronic fatigue 2006 Jul spectroscopy. Vis-NIR spectra in the 600-1100 nm region for sera from 77 CFS patients and 71
Tajima S, Disease Control, syndrome by 14;345(4):1513-6. healthy donors were subjected to principal component analysis (PCA) and soft independent modeling
Watanabe Y, Research Institute visible and near- Epub 2006 May of class analogy (SIMCA) to develop multivariate models to discriminate between CFS patients and
Ikuta K. for Microbial infrared 22. healthy donors. The model was further assessed by the prediction of 99 masked other determinations
Diseases, Osaka spectroscopy in (54 in the healthy group and 45 in the CFS patient group). The PCA model predicted successful
University, serum samples. discrimination of the masked samples. The SIMCA model predicted 54 of 54 (100%) healthy donors
Yamadaoka, Suita, and 42 of 45 (93.3%) CFS patients of Vis-NIR spectra from masked serum samples correctly. These
Japan. results suggest that Vis-NIR spectroscopy for sera combined with chemometrics analysis could
provide a promising tool to objectively diagnose CFS.
Schikler KN. Potential Pediatrics. 2006 Letter
polygenic Oct;118(4):1799-
influences on 800; author reply
chronic fatigue 1800. Comment
syndrome. on: Pediatrics.
2006
Jun;117(6):2074-9.
Schonfeldt- Bupropion Pharmacopsychiatr While psychoeducational strategies and general support are always indicated for the treatment of
Lecuona C, augmentation in y. 2006 chronic fatigue syndrome (CFS), pharmacological strategies are yet not well established.
Connemann BJ, the treatment of Jul;39(4):152-4. Antidepressants such as selective serotonin re-uptake inhibitors have been shown to influence
Wolf RC, Braun chronic fatigue positively symptoms and immunological parameters. However, a considerable part of CFS patients do
M, Freudenmann syndrome with not satisfactorily respond to them. Bupropion, a centrally acting catecholamine-transporter blocker
RW. coexistent major without classic psycho-analeptic properties, shows theoretical potential to improve fatigue symptoms.
depression In the reported case paroxetine was augmented with bupropion at high dosage, a strategy which
episode. consecutively led to a rapid relief of CFS-symptoms.
Sene D, Saadoun Service de [Update in Rev Med Interne. INTRODUCTION: Since the discovery of the hepatitis C virus, many manifestations, so called extra-
D, Limal N, Piette medecine interne, Hepatitis C virus 2006 Nov 7; [Epub hepatic manifestations (EHM), are largely reported with more or less relationship proofs.
JC, Cacoub P. hopital de la Pitie- associated ahead of print] ACTUALITIES AND MAIN POINTS: This article proposes a review of the main extra-hepatic
Salpetriere, 91, extrahepatic manifestations associated with the Hepatis C Virus infection and which remain a topical subject,
boulevard de manifestations.] more than fifteen years after the discovery of this virus. Mixed cryoglobulin and its vasculitic
l'Hopital, 75651 [Article in French] manifestations are still one of the more frequent Hepatis C Virus associated-extra-hepatic
Paris cedex 13, manifestations. Its management may be critically changed due to the increasing use of anti-CD20
France. therapy. Among other HCV-EHM, the following extra-hepatic manifestations are still of interest: the
chronic fatigue syndrome, the sicca syndrome, the non-insulin-dependent diabetes mellitus, malignant
B cell proliferations, mainly the Hepatis C Virus-related splenic lymphoma with villous lymphocytes
and the production of auto-antibodies. PERSPECTIVES AND PROJECTS: The mechanisms
underlying these HCV-associated EHM are ill-elucidated and still remain of great interest as proved
by current studies. The use of anti-CD20 antibodies in the treatment of cryoglobulinemic vasculitis is
also under investigation.
Shapiro CM. Chronic fatigue J Psychosom Res.
and chronic fatigue 2006

syndrome: Jun;60(6):549-50.
pathogenesis and
measurement
scales.
Shepherd C. The debate: Br J Nurs. 2006 Almost every aspect of myalgic encephalomyelitis (or encephalopathy) and chronic fatigue syndrome
myalgic Jun 22-Jul is the subject of disagreement and uncertainty -- something that has undoubtedly hampered
encephalomyelitis 12;15(12):662-9. recognition, understanding and research. Although the pathogenesis remains the subject of intense
and chronic fatigue medical debate, a number of predisposing, precipitating and perpetuating factors are now starting to
syndrome. emerge. Therapeutic nihilism is no longer appropriate as there is a great deal that can be done to
alleviate some of the more distressing symptoms and improve quality of life for these patients.
Shor S Lyme Disease Journal of Chronic Objective: Chronic Fatigue Syndrome (CFS) by definition represents a diagnosis of exclusion. Late
Presenting as Fatigue Syndrome stage or "Chronic Lyme" infection with or without "co-infections" is a difficult diagnosis to establish.
Chronic Fatigue 2006; 13(4): 73-82 The symptom complex of both conditions can be very similar. This case study represents an attempt
Syndrome to support serious consideration for a subpopulation of patients otherwise diagnosed with "CFS," as
actually representing chronic Lyme disease. Method: A case study is presented of a 33-year-old man,
who for two years, was being managed as having CFS. However, after ~2 years of utilizing multiple
modalities of management with limited success, the diagnosis of Lyme was reconsidered. Historical
exposure risks to Lyme in this individual were high. He had prolonged exposure in the highly tick-
infested mountains of North Carolina for 18 months, several years prior to becoming ill. More
aggressive investigation confirmed the diagnosis of Lyme. Appropriate changes in management were
associated with an improved level of functioning that was far in excess of what maximal management
of CFS was able to achieve. The features of CFS and chronic Lyme can be very similar and include
the following: Profound fatigue often associated with cognitive impairment. Other common
symptoms related to both of these conditions include sleep disturbances, fibromyalgia, and
dysautonomias. In pursuing clarification of this diagnosis, the author was exposed to a contrast in
medical opinion regarding diagnostic tools and criteria that were perceived as creating potential
barriers to the management of patients presenting with these symptoms. Conclusion: Acceptance and
awareness of the possibility that Lyme disease can present as CFS has important therapeutic and
prognostic implications.
Shor S. Lyme Disease Journal of Chronic No abstract available at September 2006
Presenting as Fatigue Syndrome
Chronic Fatigue 2006;13(4):
Syndrome Profile
A Case Report
Shuttleworth A. Understanding Nurs Times. 2006
chronic fatigue. Jan 17-
23;102(3):20-1.
Siegel SD, Antoni Department of Impaired natural J Psychosom Res. OBJECTIVE: The diagnostic criteria of chronic fatigue syndrome (CFS) define a heterogeneous
MH, Fletcher Psychology, immunity, 2006 population composed of several subgroups. Past efforts to identify subgroup markers have met with
MA, Maher K, Behavioral cognitive Jun;60(6):559-66. mixed success. This study was designed to examine natural killer cell activity (NKCA) as a potential
Segota MC, Medicine Research dysfunction, and subgroup marker by comparing the clinical presentations of CFS patients with and without clinically
Klimas N. Center, University physical symptoms reduced NKCA. METHODS: Forty-one female CFS patients were classified into having either low or
of Miami, FL, in patients with normal NKCA levels. These subgroups were then compared on objective measures of cognitive
USA. chronic fatigue functioning and subjective assessments of fatigue, vigor, cognitive impairment, and daytime
syndrome: dysfunction. RESULTS: Relative to CFS patients in the normal-NKCA subgroup, low-NKCA patients
preliminary reported less vigor, more daytime dysfunction, and more cognitive impairment. In addition, low-
evidence for a NKCA patients performed less on objective measures of cognitive functioning relative to normal-
subgroup? NKCA patients. CONCLUSIONS: The results are offered as preliminary evidence in support of using
NKCA as an immunological subgroup marker in CFS. Findings are also discussed in terms of known
associations between dysregulated immune functions, somatic symptoms, and psychological stress.
Smith AK, White Centers for Polymorphisms in Pharmacogenomic Chronic fatigue syndrome (CFS) is characterized by persistent or relapsing fatigue that is not
PD, Aslakson E, Disease Control genes regulating s. 2006 alleviated by rest, causes substantial reduction in activities and is accompanied by a variety of
Vollmer-Conna and Prevention, the HPA axis Apr;7(3):387-94. symptoms. Its unknown etiology may reflect that CFS is heterogeneous. Latent class analyses of
U, Rajeevan MS. Division of Viral associated with symptoms and physiological systems were used to delineate subgroups within a population-based
and Rickettsial empirically sample of fatigued and nonfatigued subjects [1] . This study examined whether genetic differences
Diseases, National delineated classes underlie the individual subgroups of the latent class solution. Polymorphisms in 11 candidate genes
Center for of unexplained related to both hypothalamic-pituitary-adrenal (HPA) axis function and mood-related
Infectious chronic fatigue. neurotransmitter systems were evaluated by comparing each of the five ill classes (Class 1, n = 33;
Diseases, 1600 Class 3, n = 22; Class 4, n = 22; Class 5, n = 17; Class 6, n = 11) of fatigued subjects with subjects
Clifton Road, defined as well (Class 2, n = 35). Of the five classes of subjects with unexplained fatigue, three
MSG41, Atlanta, classes were distinguished by gene polymorphsims involved in either HPA axis function or
GA 30333, USA. neurotransmitter systems, including proopiomelanocortin (POMC), nuclear receptor subfamily 3,
group C, member 1 (NR3C1), monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), and
tryptophan hydroxylase 2 (TPH2). These data support the hypothesis that medically unexplained
chronic fatigue is heterogeneous and presents preliminary evidence of the genetic mechanisms
underlying some of the putative conditions.
Smith WR, Department of Mortality in a Psychol Med. 2006 BACKGROUND: Comprehensive studies of mortality among patients with chronic fatigue (CF) and
Noonan C, Psychiatry, cohort of Sep;36(9):1301-6. chronic fatigue syndrome (CFS) have not been published, but several sources suggest that CFS is
Buchwald D. University of chronically associated with an elevated risk for suicide. METHOD: Data on 1201 chronically fatigued patients
Washington, fatigued patients. followed in a university-affiliated tertiary-care clinic for up to 14 years were submitted to the Center
Seattle, WA, USA. for Disease Control and Prevention (CDC) National Death Index (NDI) to evaluate all-cause and
wrsmith@u.washin suicide-caused death rates against standardized mortality rates (SMRs). We used Life Table Analysis
gton.edu to examine the influence of sex and diagnoses of CFS and depression. RESULTS: All-cause mortality
in chronically fatigued patients was no higher than expected, but suicide-caused death rates were
more than eight times higher than in the US general population. The significant elevation in the SMR
of suicide was restricted to those who did not meet criteria for CFS [SMR(CF)=14.2, 95% confidence
interval (CI) 5.7-29.3 versus SMR(CFS)=3.6, 95% CI 0.4-12.9]. Among chronically fatigued patients
who did not meet CFS criteria, those with a lifetime history of major depression (MD) had higher
suicide-caused death rates than among their non-depressed counterparts (SMR(MD)=19.1, 95% CI
7.0-41.5 versus SMR(NMD)=5.6, 95% CI 0.1-31.4), although the difference was not significant.
CONCLUSIONS: CFS does not appear to be associated with increased all-cause mortality or suicide
rates. Clinicians, however, should carefully evaluate patients with CF for depression and suicidality.
Smith WR, White Department of A case control BMC Psychiatry. BACKGROUND: Patients with chronic fatigue syndrome typically report high levels of physical
PD, Buchwald D. Psychiatry and study of premorbid 2006 Nov 13;6:53. activity before becoming ill. Few studies have examined premorbid and current activity levels in
Behavioral and currently chronically fatigued patients. METHODS: In a case-control study, 33 patients with chronic,
Sciences, reported physical unexplained, disabling fatigue attending a university-based clinic specializing in fatigue were
University of activity levels in compared to 33 healthy, age- and sex-matched controls. Patients rated their activity levels before their
Washington, chronic fatigue illness and currently, using scales designed for this purpose. Controls reported their level of activity
Seattle, WA, USA. syndrome. of 2 years previously and currently. Chi-square analyses, Student's t tests, and Wilcoxon signed rank
wrsmith@u.washin tests were used in pair matched analyses. RESULTS: Compared to healthy controls, patients with
gton.edu chronic, unexplained fatigue rated themselves as more active before their illness (p < or = 0.001) and
less active currently (p < or = 0.001). The patients also reported they currently stood or walked less
than the controls (median [inter-quartile range] = 4 2345 versus 9 [7.5-12] hours, p < or = 0.001), and
spent more time reclining (median [inter-quartile range] = 12 10111213141516 versus 8 [8-9.5] hours,
p < or = 0.001). These differences remained significant for the subset of patients who met strict
criteria for chronic fatigue syndrome or fibromyalgia. CONCLUSION: Patients with chronic,
unexplained, disabling fatigue reported being more active before becoming ill than healthy controls.
This finding could be explained by greater premorbid activity levels that could predispose to illness,
or by an overestimation of previous activity. Either possibility could influence patients' perceptions of
their current activity levels and their judgments of recovery. Perceived activity should be addressed as
part of management of the illness.
St Clair Gibson UCT/MRC Evaluation of Clin J Sport Med. OBJECTIVE: This study compared differences in maximal strength and aerobic capacity and
A, Grobler LA, Research Unit of maximal exercise 2006 Jan;16(1):39- symptoms of fatigue and depression in athletes with acquired training intolerance (ATI) and control
Collins M, Exercise Science performance, 45. athletes (CON) matched for age and current training volume who did not have symptoms of excessive
Lambert MI, and Sports fatigue, and or chronic fatigue associated with their sporting activity. SETTING: University of Cape Town, Sports
Sharwood K, Medicine, depression in Science Institute of South Africa. PARTICIPANTS: Twenty ATI and 10 CON athletes participated in
Derman EW, Department of athletes with the trial. Although the ATI athletes reported symptoms of excessive fatigue during exercise, or
Noakes TD. Human Biology, acquired chronic symptoms of fatigue that occurred at rest and during activities of daily living, they did not fulfill the
University of Cape training criteria for a diagnosis of chronic fatigue syndrome. MAIN OUTCOME MEASURES: A training and
Town, Cape Town, intolerance. comprehensive medical history was recorded from all subjects. The Beck Depression Inventory Short
South Africa. Form (BDI-SF) was used to assess levels of depression in both ATI and control subjects. Maximal
agibson@sports.uc force output during a 5-second isometric voluntary knee extensor muscle contraction, and maximal
t.ac.za aerobic capacity (VO2max), maximal heart rate (HRmax), and maximal blood lactate concentrations
during a treadmill running test were measured in all subjects. RESULTS: There were no differences
in maximal isometric force output, peak treadmill running speed, VO2max, HRmax, or blood lactate
concentration at rest or after maximal exercise testing between the ATI and CON athletes. However,
the BDI-SF scores were higher in the ATI (7.7 +/- 6.6 arbitrary units) than in the CON athletes (1.7
+/- 1.5 arbitrary units; (P = 0.0052). CONCLUSIONS: These findings suggest that the symptoms of
excessive fatigue and acquired training intolerance described by these ATI athletes do not affect their
maximal isometric and maximal aerobic capacity, and may be associated with psychologic depression
in these athletes.
Staines DR. Phosphodiesterase Med Hypotheses.
inhibitors may be 2006;66(1):203-4.
indicated in the Epub 2005 Sep 19.
treatment of
postulated
vasoactive
neuropeptide
autoimmune
fatigue-related
disorders.
Staines DR. Gold Coast Public Postulated Clin Dev Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised
Health Unit, 10-12 vasoactive Immunol. 2006 by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional
Young Street, neuropeptide Mar;13(1):25-39. impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome
Southport, Qld, autoimmunity in (SIDS) surprisingly may have certain features in common with these conditions. Post-infection
4215, Australia. fatigue-related sequelae may be possible contributing factors although ongoing infection is unproven. Immunological
don_staines@healt conditions: a brief aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of
h.qld.gov.au review and molecular mimicry, inappropriate immunological memory and autoimmunity. Adenylate cyclase-
hypothesis. activating VNs including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive
intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) act as hormones,
neurotransmitters, neuroregulators, immune modulators and neurotrophic substances. They and their
receptors are potentially immunogenic. VNs are widely distributed in the body particularly in the
central and peripheral nervous systems and have been identified in the gut, adrenal gland, blood cells,
reproductive system, lung, heart and other tissues. They have a vital role in maintaining cardio-
respiratory function, thermoregulation, memory, concentration and executive functions such as
emotional responses including social cues and appropriate behaviour. They are co-transmitters for a
number of neurotransmitters including acetylcholine and gaseous transmitters, are potent immune
regulators with primarily anti-inflammatory activity, and have a significant role in protection of the
nervous system against toxic assault as well as being important in the maintenance of homeostasis.
This paper describes a biologically plausible mechanism for the development of certain fatigue-
related syndromes based on loss of immunological tolerance to these VNs or their receptors following
infection, other events or de novo resulting in significant pathophysiology possibly mediated via CpG
fragments and heat shock (stress) proteins. These conditions extend the public health context of
autoimmunity and VN dysregulation and have implications for military medicine where radiological,
biological and chemical agents may have a role in pathogenesis. Possible treatment and prevention
options are considered.
Stormorken E. [A step backwards Tidsskr Nor Letter
for the patients] Laegeforen. 2006
[Article in Oct
Norwegian] 19;126(20):2688-
9; author reply
2689.
Stouten B, Chronic Fatigue Journal of Chronic
Goudsmit E, Syndrome: Fatigue Syndrome
Howes S. Editorial Bias in 2006;13(1): 71-73
the British Medical
Journal. Response
to the Letter to the
Editor
Takahashi T, Yu Department of Beneficial effect Evid Based The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a
F, Zhu SJ, General Medicine, of brewers' yeast Complement mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella
Moriya J, Sumino Kanazawa Medical extract on daily Alternat Med. abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per
H, Morimoto S, University, activity in a 2006 day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity
Yamaguchi N, Kahoku-gun, murine model of Mar;3(1):109-15. in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight
Kanda T. Ishikawa, Japan. chronic fatigue Epub 2006 Jan 23. (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW),
syndrome. SW/BW ratio, percent splenic follicular area and expression levels of interferon-gamma (IFN-
gamma) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of
sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in
the treated group than in the control. There was no difference in BW between both groups through the
experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no
mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the
treated mice together with elevation of splenic follicular area. There were suppressed IFN-gamma and
IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a
protective effect on the marked reduction in activity following repeated BA injection via
normalization of host immune responses.
Tanaka M, Department of Reduced BMC Neurol. 2006 BACKGROUND: Although the neural mechanism of chronic fatigue syndrome has been investigated
Sadato N, Okada Physiology, Osaka responsiveness is Feb 22;6:9. by a number of researchers, it remains poorly understood. METHODS: Using functional magnetic
T, Mizuno K, City University an essential feature resonance imaging, we studied brain responsiveness in 6 male chronic fatigue syndrome patients and
Sasabe T, Tanabe Graduate School of chronic fatigue in 7 age-matched male healthy volunteers. Responsiveness of auditory cortices to transient, short-
HC, Saito DN, of Medicine, 1-4-3 syndrome: a fMRI lived, noise reduction was measured while subjects performed a fatigue-inducing continual visual
Onoe H, Asahimachi, study. search task. RESULTS: Responsiveness of the task-dependent brain regions was decreased after the
Kuratsune H, Osaka 545-8585, fatigue-inducing task in the normal and chronic fatigue syndrome subjects and the decrement of the
Watanabe Y. Japan. masa- responsiveness was equivalent between the 2 groups. In contrast, during the fatigue-inducing period,
t@msic.med.osaka although responsiveness of auditory cortices remained constant in the normal subjects, it was
-cu.ac.jp attenuated in the chronic fatigue syndrome patients. In addition, the rate of this attenuation was
positively correlated with the subjective sensation of fatigue as measured using a fatigue visual
analogue scale, immediately before the magnetic resonance imaging session. CONCLUSION:
Chronic fatigue syndrome may be characterised by attenuation of the responsiveness to stimuli not
directly related to the fatigue-inducing task.
Taylor RR Rehabilitation Journal of Chronic Over the past two decades, a small but growing number of rehabilitation programs for individuals
Programs for Fatigue Syndrome with chronic fatigue syndrome (CFS) have been initiated. The aims of this paper were to review
Individuals with 2006;13(1): 41-55 existing literature on these programs, to compare and contrast findings emerging from inpatient and
Chronic Fatigue outpatient programs, and to comment on the rigor and quality of methodologies used in outcomes
Syndrome A research in this area. The studies reviewed herein varied widely in case selection criteria, program
Review intensity, length of participation, program content, and outcome variables measured. Moreover, many
were limited by selection bias, the absence of valid and reliable measures, and the absence of a
control group. These limitations made it difficult to draw definitive conclusions regarding the
effectiveness of any single approach to rehabilitation (whether inpatient or outpatient). However,
there is some preliminary evidence that both inpatient and outpatient rehabilitation programs may
lead to improvements in physical and occupational functioning, decreased perception of symptom
severity, improved quality of life, and greater resource acquisition-at least for certain subgroups of
individuals with CFS that participate in specific types of programs. Taken together, these preliminary
findings support the need for additional funding and support for the development of comprehensive
rehabilitative program centers that include both inpatient and outpatient programs with follow-up
sessions and ongoing evaluation. Recommendations for future program development and outcomes
research in this area are discussed.
Taylor RR, Conservation of Journal of Chronic No abstract available at September 2006
Kulkarni S, Resources and Fatigue Syndrome
Shiraishi Y. Quality of Life in 2006;13(4):

Individuals with
Chronic Fatigue
Syndrome
Taylor RR, Conservation of Journal of Chronic Objective: To examine the relationship between resources and quality of life in individuals with
Supriya Resources and Fatigue Syndrome chronic fatigue syndrome (CFS). Participants and Study Design: A cross-sectional design was used to
Kulkarni, Yukiko Quality of Life in 2006; 13(4): 5-18 describe associations between resource loss and gain and quality of life for 47 individuals diagnosed
Shiraishi Individuals with with CFS. Main Outcome Measures: The Conservation of Resources Evaluation was used to measure
Chronic Fatigue resources in terms of perceived loss and gain. Health-related quality of life was assessed with the
Syndrome Quality of Life Index. Results: Total resource loss and total resource gain were significant correlates
of overall quality of life. Gains in self-esteem, energy, and work resources were associated with
higher-perceived quality of life. Material loss and energy loss were associated with lower-perceived
quality of life. Conclusions: Findings for the relationships between perceived resources of self-
esteem, work, material items, and energy and perceived quality of life can be used inform future
rehabilitation efforts. These relationships appear to occur independently of illness severity among
individuals CFS
Taylor RR, Department of Long-term J Psychosom Res. OBJECTIVE: To assess the long-term effects of an integrative rehabilitation program on the overall
Thanawala SG, Occupational outcomes of an 2006 quality of life of individuals with chronic fatigue syndrome (CFS). METHODS: This study utilized a
Shiraishi Y, Therapy, College integrative Dec;61(6):835-9. within-subjects, repeated measures cohort design. Twenty-three subjects diagnosed with CFS attended
Schoeny ME. of Applied Health rehabilitation eight sessions of an illness-management group followed by 7 months of goal-oriented, individualized
Sciences, program on quality counseling that occurred once weekly for 30 min per session. Quality of life was assessed at five time
University of of life: a follow-up points (baseline, following the group phase, following the one-on-one phase, and 4 and 12 months
Illinois at Chicago, study. following program completion). RESULTS: A within-subjects repeated measures ANOVA revealed
Chicago, IL significant increases in overall quality of life for up to 1 year following program completion [F(4,
60612, USA. 21)=23.5, P<.001]. CONCLUSIONS: Definitive conclusions about program efficacy are limited by
rtaylor@uic.edu design issues. However, findings suggest that the program may have led to improvement in quality of
life for up to 1 year following program completion.
Teitelbaum JE, Fibromyalgia and The use of D- J Altern OBJECTIVES: Fibromyalgia (FMS) and chronic fatigue syndrome (CFS) are debilitating syndromes
Johnson C, St Fatigue Centers, ribose in chronic Complement Med. that are often associated with impaired cellular energy metabolism. As D-ribose has been shown to
Cyr J. Dallas, TX, USA. fatigue syndrome 2006 increase cellular energy synthesis in heart and skeletal muscle, this open-label uncontrolled pilot
Endfatigue@aol.co and fibromyalgia: Nov;12(9):857-62. study was done to evaluate if D-ribose could improve symptoms in fibromyalgia and/or chronic
m a pilot study. fatigue syndrome patients. DESIGN: Forty-one (41) patients with a diagnosis of FMS and/or CFS
were given D-ribose, a naturally occurring pentose carbohydrate, at a dose of 5 g t.i.d. for a total of
280 g. All patients completed questionnaires containing discrete visual analog scales and a global
assessment pre- and post-D-ribose administration. RESULTS: D-ribose, which was well-tolerated,
resulted in a significant improvement in all five visual analog scale (VAS) categories: energy; sleep;
mental clarity; pain intensity; and well-being, as well as an improvement in patients' global
assessment. Approximately 66% of patients experienced significant improvement while on D-ribose,
with an average increase in energy on the VAS of 45% and an average improvement in overall well-
being of 30% (p < 0.0001). CONCLUSIONS: D-ribose significantly reduced clinical symptoms in
patients suffering from fibromyalgia and chronic fatigue syndrome.
ter Wolbeek M, Laboratory of Severe fatigue in Pediatrics. 2006 OBJECTIVE: The purpose of this study was to determine the prevalence of severe fatigue in
van Doornen LJ, Psychoneuroimmu adolescents: a Jun;117(6):e1078- adolescent boys and girls, to explore the role of lifestyle factors in fatigue, and to investigate whether
Kavelaars A, nology, University common 86. severe fatigue in a healthy population is associated with depression, anxiety, and comorbid factors
Heijnen CJ. Medical Center phenomenon? also observed in chronic fatigue syndrome patients. METHODS: In a sample of 1718 boys and 1749
Utrecht, Utrecht, girls, fatigue severity and duration were measured using a multidimensional questionnaire (Checklist
The Netherlands. Individual Strength). In addition, self-reports of depressive symptoms, anxiety, chronic fatigue
syndrome-related symptoms, and lifestyle characteristics were assessed by means of questionnaires.
Prevalence rates of severe fatigue and severe fatigue for > or =1 month, based on a clinical cutoff
score of the Checklist Individual Strength, were determined for boys and girls separately, and gender-
specific predictors of fatigue were identified by multiple regression analysis. RESULTS: The data
showed high prevalence rates of severe fatigue in adolescents. Remarkable differences between boys
and girls were observed: 20.5% of girls and 6.5% of the boys scored above the clinical cutoff score on
the Checklist Individual Strength. Of these subjects 80.0% of the girls and 61.5% of the boys reported
severe fatigue for > or =1 month. Of the examined lifestyle characteristics, only sleep characteristics
and the participation in sports played a role in predicting fatigue in both genders. Moreover, in girls,
fatigue was associated with higher age, an early menarche, medication use, and the absence of an
additional job. Overall, girls scored higher on depression, anxiety, and chronic fatigue syndrome-
related symptoms. However, the relation between fatigue and these comorbid symptoms did not differ
between genders. In both girls and boys, the duration of fatigue was positively related to fatigue
severity, severity of depression and anxiety, and the number of chronic fatigue syndrome-related
symptoms. CONCLUSIONS: Fatigue prevalence among adolescents is high, especially in girls.
Adolescent girls seem to be more vulnerable to symptoms of fatigue and comorbidity than boys.
Interestingly, despite a female predominance in complaints, the relation between fatigue and
depression, anxiety, and chronic fatigue syndrome-related symptoms was not gender specific and
emerged as a cluster. In both genders, fatigue duration was associated with the severity of fatigue and
the level of psychological comorbidity and chronic fatigue syndrome-related symptoms, and we,
therefore, hypothesize that enduring severe fatigue may form a risk factor for the development of
chronic fatigue syndrome.
Tharakan B, Plummer Trichopus Phytother Res. Chronic fatigue is a complex and little understood symptom for which there is no safe and effective
Dhanasekaran M, Movement zeylanicus 2006 pharmacotherapy. The present study was conducted to investigate the effectiveness of Trichopus
Brown-Borg HM, Disorders Center, combats fatigue Mar;20(3):165-8. zeylanicus whole plant powder on fatigue in young Sprague Dawley rats, and aged normal and long-
Manyam BV. Department of without living mutant Ames dwarf mice. Fatigue was evaluated by subjecting the animals to a forced swim
Neurology, Scott amphetamine- test. Trichopus zeylanicus (250 and 500 mg/kg) treated young Sprague-Dawley rats resisted fatigue at
& White Clinic, mimetic activity. a significant level (p < 0.005) compared with controls by an extended swim time in the forced swim
Temple, TX test. Oral Trichopus zeylanicus (500 mg/kg) treatment for 2 weeks significantly increased the
76508, USA. mobility time in the aged mutant (p < 0.05) and normal mice (p < 0.01) and significantly increased
the swim time in the forced swim test in the aged normal mice (p < 0.05). Amphetamine-mimetic
activity in Trichopus zeylanicus was excluded by suitable tests. These results show that Trichopus
zeylanicus whole plant powder has anti-fatigue effects in young Sprague-Dawley rats and aged
normal and mutant Ames dwarf mice providing scientific evidence for the Kani tribal practice in
India. Copyright 2006 John Wiley & Sons, Ltd.
Tharakan B, Plummer Botanical therapies Phytother Res. Chronic fatigue often occurs in aging and in various neurological, psychiatric and systemic diseases.
Manyam BV. Movement in chronic fatigue. 2006 The available therapies in modern medicine are limited. The exploration of potential alternative
Disorders Center, Feb;20(2):91-5. therapies from traditional medicine is reviewed, as there are several botanicals with experimental
Department of evidence of efficacy based on animal models and clinical studies. Copyright 2006 John Wiley &
Neurology, Scott Sons, Ltd.
and White Clinic
and the Texas

A&M University
System, HSC
College of
Medicine, Temple,
Texas, USA.
Thomas HV, Department of Systematic review Psychol Med. 2006 BACKGROUND: Gulf War veterans have a number of health complaints. We therefore decided to
Stimpson NJ, Psychological of multi-symptom Jun;36(6):735-47. carry out a systematic review to identify and summarize the findings from studies that have assessed
Weightman AL, Medicine, School conditions in Gulf Epub 2006 Jan 26. multi-symptom conditions in Gulf War veterans and in an unexposed comparison group. METHOD:
Dunstan F, Lewis of Medicine, War veterans. Studies published between January 1990 and May 2004 were identified by searching a large number
G. Cardiff University, of electronic databases. Reference lists and websites were also searched and key researchers were
UK. contacted. Studies were included if they compared the prevalence of chronic fatigue syndrome,
multiple chemical sensitivity, CDC-defined chronic multi-symptom illness, fibromyalgia, or
symptoms of either fatigue or numbness and tingling in Gulf War veterans and non-Gulf veterans. A
total of 2401 abstracts were independently reviewed by two authors. RESULTS: Twenty-three
publications fulfilled the inclusion criteria. Gulf deployment was most strongly associated with
chronic fatigue syndrome (OR 3.8, 95% CI 2.2-6.7). Gulf War veterans were also approximately three
and a half times more likely than non-Gulf veterans to report multiple chemical sensitivity or chronic
multi-symptom illness as defined by CDC. The methodological quality of the studies varied but the
later and larger studies were of a high methodological standard with robust sampling strategies,
adequate response rates and good adjustment for confounders. CONCLUSIONS: The results support
the hypothesis that deployment to the Gulf War is associated with greater reporting of multi-symptom
conditions.
Thomas MA, Centre for An investigation of Hum Two hundred and seventy-five patients fulfilling the Centre for Disease Control (CDC) criteria for
Smith AP. Occupational and the long-term Psychopharmacol. Chronic Fatigue Syndrome (CFS) completed measures assessing illness history, global ratings of well
Health benefits of 2006 being, sleep, activity and psychopathology at baseline, 6 months, 18 months and 3 year follow-up.
Psychology, antidepressant Dec;21(8):503-9. Forty-nine of these patients had been prescribed antidepressant medication, namely Tricyclic drugs or
School of medication in the Selective Serotonin Re-uptake Inhibitors (SSRI). Data from the current study suggests that patients in
Psychology, recovery of the antidepressant medication group recover at a faster rate over time when compared to the untreated
Cardiff University, patients with patient sample. In addition, the positive effects of antidepressant therapy are maintained at the 3-year
UK. chronic fatigue follow-up point. It appears from these data that the SSRI in particular are responsible for
thomasma@cf.ac.u syndrome. improvements in the condition. Most importantly, these improvements include a reduction in the
k levels of fatigue recorded by patients. These findings have not been demonstrated in previous studies
of the effect of antidepressant therapy for patients with this illness and this may reflect the short time
periods studied in the earlier research.
Thompson TD, Academic Unit of Homeopathy--what BMC Complement BACKGROUND: Research in homeopathy has traditionally addressed itself to defining the
Weiss M. Primary Care, are the active Altern Med. 2006 effectiveness of homeopathic potencies in comparison to placebo medication. There is now increasing
Cotham House, ingredients? An Nov 13;6:37. awareness that the homeopathic consultation is in itself a therapeutic intervention working
Cotham Hill, exploratory study independently or synergistically with the prescribed remedy. Our objective was to identify and
Bristol BS6 6JL, using the UK evalute potential "active ingredients" of the homeopathic approach as a whole, in a prospective
UK. Medical Research formal case series, which draws on actual consultation data, and is based on the MRC framework for
trevor.thompson@ Council's the evaluation of complex interventions. METHODS: Following on from a theoretical review of how
bris.ac.uk framework for the homeopathic care might mediate its effects, 18 patients were prospectively recruited to a case series
evaluation of based at Bristol Homeopathic Hospital. Patients, who lived with one of three index conditions, were
complex interviewed before and after a five visit "package of care". All consultations were recorded and
interventions. transcribed verbatim. Additional data, including generic and condition-specific questionnaires,
artwork and "significant other" reports were collected. Textual data was subject to thematic analysis
and triangulated with other sources. RESULTS: We judged that around one third of patients had
experienced a major improvement in their health over the study period, a third had some
improvement and a third had no improvement. Putative active ingredients included the patients'
"openness to the mind-body connection", consultational empathy, in-depth enquiry into bodily
complaints, disclosure, the remedy matching process and, potentially, the homeopathic remedies
themselves. CONCLUSION: This study has has identified, using primary consultation and other data,
a range of factors that might account for the effectiveness of homeopathic care. Some of these, such
as empathy, are non-specific. Others, such as the remedy matching process, are specific to
homeopathy. These findings counsel against the use of placebo-controlled RCT designs in which both
arms would potentially be receiving specific active ingredients. Future research in homeopathy should
focus on pragmatic trials and seek to confirm or refute the therapeutic role of constructs such as
patient "openness", disclosure and homeopathicity.
Toda K, Kimura Department of Efficacy of Hiroshima J Med Chronic fatigue syndrome (CFS) is a disorder that causes general fatigue and chronic widespread
H. Rehabilitation, neurotropin in Sci. 2006 pain. A 28-year-old male visited an outpatient department due to general fatigue and pain involving
Hiroshima chronic fatigue Mar;55(1):35-7. the entire body. He did not suffer from fibromyalgia, but he was diagnosed with CFS. At the initial
Prefectural syndrome: a case visit, he complained of lack of concentration, memory decline, frequent urination, insomnia and
Rehabilitation report. occasional difficulty of emotional control, as well as general fatigue and pain involving the entire
Center, Higashi- body. Four tablets of Neurotropin per day alone were administered. General fatigue and pain were
Hiroshima, gradually alleviated one week later. His sleep condition, concentration power, and memory also
Hiroshima, Japan. improved two weeks later. Medication was discontinued from 11 weeks based on the patient's
judgment as he felt little general fatigue and pain involving the entire body. Treatment was completed
3 months later. The symptoms disappeared and did not recur five months after the discontinuation of
Neurotropin. He was looking for a job without fatigue and pain 8 months later (5 months after the
cessation of treatment). The functional mechanisms of Neurotropin in CFS are unknown.
Torenbeek M, Het Roessingh, [Favourable results Ned Tijdschr OBJECTIVE: To determine whether a specific course of interdisciplinary rehabilitation might lead to
Mes CA, van Centrum voor of a rehabilitation Geneeskd. 2006 clinically significant changes in fatigue, experienced disability and physical function in patients with
Liere MJ, Revalidatie, programme with Sep the chronic-fatigue syndrome (CFS). DESIGN: Prospective and uncontrolled. METHOD: 'Het
Schreurs KM, ter divisie cognitive 23;150(38):2088- Roessingh', a rehabilitation centre in Enschede, the Netherlands, has developed an interdisciplinary
Meer R, Pijnrevalidatie, behavioural 94. Comment in: clinical rehabilitation programme for patients with CFS in cooperation with the 'Nijmeegs
Kortleven GC, Enschede. therapy and graded Ned Tijdschr Kenniscentrum Chronische Vermoeidheid' [Chronic-Fatigue Knowledge Centre] in Nijmegen, the
Warmerdam CG. m.torenbeek@roes physical activity in Geneeskd. 2006 Netherlands. In this programme, physical, mental and social activities are gradually increased on the
singh.nl patients with the Sep basis of cognitive behavioural principles and graded activity. Of the 127 successive persons who
chronic-fatigue 23;150(38):2067- enrolled for the therapy during the period from August 2000 to December 2004, 99 fulfilled the
syndrome] [Article 8. inclusion criteria; they had a median duration of symptoms of 6 years. The results of treatment were
in Dutch] evaluated by a measurement with the 'Checklist individuele spankracht' [Checklist individual muscle
tone] before and after treatment and the scores on the 'Patientspecifieke beperkingen' [Patient-specific
disability] and the Short form-36. The measured data were complete in 74 patients. RESULTS:
Before rehabilitation, the levels of fatigue, disability and distress were high. After treatment, the
studied population showed significant improvement in fatigue, experienced disability and physical
function. The magnitude of the improvement was generally 'average'. At the end of treatment, 70% of
the patients were clinically less fatigued, 68% experienced less disability and 55% functioned better
physically. In 34% the level of fatigue was normalised after treatment, but 9.5% of the patients was
more fatigue. CONCLUSION: The rehabilitation programme offered for CFS led to significant
improvements in function and fatigue.
Torres-Harding Psychosocial and Journal of Chronic Background: Few studies have examined the problem of chronic fatigue in children and adolescents
SR, Jordan J, Physical Impact of Fatigue Syndrome and its potential impact on functioning. Chronic fatigue may have a negative impact on school
Jason LA, Arias Chronic Fatigue in 2006;13(2/3): 55- functioning, family activities, psychological well-being, physical functioning, and severity of medical
R. a Community- 74 symptomatology. Objectives: This study compared psychosocial, family, and physical functioning
Based Sample of between a randomly selected community based sample of 36 children and adolescents with chronic
Children and fatigue and a group of 21 children and adolescents without fatigue. Methods: Children and parents
Adolescents completed a comprehensive medical history questionnaire and questionnaires assessing psychological
functioning, family functioning, and school attendance. Results: Results indicated that children with
chronic fatigue tended to have more difficulties in overall physical and psychological functioning, as
measured by the Child Health Questionnaire and the Child Behavior Checklist. In addition, children
in the chronic fatigue group experienced disruptions in a range of activities and reported more severe
physical symptomatology when compared to children without fatigue. Conclusions: Findings suggest
that children and adolescents with chronic fatigue may have a range of associated difficulties,
including limitations in physical and psychosocial functioning and a negative impact on the ability to
engage in normative activities.
Underhill RA, Prevalence of Journal of Chronic The prevalence of CFS (Chronic Fatigue Syndrome) and chronic fatigue were investigated in family
O'Gorman RL Chronic Fatigue Fatigue Syndrome members of CFS patients using a questionnaire-based study. Significant differences were seen
Syndrome and 2006;13(1): 3-13 between the prevalence of CFS in all groups of family members relative to the published community
Chronic Fatigue prevalence of 0.422% (spouses/partners: 3.2%, p < 0.001; offspring: 5.1%, p < .001; parents and
Within Families of siblings: 1.1%, p < 0.02; second and third degree blood relatives 0.8%, p < 0.02). The prevalence of
CFS Patients CFS was higher in genetically unrelated household contacts and in nonresident genetic relatives than
in the community, indicating that both household contact and genetic relationship are risk factors for
CFS
Van Damme S, Department of Well-being in J Psychosom Res. OBJECTIVE: Research in chronic pain patients has shown that accepting the chronic nature of their
Crombez G, Van Experimental- patients with 2006 illness is positively related to quality of life. The aim of this study was to investigate whether
Houdenhove B, Clinical and chronic fatigue Nov;61(5):595-9. acceptance is also associated with better well-being in patients suffering from chronic fatigue
Mariman A, Health syndrome: the role syndrome (CFS). METHODS: Ninety-seven patients completed a battery of questionnaires measuring
Michielsen W. Psychology, Ghent of acceptance. fatigue, functional impairment, psychological distress, and acceptance. RESULTS: Results indicated
University, Ghent, that acceptance has a positive effect upon fatigue and psychological aspects of well-being. More
Belgium. specifically, acceptance was related to more emotional stability and less psychological distress,
stefaan.vandamme beyond the effects of demographic variables, and fatigue severity. CONCLUSION: We suggest that
@ugent.be promoting acceptance in patients with CFS may often be more beneficial than trying to control
largely uncontrollable symptoms.
van de Putte EM, Department of How fatigue is Arch Dis Child. AIMS: To assess the relation between fatigue and somatic symptoms in healthy adolescents and
Engelbert RH, Paediatrics, related to other 2006 adolescents with chronic fatigue syndrome/myalgic encephalopathy (CFS/ME). METHODS: Seventy
Kuis W, Kimpen Wilhelmina somatic symptoms. Oct;91(10):824-7. two adolescents with CFS were compared within a cross-sectional study design with 167 healthy
JL, Uiterwaal CS. Children's Epub 2006 Jun 5. controls. Fatigue and somatic complaints were measured using self-report questionnaires, respectively
Hospital, the subscale subjective fatigue of the Checklist Individual Strength (CIS-20) and the Children's
University Medical Somatization Inventory. RESULTS: Healthy adolescents reported the same somatic symptoms as
Center Utrecht, adolescents with CFS/ME, but with a lower score of severity. The top 10 somatic complaints were the
Utrecht, The same: low energy, headache, heaviness in arms/legs, dizziness, sore muscles, hot/cold spells,
Netherlands. weakness in body parts, pain in joints, nausea/upset stomach, back pain. There was a clear positive
E.vandePutte@um relation between log somatic symptoms and fatigue (linear regression coefficient: 0.041 points log
cutrecht.nl somatic complaints per score point fatigue, 95% CI 0.033 to 0.049) which did not depend on disease
status. CONCLUSIONS: Results suggest a continuum with a gradual transition from fatigue with
associated symptoms in healthy adolescents to the symptom complex of CFS/ME.
van de Putte EM, Department of Mirrored Pediatrics. 2006 OBJECTIVE: Our aim with this study was to assess the relation between chronic fatigue syndrome in
van Doornen LJ, Pediatrics, symptoms in Jun;117(6):2074-9. adolescents and fatigue and associated symptoms in their fathers and mothers, more specifically the
Engelbert RH, Wilhelmina mother and child presence of chronic fatigue syndrome-like symptoms and psychologic distress. METHOD: In this
Kuis W, Kimpen Children's with chronic cross-sectional study, 40 adolescents with chronic fatigue syndrome according to the Centers for
JL, Uiterwaal CS. Hospital, fatigue syndrome. Disease Control and Prevention criteria were compared with 36 healthy control subjects and their
University Medical respective parents. Questionnaires regarding fatigue (Checklist Individual Strength), fatigue-
Center, Utrecht, associated symptoms, and psychopathology (Symptom Checklist-90) were applied to the children and
The Netherlands. their parents. RESULTS: Psychologic distress in the mother corresponds with an adjusted odds ratio
e.vandeputte@wkz of 5.6 for the presence of CFS in the child. The presence of fatigue in the mother and dimensional
.azu.nl assessment of fatigue with the Checklist Individual Strength revealed odds ratios of, respectively,
5.29 and 2.86 for the presence of chronic fatigue syndrome in the child. An increase of 1 SD of the
hours spent by the working mother outside the home reduced the risk for chronic fatigue syndrome in
their child with 61%. The fathers did not show any risk indicator for chronic fatigue syndrome in their
child. CONCLUSIONS: Mothers of adolescents with chronic fatigue syndrome exhibit fatigue and
psychologic symptoms similar to their child in contrast with the fathers. The striking difference
between the absent association in fathers and the evident association in mothers suggests that the
shared symptom complex of mother and child is the result of an interplay between genetic
vulnerability and environmental factors.
van Heukelom Department of Influence of Eur J Neurol. 2006 The effect of melatonin, a chronobiotic drug, was explored in 29 patients with chronic fatigue
RO, Prins JB, Neurology, Sleep- melatonin on Jan;13(1):55-60. syndrome (CFS) and Dim Light Melatonin onset (DLMO) later than 21.30 hours, reflective of
Smits MG, Wake Disorders fatigue severity in delayed circadian rhythmicity. The patients took 5 mg of melatonin orally, 5 h before DLMO during
Bleijenberg G. and patients with 3 months. Their responses to the checklist individual strength (CIS), a reliable questionnaire
Chronobiology, chronic fatigue measuring the severity of personally experienced fatigue, were assessed twice with a 6-week interval
Hospital De syndrome and late immediately before the treatment and once after 3 months treatment. In the pre-treatment period the
Gelderse Vallei, melatonin fatigue sub-score improved significantly. After treatment, the total CIS score and the sub-scores for
Ede, and secretion. fatigue, concentration, motivation and activity improved significantly. The sub-score fatigue
Department of normalized in two of the 29 patients in the pre-treatment period and in eight of 27 patients during
Medical treatment. This change was significant. In the patients with DLMO later than 22.00 hours (n=21) the
Psychology, total CIS score and the sub-scores for fatigue, concentration and activity improved significantly more
Radbound than in the patients (n=8) with DLMO earlier than 22.00 hours. Melatonin may be an effective
University Medical treatment for patients with CFS and late DLMO, especially in those with DLMO later than 22.00
Centre, Nijmegen, hours.
The Netherlands.
Van Hoof E, De Pediatric Chronic Journal of Chronic Pediatric chronic fatigue syndrome (CFS) posits even more challenges for professional caregivers in
Becker P, De Fatigue Syndrome Fatigue Syndrome comparison with adult CFS samples. Most children with CFS display a decrease in school attendance
Meirleir K. and Muchausen- 2006;13(2/3): 45- and a decrease in social activities. As several conditions such as school phobia, primary psychiatric
by-Proxy: A Case 53 disorders or family disturbance present the same characteristics, the diagnostic process appears more
Study complex. Family disturbance, moreover, is often specified as child abuse, neglect or even
Muchausen-by-proxy. As skepticism is frequently associated with a diagnosis of CFS, patients and

parents must fend for themselves fighting allegations of child abuse and neglect. This case study
illustrates what happens when such allegations are put forward.
Van Houdenhove Chronic Fatigue In search of a new J Psychosom Res. OBJECTIVE: The purpose of this study is to investigate changes in action-proneness (a cognitive and
B, Bruyninckx K, Reference Centre, balance. Can high 2006 behavioral tendency toward direct action) after a multidisciplinary group intervention, including
Luyten P. University "action-proneness" Jun;60(6):623-5. cognitive behaviour therapy (CBT) and graded exercise therapy (GET). METHODS: Patients with
Hospitals, K.U. in patients with chronic fatigue syndrome (n=62) completed three versions of a Dutch self-report questionnaire
Leuven, Leuven, chronic fatigue evaluating action-proneness retrospectively that is (1) before illness onset, (2) before treatment and
Belgium. syndrome be (3) after treatment. Significant others (n=62) also gave their opinion about the patients' action-
boudewijn.vanhou changed by a proneness at time points 1 and 2. RESULTS: Premorbid action-proneness levels considerably dropped
denhove@uz.kuleu multidisciplinary after illness onset. After treatment, action-proneness levels significantly increased again, although
ven.ac.be group treatment? levels remained below premorbid levels. CONCLUSION: High action-proneness retrospectively
reported by CFS patients can be adaptively modified by a multidisciplinary group treatment including
CBT and GET.
Van Houdenhove Psychiatric Br J Psychiatry.
B. comorbidity and 2006 Apr;188:395;
chronic fatigue author reply 396.
syndrome.
van Staden WC. Department of Conceptual issues Curr Opin PURPOSE OF REVIEW: To review the conceptual problems in distinguishing between
Psychiatry, in undifferentiated Psychiatry. 2006 undifferentiated somatoform disorder and chronic fatigue syndrome, for both may present with
University of somatoform Nov;19(6):613-8. fatigue as the main symptom. RECENT FINDINGS: The differences and/or similarities between
Pretoria, Pretoria, disorder and undifferentiated somatoform disorder and chronic fatigue syndrome have not been studied,
South Africa. chronic fatigue conceptually or empirically. The literature fails to present discriminant validity of chronic fatigue
cwvanstaden@ico syndrome. syndrome in relation to undifferentiated somatoform disorder. A critical feature is implied in the
n.co.za definition of undifferentiated somatoform disorder but absent from the definitions of chronic fatigue
syndrome: some patients experience their fatigue as being exclusively physical and not as mental,
which is prima facie peculiar, for fatigue is necessarily a mental experience. One is not able to
experience fatigue without a mind (or a brain). This experience is characterized as a 'mindless'
fatigue, underpinned by pathological reductionist thinking. By not recognizing this critical feature,
diagnostic endeavours may perpetuate the problem as a function of the patient's difficulty.
SUMMARY: Proponents of chronic fatigue syndrome should distinguish chronic fatigue syndrome
from undifferentiated somatoform disorder, if chronic fatigue syndrome is a distinct entity at all.
Further, the 'mindless' quality is a critical feature that needs consideration in refining the concept of
undifferentiated somatoform disorder.
Vermeulen RC, CFS and Pain Azithromycin in J Transl Med. ABSTRACT: BACKGROUND: CFS is a clinical state with defined symptoms, but undefined cause.
Scholte HR. Research Center Chronic Fatigue 2006 Aug 15;4:34. The patients may show a chronic state of immune activation and treatment with an antibiotic in this
Amsterdam, Syndrome (CFS), subgroup has been suggested. METHODS: In a retrospective study, the response of CFS patients to
Waalstraat 25-31, an analysis of azithromycin, an antibiotic and immunomodulating drug, has been scored from the patients records
1078 BR clinical data. and compared with clinical and laboratory data. Azithromycin was not the first choice therapy, but
Amsterdam, The offered when the effect of counseling and L-carnitine was considered insufficient by the patient and
Netherlands. the clinician. RESULTS: Of the 99 patients investigated, 58 reported a decrease in the symptoms by
rv@cvscentrum.nl. the use of azithromycin. These responding patients had lower levels of plasma acetylcarnitine.
CONCLUSION: The efficacy of azithromycin in the responsive patients could be explained by the
modulating effect on a chronic primed state of the immune cells of the brain, or the activated
peripheral immune system. Their lower acetylcarnitine levels may reflect a decreased antioxidant
defense and/or an increased consumption of acetylcarnitine caused by oxidative stress.
Vermeulen RC. CFS and Pain Translation and Popul Health Metr. ABSTRACT: BACKGROUND: In a study by Wagner et al., the CDC Symptom Inventory was
Research Center validation of the 2006 Oct 18;4:12. validated in a population selected from the inhabitants of a city in the USA, and proofed reliable for
Amsterdam, Dutch language the assessment of the accompanying symptoms of CFS. The Dutch translation of the CDC Symptom
Amsterdam, The version of the Inventory is compared to the original and the psychometric properties are presented for patients in a
Netherlands. CDC Symptom tertiary care setting. METHODS: One hundred thirty-nine consecutive patients who visited the CFS
rv@cvscentrum.nl. Inventory for Center Amsterdam for the first time were asked to complete the CDC Symptom Inventory in the
assessment of Dutch Language Version (DLV) together with the usual set of questionnaires. Sixty-one patients had
Chronic Fatigue Chronic Fatigue (CF) and 78 patients fulfilled the criteria for CFS. Forty-three healthy accompanying
Syndrome (CFS). persons completed the CDC Symptom Inventory DLV, the Physical Functioning scale of the Medical
Outcome Survey Short Form-36 DLV, and the Fatigue and Concentration scales of the Checklist
Individual Strength (CIS-20). RESULTS: The healthy controls group contained fewer women and
was overall older than the patient groups. The influence of gender on the CDC Symptom Inventory
DLV was significant but the effect of age was not. The Dutch version had a good internal consistency
and convergent validity. The results were comparable to the original English version, but the sex-
related difference needs further study. CONCLUSION: The Dutch version of the CDC Symptom
Inventory is a reliable tool for the assessment of the secondary criteria for CFS. The results show that
it is comparable to the outcome of studies in English speaking countries.
Vernon SD, Centers for The challenge of Pharmacogenomic Chronic fatigue syndrome (CFS) is a debilitating illness characterized by multiple unexplained
Reeves WC. Disease Control integrating s. 2006 symptoms including fatigue, cognitive impairment and pain. People with CFS have no characteristic
and Prevention, disparate high- Apr;7(3):345-54. physical signs or diagnostic laboratory abnormalities, and the etiology and pathophysiology remain
National Center content data: Comment in: unknown. CFS represents a complex illness that includes alterations in homeostatic systems, involves
for Infectious epidemiological, Pharmacogenomic multiple body systems and results from the combined action of many genes, environmental factors
Diseases, Atlanta, clinical and s. 2006 and risk-conferring behavior. In order to achieve understanding of complex illnesses, such as CFS,
GA, USA. laboratory data Apr;7(3):341-3. studies must collect relevant epidemiological, clinical and laboratory data and then integrate, analyze
sdv2@cdc.gov collected during an and interpret the information so as to obtain meaningful clinical and biological insight. This issue of
in-hospital study Pharmacogenomics represents such an approach to CFS. Data was collected during a 2-day in-
of chronic fatigue hospital study of persons with CFS, other medically and psychiatrically unexplained fatiguing
syndrome. illnesses and nonfatigued controls identified from the general population of Wichita, KS, USA. While
in the hospital, the participants' psychiatric status, sleep characteristics and cognitive functioning was
evaluated, and biological samples were collected to measure neuroendocrine status, autonomic
nervous system function, systemic cytokines and peripheral blood gene expression. The data
generated from these assessments was made available to a multidisciplinary group of 20 investigators
from around the world who were challenged with revealing new insight and algorithms for integration
of this complex, high-content data and, if possible, identifying molecular markers and elucidating
pathophysiology of chronic fatigue. The group was divided into four teams with representation from
the disciplines of medicine, mathematics, biology, engineering and computer science. The papers in
this issue are the culmination of this 6-month challenge, and demonstrate that data integration and
multidisciplinary collaboration can indeed yield novel approaches for handling large, complex
datasets, and reveal new insight and relevance to a complex illness such as CFS.
Vernon SD, Center for Challenges for Pharmacogenomic Chronic fatigue syndrome (CFS) is prevalent, disabling and costly. Despite extensive literature
Whistler T, Infectious molecular s. 2006 describing the epidemiology and clinical aspects of CFS, it has been recalcitrant to diagnostic
Aslakson E, Diseases, Division profiling of Mar;7(2):211-8. biomarker discovery and therapeutic intervention. This is due to the fact that CFS is a complex illness
Rajeevan M, of Viral and chronic fatigue defined by self-reported symptoms and diagnosed by the exclusion of medical and psychiatric
Reeves WC. Rickettsial syndrome. diseases that may explain the symptoms. Studies attempting to dissect the pathophysiology are
Diseases, National challenging to design as CFS affects multiple body systems, making the choice of which system to
Centers for study dependent on an investigators area of expertise. However, the peripheral blood appears to be
Disease Control facilitating the molecular profiling of several diseases, such as CFS, that involve bodywide
and Prevention, perturbations that are mediated by the CNS. Successful molecular profiling of CFS will require the
Atlanta, GA integration of genetic, genomic and proteomic data with environmental and behavioral data to define
30333, USA. the heterogeneity in order to optimize intervention.
svernon@cdc.gov
Vervoort T, Department of Brief Report: The J Pediatr Psychol. Objective This study examined the actual and estimated empathic accuracy (EA) of the parents of
Crombez G, Experimental- Accuracy of 2006 Sep 29; adolescents with chronic fatigue syndrome (CFS). Methods The actual EA of both parents (n = 24)
Buysse A, Clinical and Parents for the [Epub ahead of was assessed in relation to the thoughts and feelings of their child (n = 14) about CFS and about other
Goubert L, De Health Thoughts and print] life events. Adolescents were also asked to estimate the parents' EA. Results For the actual EA, both
Backer T, Ickes Psychology, Ghent Feelings of Their parents were significantly less accurate regarding the adolescent's thoughts and feelings about CFS
W. University, Adolescent than about other life events. Fathers were just as empathically accurate as mothers. For the estimated
Belgium; Research Suffering from EA, however, results indicated that adolescents perceived their mother to be more empathically
Institute for Chronic Fatigue: A accurate than their father. Actual EA and estimated EA about CFS were negatively correlated for
Psychology and Preliminary Study fathers, not for mothers. Conclusions Results are discussed in terms of the importance of assessing
Health, The of Empathy. EA in relation to other dimensions of empathic understanding and distress in the observer.
Netherlands.
Vollmer-Conna University of New An empirical Pharmacogenomic OBJECTIVES: To test the hypothesis that medically unexplained chronic fatigue and chronic fatigue
U, Aslakson E, South Wales, delineation of the s. 2006 syndrome (CFS) are heterogeneous conditions, and to define the different conditions using both
White PD. School of heterogeneity of Apr;7(3):355-64. symptom and laboratory data. METHODS: We studied 159 women from KS, USA. A total of 51 of
Psychiatry, 30 chronic these suffered from fatigue consistent with established criteria for CFS, 55 had chronic fatigue of
Botany Street, unexplained insufficient symptoms/severity for a CFS diagnosis and 53 were healthy controls matched by age and
Sydney UNSW fatigue in women. body mass index (BMI) against those with CFS. We used principal components analyses to define
2052, Australia. factors that best described the variable space and to reduce the number of variables. The 38 most
ute@unsw.edu.au explanatory variables were then used in latent class analyses to define discrete subject groups.
RESULTS: Principal components analyses defined six discrete factors that explained 40% of the
variance. Latent class analyses provided several interpretable solutions with four, five and six classes.
The four-class solution was statistically most convincing, but the six-class solution was more
interpretable. Class 1 defined 41 (26%) subjects with obesity and relative sleep hypnoea. Class 2 were
38 (24%) healthy subjects. Class 3 captured 24 (15%) obese relatively hypnoeic subjects, but with
low heart rate variability and cortisol. Class 4 were 23 (14%) sleep-disturbed and myalgic subjects
without obesity or significant depression. The two remaining classes with 22 (14%) and 11 (7%)
subjects consisted of the most symptomatic and depressed, but without obesity or hypnoea. Class 5
had normal sleep indices. Class 6 was characterized by disturbed sleep, with low sleep heart rate
variability, cortisol, and sex hormones. CONCLUSION: Chronic medically unexplained fatigue is
heterogeneous. The putative syndromes were differentiated by obesity, sleep hypnoea, depression,
physiological stress response, sleep disturbance, interoception and menopausal status. If these
syndromes are externally validated and replicated, they may prove useful in determining the causes,
pathophysiology and treatments of CFS.
Wallace DJ. Cedars- Is there a role for Curr Pharm Des. Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the
Sinai/David cytokine based 2006;12(1):17-22. regulation of cell growth and repair and also have immune modulating properties. Cytokines play a
Geffen School of therapies in role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching.
Medicine at fibromyalgia. A review of the fibromyalgia literature and related studies suggest that IL-1, IL-6 and IL-8 are
UCLA, Los dysregulated in the syndrome. Therapies directed against these cytokines may be of potential
Angeles, CA, importance in the management of fibromyalgia.
USA.
dwallace@ucla.ed
u
Wallesch CW. [Fatigue and Fortschr Neurol Editorial
multiple sclerosis] Psychiatr. 2006
[Article in Sep;74(9):495-6.
German]
Waltman P, New York Interpreter of Pharmacogenomic Comprehensive, systematic and integrated data-centric statistical approaches to disease modeling can
Pearlman A, University, maladies: s. 2006 provide powerful frameworks for understanding disease etiology. Here, one such computational
Mishra B. Courant Institute redescription Apr;7(3):503-9. framework based on redescription mining in both its incarnations, static and dynamic, is discussed.
of Mathematical mining applied to The static framework provides bioinformatic tools applicable to multifaceted datasets, containing
Sciences, 715 biomedical data genetic, transcriptomic, proteomic, and clinical data for diseased patients and normal subjects. The
Broadway, New analysis. dynamic redescription framework provides systems biology tools to model complex sets of
York, NY 10003, regulatory, metabolic and signaling pathways in the initiation and progression of a disease. As an
USA. example, the case of chronic fatigue syndrome (CFS) is considered, which has so far remained
mishra@nyu.edu intractable and unpredictable in its etiology and nosology. The redescription mining approaches can
be applied to the Centers for Disease Control and Prevention's Wichita (KS, USA) dataset, integrating
transcriptomic, epidemiological and clinical data, and can also be used to study how pathways in the
hypothalamic-pituitary-adrenal axis affect CFS patients.
Wang JJ, Meng Institute of [On the important Zhongguo Zhen OBJECTIVE: To probe into the role of Siguan points in treatment of chronic fatigue syndrome.
H, Cui CB, Song Acupuncture & role of Siguan Jiu. 2006 METHODS: Based on diagnosis, pathogenesis and etiology of chronic fatigue syndrome in TCM, the
YJ, Wang XH, Moxibustion, points in treatment Feb;26(2):116-9. role of Siguan points in treatment of chronic fatigue syndrome were induced by means of relative
Wu ZC. China Academy of of chronic fatigue literatures of Siguan points in recent 10 years from 3 aspects. CONCLUSION: Acupuncture at Siguan
TCM, Beijing syndrome] [Article as main points has a better therapeutic effect on chronic fatigue syndrome.
100700, China. in Chinese]
wjj751@sina.com
Wearden AJ, School of Fatigue BMC Med. 2006 BACKGROUND: Chronic fatigue syndrome, also known as ME (CFS/ME), is a condition
Riste L, Dowrick Psychological Intervention by Apr 7;4:9. characterised primarily by severe, disabling fatigue, of unknown origin, which has a poor prognosis
C, Chew-Graham Sciences, Nurses and serious personal and economic consequences. Evidence for the effectiveness of any treatment for
C, Bentall RP, University of Evaluation--the CFS/ME in primary care, where most patients are seen, is sparse. Recently, a brief, pragmatic
Morriss RK, Manchester, FINE Trial. A treatment for CFS/ME, based on a physiological dysregulation model of the condition, was shown to
Peters S, Dunn G, Manchester, M13 randomised be successful in improving fatigue and physical functioning in patients in secondary care. The
Richardson G, 9PL, UK. controlled trial of treatment involves providing patients with a readily understandable explanation of their symptoms,
Lovell K, Powell alison.wearden@m nurse led self-help from which flows the rationale for a graded rehabilitative plan, developed collaboratively with the
P. anchester.ac.uk treatment for therapist. The present trial will test the effectiveness and cost-effectiveness of pragmatic
patients in primary rehabilitation when delivered by specially trained general nurses in primary care. We selected a
care with chronic client-centred counselling intervention, called supportive listening, as a comparison treatment.
fatigue syndrome: Counselling has been shown to be as effective as cognitive behaviour therapy for treating fatigue in
study protocol. primary care, is more readily available, and controls for supportive therapist contact time. Our control
[ISRCTN7415661 condition is treatment as usual by the general practitioner (GP). METHODS AND DESIGN: This
0]. study protocol describes the design of an ongoing, single-blind, pragmatic randomized controlled trial
of a brief (18 week) self-help treatment, pragmatic rehabilitation, delivered by specially trained
nurse-therapists in patients' homes, compared with nurse-therapist delivered supportive listening and
treatment as usual by the GP. An economic evaluation, taking a societal viewpoint, is being carried
out alongside the clinical trial. Three adult general nurses were trained over a six month period to
deliver the two interventions. Patients aged over 18 and fulfilling the Oxford criteria for CFS are
assessed at baseline, after the intervention, and again one year later. Primary outcomes are self-
reported physical functioning and fatigue at one year, and will be analysed on an intention-to-treat
basis. A qualitative study will examine the interventions' mechanisms of change, and also GPs'
drivers and barriers towards referral.
Weidenhammer Zentrum fur [Chronic fatigue in Rehabilitation Chronic exhaustion and fatigue are increasingly important in rehabilitation medicine. Objectives of
W, Wessel A, naturheilkundliche complementary (Stuttg). 2006 this study were (a) to describe the effects of in-patient rehabilitation on patients with chronic fatigue
Hutter A, Forschung, II. rehabilitative Oct;45(5):299-308. syndromes, (b) to identify predictors for treatment outcome, and (c) to analyze the impact of
Melchart D, Medizinische medicine-- comprehensive diagnosing on these issues. A total of 171 patients with chronic exhaustion or fatigue
Schroder A. Klinik und predictors of the (90 % female, mean age 55 +/- 10 yrs) from a rehabilitation hospital with a complementary medicine-
Poliklinik, TU outcomes] [Article based treatment concept were included in a prospective observational study. Within the longitudinal
Munchen, in German] study patients were examined three times (on admission to hospital, at discharge as well as six months
Kaiserstrasse 9, later). Participation rate of the postal inquiry was 69 %. Besides items constructed ad hoc, Patient
80801 Munich. questionnaires included the Symptom Checklist and assessment instruments for depression, quality of
Wolfgang.Weiden life, sense of coherence as well as for changes in experience and behaviour. Treatment outcome was
hammer@ltz.tu- defined as sum score of binary-coded response criteria. The pattern of complaints differed clearly
muenchen.de between diagnostic subgroups (neurasthenia, affective disorders, adjustment disorders) before
treatment. At discharge from hospital patients showed clinically relevant improvements lasting for six
months after rehabilitation. Multiple regression analyses revealed a statistically significant
relationship (R (mult) = 0.59) between predictors and outcome at discharge from hospital. A better
result was associated with higher trust in treatment success, active information seeking on
complementary medicine, healthier feeding habits, better somatic health and a decreased mental
status, with regard to the status before treatment. The prediction of outcome after six months was
comparably poorer (R (mult) = 0.42). Treatment success was higher in the absence of a diagnosis of
neurasthenia, in patients accepting the group-oriented treatment concept and in patients not believing
that their disease was due to their own way of living. Trust in the success of the treatment was a
highly ranked predictor for longer lasting outcome, too. The results underline the importance of
motivation aspects for treatment outcome indicating that individual expectations and attitudes should
be considered in a more distinct way when allocating patients to rehabilitative programmes.
Weir PT, Harlan Department of The incidence of J Clin Rheumatol. BACKGROUND: The epidemiology of fibromyalgia is poorly defined. The incidence of
GA, Nkoy FL, Family and fibromyalgia and 2006 fibromyalgia has not been determined using a large population base. Previous studies based on
Jones SS, Preventive its associated Jun;12(3):124-8. prevalence data demonstrated that females are 7 times more likely to have fibromyalgia than males
Hegmann KT, Medicine, comorbidities: a and that the peak age for females is during the childbearing years. OBJECTIVE: We have calculated
Gren LH, Lyon University of Utah, population-based the incidence rate of fibromyalgia in a large, stable population and determined the strength of
JL. Salt Lake City, retrospective association between fibromyalgia and 7 comorbid conditions. METHODS: We conducted a
Utah 84108, USA. cohort study based retrospective cohort study of a large, stable health insurance claims database (62,000 nationwide
peter.weir@hsc.ut on International enrollees per year). Claims from 1997 to 2002 were examined using the International Classification of
ah.edu Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes to identify fibromyalgia cases (ICD
Diseases, 9th code 729.1) and 7 predetermined comorbid conditions. RESULTS: A total of 2595 incident cases of
Revision codes. fibromyalgia were identified between 1997 and 2002. Age-adjusted incidence rates were 6.88 cases
per 1000 person-years for males and 11.28 cases per 1000 person-years for females. Females were
1.64 times (95% confidence interval = 1.59-1.69) more likely than males to have fibromyalgia.
Patients with fibromyalgia were 2.14 to 7.05 times more likely to have one or more of the following
comorbid conditions: depression, anxiety, headache, irritable bowel syndrome, chronic fatigue
syndrome, systemic lupus erythematosus, and rheumatoid arthritis. CONCLUSION: Females are
more likely to be diagnosed with fibromyalgia than males, although to a substantially smaller degree
than previously reported, and there are strong associations for comorbid conditions that are commonly
thought to be associated with fibromyalgia.
Whistler T, Centers for Gene expression Pharmacogenomic Quantitative trait analysis (QTA) can be used to test whether the expression of a particular gene
Taylor R, Disease Control correlates of s. 2006 significantly correlates with some ordinal variable. To limit the number of false discoveries in the
Craddock RC, and Prevention, unexplained Apr;7(3):395-405. gene list, a multivariate permutation test can also be performed. The purpose of this study is to
Broderick G, Viral Exanthems fatigue. identify peripheral blood gene expression correlates of fatigue using quantitative trait analysis on
Klimas N, Unger and Herpesvirus gene expression data from 20,000 genes and fatigue traits measured using the multidimensional
ER. Branch, Atlanta, fatigue inventory (MFI). A total of 839 genes were statistically associated with fatigue measures.
GA 30333, USA. These mapped to biological pathways such as oxidative phosphorylation, gluconeogenesis, lipid
taw6@cdc.gov metabolism, and several signal transduction pathways. However, more than 50% are not functionally
annotated or associated with identified pathways. There is some overlap with genes implicated in
other studies using differential gene expression. However, QTA allows detection of alterations that
may not reach statistical significance in class comparison analyses, but which could contribute to
disease pathophysiology. This study supports the use of phenotypic measures of chronic fatigue
syndrome (CFS) and QTA as important for additional studies of this complex illness. Gene expression
correlates of other phenotypic measures in the CFS Computational Challenge (C3) data set could be
useful. Future studies of CFS should include as many precise measures of disease phenotype as is
practical.
Whitehead L. Department of Toward a Int J Nurs Stud. BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an illness
Nursing and trajectory of 2006 associated with high levels of physical and cognitive disability over a prolonged period of time.
Midwifery, identity Nov;43(8):1023- Recovery from CFS/ME can be interspersed with relapses. Further, the legitimacy of the illness
University of reconstruction in 31. Epub 2006 continues to be questioned within and beyond the health profession. AIM: This paper examines the
Stirling, Western chronic fatigue Mar 9. reconstruction of self-identity for those experiencing CFS/ME. METHOD: This longitudinal
Isles Hospital, syndrome/myalgic qualitative study involved up to three in-depth interviews with 17 people with CFS/ME and family
Macaulay Road, encephalomyelitis: members. RESULTS: A trajectory that describes transitions in identity over time and the range of
Stornoway, UK. a longitudinal elements that influence these is proposed. During the acute phase of illness, characterised by total
lw6@stir.ac.uk qualitative study. debility, people adopted the traditional sick role. The medium term phase highlighted movement
between disability as part of the total self, total debility, and/or the adoption of a supernormal
identity. The longer-term phase was defined for the majority of participants as the positive
reconstruction of self. Identity was contingent with positive and negative experiences and responses
co-existing with the potential to 'tip' the balance and perceived identity. In the longer term people's
identity became more static with the development of coping strategies to maintain this. The trajectory
can be described as pendular and movement between each type of identity was possible during all
phases of the illness experience depending on the nature and impact of the illness and responses given
to these. The proposed trajectory represents a dynamic model of identity reconstruction.
CONCLUSION: Understanding the patients' experience and recognising that different stages may
exist is important for health professionals. This awareness can enhance shared understanding and
opportunities to work with people in negotiating the impact of illness.

Whitehead LC. University of Quest, chaos and Soc Sci Med. 2006 Chronic illness is disruptive, threatening people's sense of identity and taken for granted assumptions.
Stirling restitution: living May;62(9):2236- Transformations in values, expectations and life priorities are likely to be experienced and in order to
Stornoway, UK. with chronic 45. Epub 2005 Oct regain a coherent sense of self, people must interpret their experiences. People with difficult to
lw6@stir.ac.uk fatigue 19. diagnose illnesses can find themselves living with greater uncertainty and stigma. This paper explores
syndrome/myalgic how people with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) describe and
encephalomyelitis. interpret their illness experience by applying Arthur Frank's narrative typologies to analyse interviews
with 17 British people with CFS/ME. The analysis proposes that a trajectory of narrative typologies is
experienced, starting with a restitution narrative, moving to a chaos narrative and, for most, back to a
restitution narrative and on to a quest narrative. The presentation of narrative types put forward by
people living with CFS/ME differ to those presented by people who are HIV positive and have been
treated for breast cancer.
Witkowski JA. The postgenomic Pharmacogenomic
era and complex s. 2006
disease. Apr;7(3):341-3.
Comment on:
Pharmacogenomic
s. 2006
Apr;7(3):345-54.
Yoshiuchi K, Department of Patients with Clin Physiol Funct Prior studies on brain blood flow in chronic fatigue syndrome (CFS) did not find consistent results.
Farkas J, Neurosciences, chronic fatigue Imaging. 2006 This may be because they used single-photon emission computed tomography to measure brain blood
Natelson BH. Fatigue Research syndrome have Mar;26(2):83-6. flow, which could not measure absolute blood flow. Therefore, the aim of this study was to test the
Center, UMDNJ- reduced absolute hypothesis that patients with CFS have reduced absolute cerebral blood flow. Xenon-computed
New Jersey cortical blood tomography blood flow studies were done on 25 CFS patients and seven healthy controls. Analyses
Medical School, flow. were done after stratifying the CFS patients based on the presence or absence of a current psychiatric
Newark, USA. disorder. Flow was diminished in both groups as follows: patients with no current psychiatric
kyoshiuc- disorders had reduced cortical blood flow in the distribution of both right and left middle cerebral
tky@umin.ac.jp arteries (P<0.05 for both) while those with current psychiatric disorders had reduced blood flow only
in the left middle cerebral artery territory (P<0.05). These data indicate that patients with CFS have
reduced absolute cortical blood flow in rather broad areas when compared with data from healthy
controls and that those devoid of psychopathology had the most reductions in cortical flow. These
data support, in part, our earlier findings that patients devoid of psychopathology are the group most
at risk of having some of the symptoms of CFS due to brain dysfunction.
Yuemei L, First Hospital The therapeutic J Tradit Chin Med. OBJECTIVE: To observe the therapeutic effects of electrical acupuncture and auricular-plaster
Hongping L, Affiliated to effects of electrical 2006 therapy for chronic fatigue syndrome (CFS). METHOD: 64 CFS patients were randomly divided into
Shulan F, Guangzhou acupuncture and Sep;26(3):163-4. two groups. 32 cases in the treatment group were treated by the electrical acupuncture and auricular-
Dongfang G. University of auricular-plaster in plaster therapy, and 32 cases in the control group with oral hydrocortisone. RESULTS: The total
Traditional 32 cases of chronic effective rates were respectively 93.75% in the treatment group and 75.00% in the control group, with
Chinese Medicine, fatigue syndrome. a statistically significant difference between the two groups (P < 0.05). CONCLUSION: Electrical
Guangzhou acupuncture and auricular-plaster therapy may show a better anti-fatigue effect than that of routine
510405, China. Western drugs.
Zuckerman JN. Academic Centre Protective J Med Virol. 2006 Hepatitis B vaccines are highly effective and safe and have been incorporated into national
for Travel efficacy, Feb;78(2):169-77. immunization programs in over 150 countries. The major humoral immune response is to the
Medicine and immunotherapeuti common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy
Vaccines and c potential, and immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is
WHO safety of hepatitis associated with different HLA-DR alleles and impaired Th cell response, among other factors such as
Collaborating B vaccines. route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen
Centre for variants have also been identified, which may have a potential impact on immunization and routine
Reference, screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis
Research and B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with
Training in Travel an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines
Medicine, Royal and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS).
Free and Several studies are in progress on treatment of chronic hepatitis B infection by immunization with
University College multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell
Medical School, vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct
University College genetic manipulation of antigen presenting cells. Copyright 2005 Wiley-Liss, Inc.
London, United
Kingdom.
j.zuckerman@med
sch.ucl.ac.uk
[No authors In this issue. Psychol Med. 2006 This issue contains two reviews, one on chronic fatigue syndrome and one on suicide and the
listed] Jul;36(7):893-4. menstrual cycle. Other sets of papers examine various aspects of suicide, addictive behaviours, and
depression, and three individual papers examine a variety of topics.
[No authors Chronic fatigue Nurs Times. 2006
listed] syndrome. Apr 4-
10;102(14):25.
[No authors Global Advisory Wkly Epidemiol
listed] Committee on Rec. 2006 Jan
Vaccine Safety, 1- 13;81(2):15-9.
2 December 2005.
[English, French]

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Authors Author Address Title Publication Abstract

heptafluorobutyryl-isobutyl derivatives of urinary metabolites. Alternative preparations utilised

Chaudhuri A. Essex Centre for Diagnosing Practitioner. 2006 Review

remain evidence-based in the care of patients.

cells, and tricyclic author reply 690-1.

Kaiser J. Biomedicine. Science. 2006 May

suggest plausible mechanisms for chronic fatiguing illness.

Goodnick PJ. Chronic Fatigue Fatigue Syndrome

effective in the long term.

and chronic fatigue 2006

Shiraishi Y. Quality of Life in 2006;13(4):

and the Texas

Muchausen-by-proxy. As skepticism is frequently associated with a diagnosis of CFS, patients and

opportunities to work with people in negotiating the impact of illness.

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