pdf 834 KB - ME Research UK


pdf 834 KB - ME Research UK

ME Research UK — Database of Research Publications 2009

Authors Author Address Title Publication Abstract

Ablin JN, Buskila

D, Clauw DJ.

Ablin JN, Odes L,

Neumann L,

Buskila D.

Adams D, Wu T,

Yang X, Tai S,

Vohra S.

University of

Michigan Chronic

Pain and Fatigue

Research Center,

Ann Arbor, MI

48106, USA.

Institute of

Rheumatology and

Internal Medicine

6, Tel Aviv

Sourasky Medical

Center, Tel Aviv,




CARE Program,

Department of


University of

Alberta, 8B19

11111 Jasper



Alberta, Canada,

T5K 0L4.

Biomarkers in


The Hebrew

version of the

FibroFatigue scale:

validation of a

questionnaire for

assessment of

fibromyalgia and

chronic fatigue


Traditional Chinese

medicinal herbs for

the treatment of

idiopathic chronic

fatigue and chronic

fatigue syndrome.

Curr Pain

Headache Rep.



Rheumatol Int.

2009 Sep 25. [Epub

ahead of print]


Database Syst Rev.

2009 Oct


Fibromyalgia is a common pain syndrome characterized by widespread pain, tenderness, and a

number of other somatic symptoms and syndromes. Although there was original skepticism that any

objective abnormalities would be identified in these individuals, at present there are many that have

been reproducibly identified, and most point to dysregulation of central nervous system function as a

key underlying pathogenic mechanism in this and related illnesses. This article reviews several

objective abnormalities or measures that have been identified or used in fibromyalgia, and indicates

which of these may be most promising to eventually use as biomarkers to follow the response to

treatment or progress of disease over time.

The objective of this study is to validate a translated Hebrew version of the FibroFatigue Scale (FFS).

The Hebrew version of the FFS was administered to 100 patients fulfilling ACR criteria for classification

of FM together with the validated Hebrew version of the Fibromyalgia Impact Questionnaire (FIQ),

the validated Hebrew version of the Short Form‐36 (SF‐36) and a Visual Analogue Scale (VAS)

measurement of pain, anxiety, depression, morning stiffness and global well being. Test‐retest

reliability was assessed using Spearman correlations. Internal consistency was evaluated with

Cronbach's alpha of reliability. Construct validity of the FFS was evaluated by correlations among the

FFS, the FIQ and the subscales of the SF‐36. Mean duration of symptoms was 10.7 years, and mean

age of participants was 53.5 years. Test‐retest reliability was between 0.46 and 0.85 for the various

FFS items. Internal consistency was 0.89 for the overall FFS. Significant correlations were obtained

between the FFS items and the SF‐36. These results support the reliability and validity of the data

obtained with the Hebrew version of the FSS for detecting and measuring symptom severity in

Hebrew speaking patients with FM.

BACKGROUND: Chronic fatigue is increasingly common. Conventional medical care is limited in

treating chronic fatigue, leading some patients to use traditional Chinese medicine therapies,

including herbal medicine. OBJECTIVES: To assess the effectiveness of traditional Chinese medicine

herbal products in treating idiopathic chronic fatigue and chronic fatigue syndrome. SEARCH

STRATEGY: The following databases were searched for terms related to traditional Chinese medicine,

chronic fatigue, and clinical trials: CCDAN Controlled Trials Register (July 2009), MEDLINE (1966‐2008),

EMBASE (1980‐2008), AMED (1985‐2008), CINAHL (1982‐2008), PSYCHINFO (1985‐2008), CENTRAL

(Issue 2 2008), the Chalmers Research Group PedCAM Database (2004), VIP Information (1989‐2008),

CNKI (1976‐2008), OCLC Proceedings First (1992‐2008), Conference Papers Index (1982‐2008), and

Dissertation Abstracts (1980‐2008). Reference lists of included studies and review articles were

examined and experts in the field were contacted for knowledge of additional studies. SELECTION

CRITERIA: Selection criteria included published or unpublished randomized controlled trials (RCTs) of

participants diagnosed with idiopathic chronic fatigue or chronic fatigue syndrome comparing

traditional Chinese medicinal herbs with placebo, conventional standard of care (SOC), or no

treatment/wait lists. The outcome of interest was fatigue. DATA COLLECTION AND ANALYSIS: 13

databases were searched for RCTs investigating TCM herbal products for the treatment of chronic

fatigue. Over 2400 references were located. Studies were screened and assessed for inclusion criteria

by two authors. MAIN RESULTS: No studies that met all inclusion criteria were identified. AUTHORS'

ME Research UK — Database of Research Publications 2009

Ament W,

Verkerke GJ.

Armitage R, Landis

C, Hoffmann R,

Lentz M, Watson

N, Goldberg J,

Buchwald D.

Department of

Biometrics, Faculty

of Health and

Technology, Zuyd


Heerlen, the




Department of


University of

Michigan, Ann

Arbor, MI, USA.



Exercise and


Power spectral

analysis of sleep

EEG in twins

discordant for

chronic fatigue


Sports Med.


422. doi:




J Psychosom Res.

2009 Jan;66(1):51‐

7. Epub 2008 Nov


CONCLUSIONS: Although studies examining the use of TCM herbal products for chronic fatigue were

located, methodologic limitations resulted in the exclusion of all studies. Of note, many of the studies

labelled as RCTs and conducted in China did not utilize rigorous randomization procedures.

Improvements in methodology in future studies is required for meaningful synthesis of data.

Physical exercise affects the equilibrium of the internal environment. During exercise the contracting

muscles generate force or power and heat. So physical exercise is in fact a form of mechanical energy.

This generated energy will deplete the energy stocks within the body. During exercise, metabolites

and heat are generated, which affect the steady state of the internal environment. Depending on the

form of exercise, sooner or later sensations of fatigue and exhaustion will occur. The physiological

role of these sensations is protection of the exercising subject from the deleterious effects of exercise.

Because of these sensations the subject will adapt his or her exercise strategy. The relationship

between physical exercise and fatigue has been the scope of interest of many researchers for more

than a century and is very complex. The exercise intensity, exercise endurance time and type of

exercise are all variables that cause different effects within the body systems, which in turn create

different types of sensation within the subject's mind during the exercise. Physical exercise affects the

biochemical equilibrium within the exercising muscle cells. Among others, inorganic phosphate,

protons, lactate and free Mg2+ accumulate within these cells. They directly affect the mechanical

machinery of the muscle cell. Furthermore, they negatively affect the different muscle cell organelles

that are involved in the transmission of neuronal signals. The muscle metabolites produced and the

generated heat of muscle contraction are released into the internal environment, putting stress on its

steady state. The tremendous increase in muscle metabolism compared with rest conditions induces

an immense increase in muscle blood supply, causing an increase in the blood circulatory system and

gas exchange. Nutrients have to be supplied to the exercising muscle, emptying the energy stocks

elsewhere in body. Furthermore, the contracting muscle fibres release cytokines, which in their turn

create many effects in other organs, including the brain. All these different mechanisms sooner or

later create sensations of fatigue and exhaustion in the mind of the exercising subject. The final effect

is a reduction or complete cessation of the exercise. Many diseases speed up the depletion of the

energy stocks within the body. So diseases amplify the effect of energy stock depletion that

accompanies exercise. In addition, many diseases produce a change of mind‐set before exercise.

These changes of mind‐set can create sensations of fatigue and exercise‐avoiding behaviour at the

onset of an exercise. One might consider these sensations during disease as a feed‐forward

mechanism to protect the subject from an excessive depletion of their energy stocks, to enhance the

survival of the individual during disease.

OBJECTIVE: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG)

frequencies in monozygotic twins discordant for chronic fatigue syndrome. METHODS: Thirteen pairs

of female twins underwent polysomnography. During the first night, they adapted to the sleep

laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was

conducted on sleep electroencephalographic records according to standard criteria, and power

spectral analysis was used to quantify delta through beta frequency bands, processed in 6‐s blocks.

Data were averaged across sleep stage within each twin and coded for sleep stage and the presence

ME Research UK — Database of Research Publications 2009

Arnold LM. Department of


University of

Cincinnati College

of Medicine,

Cincinnati, Ohio,


Aslakson E,

Vollmer‐Conna U,

Reeves WC, White


Centers for Disease

Control and


Atlanta, Georgia,



Pain and the brain:


widespread pain.

Replication of an

empirical approach

to delineate the

heterogeneity of




J Clin Psychiatry.



Popul Health Metr.

2009 Oct 5;7:17.

or absence of chronic fatigue syndrome (CFS). A completely within‐subjects repeated measure

multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions

and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs.

RESULTS: No significant differences in spectral power in any frequency band were found between

those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in

five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects

genetic influences on the sleep electroencephalogram rather than disease‐specific sleep pathology.

CONCLUSIONS: The genetic influences on sleep polysomnography and microarchitecture appear to be

stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep

complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms

that probe sleep regulation may provide a better description of sleep abnormalities in CFS.

Chronic widespread pain is associated with several medical and psychiatric disorders including, but

not limited to, chronic fatigue syndrome, fibromyalgia, mood disorders, hepatitis, endocrine

disorders such as hypothyroidism, and rheumatologic disorders such as rheumatoid arthritis. Careful

and comprehensive differential diagnosis must be performed to ensure a correct diagnosis before an

appropriate treatment can be selected. Fibromyalgia, in particular, is challenging to diagnose and

treat because it shares many characteristics with other disorders and is commonly concurrent with

major mood disorders. A comprehensive disease management strategy including patient education,

pharmacotherapy, cognitivebehavioral therapy, and aerobic and other forms of exercise can be

beneficial for many patients with fibromyalgia. 2009 Physicians Postgraduate Press, Inc.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) is defined by self‐reported symptoms.

There are no diagnostic signs or laboratory markers, and the pathophysiology remains inchoate. In

part, difficulties identifying and replicating biomarkers and elucidating the pathophysiology reflect the

heterogeneous nature of the syndromic illness CFS. We conducted this analysis of people from

defined metropolitan, urban, and rural populations to replicate our earlier empirical delineation of

medically unexplained chronic fatigue and CFS into discrete endophenotypes. Both the earlier and

current analyses utilized quantitative measures of functional impairment and symptoms as well as

laboratory data. This study and the earlier one enrolled participants from defined populations and

measured the internal milieu, which differentiates them from studies of clinic referrals that examine

only clinical phenotypes. METHODS: This analysis evaluated 386 women identified in a population‐

based survey of chronic fatigue and unwellness in metropolitan, urban, and rural populations of the

state of Georgia, USA. We used variables previously demonstrated to effectively delineate

endophenotypes in an attempt to replicate identification of these endophenotypes. Latent class

analyses were used to derive the classes, and these were compared and contrasted to those

described in the previous study based in Wichita, Kansas. RESULTS: We identified five classes in the

best fit analysis. Participants in Class 1 (25%) were polysymptomatic, with sleep problems and

depressed mood. Class 2 (24%) was also polysymptomatic, with insomnia and depression, but

participants were also obese with associated metabolic strain. Class 3 (20%) had more selective

symptoms but was equally obese with metabolic strain. Class 4 (20%) and Class 5 (11%) consisted of

nonfatigued, less symptomatic individuals, Class 4 being older and Class 5 younger. The classes were

ME Research UK — Database of Research Publications 2009

Attree EA, Dancey

CP, Pope AL.


Fernández A,

Pérez Martín A,


Martínez M, Arruti

Bustillo M,


Hernández FJ, de

la Cruz Labrado J,


Peñas R, Gutiérrez

Rivas E, Palacín

Delgado C, Rivera

Redondo J, Ramón

Giménez JR.

University of East

London, School of


London, United




Carlos III Health

Institute, Sinesio

Delgado, n degrees

6, 28029, Madrid,

Spanish Society of

Primary Care


Narváez, 15 1

degrees Izda,

28009, Madrid,



An assessment of


memory retrieval

in women with

chronic fatigue

syndrome using a


environment: an

initial study.

Chronic fatigue



diagnosis and



Behav. 2009


BMC Psychiatry.

2009 Oct 23;9

Suppl 1:S1.

generally validated by independent variables. People with CFS fell equally into Classes 1 and 2.

Similarities to the Wichita findings included the same four main defining variables of obesity, sleep

problems, depression, and the multiplicity of symptoms. Four out of five classes were similar across

both studies. CONCLUSION: These data support the hypothesis that chronic medically unexplained

fatigue is heterogeneous and can be delineated into discrete endophenotypes that can be replicated.

The data do not support the current perception that CFS represents a unique homogeneous disease

and suggests broader criteria may be more explanatory. This replication suggests that delineation of

endophenotypes of CFS and associated ill health may be necessary in order to better understand

etiology and provide more patient‐focused treatments.

People with chronic fatigue syndrome (CFS) have increased rates of depression, anxiety, and illness

intrusiveness; they may also suffer from cognitive problems such as retrospective memory (RM)

deficits and concentration difficulties that can stem from diminished information‐processing

capability. We predicted that this diminished capacity may also lead to deficits in other cognitive

functions, such as prospective memory (ProM). Event‐, time‐, and activity‐based ProM was assessed

in 11 women with CFS and 12 healthy women using a computer‐generated virtual environment (VE).

RM was assessed using a free‐recall test, and subjective assessment of both ProM and RM was

assessed by questionnaire. Groups were equivalent in age and measures of IQ. People with CFS

performed slightly worse than healthy controls on both the event‐ and time‐based ProM measures,

although these were not statistically significant. However, the CFS group performed significantly

worse than the healthy controls on both the free recall‐task and on subjective assessment of both RM

and ProM. Women with CFS do have some subtle decrements in memory, particularly RM. However,

it is possible that the decrements found in the present sample would be greater in real life. Further

studies utilizing both healthy controls and illness controls are now needed to ascertain how sensitive

the VE measure is and to inform the development of tasks in the VE that place progressively

increasing demands on working memory capacity.

Chronic fatigue syndrome is characterised by intense fatigue, with duration of over six months and

associated to other related symptoms. The latter include asthenia and easily induced tiredness that is

not recovered after a night's sleep. The fatigue becomes so severe that it forces a 50% reduction in

daily activities. Given its unknown aetiology, different hypotheses have been considered to explain

the origin of the condition (from immunological disorders to the presence of post‐traumatic oxidative

stress), although there are no conclusive diagnostic tests. Diagnosis is established through the

exclusion of other diseases causing fatigue. This syndrome is rare in childhood and adolescence,

although the fatigue symptom per se is quite common in paediatric patients. Currently, no curative

treatment exists for patients with chronic fatigue syndrome. The therapeutic approach to this

syndrome requires a combination of different therapeutic modalities. The specific characteristics of

the symptomatology of patients with chronic fatigue require a rapid adaptation of the educational,

healthcare and social systems to prevent the problems derived from current systems. Such patients

require multidisciplinary management due to the multiple and different issues affecting them. This

document was realized by one of the Interdisciplinary Work Groups from the Institute for Rare

Diseases, and its aim is to point out the main social and care needs for people affected with Chronic

ME Research UK — Database of Research Publications 2009


Fernández A,

Pérez Martín A,


Martínez M, Arruti

Bustillo M,


Hernández FJ, de

la Cruz Labrado J,


Peñas R, Gutiérrez

Rivas E, Palacín

Delgado C, Ramón

Giménez JR, Rivera

Redondo J.


Fernández A,

Pérez Martín A,


Martínez M.

Bartley EJ, Rhudy

JL, Williams AE.

Instituto de

Investigación de


Raras, Instituto de

Salud Carlos III,

Madrid, España;

Sociedad Española

de Medicos de

Atención Primaria,

Madrid, España.

Instituto de Salud

Carlos III, CS Los

Cármenes, Madrid,


Department of

Psychology, The

University of Tulsa,

Oklahoma 74104,


[Chronic fatigue


Summary of the



[Article in Spanish]

[Chronic fatigue




[Article in Spanish]


assessment of


processing in


Aten Primaria.



Epub 2009 Sep 18.

Aten Primaria.



Epub 2009 Sep 9.

J Pain. 2009


60. Epub 2009 Jul


Fatigue Syndrome. For this, it includes not only the view of representatives for different scientific

societies, but also the patient associations view, because they know the true history of their social

and sanitary needs. In an interdisciplinary approach, this work also reviews the principal scientific,

medical, socio‐sanitary and psychological aspects of Chronic Fatigue Syndrome.

Fibromyalgia syndrome (FMS) is a chronic pain disorder associated with widespread musculoskeletal

pain, tenderness, and fatigue. Additionally, correlational research suggests negative affect (eg,

depression, anxiety) and deficits in positive affect may contribute to FMS symptomatology. However,

well‐controlled, experimental research is necessary to ascertain whether patients with FMS have

problems in affective processing. The present study used a well‐validated picture‐viewing paradigm to

evoke emotional responses in 17 patients with FMS and 17 sex‐ and age‐matched healthy control

participants. Each participant viewed pleasant (erotica), neutral, and unpleasant (attack related)

pictures, and abrupt white noises were delivered during two‐thirds of the pictures to evoke startle

eyeblinks. Appetitive and defensive responding was assessed from subjective (valence/pleasure and

arousal ratings) and physiological (corrugator EMG, heart rate, skin‐conductance response, startle‐

reflex modulation) reactions to pictures. Results suggested FMS was associated with greater defensive

activation (displeasure, subjective arousal, corrugator EMG) to the unpleasant, threat‐related

pictures, but not deficits in appetitive activation to erotic pictures. Although preliminary, these data

suggest individuals with FMS have deficits in affective processing, but this dysregulation may be

limited to defensive activation. Implications for treatment and future research are discussed.

PERSPECTIVE: Fibromyalgia is a debilitating disease associated with affective distress. Results from the

ME Research UK — Database of Research Publications 2009

Baumann K,

Krayenbühl P.

Klinik und Poliklinik

für Innere Medizin,



Beever R. Richard.beever@n


Ben‐Zvi A, Vernon

SD, Broderick G.

Department of

Chemical and



University of



Alberta, Canada.

[Fatigue][Article in


Far‐infrared saunas

for treatment of

cardiovascular risk

factors: summary

of published




correction of



axis dysfunction.

Praxis (Bern 1994).

2009 Apr


Can Fam Physician.

2009 Jul;55(7):691‐


PLoS Comput Biol.



Epub 2009 Jan 23.

present study suggest that FMS is associated with enhanced defensive activation to nonpainful

threat‐related stimuli, but not deficits in appetitive reactions to erotic stimuli. These findings have

implications for the treatment and study of FMS.

OBJECTIVE: To review the literature about the health benefits of far‐infrared sauna (FIRS) use.

QUALITY OF EVIDENCE: A search of Web of Science, EBSCO, Ovid MEDLINE, Ovid HealthSTAR, and

EMBASE using the terms far‐infrared and sauna, refined by limiting the search to studies of humans

published in English, yielded 9 relevant papers (level I or level II evidence). MAIN MESSAGE: Far‐

infrared saunas are approved by the Canadian Standards Association and are sold to the public. The

manufacturers claim numerous health benefits; however, the published evidence to substantiate

these claims is limited. Four papers support the use of FIRS therapy for those with congestive heart

failure and 5 papers support its use for those with coronary risk factors. CONCLUSION: There is limited

moderate evidence supporting FIRS efficacy in normalizing blood pressure and treating congestive

heart failure; fair evidence, from a single study, supporting FIRS therapy in chronic pain; weak

evidence, from a single study, supporting FIRS therapy in chronic fatigue syndrome; weak evidence,

from a single study, supporting FIRS therapy for obesity; and consistent fair evidence to refute claims

regarding the role of FIRSs in cholesterol reduction.

The hypothalamic‐pituitary‐adrenal (HPA) axis is a major system maintaining body homeostasis by

regulating the neuroendocrine and sympathetic nervous systems as well modulating immune

function. Recent work has shown that the complex dynamics of this system accommodate several

stable steady states, one of which corresponds to the hypocortisol state observed in patients with

chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the

development of treatment strategies. Here we use model‐based predictive control (MPC)

methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal

hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model

of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that

displays robust properties in the face of significant biological variability and measurement uncertainty

requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone

levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally

progress to a stable attractor defined by normal hormone levels. Suppression of biologically available

cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing

enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can

therefore be designed that maximally exploit system dynamics to provide a robust response to

treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly,

a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and

challenges the conventional strategy of supplementing cortisol levels, an approach based on steady‐

state reasoning.

ME Research UK — Database of Research Publications 2009

Bito S. Department of

Clinical Education,

National Hospital


Tokyo Medical


Bjørkum T, Wang

CE, Waterloo K.

Blaney GP, Albert

PJ, Proal AD.

Sogndal BUP,

Postboks 184,

6851 Sogndal.



Stillpoint Centre,

Vancouver, British

Columbia, Canada.




somatic syndrome

in general practice]

[Article in



experience with

treatment of

chronic fatigue


in Norwegian]

Vitamin D

metabolites as

clinical markers in

autoimmune and

chronic disease.

Nippon Rinsho.



Tidsskr Nor

Laegeforen. 2009



Ann N Y Acad Sci.



General practitioners (GPs) see many patients with various symptoms such as dizziness, general

fatigue, chronic headache, numbness, chronic upper abdominal pain and chronic diarrhea and these

patients often have no abnormal findings in diagnostic tests. Even some specific conditions are

categorized as "diseases" such as "fibromyalgia" and "non‐ulcer dyspepsia", the patients actually

suffer from various illnesses and have common questions. One is "Why am I suffering from such

illness?" and the other is "How can I waive from the suffering?". GPs should usually face with these

patients' questions. Even without categorization by "functional somatic syndrome", GPs provide

continuity of care and sometimes provide prescriptions for such patients. The concept of postmodern

is essential in management of functional somatic syndrome.

BACKGROUND: Chronic fatigue syndrome is a highly debated condition. Little is known about causes

and treatment. Patients" experience is important in this context. MATERIAL AND METHODS:828

persons with chronic fatigue syndrome (ICD‐10 code: G93.3) were included in the study. They were

recruited through two Norwegian patient organizations (ME‐association and MENiN). The participants

filled in a questionnaire on their experience with various approaches to alleviate their condition.

RESULTS: Pacing was evaluated as useful by 96% of the participants, rest by 97%, and 96% of the

participants considered complete shielding and quietness to be useful. 57% of the participants who

had received help to identify and challenge negative thought patterns regarded this useful. 79% of

the participants with experience from graded training regarded this to worsen their health status.

Overall, the results were similar, irrelevant of the severity of the condition. INTERPRETATION:Most

participants in this study evaluated pacing, rest and complete shielding and quietness to be useful.

The experience of the participants indicate that cognitive behaviour therapy can be useful for some

patients, but that graded training may cause deterioration of the condition in many patients. The

results must, however, be interpreted with care, as the participants are not a representative sample,

and we do not know the specific content of the approaches.

Recent research has implicated vitamin D deficiency (serum levels of 25‐hydroxyvitamin D 110 pmol/L.

However, there was little association with vitamin D deficiency or the other inflammatory markers,

meaning that the results challenge the assumption that serum levels of 25‐D are a sensitive measure

of the autoimmune disease state. Rather, these findings support the use of 1,25‐D as a clinical marker

in autoimmune conditions. High levels of 1,25‐D may result when dysregulation of the VDR by

bacterial ligands prevents the receptor from expressing enzymes necessary to keep 1,25‐D in a normal


Bol Y, Duits AA, Department of The psychology of J Psychosom Res. Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS), but it is difficult

ME Research UK — Database of Research Publications 2009

Hupperts RM,

Vlaeyen JW,

Verhey FR.

Boneva RS, Lin JM,

Maloney EM,

Jones JF, Reeves




University Medical

Center, Maastricht,

The Netherlands.



Centers for Disease

Control and


Atlanta, Georgia

30333, USA.


Boone KB. Center for Forensic

Studies, Alliant


University ‐ LA,

1000 South

Fremont Avenue,


CA91803, USA.



fatigue in patients

with multiple

sclerosis: a review.

Use of medications

by people with

chronic fatigue

syndrome and

healthy persons: a


study of fatiguing

illness in Georgia.

Fixed belief in



despite normal





2009 Jan;66(1):3‐

11. Epub 2008 Sep


Health Qual Life

Outcomes. 2009

Jul 20;7:67.

Clin Neuropsychol.



to define and measure. Today, MS‐related fatigue is not fully understood, and evidence related to

explanatory pathophysiological factors are conflicting. Here, we evaluate the contribution of

psychological factors to MS‐related fatigue. Insight into the possible underlying psychological

mechanisms might help us to develop adequate psychological interventions and to improve the

overall management of fatigue. Conceptual issues and the relationships between MS‐related fatigue

and mood, anxiety, cognition, personality, and cognitive‐behavioral factors are discussed, and the

implications for clinical practice and research are presented.

BACKGROUND: Chronic fatigue syndrome (CFS) is a debilitating condition of unknown etiology and no

definitive pharmacotherapy. Patients are usually prescribed symptomatic treatment or self‐medicate.

We evaluated prescription and non‐prescription drug use among persons with CFS in Georgia and

compared it to that in non‐fatigued Well controls and also to chronically Unwell individuals not fully

meeting criteria for CFS. METHODS: A population‐based, case‐control study. To identify persons with

possible CFS‐like illness and controls, we conducted a random‐digit dialing telephone screening of

19,807 Georgia residents, followed by a detailed telephone interview of 5,630 to identify subjects

with CFS‐like illness, other chronically Unwell, and Well subjects. All those with CFS‐like illness (n =

469), a random sample of chronically Unwell subjects (n = 505), and Well individuals (n = 641) who

were age‐, sex‐, race‐, and geographically matched to those with CFS‐like illness were invited for a

clinical evaluation and 783 participated (48% overall response rate). Clinical evaluation identified 113

persons with CFS, 264 Unwell subjects with insufficient symptoms for CFS (named ISF), and 124 Well

controls; the remaining 280 subjects had exclusionary medical or psychiatric conditions, and 2

subjects could not be classified. Subjects were asked to bring all medications taken in the past 2

weeks to the clinic where a research nurse viewed and recorded the name and the dose of each

medication. RESULTS: More than 90% of persons with CFS used at least one drug or supplement

within the preceding two weeks. Among users, people with CFS used an average of 5.8 drugs or

supplements, compared to 4.1 by ISF and 3.7 by Well controls. Persons with CFS were significantly

more likely to use antidepressants, sedatives, muscle relaxants, and anti‐acids than either Well

controls or the ISF group. In addition, persons with CFS were significantly more likely to use pain‐

relievers, anti‐histamines and cold/sinus medications than were Well controls. CONCLUSION: Medical

care providers of patients with chronic fatigue syndrome should be aware of polypharmacy as a

problem in such patients, and the related potential iatrogenic effects and drug interactions.

A subset of patients who present for neuropsychological testing report dysfunction in daily life

activities secondary to cognitive deficits, but are found on formal testing to have no objective

abnormalities, raising the possibility of "neurocognitive hypochondriasis." Such a case is presented,

and the factors that appear to give rise to this presentation are explored. Cases of hypochondriacal

overconcern regarding cognitive function are likely not rare, particularly given research showing there

is little correlation between objective report of cognitive dysfunction and actual test scores in such

conditions as mild traumatic brain injury, chronic fatigue syndrome, fibromyalgia, toxic mold

exposure, and post‐polio syndrome.

ME Research UK — Database of Research Publications 2009

Bramsen I. Can CBT


change grey

matter volume in

chronic fatigue


Comment in:

Brain. 2009

Jul;132(Pt 7):e119;

author reply

e120.Comment on:

Brain. 2008



Brimmer DJ,

McCleary KK,

Lupton TA, Faryna

KM, Reeves WC.

Bruusgaard D,

Natvig B.

Chronic Viral

Diseases Branch,


Center for


Diseases, Centers

for Disease Control

and Prevention,

Atlanta, GA 30333,



Seksjon for

arbeids‐ og


Universitetet i

Oslo, Postboks

1130, Blindern

0318 Oslo,


Continuing medical


challenges in

chronic fatigue






[Article in


Brain. 2009


6):e110; author

reply e111. Epub

2008 Aug 29.

BMC Med Educ.

2009 Dec 2;9:70.

Tidsskr Nor

Laegeforen. 2009



BACKGROUND: Chronic fatigue syndrome (CFS) affects at least 4 million people in the United States,

yet only 16% of people with CFS have received a diagnosis or medical care for their illness. Educating

health care professionals about the diagnosis and management of CFS may help to reduce population

morbidity associated with CFS. METHODS: This report presents findings over a 5‐year period from

May 2000 to June 2006 during which we developed and implemented a health care professional

educational program. The objective of the program was to distribute CFS continuing education

materials to providers at professional conferences, offer online continuing education credits in

different formats (e.g., print, video, and online), and evaluate the number of accreditation certificates

awarded. RESULTS: We found that smaller conference size (OR = 80.17; 95% CI 8.80, 730.25), CFS

illness related target audiences (OR = 36.0; 95% CI 2.94, 436.34), and conferences in which CFS

research was highlighted (OR = 4.15; 95% CI 1.16, 14.83) significantly contributed to higher

dissemination levels, as measured by visit rates to the education booth. While print and online

courses were equally requested for continuing education credit opportunities, the online course

resulted in 84% of the overall award certificates, compared to 14% for the print course. This remained

consistent across all provider occupations: physicians, nurses, physician assistants, and allied health

professionals. CONCLUSION: These findings suggest that educational programs promoting materials at

conferences may increase dissemination efforts by targeting audiences, examining conference

characteristics, and promoting online continuing education forums.

ME Research UK — Database of Research Publications 2009

Burkhard B, Kittel


Burton C, Knoop

H, Popovic N,

Sharpe M,

Bleijenberg G.

Byrnes A, Jacks A,


K, Evengard B,

Wright FA,

Pedersen NL,

Sullivan PF.

Carlo‐Stella N,

Bozzini S, De

Silvestri A, Sbarsi I,




Dienst der


ng in Bayern,


Division of

Community Health

Sciences, General

Practice Section,

University of

Edinburgh, West

Richmond Street,

Edinburgh, UK.



Department of


University of North

Carolina at Chapel

Hill, Chapel Hill,

North Carolina,

United States of


Genetics and




methods for

etheric formative

forces] [Article in



complexity of

activity patterns in

patients with

Chronic Fatigue

Syndrome: a case

control study.

Gene expression in

peripheral blood

leukocytes in

monozygotic twins

discordant for

chronic fatigue: no

evidence of a


Molecular study of

receptor for

advanced glycation


zin. 2009 Sep


Biopsychosoc Med.

2009 Jun 2;3:7.

PLoS One. 2009

Jun 5;4(6):e5805.

Int J


Pharmacol. 2009

Rudolf Steiner, the founder of anthroposophy, suggested the development of visualisation methods

for "etheric formative forces". The essential methods, their "spiritual scientific" basis and indications

are described and their claims critically tested. Summary: The methods are not validated, the key

criteria for diagnostic tests (reproducibility, sensitivity, specifity) are not given.

ABSTRACT: BACKGROUND: Chronic fatigue syndrome (CFS) is an illness characterised by pervasive

physical and mental fatigue without specific identified pathological changes. Many patients with CFS

show reduced physical activity which, though quantifiable, has yielded little information to date.

Nonlinear dynamic analysis of physiological data can be used to measure complexity in terms of

dissimilarity within timescales and similarity across timescales. A reduction in these objective

measures has been associated with disease and ageing. We aimed to test the hypothesis that activity

patterns of patients with CFS would show reduced complexity compared to healthy controls.

METHODS: We analysed continuous activity data over 12 days from 42 patients with CFS and 21

matched healthy controls. We estimated complexity in two ways, measuring dissimilarity within

timescales by calculating entropy after a symbolic dynamic transformation of the data and similarity

across timescales by calculating the fractal dimension using allometric aggregation. RESULTS: CFS

cases showed reduced complexity compared to controls, as evidenced by reduced dissimilarity within

timescales (mean (SD) Renyi(3) entropy 4.05 (0.21) vs. 4.30 (0.09), t = ‐6.6, p < 0.001) and reduced

similarity across timescales (fractal dimension 1.19 (0.04) vs. 1.14 (0.04), t = 4.2, p < 0.001). This

reduction in complexity persisted after adjustment for total activity. CONCLUSION: Patients with CFS

show evidence of reduced complexity of activity patterns. Measures of complexity applied to activity

have potential value as objective indicators for CFS.

BACKGROUND: Chronic fatiguing illness remains a poorly understood syndrome of unknown

pathogenesis. We attempted to identify biomarkers for chronic fatiguing illness using microarrays to

query the transcriptome in peripheral blood leukocytes. METHODS: Cases were 44 individuals who

were clinically evaluated and found to meet standard international criteria for chronic fatigue

syndrome or idiopathic chronic fatigue, and controls were their monozygotic co‐twins who were

clinically evaluated and never had even one month of impairing fatigue. Biological sampling

conditions were standardized and RNA stabilizing media were used. These methodological features

provide rigorous control for bias resulting from case‐control mismatched ancestry and experimental

error. Individual gene expression profiles were assessed using Affymetrix Human Genome U133 Plus

2.0 arrays. FINDINGS: There were no significant differences in gene expression for any transcript.

CONCLUSIONS: Contrary to our expectations, we were unable to identify a biomarker for chronic

fatiguing illness in the transcriptome of peripheral blood leukocytes suggesting that positive findings

in prior studies may have resulted from experimental bias.

The receptor for advanced glycation end product (RAGE) is thought to play an important role in

inflammation. Chronic fatigue syndrome (CFS) is a long‐lasting fatigue that compromises at least 50%

of a subject's daily activities without other known cause. Immune dysfunction has been implicated

ME Research UK — Database of Research Publications 2009

Pizzochero C,

Lorusso L,

Martinetti M,

Cuccia M.

Cathébras P,

Lauwers A.

Chalder T, Deary

V, Husain K,

Walwyn R.

University of Pavia,

Pavia, Italy.

Service de

médecine interne,

hôpital Nord, CHU

de Saint‐Etienne,

42055 Saint‐

Etienne Cedex 2,




Department of


Medicine and

Psychiatry, King's

College London,

Weston Education

Centre, London,


endproduct gene

promoter and

identification of

specific HLA


possibly involved

in chronic fatigue


[Should we make

the diagnosis of


cle in French]



behaviour therapy

versus psycho‐

education for

chronic fatigue

syndrome in 11‐ to

18‐year‐olds: a



treatment trial.



Rev Prat. 2009 Jan


Psychol Med. 2009

Nov 6:1‐11. [Epub

ahead of print]

and an association with a peculiar genetic cytokine profile, predisposing to an immunomodulatory

response of inflammatory nature, was found. The aim of this study is to analyse RAGE polymorphisms

and HLA‐DRB1 alleles in seventy‐five Italian CFS patients and 141 controls matched for age, sex and

ethnicity. These two groups underwent genomic study for RAGE 374T/A and 429C/T promoter

polymorphisms; moreover, 46 patients and 186 controls were typed for HLA‐DRB1 at low resolution

molecular level. Of these, 31 patients and 99 controls also underwent high resolution analysis to

define the HLA‐DRB1*11 and DRB1*13 alleles. The haplotypes RAGE‐374T, DRB1*04; RAGE‐374T,

DRB1*09; RAGE‐374T, DRB1*11; RAGE‐374A, DRB1*13; RAGE‐429T, DRB1*04 and RAGE‐429C,

DRB1*11 were significantly more frequent in CFS patients, whereas RAGE‐429C, DRB1*07 would

seem protective. A significantly lower frequency of DRB1*1104 (5.4% vs 12.9% p=0.04, OR=0.39) and

a significantly higher frequency of HLA‐DRB1*1301 (13.0% vs 5.1% p=0.006, OR= 2.79) were found in

CFS patients. A synergic effect was observed with RAGE polymorphism. The OR values strengthened in

the following cis combinations: RAGE‐374A, HLA‐DRB1*1104 (OR=0.27) and RAGE‐374A,

HLADRB1*1301 (OR=6.23). HLA haplotypes rather than single alleles of RAGE or of DRB1 genes seem

to be involved in CFS, probably including a subregion of major interest.

Fibromyalgia is a functional somatic syndrome characterized by widespread musculoskeletal pain,

fatigue, poor sleep, and exercise intolerance, frequently (but inconstantly) associated with

psychological distress. Fibromyalgia is a common condition, affecting predominantly middle‐aged

women, with a chronic course. Fibromaylgia should be differentiated from, and may be associated

with, a number of metabolic, rheumatic, neurological or psychiatric conditions. The most plausible

pathophysiologic mechanism involves an alteration of pain modulation at the peripheral and central

levels of the nervous system ("sensitization"). Psychosocial factors play an important role in

precipitating and maintaining symptoms, health care utilization, and disablement. Treatments of

fibromyalgia rely mainly on the acknowledgement of pain and distress, patient education, analgesics,

balneotherapy and physiotherapy, physical reconditioning (aerobic exercise), and certain


BACKGROUND: Only one previous randomized controlled trial (RCT) has examined the efficacy of

cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) in children. The aim of this

study was to compare family‐focused CBT with psycho‐education for CFS in adolescents.MethodSixty‐

three 11‐ to 18‐year‐olds (43 girls, 20 boys) with CFS were randomly assigned to either family‐focused

CBT or psycho‐education delivered over 6 months. School attendance was the main outcome, which

was assessed at the end of treatment and at 3, 6 and 12 months follow‐up. RESULTS: At the main

outcome point (the 6‐month follow‐up) both groups had improved similarly. However, although those

who received family‐focused CBT were attending school for longer than those who received psycho‐

education, at discharge from treatment and at 3 months follow‐up, they improved less quickly across

the follow‐up period. CONCLUSIONS: Adolescents with CFS get back to school more quickly after

family‐focused CBT. This is important as they are at a crucial stage of their development. However,

the finding that psycho‐education was as effective as family‐focused CBT at 6 and 12 months follow‐

up has important implications for health service delivery.

Chastin SF, Granat Glasgow Methods for Gait Posture. 2009 The purpose of this study was to develop and test a generic technique to robustly quantify the

ME Research UK — Database of Research Publications 2009

MH. Caledonian

University, School

of Health and

Social Care,

Cowcaddens Road,

Glasgow G4 0BA,

Scotland, UK.

Chen LH, Wilson

ME, Davis X,

Loutan L, Schwartz

E, Keystone J, Hale

D, Lim PL,

McCarthy A,

Gkrania‐Klotsas E,

Schlagenhauf P;




Collaborators: von

Sonnenburg F,

Gelman SS,

Chappuis F, Kain

KC, Field V,

Burchard GD,

Libman MD,

Maclean JD, Leder

K, Torresi J, Brown

G, Parola P, Simon

F, Delmont J, Kass

R, Carosi G,

Castelli F, Pandey

P, Shaw M,

Kozarsky PE,

Franco‐Paredes C,

Piyaphanee W,

Silachamroon U,

Harvard University,






objective measure,

quantification and

analysis of


behaviour and


Illness in long‐term

travelers visiting



Oct 23. [Epub

ahead of print]

Emerg Infect Dis.




pattern of sedentary behaviour from objective records. The technique was applied to four groups of

subjects: a healthy group with an active occupation (N=54), a healthy group with a sedentary

occupation (N=53), a group of subjects with chronic low back pain (N=5) and a group of subjects with

chronic fatigue syndrome (N=14). This study presents the first evidence that bouts of sedentary

activity are power law distributed. Results showed that there was no significant difference in total

sedentary time between the groups, however, the patterns of accumulation of sedentary time were

significantly different for the groups. Sedentary groups accumulated their total sedentary time from a

small number of longer sedentary bouts. Active groups tended to break their sedentary time into a

greater number of shorter bouts. This suggests that the power law exponent alpha and the GINI index

G, used to describe the pattern of accumulation of sedentary time, could be used to evaluate and

quantify sedentary behaviour.

Length of travel appears to be associated with health risks. GeoSentinel Surveillance Network data for

4,039 long‐term travelers (trip duration >6 months) seen after travel during June 1, 1996, through

December 31, 2008, were compared with data for 24,807 short‐term travelers (trip duration 1 month,

eosinophilia, cutaneous leishmaniasis, schistosomiasis, and Entamoeba histolytica diarrhea. Areas of

concern for long‐term travelers were vector‐borne diseases, contact‐transmitted diseases, and

psychological problems. Our results can help prioritize screening for and diagnosis of illness in long‐

term travelers and provide evidence‐based pretravel advice.

ME Research UK — Database of Research Publications 2009

Tachikawa N,

Sagara H, Connor

BA, Kanagawa S,

Kato Y, Jensenius

M, Haulman NJ,

Roesel D, Jong EC,

Coyle CM, Wittner

M, López‐Vélez R,

Pérez‐Molina JA,

Nutman TB, Klion

AD, Hagmann S,

Miller A, Weber R,

Steffen R, Stauffer

WM, Walker PF,

Freedman DO,

Ansdell V, Wilder‐

Smith A, Sack B,

McKenzie R,

Caumes E,

Pérignon A, Licitra

C, Crespo A,

Barnett ED,

Gurtman A, Perret

C, Valdivieso F,

Muller R, Cahill JD,

McKinley G,

McLellan S,

MacDonald S,

Lynch MW,

Borwein S, Anglim


Chew‐Graham C,

Dixon R, Shaw JW,

Smyth N, Lovell K,

Peters S.

School of



University of


Manchester, M13

9PL, UK.



Practice Nurses'

views of their role

in the

management of

Chronic Fatigue


c Encephalitis: a

qualitative study.

BMC Nurs. 2009

Jan 22;8:2.

ABSTRACT: BACKGROUND: NICE guidelines suggest that patients with Chronic Fatigue

Syndrome/Myalgic Encephalitis (CFS/ME) should be managed in Primary Care. Practice Nurses are

increasingly being involved in the management of long‐term conditions, so are likely to also have a

growing role in managing CFS/ME. However their attitudes to, and experiences of patients with

CFS/ME and its management must be explored to understand what barriers may exist in developing

their role for this group of patients. The aim of this study was to explore Practice Nurses'

understanding and beliefs about CFS/ME and its management. METHODS: Semi‐structured interviews

with 29 Practice Nurses. Interviews were transcribed verbatim and an iterative approach used to

develop themes from the dataset. RESULTS: Practice nurses had limited understanding about CFS/ME

ME Research UK — Database of Research Publications 2009

Chia JK, Chia AY,

Voeller M, Lee TM,

Chang R.

Cho HJ, Menezes

PR, Hotopf M,

Bhugra D, Wessely


Cho JH, Cho CK,

Shin JW, Son JY,

Kang W, Son CG.

EV Med Research,

United States;

Department of



University of São

Paulo Medical

School, University


University of São

Paulo, Brazil.



East‐West Cancer

Center, Dunsan

Oriental Hospital

of Oriental Medical

College of

Acute enterovirus

infection followed

by myalgic


chronic fatigue


(ME/CFS) and viral



epidemiology of

chronic fatigue

syndrome in

Brazilian and

British primary

care: prevalence

and recognition.

Myelophil, an

extract mix of

Astragali Radix and

Salviae Radix,


J Clin Pathol. 2009

Oct 14. [Epub

ahead of print]

Br J Psychiatry.



Complement Ther

Med. 2009


Epub 2009 Jan 23.

which had been largely gained through contact with patients, friends, personal experiences and the

media rather than formal training. They had difficulty seeing CFS/ME as a long term condition. They

did identify a potential role they could have in management of CFS/ME but devalued their own skills

in psychological intervention, and suggested counselling would be an appropriate therapeutic option.

They recognised a need for further training and on going supervision from both medical and

psychological colleagues. Some viewed the condition as contentious and held pejorative views about

CFS/ME. Such scepticism and negative attitudes will be a significant barrier to the management of

patients with CFS/ME in primary care. CONCLUSION: The current role of Practice Nurses in the

ongoing management of patients with CFS/ME is limited. Practice Nurses have little understanding of

the evidence‐base for treatment of CFS/ME, particularly psychological therapies, describing

management options in terms of advice giving, self‐help or counselling. Practice Nurses largely

welcomed the potential development of their role in this area, but identified barriers and training

needs which must be addressed to enable them to feel confident managing of patients with this

condition. Training must begin by addressing negative attitudes to patients with CFS/ME.

A number of infections have been associated with myalgia encephalomyelitis/chronic fatigue

syndrome (ME/CFS). Often occurring in epidemics, enteroviruses are significant causes of respiratory,

gastrointestinal infections, non‐specific flu‐like illnesses, and many disseminated infections. It has

been difficult to demonstrate causality for chronic diseases without having well‐documented cases of

acute enterovirus infections. In this report, we described 3 patients presenting with acute enterovirus

infections, which were followed by ME/CFS, and the persistent viral infections were demonstrated by

finding enterovirus VP1 protein and RNA in the stomach.

BACKGROUND: Although fatigue is a ubiquitous symptom across countries, clinical descriptions of

chronic fatigue syndrome have arisen from a limited number of high‐income countries. This might

reflect differences in true prevalence or clinical recognition influenced by sociocultural factors. AIMS:

To compare the prevalence, physician recognition and diagnosis of chronic fatigue syndrome in

London and São Paulo. METHOD: Primary care patients in London (n=2459) and São Paulo (n=3914)

were surveyed for the prevalence of chronic fatigue syndrome. Medical records were reviewed for

the physician recognition and diagnosis. RESULTS: The prevalence of chronic fatigue syndrome

according to Centers for Disease Control 1994 criteria was comparable in Britain and Brazil: 2.1% v.

1.6% (P=0.20). Medical records review identified 11 diagnosed cases of chronic fatigue syndrome in

Britain, but none in Brazil (P

ME Research UK — Database of Research Publications 2009


University, Seo‐gu,

Daejeon, South


Chong YY, Ng BY. Department of

Rheumatology and


Singapore General





Chrousos GP, Kino


First Department

of Pediatrics,

Athens University

Medical School,

Athens, Greece.



Clauw DJ. Chronic Pain &

Fatigue Research


Department of


chronic fatigue: a



controlled pilot


Clinical aspects

and management

of fibromyalgia



signaling in the

cell. Expanding


implications to

complex human

behavioral and

somatic disorders.

Fibromyalgia: an


Ann Acad Med

Singapore. 2009



Ann N Y Acad Sci.



Am J Med. 2009



subjectively characterised, and the expression of 42 cytokines was evaluated using an antibody array.

RESULTS: Myelophil administration (3g per day) significantly decreased the fatigue severity score

compared with the control (p

ME Research UK — Database of Research Publications 2009

Coffin JM, Stoye


Courjaret J,

Schotte CK,

Wijnants H,

Moorkens G,

Cosyns P.

Crawley E, Hunt L,

Stallard P.

University of

Michigan, Ann

Arbor, Michigan

48106, USA.



Department of


Microbiology, Tufts

University, Boston,

MA 02111, USA.



Department of


University Hospital

Antwerp, Edegem,




Centre of Child and

Adolescent Health,

Hampton House,

Virology. A new

virus for old


Chronic fatigue

syndrome and

DSM‐IV personality


Anxiety in children

with CFS/ME.

Science. 2009 Oct


1. Epub 2009 Oct

8. Comment on:

Science. 2009 Oct



J Psychosom Res.

2009 Jan;66(1):13‐

20. Epub 2008 Nov


Eur Child Adolesc

Psychiatry. 2009


several chronic pain disorders that coaggregate with fibromyalgia, which is itself a product of genetic

and environmental factors. Thus, aberrational central pain processing is implicated in irritable bowel

syndrome, temporomandibular disorder, chronic low back pain, and certain other chronic pain

disorders. Fibromyalgia and related disorders appear to reflect deficiencies in serotonergic and

noradrenergic, but not opioidergic, transmission in the central nervous system. The heightened state

of pain transmission may also be owing to increases in pronociceptive neurotransmitters such as

glutamate and substance P. In some cases, psychological and behavioral factors are also in play.

Although the overlapping symptomatology between fibromyalgia and related disorders may present

diagnostic challenges, proper examination and observation can help clinicians make an accurate

diagnosis. In recent years, the vastly improved understanding of the mechanism underlying

fibromyalgia and the related spectrum of diseases has fostered rapid advances in the therapy of these

chronic pain disorders by both pharmacologic and nonpharmacologic interventions. (c) 2009 Elsevier


OBJECTIVE: Personality is an important factor in the research of the chronic fatigue syndrome (CFS).

Although some studies report a high rate of personality disorders‐‐around the 40% level‐‐in samples

of patients with CFS, the generalizability of these findings can be questioned. The present study

evaluates the prevalence of Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition,

Text Revision (DSM‐IV‐TR) personality disorders in a sample of female CFS patients and in two control

groups. METHOD: The ADP‐IV questionnaire (Assessment of DSM Personality Disorders IV) was used

to assess the DSM‐IV‐TR personality disorders at a dimensional and categorical level in a sample of 50

female CFS patients and in two matched control samples of Flemish civilians (n=50) and psychiatric

patients (n=50). RESULTS: The results indicate a striking lack of statistical significant differences

between the CFS sample and the Flemish control group at the level of dimensional Trait scores,

number of criteria, and prevalence rates of personality disorder diagnoses. Unsurprisingly, higher

scores at these levels were obtained within the psychiatric sample. The prevalence of an Axis II

disorder was 12% in the Flemish and CFS samples, whereas the psychiatric sample obtained a

prevalence of 54%. CONCLUSION: The prominent absence of any significant difference in personality

disorder characteristics between the female Flemish general population and the CFS samples seems

to suggest only a minor etiological role for personality pathology, as defined by the DSM‐IV Axis II,

within CFS.

Anxiety symptoms are commonly described in children with chronic fatigue syndrome or myalgic

encephalopathy (CFS/ME) but to date there has been little information on the type of anxiety children

experience or the relationship between anxiety and school attendance, disability or fatigue. The aim

ME Research UK — Database of Research Publications 2009

Crawley E, Sterne


Creavin ST, Dunn

KM, Mallen CD,

Nijrolder I, van der

Windt DA.

Cotham Hill, Bristol

BS6 6JS, UK.



Centre for Child

and Adolescent

Health, University

of Bristol, Bristol,




Arthritis Research

Campaign National

Primary Care

Centre, Keele


Staffordshire ST5

5BG, United


between school

absence and

physical function in

paediatric chronic




Co‐occurrence and

associations of

pain and fatigue in

a community

sample of Dutch


Epub 2009 May 19. of this study was to first describe the prevalence and type of anxiety symptoms in children with

CFS/ME compared with a normal European population, and secondly to investigate the association of

anxiety symptoms with age, gender, school attendance, fatigue, and physical function in paediatric

CFS/ME. Data were prospectively collected on children and young people with CFS/ME referred to a

large specialist CFS/ME service. One hundred and sixty‐four children with CFS/ME had complete data

for the Spence Children's Anxiety Scale. Teenage girls had the highest rates of total anxiety symptoms

with 38% (95% CI 27‐49) over the cut off (top 10% of normal European population) and significantly

higher rates of symptoms in each subscale. Younger girls were more likely to score over the cut off in

separation anxiety (37%, 19‐40) and social phobia (39%, 25‐47). There was no evidence of association

between total anxiety symptoms and: time at school, time to assessment, pain or age. Associations

with fatigue and physical function were attenuated when adjusted for other variables. Although

anxiety symptoms are high in CFS/ME, particularly in teenage girls, it does not appear to be

associated with school attendance or other measures of disability. Separation anxiety and social

phobia were the most clearly elevated in paediatric CFS/ME.

Arch Dis Child.



Epub 2008 Nov 11.

Eur J Pain. 2009

Jun 17. [Epub

ahead of print]

OBJECTIVE: To investigate factors associated with school attendance and physical function in

paediatric chronic fatigue syndrome/myalgic encephalopathy (CFS/ME). DESIGN: Cross‐sectional

study. SETTING: Regional specialist CFS/ME service. PATIENTS: Children and young people aged under

18 years. OUTCOME MEASURES: Self‐reported school attendance and physical function measured

using the physical function subscale of the Short Form 36. METHODS: Linear and logistic regression

analysis of data from self‐completed assessment forms on children attending a regional specialist

service between 2004 and 2007. Analyses were done in two groups of children: with a completed

Spence Children's Anxiety Scale (SCAS) and with a completed Hospital Anxiety and Depression Scale

(HADS). RESULTS: Of 211 children with CFS/ME, 62% attended 40% of school or less. In children with

completed SCAS, those with better physical function were more likely to attend school (adjusted odds

ratio (OR) 1.70; 95% CI 1.36 to 2.13). This was also true for those with completed HADS (adjusted OR

2.05; 95% CI 1.4 to 3.01). Increasing fatigue and pain and low mood were associated with worse

physical function. There was no evidence that anxiety, gender, age at assessment, family history of

CFS/ME or time from onset of symptoms to assessment in clinic were associated with school

attendance or physical function. IMPLICATIONS: Paediatricians should recognise that reduced school

attendance is associated with reduced physical function rather than anxiety. Improving school

attendance in children with CFS/ME should focus on evidence‐based interventions to improve

physical function, particularly concentrating on interventions that are likely to reduce pain and


Widespread pain and chronic fatigue are common in the general population. Previous research has

demonstrated co‐occurrence of syndromes that are associated with pain and fatigue (fibromyalgia

and chronic fatigue syndrome), but there is limited existing data on the co‐occurrence of these

symptoms in general. This study investigates the co‐occurrence of pain and fatigue, and characterises

people with these symptoms individually, and in combination. A postal questionnaire was sent to a

random sample of 4741 community dwelling Dutch adults registered with five general practices.

There were 2447 participants (adjusted response=53.5%). Persistent fatigue was reported by 60% of

ME Research UK — Database of Research Publications 2009

Cuadros J, Vargas


Daley M, Morin

CM, LeBlanc M,

Grégoire JP,

Savard J,

Baillargeon L.

Kingdom. the 451 subjects with chronic widespread pain. Chronic widespread pain was reported by 33% of the

809 responders with persistent fatigue. Anxiety and depression were more common in subjects who

reported both symptoms than those who reported either one or neither. Participants who had

chronic disease, high body mass index, low activity levels or did not perceive ability to influence

health had higher adjusted odds of reporting both symptoms (but not one alone) than subjects not

having these characteristics. Pain and fatigue occur more often than would be expected by chance

and there are a number of reasons for this. Clinicians should be aware that co‐occurrence of the

symptoms is common, especially in people who have high BMI or chronic disease, and that people

with both symptoms are often anxious or depressed. Further work should address longitudinal

associations of pain and fatigue.



Ecole de


Université Laval,

Quebec, Canada

G1K 0A6.

A new mind‐body

approach for a

total healing of

fibromyalgia: a

case report.

Insomnia and its

relationship to


utilization, work


productivity and


Am J Clin Hypn.

2009 Jul;52(1):3‐


Sleep Med. 2009


Epub 2008 Aug 26.

Fibromyalgia is a severe, chronic and widespread pain syndrome with no definite treatment protocol.

Several medications are currently in use to treat this condition. Various pharmacological treatments,

as well as alternative mind‐body therapies, have been directed towards reducing fatigue and pain, but

these treatments have only resulted in a partial relief of symptoms with no long‐term or permanent

effects. This study shows the results obtained from four female patients suffering from fibromyalgia

after undergoing a mind‐body treatment in which psychosocial genomic postulates as well as

ideodynamic hand movements were the main tools employed in their healing. It is suggested that a

mind‐body oriented treatment could generate stable and permanent changes that enable patients to

experience a total recovery from fibromyalgia.

BACKGROUND AND PURPOSE: To document and provide a micro analysis of the relationship between

insomnia and health problems, health‐care use, absenteeism, productivity and accidents.

PARTICIPANTS AND METHODS: A population‐based sample of 953 French‐speaking adults from

Québec, Canada. Participants were categorized as having insomnia syndrome (SYND) or insomnia

symptoms (SYMPT) or as good sleepers (GS). They completed questionnaires on sleep, health, use of

health‐care services and products, accidents, work absences and reduced work productivity. Data

were also obtained from the Québec‐government‐administered health insurance board on selected

variables (e.g., consultations with health‐care professionals, diagnoses). RESULTS: There were

significantly more individuals in the SYND group relative to the GS group reporting at least one

chronic health problem (83% vs. 53%; OR: 2.78) and who had consulted a health‐care professional in

the past year (81% vs. 60%; OR: 2.8). There were also higher proportions of individuals in the SYND

group than in the GS group who had used prescription medications (57% vs. 30.7%; OR: 2.8), most

notably to treat insomnia, mood and anxiety disorders, or who had used over‐the‐counter products

(75.6% vs. 62.0%; OR: 1.8) and alcohol as a sleep aid (17.8% vs. 3.9%; OR: 4.6). In terms of daytime

function, 25.0% of the SYND had been absent from work relative to 17.1% of GS (OR: 1.7), 40.6%

reported having experienced reduced productivity compared to 12.3% of GS (OR: 4.8) and non‐

motor‐vehicle accidents occurred at higher rates in the SYND group (12.5% vs. 6.4% for GS; OR: 2.4).

No differences were found for hospitalisations or motor‐vehicle accidents. Most of the associations

remained significant even after controlling for psychiatric comorbidity. Rates for the SYMPT group

were situated between SYND and GS on all major dependent variables. Furthermore, insomnia and

fatigue were perceived as contributing significantly to accidents, absences and decreased work

ME Research UK — Database of Research Publications 2009

De Lange FP,

Knoop H,

Bleijenberg G, Van

der Meer JW,

Hagoort P, Toni I.

de Tommaso M,

Sardaro M,

Serpino C,

Costantini F,

Vecchio E,

Prudenzano MP,

Lamberti P, Livrea


Deangelis TM,

Shen L.

Neurological and





ogy of Pain Unit,

University of Bari,

Bari, Italy.



Mount Sinai School

of Medicine, New

York, NY, USA.

The experience of

fatigue in the


on: Psychol

Med. 2008



comorbidity in



Outbreak of




following exposure

to aerosolized

porcine neural


Psychol Med. 2009


Epub 2008 Dec 18.

Cephalalgia. 2009


Epub 2009 Dec 15.

Mt Sinai J Med.



productivity, regardless of insomnia status. CONCLUSIONS: This study indicates that insomnia is

associated with significant morbidity in terms of health problems and health‐care utilization, work

absenteeism and reduced productivity, and risk of non‐motor‐vehicle accidents. Future studies should

evaluate whether treating insomnia can reverse this morbidity.

Fibromyalgia syndrome (FMS) is a chronic pain condition of unknown aetiology characterized by

diffuse pain and tenderness at tender points. The aim of the study was to assess the prevalence and

clinical features of FMS in the different forms of primary headaches, in a tertiary headache centre.

Primary headache patients (n = 217) were selected and submitted to the Total Tenderness Score,

anxiety and depression scales, Migraine Disability Assessment, allodynia questionnaire, Short Form 36

Health Survey and the Medical Outcomes Study‐Sleep Scale. In patients with FMS, the

Multidimensional Assessment of Fatigue, the Pain Visual Analog Scale, the Manual Tender Point

Survey and the Fibromyalgia Impact Questionnaire were employed. FMS was present in 36.4% of

patients and prevailed significantly in tension‐type headache and in patients with higher headache

frequency. Headache frequency, pericranial muscle tenderness, anxiety and sleep inadequacy were

especially associated with FMS comorbidity. In the FMS patients, fatigue and pain at tender points

were significantly correlated with headache frequency. FMS seems increasingly prevalent with

increased headache frequency, for the facilitation of central sensitization phenomena favoured by

anxiety and sleep disturbances.

In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained

neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN.

The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness,

and tingling in their extremities as well as weakness. The symptoms were described as more sensory

than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root

irritation. An epidemiological investigation revealed that the only commonality between cases was

their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases

remained asymptomatic and all cultures for known pathogens were negative, the etiology of the

syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic

inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings,

revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features

clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory

testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the

observed inflammation was the result of 1 or more unidentified antigens. This syndrome was

ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune

reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive

ME Research UK — Database of Research Publications 2009

Decker MJ, Eyal S,

Shinar Z, Fuxman

Y, Cahan C, Reeves

WC, Baharav A.

Decker MJ,

Tabassum H, Lin

JM, Reeves WC.

Chronic Viral

Diseases Branch,

National Center for

Zoonotic, Vector‐

borne Enteric

Diseases, Centers

for Disease Control

and Prevention,

1600 Clifton Road,

Mail Stop A‐15,

Atlanta, GA,

30333, USA,


Chronic Viral

Diseases Branch,

National Center for

Zoonotic, Vector‐

borne Enteric

Diseases, Centers

for Disease Control

and Prevention,

1600 Clifton Road,

Mail Stop A‐15,

Atlanta, Georgia,



Validation of ECG‐

derived sleep

architecture and

ventilation in sleep

apnea and chronic

fatigue syndrome.


raphic correlates

of Chronic Fatigue


Sleep Breath. 2009

Oct 9. [Epub ahead

of print]

Behav Brain Funct.

2009 Oct 6;5:43.

inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar

cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been

identified have since stopped the use of compressed air in removing pork brains. All cases have

stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study

of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the

value of epidemiological principles in the identification and containment of outbreaks while

researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt

Sinai J Med 76:442‐447, 2009. (c) 2009 Mount Sinai School of Medicine.

PURPOSE: Newly developed algorithms putatively derive measures of sleep, wakefulness, and

respiratory disturbance index (RDI) through detailed analysis of heart rate variability (HRV). Here, we

establish levels of agreement for one such algorithm through comparative analysis of HRV‐derived

values of sleep‐wake architecture and RDI with those calculated from manually scored

polysomnographic (PSG) recordings. METHODS: Archived PSG data collected from 234 subjects who

participated in a 3‐day, 2‐night study characterizing polysomnographic traits of chronic fatigue

syndrome were scored manually. The electrocardiogram and pulse oximetry channels were scored

separately with a novel scoring algorithm to derive values for wakefulness, sleep architecture, and

RDI. RESULTS: Four hundred fifty‐four whole‐night PSG recordings were acquired, of which, 410 were

technically acceptable. Comparative analyses demonstrated no difference for total minutes of sleep,

wake, NREM, REM, nor sleep efficiency generated through manual scoring with those derived through

HRV analyses. When NREM sleep was further partitioned into slow‐wave sleep (stages 3‐4) and light

sleep (stages 1‐2), values calculated through manual scoring differed significantly from those derived

through HRV analyses. Levels of agreement between RDIs derived through the two methods revealed

an R = 0.89. The Bland‐Altman approach for determining levels of agreement between RDIs generated

through manual scoring with those derived through HRV analysis revealed a mean difference of ‐0.7

+/‐ 8.8 (mean +/‐ two standard deviations). CONCLUSION: We found no difference between values of

wakefulness, sleep, NREM, REM sleep, and RDI calculated from manually scored PSG recordings with

those derived through analyses of HRV.

ABSTRACT: BACKGROUND: Unremitting fatigue and unrefreshing sleep, hallmark traits of Chronic

Fatigue Syndrome (CFS), are also pathognomonic of sleep disorders. Yet, no reproducible

perturbations of sleep architecture, multiple sleep latency times or Epworth Sleepiness Scores are

found to be associated consistently with CFS. This led us to hypothesize that sleep homeostasis,

rather than sleep architecture, may be perturbed in CFS. To probe this hypothesis, we measured and

compared EEG frequencies associated with restorative sleep between persons with CFS and matched

controls, both derived from a population‐based sample. METHODS: We evaluated overnight

polysomnography (PSG) in 35 CFS and 40 control subjects. PSG records were manually scored and

epochs containing artifact removed. Fast Fourier Transformation was utilized to deconstruct

individual EEG signals into primary frequency bands of alpha, delta, theta, sigma, and beta frequency

domains. The spectral power of each frequency domain for each sleep state was compared between

persons with CFS and matched controls. RESULTS: In persons with CFS, delta power was diminished

during slow wave sleep, but elevated during both stage 1 and REM. Alpha power was reduced during

ME Research UK — Database of Research Publications 2009

Dennis D,

Robertson D,

Curtis L, Black J.

Dennison L,

Stanbrook R,

Moss‐Morris R,

Yardley L, Chalder


Northside Hospital,




Fungal exposure

endocrinopathy in

sinusitis with

growth hormone

deficiency: Dennis‐





therapy and


for chronic fatigue

syndrome in young

Toxicol Ind Health.

2009 Oct‐


80. Epub 2009 Oct


Br J Health

Psychol. 2009 May

6. [Epub ahead of


stage 2, slow wave, and REM sleep. Those with CFS also had significantly lower theta, sigma, and beta

spectral power during stage 2, Slow Wave Sleep, and REM. DISCUSSION: Employing quantitative EEG

analysis we demonstrate reduced spectral power of cortical delta activity during SWS. We also

establish reduced spectral power of cortical alpha activity, with the greatest reduction occurring

during REM sleep. Reductions in theta, beta, and sigma spectral power were also apparent.

CONCLUSION: Unremitting fatigue and unrefreshing sleep, the waking manifestations of CFS, may be

the consequence of impaired sleep homeostasis rather than a primary sleep disorder.

A retrospective study was carried out on 79 patients with a history of mold exposure, fatigue, and

chronic rhinosinusitis (CRS) to determine whether there is a causal relationship between fungal

exposure and chronic sinusitis, fatigue, and anterior hypopituitarism, especially growth hormone

deficiency (GHD). Of the patients, 94% had a history of CRS, endoscopically and/or computed

tomography (CT) confirmed; 100% had chronic fatigue and 100% had either significant history of

indoor mold exposure and/or positive mold plate testing as measured by settle plates, with an

average colony count of 21 (0‐4 normal). A total of 62 had positive mold plate testing and 17 had

positive history of mold exposure. Of 75, 73 (97.3%) had positive serum immunoglobulin G (IgG)‐

specific antibodies to fungal antigens. Out of 8, 7 were positive for urinary trichothecenes. Resting

levels of insulin‐like growth factor 1 (IGF‐1) averaged 123 ng/mL (range 43‐285, normal 88‐249

ng/mL). Despite normal resting levels of IGF‐1, significant deficiency of serum human growth

hormone (GH) was confirmed by insulin tolerance test (ITT) in 40 of 50 tested. In all, 51% (40/79)

were GH deficient. Primary or secondary hypothyroidism in T3 and/or T4 was seen in 81% (64/79)

patients; 75% (59/79) had adrenocorticotrophic hormone (ACTH) deficiency. Fungal exposure

endocrinopathy likely represents the major cause of GHD, affecting approximately 4.8 million people

compared to approximately known 60,000 cases from all other causes. A literature review indicates a

possible mechanism of GHD in fungal exposure is that the fungal glucan receptors in the

lenticulostellate cells of the anterior pituitary bind to fungal cells wall glucans and activate the innate

immune system, which activates macrophages that destroy the fungus and lenticulostellate tissue.

Treatment of patients included normal saline nasal irrigations, antifungal and antibiotic nasal sprays,

appropriate use of oral antibiotics and antifungals, facial steamer with CitriDrops. Thymate and/or

Intramax vitamin supplements, hormone replacement, and reduction of indoor mold levels.

Resolution of rhinosinusitis was seen in 93% (41 of 45) of the patients who achieved a mold count by

settling plates of 0‐4 colonies. Thirty patients were unable to lower their mold counts below four

colonies and had various degrees of mucosal disease and fatigue remaining. Fatigue was improved in

all 37 patients who received GH and cortisol and/or thyroid hormone, which were deficient. Fatigue

was partially relieved in 7 of the 37 who did not achieve mold counts of fewer than four colonies.

Objectives Recent trials have produced optimistic results for family‐focussed cognitive behavioural

therapy (CBT) for chronic fatigue syndrome (CFS) in young people. This study sought to examine the

under‐researched question of the views and experiences of patients and families who take part.

Design Semi‐structured interviews and qualitative analysis were chosen in order to address clients'

perspectives in depth. Methods Sixteen young people and sixteen parents who participated in a trial

of CBT versus psycho‐education (PE) for CFS were interviewed. Key themes were discerned using

ME Research UK — Database of Research Publications 2009

Dickson A, Toft A,

O'Carroll RE.

Dinos S, Khoshaba

B, Ashby D, White

PD, Nazroo J,

Wessely S, Bhui


School of Health

and Social

Sciences, Napier


Edinburgh, UK.



Centre for

Psychiatry, Barts

and the London

School of Medicine

and Dentistry,

Queen Mary

University of

London, London,



people: Reflections

from the families'



l functioning,

illness perception,

mood and quality

of life in chronic

fatigue syndrome,


thyroid disease

and healthy


A systematic

review of chronic

fatigue, its

syndromes and



severity, co‐

morbidity and


Psychol Med. 2009


Epub 2009 Jan 15.

Int J Epidemiol.



Epub 2009 Apr 6.

inductive thematic analysis. Results Most families had low expectations of a cure but hope for

improvement. Generally speaking, participants found both CBT and PE acceptable and helpful.

Behavioural aspects of CBT (e.g. goal‐setting, graded activity) were found helpful. The opportunity to

gain support, recognition and validation was important. Cognitive elements of therapy were

sometimes deemed inappropriate and some felt emotional aspects of CFS were not adequately

addressed. Participants were ambivalent towards the extent of family involvement. Negative

experiences related to the therapy setting and feeling inappropriately labeled. Most participants felt

therapy was a stepping‐stone towards normal life, although many felt recovery was incomplete. Very

few differences were found between themes from CBT and PE participants. A notable exception was

that every young person who experienced CBT described therapy as helpful, whereas the participants

who strongly opposed the therapy approach had all experienced PE. Conclusions The detailed insights

regarding families' therapy experiences suggest areas of improvement for service delivery and topics

for further investigation.

BACKGROUND: This study attempted to longitudinally investigate neuropsychological function, illness

representations, self‐esteem, mood and quality of life (QoL) in individuals with chronic fatigue

syndrome (CFS) and compared them with both healthy participants and a clinical comparison group of

individuals with autoimmune thyroid disease (AITD). METHOD: Neuropsychological evaluation was

administered at two time points, five weeks apart. Twenty‐one individuals with CFS, 20 individuals

with AITD and 21 healthy participants were matched for age, pre‐morbid intelligence, education level

and socio‐economic status (SES). All groups also completed measures of illness perceptions, mood,

self‐esteem and QoL at both time points. RESULTS: The CFS group showed significantly greater

impairment on measures of immediate and delayed memory, attention and visuo‐constructional

ability, and reported significantly higher levels of anxiety and depression. After controlling for the

effects of mood, the CFS group still demonstrated significant impairment in attention. The CFS group

also reported significantly lower self‐reported QoL than the AITD and healthy participants. In terms of

illness perceptions, the AITD group believed that their condition would last longer, that they had

more treatment control over their condition, and reported less concern than the CFS group.

CONCLUSIONS: These results suggest that the primary cognitive impairment in CFS is attention and

that this is not secondary to affective status. The lower treatment control perceptions and greater

illness concerns that CFS patients report may be causally related to their affective status.

BACKGROUND: Chronic Fatigue Syndrome (CFS) is characterized by unexplained fatigue that lasts for

at least 6 months alongside a constellation of other symptoms. CFS was historically thought to be

most common among White women of higher socio‐economic status. However, some recent studies

in the USA suggest that the prevalence is actually higher in some minority ethnic groups. If there are

convincing differences in prevalence and risk factors across all or some ethnic groups, investigating

the causes of these can help unravel the pathophysiology of CFS. METHODS: A systematic review was

conducted to explore the relationship between fatigue, chronic fatigue (CF‐‐fatigue lasting for 6

months), CFS and ethnicity. Studies were population‐based and health service‐based. Meta‐analysis

was also conducted to examine the population prevalence of CF and CFS across ethnic groups.

RESULTS: Meta‐analysis showed that compared with the White American majority, African Americans

ME Research UK — Database of Research Publications 2009

Donalek JG. Department of

Nursing, DePaul


Chicago, IL 60614,




Drachler Mde L,

Leite JC, Hooper L,

Hong CS, Pheby D,

Nacul L, Lacerda E,

Campion P, Killett

A, McArthur M,

Poland F.

k and Native Americans have a higher risk of CFS [Odds Ratio (OR) 2.95, 95% confidence interval (CI):

0.69‐10.4; OR = 11.5, CI: 1.1‐56.4, respectively] and CF (OR = 1.56, CI: 1.03‐2.24; OR = 3.28, CI: 1.63‐

5.88, respectively). Minority ethnic groups with CF and CFS experience more severe symptoms and

may be more likely to use religion, denial and behavioural disengagement to cope with their condition

compared with the White majority. CONCLUSIONS: Although available studies and data are limited, it

does appear that some ethnic minority groups are more likely to suffer from CF and CFS compared

with White people. Ethnic minority status alone is insufficient to explain ethnic variation of

prevalence. Psychosocial risk factors found in high‐risk groups and ethnicity warrant further

investigation to improve our understanding of aetiology and the management of this complex


School of Allied

Health Professions,

University of East

Anglia, Norwich,

NR4 7TJ, UK.



When a parent is

chronically ill:

chronic fatigue


The expressed

needs of people

with chronic




a systematic


Nurs Res. 2009



BMC Public Health.

2009 Dec 11;9:458.

BACKGROUND: Chronic illness may reshape not only the life of the ill parent but also that of the entire

family, but research in this area remains limited. More specifically, little is known about how an ill

parent and the family respond to a particularly devastating and controversial chronic illness, chronic

fatigue syndrome (CFS). OBJECTIVES: The objective of this study was to describe the responses of the

parent and the ensuing family system responses to the presence of chronic fatigue syndrome as a

chronic parental illness. METHODS: Parents were interviewed individually, and then the ill parent and

as many immediate family members as possible were interviewed collectively. After consent or

assent, interviews were audiotaped and transcribed. Thematic analyses at the individual, intrafamily,

and across‐family levels were used to explore these phenomena. RESULTS: Eight ill parents first

described the onset of illness, an ongoing struggle to receive diagnosis and care, and the significance

of the illness in transforming present and future roles. Multiple members of the family together with

the ill parent described how they struggled with the reality of the illness, the shifting roles and

responsibilities, the reduced family income, and the frequent social isolation that could be

exacerbated by the controversial nature of the illness. Families described and demonstrated their

struggles to maintain normal family life and plans in the face of continuing uncertainty. DISCUSSION:

This study is situated within current scholarship on family responses to chronic parental illness. The

value of the family research interview is affirmed. Recommendations are made for future directions in

family nursing research exploring responses of families in which a parent is chronically ill.

BACKGROUND: We aimed to review systematically the needs for support in managing illness and

maintaining social inclusion expressed by people with chronic fatigue syndrome/myalgic

encephalomyelitis (CFS/ME) METHODS: We carried out a systematic review of primary research and

personal ('own') stories expressing the needs of people with CFS/ME. Structured searches were

carried out on Medline, AMED, CINAHL, EMBASE, ASSIA, CENTRAL, and other health, social and legal

databases from inception to November 2007. Study inclusion, data extraction and risk of bias were

assessed independently in duplicate. Expressed needs were tabulated and a conceptual framework

developed through an iterative process. RESULTS: Thirty two quantitative and qualitative studies,

including the views of over 2500 people with CFS/ME with mainly moderate or severe illness severity,

met the inclusion criteria. The following major support needs emerged: 1) The need to make sense of

symptoms and gain diagnosis, 2) for respect and empathy from service providers, 3) for positive

attitudes and support from family and friends, 4) for information on CFS/ME, 5) to adjust views and

ME Research UK — Database of Research Publications 2009

Dworzańska E,


K, Stelmasiak Z.

Katedra i Klinika



Medyczny w



Publiczny Szpital

Kliniczny nr 4, ul.

Jaczewskiego 8,

20‐954 Lublin,




[Fatigue in


sclerosis][Article in


Dyer C. High court rejects

challenge to NICE

guidelines on

chronic fatigue


Edd EM, Flores S. College of Nursing,

New York

University, John A.

Hartford Institute

for Geriatric

Nursing, New York

University, New

York, NY, USA.

Evans KM,

Flanagan DE,

Department of

Endocrinology and

Sleepiness or

excessive daytime


Chronic fatigue: is

it endocrinology?

Neurol Neurochir

Pol. 2009 Jan‐


BMJ. 2009 Mar

17;338:b1110. doi:



Geriatr Nurs. 2009



Clin Med. 2009


priorities, 6) to develop strategies to manage impairments and activity limitations, and 7) to develop

strategies to maintain/regain social participation. CONCLUSIONS: Although the studies were

heterogeneous, there was consistent evidence that substantial support is needed to rebuild lives.

Gaining support depends ‐ most importantly ‐ on the ability of providers of health and social care,

colleagues, friends and relatives, and those providing educational and leisure services, to understand

and respond to those needs.

Fatigue is one of the most common symptoms of multiple sclerosis (MS) and is associated with

reduced quality of life. The fatigue syndrome is characterized by uncontrollable apathy, exhaustion,

fatigability and lack of energy. The mechanisms underlying fatigue in MS are still poorly understood

but studies suggest that immune and neuroendocrine factors may play a causative role in the

development of fatigue. The first step in management of MS‐related fatigue is identifying and

eliminating any secondary causes (adverse effects of drugs, infections, sleep disorders, metabolic

diseases). As the fatigue syndrome in patients with MS cannot be evaluated objectively in the routine

clinical setting, a number of scales have been developed. The Fatigue Severity Scale is a general scale.

Additional scales that have been tested in MS include the Fatigue Impact Scale. Therapy of fatigue

syndrome consists of modafinil, amantadine, pemoline and non‐pharmacological management.

Excessive daytime somnolence (EDS) is associated with age‐related changes, environment, circadian

rhythm or sleep pattern disorder, insomnia, medications, lifestyle factors, depression, pain, and

illness. The notion of "sleep architecture" connotes a structure that describes the sleep cycle (i.e.,

stages) and wakefulness during a single sleep period‐that is, rapid eye movement (REM) and non‐

REM sleep. Circadian rhythms perform a variety of functions including regulation of the quality and

distribution of the stages of sleep. Insomnia includes delayed sleep onset as well as premature

wakening; sleep is nonrestorative. Comorbidities associated with insomnia are Alzheimer's disease

and other dementias, delirium, depression, congestive heart failure, chronic obstructive pulmonary

disease, gastroesophageal reflux disease, pain, degenerative diseases of the neurological system, and

sleep apnea. Continuous inadequate sleep affects cognitive function, physical performance, overall

well‐being, and quality of life. There is a greater risk of falls from insomnia than is the use of hypnotics

to manage it. Sleep disruption among older adults is underrecognized and undertreated. Assessment

using valid tools can be performed rapidly. There are a variety of treatment options, including sleep

hygiene and pharmacological and alternative modalities.

Fatigue and stress‐related illnesses often become diagnoses of exclusion after extensive investigation.

'Tired all the time' is a frequent reason for referral to the endocrine clinic, the implicit question being‐

ME Research UK — Database of Research Publications 2009

Wilkin TJ. Metabolism,

Peninsula Medical

School, Plymouth

and Derriford





Exley C, Swarbrick

L, Gherardi RK,

Authier FJ.

Fletcher MA, Zeng

XR, Barnes Z, Levis

S, Klimas NG.

Birchall Centre for


Chemistry and

Materials Science,

Keele University,

Staffordshire ST5

5BG, UK.



Department of


University of

Miami Miller

School of

Medicine, 1600

NW 10th Ave,

Miami, FL, USA.



A role for the body

burden of

aluminium in



myofasciitis and

chronic fatigue


Plasma cytokines

in women with

chronic fatigue


Med Hypotheses.



Epub 2008 Nov 11.

J Transl Med. 2009

Nov 12;7:96.

‐is there a subtle endocrine pathology contributing to the patient's symptoms? Often initial

assessment suggests not but there are no clear data to address the question of whether overt

pathology will develop in the future. This study observed outcomes after five years in 101 consecutive

and unselected referrals to secondary care for 'fatigue?cause', where initial assessment did not

suggest treatable endocrine pathology. The findings suggest that the clinical diagnosis of fatigue,

based on history and tests to exclude anaemia, hypothyroidism and diabetes, is secure: these

patients do not subsequently demonstrate excess morbidity and mortality, and their presenting

symptoms are not early features of significant endocrine pathology.

Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may

be caused by adverse reactions to aluminium‐containing adjuvants in vaccines. While a little is known

of disease aetiology both conditions are characterised by an aberrant immune response, have a

number of prominent symptoms in common and are coincident in many individuals. Herein, we have

described a case of vaccine‐associated chronic fatigue syndrome and macrophagic myofasciitis in an

individual demonstrating aluminium overload. This is the first report linking the latter with either of

these two conditions and the possibility is considered that the coincident aluminium overload

contributed significantly to the severity of these conditions in this individual. This case has

highlighted potential dangers associated with aluminium‐containing adjuvants and we have

elucidated a possible mechanism whereby vaccination involving aluminium‐containing adjuvants

could trigger the cascade of immunological events which are associated with autoimmune conditions

including chronic fatigue syndrome and macrophagic myofasciitis.

BACKGROUND: Chronic Fatigue Syndrome (CFS) studies from our laboratory and others have

described cytokine abnormalities. Other studies reported no difference between CFS and controls.

However, methodologies varied widely and few studies measured more than 4 or 5 cytokines.

Multiplex technology permits the determination of cytokines for a large panel of cytokines

simultaneously with high sensitivity and with only 30 ul of plasma per sample. No widely accepted

laboratory test or marker is available for the diagnosis or prognosis of CFS. This study screened

plasma factors to identify circulating biomarkers associated with CFS. METHODS: Cytokines were

measured in plasma from female CFS cases and female healthy controls. Multiplex technology

provided profiles of 16 plasma factors including the pro ‐inflammatory cytokines: tumor necrosis

factor alpha (TNFalpha), lymphotoxin alpha (LTalpha), interleukin (IL) ‐ IL‐Ialpha, IL‐1beta, IL‐6; TH1

cytokines: interferon gamma (IFNgamma), IL‐12p70, IL‐2, IL‐15; TH2: IL‐4, IL‐5; TH17 cytokines, IL‐17

and IL‐23; anti‐inflammatory cytokines IL‐10, IL‐13; the inflammatory mediator and neutrophil

attracting chemokine IL‐8 (CXCL8). Analysis by receiver operating characteristic (ROC) curve assessed

the biomarker potential of each cytokine. RESULTS: The following cytokines were elevated in CFS

compared to controls: LTalpha, IL‐1alpha, IL‐1beta, IL‐4, IL‐5, IL‐6 and IL‐12. The following cytokines

were decreased in CFS: IL‐8, IL‐13 and IL‐15. The following cytokines were not different: TNFalpha,

IFNgamma, IL‐2, IL‐10, IL‐23 and IL‐17. Applying (ROC) curve analyses, areas under the curves (AUC)

for IL‐5 (0. 84), LTalpha (0.77), IL‐4 (0.77), IL‐12 (0.76) indicated good biomarker potential. The AUC of

IL‐6 (0.73), IL‐15 (0.73), IL‐8 (0.69), IL‐13 (0.68) IL‐1alpha (0.62), IL‐1beta (0.62) showed fair potential

as biomarkers. CONCLUSION: Cytokine abnormalities are common in CFS. In this study, 10 of 16

ME Research UK — Database of Research Publications 2009

Flor‐Henry P, Lind

JC, Koles ZJ.

Alberta Hospital

Edmonton, Box

307, Edmonton,


Alberta, Canada

T5J 2J7.

Fluge Ø, Mella O. Department of

Oncology and

Medical Physics,



Hospital, N‐5021

Bergen, Norway.



EEG source

analysis of chronic

fatigue syndrome.

Clinical impact of

B‐cell depletion

with the anti‐CD20

antibody rituximab

in chronic fatigue

syndrome: a

preliminary case


Psychiatry Res..

[Epub ahead of


BMC Neurol. 2009

Jul 1;9:28.

cytokines examined showed good to fair promise as biomarkers. However, the cytokine changes

observed are likely to more indicative of immune activation and inflammation, rather than specific for

CFS. As such, they are targets for herapeutic strategies. Newer techniques allow evaluation of large

panels of cytokines in a cost effective fashion.

Sixty‐one dextral, unmedicated women with chronic fatigue syndrome (CFS) diagnosed according to

the Fukuda criteria (1994) and referred for investigation by rheumatologists and internists were

studied with quantitative EEG (43 channels) at rest with eyes open and during verbal and spatial

cognitive activation. The EEGs from the patients were compared with recordings from 80 dextral

healthy female controls. Only those subjects who could provide 20 1‐s artefact‐free segments of EEG

were admitted into the study. The analysis consisted of the identification of the spatial patterns in the

EEGs that maximally differentiated the two groups and the estimation of the cortical source

distributions underlying these patterns. Spatial patterns were analyzed in the alpha (8‐13Hz) and beta

(14‐20Hz) bands and the source distributions were estimated using the Borgiotti‐Kaplan

BEAMFORMER algorithm. The results indicate that the spatial patterns identified were effective in

separating the two groups, providing a minimum correct retrospective classification rate of 72% in

both frequency bands while the subjects were at rest to a maximum of 83% in the alpha band during

the verbal cognitive condition. Underlying cortical source distributions showed significant differences

between the two groups in both frequency bands and in all cognitive conditions. Lateralized cortical

differences were evident between the two groups in the both frequency bands during both the verbal

and spatial cognitive conditions. During these active cognitive conditions, the CFS group showed

significantly greater source‐current activity than the controls in the left frontal‐temporal‐parietal

regions of the cortex.

BACKGROUND: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. A patient with CFS

had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic

chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to

methotrexate treatment, which induces immunomodulation in part through B‐cell depletion.

METHODS: In a case series, this patient and two additional CFS patients were B‐cell depleted by

infusion of the monoclonal anti‐CD20 antibody rituximab. RESULTS: All three had improvement of all

CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3

slight improvement from the same time, but then improved markedly from 26 weeks after

intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all

were retreated with a single (patient 1) or double rituximab infusion (patients 2 and 3). Again, all

three had marked symptom improvement, mimicking their first response. After new symptom

recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from

this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again

with a marked clinical benefit. No unexpected toxicity was seen. CONCLUSION: These observations

suggest that B‐lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all

CFS symptoms, the delayed symptom relief following B‐cell depletion, the kinetics of relapses, and the

effect also from methotrexate treatment, provide suggestive evidence that B‐cells play a significant

role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions

ME Research UK — Database of Research Publications 2009

Fluge Ø, Mella O. Department of

Oncology and

Medical Physics,



Hospital, N‐5021

Bergen, Norway.



Fomicheva EE,

Filatenkova TA,

Rybakina EG.

Forstenius L,

Helmfrid S.

Frémont M,

Metzger K, Rady

H, Hulstaert J, De

Meirleir K.

Protea Biopharma,


100, 1731 Zellik,


Clinical impact of

B‐cell depletion

with the anti‐CD20

antibody rituximab

in chronic fatigue

syndrome: a

preliminary case


[Activity of



axis by induction of


chronic fatigue

syndrom][Article in


[Chronic fatigue


than just chronic

fatigue] [Article in


Detection of

herpesviruses and

parvovirus B19 in

gastric and

BMC Neurol. 2009

Jul 1;9:28.

Ross Fiziol Zh Im I

M Sechenova.

2009 Jan;95(1):11‐



2009 Sep 9‐


In Vivo. 2009 Mar‐


aimed at modifying B‐cell number and function. More systematic investigations of this therapeutic

strategy, and of its biological basis, are now needed.

BACKGROUND: Chronic fatigue syndrome (CFS) is a disease of unknown aetiology. A patient with CFS

had unexpected, marked recovery of CFS symptoms lasting for five months during and after cytotoxic

chemotherapy for Hodgkin's disease. We reasoned that the transient CFS recovery was related to

methotrexate treatment, which induces immunomodulation in part through B‐cell depletion.

METHODS: In a case series, this patient and two additional CFS patients were B‐cell depleted by

infusion of the monoclonal anti‐CD20 antibody rituximab. RESULTS: All three had improvement of all

CFS symptoms. Patients 1 and 2 had major amelioration from 6 weeks after intervention, patient 3

slight improvement from the same time, but then improved markedly from 26 weeks after

intervention. The symptomatic effect lasted until weeks 16, 18 and 44, respectively. At relapse, all

were retreated with a single (patient 1) or double rituximab infusion (patients 2 and 3). Again, all

three had marked symptom improvement, mimicking their first response. After new symptom

recurrence, patients 1 and 2 were given weekly oral methotrexate, patient 1 having effect also from

this agent. Patients 1 and 2 were again treated for a third rituximab infusion after new relapse, again

with a marked clinical benefit. No unexpected toxicity was seen. CONCLUSION: These observations

suggest that B‐lymphocytes are involved in CFS pathogenesis for a subset of patients. Benefit for all

CFS symptoms, the delayed symptom relief following B‐cell depletion, the kinetics of relapses, and the

effect also from methotrexate treatment, provide suggestive evidence that B‐cells play a significant

role in the ongoing clinical features, and that CFS may be amenable to therapeutic interventions

aimed at modifying B‐cell number and function. More systematic investigations of this therapeutic

strategy, and of its biological basis, are now needed.

Changes in the activity of hypothalamic‐pituitary adrenal (HPA) axis were investigated in experimental

model of chronic fatigue syndrome (CFS) induced by intraperitoneal administration of synthetic

double‐stranded RNA (polyriboinosinic: polyribocytidylic acid, Poly I : C) to rats in the dose of 3 mg/kg

body weight. In order to reveal functional changes in different links of the HPA axis, standard probes

with intraperitoneal administration of ACTH and hydrocortisone against the background of cold stress

application and Poly I : C injections were performed. A single injection of Poly I : C led to disordered

HPA axis functions which was manifested by decreased sensitivity of the cells in the adrenal gland in

response to ACTH, and suppression of the mechanism of negative feedback resulting in significant fall

of cortisocterone concentration in standard assays with ACTH and hydrocortisone administration.

BACKGROUND: Human herpesvirus‐6 (HHV‐6), Epstein‐Barr virus and parvovirus B19 have been

suggested as etiological agents of chronic fatigue syndrome but none of these viruses is consistently

detected in all patients. However, active viral infections may be localized in specific tissues, and,

therefore, are not easily detectable. The aim of this study was to investigate the presence of HHV‐6,

ME Research UK — Database of Research Publications 2009



Frenger P. A Working

Hypothesis, Inc.,

Houston, TX.

Friedberg F, Sohl


Friedberg F, Sohl


Stony Brook




Department of

Psychiatry and

Behavioral Science

Putnam Hall, Stony

Brook University,

NY 11794‐8790,




intestinal mucosa

of chronic fatigue

syndrome patients.




emulator ‐ biomed



therapy in chronic

fatigue syndrome:

is improvement

related to

increased physical



change in chronic

fatigue syndrome:

what home‐based



Biomed Sci



J Clin Psychol. 2009


J Behav Med. 2009


Epub 2008 Dec 20.

HHV‐7, EBV and parvovirus B19 in the gastro‐intestinal tract of CFS patients. PATIENTS AND

METHODS: Using real‐time PCR, viral DNA loads were quantified in gastro‐intestinal biopsies of 48 CFS

patients and 35 controls. RESULTS: High loads of HHV‐7 DNA were detected in most CFS and control

biopsies. EBV and HHV‐6 were detected in 15‐30% of all biopsies. Parvovirus B19 DNA was detected

in 40% of the patients versus less than 15% of the controls. CONCLUSION: Parvovirus B19 may be

involved in the pathogenesis of CFS, at least for a subset of patients. The gastro‐intestinal tract

appears as an important reservoir of infection for several potentially pathogenic viruses.

Fibromyalgia Syndrome is a chronic disorder characterized by abnormal pain, fatigue, depression,

cognitive dysfunction and sleep disturbance. The body's immune, hormonal, and nervous systems are

involved. The author proposes a model from his clinical practice where a relapsing human Herpesvirus

4 infection of ss‐lymphocytes causes inappropriate activation of immune system components, thus

leading to typical FMS signs and symptoms. This clinical model was subsequently embodied in a

computer based on the author's human nervous system function emulator, which imitates the brain's

biochemicalneural‐cognitive operations. This Forth language emulator program runs on a

multiprocessor network recently enhanced with 8‐core 32‐bit CPUs. Supplemental analog circuit

boards provide support for an artificial neural network, synthetic emotion and cellular substrate‐

receptor binding activity simulation. The effects of antiviral antibiotics and other chemicals on this

disease are included in the emulator.

This multiple case study of cognitive‐behavioral treatment (CBT) for chronic fatigue syndrome (CFS)

compared self‐report and behavioral outcomes. Eleven relatively high‐functioning participants with

CFS received 6‐32 sessions of outpatient graded‐activity oriented CBT. Self‐report outcomes included

measures of fatigue impact, physical function, depression, anxiety, and global change. Behavioral

outcomes included actigraphy and the 6‐minute walking test. Global change ratings were very much

improved (n=2), much improved (n=2), improved (n=5), and no change (n=2). Of those reporting

improvement, clinically significant actigraphy increases (n=3) and decreases (n=4) were found, as well

as no significant change (n=2). The nature of clinical improvement in CBT trials for high‐functioning

CFS patients may be more ambiguous than that postulated by the cognitive‐behavioral model.

The purpose of this 2‐year prospective study was to compare standard self‐report and ecologically‐

based outcome measures in patients with chronic fatigue syndrome (CFS). Standard measures

assessed physical function, fatigue impact, psychological variables, and global impression of change

ratings. Ecological measures included actigraphy, a structured activity record, and an electronic

fatigue/energy diary. Results for this high functioning sample (N = 75) revealed that self‐report global

improvement was significantly associated with lower momentary fatigue and fatigue impact, and a

higher frequency of standing up (at home), but not with actigraphy or psychological variables.

However, actigraphy change was significantly correlated with change in self‐report physical function.

At follow‐up, only a small minority (

ME Research UK — Database of Research Publications 2009

Fukunaga M. Department of


Medicine, Faculty

of Medicine,

Kansai Medical


Godás Sieso T,

Gómez Gil E,

Salamero Baró M,


.com infectious

aetiologies for

multiple sclerosis,

schizophrenia and

the chronic fatigue

syndrome and

their treatment

with antibiotics.

Instituto de


Servicio de

Psicología, Unidad

[Overview of

functional somatic


[Article in



between chronic

fatigue syndrome

and type A



Epub 2009 Mar 6.

Nippon Rinsho.



Med Clin (Barc).

2009 Oct


Epub 2009 Jul 10.

attempting to find a common infectious aetiology for the two diseases. Chlamydia pneumoniae,

which belongs to the rickettsial family of microorganisms has been linked to both diseases. It is

postulated that since rickettsial microorganisms are ubiquitous in human populations they and the

human species normally live in peaceful coexistence. In rare cases, for unknown reasons, varieties of

them may become aggressive and pathogenic. The kynurenic acid hypothesis of schizophrenia has

attracted much attention. It also seems to have initiated a paradigmatic shift from the hitherto

prevailing serological research approach to one which focuses on immunological factors. An open

clinical pilot study in which, during 2006, eight female and five male patients with psychotic

symptoms were treated with a combination of antibiotics is presented, to which, in the beginning of

2007 two female patients suffering from severe and long standing chronic fatigue syndrome were

added. On one year follow‐up, six out of the eight female patients showed stable excellent treatment

results, whereas two were rated as showing significant treatment results. Four of the five men who

entered the study were suffering from chronic schizophrenia, whereas the fifth, was a case of severe

acute catatonic schizophrenia. Two of the male patients showed significant treatment results,

whereas three of them were rated as having had a slight to moderate improvement. No less than

three of the women had suffered their first episode of psychosis after giving birth to their first (and

only) child. This finding, as these women all responded excellently to treatment with antibiotics,

indicates that post partum psychosis could be regarded as an infectious complication of childbirth of,

as to the causative agent, unknown aetiology. High priority ought therefore be given to initiate

controlled clinical trials with antibiotic treatment of this serious condition. The otherwise promising

results of the pilot study seem to warrant further and controlled clinical trials with treatment with

antibiotics of patients with psychotic symptoms. As the second patient with psychotic symptoms to

enter the study, had a long standing history of chronic fatigue, where an initial treatment with the

antidepressant fluoxetine had only worsened her condition, whereas ninety days of treatment with

antibiotics, combined with vitamin B injections, effected a complete recovery, the author decided,

when two patients with long standing and incapacitating chronic fatigue syndromes sought the clinic

in February and March 2007, to include them in the study. The first of them, after sixty days of

treatment with antibiotics showed excellent treatment results on follow‐up one year later, whereas

the second, who also took the combination of antibiotics for sixty days, was rated as having shown a

significant improvement.

BACKGROUND AND OBJECTIVE: To quantify the relationship between Chronic Fatigue Syndrome (CFS)

and Type A Behaviour Pattern (TABP) PATIENTS AND METHOD: The Jenkins Activity Survey (JAS) was

administered to 82 patients diagnosed with CFS to determine the prevalence of TABP. Subjects' mean

z scores on the JAS were compared with those from the general population (healthy controls) and

ME Research UK — Database of Research Publications 2009

JM, Fernandez‐

Solá J.

Godfrey E, Cleare

A, Coddington A,

Roberts A,

Weinman J,

Chalder T.

Goedendorp MM,

Knoop H,

Schippers GM,

Bleijenberg G.

de fatiga crónica,

Hospital Clínic de


Barcelona, España.

Department of

Psychology, Kings

College London,

London, UK.

Expert Centre for

Chronic Fatigue,



Nijmegen Medical

Centre, Nijmegen,

The Netherlands.



Goldenberg DL. Department of



Hospital, Newton,


02462, USA.



behaviour] [Article

in Spanish]

Chronic fatigue

syndrome in

adolescents: do


expectations of

their child's

intellectual ability

match the child's


The lifestyle of

patients with

chronic fatigue

syndrome and the

effect on fatigue

and functional


Diagnosis and


diagnosis of


J Psychosom Res.



Epub 2009 Apr 16.

J Hum Nutr Diet.



Epub 2009 Feb 17.

Am J Med. 2009



from patients with ischemic cardiopathy (pathologic controls). RESULTS: CFS patients' mean score on

the JAS was 5 points higher than that of the general population (healthy controls) and 2 points higher

than that of patients with ischemic cardiopathy. CONCLUSIONS: TABP appears to be related with CFS

and should be taken into account in the treatment of these patients.

OBJECTIVE: This cross‐sectional study aimed to measure the discrepancy between actual and

perceived IQ in a sample of adolescents with CFS compared to healthy controls. We hypothesized that

adolescents with CFS and their parent would have higher expectations of the adolescent's intellectual

ability than healthy adolescents and their parent. METHODS: The sample was 28 CFS patients and 29

healthy controls aged 11‐19 years and the parent of each participant. IQ was assessed using the AH4

group test of general intelligence and a self‐rating scale which measured perceived IQ. RESULTS:

Parents' perceptions of their children's IQ were significantly higher for individuals with CFS than

healthy controls. CONCLUSIONS: High expectations may need to be addressed within the context of


BACKGROUND: Little is known about the lifestyle of patients with chronic fatigue syndrome (CFS) and

its influence on symptoms of CFS. The present study aimed to investigate the lifestyle of patients with

CFS, and to assess whether lifestyle factors are related to fatigue and functional impairments.

METHODS: Two hundred and forty‐seven patients fulfilling the Center for Disease Control criteria for

CFS were included. Validated questionnaires were used to collect data on lifestyle factors, smoking,

intake of alcohol, fat, fibres, fruit and vegetables, body mass index (BMI), fatigue severity and

functional impairments. RESULTS: Of the CFS patients, 23% smoked, 32% had an unhealthy BMI, and

none had an unhealthy alcohol intake. A majority had an unhealthy food intake: 70% had unhealthy

fat, fruit and vegetable intake, and 95% had unhealthy fibre intake. Compared with the general Dutch

population, significantly fewer CFS patients were overweight. Significantly more female CFS patients

abstained from alcohol, and fewer male CFS patients smoked. Unhealthy lifestyle factors were not

significantly associated with fatigue severity or functional impairments. CONCLUSIONS: CFS patients

tend to lead a healthier lifestyle compared to the general Dutch population. However, no relationship

was found between lifestyle factors and fatigue severity and functional impairments in CFS.

Fibromyalgia is a chronic functional illness that presents with widespread musculoskeletal pain as well

as a constellation of symptoms including fatigue, cognitive dysfunction, sleep difficulties, stiffness,

anxiety, and depressed mood. The diagnosis of fibromyalgia, similar to other functional disorders,

requires that organic diseases are not causing the symptoms. Systemic and rheumatic diseases can be

ruled out by a patient history, physical examination, and laboratory investigations. Because there are

no specific laboratory tests for fibromyalgia, the 1990 American College of Rheumatology (ACR)

classification criteria have been used in clinical settings; however, they are not ideal for individual

patient diagnosis. Clinicians should be aware of limitations inherent in using tender points in the

diagnosis of fibromyalgia. The multiple symptoms of fibromyalgia often overlap with those of related

disorders and may further complicate the diagnosis. One of the most challenging diagnostic dilemmas

that clinicians face is distinguishing fibromyalgia from other central pain disorders (e.g., irritable

bowel syndrome, chronic fatigue syndrome, migraine). Screening questions based on published

criteria can be used as a first approach in diagnosing functional illnesses. Numerous studies report a

ME Research UK — Database of Research Publications 2009

Gordon B, Lubitz L. Physiotherapy


Austin Hospital,

Heidelberg, Vic,




Gottfries CG,

Matousek M,

Zachrisson O.

Goudsmit EM, Ho‐

Yen DO, Dancey


Institutionen för


och fysiologi,






School of


University of East

London, London,





outcomes of an

adolescent chronic

fatigue syndrome




disturbances can

explain chronic

fatigue syndrome.

Biological findings

point towards


[Article in Swedish]

Learning to cope

with chronic

illness. Efficacy of a


treatment for

people with

chronic fatigue


J Paediatr Child

Health. 2009



2009 Sep 2‐



Patient Educ

Couns. 2009


Epub 2009 Jul 2.

Comment in:

Patient Educ

Couns. 2009


higher prevalence of psychiatric disorders in patients with fibromyalgia. Therefore, a careful history

and evaluation should be taken for the presence of primary mood disturbances. To date, there is no

"gold standard" for diagnosing fibromyalgia. Until a better clinical case definition of fibromyalgia

exists, all diagnostic criteria should be interpreted with caution, considered rudimentary, and subject

to modification. (c) 2009 Elsevier Inc.

INTRODUCTION: Chronic fatigue syndrome (CFS) is a condition of prolonged and disabling fatigue,

which is accompanied by characteristic constitutional and neuropsychiatric symptoms. In children and

adolescents, this condition occurring at a developmentally vulnerable time adds to the disability

affecting self‐concept, autonomy, body image, socialisation, sexuality and academic problems. This

case series looks at the effects of a graded exercise programme on physical outcomes, fatigue and

mental state in an adolescent population. METHODS: Data sets from 16 adolescents who completed

combined exercise training as part of the 4‐week inpatient intensive CFS programme at the Austin

Hospital, Melbourne were analysed. All patients completed an exercise assessment and three

questionnaires before beginning any training. A paediatrician (LL) confirmed the diagnosis according

to the Fukuda criteria in all patients. Exercise was carefully supervised and prescribed daily by an

exercise physiologist (BG) according to each individual's ability and response with the basic aim of

increasing exercise tolerance and improving muscle strength and endurance. RESULTS: There was an

18% improvement in volitional time to fatigue (P= 0.02) and 17% improvement in peak oxygen uptake

(VO(2peak)) (P= 0.01). Upper body strength and function improved with a remarkable 70% increase

in the number of push‐ups. Fatigue severity was reported to improve by 13% (P= 0.01) and depression

index improved significantly by 42% (P= 0.02). CONCLUSIONS: The significance of these improvements

cannot be underestimated as an improvement in physical capacity through increased time to fatigue

and less severe fatigue allows adolescents to resume school, social and family activities.

OBJECTIVE: The aim of this study was to determine the efficacy of an out‐patient, multi‐component

programme developed for patients with chronic fatigue syndrome (CFS). METHODS: Twenty‐two

patients were assessed before and after six months of treatment. Findings were compared with 22

individuals on the waiting list. The programme offered medical care as well as information and

counselling to help patients to understand, accept and cope with their illness. RESULTS: At six months,

there were significant differences between the groups for fatigue, self‐efficacy and anxiety. Overall,

82% of the treated patients reported feeling better and 23% had improved to such a degree that they

were discharged from the clinic. The gains were maintained at twelve months. CONCLUSION: This

programme was found to be both helpful and acceptable and may provide a useful first‐line

ME Research UK — Database of Research Publications 2009

Goudsmit EM,

Stouten B, Howes


Gow JW, Hagan S,

Herzyk P, Cannon

C, Behan PO,

Chaudhuri A.

Gupta A, Vij G,

Sharma S, Tirkey

N, Rishi P, Chopra


Hadlandsmyth K,

Vowles KE.

University of East

London, UK.



Essex Centre for




Hospital, Romford,

RM7 0BE, UK.




Division, University

Institute of


Sciences, Panjab



160014, India.

Bath and Wiltshire

Adult Chronic


intrusiveness in



an exploratory


A gene signature

for post‐infectious

chronic fatigue


Curcumin, a



attenuates chronic

fatigue syndrome

in murine water

immersion stress


Does depression

mediate the

J Health Psychol.




Genomics. 2009

Jun 25;2:38.



Epub 2008 Jun 17.

J Psychosom Res.

2009 Jan;66(1):31‐

intervention for many patients with CFS. PRACTICE IMPLICATIONS: Short, pragmatic programmes may

be as effective as cognitive‐behaviour therapy.

This study assessed the relationship between illness intrusiveness, symptoms, disability and

depression in patients with myalgic encephalomyelitis (ME). Participants were 16 patients with ME

and eight patients with ME plus co‐morbid disorders. The patients with co‐morbid disorders reported

greater illness intrusiveness than the patients with ME alone, but there were no differences between

the groups on the other variables. Significant correlations were found between illness intrusiveness

on the one hand, and fatigue, cognitive dysfunction, disability and depression, on the other. We

conclude that ME is a disabling illness, which has a major impact on various life domains.

ABSTRACT: BACKGROUND: At present, there are no clinically reliable disease markers for chronic

fatigue syndrome. DNA chip microarray technology provides a method for examining the differential

expression of mRNA from a large number of genes. Our hypothesis was that a gene expression

signature, generated by microarray assays, could help identify genes which are dysregulated in

patients with post‐infectious CFS and so help identify biomarkers for the condition. METHODS:

Human genome‐wide Affymetrix GeneChip arrays (39,000 transcripts derived from 33,000 gene

sequences) were used to compare the levels of gene expression in the peripheral blood mononuclear

cells of male patients with post‐infectious chronic fatigue (n = 8) and male healthy control subjects (n

= 7). RESULTS: Patients and healthy subjects differed significantly in the level of expression of 366

genes. Analysis of the differentially expressed genes indicated functional implications in immune

modulation, oxidative stress and apoptosis. Prototype biomarkers were identified on the basis of

differential levels of gene expression and possible biological significance CONCLUSION: Differential

expression of key genes identified in this study offer an insight into the possible mechanism of chronic

fatigue following infection. The representative biomarkers identified in this research appear

promising as potential biomarkers for diagnosis and treatment.

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case

studies. However, data demonstrating scientific validation of epidemiological claims regarding

effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is

designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of

immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA)

antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on

chronic water‐immersion stress test for 10 min daily for 19 days and the immobility time was taken as

the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the

immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis

factor‐alpha (TNF‐alpha) levels. Concurrent treatment with curcumin resulted in significantly

decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative

stress as well as TNF‐alpha levels. These findings strongly suggest that during immunological

activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the

treatment of chronic fatigue syndrome.

OBJECTIVE: Chronic fatigue syndrome (CFS) is often associated with significant levels of disability.

Although fatigue and depression have been found to be independently related to severity of

ME Research UK — Database of Research Publications 2009

Haig‐Ferguson A,

Tucker P, Eaton N,

Hunt L, Crawley E.

Hamilton WT,

Gallagher AM,

Thomas JM, White


Fatigue Syndrome

Service, Royal

National Hospital

for Rheumatic

Diseases, Bath, UK.


Centre for Child

and Adolescent

Health, University

of Bristol, Bristol,

UK. andrew.haig‐



Academic Unit of

Primary Health

Care, University of

Bristol, Bristol, UK.

relation between

fatigue severity

and disability in

chronic fatigue



Memory and

attention problems

in children with

chronic fatigue

syndrome or



Risk markers for

both chronic

fatigue and

irritable bowel

5. Epub 2008 Nov


Arch Dis Child.



Epub 2008 Nov 11.

Psychol Med. 2009


21. Epub 2009 Apr


disability, it is not clear how these three factors are mutually related. The present study sought to

address this issue by specifically testing a model of mediation whereby depression was hypothesized

to influence relations between fatigue and disability. METHODS: Participants included 90 individuals

seeking treatment for CFS at a tertiary care facility. Each provided demographic information and

completed standardized measures of depression and fatigue severity, as well as a measure of

disability, which assessed difficulties in physical, psychosocial, and independence domains. RESULTS:

Analyses indicated that depression and fatigue were positively correlated with one another, as well as

all three disability domains. Analyses of mediation indicated that depression completely mediated the

relation between fatigue and psychosocial disability and partially mediated the relation between

fatigue and the other two disability domains. Indirect effects tests indicated that the inclusion of

depression in the statistical models was statistically meaningful. CONCLUSIONS: These results

replicate previous findings that fatigue and depression are independently related to disability in those

with CFS. A more complex statistical model, however, suggested that depression severity

substantially influenced the strength of the relation between fatigue and disability levels across a

range of domains, including complete mediation in areas involving psychosocial functioning. These

results may aid in clarifying contemporary conceptualizations of CFS and provide guidance in the

identification of appropriate treatment targets.

OBJECTIVE: To understand more about the problems children with chronic fatigue syndrome (CFS) or

myalgic encephalopathy (ME) experience with memory and attention, and to test the feasibility of

quantitative measurement of both memory and attention. DESIGN: Four‐item semistructured

questionnaire and neuropsychological test battery with 10 psychometric subtests. SETTING: Family

home of the child taking part. PATIENTS: 20 children with a diagnosis of CFS/ME experiencing memory

and/or concentration problems were recruited between April and October 2007 from a regional

CFS/ME clinical service (female 13; average age 13.5 years; range 8‐16). METHODS: Each child, parent

and teacher was asked to describe the child's memory and attention problems. Responses were

subject to thematic analysis by two independent researchers. In addition, each child completed a

battery of 10 tests to measure: processing speed; attention; immediate and delayed memory;

working memory; executive function. Raw scores were converted into age‐scaled scores and the

children's psychometric scores on the 10 tests taken were compared with normative data using t

tests. RESULTS: Children with CFS/ME, their parents and teachers described problems with focussed

attention, sustained attention, recall and stress. Scores for sustained attention (mean 8.1, 95% CI 6.3

to 9.9), switching attention (7.5, 5.5 to 9.4), divided attention (6.9, 5.5 to 8.2), auditory learning (8.2,

6.8 to 9.6) and immediate recall (8.7, 7.3 to 10.0) appeared lower than the normative mean of 10.

CONCLUSIONS: Children with CFS/ME appear to experience problems with attention, which may have

adverse implications for verbal memory. These cognitive problems may explain some of the

educational difficulties associated with CFS.

BACKGROUND: Fatigue syndromes and irritable bowel syndrome (IBS) often occur together.

Explanations include being different manifestations of the same condition and simply sharing some

symptoms. METHOD: A matched case‐control study in UK primary care, using data collected

prospectively in the General Practice Research Database (GPRD). The main outcome measures were:

ME Research UK — Database of Research Publications 2009

Hannonen P. Keski‐Suomen





19, 40620


Hardy SE. Division of

Geriatric Medicine,

University of

Pittsburgh School

of Medicine,



15213, USA.



syndromes: a

prospective case‐

control study in

primary care.

[Is diagnosing



in Finnish]


for the treatment

of depressive


including fatigue

and apathy, in

medically ill older

adults and

terminally ill




Am J Geriatr


2009 Feb;7(1):34‐


health‐care utilization, specific symptoms and diagnoses. Risk markers were divided into distant (from

3 years to 1 year before diagnosis) and recent (1 year before diagnosis). RESULTS: A total of 4388

patients with any fatigue syndrome were matched to two groups of patients: those attending for IBS

and those attending for another reason. Infections were specific risk markers for both syndromes,

with viral infections being a risk marker for a fatigue syndrome [odds ratios (ORs) 2.3‐6.3], with a

higher risk closer to onset, and gastroenteritis a risk for IBS (OR 1.47, compared to a fatigue

syndrome). Chronic fatigue syndrome (CFS) shared more distant risk markers with IBS than other

fatigue syndromes, particularly other symptom‐based disorders (OR 3.8) and depressive disorders (OR

2.3), but depressive disorders were a greater risk for CFS than IBS (OR 2.4). Viral infections were more

of a recent risk marker for CFS compared to IBS (OR 2.8), with gastroenteritis a greater risk for IBS (OR

2.4). CONCLUSIONS: Both fatigue and irritable bowel syndromes share predisposing risk markers, but

triggering risk markers differ. Fatigue syndromes are heterogeneous, with CFS sharing predisposing

risks with IBS, suggesting a common predisposing pathophysiology.

Fibromyalgia is a controversial pain syndrome with chronic widespread pain (occurring on both sides

of the body as well as axially below and above the waist) and unexplained fatigue as the

predominating features. Fibromyalgia involves lots of symptoms focusing on different organ systems.

In sensory examination the most significant finding is general allodynia. The widespread chronic pain

and tender points at certain locations as reported by the patient differentiate fibromyalgia patients

from those suffering from other diseases of the musculoskeletal system.

BACKGROUND: Depressive symptoms, fatigue, and apathy are common symptoms among medically ill

older adults and patients with advanced disease, and have been associated with morbidity and

mortality. Methylphenidate has been used to treat these symptoms because of its rapid effect.

Despite the long history of methylphenidate use for the treatment of depressive symptoms, fatigue,

and apathy, there is little definitive evidence to support its use. OBJECTIVE: The aim of this paper was

to review the efficacy and tolerability of methylphenidate in the treatment of depressive symptoms,

fatigue, and apathy in medically ill older adults and adults receiving palliative care. METHODS: English‐

language articles presenting systematic reviews, clinical trials, or case series describing the use of

methylphenidate for the treatment of depressive symptoms, fatigue, or apathy in medically ill older

adults or adults receiving palliative care were identified. The key words methylphenidate and either

depressive, depression, fatigue, or apathy were used to search the Cochrane Database, MEDLINE,

PsycINFO, and International Pharmaceutical Abstracts. Included articles addressed depressive

symptoms, fatigue, or apathy in (1) older adults (generally, age > or =65 years), particularly those with

comorbid medical illness; (2) adults receiving palliative care; and (3) adults with other chronic

illnesses. I excluded articles regarding treatment of depression in healthy young adults; bipolar

disorder and attention‐deficit/hyperactivity disorder; and narcolepsy, chronic fatigue syndrome, and

related disorders. RESULTS: A total of 19 controlled trials of methylphenidate in medically ill older

adults or patients in palliative care were identified. Unfortunately, their conflicting results, small

sample sizes, and poor methodologic quality limited the ability to draw inferences regarding the

efficacy of methylphenidate, although evidence of tolerability was stronger. The available evidence

ME Research UK — Database of Research Publications 2009

Harvey SB,

Wessely S, Kuh D,

Hotopf M.

Harvey SB,

Wessely S.

Harvey SB,

Wessely S.

Institute of

Psychiatry, King's

College London,

London, UK.



Institute of

Psychiatry, King's

College London,

The relationship

between fatigue

and psychiatric


evidence for the

concept of


Tired all the time:

can new research

on fatigue help


t on: Br J Gen

Pract. 2009



Chronic fatigue


identifying zebras

J Psychosom Res.



Epub 2009 Mar 3.

Br J Gen Pract.



BMC Med. 2009

Oct 12;7:58.

Comment on: BMC

suggests possible effectiveness of methylphenidate for depressive symptoms, fatigue, and apathy in

various medically ill populations. CONCLUSION: In the absence of definitive evidence of effectiveness,

trials of low‐dose methylphenidate in medically ill adults with depression, fatigue, or apathy, with

monitoring for response and adverse effects, are appropriate.

OBJECTIVE: Fatigue and psychiatric disorders frequently occur comorbidly and share similar

phenomenological features. There has been debate as to whether chronic fatigue, or neurasthenia,

should be considered an independent syndrome distinct from psychiatric disorders. We aimed to

establish whether persistent fatigue can occur independently from psychiatric disorders and to test

the hypothesis that fatigue without comorbid psychiatric symptoms has unique premorbid risk

factors. We also aimed to investigate the psychological outcome of any individuals with fatigue.

METHODS: The MRC National Survey of Health and Development was used to prospectively follow

5362 participants from birth. A sample of nonfatigued individuals without psychiatric disorder was

selected at age 36 and followed until age 43 years (n=2714). At age 43, the presence of new onset

fatigue and/or psychiatric disorder was assessed. Information on a number of potential premorbid

risk factors was collected between ages 0 and 36 years. Individuals with fatigue but no comorbid

psychiatric disorder were then followed up at age 53 years. RESULTS: At age 43 years, 201 (7.4%)

participants reported significant levels of new onset fatigue in the absence of comorbid psychiatric

disorder. Despite the absence of case level psychiatric disorder, these individuals did report increased

levels of some psychological symptoms. Excessive childhood energy (adjusted OR 2.63, 95% CI 1.55‐

4.48, P

ME Research UK — Database of Research Publications 2009

Häuser W,

Bernardy K,

Uçeyler N,

Sommer C.

Häuser W, Grulke

N, Michalski D,

Hoffmann A,

Akritidou I,

Klauenberg S,

Maier C, Hinz A.

London, UK.



Department of

Internal Medicine,



Winterberg 1, D‐






Zentrum für



nnere Medizin I,



amongst the


Treatment of


syndrome with

antidepressants: a


[Intensity of limb

pain and fatigue in




disorders and

Med. 2009;7:57. serious or easily treatable causes of fatigue being overlooked, whilst too many increases the risk of

iatrogenic harm and reduces the opportunity for early focused treatment. A paper by Jones et al

published this month in BMC Medicine may help clinicians in deciding how to undertake such

investigations. Their results suggest that if clinicians look for common psychiatric and medical

conditions in those complaining of prolonged fatigue, the rate of detection will be higher than

previously estimated. The most common co‐morbid condition identified was depression, suggesting a

simple mental state examination remains the most productive single investigation in any new person

presenting with unexplained fatigue. Currently, most diagnostic criteria advice CFS should not be

diagnosed when an active medical or psychiatric condition which may explain the fatigue is identified.

We discuss a number of recent prospective studies that have provided valuable insights into the

aetiology of chronic fatigue and describe a model for understanding chronic fatigue which may be

equally relevant regardless of whether or not an apparent medical cause for fatigue can be identified.

See the associated research paper by Jones et al: http://www.biomedcentral.com/1741‐7015/7/57.

JAMA. 2009 Jan


Schmerz. 2009


CONTEXT: Fibromyalgia syndrome (FMS) is a chronic pain disorder associated with multiple

debilitating symptoms and high disease‐related costs. Effective treatment options are needed.

OBJECTIVES: To determine the efficacy of antidepressants in the treatment of FMS by performing a

meta‐analysis of randomized controlled clinical trials. DATA SOURCES: MEDLINE, PsycINFO, Scopus,

and the Cochrane Library databases were searched through August 2008. Reference sections of

original studies, meta‐analyses, and reviews on antidepressants in FMS were reviewed. STUDY

SELECTION: Randomized placebo‐controlled trials with tricyclic and tetracyclic antidepressants (TCAs),

selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors

(SNRIs), and monoamine oxidase inhibitors (MAOIs) were analyzed. DATA EXTRACTION AND DATA

SYNTHESIS: Two authors independently extracted data. Effects were summarized using standardized

mean differences (SMDs) by a random‐effects model. RESULTS: Eighteen randomized controlled trials

(median duration, 8 weeks; range, 4‐28 weeks) involving 1427 participants were included. Overall,

there was strong evidence for an association of antidepressants with reduction in pain (SMD, ‐0.43;

95% confidence interval [CI], ‐0.55 to ‐0.30), fatigue (SMD, ‐0.13; 95% CI, ‐0.26 to ‐0.01), depressed

mood (SMD, ‐0.26; 95% CI, ‐0.39 to ‐0.12), and sleep disturbances (SMD, ‐0.32; 95% CI, ‐0.46 to ‐0.18).

There was strong evidence for an association of antidepressants with improved health‐related quality

of life (SMD, ‐0.31; 95% CI, ‐0.42 to ‐0.20). Effect sizes for pain reduction were large for TCAs (SMD, ‐

1.64; 95% CI, ‐2.57 to ‐0.71), medium for MAOIs (SMD, ‐0.54; 95% CI, ‐1.02 to ‐0.07), and small for

SSRIs (SMD, ‐0.39; 95% CI, ‐0.77 to ‐0.01) and SNRIs (SMD, ‐0.36; 95% CI, ‐0.46 to ‐0.25).

CONCLUSION: Antidepressant medications are associated with improvements in pain, depression,

fatigue, sleep disturbances, and health‐related quality of life in patients with FMS.

BACKGROUND: A symptom‐based diagnosis of fibromyalgia syndrome (FMS) without tender point

examination is needed for primary care. We tested if a symptom‐based diagnosis of FMS can be

founded on the intensity of the symptoms musculoskeletal pain and fatigue. METHODS: FMS patients

from 4 different settings (n=464 members of the German Fibromyalgia Association DFV, n=33 from a

private practice of rheumatology, n=36 from a tertiary care pain department, n=162 from medical

expertise), patients with depressive disorders from 2 different settings (n=24 from a university

ME Research UK — Database of Research Publications 2009

Heim C, Nater UM,

Maloney E,

Boneva R, Jones

JF, Reeves WC.

Hickie I,

Davenport T,

Vernon SD,

Nisenbaum R,

Reeves WC, Hadzi‐

Pavlovic D, Lloyd

A; International






Department of

Psychiatry and


Sciences, Emory

University School

of Medicine,



Research Bldg, Ste

4311, Atlanta, GA

30322, USA.



Brain and Mind

Research Institute,


NSW, Australia.



chronic back pain.

A criterion for


icle in German]

Childhood trauma

and risk for chronic

fatigue syndrome:

association with



Are chronic fatigue

and chronic fatigue

syndrome valid

clinical entities

across countries

and health‐care


Arch Gen

Psychiatry. 2009


Aust N Z J

Psychiatry. 2009


department of psychiatry, n=311 from an out‐patient university psychosomatic department), patients

with chronic back pain from an out‐patient training center (n=691) and persons from a representative

German population sample (n=1977) were compared using the subscales of the Giessen subjective

complaints list GBB 24. RESULTS: The greatest mean differences between FMS patients and the other

samples were found within the subscales "limb pains" and "fatigue". FMS patients scored higher in

the subscales "heart problems" and "dyspepsia", but both subscales did not contribute to a

differentiation of the samples. The rates of reclassification of the subsamples based on the subscales

"limb pains" and "fatigue" ranged between 80 and 93%. CONCLUSION: High levels of the intensity of

chronic widespread musculoskeletal pain and chronic fatigue may form the basis of a symptom‐based

diagnosis of FMS.

CONTEXT: Childhood trauma appears to be a potent risk factor for chronic fatigue syndrome (CFS).

Evidence from developmental neuroscience suggests that early experience programs the

development of regulatory systems that are implicated in the pathophysiology of CFS, including the

hypothalamic‐pituitary‐adrenal axis. However, the contribution of childhood trauma to

neuroendocrine dysfunction in CFS remains obscure. OBJECTIVES: To replicate findings on the

relationship between childhood trauma and risk for CFS and to evaluate the association between

childhood trauma and neuroendocrine dysfunction in CFS. Design, Setting, and PARTICIPANTS: A case‐

control study of 113 persons with CFS and 124 well control subjects identified from a general

population sample of 19 381 adult residents of Georgia. MAIN OUTCOME MEASURES: Self‐reported

childhood trauma (sexual, physical, and emotional abuse; emotional and physical neglect),

psychopathology (depression, anxiety, and posttraumatic stress disorder), and salivary cortisol

response to awakening. RESULTS: Individuals with CFS reported significantly higher levels of childhood

trauma and psychopathological symptoms than control subjects. Exposure to childhood trauma was

associated with a 6‐fold increased risk of CFS. Sexual abuse, emotional abuse, and emotional neglect

were most effective in discriminating CFS cases from controls. There was a graded relationship

between exposure level and CFS risk. The risk of CFS conveyed by childhood trauma further increased

with the presence of posttraumatic stress disorder symptoms. Only individuals with CFS and with

childhood trauma exposure, but not individuals with CFS without exposure, exhibited decreased

salivary cortisol concentrations after awakening compared with control subjects. CONCLUSIONS: Our

results confirm childhood trauma as an important risk factor of CFS. In addition, neuroendocrine

dysfunction, a hallmark feature of CFS, appears to be associated with childhood trauma. This possibly

reflects a biological correlate of vulnerability due to early developmental insults. Our findings are

critical to inform pathophysiological research and to devise targets for the prevention of CFS.

OBJECTIVE: The validity of the diagnosis of chronic fatigue syndrome and related chronic fatigue

states remains controversial, particularly in psychiatry. This project utilized international

epidemiological and clinical research data to test construct validity across diagnostic categories,

health‐care settings and countries. Relevant demographic, symptom and diagnostic data were

obtained from 33 studies in 21 countries. The subjects had fatigue lasting 1‐6 months (prolonged

fatigue), or >6 months (chronic fatigue), or met diagnostic criteria for chronic fatigue syndrome.

METHOD: Common symptom domains were derived by factor analytic techniques. Mean scores on

ME Research UK — Database of Research Publications 2009

Chronic Fatigue

Syndrome Study


Hokama Y,

Campora CE, Hara

C, Kuribayashi T,

Le Huynh D,

Yabusaki K.

Huang LC, Hsu SY,

Lin E.

Department of

Pathology, John A.

Burns School of


University of

Hawaii at Mânoa,

Honolulu, Hawaii

96822, USA.

Department of


National Taiwan

University Hospital

Yun‐Lin Branch,




Hui JS. Institute of

Acupuncture and

Moxibustion, China

Academy of

Chinese Medical

Sciences, Beijing

100700, China.


antibodies in the

sera of patients

with diagnosed

chronic fatigue


A comparison of


methods for

predicting Chronic

Fatigue Syndrome

based on genetic



treatment of

chronic fatigue


J Clin Lab Anal.


J Transl Med. 2009

Sep 22;7:81.

J Tradit Chin Med.



each symptom factor were compared across diagnostic categories, health‐care settings and countries.

RESULTS: Data were obtained on 37,724 subjects (n = 20,845 female, 57%), including from

population‐based studies (n = 15,749, 42%), studies in primary care (n = 19 472, 52%), and secondary

or specialist tertiary referral clinics (n = 2503, 7%). The sample included 2013 subjects with chronic

fatigue, and 1958 with chronic fatigue syndrome. A five‐factor model of the key symptom domains

was preferred ('musculoskeletal pain/fatigue', 'neurocognitive difficulties', 'inflammation', 'sleep

disturbance/fatigue' and 'mood disturbance') and was comparable across subject groups and settings.

Although the core symptom profiles were similar, some differences in symptoms were observed

across diagnostic categories, health‐care settings and between countries. CONCLUSIONS: The

construct validity of chronic fatigue and chronic fatigue syndrome is supported by an empirically

derived factor structure from existing international datasets.

Examination of anticardiolipin antibodies (ACAs) in the sera of patients clinically diagnosed with

chronic fatigue syndrome (CFS) using an enzyme‐linked immunoassay procedure demonstrated the

presence of immunoglobulin M isotypes in 95% of CFS serum samples tested. The presence of

immunoglobulin G and immunoglobulin A isotypes were also detected in a subset of the samples.

Future studies will focus on elucidating whether alterations to mitochondrial inner membranes

and/or metabolic functions play a possible role in the expression of ACAs.

BACKGROUND: In the studies of genomics, it is essential to select a small number of genes that are

more significant than the others for the association studies of disease susceptibility. In this work, our

goal was to compare computational tools with and without feature selection for predicting chronic

fatigue syndrome (CFS) using genetic factors such as single nucleotide polymorphisms (SNPs).

METHODS: We employed the dataset that was original to the previous study by the CDC Chronic

Fatigue Syndrome Research Group. To uncover relationships between CFS and SNPs, we applied three

classification algorithms including naive Bayes, the support vector machine algorithm, and the C4.5

decision tree algorithm. Furthermore, we utilized feature selection methods to identify a subset of

influential SNPs. One was the hybrid feature selection approach combining the chi‐squared and

information‐gain methods. The other was the wrapper‐based feature selection method. RESULTS: The

naive Bayes model with the wrapper‐based approach performed maximally among predictive models

to infer the disease susceptibility dealing with the complex relationship between CFS and SNPs.

CONCLUSION: We demonstrated that our approach is a promising method to assess the associations

between CFS and SNPs.

ME Research UK — Database of Research Publications 2009

Hurwitz BE,

Coryell VT, Parker

M, Martin P,

Laperriere A,

Klimas NG,

Sfakianakis GN,

Bilsker MS.


Medicine Research

Center, University

of Miami, Miami,

FL 33136, USA.



Inamitsu T. Section of


Medicine, Fukuoka

Dental College.

Jammes Y,

Steinberg JG,

Delliaux S,

Brégeon F.


(P2COE), Faculté

de Médecine,

Université de la


North Hospital,


Publique ‐

Chronic fatigue

syndrome: illness

severity, sedentary

lifestyle, blood

volume and

evidence of

diminished cardiac



somatic syndrome

in dental practice]

[Article in


Chronic fatigue



increased exercise‐

induced oxidative

stress and reduced

cytokine and Hsp


Clin Sci (Lond).

2009 Oct


Comment in: Clin

Sci (Lond). 2010


Nippon Rinsho.



J Intern Med. 2009


206. Epub 2009

May 19.

The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue

syndrome) cohort were present and linked to illness severity and sedentary lifestyle. Follow‐up

analyses assessed whether differences in cardiac output levels between CFS and control groups were

corrected by controlling for cardiac contractility and TBV (total blood volume). The 146 participants

were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non‐severe

(n=26), and two healthy non‐CFS control groups based on physical activity, sedentary (n=58) and non‐

sedentary (n=32). Controls were matched to CFS participants using age, gender, ethnicity and body

mass. Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac

volume (i.e. stroke index and end‐diastolic volume) and 25.1% lower contractility (velocity of

circumferential shortening corrected by heart rate) than the control groups. Dual tag blood volume

assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood

cell volume) than control groups. Of the CFS subjects with a TBV deficit (i.e. > or = 8% below ideal

levels), the mean+/‐S.D. percentage deficit in TBV, PV and RBCV were ‐15.4+/‐4.0, ‐13.2+/‐5.0 and ‐

19.1+/‐6.3% respectively. Lower cardiac volume levels in CFS were substantially corrected by

controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility

levels. Analyses indicated that the TBV deficit explained 91‐94% of the group differences in cardiac

volume indices. Group differences in cardiac structure were offsetting and, hence, no differences

emerged for left ventricular mass index. Therefore the findings indicate that lower cardiac volume

levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac

contractility levels, but were probably a consequence of a co‐morbid hypovolaemic condition. Further

study is needed to address the extent to which the cardiac and blood volume alterations in CFS have

physiological and clinical significance.

Functional somatic syndromes (FSSs) are common in dental as well as medical practice. Many patients

with unexplained symptoms in oro‐maxillo‐facial areas visit dentists, but they are not diagnosed and

treated properly. Temporomandibular disorder, atypical facial pain, and glossodynia (burning mouth

syndrome) are included in dental FSSs. These diseases overlap with each other and with FSSs in other

organs, such as myofacial pain syndrome, tension‐type headache, fibromyalgia, and chronic fatigue

syndrome. They coexist with mental disorders, such as anxiety disorder, mood disorder, and

somatoform disorder. Multidisciplinary and holistic approaches should be applied to dental FSSs;

pharmacological therapy (antidepressants), physical therapy, and cognitive‐behavioral therapy.

Clinicians have to support a patient in"enjoying his/her life with symptoms". Dental specialists in "oral

medicine" with psychosomatic viewpoints are now required.

OBJECTIVES: As heat shock proteins (Hsp) protect the cells against the deleterious effects of oxidative

stress, we hypothesized that Hsp expression might be reduced in patients suffering from chronic

fatigue syndrome (CFS) who present an accentuated exercise‐induced oxidative stress. DESIGN: This

case‐control study compared nine CFS patients to a gender‐, age‐ and weight‐matched control group

of nine healthy sedentary subjects. INTERVENTIONS: All subjects performed an incremental cycling

exercise continued until exhaustion. We measured ventilation and respiratory gas exchange and

evoked compound muscle potential (M‐wave) recorded from vastus lateralis. Repetitive venous blood

sampling allowed measurements of two markers of oxidative stress [thiobarbituric acid reactive

ME Research UK — Database of Research Publications 2009

Jason L, Benton M,

Torres‐Harding S,

Muldowney K.

Jason L, Porter N,

Shelleby E, Till L,

Bell DS, Lapp CW,

Rowe K, De

Meirleir K.

Jason LA, Roesner

N, Porter N,

Parenti B,

Mortensen J, Till L.

Hôpitaux de

Marseille, France.



DePaul University,

Center for


Research, Chicago,

IL 60614, USA.



Center for


Research, DePaul


Chicago, IL 60614,




The impact of

energy modulation

on physical

functioning and

fatigue severity

among patients

with ME/CFS.

Severe versus

Moderate criteria

for the new

pediatric case

definition for


DePaul University. Provision of social

support to

individuals with

chronic fatigue


Patient Educ

Couns. 2009


Epub 2009 Apr 8.

Comment in:

Patient Educ

Couns. 2009


Child Psychiatry

Hum Dev. 2009


Epub 2009 Jun 10.

J Clin Psychol. 2009

Nov 9. [Epub

ahead of print]

substances (TBARS) and reduced ascorbic acid (RAA)], two cytokines (IL‐6 and TNF‐alpha) and two Hsp

(Hsp27 and Hsp70) at rest, during maximal exercise and the 60‐min recovery period. RESULTS:

Compared with controls, resting CFS patients had low baseline levels of RAA and Hsp70. Their

response to maximal exercise associated (i) M‐wave alterations indicating reduced muscle membrane

excitability, (ii) early and accentuated TBARS increase accompanying reduced changes in RAA level,

(iii) absence of significant increase in IL‐6 and TNF‐alpha, and (iv) delayed and marked reduction of

Hsp27 and Hsp70 variations. The post‐exercise increase in TBARS was accentuated in individuals

having the lowest variations of Hsp27 and Hsp70. CONCLUSIONS: The response of CFS patients to

incremental exercise associates a lengthened and accentuated oxidative stress, which might result

from delayed and insufficient Hsp production.

OBJECTIVE: The energy envelope postulates that patients with Myalgic Encephalomyelitis/chronic

fatigue syndrome (ME/CFS) will improve functioning when maintaining expended energy levels at the

same level as available energy level. METHODS: Estimated weekly Energy Quotients were established

by dividing expended energy level by perceived energy level and multiplying by 100. Two groups of

patients were identified following participation in a non‐pharmacologic intervention trial. Some were

able to keep expended energy close to available energy and others were not successful at this task.

RESULTS: Those who were able to stay within their energy envelope had significant improvements in

physical functioning and fatigue severity. CONCLUSION: Findings suggest that helping patients with

ME/CFS maintain appropriate energy expenditures in coordination with available energy reserves can

help improve functioning over time. PRACTICE IMPLICATIONS: Health care professionals that treat

patients with ME/CFS might incorporate strategies that help patients self‐monitor and self‐regulate

energy expenditures.

The new diagnostic criteria for pediatric ME/CFS are structurally based on the Canadian Clinical Adult

case definition, and have more required specific symptoms than the (Fukuda et al. Ann Intern Med

121:953‐959, 1994) adult case definition. Physicians specializing in pediatric ME/CFS referred thirty‐

three pediatric patients with ME/CFS and 21 youth without the illness. Those who met ME/CFS

criteria were separated into Severe and Moderate categories. Significant differences were found for

symptoms within each of the six major categories: fatigue, post‐exertional malaise, sleep, pain,

neurocognitive difficulties, and autonomic/neuroendocrine/immune manifestations. In general, the

results showed participants who met the Severe ME/CFS criteria reported the highest scores, the

Moderate ME/CFS group show scores that were a little lower, and the control group evidenced the

lowest scores. Findings indicate that the Pediatric Case Definition for ME/CFS can distinguish between

those with this illness and controls, and between those with Severe versus Moderate manifestations

of the illness.

The present study evaluated a buddy program designed to provide support for individuals with

chronic fatigue syndrome (CFS). The intervention involved weekly visits by a student paraprofessional,

who helped out with tasks that needed to be done in an effort to reduce some of the taxing demands

and responsibilities that participants regularly encountered. This model of rehabilitation focused on

avoiding overexertion in persons with CFS, aiming to avoid setbacks and relapses while increasing

their tolerance for activity. Participants with CFS were randomly assigned to either a 4‐month buddy

ME Research UK — Database of Research Publications 2009

Jones JF, Lin JM,

Maloney EM,

Boneva RS, Nater

UM, Unger ER,

Reeves WC.

Jørstad RG, Nøjd


Kaabia N, Letaief


Chronic Viral

Diseases Branch,


Center for


Diseases, Centers

for Disease Control

and Prevention,

1600 Clifton Road,

MS A15, Atlanta,

GA 30333, USA.


Service de

médecine interne

An evaluation of



c conditions in the

definition of

chronic fatigue



claims following


vaccine B trial]

[Article in


ent on: Tidsskr

Nor Laegeforen.

2009 Mar


[Q Fever in Tunisia]

[Article in French]

BMC Med. 2009

Oct 12;7:57.

Comment in: BMC

Med. 2009;7:58.

Tidsskr Nor

Laegeforen. 2009



Pathol Biol (Paris).

2009 Jul;57(5):439‐

intervention or a control condition. Posttest results showed that individuals who received a student

buddy intervention had significantly greater reductions in fatigue severity and increases in vitality

than individuals in the control condition. There were no significant changes between groups for

physical functioning and stress. Buddy interventions that help patients with CFS reduce overexertion

and possibly remain within their energy envelopes can be thought of as representing a different

paradigm than nonpharmacologic interventions that focus only on increasing levels of activity through

graded exercise. (c) 2009 Wiley Periodicals, Inc. J Clin Psychol 66:1‐10, 2010.

BACKGROUND: The diagnosis of chronic fatigue syndrome (CFS) in research studies requires the

exclusion of subjects with medical and psychiatric conditions that could confound the analysis and

interpretation of results. This study compares illness parameters between individuals with CFS who

have and those who do not have exclusionary conditions. METHODS: We used a population‐based

telephone survey of randomly selected individuals, followed by a clinical evaluation in the study

metropolitan, urban, and rural counties of Georgia, USA. The medical and psychiatric histories of the

subjects were examined and they underwent physical and psychiatric examinations and laboratory

screening. We also employed the multidimensional fatigue inventory (MFI), the medical outcomes

survey short form‐36 (SF‐36) and the US Centres for Disease Control and Prevention symptom

inventory (SI). RESULTS: Twenty‐nine percent (1,609) of the 5623 subjects who completed the

detailed telephone interview reported exclusionary diagnoses and we diagnosed an exclusionary

condition in 36% of 781 clinically evaluated subjects. Both medical and psychiatric exclusionary

conditions were more common in women, blacks and participants from rural areas. Subjects with and

without exclusions had similar levels of fatigue and impairment as measured by the MFI and SF‐36;

those with CFS‐like illness (not meeting the formal CFS definition) were more likely to have an

exclusionary diagnosis. After adjusting for demographics, body mass index, fatigue subscales, SF‐36

subscales and CFS symptoms, CFS‐like illness did not remain significantly associated with having an

exclusionary diagnosis. CONCLUSION: Medical and psychiatric illnesses associated with fatigue are

common among the unwell. Those who fulfill CFS‐like criteria need to be evaluated for potentially

treatable conditions. Those with exclusionary conditions are equally impaired as those without


Q fever is a common zoonosis with almost a worldwide distribution caused by Coxiella burnetii. Farm

animals and pets are the main reservoirs of infection and transmission to humans is usually via

ME Research UK — Database of Research Publications 2009

Kane JM, Correll

CU, Goff DC,

Kirkpatrick B,

Marder SR, Vester‐

Blokland E, Sun W,

Carson WH,

Pikalov A,



Kang HK, Li B,

Mahan CM, Eisen

SA, Engel CC.

et maladies

infectieuses, CHU

Farhat‐Hached, rue


4000 Sousse,




Department of

Psychiatry, The

Zucker Hillside

Hospital, Glen

Oaks, NY 11004‐

1150, USA.


Department of

Veterans Affairs,




Washington DC

A multicenter,




controlled, 16‐

week study of


aripiprazole for

schizophrenia or




treated with

quetiapine or



Health of US

veterans of 1991

Gulf War: a follow‐

up survey in 10


43. Epub 2008 Jun


J Clin Psychiatry.




J Occup Environ

Med. 2009


inhalation of contaminated aerosols. Infection in humans is often asymptomatic, but it can manifest

as an acute disease (usually a self‐limited flu‐like illness, pneumonia or hepatitis) or as a chronic form

(mainly endocarditis, but also hepatitis and chronic‐fatigue syndrome). In Tunisia, although

prevalence of anti‐Coxiella burnetii was high among blood donors, Q fever was rarely reported and

frequently miss diagnosed by physicians. This study is a review of epidemiological and clinical

particularities of Q fever in Tunisia.

OBJECTIVE: Combining antipsychotics is common practice in the treatment of schizophrenia. This

study investigated aripiprazole adjunctive to risperidone or quetiapine for treating schizophrenia and

schizoaffective disorder. METHOD: In this multicenter, double‐blind, 16‐week, placebo‐controlled

study conducted at 43 American sites from July 2006 to October 2007, patients with chronic, stable

schizophrenia or schizoaffective disorder diagnosed with DSM‐IV‐TR were randomly assigned to

receive aripiprazole (2‐15 mg/d) or placebo in addition to a stable regimen of quetiapine (400‐800

mg/d) or risperidone (4‐8 mg/d). The primary outcome measure was the mean change from baseline

to endpoint (week 16, last observation carried forward) in the Positive and Negative Syndrome Scale

(PANSS) total score. RESULTS: 323 subjects being treated with either risperidone (n = 177) or

quetiapine (n = 146) were randomly assigned to receive adjunctive aripiprazole (n = 168) or placebo (n

= 155). Baseline characteristics were similar (mean PANSS total score: aripiprazole, 74.5; placebo,

75.9) except for history of suicide attempts (aripiprazole, 27%; placebo, 40%). Nearly 70% of subjects

in each arm completed the trial. Adjunctive aripiprazole and placebo groups were similar in the mean

change from baseline to endpoint in the PANSS total score (aripiprazole, ‐8.8; placebo, ‐8.9; P = .942).

The incidence of treatment‐emergent adverse events was similar between groups. Mean changes in

Simpson‐Angus Scale, Abnormal Involuntary Movement Scale, and Barnes Akathisia Rating Scale

scores were not statistically significantly different. Adjunctive aripiprazole was associated with

statistically significantly greater decreases in mean serum prolactin levels from baseline than was

adjunctive placebo (‐12.6 ng/mL for aripiprazole vs ‐2.2 ng/mL for placebo; P < .001), an effect that

was seen in the risperidone subgroup (‐18.7 ng/mL vs ‐1.9 ng/mL; P < .001) but not in the quetiapine

subgroup (‐3.01 ng/mL vs +0.15 ng/mL; P = .104). CONCLUSIONS: The addition of aripiprazole to

risperidone or quetiapine was not associated with improvement in psychiatric symptoms but was

generally safe and well tolerated. Further research is warranted to explore whether antipsychotic

combination therapy offers benefits to particular patient populations‐for example, in cases of

hyperprolactinemia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00325689. Copyright 2009

Physicians Postgraduate Press, Inc.

OBJECTIVE: To assess periodically the health status of a cohort of 1991 Gulf War veterans by

comparing various health outcomes with those of their military peers who were not deployed to the

Gulf. METHODS: We conducted a follow‐up health survey to collect health information among

population‐based samples of 30,000 veterans (15,000 Gulf War veterans and 15,000 Gulf Era

veterans) using a structured questionnaire. RESULTS: Gulf veterans reported significantly higher rates

of unexplained multi‐symptom illness, chronic fatigue syndrome‐like illness, posttraumatic stress

ME Research UK — Database of Research Publications 2009

20420, USA.


Karlsson I [Fatigue

syndromes do not

belong among

depressive and







2008 Nov 19‐


Kato K, Sullivan

PF, Evengård B,

Pedersen NL.

Kato YH, Yamate

M, Tsujikawa M,

Nishigaki H,

Tanaka Y, Yunoki

M, Kuratsune H,

Watanabe Y, Ikuta

School of Nursing

and Rehabilitation,


University of

Health and

Welfare at


Kanagawa, Japan.



A population‐

based twin study

of functional



No apparent

difference in the

prevalence of

parvovirus B19

infection between

chronic fatigue


2009 Jan 14‐


author reply 132.

Psychol Med. 2009


505. Epub 2008

Jun 26.

J Clin Virol. 2009


Epub 2009 Feb 5.

disorder, functional impairment, health care utilization, a majority of selected physical conditions and

all mental disorders queried during the survey than did Gulf Era veteran controls. CONCLUSIONS:

Fourteen years after deployment, 1991 Gulf War veterans continue to report a higher prevalence of

many adverse health outcomes, compared with Gulf Era veterans.


BACKGROUND: The mechanisms underlying the co‐occurrence of the functional somatic syndromes

are largely unknown. No empirical study has explicitly examined how genetic and environmental

factors influence the co‐morbidity of these syndromes. We aimed to examine how the co‐morbidity

of functional somatic syndromes is influenced by genetic and environmental factors that are in

common to the syndromes. METHOD: A total of 31318 twins in the Swedish Twin Registry aged 41‐64

years underwent screening interviews via a computer‐assisted telephone system from 1998 to 2002.

Four functional somatic syndromes (chronic widespread pain, chronic fatigue, irritable bowel

syndrome, and recurrent headache) and two psychiatric disorders (major depression and generalized

anxiety disorder) were assessed using structured questions based on standard criteria for each illness

in a blinded manner. RESULTS: Multivariate twin analyses revealed that a common pathway model

with two latent traits that were shared by the six illnesses fit best to the women's data. One of the

two latent traits loaded heavily on the psychiatric disorders, whereas the other trait loaded on all four

of the functional somatic syndromes, particularly chronic widespread pain, but not on the psychiatric

disorders. All illnesses except the psychiatric disorders were also affected by genetic influences that

were specific to each. CONCLUSIONS: The co‐occurrence of functional somatic syndromes in women

can be best explained by affective and sensory components in common to all these syndromes, as

well as by unique influences specific to each of them. The findings clearly suggest a complex view of

the multifactorial pathogenesis of these illnesses.

ME Research UK — Database of Research Publications 2009

K. syndrome patients

and healthy

controls in Japan.

Katz BZ, Shiraishi

Y, Mears CJ, Binns

HJ, Taylor R.

Department of

Pediatrics, Division

of Infectious




Feinberg School of

Medicine and


Memorial Hospital,

Chicago, Illinois

60614, USA.



Chronic fatigue

syndrome after


mononucleosis in


Kean S. Virology. Chronic

fatigue and

prostate cancer: a



Kelsall HL,

McKenzie DP, Sim

MR, Leder K,

Forbes AB, Dwyer


Monash Centre for

Occupational and



Department of

Epidemiology and


Medicine, Monash

University, Alfred






psychological, and


comorbidities of


illness in Australian

male veterans of

the 1991 Gulf War.

Pediatrics. 2009


Science. 2009 Oct


Am J Epidemiol.

2009 Oct


Epub 2009 Sep 17.

OBJECTIVE: The goal was to characterize prospectively the course and outcome of chronic fatigue

syndrome in adolescents during a 2‐year period after infectious mononucleosis. METHODS: A total of

301 adolescents (12‐18 years of age) with infectious mononucleosis were identified and screened for

nonrecovery 6 months after infectious mononucleosis by using a telephone screening interview.

Nonrecovered adolescents underwent a medical evaluation, with follow‐up screening 12 and 24

months after infectious mononucleosis. After blind review, final diagnoses of chronic fatigue

syndrome at 6, 12, and 24 months were made by using established pediatric criteria. RESULTS: Six, 12,

and 24 months after infectious mononucleosis, 13%, 7%, and 4% of adolescents, respectively, met the

criteria for chronic fatigue syndrome. Most individuals recovered with time; only 2 adolescents with

chronic fatigue syndrome at 24 months seemed to have recovered or had an explanation for chronic

fatigue at 12 months but then were reclassified as having chronic fatigue syndrome at 24 months. All

13 adolescents with chronic fatigue syndrome 24 months after infectious mononucleosis were female

and, on average, they reported greater fatigue severity at 12 months. Reported use of steroid therapy

during the acute phase of infectious mononucleosis did not increase the risk of developing chronic

fatigue syndrome. CONCLUSIONS: Infectious mononucleosis may be a risk factor for chronic fatigue

syndrome in adolescents. Female gender and greater fatigue severity, but not reported steroid use

during the acute illness, were associated with the development of chronic fatigue syndrome in

adolescents. Additional research is needed to determine other predictors of persistent fatigue after

infectious mononucleosis.

Multisymptom illness is more prevalent in 1991 Gulf War veterans than in military comparison

groups; less is known about comorbidities. The authors compared physical, psychological, and

functional comorbidities in Australian male Gulf War I veterans with those in actively (non‐Gulf)

deployed and nondeployed military personnel by using a questionnaire and medical assessment in

2000‐2002. Multisymptom illness was more common in male Gulf War veterans than in the

comparison group (odds ratio (OR) = 1.80, 95% confidence interval (CI): 1.48, 2.19). Stratifying by

deployment status in the comparison group made little difference in this association. Gulf War

veterans with multisymptom illness had increased psychiatric disorders, including major depression

(OR = 6.31, 95% CI: 4.19, 9.52) and posttraumatic stress disorder (OR = 9.77, 95% CI: 5.39, 18.59);

increased unexplained chronic fatigue (OR = 13.32, 95% CI: 7.70, 23.05); and more reported

functional impairment and poorer quality of life, but objective physical and laboratory outcomes were

similar to those for veterans without multisymptom illness. Similar patterns were found in the

comparison groups; differences across the 3 groups were statistically significant for only

ME Research UK — Database of Research Publications 2009

Kerr JR, Gough J,

Richards SC, Main

J, Enlander D,

McCreary M,

Komaroff AL, Chia


.monash.edu.au hospitalization, obstructive liver disease, and Epstein‐Barr virus exposure. Multisymptom illness is

more prevalent in Gulf War I veterans, but the pattern of comorbidities is similar for actively deployed

and nondeployed military personnel.

St George's

University of


Antibody to

parvovirus B19


protein is

associated with

chronic arthralgia

in patients with

Chronic Fatigue

Syndrome /




Kindlon T. Response to:


performance and

chronic pain in

chronic fatigue

syndrome: the role

of pain


Kindlon T. Change in grey

matter volume

cannot be

assumed to be due

to cognitive



Kindlon TP. Chronic fatigue

syndrome. Many

questions remain

about treatments

J Gen Virol.. [Epub

ahead of print]

Pain Med. 2009


author reply 1145‐

6. Epub 2009 Sep

9. Comment on:

Pain Med. 2008


Brain. 2009

Jul;132(Pt 7):e119;

author reply e120.

Epub 2009 Jan 29.

Comment on:

Brain. 2009


6):e110; author

reply e111.

BMJ. 2009 Apr

7;338:b1371. doi:



Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (CFS/ME) is a neuro‐immune disease of

uncertain pathogenesis. Human parvovirus B19 infection has been shown to occur just prior to

development of the onset of CFS/ME in several cases, although B19 seroprevalence studies do not

shown any significant differences between CFS/ME and controls. In this study, we analysed parvovirus

B19 markers in CFS/ME patients (n=200), diagnosed according to Fukuda CDC criteria, and normal

blood donors (n=200). Serum from each subject was tested for anti‐B19 VP2 IgM and IgG (by Biotrin

ELISA), anti‐B19 NS1 IgM and IgG (by immunoflourescence), and B19 DNA by real‐time PCR. CFS/ME

patients and normal blood donors had a similar B19 seroprevalence (75% versus 78%, respectively).

Eighty‐three CFS patients (41.5%) as compared with fourteen (7%) of normal blood donors tested

positive for anti‐B19 NS1 IgG (chi(2)= 64.8; P

ME Research UK — Database of Research Publications 2009

Knoop H, van der

Meer JW,

Bleijenberg G.

Kuitwaard K, Bos‐

Eyssen ME,


Markens PH, van

Doorn PA.

Department of


Erasmus MC,

University Medical

Center, Rotterdam,

The Netherlands.



Kumar A, Garg R. Pharmacology

Division, University

Institute of


Sciences, Panjab



160014, India.



Kuo YH, Tsai WJ,

Loke SH, Wu TS,

National Research

Institute of

for CFS.

Chronic fatigue in

Gulf War veterans:

should it be

treated as chronic

fatigue syndrome?


vaccinations and


symptoms in GBS

and CIDP.

Protective effects

of antidepressants

against chronic

fatigue syndrome‐

induced behavioral

changes and





Psychol Med. 2009


Epub 2009 Apr 23.

Comment on:

Psychol Med. 2008


J Peripher Nerv

Syst. 2009


Fundam Clin

Pharmacol. 2009


Epub 2009 Jan 10.

J Ethnopharmacol.

2009 Feb

We determined the frequency of recurrent Guillain‐Barré syndrome (GBS), whether vaccinations led

to recurrences of GBS or an increase of disability in chronic inflammatory demyelinating

polyradiculoneuropathy (CIDP) and we assessed the prevalence of pain, fatigue and the impact on

quality of life after GBS and CIDP. Additionally, we assessed the presence of common auto‐immune

disorders. Four hundred and sixty‐one members of the Dutch society of neuromuscular disorders

received a questionnaire. Two hundred and forty‐five GBS and seventy‐six CIDP patients were

included (response rate 70%). Nine patients had a confirmed recurrent GBS, and two patients had

experienced both GBS and CIDP. Common auto‐immune diseases were reported in 9% of GBS and 5%

of CIDP patients. None of the 106 GBS patients who received a flu vaccination (range 1‐37 times, total

775 vaccinations) reported a recurrence thereafter. Five out of twenty‐four CIDP patients who

received a flu vaccination (range 1‐17 times) reported an increase in symptoms. Pain or severe fatigue

was reported in about 70% of patients after the diagnosis of GBS (median 10 years) or after onset of

CIDP (median 6 years), and quality of life was significantly reduced. Flu vaccinations seem relatively

safe. GBS and CIDP patients often experience pain, fatigue and a reduced quality of life for many years

after the diagnosis.

Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes

with daily activities. The aim of this study was to explore the protective effects of antidepressants in

an animal model of CFS in mice. Male albino mice were forced to swim individually for a period of 6‐

min session each for 7 days. Imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg) and

citalopram (5 and 10 mg/kg) were administered 30 min before forced swimming test on each day.

Various behavior tests (immobility time, locomotor activity, anxiety‐like behavior by plus maze and

mirror chamber) followed by biochemical parameters (lipid peroxidation, reduced glutathione,

catalase and nitrite level) were assessed in chronic stressed mice. Chronic forced swimming for 7 days

significantly caused increase in immobility period, impairment in locomotor activity, anxiety‐like

behavior, and oxidative stress (raised lipid peroxidation, nitrite activity and reduced glutathione and

catalase activity) as compared with naïve mice (P < 0.05). Seven days of pretreatment with

imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg), and citalopram (5 and 10 mg/kg)

significantly reduced immobility time, improved locomotor activity and anti‐anxiety effect (in both

plus maze and mirror chamber test), and attenuated oxidative stress in chronic stressed mice as

compared with control (chronic fatigues) (P < 0.05). These results suggested that these drugs have

protective effect and could be used in the management of chronic fatigue like conditions.

AIM OF THE STUDY: Alteration of immune function may be associated with chronic fatigue syndrome

(CFS) and this study reveals the immunoregulatory effect of Astragalus membranaceus flavonoids

ME Research UK — Database of Research Publications 2009

Chiou WF. Chinese Medicine,

Taipei, Taiwan,


Kuwabara N, Itoh

Y, Igarshi T,

Fukunaga Y.

Lam MH, Wing YK,

Yu MW, Leung

CM, Ma RC, Kong

AP, So WY, Fong

SY, Lam SP.

Department of

Pediatrics, Nippon

Medical School,

Bunkyo City,

Tokyo, Japan.

Department of

Psychiatry, The

Chinese University

of Hong Kong,


flavonoids (AMF)

ameliorate chronic

fatigue syndrome

induced by food

intake restriction

plus forced


Autoantibodies to

lens epithelium‐

derived growth


n co‐activator P75

(LEDGF/P75) in

children with

chronic nonspecific

complaints and

with positive



Mental morbidities

and chronic fatigue

in severe acute



survivors: long‐

term follow‐up.


Epub 2008 Dec 6.




Arch Intern Med.

2009 Dec


(AMF). MATERIALS AND METHODS: CF rats were induced by food intake restriction plus forced

swimming for 6 weeks. RESULTS: An atrophied spleen associated with a significantly decreased

spleen/body weight ratio and a reduced spleen cells proliferation was found in CF rats when

compared with home cage controls. AMF given orally at 20, 50 and 100 mg/kg body weight once a

day consecutively for 6 weeks could recover the reduced cell proliferation. A switch to Th1‐dominated

immune regulation was observed in CF rats as the cultured splenocytes produced more interleukin‐2

(IL‐2) but less IL‐4 when compared with controls. Supplementation with AMF could significantly

counteract the aberrant cytokine production and rats received AMF exhibited higher endurance

capacity to swim when compared with those without AMF administration. Checking the spectrum

signals confirmed that the three major isoflavones contained in AMF were ononin, formononetin, and

demethylhomopterocarpin. CONCLUSION: Alterations of immune function may be associated with

CFS and the tonic effects of AMF against CF may be attributable to balance the abnormal cytokine

level by isoflavones.

Autoimmune fatigue syndrome (AIFS) is characterized by chronic nonspecific complaints, consistently

positive antinuclear antibodies (ANA), and lack of alternate medical explanations. A newly recognized

antibody, named anti‐Sa, was detected in approximately 40% of the patients by Western blot (WB)

using HeLa extract. Some patients with AIFS later develop chronic fatigue syndrome (CFS), and most

of them are positive for anti‐Sa. On the other hand, Muro et al. reported anti‐DFS70 in patients with

CFS. Anti‐Sa and anti‐DFS70 were turned out to be same specificities by exchanging studies of blind

sera. The target antigen of anti‐DFS70 was identified as lens epithelium derived growth

factor/transcription co‐activator p75 (LEDGF/p75). The objectives of this study are to confirm whether

the target antigen of anti‐Sa is also LEDGF/p75, and to develop ELISA system by using recombinant

protein. Recombinant protein of LEDGF/p75 was purchased from Protein One (Bethesda, MD, USA).

We developed an ELISA system to detect anti‐LEDGF/p75 by coating this recombinant protein. 226

sera of AIFS patients (including 36 CFS patients) were applied to this ELISA assay and Western

immunoblot, and it was revealed that anti‐Sa‐positive sera defined by WB and sera positive for anti‐

LEDGF/p75 on ELISA were identical. Moreover, reactivities of anti‐Sa on WB were inhibited by pre‐

incubating with recombinant LEDGF/p75, and eluted antibodies from the nitrocellulose membrane

could react on the ELISA. These results confirm that the Sa antigen is LEDGF/p75. The ELISA assay

using recombinant LEDGF/p75 could be a promising tool for measuring anti‐Sa and consequently for

diagnosing CFS.

BACKGROUND: Short‐term follow‐up studies of severe acute respiratory syndrome (SARS) survivors

suggested that their physical conditions continuously improved in the first year but that their mental

health did not. We investigated long‐term psychiatric morbidities and chronic fatigue among SARS

survivors. METHODS: All SARS survivors from the hospitals of a local region in Hong Kong were

assessed by a constellation of psychometric questionnaires and a semistructured clinical interview for

the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to determine the presence

of psychiatric disorders and chronic fatigue problems. RESULTS: Of 369 SARS survivors, 233 (63.1%)

participated in the study (mean period of time after SARS, 41.3 months). Over 40% of the respondents

had active psychiatric illnesses, 40.3% reported a chronic fatigue problem, and 27.1% met the

ME Research UK — Database of Research Publications 2009

Land ST. Loddon, Norwich,




Lansang MC,

Farmer T, Kennedy


Lee E, Cho S, Kim

K, Park T.

Department of

Medicine, Division

of Endocrinology,

University of


Gainesville, Florida

32610, USA.




Program in


Seoul National

University, Seoul,

Republic of Korea.


20 years ago: The



Journal, January


Diagnosing the



absorption of

intra‐articular and

epidural steroid


An integrated

approach to infer

causal associations

among gene



variation, and

Homeopathy. 2009


discussion 71‐2.

Endocr Pract. 2009



Genomics. 2009


Epub 2009 Jun 18.

modified 1994 Centers for Disease Control and Prevention criteria for chronic fatigue syndrome.

Logistic regression analysis suggested that being a health care worker at the time of SARS infection

(odds ratio [OR], 3.24; 95% confidence interval [CI], 1.12‐ 9.39; P = .03), being unemployed at follow‐

up (OR, 4.71; 95% CI, 1.50‐14.78; P = .008), having a perception of social stigmatization (OR, 3.03; 95%

CI, 1.20‐7.60; P = .02), and having applied to the SARS survivors' fund (OR, 2.92; 95% CI, 1.18‐7.22; P =

.02) were associated with an increased risk of psychiatric morbidities at follow‐up, whereas

application to the SARS survivors' fund (OR, 2.64; 95% CI, 1.07‐6.51; P = .04) was associated with

increased risk of chronic fatigue problems. CONCLUSIONS: Psychiatric morbidities and chronic fatigue

persisted and continued to be clinically significant among the survivors at the 4‐year follow‐up.

Optimization of the treatment of mental health morbidities by a multidisciplinary approach with a

view for long‐term rehabilitation, especially targeting psychiatric and fatigue problems and functional

and occupational rehabilitation, would be needed.

OBJECTIVE: To present a case series of patients who were misdiagnosed with endocrine disorders

because of failure to recognize the systemic absorption of intra‐articular and epidural steroids and to

discuss the utility of performing a urine screen to detect synthetic glucocorticoids. METHODS: In this

case series, we describe the clinical, laboratory, and imaging findings of 3 patients referred to our

clinic, each with a presumed endocrine disorder. RESULTS: Patient 1 was a 54‐year‐old woman with

weakness, loss of appetite, and a hormonal profile suggestive of hypopituitarism. Patient 2 was a 49‐

year‐old woman with chronic fatigue and history of physical abuse, whose history and test results

were compatible with growth hormone deficiency secondary to head trauma. Patient 3 was a 46‐

year‐old woman who was diagnosed with endogenous Cushing syndrome despite normal 24‐hour

urinary cortisol excretion. In each case, we subsequently elicited a history of intra‐articular or epidural

glucocorticoid injections, and a urine screen documented the presence of synthetic glucocorticoids.

Systemic absorption of the injected steroids was thus determined to be the cause of the symptoms

and abnormal laboratory findings in each case. CONCLUSIONS: The potential for harm from intra‐

articular and epidural glucocorticoid administration is underrecognized by physicians, leading to

expensive investigation, false diagnoses, and unnecessary treatment. A urine screen for synthetic

glucocorticoids is a valuable adjunct towards appropriate diagnosis.

Gene expression data and genotype variation data are now capable of providing genome‐wide

patterns across many different clinical conditions. However, the separate analysis of these data has

limitations in elucidating the complex network of gene interactions underlying complex traits, such as

common human diseases. More information about the identity of key driver genes of common

diseases comes from integrating these two heterogeneous types of data. We developed a two‐step

procedure to characterize complex diseases by integrating genotype variation data and gene

expression data. The first step elucidates the causal relationship among genetic variation, gene

ME Research UK — Database of Research Publications 2009

Lee P, Greenfield

JR, Campbell LV.

om disease. expression level, and disease. Based on the causal relationship determined at the first step, the

second step identifies significant gene expression traits whose effects on disease status or whose

responses to disease status are modified by the specific genotype variation. For the selected

significant genes, a pathway enrichment analysis can be performed to identify the genetic mechanism

of a complex disease. The proposed two‐step procedure was shown to be an effective method for

integrating three different levels of data, i.e., genotype variation, gene expression and disease status.

By applying the proposed procedure to a chronic fatigue syndrome (CFS) dataset, we identified a list

of potential causal genes for CFS, and found an evidence for difference in genetic mechanisms of the

etiology between CFS without 'a major depressive disorder with melancholic features' (CFS) and CFS

with 'a major depressive disorder with melancholic features' (CFS‐MDD/m). Especially, the SNPs

within NR3C1 gene were shown to differently influence the susceptibility of developing CFS and CFS‐

MDD/m through integrative action with gene expression levels.

Vitamin D


novel mechanism

of statin‐induced


Lemle MD. Hypothesis:

chronic fatigue

syndrome is

caused by

dysregulation of

hydrogen sulfide


Li H, Meng S,

Levine SM,

Stratton CW, Tang


Department of



University School

of Medicine,

Nashville, TN

37232, United




detection of


herpesvirus‐6 and


differentiation of

variants A and B.

Clin Endocrinol

(Oxf). 2009


Epub 2008 Oct 16.

Med Hypotheses.



Epub 2008 Sep 16.

J Clin Virol. 2009


Epub 2009 Jun 21.

BACKGROUND: The current limitations of laboratory testing for the detection of human herpesvirus

virus 6 (HHV‐6) in clinical specimens with low HHV‐6 viral loads make this area a priority for further

research and development. OBJECTIVES: To develop and validate a sensitive qualitative assay for

simultaneous HHV‐6 detection and variant differentiation. METHODS: We developed a diagnostic

procedure, which combines a magnetic bead‐based nucleic acid extraction, PCR amplification, and

colorimetric microtiter plate identification (MAG‐PCR‐EIA), for the sensitive detection of HHV‐6 and

the simultaneous differentiation of HHV‐6A and HHV‐6B. RESULTS: Analytic sensitivities of the MAG‐

PCR‐EIA assay were 10 copies per reaction for both HHV‐6A and HHV‐6B variants, which is equivalent

to 20 copies/ml when 1ml of clinical specimen was processed. A proficiency panel containing 11

blinded specimens covering HHV‐6A viral loads from 0 to 100,000 copies was tested, and the MAG‐

PCR‐EIA was able to detect the lowest concentration at one copy in 200microl. A panel of 27 urine

specimens, which were collected from patients with and without chronic fatigue syndrome, was

tested by the MAG‐PCR‐EIA. HHV‐6 was detected in two (HHV‐6A) patients who have chromosomally

integrated HHV‐6A and in one (HHV‐6B) patient who was a healthy control and diagnosed as cervical

cancer later on. The HHV‐6 results did not correlate with results previously determined by HHV‐6

antigenemia in urine. CONCLUSION: With large specimen volumes processed and an additional signal

ME Research UK — Database of Research Publications 2009

Li ZC, Zhao Y, Dou

ZH, Yu L, Wu H,

Zhang FJ.

Liang CZ, Li HJ,

Wang ZP, Xing JP,

Hu WL, Zhang TF,

Ge WW, Hao ZY,

Zhang XS, Zhou J,

Li Y, Zhou ZX, Tang

ZG, Tai S.

Department of


Diseases, Beijing

Youan Hospital,

Capital Medical

University, Beijing

100069, China.

Department of

Urology, The First

Affiliated Hospital

of Anhui Medical

University, Hefei,


[Clinical features of

66 children with




in Chinese]

The prevalence of


symptoms in


Zhongguo Dang

Dai Er Ke Za Zhi.

2009 Feb;11(2):93‐


J Urol. 2009


Epub 2009 Jun 13.

Comment in: J

Urol. 2009


amplification incorporated, the MAG‐PCR‐EIA provides a sensitive and qualitative system for HHV‐6

detection and simultaneous variant differentiation. Clinical relevance of the assay awaits further


OBJECTIVE: To study the clinical features of pediatric acquired immunodeficiency syndrome(AIDS).

METHODS: The epidemiological, clinical and laboratory data of 66 children with AIDS were

retrospectively studied. RESULTS: Of the 66 patients, 46 (69.7%) were male and 20 (30.3%) were

female, with a mean age of 8.7 years (ranged 2‐16 years). The mean age at diagnosis was 7.7 years

(ranged 2‐15 years). Vertical transmission as the route of infection was documented in 48 cases

(72.7%). Fourteen children (21.2%) were infected through blood or blood products. The route of

infection could not be identified in 4 cases (6.1%). Body weight loss was noted in 43 cases (65.2%),

anemia in 42 cases (63.7%), fever in 40 cases (60.6%), fatigue in 38 cases (57.6%), rash in 31 cases

(47.0%), chronic cough in 28 cases (12.1%), chronic diarrhea in 24 cases (36.4%), CNS involvement in

16 cases (24.2%), oral thrush in 13 cases (19.7%), and hepatosplenomegaly in 12 cases (18.2%). Body

height of 30 cases (45.4%) and body weight of 26 cases (39.4%) ranked the lower level. The immune

system was severely suppressed in 59 cases (89.4%) and moderately suppressed in 7 cases (10.6%).

CONCLUSIONS: Vertical transmission remained the most common route of pediatric HIV infection.

There were various clinical manifestations in children with AIDS. The immune systems of the majority

of children with this disorder were severely suppressed.

PURPOSE: We studied the prevalence of prostatitis‐like symptoms and identified their associated risk

factors in a population based Chinese sample. MATERIALS AND METHODS: A volunteer group of

15,000 eligible men residing in Beijing, Anhui, Xi'an, Guangzhou and Gansu cities or provinces were

invited randomly to take part in the survey to complete a questionnaire that elicited information

regarding sociodemographics, Eysenck personality questionnaire, current stress and health ratings,

lifestyle, medical history, expressed prostatic secretion evaluation, score of the National Institutes of

Health Chronic Prostatitis Symptom Index and International Index of Erectile Function‐5. RESULTS:

Information on 12,743 (84.95%) men was collected. Of these men 1,071 (8.4%) reported prostatitis‐

like symptoms (mean National Institutes of Health Chronic Prostatitis Symptom Index pain score 7.55

+/‐ 3.22). The percent of chronic prostatitis was 4.5% (571) among the symptoms group according to

past urological history and expressed prostatic secretion evaluation. Subjects with prostatitis‐like

symptoms (mean age 34.56 +/‐ 13.48 years) had higher mean pain and urinary symptoms scores (7.53

+/‐ 3.22 and 2.84 +/‐ 2.72, respectively) compared with subjects without prostatitis‐like symptoms

(1.18 +/‐ 2.32 and 0.72 +/‐ 1.66 for pain and urinary symptoms scores, respectively, mean age 30.7 +/‐

10.17) (pain and symptoms scores, p

ME Research UK — Database of Research Publications 2009

Baltzan M, Rizzo

D, Fichten CS,

Bailes S.

Light AR, White

AT, Hughen RW,

Light KC.

Lim JY, Kim KE,

Choe G.

Psychiatry, SMBD‐

Jewish General




Montreal, Quebec,




Department of


University of Utah,

Salt Lake City, Utah

84132‐2304, USA.



Department of


Seoul National

University College

of Medicine, Seoul

National University

Bundang Hospital,


Lin E, Hsu SY. Vita Genomics,

Inc., Jung‐Shing

Road, Wugu


functioning in

chronic fatigue


Moderate exercise


expression for


adrenergic, and

immune genes in

chronic fatigue

syndrome patients

but not in normal






syndrome in a

polio survivor.

A Bayesian

approach to gene‐

gene and gene‐




J Pain. 2009


112. Epub 2009 Jul


Am J Phys Med

Rehabil. 2009



s. 2009


considered a chronic fatigue syndrome (CFS) comorbidity, rather than a diagnostic exclusion criterion;

and (2) to compare sleep/wake/ psychopathology in individuals with CFS, controls and another illness.

Participants (CFS, SAHS, controls) completed questionnaires and were evaluated for SAHS; 68 percent

were subsequently diagnosed with SAHS. CFS participants with and without SAHS did not differ. Both

clinical groups were less well adjusted than controls. We conclude that SAHS should not be an

exclusion criterion for CFS and that psychological problems in CFS seem a consequence of coping with


Chronic fatigue syndrome (CFS) is characterized by debilitating fatigue, often accompanied by

widespread muscle pain that meets criteria for fibromyalgia syndrome (FMS). Symptoms become

markedly worse after exercise. Previous studies implicated dysregulation of the sympathetic nervous

system (SNS), and immune system (IS) in CFS and FMS. We recently demonstrated that acid sensing

ion channel (probably ASIC3), purinergic type 2X receptors (probably P2X4 and P2X5) and the

transient receptor potential vanilloid type 1 (TRPV1) are molecular receptors in mouse sensory

neurons detecting metabolites that cause acute muscle pain and possibly muscle fatigue. These

molecular receptors are found on human leukocytes along with SNS and IS genes. Real‐time,

quantitative PCR showed that 19 CFS patients had lower expression of beta‐2 adrenergic receptors

but otherwise did not differ from 16 control subjects before exercise. After a sustained moderate

exercise test, CFS patients showed greater increases than control subjects in gene expression for

metabolite detecting receptors ASIC3, P2X4, and P2X5, for SNS receptors alpha‐2A, beta‐1, beta‐2,

and COMT and IS genes for IL10 and TLR4 lasting from 0.5 to 48 hours (P < .05). These increases were

also seen in the CFS subgroup with comorbid FMS and were highly correlated with symptoms of

physical fatigue, mental fatigue, and pain. These new findings suggest dysregulation of metabolite

detecting receptors as well as SNS and IS in CFS and CFS‐FMS. PERSPECTIVE: Muscle fatigue and pain

are major symptoms of CFS. After moderate exercise, CFS and CFS‐FMS patients show enhanced gene

expression for receptors detecting muscle metabolites and for SNS and IS, which correlate with these

symptoms. These findings suggest possible new causes, points for intervention, and objective

biomarkers for these disorders.

We describe a 38‐yr‐old polio survivor with newly developed weakness from myotonic dystrophy. He

suffered muscle atrophy and weakness in his legs as a result of poliomyelitis at the age of 3 yrs. After

a stable interval of about 30 yrs, he felt new weakness and fatigue in his legs. Electromyography

revealed generalized myotonic discharges, early recruitment, and findings of chronic denervation in

his left leg. Genetic testing was consistent with myotonic dystrophy type 1. A biopsy from the right

gastrocnemius revealed findings of both myotonic dystrophy and chronic denervation. This case

report shows the importance of considering other uncommon conditions in the differential diagnoses

of postpolio syndrome.

INTRODUCTION: In the study of genomics, it is essential to address gene‐gene and gene‐environment

interactions for describing the complex traits that involves disease‐related mechanisms. In this work,

our goal is to detect gene‐gene and gene‐environment interactions resulting from the analysis of

ME Research UK — Database of Research Publications 2009

Lin JM, Brimmer

DJ, Boneva RS,

Jones JF, Reeves


Shiang, Taipei,




Chronic Viral

Diseases Branch,

National Center for

Zoonotic, Vector‐

Borne and Enteric

Diseases, Centers

for Disease Control

and Prevention,

Atlanta, GA 30333,




interactions in

chronic fatigue


Barriers to


utilization in

fatiguing illness: a


study in Georgia.

BMC Health Serv

Res. 2009 Jan


chronic fatigue syndrome patients' genetic and demographic factors including SNPs, age, gender and

BMI. MATERIALS & METHODS: We employed the dataset that was original to the previous study by

the Centers for Disease Control and Prevention Chronic Fatigue Syndrome Research Group. To

investigate gene‐gene and gene‐environment interactions, we implemented a Bayesian based

method for identifying significant interactions between factors. Here, we employed a two‐stage

Bayesian variable selection methodology based on Markov Chain Monte Carlo approaches. RESULTS:

By applying our Bayesian based approach, NR3C1 was found in the significant two‐locus gene‐gene

effect model, as well as in the significant two‐factor gene‐environment effect model. Furthermore, a

significant gene‐environment interaction was identified between NR3C1 and gender. These results

support the hypothesis that NR3C1 and gender may play a role in biological mechanisms associated

with chronic fatigue syndrome. CONCLUSION: We demonstrated that our Bayesian based approach is

a promising method to assess the gene‐gene and gene‐environment interactions in chronic fatigue

syndrome patients by using genetic factors, such as SNPs, and demographic factors such as age,

gender and BMI.

BACKGROUND: The purpose of this study was to determine the prevalence of barriers to healthcare

utilization in persons with fatiguing illness and describe its association with socio‐demographics, the

number of health conditions, and frequency of healthcare utilization. Furthermore, we sought to

identify what types of barriers interfered with healthcare utilization and why they occurred.

METHODS: In a cross‐sectional population‐based survey, 780 subjects, 112 of them with chronic

fatigue syndrome (CFS), completed a healthcare utilization questionnaire. Text analysis was used to

create the emerging themes from verbatim responses regarding barriers to healthcare utilization.

Multiple logistic regression was performed to examine the association between barriers to healthcare

utilization and other factors. RESULTS: Forty percent of subjects reported at least one barrier to

healthcare utilization. Of 112 subjects with CFS, 55% reported at least one barrier to healthcare

utilization. Fatiguing status, reported duration of fatigue, insurance, and BMI were significant risk

factors for barriers to healthcare utilization. After adjusting for socio‐demographics, medication use,

the number of health problems, and frequency of healthcare utilization, fatiguing status remained

significantly associated with barriers to healthcare utilization. Subjects with CFS were nearly 4 times

more likely to forego needed healthcare during the preceding year than non‐fatigued subjects while

those with insufficient fatigue (ISF) were nearly 3 times more likely.Three domains emerged from text

analysis on barriers to healthcare utilization: 1) accessibility; 2) knowledge‐attitudes‐beliefs (KABs);

and, 3) healthcare system. CFS and reported duration of fatigue were significantly associated with

each of these domains. Persons with CFS reported high levels of healthcare utilization barriers for

each domain: accessibility (34%), healthcare system (25%), and KABs (19%). In further examination of

barrier domains to healthcare utilization, compared to non‐fatigued persons adjusted ORs for CFS

having "accessibility", "KAB" and "Healthcare System" barrier domains decreased by 40%, 30%, and

19%, respectively. CONCLUSION: Barriers to healthcare utilization pose a significant problem in

persons with fatiguing illnesses. Study results suggested two‐fold implications: a symptom‐targeted

model focusing on symptoms associated with fatigue; and an interactive model requiring efforts from

patients and providers to improve interactions between them by reducing barriers in accessibility,

ME Research UK — Database of Research Publications 2009

Lin JM, Brimmer

DJ, Maloney EM,

Nyarko E, Belue R,

Reeves WC.

Lombardi VC,

Ruscetti FW, Das

Gupta J, Pfost MA,

Hagen KS,

Peterson DL,

Ruscetti SK, Bagni

RK, Petrow‐

Sadowski C, Gold

B, Dean M,

Silverman RH,

Mikovits JA.

Lorusso L,

Mikhaylova SV,

Capelli E, Ferrari D,

Ngonga GK,

Ricevuti G.

Chronic Viral

Diseases Branch,

National Center for

Zoonotic, Vector‐

borne and Enteric

Diseases, Centers

for Disease Control

and Prevention,

Mail Stop A‐15,

1600 Clifton Rd,

NE, Atlanta, GA,




Peterson Institute,

Reno, NV 89557,


Department of

Neurology, Mellino

Mellini Hospital,

Chiari, Brescia,


Further validation

of the


Fatigue Inventory

in a US adult

population sample.

Detection of an


retrovirus, XMRV,

in blood cells of

patients with

chronic fatigue



aspects of chronic

fatigue syndrome.

Popul Health Metr.

2009 Dec 15;7:18.

Science. 2009 Oct


9. Epub 2009 Oct

8. Comment in:

Science. 2009 Oct



Autoimmun Rev.

2009 Feb;8(4):287‐

91. Epub 2008 Sep


KABs, and healthcare system.

ABSTRACT: BACKGROUND: The Multidimensional Fatigue Inventory (MFI‐20) was developed in 1995.

Since then, it has been widely used in cancer research and cancer‐related illnesses but has never been

validated in fatiguing illnesses or in a large US population‐selected sample. In this study, we sought to

examine the reliability and validity of the MFI‐20 in the population of the state of Georgia, USA.

Further, we assessed whether the MFI‐20 could serve as a complementary diagnostic tool in

chronically fatigued and unwell populations. METHODS: The data derive from a cross‐sectional

population‐based study investigating the prevalence of chronic fatigue syndrome (CFS) in Georgia.

The study sample was comprised of three diagnostic groups: CFS‐like (292), chronically unwell (269),

and well (222). Participants completed the MFI‐20 along with several other measures of psychosocial

functioning, including the Medical Outcomes Survey Short Form‐36 (SF‐36), the Zung Self‐Rating

Depression Scale (SDS), and the Spielberger State‐Trait Anxiety Inventory (STAI). We assessed the five

MFI‐20 subscales using several criteria: inter‐item correlations, corrected item‐total correlations,

internal consistency reliability (Cronbach's alpha coefficients), construct validity, discriminant (known‐

group) validity, floor/ceiling effects, and convergent validity through correlations with the SF‐36, SDS,

and STAI instruments. RESULTS: Averaged inter‐item correlations ranged from 0.38 to 0.61, indicating

no item redundancy. Corrected item‐total correlations for all MFI‐20 subscales were greater than

0.30, and Cronbach's alpha coefficients achieved an acceptable level of 0.70. No significant

floor/ceiling effect was observed. Factor analysis demonstrated factorial complexity. The MFI‐20 also

distinguished clearly between three diagnostic groups on all subscales. Furthermore, correlations with

depression (SDS), anxiety (STAI), and functional impairment (SF‐36) demonstrated strong convergent

validity. CONCLUSIONS: This study provides support for the MFI‐20 as a valuable tool when used in

chronically unwell and well populations. It also suggests that the MFI‐20 could serve as a

complementary diagnostic tool in fatiguing illnesses, such as CFS.

Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to

affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS

patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus‐

related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell

culture experiments revealed that patient‐derived XMRV is infectious and that both cell‐associated

and cell‐free transmission of the virus are possible. Secondary viral infections were established in

uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B

cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may

be a contributing factor in the pathogenesis of CFS.

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterises unexplained disabling

fatigue and a combination of non‐specific accompanying symptoms for at least 6 months, in the

absence of a medical diagnosis that would otherwise explain the clinical presentation. Other common

symptoms include headaches, myalgia, arthralgia, and post‐exertional malaise; cognitive difficulties,

with impaired memory and concentration; unrefreshing sleep; and mood changes. Similar disorders

ME Research UK — Database of Research Publications 2009

Lundin A. FoUU‐sektionen,

Psykiatri Nordöst,






Lyle N, Gomes A,

Sur T, Munshi S,

Paul S, Chatterjee

S, Bhattacharyya


Department of


Institute of Post

Graduate Medical

Education &

Research, 244‐B, A.

J. C. Bose Road,

Kolkata 700020,




[Chronic fatigue

syndrome‐‐a useful

diagnosis?] [Article

in Swedish]

The role of


properties of


jatamansi in

alleviation of the

symptoms of the

chronic fatigue



2009 Sep 2‐



Behav Brain Res.

2009 Sep


Epub 2009 Apr 16.

have been described for at least two centuries and have been differently named neurasthenia, post‐

viral fatigue, myalgic encephalomyelitis and chronic mononucleosis. Recent longitudinal studies

suggest that some people affected by chronic fatigue syndrome improve with time but that most

remain functionally impaired for several years. The estimated worldwide prevalence of CFS is 0.4‐1%

and it affects over 800,000 people in the United States and approximately 240,000 patients in the UK.

No physical examination signs are specific to CFS and no diagnostic tests identify this syndrome. The

pathophysiological mechanism of CFS is unclear. The main hypotheses include altered central nervous

system functioning resulting from an abnormal immune response against a common antigen; a

neuroendocrine disturbance; cognitive impairment caused by response to infection or other stimuli in

sentient people. The current concept is that CFS pathogenesis is a multifactorial condition. Various

studies have sought evidence for a disturbance in immunity in people with CFS. An alteration in

cytokine profile, a decreased function of natural killer (NK) cells, a presence of autoantibodies and a

reduced responses of T cells to mitogens and other specific antigens have been reported. The

observed high level of pro‐inflammatory cytokines may explain some of the manifestations such as

fatigue and flu‐like symptoms and influence NK activity. Abnormal activation of the T lymphocyte

subsets and a decrease in antibody‐dependent cell‐mediated cytotoxicity have been described. An

increased number of CD8+ cytotoxic T lymphocytes and CD38 and HLA‐DR activation markers have

been reported, and a decrease in CD11b expression associated with an increased expression of CD28+

T subsets has been observed. This review discusses the immunological aspects of CFS and offers an

immunological hypothesis for the disease processes.

An experimental model of chronic fatigue syndrome (CFS) is utilized for evaluation of antidepressant,

anti‐stress effects, wherein the rat is forced to swim in water for 15 min/day on 21 consecutive days.

Rats were divided into stressed control, stressed plus standard drug (Panax ginseng) and stressed plus

200 and 500 mg/kg of test drug, i.e., Nardostachys jatamansi extract (NJE) given orally. The immobility

during each 5 min periods of 0‐5, 5‐10 and 10‐15 min of stress were noted. Similarly the climbing

(struggling) behaviour was noted in the above four groups of rats in intervals of 5 min. The locomotor

activity and also the anxiety state in animals were evaluated in an elevated plus maze after CFS in all

the four groups. There was a significant increase in despair behaviour and anxiety in stressed control

animals on successive days of CFS. Locomotor activity gradually decreased in stressed control group.

Treatment with NJE (200 and 500 mg/kg) significantly reversed both paradigms. Biochemical analysis

showed that CFS significantly increased lipid peroxidation, nitrite and superoxide dismutase levels and

decreased catalase level in rat brain. Administration of NJE (200 and 500 mg/kg) tended to normalize

both augmented lipid peroxidation, nitrite, superoxide dismutase activities and catalase level

ME Research UK — Database of Research Publications 2009

Maes M,

Mihaylova I,

Kubera M,

Uytterhoeven M,

Vrydags N,

Bosmans E.

Maes Clinics,

Antwerp, Belgium.



Maes M, Twisk FN. Maes Clinics,

Antwerp, Belgium.



Increased 8‐


deoxyguanosine, a

marker of

oxidative damage

to DNA, in major

depression and



/ chronic fatigue


Why myalgic


chronic fatigue


(ME/CFS) may kill

you: disorders in

the inflammatory

and oxidative and

nitrosative stress

(IO&NS) pathways

may explain


disorders in


Neuro Endocrinol

Lett. 2009 Dec

30;30(6). [Epub

ahead of print]

Neuro Endocrinol

Lett. 2009 Dec

30;30(6). [Epub

ahead of print]

significantly. NJE per se has an antioxidant effect. The results indicate that CFS may lead to oxidative

stress, which is mitigated by NJE and so its antioxidant property may be responsible for anti‐stress

effect of NJE.

There is now evidence that major depression and myalgic encephalomyelitis / chronic fatigue

syndrome (ME/CFS) are accompanied by partially overlapping pathophysiological mechanisms, i.e.

activation of various inflammatory and oxidative & nitrosative (IO&NS) pathways. The aim of the

present study was to examine the urinary excretion of 8‐hydroxy‐deoxyguanosine (8‐OhdG), a marker

of oxidative damage to DNA, in depression; ME/CFS; and depression and ME/CFS. Toward this end,

morning urine was sampled for the assays of 8‐OHdG and creatinine, in 44 patients with ME/CFS; 25

with major depression; 23 with depression and ME/CFS; and 17 normal controls. Severity of fatigue

and somatic symptoms was measured by means of the Fibromyalgia and CFS Rating (FF) scale. We

found that 49.0% of the variance in the urinary excretion of 8‐OHdG was predicted by the regression

on creatinine. Consequently, the urinary 8‐OHdG excretion should be expressed as the residualized 8‐

OHdG values after partialling out the effects of creatinine and not by computing the 8‐OHdG /

creatinine ratio. We found that the residualized urinary excretion of 8‐OHdG (adjusted for creatinine)

was significantly higher in patients with depression and ME/CFS than in normal controls and all other

patients. In the patient group, there were significant correlations between the urinary 8‐OHdG and

the total score on the FF scale and sadness and flu‐like malaise. The findings show increased

oxidatively generated DNA damage in patients with major depression and ME/CFS and, therefore,

further extent the role played by IO&NS pathways in the pathophysiology of both disorders. Since

oxidatively damage to DNA is a risk factor for atherosclerosis and neurodegeneration, our results also

explain previous findings on increased cardiovascular morbidity in depression and ME/CFS, and

neurodegenerative processes in depression.

There is evidence that disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways and

a lowered antioxidant status are important pathophysiological mechanisms underpinning myalgic

encephalomyelitis / chronic fatigue syndrome (ME/CFS). Important precipitating and perpetuating

factors for ME/CFS are (amongst others) bacterial and viral infections; bacterial translocation due to

an increased gut permeability; and psychological stress. Recently, Jason et al (2006) reported that the

mean age of patients with myalgic encephalomyelitis/chronic fatigue syndrome dying from heart

failure, i.e. 58.7 years, is significantly lower than the age of those dying from heart failure in the

general US population, i.e. 83.1 years. These findings implicate that ME/CFS is a risk factor to cardio‐

vascular disorder. This review demonstrates that disorders in various IO&NS pathways provide

explanations for the earlier mortality due to cardiovascular disorders in ME/CFS. These pathways are:

a) chronic low grade inflammation with extended production of nuclear factor kappa B and COX‐2 and

increased levels of tumour necrosis factor alpha; b) increased O&NS with increased peroxide levels,

and phospholipid oxidation including oxidative damage to phosphatidylinositol; c) decreased levels of

specific antioxidants, i.e. coenzyme Q10, zinc and dehydroepiandrosterone‐sulphate; d) bacterial

translocation as a result of leaky gut; e) decreased omega‐3 polyunsatutared fatty acids (PUFAs), and

increased omega‐6 PUFA and saturated fatty acid levels; and f) the presence of viral and bacterial

infections and psychological stressors. The mechanisms whereby each of these factors may contribute

ME Research UK — Database of Research Publications 2009

Maes M, Twisk FN. Maes Clinics,

Antwerp, Belgium.


Maes M. Clinical Research

Centre of Mental

Health (CRC‐MH),

Antwerp, Belgium.


Maes M. Maes Clinics,

Antwerp, Belgium.



Chronic fatigue

syndrome: la bête

noire of the

Belgian health care


Inflammatory and

oxidative and

nitrosative stress



chronic fatigue,

somatization and



"Functional" or


symptoms, e.g. a

flu‐like malaise,

Neuro Endocrinol



Curr Opin

Psychiatry. 2009


Neuro Endocrinol

Lett. 2009 Nov

29;30(5). [Epub

ahead of print]

towards cardio‐vascular disorder in ME/CFS are discussed. ME/CFS is a multisystemic metabolic‐

inflammatory disorder. The aberrations in IO&NS pathways may increase the risk for cardiovascular


The World Health Organization acknowledges Myalgic Encephalomyelitis (ME)/Chronic Fatigue

Syndrome (CFS) to be a medical illness. ME/CFS is characterized by disorders in the inflammatory and

oxidative and nitrosative stress (IO&NS) pathways. In 2002, the Belgian government started with the

development of CFS "Reference Centers", which implement a "psychosocial" model. The medical

practices of these CFS Centers are defined by the Superior Health Council, e.g. treatment should be

based upon Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET); and biological

assessments and treatments of ME/CFS should not be employed. Recently, the Belgian government

has evaluated the outcome of the treatments at the CFS Centers. They concluded that a

"rehabilitation therapy" with CBT/GET yielded no significant efficacy in the treatment of ME/CFS and

that CBT/GET cannot be considered to be curative therapies. In case reports, we have shown that

patients who were "treated" at those CFS centers with CBT/GET in fact suffered from IO&NS

disorders, including intracellular inflammation, an increased translocation of gram‐negative

enterobacteria (leaky gut), autoimmune reactions and damage by O&NS. Considering the fact that

these findings are exemplary for ME/CFS patients and that GET may even be harmful, it means that

many patients are maltreated by the Belgian CFS Centers. Notwithstanding the above, the

government and the CFS Centers not only continue this unethical and immoral policy, but also

reinforce their use of CBT/GET in patients with ME/CFS treated at those Centers.

PURPOSE OF REVIEW: The aim of this paper is to review recent findings on inflammatory and

oxidative and nitrosative stress (IO&NS) pathways in chronic fatigue and somatization disorder.

RECENT FINDINGS: Activation of IO&NS pathways is the key phenomenon underpinning chronic

fatigue syndrome (CFS): intracellular inflammation, with an increased production of nuclear factor

kappa beta (NFkappabeta), cyclo‐oxygenase‐2 (COX‐2) and inducible NO synthase (iNOS); and damage

caused by O&NS to membrane fatty acids and functional proteins. These IO&NS pathways are

induced by a number of trigger factors, for example psychological stress, strenuous exercise, viral

infections and an increased translocation of LPS from gram‐bacteria (leaky gut). The 'psychosomatic'

symptoms experienced by CFS patients are caused by intracellular inflammation (aches and pain,

muscular tension, fatigue, irritability, sadness, and the subjective feeling of infection); damage caused

by O&NS (aches and pain, muscular tension and fatigue); and gut‐derived inflammation (complaints

of irritable bowel). Inflammatory pathways (monocytic activation) are also detected in somatizing

disorder. SUMMARY: 'Functional' symptoms, as occurring in CFS and somatization, have a genuine

organic cause, that is activation of peripheral and central IO&NS pathways and gut‐derived

inflammation. The development of new drugs, aimed at treating those disorders, should target these

IO&NS pathways.

FULL TITLE: "Functional" or "psychosomatic" symptoms, e.g. a flu‐like malaise, aches and pain and

fatigue, are major features of major and in particular of melancholic depression: time to amend the

diagnostic criteria for major depression and the rating scales that measure severity of illness.

BACKGROUND: Major depression is characterized by multifarious symptoms and symptoms clusters,

ME Research UK — Database of Research Publications 2009

Magnus P,

Brubakk O, Nyland

H, Wold BH,

Gjessing HK,

Brandt I, Eidem T,

Nøkleby H, Stene‐

Larsen G.

Maloney EM,

Boneva R, Nater

UM, Reeves WC.

Division of



Institute of Public

Health, Oslo,




Chronic Viral

Diseases Branch,

National Center for

Zoonotic, Vector‐

borne and Enteric

Diseases, Centers

for Disease Control

and Prevention,

1600 Clifton Road,

MS A‐15, Atlanta,

aches and pain and

fatigue, are major

features of major

and in particular of


depression: time

to amend the

diagnostic criteria

for major

depression and.

Vaccination as

teenagers against


disease and the

risk of the chronic

fatigue syndrome.

Chronic fatigue

syndrome and high

allostatic load:

results from a


case‐control study

in Georgia.

Vaccine. 2009 Jan

1;27(1):23‐7. Epub

2008 Nov 5.

Psychosom Med.



Epub 2009 May 4.

such as the melancholic and anxiety symptom clusters. There is a strong comorbidity and a biological

similarity between major depression and myalgic encephalomyelitis / chronic fatigue syndrome

(ME/CFS). AIM: The aim of the present study was to examine "psychosomatic" symptoms reminiscent

of ME/CFS in major depression. Toward this end, we examined the 12‐item Fibromyalgia and Chronic

Fatigue Syndrome Rating (FF) Scale and the Hamilton Depression Rating Scale (HDRS) in 103 major

depressed patients by means of multivariate pattern recognition methods. RESULTS: Our findings

support the existence of two factors, i.e. a fatigue and somatic (F&S) factor, i.e aches and pain,

muscular tension, fatigue, concentration difficulties, failing memory, irritability, irritable bowel,

headache, and a subjective experience of infection; and a depression factor, i.e. sadness, irritability,

sleep disorders, autonomic symptoms, and a subjective experience of infection. Cluster analysis

performed on the 12 FF items found two different clusters, which were separated by highly significant

differences in the F&S items, the most significant being a subjective experience of infection, aches

and pain, muscular tension, fatigue, concentration difficulties and failing memory. Multivariate

analyses showed that the differences between both clusters were quantitatively, and not

qualitatively, and reflected the severity of the F&S dimension. There was a strong association

between the F&S symptoms and melancholia and chronic depression. Treatment resistant depression

was characterized by higher scores on the depression factor score. There was a strong correlation

between the HDRS score and the FF items, fatigue, a subjective experience of infection, and sadness.

CONCLUSIONS: Our findings show that F&S symptoms are a major feature of depression and largely

predict severity of illness, and chronic and melancholic depression. It is concluded that the diagnostic

criteria of depression and melancholia and rating scales to measure severity of illness should be

modified to include the F&S symptom profile.

The etiology of chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) is unknown. In

Norway, a vaccine against Neisseria meningitides group B was administered to teenagers in 1988‐‐

1989 in a protection trial. In order to estimate the relative risk of CFS/ME according to vaccine history,

we conducted a case‐control study in 2007, with 201 cases diagnosed at one of two hospitals and 389

controls. The adjusted odds ratio for CFS/ME was 1.06 (95% CI: 0.67‐1.66) for subjects who received

the active vaccine contrasted to subjects who did not. Using this design, no statistically significant

association between vaccination against meningococcal disease in teenagers and occurrence of

CFS/ME could be observed.

OBJECTIVE: To confirm the association of chronic fatigue syndrome (CFS) with high allostatic load (AL)

level, examine the association of subsyndromal CFS with AL level, and investigate the effect of

depression on these relationships and the association of AL with functional impairment, fatigue,

symptom severity, fatigue duration, and type of CFS onset. AL represents the cumulative physiologic

effect of demands to adapt to stress. METHODS: Population‐based case‐control study of 83 persons

with CFS, 202 persons with insufficient symptoms or fatigue for CFS (ISF), and 109 well controls living

in Georgia. Unconditional logistic regression was used to generate odds ratios (ORs) as measures of

the association of AL with CFS. RESULTS: Relative to well controls, each 1‐point increase in allostatic

load index (ALI) was associated with a 26% increase in likelihood of having CFS (OR(adjusted) = 1.26,

95% Confidence Interval (CI) = 1.00, 1.59). This association remained in the presence and absence of

ME Research UK — Database of Research Publications 2009

Mantovani G,

Macciò A,

Madeddu C, Serpe

R, Antoni G, Massa

E, Dessì M,

Panzone F.

Marchesini G,

Bianchi G.

Marmion BP,

Sukocheva O,

Storm PA,

Lockhart M, Turra

M, Kok T, Ayres J,

Routledge H,

Graves S.

GA 30333, USA.


Department of

Medical Oncology,

University of

Cagliari, Cagliari,




Q fever Research

Group, SA


Institute, Adelaide,




Phase II


study of the

efficacy and safety

of COX‐2 inhibitor

celecoxib on

patients with

cancer cachexia.

Nonalcoholic fatty

liver disease:

Disease and


effects on quality

of life.

Q fever:

persistence of

antigenic non‐

viable cell residues

of Coxiella burnetii

in the host‐‐

implications for

post Q fever

infection fatigue

syndrome and

other chronic

J Mol Med. 2009

Oct 3. [Epub ahead

of print]

Nat Rev


Hepatol. 2009


QJM. 2009


84. Epub 2009 Jun

25. Comment in:

QJM. 2009


depression (OR(adjusted) = 1.35, CI = 1.07, 1.72; OR(adjusted) = 1.35, CI = 1.10, 1.65). Compared with

the ISF group, each 1‐point increase in ALI was associated with a 10% increase in likelihood of having

CFS (OR(adjusted) = 1.10, CI = 0.93, 1.31). Among persons with CFS, the duration of fatigue was

inversely correlated with ALI (r = ‐.26, p = .047). CONCLUSIONS: Compared with well controls, persons

with CFS were significantly more likely to have a high AL. AL increased in a gradient across well, ISF,

and CFS groups.

Chronic inflammation is one of the main features of cancer cachexia. Experimental and clinical studies

showed that cyclooxygenase‐2 inhibitors, such as celecoxib, may be beneficial in counteracting major

symptoms of this devastating syndrome. We carried out a prospective phase II clinical trial to test the

safety and effectiveness of an intervention with the COX‐2 inhibitor celecoxib (300 mg/day for 4

months) on key variables of cachexia (lean body mass, resting energy expenditure, serum levels of

proinflammatory cytokines, and fatigue) in patients with advanced cancer at different sites. A sample

of 24 patients was enrolled from January to December 2008 and all were deemed assessable. A

significant increase of lean body mass and a significant decrease of TNF‐alpha were observed.

Moreover, an improvement of grip strength, quality of life, performance status, and Glasgow

prognostic score was shown. There were no grade 3/4 toxicities. Patient compliance was very good;

no patient had to reduce the celecoxib dosage nor interrupt treatment. Our results showed that the

COX‐2 selective inhibitor celecoxib is an effective single agent for the treatment of cancer cachexia.

Although the treatment of cancer cachexia, a multifactorial syndrome, is more likely to yield success

with a multitargeted approach; in the present study, we were able to show that a treatment, such as

celecoxib, addressing a single target, albeit very important as chronic inflammation, could have

positive effects. Therefore, phase III clinical trials are warranted to test the efficacy and safety of


Nonalcoholic fatty liver disease has long been neglected by health‐care professionals unless affected

patients develop cirrhosis; however, new research shows this disease impairs health‐related quality of

life. The association of nonalcoholic fatty liver disease with chronic metabolic diseases and

cardiovascular complications restricts our ability to define a specific role for liver damage in the poor

perceived health status of these patients.

BACKGROUND: Our previous studies of persistence of Coxiella burnetii in humans after an initial acute

Q fever infection revealed raised, maintained antibody levels and low levels of coxiella genomic DNA

at the age of 5 years from onset in Australian patients and at 12 years in patients in the 1989

Birmingham UK Q fever outbreak. Attempts to isolate the coxiella in standard cell culture and

susceptible mice by serial passage of PCR positive PBMC and bone marrow were negative. AIM: To

retest PCR positive patient samples by more sensitive methods for viable coxiellas and for the coxiella

cell components of antigen and specific lipopolysaccharide (LPS). To re‐interpret the previous results

in the light of the new information. To review the pertinent literature for a concept of an immuno‐

modulatory complex generated by the current studies. DESIGN: Laboratory case study. METHODS:

Stored patient samples were inoculated into SCID mice that were followed for 60 days. Mouse spleen

and liver samples were then examined by PCR assay for targets in the COM1 and IS1111a sequences

ME Research UK — Database of Research Publications 2009

Martinez D, Cassol

CM, Rahmeier L.

Mathew SJ, Mao

X, Keegan KA,

Levine SM, Smith

EL, Heier LA,

Otcheretko V,

Coplan JD, Shungu


Matsuda Y, Matsui

T, Kataoka K,

Fukada R, Fukuda

S, Kuratsune H,

Department of

Psychiatry, Mount

Sinai School of

Medicine, New

York, NY, USA.

Department of


Osaka City


sequelae. and for antigens by IFA with a polyclonal rabbit antiserum to C. burnetii Phase 1 and a monoclonal

antiserum to Phase 1 LPS (details; O. Sukocheva et al., unpublished data). RESULTS: All specimens,

including a recently excised heart valve from a Birmingham patient with late developing endocarditis,

were infection negative in SCID mice. Dilutions of SCID mouse spleen and liver homogenates titrated

in PCR assays were negative at dilutions attained by control mice inoculated with an endpoint dilution

of a viable prototype strain of C. burnetii. Sections of the spleens from all specimens showed a

complex of coxiella antigen‐LPS by IFA. DISCUSSION/REVIEW: We advance a concept of long‐term

persistence of a non‐infective, non‐biodegraded complex of coxiella cell components with its antigens

and specific LPS [so called Immunomodulatory complex (IMC)] associated with traces of genomic DNA

that signalled its presence in our earlier studies. The IMC's survival in patients for at least 12 years,

and in one patient for 70 years implies a capacity for serial passage in macrophages with effective

down‐regulation of their biodegrading functions. The review assesses the compatibility of the IMC

concept in relation to cogent literature on C. burnetii interactions with macrophage and cell‐mediated

immunity. Some remaining gaps in our knowledge of the organ sites and duration of carriage of viable

coxiellas after initial infection are also identified.

How much sleep

apnea is too



cerebrospinal fluid

lactate is increased

in chronic fatigue


compared with

generalized anxiety

disorder: an in vivo

3.0 T (1)H MRS

imaging study.

A two‐year follow‐

up study of chronic

fatigue syndrome

comorbid with

Arthritis Res Ther.


author reply 410‐1.

Epub 2009 Jul 15.

Comment on:

Arthritis Res Ther.


NMR Biomed.



Psychiatry Clin

Neurosci. 2009


Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the

illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders. We

compared lateral ventricular volumes derived from tissue‐segmented T(1)‐weighted volumetric MRI

data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging ((1)H

MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with

those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched

group‐wise for age, sex, body mass index, handedness, and IQ. Mean lateral ventricular lactate

concentrations measured by (1)H MRSI in CFS were increased by 297% compared with those in GAD

(P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling

for ventricular volume, which did not differ significantly between the groups. Regression analysis

revealed that diagnosis accounted for 43% of the variance in ventricular lactate. CFS is associated with

significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence

of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress

abnormalities in the disorder.

AIMS: Chronic fatigue syndrome patients often have comorbid psychiatric disorders such as major

depressive disorders and anxiety disorders. However, the outcomes of chronic fatigue syndrome and

the comorbid psychiatric disorders and the interactions between them are unknown. Therefore, a

two‐year prospective follow‐up study was carried out on chronic fatigue syndrome patients with

ME Research UK — Database of Research Publications 2009

Tajima S,

Yamaguti K, Kato

YH, Kiriike N.

Maurer MS,

Cuddihy P,

Weisenberg J,

Delisle S, Strong

BM, Gao Q,

Kachnowski S,

Howell J.

Graduate School of

Medicine, Osaka,






Department of



University Medical

Center, New York,

New York, USA.





The prevalence

and impact of

anergia (lack of

energy) in subjects

with heart failure

and its associations

with actigraphy.

J Card Fail. 2009


Epub 2008 Dec 6.

comorbid psychiatric disorders. METHODS: A total of 155 patients who met the Japanese case

definition of chronic fatigue syndrome were enrolled in this study. Comorbid psychiatric disorders

were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition

criteria. Patients with comorbid psychiatric disorders received psychiatric treatment in addition to

medical therapy for chronic fatigue syndrome. Seventy patients participated in a follow‐up interview

approximately 24 months later. RESULTS: Of the 70 patients with chronic fatigue syndrome, 33

patients were diagnosed as having comorbid psychiatric disorders including 18 major depressive

disorders. Sixteen patients with psychiatric disorders and eight patients with major depressive

disorders did not fulfill the criteria of any psychiatric disorders at the follow up. As for chronic fatigue

syndrome, nine out of the 70 patients had recovered at the follow up. There is no significant influence

of comorbid psychiatric disorders on the outcome of chronic fatigue syndrome. CONCLUSIONS:

Chronic fatigue syndrome patients have a relatively high prevalence of comorbid psychiatric

disorders, especially major depressive disorders. The outcomes of chronic fatigue syndrome and

psychiatric disorders are independent. Therefore treatment of comorbid psychiatric disorders is

necessary in addition to the medical treatment given for chronic fatigue syndrome.

BACKGROUND: Anergia (lack of energy) is a newly delineated, criterion‐based geriatric syndrome.

Because heart failure (HF) is a common chronic condition among older adults and a because a cardinal

symptom of HF is reduced energy, we characterized the degree of anergia in subjects with HF and

evaluated its relevance to disease severity, functional performance, and quality of life. METHODS AND

RESULTS: Prospective 3‐month cohort study among a convenience sample of 61 subjects (61 +/‐ 15

years, 48% women, ejection fraction 41 +/‐ 16%) with New York Heart Association (NYHA) Class I‐III HF

were studied. The criterion for anergia was based on the major criterion "sits around for lack of

energy" and any 2 of 6 minor criteria. Principal measures in addition to demographic and clinical

characteristics included functional performance (NYHA class, 6‐minute walk, cardiopulmonary

exercise testing), plasma B‐type natriuretic peptide, and quality of life (SF‐12 and Minnesota Living

with Heart Failure Questionnaire). To evaluate the relevance of anergia to daily function, each subject

wore an Actigraph, a watch‐like wrist device that continuously and automatically monitors patient

activity levels and energy expenditure, for 3 months. Anergia was prevalent in 39% of this population.

Anergia was associated with decrements in functional capacity (higher NYHA Class and lower 6‐

minute walk distance) as well as reduction in quality of life, but was not associated with ejection

fraction. Actigraphy data demonstrated that HF subjects with anergia spent significantly less time

performing moderate physical activity and the peak activity counts per day were significantly lower

than HF subjects without anergia. Additionally, the amplitude of circadian rhythm was lower,

suggesting altered sleep and activity patterns in HF subjects with anergia compared with those

without anergia. Over the 3 months of follow‐up, there was a significant association between anergia

and intercurrent hospitalization. CONCLUSIONS: Anergia is significantly associated with several of the

cardinal domains of HF. Its presence is associated with demonstrable differences in both physical

activity and circadian rhythm as measured by actigraphy and an increased risk of hospitalizations.

Accordingly, anergia may be a target for intervention among HF subjects.

May M, Emond A, Bristol University, Phenotypes of Arch Dis Child. OBJECTIVE: To investigate the heterogeneity of chronic fatigue syndrome (CFS/ME) in children and

ME Research UK — Database of Research Publications 2009

Crawley E. United Kingdom. Chronic Fatigue

Syndrome in

Children and

Young People.

McKay PG, Duffy

T, Martin CR.

Mease PJ, Clauw

DJ, Gendreau RM,

Rao SG, Kranzler J,

Chen W, Palmer


School of Health,

Nursing and


University of West

of Scotland, Ayr,




Associates, 1101

Madison Street,

Suite 1000, Seattle,

WA 98104, USA.



Are chronic fatigue

syndrome and

fibromyalgia the

same? Implications

for the provision of


mental health


The efficacy and

safety of

milnacipran for

treatment of

fibromyalgia. a




trial.Erratum in:

2009 Oct 19. [Epub

ahead of print]

J Psychiatr Ment

Health Nurs. 2009


J Rheumatol. 2009


young people. SETTING: Regional specialist CFS/ME service. Patients: Children and young people aged

< 19 years old. METHODS: Exploratory factor analysis was performed on symptoms present at

assessment in 333 children and young people with CFS/ME. Linear and logistic regression analysis of

data from self completed assessment forms was used to explore the associations between the

retained factors and sex, age, length of illness, depression, anxiety and markers of severity (fatigue,

physical function, pain and school attendance). RESULTS: Three phenotypes were identified using

factor analysis: Musculoskeletal (Factor 1) had loadings on muscle and joint pain and hypersensitivity

to touch, and was associated with worse fatigue (regression coefficient 0.47, 95% CI 0.25, 0.68, p

ME Research UK — Database of Research Publications 2009

Mease PJ. Seattle



Swedish Medical

Center, Seattle,

Washington, USA.



Meeus M,

Mistiaen W,

Lambrecht L, Nijs


Department of

Health Sciences,



31, 2170 Merksem,


J Rheumatol. 2009


Further strategies

for treating

fibromyalgia: the

role of serotonin







between cancer

and chronic fatigue

syndrome: the

common link to


Am J Med. 2009



Anticancer Res.




treated patients met criteria as FM responders versus placebo (milnacipran 200 mg/day, p = 0.017;

milnacipran 100 mg/day, p = 0.028). A significantly higher percentage of patients treated with

milnacipran 200 mg/day also met criteria as FM pain responders versus placebo (p = 0.032).

Significant pain reductions were observed after Week 1 with both milnacipran doses. At 15 weeks,

milnacipran 200 mg/day led to significant improvements over placebo in pain (realtime, daily and

weekly recall; all measures, p < 0.05), PGIC (p < 0.001), fatigue (p = 0.016), cognition (p = 0.025), and

multiple SF‐36 domains. Milnacipran was safe and well tolerated by the majority of patients during 27

weeks of treatment; nausea and headache were the most common adverse events. CONCLUSION:

Milnacipran is safe and effective for the treatment of multiple symptoms of FM.

Fibromyalgia and associated conditions such as irritable bowel syndrome and temporomandibular

disorder involve dysfunctions in central sensitization and pain modulation. Central nervous system

dysfunction may also contribute to other symptoms characteristic of fibromyalgia, such as fatigue and

sleep disturbance. Two key neurotransmitters in the pain modulation pathway are serotonin and

norepinephrine. Preclinical studies using animal models of chronic pain have shown that

pharmacologic agents that combine serotonergic and noradrenergic reuptake inhibition, thus

augmenting the function of these neurotransmitters, have stronger analgesic effects than agents that

inhibit reuptake of either neurotransmitter alone. Although tricyclic antidepressants (TCAs) inhibit

reuptake of both serotonin and norepinephrine and have shown efficacy for the treatment of

fibromyalgia, long‐term use of these drugs is limited owing to poor tolerability. Unlike TCAs, the

newer dual reuptake inhibitors of serotonin and norepinephrine, such as the drugs approved by the

US Food and Drug Administration (FDA) for fibromyalgia, milnacipran and duloxetine, do not possess

significant affinity for other neurotransmitter systems, resulting in diminished side effects and

enhanced tolerability. Both duloxetine and milnacipran have shown efficacy in clinical trials by

improving pain and other symptoms associated with fibromyalgia. Both compounds inhibit the

serotonin and norepinephrine transporters; however, there is a difference in their affinities and

selectivity for these transporters. Although duloxetine has affinity for both receptors, it is somewhat

more selective for the serotonin transporter. In contrast, milnacipran is somewhat more selective for

norepinephrine than serotonin reuptake inhibition. Pharmacologic agents that specifically target

serotonin and norepinephrine reuptake may prove to be valuable tools in the treatment of

fibromyalgia. (c) 2009 Elsevier Inc.

Cancer and chronic fatigue syndrome (CFS) are both characterised by fatigue and severe disability.

Besides fatigue, certain aspects of immune dysfunctions appear to be present in both illnesses. In this

regard, a literature review of overlapping immune dysfunctions in CFS and cancer is provided. Special

emphasis is given to the relationship between immune dysfunctions and fatigue. Abnormalities in

ribonuclease (RNase) L and hyperactivation of nuclear factor kappa beta (NF‐kappaB) are present in

CFS and in prostate cancer. Malfunctioning of natural killer (NK) cells has long been recognised as an

important factor in the development and reoccurrence of cancer, and has been documented

repeatedly in CFS patients. The dysregulation of the RNase L pathway, hyperactive NF‐kappaB leading

to disturbed apoptotic mechanisms and oxidative stress or excessive nitric oxide, and low NK activity

may play a role in the two diseases and in the physiopathology of the common symptom fatigue.

ME Research UK — Database of Research Publications 2009

Menzies V, Lyon


Million M, Lepidi

H, Raoult D.

CNRS, UMR 6236,

IRD 198, unité de

recherche sur les


infectieuses et



faculté de


université de la

Méditerranée, 27,

boulevard Jean‐

Moulin, 13385

Marseille cedex 05,




Integrated Review

of the Association

of Cytokines With

Fibromyalgia and

Fibromyalgia Core


[Q fever: current

diagnosis and


options][Article in


Miwa K, Fujita M. Increased oxidative

stress suggested

by low serum

Biol Res Nurs. 2009

Nov 22. [Epub

ahead of print]

Med Mal Infect.

2009 Feb;39(2):82‐

94. Epub 2008 Nov


Int J Cardiol. 2009

Aug 14;136(2):238‐

9. Epub 2008 Aug

However, in cancer the relation between the immune dysfunctions and fatigue has been poorly

studied. Immunological abnormalities to such as a dysregulated RNase L pathway, hyperactive NF‐

kappaB, increased oxidative stress and reduced NK cytotoxicity, among others, are present in both

diseases. These anomalies may be part of the physiopathology of some of the common complaints,

such as fatigue. Further studies to confirm the hypotheses given here are warranted.

Fibromyalgia (FMS) is a chronic widespread pain (CWP) and fatigue syndrome that affects three to six

million adults in the United States. Core symptoms of FMS include pain, fatigue, and mood and sleep

disturbances. To date, consensus has not been reached among researchers regarding the

pathogenesis of FMS nor the specific role of cytokine activation on the neuroendocrine‐immune

response patterns in persons with FMS. The purpose of this article is to describe and synthesize the

results of research studies focused on the relationship between cytokines and FMS and among

cytokines and core symptoms of FMS. There is some support in the literature for relationships among

FMS symptoms and cytokines; however, there are discrepant findings related to whether

proinflammatory and anti‐inflammatory cytokines are elevated or reduced in persons with FMS and

whether their levels correlate with the core symptoms of this disorder. Although the use of cytokine

biomarkers must be considered exploratory at this time due to the lack of consistent empirical

findings, biobehavioral research focused on understanding the relationship of FMS with cytokines

may lead to a better understanding of this complex syndrome. This knowledge may ultimately

contribute to the development of interventions for symptom management that address not only the

symptom manifestation but also a biological mediator of symptoms.

Q fever is a zoonotic disease caused by the ubiquitous pathogen Coxiella burnetii responsible for

acute and chronic clinical manifestations. Its geographically heterogeneous prevalence seems mainly

related to the clinician interest and the availability of a reference center. Its polymorphic clinical

expression imposes reference to diagnosis in presence of pneumonia, hepatitis, prolonged fever or

endocarditis with no proof of its etiology. The diagnosis is mainly serological. If acute Q fever is most

often benign, endocarditis is constantly fatal without treatment. The treatment is effective and well

tolerated, but must be adapted to the acute or chronic pattern, the presence of a heart valve disease,

an aneurysm or a vascular prosthesis, an immunodeficiency and the specific problem of pregnancy.

Serum alpha‐tocopherol concentrations were determined in 50 patients with chronic fatigue

syndrome (CFS) and 40 control subjects (Control). Prevalence of each or any coronary risk factor was

not significantly different between CFS and Control. CFS had significantly lower alpha‐tocopherol

ME Research UK — Database of Research Publications 2009

Miwa K, Fujita M. Department of

Internal Medicine,

Nanto Family and


Medical Center,

577 Matsubara,

Nanto, Toyama

939‐1518, Japan.

Miwa K, Fujita M. Department of

Internal Medicine,

Nanto Family and


Medical Center,

Nanto, Toyama,




vitamin E

concentrations in

patients with

chronic fatigue


Cardiac function

fluctuates during

exacerbation and

remission in young

adults with chronic

fatigue syndrome

and "small heart".


dysfunction with

low cardiac output

due to a small

heart in patients

with chronic

fatigue syndrome.

6. concentrations than Control. The concentrations were significantly lower in the subjects with any

coronary risk factors than those without in CFS as well as Control. Even among the subjects with any

coronary risk factors and also among those without, CFS had significantly lower alpha‐tocopherol

concentrations than Control. In conclusion, CFS had significantly lower alpha‐tocopherol

concentrations irrespective of coronary risk factors than Control, suggesting the presence of increased

oxidative stress in CFS.

J Cardiol. 2009


Epub 2009 Mar 28.

Intern Med.


54. Epub 2009 Nov


BACKGROUND: "Small heart syndrome", previously referred to as so‐called "neurocirculatory

asthenia" associated with a small heart shadow on the chest roentgenogram, is characterized by

weakness or fatigue even after mild exertion, palpitation, dyspnea, and fainting, many of which

resemble symptoms in patients with chronic fatigue syndrome (CFS). METHODS AND RESULTS: The

study population comprised 42 patients with CFS younger than 40 years of age. Cardiothoracic ratio

was determined on the chest roentgenogram and echocardiographic examination was performed to

evaluate both the cardiac chamber size and function. "Small heart" (cardiothoracic ratio

ME Research UK — Database of Research Publications 2009

Miyaoka H,

Miyachi H, Oishi S.

Moniuszko A,

Czupryna P,

Zajkowska J,

Pancewicz SA,

Grygorczuk S,

Kondrusik M.

Department of


Kitasato University,

School of


Department of

Infectious Diseases



Medical University

of Bialystok,




Murakami M. Department of


Internal Medicine,

Nihon University

Itabashi Hospital.

Mutsuura H,

Kanbara K,

Department of


[Is "functional

somatic syndrome"

clinically useful?]

[Article in


[Post Lyme

syndrome as a


problem][Article in


[Treatment of

myalgia] [Article in


Depression and

anxiety correlate

Nippon Rinsho.



Pol Merkur

Lekarski. 2009



Nippon Rinsho.



Appl Psychophysiol

Biofeedback. 2009

reduced left ventricular ejection fraction. CONCLUSION: Cardiovascular symptoms are common in CFS

patients. Cardiac dysfunction with low cardiac output due to small left ventricular chamber may

contribute to the development of chronic fatigue as a constitutional factor in a considerable number

of CFS patients.

The functional somatic syndrome is applied to several syndromes characterized by medically

unexplained physical symptoms, such as irritable bowel syndrome, fibromyalgia, chronic fatigue

syndrome, etc. Both physical and psychiatric treatments are usually necessary for these syndromes

and the term functional somatic syndrome was advocated to inform clinicians in America of this fact.

However, We believe this term will not be useful in Japan, because most Japanese clinicians are

already aware of this fact and treatment is different in each syndrome included in FSS.

Lyme disease is a chronic tick borne disease, caused by spirochetes B. burgdorferi. The condition

influences mostly on skin, nervous system, skeletal system and circulatory system. Recently more and

more reports of so called "Post Lyme syndrome (PLS)" have appeared. PLS is a new clinical, diagnostic

and therapeutic problem connected with patients with a history of Lyme disease (with proper

antibiotic treatment). The symptoms of Post Lyme Syndrome may be present throughout months or

even years. These are: fatigue, widespread musculoskeletal pain, dysmnesia, concentration

difficulties. Pathogenesis of PLS is unknown. It is suspected that main factors responsible for PLS are:

slow regression of infection, its turning into chronic process and permanent destruction of tissues or

induction of immunological response against B. burgdorferi. Diagnostic of PLS is difficult. Mostly

results of serological examination are negative. In some cases antibodies titer is positive as a sign of

past disease. So far there is no causative treatment of PLS. Antidepressants, painkillers and anti‐

inflammatory medicines are recommended.

Fibromyalgia (FM) conceptualized by the American College of Rheumatology is characterized by long‐

lasting chronic widespread pain and stiffness of the fibro‐muscular system associated with various

unidentified symptoms. Since most of the patients are female and the onset and clinical course of FM

involves various kinds of bio‐psychosocial stress factors, it is very important to consider the

psychosomatic background of the patient. The symptom of FM is not readily improved with

conventional analgesic drugs, antirheumatic agents or various kinds of physiotherapy, however

current guidelines recommend tricyclic antidepressants, SSRIs and SNRIs as first‐line therapies to treat

the multiple symptom of the FM. It is considered that antidepressants may operate the functional

impairment of descending (efferent) analgesic system, in which serotonin and noradrenaline take an

important role. Among 199 certified physicians of the Japanese Society of Psychosomatic Medicine,

the largest number of respondents selected SSRI, SNRI and other antidepressants as first‐line drugs.

Because the psychological and physical exhaustion due to an irregular life style, physical strain, and

accumulated fatigue may be the key stress factors for the organization of symptoms, psychosomatic

approach and guidance should be conducted to enable patients to reduce stress in daily life. For the

problems of personality and psychological stress, counseling and advanced psychotherapy such as

cognitive behavioral therapy (CBT) should be also conducted.

Patients presenting with functional somatic syndrome (FSS) are common, and the symptoms are

persistent and difficult to treat for doctors and costly for society. The aim of this study was to clarify

ME Research UK — Database of Research Publications 2009

Fukunaga M,

Yamamoto K, Ban

I, Kitamura K,

Nakai Y.

Myhill S, Booth

NE, McLaren‐

Howard J.

Nakagami A,

Tsujiuchi T.

Medicine, Kansai

Medical University,


Osaka 570‐8507,




Graduate School of

Human Sciences,

Waseda University.

differently with

salivary free

cortisol in the

morning in

patients with

functional somatic


Chronic fatigue

syndrome and




somatic syndromes

from the view of



[Article in



Epub 2009 Aug 7.

Int J Clin Exp Med.


Epub 2009 Jan 15.

Nippon Rinsho.



the common pathophysiology of FSS, especially the relationship between hypothalamic‐pituitary‐

adrenal (HPA) axis function and psychological characteristics of patients with FSS. The subjects were

45 patients with FSS and 29 healthy controls. Salivary free cortisol was measured in the morning, and

psychological tests examining depression, anxiety and quality of life (QOL) were performed on the

same day. In patients with FSS, depressive scores showed a significant negative correlation with

salivary free cortisol in the morning, although in healthy controls, cortisol showed a significant

positive correlation with depressive scores. In addition, the correlation between other psychological

test scores and cortisol secretion in patients with FSS contrasted with that of controls. The

relationship between cortisol and depression, anxiety or QOL, suggests that the HPA axis of patients

with FSS is dysfunctional and does not function properly when patients with FSS are under stress. This

dysfunction may explain the pathology of medically unexplained persistent symptoms of patients with


This study aims to improve the health of patients suffering from chronic fatigue syndrome (CFS) by

interventions based on the biochemistry of the illness, specifically the function of mitochondria in

producing ATP (adenosine triphosphate), the energy currency for all body functions, and recycling

ADP (adenosine diphosphate) to replenish the ATP supply as needed. Patients attending a private

medical practice specializing in CFS were diagnosed using the Centers for Disease Control criteria. In

consultation with each patient, an integer on the Bell Ability Scale was assigned, and a blood sample

was taken for the "ATP profile" test, designed for CFS and other fatigue conditions. Each test

produced 5 numerical factors which describe the availability of ATP in neutrophils, the fraction

complexed with magnesium, the efficiency of oxidative phosphorylation, and the transfer efficiencies

of ADP into the mitochondria and ATP into the cytosol where the energy is used. With the consent of

each of 71 patients and 53 normal, healthy controls the 5 factors have been collated and compared

with the Bell Ability Scale. The individual numerical factors show that patients have different

combinations of biochemical lesions. When the factors are combined, a remarkable correlation is

observed between the degree of mitochondrial dysfunction and the severity of illness (P

ME Research UK — Database of Research Publications 2009

Nakao M. Department of

Hygiene and Public

Health & Division

of Psychosomatic

Medicine, Teikyo

University School

of Medicine.

Nater UM, Lin JM,

Maloney EM,

Jones JF, Tian H,

Boneva RS, Raison

CL, Reeves WC,

Heim C.

Neu D, Cappeliez

B, Hoffmann G,

Verbanck P,

Linkowski P, Le

Bon O.

Chronic Viral

Diseases Branch,

National Center for

Zoonotic, Vector‐

borne and Enteric

Diseases, Centers

for Disease Control

and Prevention,

Atlanta, GA 30333,




Hospital, Sleep

Laboratory, and

Unit for


U78, Université

Libre de Bruxelles

(U.L.B), Brussels,




[Etiology of

functional somatic


[Article in



comorbidity in

persons with

chronic fatigue


identified from

the Georgia


High slow‐wave

sleep and low‐light

sleep: chronic

fatigue syndrome

is not likely to be a

primary sleep


Nippon Rinsho.



Psychosom Med.



Epub 2009 May 4.

J Clin





Functional somatic syndromes are defined as several related syndromes that are characterized more

by symptoms, suffering, and disability than by structural or functional abnormality. These syndromes

include irritable bowel syndrome, tension‐type headache, chronic fatigue syndrome, and

fibromyalgia. Such syndromes have similarities in terms of definition, diagnosis, etiology, and

treatment. To elucidate the pathogenesis of functional somatic syndromes, it is important to focus on

gender‐related factors, comorbidities of depression and anxiety, physiological responses like

autonomic nervous function and hypothalamic‐pituitary‐adrenal axis, and patient‐doctor relationship.

Based on recent literatures, mood state and somatosensory amplification are suggested to play an

important role in the psychopathological mechanism of functional somatic syndromes, and genetic

and environmental factors need to be considered as well.

OBJECTIVE: To compare the prevalence of psychiatric disorders in persons with chronic fatigue

syndrome (CFS) identified from the general population and a chronically ill group of people presenting

with subsyndromic CFS‐like illness ("insufficient symptoms or fatigue" (ISF)). Previous studies in CFS

patients from primary and tertiary care clinics have found high rates of psychiatric disturbance, but

this may reflect referral bias rather than true patterns of comorbidity with CFS. METHODS: We used

random digit dialing to identify unwell individuals. A detailed telephone interview identified those

with CFS‐like illness. These individuals participated in a 1‐day clinical evaluation to confirm CFS or ISF

status. We identified 113 cases of CFS and 264 persons with ISF. To identify current and lifetime

psychiatric disorders, participants completed the Structured Clinical Interview for DSM‐IV. RESULTS:

Sixty‐four persons (57%) with CFS had at least one current psychiatric diagnosis, in contrast to 118

persons (45%) with ISF. One hundred one persons (89%) with CFS had at least one lifetime psychiatric

diagnosis compared with 208 persons (79%) with ISF. Of note, only 11 persons (9.8%) with CFS and 25

persons (9.5%) with ISF reported having seen a mental healthcare specialist during the past 6 months.

CONCLUSIONS: Our findings indicate that current and lifetime psychiatric disorders commonly

accompany CFS in the general population. Most CFS cases with comorbid psychiatric conditions had

not sought appropriate help during the past 6 months. These results demonstrate an urgent need to

address psychiatric disorders in the clinical care of CFS cases.

The status of chronic fatigue syndrome (CFS) is still under debate. Mainstream views still often

consider it as an undetected primary sleep disorder or as the psychosomatic expression of a related

anxiety or depression syndrome. Both primary sleep disorder and CFS are often related to

unrefreshing sleep and affective daytime symptoms. The present study compares nonrapid eye

movement sleep distribution between patients with a primary sleep disorder and "pure" CFS patients

without sleep or mood disorders. Intensity measures of affective symptoms are also analyzed. Sleep

variables of 32 pure CFS (mean age, 41.9 +/‐ 8.7 years; 25 women), 30 Sleep Apnea Hypopnea

Syndrome patients (mean age, 43.7 +/‐ 6.7 years; 13 women), and 14 healthy controls (mean age,

40.2 +/‐ 7.6 years; 9 women) were compared. Related affective symptoms were assessed using the

self‐reported Zung anxiety and depression scales. The study confirms previous reports on increased

slow‐wave sleep in CFS patients. Both patient groups showed similar sleep duration and efficiency.

Sleep efficiency was lower in both patient groups compared with controls. CFS patients showed a

ME Research UK — Database of Research Publications 2009

Newton JL, Sheth

A, Shin J, Pairman

J, Wilton K, Burt

JA, Jones DE.

Ocon AJ, Medow

MS, Taneja I,

Clarke D, Stewart



Investigation Unit,

Institute of Cellular




Newcastle NE2

4HH, UK.



Department of

Physiology, The

Center for

Hypotension, New

York Medical

College, Valhalla,

New York 10532,


Lower ambulatory

blood pressure in

chronic fatigue


Decreased upright

cerebral blood

flow and cerebral

autoregulation in





Psychosom Med.



Epub 2009 Mar 17.

Am J Physiol Heart

Circ Physiol. 2009


73. Epub 2009 Jun


higher microarousal index than controls. Anxiety, but not depression symptoms were more intense in

the CFS group. The distribution of nonrapid eye movement sleep in CFS differs sizeably from what

can be observed in a primary sleep disorder.

OBJECTIVE: To examine blood pressure circadian rhythm in subjects with chronic fatigue syndrome

(CFS) and appropriate normal and fatigued controls to correlate parameters of blood pressure

regulation with perception of fatigue in an observational cohort study. The cause of CFS remains

unknown and there are no effective treatments. METHODS: To address whether inactivity was a

confounder, we performed a 24‐hour ambulatory blood pressure monitoring in the following three

subject groups: 1) CFS patients (Fukuda Diagnostic criteria) (n = 38); 2) normal controls (n = 120); and

3) a fatigue comparison group (n = 47) with the autoimmune liver disease primary biliary cirrhosis

(PBC). All patients completed a measure of fatigue severity (Fatigue Impact Scale). In view of the

different demographics between the patient groups, patients were age‐ and sex‐matched on a case‐

by‐case basis to normal controls and blood pressure parameters were compared. RESULTS: Compared

with the control population, the CFS group had significantly lower systolic blood pressure (p < .0001)

and mean arterial blood pressure (p = .0002) and exaggerated diurnal variation (p = .009). There was a

significant inverse relationship between increasing fatigue and diurnal variation of blood pressure in

both the CFS and PBC groups (p < .05). CONCLUSION: Lower blood pressure and abnormal diurnal

blood pressure regulation occur in patients with CFS. We would suggest the need for a randomized,

placebo‐controlled trial of agents to increase blood pressure such as midodrine in CFS patients with

an autonomic phenotype.

Postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance, has signs and

symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive deficits consistent

with reductions in cerebrovascular perfusion. We hypothesized that young, normocapnic POTS

patients exhibit abnormal cerebral autoregulation (CA) that results in decreased static and dynamic

cerebral blood flow (CBF) autoregulation. All subjects had continuous recordings of mean arterial

pressure (MAP) and CBF velocity (CBFV) using transcranial Doppler sonography in both the supine

supine position and during a 70 degrees head‐up tilt. During tilt, POTS patients (n = 9) demonstrated a

higher heart rate than controls (n = 7) (109 +/‐ 6 vs. 80 +/‐ 2 beats/min, P < 0.05), whereas controls

demonstrated a higher MAP than POTS (87 +/‐ 2 vs. 77 +/‐ 3 mmHg, P < 0.05). Also during tilt, mean

CBFV decreased 19.5 +/‐ 2.6% in POTS patients versus 10.3 +/‐ 2.0% in controls (P < 0.05). We then

used a transfer function analysis of MAP and CFBV in the frequency domain to quantify these

changes. The low‐frequency (LF; 0.04‐0.15 Hz) component of CBFV variability increased during tilt in

POTS patients (supine: 3 +/‐ 0.9 vs. tilt: 9 +/‐ 2, P < 0.02). In POTS patients, there was an increase in LF

and high‐frequency coherence between MAP and CBFV, an increase in LF gain, and a lack of

significant change in phase. Static CA may be less effective in POTS patients compared with controls,

since immediately after tilt CBFV decreased more in POTS patients and was highly oscillatory and

autoregulation did not restore CBFV to baseline values until the subjects became supine. Dynamic CA

may be less effective in POTS patients because MAP and CBFV during tilt became almost perfectly

synchronous. We conclude that dynamic and static autoregulation of CBF are less effective in POTS

patients compared with control subjects during orthostatic challenge.

ME Research UK — Database of Research Publications 2009

Ogawa H, Hida W. Health


Center, Tohoku


Oka T, Kanemitsu


Oliveira WR,

Ferreira GN, Rady

PL, Festa C, Tyring



OD, Cuccia M,

Bozzini S, Bassi N,

Moscavitch S,

Diaz‐Gallo LM,

Blank M, Agmon‐

Levin N, Shoenfeld


Department of



Graduate School of

Medical Sciences,

Kyushu University.

Department of


University of São

Paulo, São Paulo,




Department of

Medicine B and

Center for


Diseases, Sheba

Medical Center,

Sackler Faculty of

Medicine, Tel Aviv



pulmonary disease

(COPD)] [Article in


[Biomedical and


treatment of

fatigue in

functional somatic

syndrome] [Article

in Japanese]



associated with


syndrome: an




polymorphisms in

the serotonin

pathway, and

human leukocyte

antigen class II

alleles in chronic

fatigue syndrome:

Nippon Rinsho.



Nippon Rinsho.



J Cutan Med Surg.

2009 Nov‐


Ann N Y Acad Sci.



Insomnia is common in many patients with chronic obstructive pulmonary disease (COPD). The causes

of insomnia are sleep induced pathophysiological effect of COPD itself, COPD comorbidities and the

presence of coexisted obstructive sleep apnea. Sleep has profound adverse effects on respiration and

gas exchange in patients with COPD. There are several mechanisms underlying oxygen desaturation

during sleep. They include decreased functional residual capacity, decreased ventilatory responses to

hypoxia and hypercapnia, impaired respiratory mechanical effectiveness, respiratory muscle fatigue,

decreased respiratory drive, and increased upper airway resistance. COPD comorbidities include DM,

cardiovascular diseases, osteoporosis, depression, and GERD. The coexistence of COPD and sleep

apnea‐hypopnea syndrome has been denominated "overlap syndrome".

Fatigue is one of the most common complaints of patients with functional somatic syndrome (FSS),

which includes chronic fatigue syndrome (CFS). Although the etiology of fatigue related to FSS

remains unclear, accumulating evidence has shown that cognitive behavioral therapy and graded

exercise therapy are effective for treating fatigue in patients with CFS. This suggests that psychosocial

intervention and physical rehabilitation, as well as biomedical treatment, play an important role in

treating fatigue in FSS patients. Here we provide an overview of the biomedical and psychosocial

treatments for fatigue in cases of FSS.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by

massive infection with human papillomaviruses (HPVs) and development of skin cancer.

Myelodysplastic syndromes (MDSs) are a group of chronic conditions that involve dysplastic

hematopoiesis, peripheral blood cytopenias, and a high incidence of progression into leukemia.

METHODS: We describe the intriguing association of these two premalignant conditions (EV and MDS)

in one patient. These diagnoses were confirmed by histopathologic examination and cytogenetic

abnormalities of bone marrow cells. RESULTS: The patient presented initially with clinical features

typical of EV and impairment of cell‐mediated immunity. In the skin lesions, HPVs 23 and 25 were

identified by nested polymerase chain reaction. Six years later, he had recurrent episodes of mucosal

bleeding with fever, weakness, and fatigue. At this time, severe refractory anemia and neutropenia

were observed, and bone marrow smears showed hypercellularity with abnormal dysplastic

megakaryocytes. The cytogenetic pattern showed abnormalities involving trisomy of chromosomes 8

and 21. The patient received a diagnosis of the indolent subtype of MDS. CONCLUSIONS: Through the

observation of our patient and review of the literature, we hypothesized that the pathomechanisms,

including the role of oncogenes and cytokines, are connected to the progression to malignancy in

these settings.

This study aimed to determine the influence of autoantibodies, polymorphisms in the serotonin

pathway, and human leukocyte antigen (HLA) class II genes on age at chronic fatigue syndrome (CFS)

onset and symptoms. Eighty‐one CFS patients were enrolled, and clinical data were recorded.

Autoantibodies to different components of the central nervous system were tested. Polymorphisms in

the promoter of the serotonin transporter gene (l/s) and a single nucleotide polymorphism in the

serotonin receptor‐2A gene (A/G) as well as HLA class II alleles were determined. Multivariate logistic‐

regression analyses were carried out. The mean age at CFS onset +/‐ SD was 33.5 +/‐ 12.5 years. An

age at CFS onset (ACFSO) during the third decade of life was associated with the serotonin receptor

ME Research UK — Database of Research Publications 2009


OD, Shoenfeld Y.

Øyane N, van den

Hoven AM, Fetveit

A, Pallesen S,

Bjorvatn B.

University, Tel

Aviv, Israel.

Department of

Internal Medicine

B and Research for


Diseases, Sheba

Medical Center,

Tel Hashomer,


Institutt for


ke fag,

Universitetet i

Bergen og







s, 5021 Bergen og

are they associated

with age at onset

and specific



vaccination, and

autoantibodies in

chronic fatigue

syndrome, cause

or coincidence?

[Symptom patterns

in chronic sleep

disorders] [Article

in Norwegian]

Ann N Y Acad Sci.



Tidsskr Nor

Laegeforen. 2009



AA genotype and the HLA‐DRB1*03 allele. An ACFSO during the fourth decade of life was associated

with the HLA‐DRB1*07 allele, whereas an ACFSO > or = 43 years was associated with having at least

one copy of the serotonin G allele. Concerning CFS symptoms, the serotonin AG genotype was

protective against depressive symptoms. Although having at least one copy of the serotonin A allele

and being female were associated with risk for arthralgia, the presence of antineuronal cell antibodies

was protective against this. Episodes of unexplained fever were associated with the HLA‐DRB1*11

allele. None of the genetic or serological features was associated with myalgia. None of the antibodies

determined correlated with any ACFSO or other symptoms. Our results reveal that in CFS, like other

autoimmune diseases, different genetic features are related to age at CFS onset and symptoms.

Chronic fatigue syndrome (CFS) is a heterogeneous syndrome of unknown etiology and

physiopathology. CFS patients complain about disabling fatigue, depression, difficulty with memory,

and concomitant skeletal and muscular pain. Interestingly enough, there is certain overlap between

CFS symptoms, autoimmune rheumatic disease, and infectious diseases. Certain neuroendocrine‐

immune abnormalities have also been described, and autoantibodies commonly described in some

autoimmune diseases have been found in CFS patients as well. An increasing number of

autoantibodies, mainly directed against other nuclear cell components, have been illustrated.

Likewise, an association between some infectious agents, antibody production, and later CFS onset

has been reported. Similarly, vaccination is depicted as playing an important role in CFS onset.

Recently, a case report pointed toward a causal association between silicone breast linkage, hepatitis

B virus vaccination, and CFS onset in a previous healthy woman. Such findings suggest that there is a

likely deregulation of the immune system influenced by specific agents (infections, vaccination, and

products, such as silicone). Evidence suggests that CFS is a complex disease in which several risk

factors might interact to cause its full expression. Thus, although different alterations have been

found in CFS patients, undoubtedly the main feature is central nervous system involvement with

immunological alterations. Therefore, a new term neuro‐psycho‐immunology must be quoted. New

studies based on this concept are needed in order to investigate syndromes, such as CFS, in which

immunological alterations are thought to be associated with concomitant psychological and health


BACKGROUND: Sleep disorders are classified into six main categories: insomnias, circadian rhythm

disorders, sleep‐related movement disorders, sleep‐related breathing disorders, hypersomnias and

parasomnias. The aim of this article is to shed light on differences between these categories with

respect to symptom patterns. MATERIAL AND METHODS: The main sources of information are the

diagnosis manual published by the American Academy of Sleep Medicine in 2005 and papers

identified through non‐systematic searches in Pubmed. RESULTS: Long sleep onset latency is most

common in patients with insomnia, delayed sleep phase syndrome and restless legs while nightly

awakenings are most common in patients with insomnia, restless legs and the sleep apnoea

syndrome. Excessive daytime sleepiness is most pronounced in patients with hypersomnia, sleep

apnoea syndrome and delayed sleep phase syndrome, whereas patients with insomnia rarely have

this problem. Fatigue is a common feature of all sleep disorders, especially insomnia. The diagnosis of

insomnia, circadian rhythm disturbances, restless legs and most parasomnias is mainly based on

ME Research UK — Database of Research Publications 2009

Pae CU, Marks

DM, Patkar AA,

Masand PS, Luyten

P, Serretti A.






Holy Family

Hospital, The

Catholic University

of Korea College of


Department of


Bucheon 420717,


South Korea.


Pall ML. The Tenth

Paradigm Research

Group and School

of Molecular

Biosciences (WSU),

638 NE 41st Ave.,

Portland, OR

97232‐3312, USA.




treatment of

chronic fatigue


focusing on the

role of


Do sauna therapy

and exercise act by

raising the

availability of



Expert Opin




Med Hypotheses.



Epub 2009 Jul 5.

anamnestic data. Objective sleep recordings are necessary to diagnose sleep apnoea syndrome,

hypersomnia and periodic leg movement during sleep. INTERPRETATION: The six sleep disorder

categories differ substantially with respect to symptom patterns. Sleep disorders can often be

distinguished from each other by use of anamnestic data without resorting to further assessment, but

objective sleep recordings are needed for accurate diagnosis of some patients.

Chronic fatigue syndrome (CFS) is characterized by chronic, medically unexplained fatigue associated

with effort‐ and stress‐intolerance, widespread pain, and impairment in sleep and concentration.

Although this constellation of symptoms is highly prevalent in clinical practice, the pathophysiological

mechanisms underlying CFS are poorly understood. Current evidence indicates similarities in

symptomatology, and possibly etiology and pathogenesis, between CFS and depression. Additionally,

there is significant overlap between CFS and the syndrome of fibromyalgia for which antidepressants

have shown consistent efficacy. Data regarding antidepressant treatment of CFS is less copious and

less uniformly positive, such that antidepressant use in CFS remains controversial. The current review

aims to summarize available data related to antidepressants and other psychotropic agents in CFS to

provide a platform for clinicians to make decisions in their treatment of this challenging syndrome.

We identified relevant studies through a PubMed literature search with a combination of the

following search terms: 'fatigue,' 'depression,' 'antidepressant,' 'etiology' (e.g., 'neurobiology,'

'neurotransmitter,' 'genetic'), 'diagnosis,' and 'treatment' (e.g., 'antidepressant' plus the specific

name). In addition, studies were also identified via the reference sections of retrieved articles. The

authors thoroughly reviewed major findings from the scanned literatures and eventually synthesized

them, providing summary, interpretation, and future directions.

Sauna therapy has been used to treat a number of different diseases known or thought to have a

tetrahydrobiopterin (BH4) deficiency. It has been interpreted to act in multiple chemical sensitivity by

increasing chemical detoxification and excretion but there is no evidence that this is its main mode of

action. Sauna therapy may act to increase BH4 availability via two distinct pathways. Increased blood

flow in heated surface tissues leads to increased vascular shear stress, inducing increased activity of

GTP cyclohydrolase I (GTPCH‐I) in those vascular tissues which will lead to increasing BH4 synthesis. A

second mechanism involves the heat shock protein Hsp90, which is induced by even modest heating

of mammalian tissues. Sauna heating of these surface tissues may act via Hsp90, which interacts with

the GTPCH‐I complex and is reported to produce increased GTPCH‐I activity by lowering its

degradation. The increased consequent availability of BH4 may lead to lowered nitric oxide synthase

uncoupling, such as has been reported for the eNOS enzyme. Increased BH4 synthesis in surface

tissues of the body will produce increased circulating BH4 which will feed BH4 to other body tissues

that may have been BH4 deficient. Similar mechanisms may act in vigorous exercise due to the

increased blood shear stresses and possibly also heating of the exercising tissues and heart. There is a

large and rapidly increasing number of diseases that are associated with BH4 depletion and these may

be candidates for sauna therapy. Such diseases as hypertension, vascular endothelial dysfunction,

multiple chemical sensitivity and heart failure are thought to be helped by sauna therapy and chronic

fatigue syndrome and fibromyalgia may also be helped and there are others that may be good

candidates for sauna therapy.

ME Research UK — Database of Research Publications 2009

Panossian A,

Wikman G.

Papadopoulos A,

Ebrecht M,

Roberts AD, Poon

L, Rohleder N,

Cleare AJ.

Paralikar VP,

Weiss MG, Agashe

M, Sarmukaddam


Swedish Herbal

Institute Research

and Development,

Spårvägen 2, SE‐

43296 Askloster,




King's College

London, Institute

of Psychiatry,

Section of

Neurobiology of

Mood Disorders,

Division of


Medicine, London

SE5 8AF, United



efficacy of

adaptogens in

fatigue, and



related to their




receptor mediated

negative feedback

in chronic fatigue

syndrome using

the low dose (0.5



suppression test.

Diagnosing chronic

fatigue syndrome.

Curr Clin

Pharmacol. 2009


Epub 2009 Sep 1.

J Affect Disord.

2009 Jan;112(1‐

3):289‐94. Epub

2008 Jun 24.

Br J Psychiatry.



author reply 369‐

The aim of this review article is to assess the level of scientific evidence presented by clinical trials of

adaptogens in fatigue, and to provide a rationale at the molecular level for verified effects. Strong

scientific evidence is available for Rhodiola rosea SHR‐5 extract, which improved attention, cognitive

function and mental performance in fatigue and in chronic fatigue syndrome. Good scientific evidence

has been documented in trails in which Schisandra chinensis and Eleutherococcus senticosus

increased endurance and mental performance in patients with mild fatigue and weakness. Based on

their efficacy in clinical studies, adaptogens can be defined as a pharmacological group of herbal

preparations that increase tolerance to mental exhaustion and enhance attention and mental

endurance in situations of decreased performance. The beneficial stress‐protective effect of

adaptogens is related to regulation of homeostasis via several mechanisms of action associated with

the hypothalamic‐pituitary‐adrenal axis and the control of key mediators of stress response such as

molecular chaperons (e.g. Hsp70), stress‐activated c‐Jun N‐terminal protein kinase (JNK1), Forkhead

Box O transcription factor DAF‐16, cortisol and nitric oxide (NO). The key point of action of

phytoadaptogens appears to be their up‐regulating and stress‐mimetic effects on the "stress‐sensor"

protein Hsp70, which plays an important role in cell survival and apoptosis. Hsp70 inhibits the

expression of NO synthase II gene and interacts with glucocorticoid receptors directly and via the JNK

pathway, thus affecting the levels of circulating cortisol and NO. Prevention of stress‐induced increase

in NO, and the associated decrease in ATP production, results in increased performance and

endurance. Adaptogen‐induced up‐regulation of Hsp70 triggers stress‐induced JNK‐1 and DAF‐16‐

mediated pathways regulating the resistance to stress and resulting in enhanced mental and physical

performance and, possibly, increased longevity.

BACKGROUND: Chronic fatigue syndrome (CFS) is associated with hypocortisolism, but it is not yet

clear the extent to which enhanced negative feedback may underlie this finding. METHODS: We

undertook a low‐dose dexamethasone (0.5 mg) suppression test in 18 CFS patients and 20 matched,

healthy controls. We measured salivary cortisol levels at 0800 h, 1200 h, 1600 h and 2000 h before

and after the administration of 0.5 mg of dexamethasone. RESULTS: Basal cortisol output was raised

in this group of CFS patients compared to controls. Overall, the percentage suppression following

dexamethasone administration was no different between CFS (mean+/‐sem: 80.4+/‐4.4%) and

controls (76.2+/‐4.9 %). However, the sub‐group of patients with CFS and comorbid depression (n=9)

showed a significant hypersuppression of salivary cortisol in response to dexamethasone (89.0+/‐

1.9%; p

ME Research UK — Database of Research Publications 2009

Pariante CM. Sections of


Psychiatry &

Stress, Psychiatry

and Immunology

(SPI‐Lab), Institute

of Psychiatry,

King's College

London, 125

Coldharbour Lane,

London SE5 9NU,




Peng H, Chen Q,

Tan Y.

Pietrangelo T,

Mancinelli R,

Toniolo L,

Laboratory Animal

Center, Chongqing

Medical University,

No. 1, Yi Xue Yuan

Road, Chongqing

400016, China.

Department of

Basic and Applied

Medical Sciences

Chronic fatigue

syndrome and the

immune system:

"findings in search

of meanings".



associated free

radical and lactic

acid accumulation



inflammation and


dysfunction: a


mechanism for

symptoms in



Pelvic Pain



profile analysis of

vastus lateralis

370. Comment on:

Br J Psychiatry.



Brain Behav

Immun. 2009


Comment on:

Brain Behav

Immun. 2009


Med Hypotheses.



Epub 2009 May 10.

Int J


Pharmacol. 2009

BACKGROUND: The prevalence of prostatitis is extremely high, with vast majority belongs to National

Institutes of Health Category III: Chronic Prostatitis (CP)/Chronic Pelvic Pain Syndromes (CPPS). The

etiology of CP/CPPS is noninfectious, with no precise mechanisms has been elucidated to date.

HYPOTHESIS: During male ejaculation, the pelvic muscles undergo coordinated intense contraction to

expel the semen out of the male genital tract, a process associated with locally increased levels of

lactic acid and free radicals as byproducts. In this regards, repetitive sexual activities with frequent

ejaculation would impede the drainage and cause accumulation of these byproducts in the pelvic

region, triggering consequent local pathophysiological changes such as edema, venous dilation and

muscular malfunction, which further leads to common complaints in CP/CPPS patients such as lower

urinary tract symptoms, pelvic discomfort and pain. RATIONALE: Large cohort studies have revealed

that frequent ejaculation is associated with higher risk of prostatitis, especially in young men. Also,

clear evidences from sports medical research has shown that intense muscular contraction will lead to

locally increased production of free radicals and lactic acid. Therefore, the pelvic muscles during

ejaculation would induce substantial increase of these byproducts, which if not cleared effectively,

could trigger series of local cellular/tissue damages resulting in inflammation, muscular fatigue and

dysfunction. If our hypothesis were validated, it could be suggested that at least in some patients, the

treatment of CP/CPPS could be tuned as dealing with post‐sports recovery, such as hot bath to

promote local blood circulation and free radical scavenger drugs such as vitamin C and E to neutralize

free radicals.

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue

that impairs normal activities. Many body systems are affected and etiology has not yet been

identified. In addition to immunological and psychological aspects, skeletal muscle symptoms are

ME Research UK — Database of Research Publications 2009

Montanari G,

Vecchiet J, Fanò G,

Fulle S.

Pietrangelo T,

Toniolo L, Paoli A,

Fulle S, Puglielli C,

Fanò G, Reggiani


Plastiras S,

Kampessi O.

Podolecki T,

Podolecki A,

Hrycek A.

(BAMS), Center for

Excellence on

Aging (CeSI),

University G.

d'Annunzio Chieti‐

Pescara, Chieti,



Dept. Basic and

Applied Medical

Sciences (BAMS),

Center for

Excellence on

Ageing (CeSI),

University ‐ G.

dAnnunzio‐ Chieti‐

Pescara, Chieti,



Department of


University of

Athens School of

Medicine Laiko


Hospital, 11527

Athens Greece.


Public Central

Clinical Hospital,

Katowice, Poland.

muscle from

patients with

chronic fatigue



characterization of

muscle fibres from

patients with

chronic fatigue

syndrome: case‐

control study.

Acute lymphocytic

crisis following

herpes simplex

type 1 virus

hepatitis in a


omised man: a

case report.



diagnostic and




Int J


Pharmacol. 2009



J Med Case

Reports. 2009 Aug


Pol Arch Med

Wewn. 2009



prominent in CFS patients. In an effort to establish which pathways might be involved in the onset

and development of muscle symptoms, we used global transcriptome analysis to identify genes that

were differentially expressed in the vastus lateralis muscle of female and male CFS patients. We found

that the expression of genes that play key roles in mitochondrial function and oxidative balance,

including superoxide dismutase 2, were altered, as were genes involved in energy production,

muscular trophism and fiber phenotype determination. Importantly, the expression of a gene

encoding a component of the nicotinic cholinergic receptor binding site was reduced, suggesting

impaired neuromuscular transmission. We argue that these major biological processes could be

involved in and/or responsible for the muscle symptoms of CFS.

Chronic fatigue syndrome (CFS) is a disabling condition characterized by unexplained chronic fatigue

that impairs normal activities. Although immunological and psychological aspects are present,

symptoms related to skeletal muscles, such as muscle soreness, fatigability and increased lactate

accumulation, are prominent in CFS patients. In this case‐control study, the phenotype of the same

biopsy samples was analyzed by determining i) fibre‐type proportion using myosin isoforms as fibre

type molecular marker and gel electrophoresis as a tool to separate and quantify myosin isoforms,

and ii) contractile properties of manually dissected, chemically made permeable and calcium‐

activated single muscle fibres. The results showed that fibre‐type proportion was significantly altered

in CSF samples, which showed a shift from the slow‐ to the fast‐twitch phenotype. Cross sectional

area, force, maximum shortening velocity and calcium sensitivity were not significantly changed in

single muscle fibres from CSF samples. Thus, the contractile properties of muscle fibres were

preserved but their proportion was changed, with an increase in the more fatigue‐prone,

energetically expensive fast fibre type. Taken together, these results support the view that muscle

tissue is directly involved in the pathogenesis of CSF and it might contribute to the early onset of

fatigue typical of the skeletal muscles of CFS patients.

INTRODUCTION: An increase in circulating lymphocytes can be seen following infections such as

infectious mononucleosis and pertussis, or in lymphoproliferative disorders such as acute and chronic

lymphocytic leukemia. Acute lymphocytic crisis following herpes simplex virus hepatitis has not been

described in the literature. CASE PRESENTATION: A 52‐year‐old man was admitted to our hospital

reporting low‐grade fever for the previous seven days, and fatigue. During the fifth day of

hospitalization, the patient developed a lymphocytic crisis and, after further tests the patient was

diagnosed as having herpes simplex virus hepatitis. CONCLUSION: This case report shows that herpes

simplex virus type 1 is a possible cause of an acute lymphocytic crisis similar to other well known

infectious agents such as Epstein‐Barr virus, cytomegalovirus, human immunodeficiency virus, human

herpes virus type 6, adenovirus, toxoplasma and human T‐cell lymphotropic virus. Furthermore, this

case report expands the clinical spectrum of herpes simplex virus hepatitis, since it is reported in a

nonimmunocompromised patient presenting with atypical acute lymphocytic syndrome.

Musculoskeletal pains are one of the most common complaints reported by patients. In 1972, Smythe

described the generalized pain and tenderness on palpation at specific points and, 4 years later, the

term fibromyalgia was introduced for determining the disease syndrome. The etiology and

pathogenesis of fibromyalgia are still unknown. This disease appears probably multi‐factorial. It is

ME Research UK — Database of Research Publications 2009

Puri BK, Agour M,

Gunatilake KD,

Fernando KA,

Gurusinghe AI,

Treasaden IH.

Puri BK,

Tsaluchidu S,

Treasaden IH.



MRI Unit, Imaging


Department, MRC

Clinical Sciences

Centre, Imperial

College School of



Hospital, Du Cane

Road, London W12

0HS, England, UK.



MRI Unit, Imaging


Department, MRC

Clinical Sciences

Centre, Imperial

College London,


Hospital, London,




concerns. considered that the changes in the neuronal activity in the central nervous system, abnormal

metabolism of biogenic amines and immunological disorders may among other things, contribute to

the development of the disease. The complaints are non characteristic and highly sujective, which

makes it substantially difficult to differentiate between fibromialgia and both chronic fatigue

syndrome and psychosomatic diseases. The treatment of fibromyalgia is complex and long‐term. The

antidepressants and psychotherapy is of vital importance. The effectiveness of locally used agents is

also being emphasized. Fibromyalgia has become a serious social problem in the well developed

countries in the recent years. Therefore, of importance are efforts to appropriately diagnose

fibromyalgia and to implement its appropriate treatment that resolves disease symptoms in a possibly

maximum degree.

An in vivo proton


study of cerebral

oxidative stress in



(chronic fatigue


Serial structural

MRI analysis and

proton and 31PMR

spectroscopy in

the investigation of

cerebral fatty acids

in major




disease, myalgic


and in forensic


Leukot Essent

Fatty Acids. 2009


6):303‐5. Epub

2009 Nov 10.

World Rev Nutr

Diet. 2009;99:31‐

45. Epub 2009 Jan


A particularly important family of antioxidant defence enzymes in the body are the glutathione

peroxidases, which remove H(2)O(2) by coupling its reduction to H(2)O with oxidation of reduced

glutathione (GSH) to oxidised glutathione (GSSG). There are suggestions that GSH in the peripheral

blood may be reduced in myalgic encephalomyelitis, which is a highly disabling neurological disease of

unknown aetiology. Since many of the symptoms relate to cerebral functioning, it would seem

probable that peripheral blood GSH findings would be reflected in lower cerebral GSH levels. The aim

of this study was to carry out the first direct assessment of cerebral GSH levels in myalgic

encephalomyelitis; the hypothesis being tested was that cerebral GSH levels would be reduced in

myalgic encephalomyelitis. Cerebral proton neurospectroscopy was carried out at a magnetic field

strength of 3T in 26 subjects; spectra were obtained from 20x20x20mm(3) voxels using a point‐

resolved spectroscopy pulse sequence. The mean cerebral GSH level in the myalgic encephalomyelitis

patients was 2.703 (SD 2.311) which did not differ significantly from that in age‐ and gender‐matched

normal controls who did not have any history of neurological or other major medical disorder (5.191,

SD 8.984; NS). Therefore our study does not suggest that GSH is reduced in the brain in myalgic

encephalomyelitis. At the present time, based on the results of this study, there is no evidence to

support the suggestion that, by taking glutathione supplements, an improvement in the brain‐related

symptomatology of myalgic encephalomyelitis may occur.

ME Research UK — Database of Research Publications 2009

Quillinan N,

Mohammad A,

Mannion G,

O'Keeffe D, Bergin

D, Coughlan R, Mc

Dermott MF,

McGonagle D.

1 Department of


Merlin Park

Hospital (Galway



Renmore, Galway,




Imaging evidence

for persistent

subclincal fasciitis

and arthritis in TNF



Periodic Syndrome

(TRAPS) between

febrile attacks.

Ann Rheum Dis.

2009 Nov 12.

[Epub ahead of


TNF Receptor‐Associated Periodic Syndrome (TRAPS) [1], formerly known as familial Hibernian fever

(FHF) [2, 3] is an archetypal hereditary periodic fever syndrome and is an autosomal dominant

condition characterised by mutations in the TNFRSF1A gene [4, 5]. Periodicity of fevers is typical of

TRAPS with peritonitis, arthritis and fasciitis. It is also well recognised that some patients continue to

feel unwell between attacks. That subclincal TRAPS is still ongoing in such circumstances is supported

by persistent acute phase response [6, 7]. There are no specific features to localise a site for this

persistent inflammatory response and, to date, no studies have been done to investigate this

interesting observation. Whole body magnetic resonance imaging (MRI) has recently been introduced

for the assessment of various skeletal pathologies including malignancy, myositis and arthritis [8‐12].

MRI in inflammatory disorders has the capacity to show both soft tissue inflammatory changes and

osteitis. We hypothesised that patients with TRAPS without obvious clinical manifestations and the

absence of fevers have subclincal disease affecting the anatomical territories that are prone to

inflammation during acute attacks. Herein, we confirm that some cases of TRAPS do indeed have

ongoing soft tissue and joint inflammation between attacks. Given that autoinflammatory disorders,

like TRAPS, are diseases of the innate immune system, these findings support the concept of

persistent innate immune activation between attacks. The Galway (Ireland) TRAPS cohort consists of

15 affected family members, 2 of whom have amyloidosis and all having the T50M mutation in the

TNFRSF1A gene [13]. A total of 9 members of this family attend the clinic regularly. Persistently raised

inflammatory markers were found in 7 of these patients, 2 members did not give consent for MRI due

to claustrophobia. A total of 5 members participated in the study, however during the course of the

study; one of these patients had normal inflammatory markers in spite of having persistently raised

markers before screening. Interview and clinical examination were performed to document

symptoms, frequency of flares, inflammatory markers and medications (Table 1). All cases described

classical attacks of fever, sweats, abdominal pain and serositis. They also had symptoms between

attacks including prominent myalgia, arthralgia, malaise and fatigue, with persistently elevated

inflammatory markers in 4 out of 5 patients confirming ongoing disease activity between attacks.

After obtaining informed consent, all 5 cases had whole body scanning on a Siemens 1.5 T MRI

(Siemens‐AG, Symphony). Images were reviewed on Agfa PACS High resolution workstation by two

fellowship trained musculoskeletal radiologists. One patient had a flare during the MRI and was

rescanned between flares. MRI results are shown in Table 1. Bilateral knee and hip effusions and bone

oedema of left tibia were found in one patient, who was asymptomatic at the time of his scan and did

not have osteoarthritis clinically or radiologically in this knee. Repeat MRI of the left knee was done. It

is possible that the knee changes could have been contributed to by ligament injury and joint

degeneration that was asymptomatic. Only one MRI of 5 was completely normal with corresponding

normal inflammatory markers (Figure 1). In conclusion, we provide MRI evidence for persistent

subclinical tissue inflammation in an identical pattern to that seen during classical attacks of TRAPS.

This suggests that the innate immune driven pathology is actually chronic and most likely represents

recurrent acute attacks of subclinical tissue inflammation. Unlike some other conditions of chronic

ME Research UK — Database of Research Publications 2009

Raison CL, Lin JM,

Reeves WC.

Ramdharry GM,

Day BL, Reilly MM,

Marsden JF.

Rao AV, Bested

AC, Beaulne TM,

Katzman MA, Iorio

Department of

Psychiatry and


Sciences, Emory

University School

of Medicine,

1365C Clifton

Road, Room 5004,

Atlanta, GA 30322,




St. George's School

of Physiotherapy



London, UK.

Integrative Care

Centre of Toronto,

3600 Ellesmere

Association of



markers with

chronic fatigue in a



in: Brain Behav

Immun. 2009


Hip flexor fatigue

limits walking in


Tooth disease.

A randomized,



Brain Behav

Immun. 2009


Epub 2008 Dec 11.

Muscle Nerve.

2009 Jul;40(1):103‐


Gut Pathog. 2009

Mar 19;1(1):6.

innate immune activation including Blau syndrome, the inflammation in TRAPS does not appear to

lead to target organ destruction [14]. The utility of whole body MRI for exploring febrile illness with a

TRAPS phenotype without TNFRS1A mutations is also worthy of consideration.

Alterations in the innate immune response may contribute to the pathogenesis of chronic fatigue

syndrome (CFS). However, studies have been limited by small sample sizes, use of patients from

tertiary care settings, inappropriate selection of controls, and failure to control for confounding

demographic, medical and behavioral factors independently associated with immune activity. It is

also not known whether specific symptoms account for observed associations between CFS and the

innate immune response. To address these limitations, the current study examined plasma

concentrations of high‐sensitivity c‐reactive protein (hs‐CRP), white blood cell count (WBC) and a

combined inflammation factor in a large population‐based sample. Log‐transformed mean plasma

concentrations of hs‐CRP were increased in subjects with CFS (n=102) and in subjects with unwellness

symptoms that did not meet diagnostic criteria for CFS (defined as "insufficient fatigue" [ISF]) (n=240)

when compared to subjects who were well (n=115). Log transformed WBC was increased in ISF and

was increased at a trend level in CFS. The combined inflammation factor was increased in both CFS

and ISF. Subjects with CFS and ISF did not differ on any of the inflammation measures. In the entire

subject population, the physical component summary score (PCS), but not the mental component

summary score (MCS), from the Medical Outcomes Study Short Form‐36 (SF‐36) was negatively

associated with each of the inflammation measures. Depressive symptoms were also associated with

increased log hs‐CRP. After adjustment for age, sex, race, location of residence, BMI, depressive

status and immune‐modulating medications, subjects classified as ISF continued to demonstrate

increased log hs‐CRP, WBC and elevations on the inflammation factor when compared to well

controls; however, associations between CFS and log hs‐CRP and the inflammation factor were no

longer statistically significant. After adjustment, PCS score also remained independently associated

with each of the inflammation measures. These findings support a role for innate immune activation

in unexplained fatigue and unwellness, but do not suggest that immune activation is specific to CFS.

Charcot‐Marie‐Tooth (CMT) disease results in distal lower limb weakness that affects walking. In this

study we assess the role of the hip flexors in compensating for distal weakness while walking and the

effects of prolonged walking on these putative compensatory strategies. Eighteen subjects with CMT

disease were compared with 14 matched controls while they walked on a treadmill to a

predetermined point of perceived effort. A significant reduction was observed in peak hip flexor

velocity during walking and hip flexor maximal voluntary contraction. In a second session following

selective fatigue of the hip flexors, hip flexor velocity decreased immediately on walking, and walking

duration was greatly reduced. This study suggests that hip flexors compensate for distal weakness and

that fatigue in the hip flexors can limit walking duration. Treatments directed toward improving

proximal muscle strength may therefore help to delay onset of hip flexor fatigue and thus prolong

walking duration.

ABSTRACT: Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad

range of symptoms, many patients report disturbances in the emotional realm, the most frequent of

which is anxiety. Research shows that patients with CFS and other so‐called functional somatic

ME Research UK — Database of Research Publications 2009

C, Berardi JM,

Logan AC.

Revicki DA, Rentz

AM, Luo MP,

Wong RL, Doward

LC, McKenna SP.

Reynolds NL,

Brown MM, Jason


Roberts AD,

Charler ML,

Papadopoulos A,

Wessely S, Chalder

T, Cleare AJ.

Road, Unit 4,

Toronto, Ontario

M1C 4Y8, Canada.


Center for Health


Research, United



Bethesda, MD,




pilot study of a

probiotic in


symptoms of

chronic fatigue




characteristics of

the ankylosing

spondylitis quality

of life


short form 36

health survey, and


assessment of

chronic illness



DePaul University. The relationship of

Fennell phases to

symptoms among

patients with

chronic fatigue


King's College

London, Institute

of Psychiatry,

Department of


Medicine, London,



predict a poor

response to



Health Qual Life

Outcomes. 2009

Jan 30;7:6.

Eval Health Prof.



Epub 2009 Aug 20.

Psychol Med. 2009

Jul 17:1‐8. [Epub

ahead of print]

disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that

pathogenic and non‐pathogenic gut bacteria might influence mood‐related symptoms and even

behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive

either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for

two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety

Inventories before and after the intervention. We found a significant rise in both Lactobacillus and

Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms

among those taking the probiotic vs controls (p = 0.01). These results lend further support to the

presence of a gut‐brain interface, one that may be mediated by microbes that reside or pass through

the intestinal tract.

The Fennell Phase Inventory (FPI) is an instrument designed to measure phases of the illnesses known

as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). The current study explored how

the FPI was related to physical and psychological functioning as well as coping style. Based on FPI

scores, 111 adults with ME/CFS were placed in one of three groups: crisis, stabilization, or resolution.

Results showed that the crisis group demonstrated significantly worse functioning than at least one

other group for depression, quality of life, mental functioning, anxiety, and self‐efficacy; and utilized

less adaptive coping styles. These results indicate that patients with ME/CFS who are in the crisis

phase tend to experience more severe psychological and physical symptoms and utilize poorer coping

strategies. Those in the resolution phase maintain the most adaptive coping strategies. Implications

for these findings are discussed.

BACKGROUND: There is evidence that patients with chronic fatigue syndrome (CFS) have mild

hypocortisolism. The clinical significance of this is unclear. We aimed to determine whether

hypocortisolism exerted any effect on the response of CFS to cognitive behavioural therapy

(CBT).MethodWe measured 24‐h urinary free cortisol (UFC) in 84 patients with Centers for Disease

Control and Prevention (CDC)‐defined CFS (of whom 64 were free from psychotropic medication) who

then received CBT in a specialist, tertiary out‐patient clinic as part of their usual clinical care. We also

ME Research UK — Database of Research Publications 2009

Roberts AD,

Papadopoulos AS,

Wessely S, Chalder

T, Cleare AJ.

Robinson M, Gray

SR, Watson MS,

Kennedy G, Hill A,

Belch JJ, Nimmo


Rodríguez MA,

Afari N, Buchwald

DS; National

Institute of

Diabetes and

Digestive and

Kidney Diseases

Working Group on

UK. therapy in chronic

fatigue syndrome?

King's College

London, Institute

of Psychiatry,

Department of


Medicine, De

Crespigny Park,

London SE5 8AF,



Institute of

Pharmacy and



University of


Glasgow, UK.

Department of


University Rey

Juan Carlos,

Madrid, Spain.

Salivary cortisol

output before and

after cognitive


therapy for chronic

fatigue syndrome.

Plasma IL‐6, its

soluble receptors

and F‐isoprostanes

at rest and during

exercise in chronic

fatigue syndrome.

Evidence for

overlap between

urological and



clinical conditions.

J Affect Disord.

2009 May;115(1‐

2):280‐6. Epub

2008 Oct 19.

Scand J Med Sci

Sports. 2009 Apr

13. [Epub ahead of


J Urol. 2009


31. Epub 2009 Sep


measured salivary cortisol output from 0800 to 2000 h in a subsample of 56 psychotropic medication‐

free patients. RESULTS: Overall, 39% of patients responded to CBT after 6 months of treatment. Lower

24‐h UFC output was associated with a poorer response to CBT but only in psychotropic medication‐

free patients. A flattened diurnal profile of salivary cortisol was also associated with a poor response

to CBT. CONCLUSIONS: Low cortisol is of clinical relevance in CFS, as it is associated with a poorer

response to CBT. Hypocortisolism could be one of several maintaining factors that interact in the

persistence of CFS.

BACKGROUND: There is evidence that patients with chronic fatigue syndrome (CFS) have mild

hypocortisolism. One theory about the aetiology of this hypocortisolism is that it occurs late in the

course of CFS via factors such as inactivity, sleep disturbance, chronic stress and deconditioning. We

aimed to determine whether therapy aimed at reversing these factors‐‐cognitive behavioural therapy

for CFS‐‐could increase cortisol output in CFS. METHODS: We measured diurnal salivary cortisol

output between 0800 and 2000 h before and after 15 sessions (or 6 months) of CBT in 41 patients

with CDC‐defined CFS attending a specialist, tertiary outpatient clinic. RESULTS: There was a

significant clinical response to CBT, and a significant rise in salivary cortisol output after CBT.

LIMITATIONS: We were unable to control for the passage of time using a non‐treated CFS group.

CONCLUSIONS: Hypocortisolism in CFS is potentially reversible by CBT. Given previous suggestions

that lowered cortisol may be a maintaining factor in CFS, CBT offers a potential way to address this.

The aim of the current study was to investigate the levels of interleukin‐6 (IL‐6), its soluble receptors

(sIL‐6R and sgp130) and F(2)‐isoprostanes, at rest and during exercise, in patients with chronic fatigue

syndrome (CFS). Six male CFS patients and six healthy controls performed an incremental exercise test

to exhaustion and a submaximal exercise bout to exhaustion. Blood samples taken in the submaximal

test at rest, immediately post‐exercise and 24 h post‐exercise were analyzed for IL‐6, sIL‐6R, sgp130

and F(2)‐isoprostanes. A further 33 CFS and 33 healthy control participants gave a resting blood

sample for IL‐6 and sIL‐6R measurement. During the incremental exercise test only power output at

the lactate threshold was lower (P

ME Research UK — Database of Research Publications 2009

Urological Chronic

Pelvic Pain.


Afari N, Buchwald

DS, Clauw D,

Dimitrakov J,

Kusek J, Mullins C,

Nyberg L, Payne C,

Peñacoba C,

Pezzone M,

Pontari M, Potts J,

Rodríguez MA,

Warren J.

Romano JM,

Jensen MP,

Schmaling KB,

Hops H, Buchwald


Rudolph T, Larsen

JP, Farbu E.

Department of

Psychiatry and



University of

Washington, Box

356560, Seattle,

WA, 98195, USA,



Department of









Illness behaviors in

patients with


chronic fatigue are

associated with

significant other


Is there a need for

long‐term follow‐

up in chronic



J Behav Med. 2009

Nov 14. [Epub

ahead of print]

Acta Neurol Scand.



52. Epub 2009 Sep


chronic prostatitis/chronic pelvic pain syndrome or vulvodynia with fibromyalgia, chronic fatigue

syndrome, temporomandibular joint and muscle disorders or irritable bowel syndrome. We

abstracted information on authorship, type of case and control groups, eligibility criteria, case

definitions, study methods and major findings. RESULTS: The literature suggests considerable

comorbidity between urological and nonurological unexplained clinical conditions. The most robust

evidence for overlap was for irritable bowel syndrome and urological unexplained syndromes with

some estimates of up to 79% comorbidity between chronic pelvic pain and symptoms of irritable

bowel syndrome. However, most studies were limited by methodological problems, such as varying

case definitions and selection of controls. CONCLUSIONS: The overlap between urological and

selected nonurological unexplained clinical conditions is substantial. Future research should focus on

using standardized definitions, and rigorously designed, well controlled studies to further assess

comorbidity, clarify the magnitude of the association and examine common pathophysiological


Chronic fatigue syndrome (CFS) and unexplained chronic fatigue (CF) are characterized by

compromised functional status and physical disability. Prior research on chronic pain has suggested

that social factors may contribute to disability. This study examined the relationship between

significant other responses and patient outcomes in patients with unexplained CF. Questionnaire data

were collected from 117 patients on physical function, fatigue, pain, illness behaviors and responses

of significant others to them, and depression. Ninety‐four SOs reported their perceptions of patient

illness behavior and their responses. Thirty‐seven of these dyads also completed a series of household

activities while being videotaped. Dyadic interactions were coded and analyzed. Both reported and

observed solicitous responses by the significant other were associated with reported and observed

patient illness behavior. Negative responses to patient illness behavior by significant others were

associated with higher levels of patient depressive symptoms. The findings provide support for the

role of operant behavioral factors in the context of chronic fatigue. They also suggest that further

research on the relationship between dysfunction and significant other responses in patients with CFS

or CF appears warranted and may have implications for treatment development.

OBJECTIVE: To evaluate the long‐term functional status and well‐being in patients with chronic

idiopathic polyneuropathy (CIP) in comparison to Guillain‐Barré syndrome (GBS) and healthy controls.

MATERIALS AND METHODS: Forty‐two CIP and 42 GBS‐patients were examined at median 5 and 6

years after disease onset and were compared with 50 healthy controls. The Fatigue Severity Scale

(FSS), Visual Analogue Scale for pain (VAS), Disability Rating Index (DRI) and Medical Outcome Study

36‐item short‐form health status scale (SF‐36) were used. Variables at onset and symptoms at follow‐

up were correlated with outcome measurements in GBS. RESULTS: Patients with CIP and GBS had

more pain and disability than healthy controls. Additionally, CIP‐patients were more fatigued than

healthy controls. Patients with CIP were more fatigued [FSS 4.9 (SD 1.6) vs 3.8 (SD 1.8); P < 0.01] and

disabled [DRI 4.1 (SD 2.3) vs 2.5 (SD 2.1); P = 0.05] than those with GBS. Physical functioning on the

SF‐36 was more impaired in CIP than GBS, compared with healthy controls. CONCLUSIONS: Patients

with CIP and GBS seem to develop persistent impairment on long‐term functional status and well‐

being, more clearly in CIP, reflecting the importance of long‐term follow‐up in further disease

ME Research UK — Database of Research Publications 2009

Sachdeva AK,

Kuhad A, Tiwari V,

Chopra K.

Sakudo A, Kato

YH, Tajima S,

Kuratsune H, Ikuta


Sakudo A,

Kuratsune H, Kato

YH, Ikuta K.




University Institute

of Pharmaceutical

Sciences, UGC

Centre of

Advanced Study,

Punjab University,

Chandigarh 160

014, India.

Department of

Virology, Center

for Infectious

Disease Control,

Research Institute

for Microbial

Diseases, Osaka


Yamadaoka, Suita,

Osaka 565‐0871,




Department of

Virology, Center

for Infectious

Disease Control,

Research Institute

for Microbial

Diseases, Osaka


Yamadaoka, Suita,

Osaka 565‐0871,




gallate ameliorates

chronic fatigue

syndrome in mice:

behavioral and



Visible and near‐

infrared spectral

changes in the

thumb of patients

with chronic

fatigue syndrome.


structural changes

of proteins in

fingernails of

chronic fatigue

syndrome patients

from Fourier‐

transform infrared


Behav Brain Res.

2009 Dec


Epub 2009 Jul 28.

Clin Chim Acta.

2009 May;403(1‐

2):163‐6. Epub

2009 Feb 25.

Clin Chim Acta.

2009 Apr;402(1‐

2):75‐8. Epub 2008

Dec 30.


Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is

still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems

to be multifactorial and the possible involvement of immune system is supported. The present study

was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of

immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus

administration, the mice showed significant increase in immobility period, post swim fatigue and

thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative‐nitrosative stress as

evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes

(superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of

tumor necrosis factor‐alpha and tissue growth factor‐beta). Chronic treatment with epigallocatechin

gallate restored these behavioral and biochemical alterations in mice. The present study points out

towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue

syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue


BACKGROUND: Chronic fatigue syndrome (CFS) patients show a persistent fatigue condition with

muscle pain and impairment of concentration, memory, and sleep. Presently, the physiological basis

of CFS remains unclear. In this study, spectroscopic differences in the thumb were compared between

103 CFS patients and 122 healthy controls to examine possible changes of levels of oxygenated or

deoxygenated hemoglobin. METHODS: Visible and near‐infrared (Vis‐NIR) spectroscopy was used to

examine possible changes in the region of 600‐1100 nm. RESULTS: Vis‐NIR spectra showed sharp

peaks at 694, 970 and 1060 nm and broad peaks in the regions of 740‐760 and 830‐850 nm. As these

peaks are possibly related to oxyhemoglobin, cytochrome c oxidase and water, levels of these factors

were compared between the two groups. Statistical analysis of the absorbance of Vis‐NIR spectra

showed a significant decrease in water content, a significant increase in oxyhemoglobin content, and

a significant increase in the oxidation of heme a+a(3) and copper in cytochrome c oxidase in CFS

patients. CONCLUSIONS: These changes imply accelerated blood flow and energy metabolism in the

thumbs of CFS patients.

BACKGROUND: Generally, nails can be an index of health, with abnormalities sometimes found under

diseased conditions. Fatigue is also supposed to affect the condition of nails. Possible differences in

infrared (IR) spectra of nail plates of chronic fatigue syndrome (CFS) patients compared to healthy

control subjects were investigated in this study. METHODS: Using an attenuated total reflection (ATR)‐

Fourier‐transform infrared (FTIR) spectrophotometer, spectra in the region of 4000‐600 cm(‐1) were

obtained. The amide I region was then separated by Fourier deconvolution and curve fitting based on

the Gauss and Lorentz formula and revealed differences in the secondary structural content of

proteins compared to healthy donors. RESULTS: The specific secondary structural pattern commonly

observed in nails of male and female CFS patients in the absence and presence of medication

indicated a decreased alpha‐helix content and increased beta‐sheet content, suggesting reduced

levels of normal elements of the nail plate. CONCLUSIONS: This provides the first evidence of

alterations in the fingernails of CFS patients which could be detected by IR spectroscopy. Possible

ME Research UK — Database of Research Publications 2009

Sampogna F,

Frontani M, Baliva

G, Lombardo GA,

Alvetreti G, Di

Pietro C, Tabolli S,

Russo G, Abeni D.

ka‐u.ac.jp explanations for the alterations will be discussed.

Health Services

Research Unit,




Rome, Italy.

Santhouse AM. South London and

Maudsley NHS

Foundation Trust,

London, UK.

Scheeres K, Knoop

H, Meer J,

Bleijenberg G.

Expert Centre

Chronic Fatigue,



Nijmegen Medical

Centre (4628), PO

Box 9101, 6500 HB

Nijmegen, The



Quality of life and


distress in patients

with cutaneous


Review: CBT

reduces fatigue in

adults with chronic

fatigue syndrome

but effects at



on: Cochrane

Database Syst Rev.



Clinical assessment

of the physical

activity pattern of

chronic fatigue


patients: a

validation of three


Br J Dermatol.



Epub 2008 Dec 16.

Evid Based Ment

Health. 2009


Health Qual Life

Outcomes. 2009

Apr 1;7:29.

BACKGROUND: Cutaneous lymphomas may have a profound impact on patients' health‐related

quality of life (HRQoL) and psychological well‐being. OBJECTIVES: To evaluate HRQoL and

psychological distress in patients with cutaneous lymphoma, and to evaluate them in relation to

personal and clinical characteristics. METHODS: Patients with cutaneous T‐cell lymphoma or

cutaneous B‐cell lymphoma (CBCL) were consecutively recruited in a dermatological hospital. Data on

HRQoL were collected using a dermatology‐specific questionnaire, the Skindex‐29, and an oncology‐

specific questionnaire, the EORTC QLQ‐C30. RESULTS: Of 95 patients, there were 24 with CBCL, 59

with mycosis fungoides (MF) and 12 with Sézary syndrome (SS). The most frequent items reported in

Skindex‐29 were itching and sensitive skin, being annoyed by the disease, worry that it could get

worse, affected interactions, and impairment in sexual life. The most frequent problems appearing

from the EORTC QLQ‐C30 analysis were fatigue, pain and insomnia. A worse HRQoL was observed for

all the scales in patients with SS, followed by MF, and CBCL. HRQoL impairment in all histotypes was

higher in women than in men, in patients with probable anxiety or depression, and when the disease

worsened. The highest prevalence of probable anxiety or depression was observed in patients

treated with systemic steroids (60%) and interferon (50%). CONCLUSIONS: The detailed evaluation of

HRQoL and psychological problems in patients with cutaneous lymphomas, and their relationship with

clinical variables, may give important information on the burden of the disease for patients, and thus

improve communication and satisfaction with care.

BACKGROUND: Effective treatment of chronic fatigue syndrome (CFS) with cognitive behavioural

therapy (CBT) relies on a correct classification of so called 'fluctuating active' versus 'passive' patients.

For successful treatment with CBT is it especially important to recognise the passive patients and give

them a tailored treatment protocol. In the present study it was evaluated whether CFS patient's

physical activity pattern can be assessed most accurately with the 'Activity Pattern Interview' (API),

the International Physical Activity Questionnaire (IPAQ) or the CFS‐Activity Questionnaire (CFS‐AQ).

METHODS: The three instruments were validated compared to actometers. Actometers are until now

the best and most objective instrument to measure physical activity, but they are too expensive and

time consuming for most clinical practice settings. In total 226 CFS patients enrolled for CBT therapy

answered the API at intake and filled in the two questionnaires. Directly after intake they wore the

ME Research UK — Database of Research Publications 2009

Schrijvers D, Van

Den Eede F, Maas

Y, Cosyns P,

Hulstijn W, Sabbe


mail.com actometer for two weeks. Based on receiver operating characteristic (ROC) curves the validity of the

three methods were assessed and compared. RESULTS: Both the API and the two questionnaires had

an acceptable validity (0.64 to 0.71). None of the three instruments was significantly better than the

others. The proportion of false predictions was rather high for all three instrument. The IPAQ had the

highest proportion of correct passive predictions (sensitivity 70.1%). CONCLUSION: The validity of all

three instruments appeared to be fair, and all showed rather high proportions of false classifications.

Hence in fact none of the tested instruments could really be called satisfactory. Because the IPAQ

showed to be the best in correctly predicting 'passive' CFS patients, which is most essentially related

to treatment results, it was concluded that the IPAQ is the preferable alternative for an actometer

when treating CFS patients in clinical practice.




Research Institute,

Faculty of


University of



1, 2610 Antwerp,




Shapiro JS. shapirjs@umich.ed



functioning in

chronic fatigue

syndrome and

major depressive

disorder: a

comparative study.

Does varicella‐

zoster virus

infection of the

peripheral ganglia

cause Chronic

Fatigue Syndrome?

J Affect Disord.

2009 May;115(1‐

2):46‐53. Epub

2008 Sep 24.

Med Hypotheses.



Epub 2009 Jun 10.

BACKGROUND: Studies comparing chronic fatigue syndrome (CFS) and major depressive disorder

(MDD) reported similarities as well as differences between the two disorders. However, whereas

psychomotor symptoms have been studied extensively in MDD, such research in CFS is more limited.

Moreover, the few studies that compared cognitive and motor performance in MDD and CFS yielded

inconsistent results. This study hence directly compares fine psychomotor functioning in both

syndromes. METHODS: Thirty‐eight patients diagnosed with CFS without a current major depressive

episode (MDE), 32 MDD patients with a current MDE and 38 healthy controls performed two

computerized copying tasks differing in complexity: a line‐copying task that mainly requires motor

effort and a figure‐copying task requiring additional cognitive efforts. All participants were female. A

multivariate general linear model was used to compute group differences. RESULT: Overall, both

patient groups performed more slowly than the controls. Compared to CFS patients, patients with

MDD needed significantly more time to copy the single lines but no such between‐group performance

difference was observed for the figure reproductions. In this latter copying task, the increasing

complexity of the figures resulted in prolonged reaction times for all three participant groups with the

effect being larger and the magnitude similar for the two patient groups. LIMITATIONS: All patients

were female and most were on psychotropic medication. CONCLUSIONS: Both the MDD and CFS

patients tested demonstrated an overall fine motor slowing, with the motor component being more

affected in the MDD patients than in the CFS patients while both patient groups showed similar

cognitive impairments.

This article posits that infection of the peripheral ganglia causes at least some cases of Chronic Fatigue

Syndrome (CFS), with a neurotropic herpesvirus, particularly varicella‐zoster virus (VZV), as the most

likely cause of the infection. Virtually all CFS symptoms could be produced by an infection of the

peripheral ganglia, with infection of the autonomic ganglia causing fatigue, postural hypotension, and

sleep disturbances, and infection of the sensory ganglia causing sensory symptoms such as chronic

pain. Furthermore, infections of the peripheral ganglia are known to cause long‐term nerve

dysfunction, which would help explain the chronic course of CFS. Herpesviruses have long been

suspected as the cause of CFS; this theory has recently been supported by studies showing that

administering antiherpes agents causes substantial improvement in some CFS patients. VZV is known

to frequently reactivate in the peripheral ganglia of previously healthy adults and cause sudden,

debilitating illness, making it a likely candidate as a cause of CFS. Moreover, many of the symptoms of

ME Research UK — Database of Research Publications 2009

Sheedy JR,

Wettenhall RE,

Scanlon D, Gooley

PR, Lewis DP,

McGregor N,

Stapleton DI, Butt

HL, DE Meirleir KL.

Sheng R, Xu X,

Tang Q, Bian D, Li

Y, Qian C, He X,

Gao X, Pan R,

Wang C, Luo Y, Xia

Y, Dai Y.

Bio21 Institute of

Biotechnology and

Molecular Science,

Department of

Biochemistry and

Molecular Biology,

Victoria, Australia.

Department of

Pharmacology of

Chinese Materia

Medica, China


University, 24 Tong

Jia Xiang Road,

Nanjing 210009,




Increased d‐lactic

Acid intestinal

bacteria in patients

with chronic

fatigue syndrome.

Polysaccharide of



Improves Chronic

Fatigue Syndrome

Induced by Poly I:C

in Mice.

In Vivo. 2009 Jul‐


Evid Based


Alternat Med..

[Epub ahead of


CFS overlap with those of herpes zoster (shingles), with the exception that painful rash is not one of

the symptoms of CFS. A model is therefore proposed in which CFS is one of the many manifestations

of zoster sine herpete; that is, herpes zoster without rash. Furthermore, re‐exposure to VZV in the

form of chickenpox has become less common in the past few decades; without such re‐exposure,

immunity to VZV drops, which could explain the increased incidence of CFS. Co‐infection with multiple

herpesviruses is a possibility, as some CFS patients show signs of infection with other herpesviruses

including Epstein‐Barr, Cytomegalovirus, and HHV6. These three herpesviruses can attack immune

cells, and may therefore promote neurotropic herpesvirus reactivation in the ganglia. The possibility

of VZV as the causal agent in CFS has previously received almost no attention; the possibility that CFS

involves infection of the peripheral ganglia has likewise been largely overlooked. This suggests that

the search for a viral cause of CFS has been far from exhaustive. Several antiherpes drugs are

available, as is a vaccine for VZV; more research into such agents as possible treatments for CFS is

urgently needed.

Patients with chronic fatigue syndrome (CFS) are affected by symptoms of cognitive dysfunction and

neurological impairment, the cause of which has yet to be elucidated. However, these symptoms are

strikingly similar to those of patients presented with D‐lactic acidosis. A significant increase of Gram

positive facultative anaerobic faecal microorganisms in 108 CFS patients as compared to 177 control

subjects (p

ME Research UK — Database of Research Publications 2009

Sigmon SC,

Herning RI, Better

W, Cadet JL,

Griffiths RR.

Silva‐Tinoco R,


L, Orea‐Tejeda A,


JJ, Vázquez‐Díaz O,


Hernández P,

Flores‐Rebollar A,

Reza‐Albarrán A.

Smith AK,

Maloney EM,

Falkenberg VR,

Dimulescu I,

Rajeevan MS.

Department of


University of

Vermont College of

Medicine, SATC‐

UHC, Room 1415,

Burlington, VT,

05401, USA.



Heart Failure

Clinic, Instituto

Nacional de

Ciencias Médicas y



Zubirán", Mexico

City, Mexico.

Division of Viral

and Rickettsial

Diseases, National

Center for

Zoonotic, Vector‐

Borne and Enteric


withdrawal, acute

effects, tolerance,

and absence of net

beneficial effects

of chronic


cerebral blood

flow velocity,

quantitative EEG,

and subjective


Developing thyroid

disorders is

associated with

poor prognosis

factors in patient

with stable chronic

heart failure.

An angiotensin‐1

converting enzyme

polymorphism is

associated with

allostatic load

mediated by C‐


gy (Berl). 2009


Epub 2009 Feb 25.

Int J Cardiol. 2009

Feb 8. [Epub ahead

of print]


rinology. 2009


606. Epub 2008

Dec 10.

spleens. PRP alleviated the abnormalities caused by poly I:C, and restored the function of hosts to

normal conditions. The findings suggest that PRP is beneficial to CFS, and the underlying mechanisms

of action involve neuroendocrine and immune systems.

RATIONALE: Although the subjective effects of caffeine abstinence, acute and chronic administration,

and tolerance are well described, the corresponding neurophysiological effects are not. OBJECTIVES:

Caffeine withdrawal, acute caffeine effects, caffeine tolerance, and net beneficial effects of chronic

caffeine administration were investigated using cerebral blood flow velocity, quantitative

electroencephalography (EEG), and subjective effects. MATERIALS AND METHODS: Sixteen regular

caffeine users participated in this double‐blind, within‐subject study during which they received acute

caffeine and placebo challenges (1) while maintained on 400 mg caffeine daily for > or =14 days and

(2) while maintained on placebo for > or =14 days. Blood flow velocity was determined for the middle

(MCA) and anterior (ACA) cerebral arteries using pulsed transcranial Doppler sonography. EEG was

recorded from 16 scalp sites. Subjective effects were assessed with questionnaires. RESULTS: Acute

caffeine abstinence (evaluated 24 h after placebo substitution) increased mean, systolic, and diastolic

velocity in the MCA and ACA and decreased pulsatility index in the MCA. Acute caffeine abstinence

increased EEG theta and decreased beta 2 power. Acute caffeine abstinence also increased measures

of Tired, Fatigue, Sluggish, and Weary and decreased ratings of Energetic, Friendly, Lively, and Vigor.

Acute caffeine effects were demonstrated across a wide range of measures, including cerebral blood

flow, EEG, and subjective effects. Tolerance and "complete" tolerance were observed on subjective

but not physiological measures. Chronic caffeine effects were demonstrated only on the measure of

EEG beta 2 power. CONCLUSION: Acute caffeine abstinence and administration produced changes in

cerebral blood flow velocity, EEG, and subjective effects. Tolerance to subjective but not physiological

measures was demonstrated. There was almost no evidence for net effects of chronic caffeine

administration on these measures. Overall, these findings provide the most rigorous demonstration to

date of physiological effects of caffeine withdrawal.

We sought to assess the developing of thyroid disorders in forty eight patients with chronic stable

heart failure and without thyroid abnormalities during six months follow‐up. Thyroid function

disorders were observed in 27.1% of the subjects: sick euthyroid syndrome (12.5%), subclinical

hypothyroidism (10.4%) and overt hypothyroidism (6.2%). Subjects with higher thyroid stimulating

hormone (TSH) levels at the end of the study had more hospitalizations. The developing of altered

thyroid profile was related to lower hemoglobin levels, smaller phase angle with bioelectrical

impedance method and more fatigue perception by the patients. This abnormal thyroid function

behavior on stable chronic heart failure and was observed as part of the disease progress and was

associated to worse prognosis factors as lower phase angle and anemia.

Allostatic load (AL) is a theoretical framework that describes the cumulative physiologic effects of

adaptation to change or stress throughout the lifespan. AL is operationalized by a composite index of

multiple biomarkers. Accordingly, genes, behavior and environment contribute to AL. To determine if

individual differences in AL may be influenced by inherent genetic variation, we calculated an

allostatic load index (ALI) for 182 Caucasian subjects derived from a population‐based study of chronic

fatigue syndrome. Nearly 65% of the subjects in this study sample reported fatiguing illness. ALI was

ME Research UK — Database of Research Publications 2009

Smith WR,

Strachan ED,

Buchwald D.

Sorensen B, Jones

JF, Vernon SD,

Rajeevan MS.

Diseases, Centers

for Disease Control

and Prevention,

1600 Clifton Road,

MSG41, Atlanta,

GA 30333, USA.

Department of

Psychiatry and


Sciences, School of


University of


Seattle, WA 98195,




Division of Viral

and Rickettsial

Diseases, National

Center for

Zoonotic, Vector‐

Borne, and Enteric

Diseases, Centers

reactive protein,

interleukin‐6 and


Coping, self‐

efficacy and

psychiatric history

in patients with

both chronic

widespread pain

and chronic



control of


activation in an

exercise model of

chronic fatigue


Gen Hosp

Psychiatry. 2009


52. Epub 2009 May


Mol Med. 2009


2):34‐42. Epub

2008 Nov 10.

calculated based on 11 measures representing metabolic, cardiovascular, inflammatory,

hypothalamic‐pituitary‐adrenal (HPA) axis and sympathetic nervous system (SNS) activities. Subjects

were dichotomized into high (ALI > or = 3) or low (ALI < 3) AL groups, and the association between

high AL and 129 polymorphisms in 32 genes related to the HPA axis, neurotransmission,

inflammation, cardiovascular and metabolic functions were evaluated. Polymorphisms in angiotensin‐

1 converting enzyme (ACE), corticotropin‐releasing hormone receptor 1 (CRHR1), and serotonin

receptors (HTR3A and HTR4) were associated with AL (p=0.0007‐0.0486), but only one polymorphism,

rs4968591, in ACE remained significant after correction for multiple comparisons. The T allele of ACE

rs4968591 was more common in subjects with high AL (67.5%) than in subjects with low AL (49.3%)

(p=0.0007), and this effect appeared independent of age, sex, body mass index and fatigue status.

Additionally, high interleukin‐6 (IL‐6; p(trend)=0.04), and C‐reactive protein (CRP; p(trend)=0.01)

levels, as well as low urinary cortisol levels in females (p=0.03) were associated with the T allele,

which may result in allele‐specific binding of the transcription factor, E2F1. Our results suggest a role

for ACE in the bidirectional communication between the central nervous and immune systems in

response to stress. Further studies will be needed (a) to replicate the association between AL and ACE

polymorphisms in population studies designed to differentiate the effects of sex, age and racial/ethnic

background, (b) to evaluate the effect of allele‐specific binding of E2F1 at rs4968591, and (c) to

examine the role of ACE in the co‐regulation of CRP, IL‐6 and cortisol.

OBJECTIVE: To investigate the relationship of coping style and self‐efficacy to functional impairment in

a group of patients with both chronic widespread pain (CWP) and chronic fatigue, as well as the

possible mediating role of psychiatric diagnosis. METHODS: We identified 138 consecutive clinic

patients who met criteria for CWP and chronic fatigue. We collected demographic and clinical

characteristics, as well as measures of emotion‐focused and problem‐focused coping styles, fatigue‐

related self‐efficacy and self‐reported general health. Psychiatric diagnoses were determined with a

structured interview. Short Form‐36 subscales of pain‐related and fatigue‐related functioning were

the dependent variables in ordinal multiple regression analyses to identify the best‐fit model for each.

RESULTS: In the final model for pain, increased functional impairment was associated with increased

emotion‐focused coping as well as less education, lower general health scores and higher body mass

index. Conversely, in the final model for fatigue, increased functional impairment was significantly

associated with less emotion‐focused coping, lower general health scores and lower self‐efficacy.

CONCLUSIONS: The unexpected finding that emotion‐focused coping was associated differently with

chronic pain and fatigue among patients who experience both symptoms is discussed in the context

of the research on the effects of self‐efficacy and possible treatment approaches.

Complement activation resulting in significant increases of C4a split product may be a marker of

postexertional malaise in individuals with chronic fatigue syndrome (CFS). This study focused on

identification of the transcriptional control that may contribute to the increased C4a in CFS subjects

after exercise. We used quantitative reverse‐transcription polymerase chain reaction to evaluate

differential expression of genes in the classical and lectin pathways in peripheral blood mononuclear

cells (PBMCs). Calibrated expression values were normalized to the internal reference gene

peptidylpropyl isomerase B (PPIB), the external reference gene ribulose‐1,5‐bisphosphate

ME Research UK — Database of Research Publications 2009

for Disease Control

and Prevention,

Atlanta, Georgia

30333, United

States of America.

Stahl SM. Department of


University of

California, San

Diego, CA, USA.



Staines DR, Brenu

EW, Marshall‐

Gradisnik S.


Health, Gold Coast

Population Health

Unit, Southport,

Gold Coast,




pathways and






affecting the


spinal barrier in




conditions: A role




2009 Jun;24 Suppl


Neuropsychiatr Dis

Treat. 2009;5:81‐9.

Epub 2009 Apr 8.

carboxylase/oxygenase large subunit (rbcL), or the geometric mean (GM) of the genes ribosomal

protein, large, P0 (RPLP0) and phosphoglycerate kinase 1 (PGK1). All nine genes tested, except

mannose‐binding lectin 2 (MBL2), were expressed in PBMCs. At 1 hour postexercise, C4, mannan‐

binding lectin serine protease 2 (MASP2) and ficolin 1 (FCN1) transcripts were detected at higher

levels (> or = 2‐fold) in at least 50% (4 of 8) of CFS subjects and were detected in 88% (7 of 8) CFS

subjects when subjects with overexpression of either C4 or MASP2 were combined. Only an increase

in the MASP2 transcript was statistically significant (PPIB, P = 0.001; GM, P = 0.047; rbcL, P = 0.045).

This result may be due to the significant but transient downregulation of MASP2 in control subjects

(PPIB, P = 0.023; rbcL, P = 0.027). By 6 hours postexercise, MASP2 expression was similar in both

groups. In conclusion, lectin pathway responded to exercise differentially in CFS than in control

subjects. MASP2 down‐regulation may act as an antiinflammatory acute‐phase response in healthy

subjects, whereas its elevated level may account for increased C4a and inflammation‐mediated

postexertional malaise in CFS subjects.

Fibromyalgia is a syndrome of widespread chronic pain associated with sleep disorders, depressed

mood, cognitive impairment and fatigue. Its etiology and pharmacopathology are poorly understood

but it is thought to result from a dysfunction of central pain processing mechanisms leading to

generalised pain sensitisation. Pain perception is the result of a bidirectional process of ascending and

descending pathways. Nociceptive input from peripheral afferent neurons is sent via the dorsal horn

of the spinal cord to the higher brain centres involved in pain perception. Some descending inhibitory

projections to the spinal cord attenuate the nociceptive effects. Numerous neurotransmitters

including serotonin, dopamine, noradrenaline and substance P are involved in these processes. In

other neuronal pathways in the brain, the same neurotransmitters are involved in mood control,

sleep regulation and cognitive function providing a neurochemical substrate for the wide range of

symptoms seen in fibromyalgia. Attenuation of neuronal hyperactivity through ligands acting at the

alpha2‐delta subunits of voltage‐dependent calcium channels and increased inhibitory activity of the

descending pathways by inhibition of serotonin and noradrenaline reuptake are two mechanisms that

are currently exploited by new medication for the treatment of fibromyalgia. Copyright (c) 2009 John

Wiley & Sons, Ltd.

Neuropsychiatric symptoms occur in a number of neurological fatigue‐related conditions including

multiple sclerosis (MS), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and chronic

fatigue syndrome (CFS). These conditions have been attributed variably to neuroinflammatory and

neurodegenerative processes. While autoimmune pathology, at least in part, has long been suspected

in these conditions proof has been elusive. Autoimmune pathomechanisms affecting the blood‐brain

barrier (BBB) or blood‐spinal barrier (BSB) may predispose the BBB/BSB to 'leakiness' and be a

precursor to additional autoimmune events resulting in neuroinflammatory or neurodegenerative

processes. The aim of the paper is to postulate immunopathology of the cerebrospinal perivascular

compartment involving certain vasoactive neuropeptides, specifically pituitary adenylate cyclase‐

activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP), in the etiology of certain

neuropsychiatric fatigue‐related conditions such as MS, ALS, PD, and CFS. Vasoactive neuropeptides

(VNs) such as PACAP and VIP have critical roles as neurotransmitters, vasodilators including perfusion

ME Research UK — Database of Research Publications 2009

Stewart JM. Department of

Pediatrics and

Physiology, New

York Medical


Hawthorne, NY

10532, USA.




inhibitors in


Chronic fatigue


comments on


blood volume and

resulting cardiac


Stubhaug B. [Treatment of

chronic fatigue


in Norwegian]

Sullivan A, Nord

CE, Evengård B.

Division of Clinical

Microbiology, F82,

Department of




University Hospital



Institutet, SE‐

14186 Stockholm,



Effect of

supplement with


producing bacteria

on fatigue and

physical activity in

patients with

chronic fatigue


Clin Sci (Lond).

2009 Oct


Comment on: Clin

Sci (Lond). 2010


Tidsskr Nor

Laegeforen. 2009



Nutr J. 2009 Jan


and hypoxia regulators, and immune and nociception modulators. PACAP and VIP are widely

distributed in the central nervous system (CNS) and have key roles in CNS blood vessels including

maintaining functional integrity of the BBB and BSB. Autoimmunity affecting these VNs would likely

have a detrimental effect on BBB and BSB functioning arguably predisposing to further pathological

processes. Virchow‐Robin spaces (VRS) are perivascular compartments surrounding small vessels

within the CNS which contribute to the BBB and BSB integrity and contain PACAP and VIP receptors.

Autoimmunity of these receptors would likely affect BBB and VRS function and therefore may

contribute to the etiology of these conditions by affecting CNS and immunological homeostasis,

including promoting neuropsychological symptomatology. PACAP and VIP, as potent activators of

adenylate cyclase (AC), have a key role in cyclic adenosine monophosphate (cAMP) production

affecting regulatory T cell (Treg) and other immune functions. Phosphodiesterase enzymes (PDEs)

catalyze cAMP and PDE inhibitors (PDEIs) maintain cAMP levels and have proven and well known

therapeutic benefit in animal models such as experimental allergic encephalomyelitis (EAE). Therefore

PDEIs may have a role in therapy for certain neuropsychiatric fatigue‐related conditions.

Cardiovascular and autonomic dysfunction have been suggested to underlie the symptoms

accompanying CFS (chronic fatigue syndrome). In the present issue of Clinical Science, Hurwitz and co‐

workers have investigated whether deficits were present in cardiac output and blood volume in a

cohort of patients with CFS and if these were linked to illness severity and sedentary lifestyle. The

results clearly demonstrate reduced cardiac stroke volume and cardiac output in more severely

afflicted patients with CFS, which is primarily attributable to a measurable reduction in blood volume.

Similar findings are observed in microgravity and bed rest deconditioning, in forms of orthostatic

intolerance and, to a lesser extent, in sedentary people. The circulatory consequences of reduced

cardiac output may help to account for many of the findings of the syndrome.

Disturbances in intestinal microbial ecology and in the immune system of the host have been

implicated as a part of the pathogenesis in chronic fatigue syndrome. Probiotic lactic acid producing

bacteria have been shown to prevent and alleviate gastrointestinal disturbances and to normalize the

cytokine profile which might be of an advantage for patients suffering from chronic fatigue syndrome.

The aim of the study was to evaluate the effect of Lactobacillus paracasei ssp. paracasei F19,

Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12 on fatigue and physical activity

in CFS patients. Fifteen patients fulfilling the criteria set by international researchers in the field at the

US Centre for Disease Control and Prevention in 1994 for chronic fatigue syndrome, were included in

the study. The patients had high fatigue severity scores and high disability scores. During the first two

weeks baseline observations without treatment were assessed, succeeded by four weeks of intake of

a probiotic product and a four‐week follow‐up period. The fatigue, health and physical activity was

assessed by the use of the Visual Analogue Scales and the SF‐12 Health Survey. Faecal samples were

collected and the normal microflora was analysed. Neurocognitive functions improved during the

ME Research UK — Database of Research Publications 2009

Sun JF, Wu RR,

Norris C, Noone

AM, Amankwa‐

Sakyi M, Slack R,

Marshall JL.

Sutcliffe K, Gray J,

Tan MP, Pairman

J, Wilton K, Parry

SW, Newton JL.



Cancer Center,


University Medical


Washington, DC.



Research Centre in

Ageing ‐


Theme, Newcastle,


Safety of chronic


capecitabine as


therapy in



Home orthostatic

training in chronic

fatigue syndrome‐‐

a randomized,


feasibility study.


Cancer Res. 2009


Eur J Clin Invest.

2010 Jan;40(1):18‐

24. Epub 2009 Nov


study period while there were no significant changes in fatigue and physical activity scores. No major

changes occurred in the gastrointestinal microflora. At the end of the study 6 of 15 patients reported

that they had improved according to the assessment described. The findings in this study that

improvement of health is possible to achieve should encourage further studies with interventions

with probiotics in patients with CFS.

BACKGROUND: Maintenance chemotherapy is not routinely used in gastrointestinal (GI) cancers.

Capecitabine is an oral formulation that is enzymatically converted to 5‐fluorouracil preferentially in

tumor tissue. We hypothesize that capecitabine could be used as a long‐term maintenance therapy to

improve outcomes in patients with high‐risk GI cancers following standard chemotherapy regimens.

METHODS: We conducted a retrospective study to assess the toxicity of maintenance capecitabine in

28 patients with a variety of advanced GI malignancies. Capecitabine 1,000 mg twice daily without

interruption was used for the first 11 patients. The dose was reduced to 1,000 mg twice daily 5 days

per week in 8 patients who developed hand‐foot syndrome. The remaining patients began treatment

on the same abbreviated schedule. All documented clinical adverse events were graded according to

the National Cancer Institute Common Terminology Criteria for Adverse Events (v3.0, 2003). RESULTS:

Main toxicities were grade 1/2 fatigue and hand‐foot syndrome. Only one grade 3 toxicity was

observed and no grade 4 toxicities were seen. We also observed a significant increase in red blood cell

mean corpuscular volume in participants, which may have potential use as a biomarker to monitor

therapeutic response. CONCLUSIONS: Fixed therapeutic doses of oral capecitabine 1,000 mg twice

daily, 5 days on, 2 days off, can be administered chronically with a high level of safety and should be

explored in larger prospective studies to demonstrate efficacy in GI malignancies, especially

pancreatic and metastatic colorectal cancers.

BACKGROUND: Orthostatic (Tilt)‐training is an effective treatment for neurally mediated hypotension

(NMH). NMH is a frequent finding in chronic fatigue syndrome (CFS). We evaluated home orthostatic

training (HOT) in CFS in a randomized placebo‐controlled feasibility study. METHODS: Thirty‐eight

patients with CFS (Fukuda Criteria) were randomly allocated to daily tilt training (n = 19) or sham

training (n = 19) for 6 months. Haemodynamic responses to standing were performed in all subjects

using continuous technology (Taskforce) at enrolment, week 1, 4 and 24. Symptom response and

compliance were assessed using diaries. RESULTS: Two patients (one from each arm) withdrew from

the study. Fourteen patients in each group complied completely or partially, and patients found the

training manageable and achievable. Compared to the sham group, blood pressure while standing

dropped to 8.0 mmHg less in the HOT group at 4 weeks (95% CI: 1.0 to 15.0, P = 0.03). At 4 weeks, the

HOT group had higher total peripheral resistance compared to the sham group; mean difference 70.2,

95% CI: ‐371.4 to 511.8. Changes were maintained at 6 months. There was no significant difference in

fatigue between groups at 4 weeks (mean difference 1.4, 95% CI: ‐13.5 to 16.2), but there was a trend

towards improvement in fatigue at 6 months. Compliers had lower fatigue compared to non‐

compliers. CONCLUSIONS: A placebo‐controlled study of HOT in CFS is feasible. HOT is well tolerated

and generally complied with. A likely physiological rationale for HOT in CFS is related to reductions in

orthostatic intolerance. An adequately powered study including strategies to enhance compliance is


ME Research UK — Database of Research Publications 2009

Tak LM, Riese H,

de Bock GH,

Manoharan A, Kok

IC, Rosmalen JG.

Tan PJ, Xu M,

Sessler DI,

Bashour CA.

Taylor A, Glover V,

Marks M,

Kammerer M.


Center for



University Medical

Center Groningen,

University of


Hanzeplein 1, 9700

RB, Groningen, The




Department of


Health Sciences,

Cleveland Clinic,

9500 Euclid

Avenue, Cleveland,

OH 44195, USA.

Imperial College

London, Institute

of Reproductive



As good as it gets?

A meta‐analysis

and systematic

review of


quality of heart

rate variability

studies in

functional somatic


Operation timing

does not affect

outcome after

coronary artery

bypass graft


Diurnal pattern of

cortisol output in



Biol Psychol. 2009


Epub 2009 May 20.





rinology. 2009


Epub 2009 Apr 29.

Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial

stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and

irritable bowel syndrome. We present the first meta‐analysis and systematic review of

methodological study quality on the association between cardiac ANS dysfunction, measured as

parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature

search revealed 23 available studies including data on 533 FSD patients. Meta‐analysis on a subgroup

of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared

to controls (weighted standardized mean difference (SMD)=‐0.32, 95% CI ‐0.63 to ‐0.01, p=0.04). The

reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity

in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot

asymmetry=0.01, 95% CI ‐0.34 to 0.36, p=0.95). The systematic review of overall methodological

quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially

in selection of healthy control subjects, blinding of researchers performing HRV measurements,

report of adequate HRV outcomes, and assessment of and adjustment for potential confounders.

Methodological study quality was, however, not a significant predictor of study findings. We conclude

that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in

FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.

BACKGROUND: Human factors such as fatigue, circadian rhythms, scheduling, and staffing may have

an impact on patient care over the course of a day across all medical specialties. Research by the

transportation industry concludes that human performance is degraded by shift work, circadian

rhythm disturbances, and prolonged duty. This study investigated whether the timing of coronary

artery bypass graft surgery affects outcomes. METHODS: The outcomes of coronary artery bypass

graft surgery patients were analyzed according to the hour of the day, day of the workweek, month,

and moon phase in which the surgery started. All patients who underwent isolated coronary artery

bypass graft surgery between January 1, 1993 and July 1, 2006 were considered for the study.The

primary outcome measurement was a compound morbidity outcome of six variables defined by the

Society of Thoracic Surgeons. These outcomes included (1) in‐hospital death, (2) acute postoperative

myocardial infarction, (3) neurologic morbidity, including focal or global neurologic deficits or death

without awakening, (4) serious infection morbidity consisting of sepsis syndrome or septic shock, (5)

new‐onset renal failure requiring dialysis, and (6) postoperative ventilatory support exceeding 72 h.

RESULTS: The composite morbidity and in‐hospital mortality rates were 4.8% and 1.4%, respectively.

The number of cases each weekday, each month of the year, and during each phase of the moon

were consistent. None of the time factors significantly affected the composite morbidity outcome.

CONCLUSIONS: Elective coronary artery bypass graft surgery can be scheduled throughout the

workday, any day of the work week and in any month of the year without compromising outcome.

This study investigated the diurnal output of saliva cortisol in women with symptoms of depression

postnatally. Twenty‐one depressed and 30 non‐depressed women at 7.5 weeks postpartum, and 21

non‐perinatal controls, collected saliva at waking, 30 min, and 3 and 12h postwaking. Women who

were not depressed postnatally showed a pattern of cortisol secretion over the day similar to non‐

perinatal controls. There was a significant difference in diurnal pattern between postnatally

ME Research UK — Database of Research Publications 2009

Thomas M, Smith


Tian H, Brimmer

DJ, Lin JM,

Tumpey AJ,

Reeves WC.



Campus, Du Cane

Road, London W12

0NN, UK.



Centre for

Occupational and

Health Psychology,

School of

Psychology, Cardiff

University, UK.

Centers for

Diseases Control

and Prevention,

Chronic Viral

Disease Branch,

Division of Viral

and Rickettsial

Diseases, Atlanta,

GA 30333, USA.


An investigation

into the cognitive

deficits associated

with chronic

fatigue syndrome.

Web usage data as

a means of

evaluating public

health messaging

and outreach.

Open Neurol J.

2009 Feb 27;3:13‐


J Med Internet

Res. 2009 Dec


depressed and postnatally non‐depressed women, due to a difference in the first two time points

(waking and +30 min): compared to the other two groups who each had a significant increase in

cortisol levels from waking to +30 min, the depressed women had significantly higher cortisol levels at

waking and no increase at +30 min. The lack of a morning rise in the depressed women is similar to

that reported for posttraumatic stress disorder and chronic fatigue syndrome and may reflect a

response, in vulnerable women, to the marked cortisol withdrawal that occurs after delivery.

This study addresses, among other things, the debate as to whether cognitive deficits do occur with a

diagnosis of Chronic Fatigue Syndrome (CFS). Previous studies have indicated a potential mismatch

between subjective patient ratings of impairment and clinical assessment. In an attempt to tackle

some of the methodological problems faced by previous research in this field, this study recruited a

large sample of CFS patients where adequate diagnosis had been made and administered an

extensive battery of measures. In doing so this study was able to replicate previous published

evidence of clear cognitive impairment in this group and demonstrate also that these deficits

occurred independent of psychopathology. The conclusion drawn is that cognitive impairments can

be identified if appropriate measures are used. Furthermore, the authors have shown that

performance changes in these measures have been used to assess both efficacy of a treatment

regime and rates of recovery.

BACKGROUND: The Internet is increasingly utilized by researchers, health care providers, and the

public to seek medical information. The Internet also provides a powerful tool for public health

messaging. Understanding the needs of the intended audience and how they use websites is critical

for website developers to provide better services to the intended users. OBJECTIVE: The aim of the

study was to examine the utilization of the chronic fatigue syndrome (CFS) website at the Centers for

Disease Control and Prevention (CDC). We evaluated (1) CFS website utilization, (2) outcomes of a

CDC CFS public awareness campaign, and (3) user behavior related to public awareness campaign

materials and CFS continuing medical education courses. METHODS: To describe and evaluate Web

utilization, we collected Web usage data over an 18‐month period and extracted page views, visits,

referring domains, and geographic locations. We used page views as the primary measure for the CFS

awareness outreach effort. We utilized market basket analysis and Markov chain model techniques to

describe user behavior related to utilization of campaign materials and continuing medical education

courses. RESULTS: The CDC CFS website received 3,647,736 views from more than 50 countries over

the 18‐month period and was the 33rd most popular CDC website. States with formal CFS programs

had higher visiting density, such as Washington, DC; Georgia; and New Jersey. Most visits (71%) were

from Web search engines, with 16% from non‐search‐engine sites and 12% from visitors who had

bookmarked the site. The public awareness campaign was associated with a sharp increase and

subsequent quick drop in Web traffic. Following the campaign, user interest shifted from information

targeting consumer basic knowledge to information for health care professionals. The market basket

analysis showed that visitors preferred the 60‐second radio clip public service announcement over the

30‐second one. Markov chain model results revealed that most visitors took the online continuing

education courses in sequential order and were less likely to drop out after they reached the

ME Research UK — Database of Research Publications 2009

Tietjen GE,

Brandes JL,

Peterlin BL, Eloff

A, Dafer RM, Stein

MR, Drexler E,

Martin VT,

Hutchinson S,

Aurora SK,

Recober A, Herial

NA, Utley C, White

L, Khuder SA.

University of

Toledo College of

Medicine, Toledo,


Tietjen, N.A.

Herial, C. Utley, L.

White, and S.A.

Khuder); Nashville


Group, Nashville,


Brandes); Drexel

University College

of Medicine,

Philadelphia, PA,

USA (B.L. Peterlin);

University of

Calgary, Calgary,

AB, Canada (A.

Eloff); Loyola

University Medical

Center, Maywood,


Dafer); John Muir

Medical Center,

Walnut Creek, CA,

USA (M.R. Stein);


Medical Center,

Brooklyn, NY, USA

(E. Drexler);

University of


Maltreatment and

Migraine (Part III).

Association With

Comorbid Pain


Headache. 2009

Oct 21. [Epub

ahead of print]

Introduction pages of the courses. CONCLUSIONS: The utilization of the CFS website reflects a high

level of interest in the illness by visitors to the site. The high utilization shows the website to be an

important online resource for people seeking basic information about CFS and for those looking for

professional health care and research information. Public health programs should consider analytic

methods to further public health by understanding the characteristics of those seeking information

and by evaluating the outcomes of public health campaigns. The website was an effective means to

provide health information about CFS and serves as an important public health tool for community


(Headache 2009;**:**‐**) Objective.‐ To evaluate in a headache clinic population the relationship of

childhood maltreatment on the prevalence of pain conditions comorbid with migraine. Background.‐

Childhood maltreatment is highly prevalent and has been frequently associated with recurrent

headache. The relationship of maltreatment and pain has, however, been a subject of some debate.

Methods.‐ Cross‐sectional data on self‐reported physician‐diagnosed pain conditions were

electronically collected from persons with migraine (diagnosed according to International

Classification of Headache Disorders‐2), seeking treatment in headache clinics at 11 centers across the

US and Canada. These included irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS),

fibromyalgia (FM), interstitial cystitis (IC), arthritis, endometriosis, and uterine fibroids. Other

information included demographics, migraine characteristics (frequency, headache‐related disability),

remote and current depression (The Patient Health Questionnaire‐9), and remote and current anxiety

(The Beck Anxiety Inventory). Patients also completed the Childhood Trauma Questionnaire regarding

sexual, emotional, and physical abuse, and emotional and physical neglect under the age of 18 years

old. Statistical analyses accounted for the survey design and appropriate procedures in SAS such as

surveymeans, surveyfreq, and surveylogistic were applied to the weighted data. Results.‐ A total of

1348 migraineurs (88% women) were included in this study (mean age 41 years). Based on physician

diagnosis or validated criteria, 31% had IBS, 16% had CFS, and 10% had FM. Diagnosis of IC was

reported by 6.5%, arthritis by 25%, and in women, endometriosis was reported by 15% and uterine

fibroids by 14%. At least 1 comorbid pain condition was reported by 61%, 2 conditions by 18%, and 3

or more by 13%. Childhood maltreatment was reported by 58% of the patients. Emotional abuse was

associated with increased prevalence of IBS, CFS, arthritis, and physical neglect with arthritis. In

women, physical abuse was associated with endometriosis and physical neglect with uterine fibroids.

Emotional abuse, and physical abuse and neglect (P < .0001 for all) were also associated with

increased total number of comorbid conditions. In ordinal logistic regression models, adjusted for

sociodemographics and current depression (prevalence 28%) and anxiety (prevalence 56%),

emotional abuse (odds ratios [OR] = 1.69, 95% confidence intervals [CI]: 1.224‐2.33) and physical

neglect (OR = 1.73, 95% CI: 1.22‐2.46) were independently associated with an increased number of

pain conditions. The cohort of women, similarly, had associations of emotional abuse (OR = 1.94, 95%

CI: 1.40‐2.72) and physical neglect (OR = 1.90, 95% CI: 1.34‐2.68) with an increased number of pain

comorbidities. Conclusion.‐ The association of childhood maltreatment and pain was stronger in those

reporting multiple pain conditions and multiple maltreatment types. This finding suggests that in

migraineurs childhood maltreatment may be a risk factor for development of comorbid pain

ME Research UK — Database of Research Publications 2009

Tietjen GE,

Brandes JL,

Peterlin BL, Eloff

A, Dafer RM, Stein

MR, Drexler E,

Martin VT,

Hutchinson S,

Aurora SK,

Recober A, Herial

NA, Utley C, White

L, Khuder SA.


Cincinnati, OH,

USA (V.T. Martin);

Orange County

Migraine &

Headache Center,

Irvine, CA, USA (S.


Swedish Headache

Center, Seattle,


Aurora); University

of Iowa, Iowa City,



The University of

Toledo College of

Medicine, Toledo,


Allodynia in


association with

comorbid pain


Headache. 2009



BACKGROUND: Cutaneous allodynia (CA) in migraine is a clinical manifestation of central nervous

system sensitization. Several chronic pain syndromes and mood disorders are comorbid with

migraine. In this study we examine the relationship of migraine‐associated CA with these comorbid

conditions. We also evaluate the association of CA with factors such as demographic profiles,

migraine characteristics, and smoking status that may have an influence on the relationships of CA to

pain and mood. METHODS: Data are from a cross‐sectional multicenter study of comorbid conditions

in persons seeking treatment in headache clinics. Diagnosis of migraine was determined by a

physician based on the International Classification of Headache Disorders‐II criteria. Participants

completed a self‐administered questionnaire ascertaining sociodemographics, migraine‐associated

allodynia, physician‐diagnosed comorbid medical and psychiatric disorders, headache‐related

disability, current depression, and anxiety. RESULTS: A total of 1413 migraineurs (mean age = 42

years, 89% women) from 11 different headache treatment centers completed a survey on the

prevalence of comorbid conditions. Aura was reported by 38% and chronic headache by 35% of the

participants. Sixty percent of the study population reported at least one migraine‐related allodynic

symptom, 10% reported > or =4 symptoms. Symptoms of CA were associated with female gender,

body mass index, current smoking, presence of aura, chronic headaches, transformed headaches,

severe headache‐related disability, and duration of migraine illness from onset. The prevalence of

self‐reported physician diagnosis of comorbid pain conditions (irritable bowel syndrome, chronic

fatigue syndrome, fibromyalgia) and psychiatric conditions (current depression and anxiety) was also

associated with symptoms of CA. Adjusted ordinal regression indicated a significant association

between number of pain conditions and severity of CA (based on symptom count). Adjusting for

sociodemographics, migraine characteristics, and current depression and anxiety, the likelihood of

reporting symptoms of severe allodynia was much higher in those with 3 or more pain conditions

(odds ratio = 3.03, 95% confidence interval: 1.78‐5.17), and 2 pain conditions (odds ratio = 2.67, 95%

confidence interval: 1.78‐4.01) when compared with those with no comorbid pain condition.

ME Research UK — Database of Research Publications 2009

Trock D . Tired, achy, and

overweight, the


nature of


on: J Clin

Rheumatol. 2007


Turan T, Izgi HB,

Ozsoy S,

Tanrıverdi F,

Basturk M,

Asdemir A, Beşirli

A, Esel E, Sofuoglu


Twisk FNM, Maes


Department of

Psychiatry, Erciyes

University Medical

School, Kayseri,




Limmen, the

Netherlands, the


The Effects of



Treatment on


terone Sulfate and

Cortisol Levels in

Patients with

Chronic Fatigue


A review on


behavorial therapy

(CBT) and graded

exercise therapy

(GET) in myalgic


J Clin Rheumatol.

2009 Feb;15(1):50.

Psychiatry Investig.

2009 Sep;6(3):204‐

210. Epub 2009

Jun 23.





CONCLUSION: Symptoms of CA in migraine were associated with current anxiety, depression, and

several chronic pain conditions. A graded relationship was observed between number of allodynic

symptoms and the number of pain conditions, even after adjusting for confounding factors. This study

also presents the novel association of CA symptoms with younger age of migraine onset, and with

cigarette smoking, in addition to confirming several previously reported findings.

OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue

syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic

neurotransmission may cause the hypothalamic‐pituitary‐adrenal axis hypoactivity seen in CFS.

Therefore, we investigated the alterations in stress hormones such as cortisol and

dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4‐week administration of

galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate

whether there are any relationships between the probable hormonal changes and cholinergic

treatment. METHODS: Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients

who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy

controls. In the patient group, four weeks after 8 mg/d galantamine hydrobromide treatment, cortisol

and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were

divided into two subgroups as responders and nonresponders according to the reduction in their

Newcastle Research Group ME/CFS Score Card (NRG) scores. RESULTS: Important findings of this

study are lower pre‐and post‐treatment cortisol levels and in all CFS patients compared to controls

(F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher

DHEAS/cortisol molar ratios which were normalized following four weeks' treatment with 8 mg/d

galantamine hydrobromide in the treatment‐respondent group (F=5.382, p=0.029; F=5.722, p=0.025,

respectively). CONCLUSION: The findings of the decrease in basal DHEAS levels and DHEAS/cortisol

molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit

hypothesis in CFS.

Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a debilitating disease

which, despite numerous biological abnormalities has remained highly controversial. Notwithstanding

the medical pathogenesis of ME/CFS, the (bio)psychosocial model is adopted by many governmental

organizations and medical profes‐sio‐nals to legitimize the combination of Cognitive Behavioral

Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this model CBT and GET

aim at eliminating presumed psychogenic and socially induced maintaining factors and reversing

deconditioning, respectively. In this review we invalidate the (bio)psychosocial model for ME/CFS and

ME Research UK — Database of Research Publications 2009

Ulvestad E. Avdeling for

mikrobiologi og




us og Gades


Universitetet i

Bergen 5021




Vallings R. Howick Health and

Medical Clinic,

New Zealand.

van Alfen N, van

der Werf SP, van

Engelen BG.

Department of



Centre Nijmegen,

Donders Center for




Nijmegen Medical

Centre, Nijmegen,

The Netherlands.

(ME) / chronic

fatigue syndrome


not only ineffective

and not evidence‐

based, but also

potentially harm

[Expert‐‐but on

what?][Article in


nt in: Tidsskr Nor

Laegeforen. 2009



A case of Chronic

Fatigue Syndrome

following H1N1

influenza (swine


Long‐term pain,

fatigue, and

impairment in



Tidsskr Nor

Laegeforen. 2009



J Clin Pathol. 2009

Oct 26. [Epub

ahead of print]

Arch Phys Med

Rehabil. 2009


demonstrate that the success claim for CBT/GET to treat ME/CFS is unjust. CBT/GET is not only hardly

more effective than non‐interventions or standard medical care, but many patients report that the

therapy had affected them adversely, the majority of them even reporting substantial deterioration.

Moreover, this review shows that exertion and thus GET most likely have a negative impact on many

ME/CFS patients. Exertion induces post‐exertional malaise with a decreased physical

performan‐ce/aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, “fatigue”,

and weakness, and a long lasting “recovery” time. This can be explained by findings that exertion may

amplify pre‐existing pa‐thophysiological abnormalities underpinning ME/CFS, such as inflammation,

immune dysfunction, oxidative and nitrosative stress, channelopathy, defec‐tive stress response

mechanisms and a hypoactive hypothalamic‐pituitary‐adrenal axis. We conclude that it is unethical to

treat patients with ME/CFS with ineffective, non‐evidence‐based and potentially harmful

“rehabilitation therapies”, such as CBT/GET.

Chronic fatigue syndrome has received much attention owing to its debilitating character. The

question as to whether the vaccine against meningococcus group B can provoke chronic fatigue

syndrome has recently been addressed. Consensus in Norway seems to be that the vaccine does not

provoke the syndrome. The article presents my reasons for questioning this conclusion.

Case report of an adolescent boy who was diagnosed as suffering from Chronic Fatigue Syndrome 5

months after infection with H1N1 influenza.

OBJECTIVES: Recently, it has become clear that neuralgic amyotrophy (NA; idiopathic and hereditary

brachial plexus neuropathy) has a less optimistic prognosis than usually assumed. To optimize

treatment and management of these patients, one needs to know the residual symptoms and

impairments they suffer. Therefore, the objective of this study was to describe the prevalence of pain,

psychologic symptoms, fatigue, functional status, and quality of life in patients with NA. SETTING:

Neurology outpatient department of an academic teaching hospital. PARTICIPANTS: NA patients

(N=89) were studied, and clinical details were recorded. Self‐report data were on average collected 2

years after the onset of the last NA episode. MAIN OUTCOME MEASURES: Pain was assessed with the

McGill Pain Questionnaire, fatigue with the Checklist Individual Strength, and psychologic distress

with the Symptom Checklist 90. Functional status and handicap were assessed with the modified

Rankin Scale and Medical Outcomes Study 36‐Item Short‐Form Health Survey. RESULTS: Pain was

ME Research UK — Database of Research Publications 2009

Van Campen E,

Van Den Eede F,

Moorkens G,

Schotte C, Schacht

R, Sabbe BG,

Cosyns P, Claes SJ.

Van Houdenhove

B, Luyten P.

Van Houdenhove

B, Van Den Eede F,

Luyten P.



Dept. of


Antwerp University

Hospital, Antwerp,


Department of


University of

Leuven, Leuven,





Department of

Liaison Psychiatry,


Hospitals K.U.

Leuven, Herestraat

49, B‐3000 Leuven,





Use of the

Temperament and


Inventory (TCI) for

assessment of

personality in

chronic fatigue


Treatment of

chronic fatigue

syndrome: how to

find a 'new





axis hypofunction

in chronic fatigue

syndrome reflect a

'crash' in the stress



2009 Mar‐


Patient Educ

Couns. 2009


Epub 2009 Sep 20.

Comment on:

Patient Educ

Couns. 2009


Patient Educ

Couns. 2009


Med Hypotheses.



Epub 2009 Feb 23.

usually localized in the right shoulder and upper arm, matching the clinical predilection site for paresis

in NA. About a quarter to a third of the patients reported significant long‐term pain and fatigue, and

half to two thirds still experienced impairments in daily life. Over one third of the individual patients

suffered from severe fatigue. The group did not fulfill the criteria of chronic fatigue or major

psychologic distress. There was no correlation of pain or fatigue with the level of residual paresis on a

Medical Research Council scale, but patients with a comorbid condition fared worse than patients

without. CONCLUSIONS: A significant number of NA patients suffer from persistent pain and fatigue,

leading to impairment. Symptoms were not correlated with psychologic distress. This makes it likely

that they are caused by residual shoulder or arm dysfunction but not as part of a chronic pain or

fatigue syndrome in these patients.

BACKGROUND: Chronic fatigue syndrome (CFS) is characterized by severe and prolonged fatigue,

along with a set of nonspecific symptoms and signs, such as sore throat, muscle pain, headaches, and

difficulties with concentration or memory. OBJECTIVE: The study examined whether CFS is associated

with specific dimensions of Cloninger's psychobiological model of personality. METHOD: Personality

profiles were compared between 38 CFS patients and 42 control subjects by means of the

Temperament and Character Inventory (TCI). RESULTS: The CFS group showed significantly higher

scores on Harm‐Avoidance and Persistence. CONCLUSION: The current study shows a significant

association between specific personality characteristics and CFS. These personality traits may be

implicated in the onset and/or perpetuation of CFS and may be a productive focus for psychotherapy.

The etiopathogenesis of chronic fatigue syndrome (CFS) remains poorly understood. Although

neuroendocrine disturbances ‐ and hypothalamic‐pituitary‐adrenal (HPA) axis hypofunction in

particular ‐ have been found in a large proportion of CFS patients, it is not clear whether these

disturbances are cause or consequence of the illness. After a review of the available evidence we

hypothesize that that HPA axis hypofunction in CFS, conceptualized within a system‐biological

perspective, primarily reflects a fundamental and persistent dysregulation of the neurobiological

stress system. As a result, a disturbed balance between glucocorticoid and inflammatory signaling

pathways may give rise to a pathological cytokine‐induced sickness response that may be the final

common pathway underlying central CFS symptoms, i.e. effort/stress intolerance and pain

hypersensitivity. This comprehensive hypothesis on HPA axis hypofunction in CFS may stimulate

ME Research UK — Database of Research Publications 2009

Van Houdenhove

B, Van Hoof E,

Becq K, Kempke S,

Luyten P, De

Meirleir K.

van Ittersum MW,

van Wilgen CP,

Hilberdink WK,

Groothoff JW, van

der Schans CP.

van Nes SI,

Vanhoutte EK,

Faber CG, Garssen

M, van Doorn PA,

Merkies IS;

PeriNomS Study



Bennett D, van

den Berg LH, Van

den Bergh PY,

Department of

Liaison Psychiatry,

University Hospital


Herestraat 49,

Leuven B‐3000,





Hanze University


University of

Applied Sciences,

Center for

Research and

Development in

Health Care and in


Groningen, The




Department of


Erasmus Medical

Centre Rotterdam,

Rotterdam, The




A comparison of

patients with

chronic fatigue

syndrome in two


contrasting clinics.

Illness perceptions

in patients with


Improving fatigue

assessment in


neuropathies: the

modified Rasch‐

built fatigue

severity scale.

J Nerv Ment Dis.




Patient Educ

Couns. 2009


Epub 2008 Sep 23.

J Peripher Nerv

Syst. 2009


diagnostic refinement of the illness, inform treatment approaches and suggest directions for future

research, particularly focusing on the neuroendocrine‐immune interface and possible links between

CFS, early and recent life stress, and depression.

Aim of the present study was to compare chronic fatigue syndrome (CFS) patients, attending 2

"ideologically" contrasting clinics for CFS, on various patient and illness characteristics. Fifty‐nine CFS

patients of each clinic, located in Leuven and Brussels (Belgium), participated. Patients did not differ

with regard to age, levels of fatigue, psychopathology, and self‐efficacy. However, patients from the

psychosocially‐oriented clinic had a lower level of education, reported more progressive illness onset,

and attributed their illness more to psychological causes. Patients in the biologically‐oriented clinic

reported more pain, and showed higher levels of social functioning, motivation and vitality, as well as

fewer limitations related to emotional problems. It is concluded that CFS patients attending the 2

clinics could not be distinguished along dualistic biological/psychosocial lines, but those reporting

sudden illness onset and making somatic attributions were more likely to be represented in the

biologically‐oriented clinic.

OBJECTIVE: Former studies in chronic diseases showed the importance of patients' beliefs and

perceptions. The Revised Illness Perception Questionnaire was developed to assess these illness

perceptions. Our goal was to investigate psychometric properties of the IPQ‐R for Fibromyalgia Dutch

language version (IPQ‐R FM‐Dlv) and to describe illness perceptions of participants with FM.

METHODS: 196 patients completed the IPQ‐R FM‐Dlv. Internal consistency, domain structure and

inter domain correlations were calculated and compared to the IPQ‐R English language version.

Scores were compared with chronic fatigue syndrome (CFS), rheumatoid arthritis (RA), and coronary

heart disease (CHD). RESULTS: Most psychometric properties were comparable to those of the

original IPQ‐R. Participants showed a lack of understanding of their illness, expected their FM to be

chronic and to have a lot of negative consequences on functioning. In 17 out of 24 domains significant

differences were found between FM and CFS, RA, and CHD patients. CONCLUSION: The IPQ‐R FM‐Dlv

showed acceptable psychometric properties, although some aspects need closer examination. Illness

perceptions of FM patients on the Dutch questionnaire were non‐comparable to CFS, RA, and CHD

patients on the English questionnaire. PRACTICE IMPLICATIONS: The IPQ‐R FM‐Dlv can be used to

assess illness perceptions of Dutch FM patients.

Fatigue is a major disabling complaint in patients with immune‐mediated neuropathies (IN). The 9‐

item fatigue severity scale (FSS) has been used to assess fatigue in these conditions, despite having

limitations due to its classic ordinal construct. The aim was to improve fatigue assessment in IN

through evaluation of the FSS using a modern clinimetric approach [Rasch unidimensional

measurement model (RUMM2020)]. Included were 192 stable patients with Guillain‐Barré syndrome

(GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or polyneuropathy

associated with monoclonal gammopathy of undetermined significance (MGUSP). The obtained FSS

data were exposed to RUMM2020 model to investigate whether this scale would meet its

expectations. Also, reliability and validity studies were performed. The original FSS did not meet the

Rasch model expectations, primarily based on two misfitting items, one of these also showing bias

towards the factor 'walking independent.' After removing these two items and collapsing the original

ME Research UK — Database of Research Publications 2009

Cornblath DR,

Dalakas M, Devigili

G, van Doorn PA,

Faber CG, Gorson

KC, Hadden RD,

Hahn AF, Hartung

HP, Hughes RA,

Lauria G, Léger JM,

Lewis RA, Lunn

MP, Merkies IS,

Nobile‐Orazio E,

Notermans NC,

Padua L, Reilly

MM, Smith B.

van Wilgen CP,

Dijkstra PU,

Versteegen GJ,

Fleuren MJ,

Stewart R, van

Wijhe M.

Vandenbergen J,

Vanheule S,

Rosseel Y, Desmet

M, Verhaeghe P.

Pain Centre,

Department of


University Medical

Centre Groningen,

University of


Groningen, The




Department of

Psychoanalysis and

Clinical Consulting,

Ghent University,

Ghent, Belgium.



Chronic pain and

severe disuse

syndrome: long‐

term outcome of

an inpatient






chronic fatigue and

core conflictual


themes: A study in

a chronically



J Rehabil Med.




Psychother. 2009

Mar;82(Pt 1):31‐

40. Epub 2008 Aug


7‐point Likert options to 4‐point response categories for the remaining items, we succeeded in

constructing a 7‐item Rasch‐built scale that fulfilled all requirements of unidimensionality, linearity,

and rating scale model. Good reliability and validity were also obtained for the modified FSS scale. In

conclusion, a 7‐item linearly weighted Rasch‐built modified FSS is presented for more proper

assessment of fatigue in future studies in patients with immune‐mediated neuropathies.

OBJECTIVE: Patients with chronic pain and severe disuse syndrome have pain with physiological,

psychological and social adaptations. The duration and severity of complaints, combined with

previously failed treatments, makes them unsuitable for treatment in primary care. DESIGN: A

prospective waiting list controlled study. PATIENTS: A total of 32 patients with chronic pain for at least

one year and severe disuse syndrome were included in an inpatient multidisciplinary cognitive

behavioural treatment. METHODS: Patients were assessed before the waiting list period, before the

clinical phase, after the clinical phase and after follow‐ups of 6 months and one year. The visual

analogue scale for pain and fatigue were assessed. Muscle strength of the arms and legs, arm

endurance and a 6‐minute walking test were used to assess physical outcome. The Symptom

Checklist‐90, RAND‐36, pain cognition list and the Tampa scale for kinesiophobia were used to assess

psychological outcome. RESULTS: Long‐term significant (p < 0.001) improvements were found for

pain, fatigue, walking distance, muscle strength, anxiety, depression, somatization, negative self‐

efficacy, and catastrophizing in the intervention period. CONCLUSION: An inpatient multidisciplinary

cognitive behavioural programme is beneficial for patients with chronic pain and a severe disuse


OBJECTIVE: Unexplained fatigue syndromes are multidimensional phenomena that involve a

constellation of symptoms. This paper explores whether typical relationship patterns are associated

with self‐reported and clinically rated fatigue symptoms in chronically fatigued patients. METHOD:

Relationship patterns were assessed by means of the core conflictual relationship theme (CCRT)

method. This method examines transference patterns, and was applied to interview data collected

from chronically fatigued patients (N=30). Chronic fatigue was assessed by means of a self‐report

questionnaire and was also rated clinically. RESULTS: Both self‐reported and clinically rated fatigue

correlated with relationship themes. The intensity of fatigue related to the perception of others as not

respecting and as negatively interfering. The typical reaction of the self to relationships consists of

feeling disrespected, anger, passivity, and reduced feelings of self‐consistency. CONCLUSION:

Patients' perception of interpersonal relationships as distressing may be pivotal in understanding

ME Research UK — Database of Research Publications 2009

Van't Leven M,

Zielhuis GA, van

der Meer JW,

Verbeek AL,

Bleijenberg G.

Veldman J, Van

Houdenhove B,

Verguts J.

Viaene M, Vermeir

G, Godderis L.

1 Department of


Biostatistics and

HTA, Radboud


Nijmegen Medical

Centre, the


Department of

Obstetrics and


University Hospital


Catholic University

Leuven, Louvain,


Department of


Environmental and


Medicine, Catholic

University of

Leuven, UZ St.

Rafaël, Leuven,


Fatigue and

chronic fatigue


complaints in the



Chronic fatigue

syndrome: a

hormonal origin? A

rare case of



Sleep disturbances

and occupational

exposure to


Eur J Public Health.

2009 Aug 18.

[Epub ahead of


Arch Gynecol

Obstet. 2009


20. Epub 2008 Sep


Sleep Med Rev.



Epub 2009 Feb 7.

these results. Implications for clinical intervention and future research are indicated.

BACKGROUND: Most knowledge on chronic fatigue (CF) and chronic fatigue syndrome (CFS) is based

on clinical studies, not representative of the general population. This study aimed to assess the

prevalence of fatigue in an adult general population and to identify associations with lifestyle factors.

METHODS: Total 22 500 residents of Nijmegen were selected at random and interviewed by

questionnaire. Data on 9062 respondents (43% response) were analysed, taken into account age,

gender and concomitant disease. Subjects were classified into four groups: not fatigued (NF,

reference group), short‐term fatigue (SF, /=6 months) and CFS‐like

fatigue (in accordance with the Center for Disease Control criteria for CFS, without clinical

confirmation). RESULTS: Our study population showed the following breakdown: NF 64.4% (95% CI

63.6‐65.6%), SF 4.9% (95% CI 4.5‐5.4%), CF 30.5% (95% CI 29.5‐31.4%) and CFS‐like fatigue 1.0% (95%

CI 0.8‐1.2%). Compared with the NF group, more of the CFS respondents were female [odds ratio (OR)

= 1.9], obese (OR = 4.1), using analgesics (OR = 7.8), had a low alcohol intake (OR = 0.4), were eating

less healthy food (OR = 0.5) and were physically less active (OR = 0.1). These associations largely

applied to the SF and CF group. The fatigue could have been due to a concomitant disease in 34 and

55.5% of the SF and CF cases, respectively. CONCLUSION: The prevalence of CF in the general

population appears to be much higher than previously indicated. Even with strict criteria for CFS, it is

estimated that approximately 1% of the adult population experiences this condition. Interestingly, a

large part of this group remains unrecognized by the general practitioner. A striking similarity in

lifestyle pattern between SF, CF and CFS calls for further research.

BACKGROUND: Membranous dysmenorrhea is a rare entity involving expulsion of fragments of

endometrium retaining the shape of the uterus. The condition is often linked to high progesterone

levels. An association with a chronic fatigue syndrome was never described. CASE: A 44‐year‐old

woman with a chronic fatigue syndrome (CFS), presented with membranous dysmenorrhea after

taking an oral contraceptive pill containing ethinylestradiol 0.02 mg and desogestrel 0.15 mg for 3

months in a continuous regimen as treatment for dysfunctional bleeding. Oral contraception was

discontinued and she resumed normal menstruations. Remarkably, she mentioned complete

disappearance of the CFS since expulsion of the tissue and started working again. CONCLUSION: The

occurrence of membranous dysmenorrhea with a dissolving chronic fatigue syndrome is very rare and

was never described before. This case suggests a hormonal dysfunction as a possible cause of chronic

fatigue syndrome. A review of the literature on membranous dysmenorrhea is presented.

A solvent can be defined as "a liquid that has the ability to dissolve, suspend or extract other

materials, without chemical change to the material or solvent". Numerous chemical or technical

processes rely on these specific properties of organic solvents in industry. Occupational exposure to

solvents is not rare and some activities may cause substantial exposure to these substances in the

workforce. Short‐term or acute exposures cause a prenarcotic syndrome, and long lasting exposure

conditions have been associated with various neurological and neuropsychiatric disorders, e.g.,

anosmia, hearing loss, colour vision dysfunctions, peripheral polyneuropathy and depression, but

most significantly with the gradual development of an irreversible toxic encephalopathy. For the last 3

decades reports and epidemiological studies have been published reporting sleep disturbances

ME Research UK — Database of Research Publications 2009

Vij G, Gupta A,

Chopra K.

Walker K, Lindner

H, Noonan M.

Wang JH, Chai TQ,

Lin GH, Luo L.




Division, University

Institute of


Sciences, Punjab



160014, India.

School of


Australian Catholic



Victoria, Australia.



The First Hospital

Affiliated to

Guangzhou TCM


Modulation of


chronic fatigue in

mouse model of

water immersion

stress by naringin,

a polyphenolic


The role of coping

in the relationship


depression and

illness severity in

chronic fatigue


Effects of the


massage on the

physical symptoms

Fundam Clin

Pharmacol. 2009


Epub 2009 Mar 11.

J Allied Health.




J Tradit Chin Med.



among other complaints, related to long‐term exposure to these compounds. In addition, the

question has been posed if solvents can be the cause of a sleep apnoea syndrome in exposed

workers, or on the contrary, if these workers are misdiagnosed and 'common' sleep apnoea

syndromes are the cause of their chronic symptoms of fatigue and memory and attentional


It is believed that physical stress, infection and oxidative stress are involved in the development of

chronic fatigue syndrome. There is little evidence stating the beneficial role of nutritional

supplements in chronic fatigue syndrome. Based on this, this study was designed to evaluate the

effect of naringin, a natural polyphenol, in a mouse model of immunologically‐induced fatigue,

wherein purified lipopolysaccharide (LPS) as well as Brucella abortus (BA) antigen was used as

immunogens. The assessment of chronic fatigue syndrome was based on chronic water‐immersion

stress test for 10 mins as well as measurement of hyperalgesia for 19 days. Immobility time and tail

withdrawal latency as well as oxidative stress were taken as the markers of fatigue. Mice challenged

with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and

oxidative stress on 19th day. Serum tumor necrosis factor‐alpha (TNF‐alpha) levels markedly

increased with LPS or BA challenge. Concurrent treatment with naringin resulted in the significant

decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative

stress as well as in TNF‐alpha levels. Present findings strongly suggest the role of oxidative stress and

immunological activation in the pathophysiology of chronic fatigue syndrome, and treatment with

naringin can be a valuable option in chronic fatigue syndrome.

The self‐regulatory model (SRM) proposes that both cognitive and emotional illness representations

influence the coping processes adopted in response to an illness. AIM: This study used the SRM to

explore the role of coping in the relationship between depression and self‐appraisals of illness

severity in a population of patients with chronic fatigue syndrome (CFS). METHODS: The sample

comprised 156 participants, 34 men and 121 women, aged between 18 and 78 yrs, who had been

medically diagnosed with CFS. Participants were asked to complete three questionnaires: the Cardiac

Depression Scale, Ways of Coping Questionnaire, and Severity Subscale of the Illness Perceptions

Questionnaire‐Revised. RESULTS: Analyses revealed that almost 70% of the participants were

moderately or severely depressed. Additionally, two particular subscales, social support seeking and

positive reappraisals, emerged as positively contributing to self‐appraisals of illness severity (beta =

0.20 [p < 0.05] and beta = 0.21 [p < 0.05], respectively), thereby supporting the SRM. Furthermore,

results indicated that a combination of depression and coping was a better predictor of illness

severity than depression alone, accounting for 22% of the variance compared with 8%, respectively.

CONCLUSIONS: The findings suggest that focusing on depression, and particularly coping styles,

during treatment interventions could have important implications for therapeutic interventions. This

could lead to better treatment strategies for health professionals who work with patients with CFS.

OBJECTIVE: To evaluate the effects of the intelligent‐turtle massage on the physical symptoms and

immune functions in patients with chronic fatigue syndrome (CFS). METHODS: 182 cases of CFS were

randomly divided into an experimental group of 91 cases treated by the intelligent‐turtle massage,

and a control group of 91 cases treated with the conventional massage method. After 2 courses of

ME Research UK — Database of Research Publications 2009

Wang JJ, Song YJ,

Wu ZC, Chu XO,

Wang QM, Wei

LN, Wang XJ,

Meng H.

Warren JW,

Howard FM, Cross

RK, Good JL,

Weissman MM,

Wesselmann U,

Langenberg P,

Greenberg P,

Clauw DJ.


510405, China.

Hospital of

Acupuncture and

Moxibustion, China

Academy of

Chinese Medical

Sciences, Beijing

100700, China.


Department of


Epidemiology and


Medicine, and


University of

Maryland School

of Medicine,


Maryland, USA.

and immune

functions in

patients with

chronic fatigue



controlled study

on influence of

acupuncture for

life quality of

patients with

chronic fatigue

syndrome] [Article

in Chinese]



syndromes in case‐

control study of



bladder syndrome.

Zhongguo Zhen Jiu.



Urology. 2009


Epub 2008 Nov 8.

treatment, the therapeutic effects were statistically analyzed with the accumulated score for the

improved clinical symptoms; and the changes of IgA, IgM and IgG were compared in 96 cases.

RESULTS: There was a significant difference between the two groups in the accumulated scores for

improvement of the symptoms (P

ME Research UK — Database of Research Publications 2009

Watanabe K. Department of




Weinstein AA,

Drinkard BM, Diao

G, Furst G, Dale JK,

Straus SE, Gerber


Center for Study of

Chronic Illness and

Disability, George

Mason University,

Fairfax, VA 22030,






alteration in

comparison with


review of its

clinical reports and

discussion of its


mechanism in the

present day, when

second generation

antipsychotics are


used][Article in



analysis of the


between aerobic

capacity and self‐

reported fatigue in

patients with



polymyositis, and

chronic fatigue



Shinkeigaku Zasshi.



PM R. 2009


generated was that some patients with IC/PBS have a systemic syndrome and not one confined to the


The syndrome of paroxysmal perceptual alteration (PPA) was first described by Yamaguchi in 1985.

Since then, many PPA cases have been reported, and its pathophysiological mechanism has been

proposed: a suppressed (blocked) mesolimbic and mesocortical dopaminergic system and sequential

compensatory increase of noradrenergic neuronal activity are crucial for the occurrence of PPA. PPA

is characterized by hypersensitivity of perception, psychedelic experience (brightening of colors,

sharpening of contrast, visual distortion, etc.), and somatic schema disorder (one feels that one is

floating, one's extremities are being pulled and elongated, etc.). PPA in chronic schizophrenic patients

occurs abruptly like an attack mainly in the evening, often precipitated by fatigue. During the attack,

patients also suffer from mood and thought alteration (anxiety, agitation, depressive mood, and

inability to distract their thoughts from one thing), but they are aware that symptoms of PPA are not

real and apprehensive about them. The attack ceases gradually and spontaneously while the patient

rests or sleeps. These clinical features are clearly different from those of schizophrenic hallucinations.

It is believed that PPA is closely related to neuroleptic treatment by conventional antipsychotics. I

reported the prevalence of PPA as 4.0% in 1991 when high potential D2 blocking agents were

prevailing. The occurrence of PPA has been significantly reduced to the present, when second

generation (atypical) antipsychotics are prevailing. However, in my inquiry in 2004, the prevalence of

PPA was 3.6% in cases treated with risperidone (RIS), while the rates were 0 in cases treated with

olanzapine (OLZ), quetiapine (QTP), and perospirone (PRS). Several cases of PPA have been reported

in patients who were treated with OLZ and PRS. Until now, no cases of PPA have been reported who

were treated with QTP and aripiprazole (APZ). The prevalence of PPA among cases treated with these

second generation antipsychotics might be related to the differences in these agents regarding their

affinity for the D2 receptor: RIS has a sustained and close binding affinity, which might be similar to

those of conventional antipsychotics, OLZ shows a sustained and loose binding affinity, PRS exhibits a

transient and close binding affinity, whereas QTP has a transient and loose binding affinity. APZ is a

partial agonist of the D2 receptor; APZ acts as an agonist under the condition of intrinsic

dopaminergic dysfunction, which might prevent the occurrence of PPA.

OBJECTIVE: To determine if self‐reported levels of physical activity and fatigue are related to peak

oxygen uptake (VO(2peak)) and whether these relationships differ among the patient groups

(rheumatoid arthritis [RA], polymyositis [PM], and chronic fatigue syndrome [CFS]). DESIGN:

Correlational investigation. SETTING: Two ambulatory research clinics at the National Institutes of

Health, Clinical Center, Bethesda, MD. PARTICIPANTS: There were 9 patients with PM, 10 with RA, and

10 with CFS. All patients met case criteria for their respective diagnoses. METHODS/MAIN OUTCOME

MEASUREMENTS: VO(2peak) during bicycle ergometry and self‐reported fatigability, fatigue, and

physical activity. VO(2peak) was used as the criterion measurement of physiological fatigue with

which the self‐reported variables were compared. RESULTS: The Pearson r revealed that self‐reported

physical activity correlated with VO(2peak) (r = 61, P = .01). However, fatigability and fatigue did not

correlate with VO(2peak). Linear regression analysis was performed to assess the effects of diagnosis

group, self‐reported activity level or fatigue, and their interaction. A trend in the data showed a

ME Research UK — Database of Research Publications 2009

Wells DL. School of


Queen's University

Belfast, Northern

Ireland, United



Wessely S. Department of


Medicine, Institute

of Psychiatry,

King's College

London, London

SE5 9RJ, UK.



Weston S,

Townsend S.


Enablement Team.


between pet

ownership and


health status in

people suffering

from chronic

fatigue syndrome.

Surgery for the

treatment of

psychiatric illness:

the need to test

untested theories.

Using a DVD to

help people with

chronic fatigue

syndrome learn

the technique of


J Altern

Complement Med.



J R Soc Med. 2009



Nurs Times. 2009

Nov 17‐


distinctive relationship between fatigue/fatigability within the 3 groups. In addition, when controlling

for group status, self‐reported activity predicted aerobic capacity as measured by VO(2peak).

CONCLUSIONS: This study confirms that patients with chronic, but stable RA, PM, or CFS are fatigued

and have significantly decreased aerobic capacity. Self‐reports of physical activity predicted

VO(2peak), and may be used as an indicator of activity‐based aerobic capacity. Self‐reports of fatigue,

however, did not correlate with VO(2peak) and hence are assessing something other than an index of

aerobic capacity, and provide additional information about patients' perceptions, which will require

further investigation.

OBJECTIVE: This study explored the association between pet ownership and self‐reported health in

people suffering from chronic fatigue syndrome (CFS). METHODS: One hundred and ninety‐three

(193) people with medically diagnosed CFS completed a postal survey designed to collect information

on illness severity, physical and psychologic health, and pet ownership practices. RESULTS: Most of

the participants were female (72.0%), over 45 years of age (57.1%) and married (41.1%) with no

children (63.1%). Pets were owned by 58.3% of the sample, with dogs and cats being the most

commonly kept types of companion animal. The general health of the participants was discovered to

be poor, as assessed by scores on the Chalder Fatigue Questionnaire (CFQ), General Health

Questionnaire‐12 (GHQ‐12), and Short‐Form‐36 (SF‐36) health survey. Pet ownership was not

significantly associated with scores on the CFQ, GHQ‐12, or SF‐36 scales, although pet owners

considered their animals to offer them a range of health benefits, notably those associated with

mental well‐being. CONCLUSIONS: Overall, findings suggest no statistically significant association

between pet ownership and self‐reported health in people with CFS. Nonetheless, people suffering

from this condition believe that their pets have the potential to enhance quality of life. Although

animals should not be regarded as a panacea for people with long‐term conditions such as CFS, they

may, nonetheless, serve a valuable, and currently underutilized, role in promoting well‐being,

whether in their own right, or in conjunction with more traditional forms of therapy.

The Shropshire Enablement Team, a specialist community rehabilitation team, has produced a DVD

and booklet on pacing for people with chronic fatigue syndrome/ME. Pacing is a technique for

managing fatigue, and involves achieving the correct balance between rest and activity. This article

explains the benefits of pacing, and how the DVD and booklet have enabled the team to better

support clients.

ME Research UK — Database of Research Publications 2009

Wormser GP,

Schwartz I.

Wormser GP,

Shapiro ED.

Wu J, Ding HS, Ye


Division of



Department of

Medicine, York

Medical College,

Munger Pavilion

Room 245,

Valhalla, NY 10595,




Division of



Department of

Medicine, New

York Medical

College, Munger

Pavilion Room 245,

Valhalla, NY 10595,




Graduate School at




Shenzhen 518055,





treatment of

animals infected

with Borrelia


Implications of

gender in chronic

Lyme disease.

[Evaluating fatigue

resistance effect of

health food by


tissue oximeter]

[Article in Chinese]

Clin Microbiol Rev.

2009 Jul;22(3):387‐


J Womens Health

(Larchmt). 2009


Guang Pu Xue Yu

Guang Pu Fen Xi.



Despite resolution of the objective manifestations of Lyme disease after antibiotic treatment, a

minority of patients have fatigue, musculoskeletal pain, and/or difficulties with concentration or

short‐term memory of uncertain etiology; these are called post‐Lyme disease symptoms or, in more

severe cases, post‐Lyme disease syndrome or "chronic Lyme disease." Several recent studies in which

Borrelia burgdorferi‐infected animals were treated with antibiotic therapy have demonstrated the

presence of PCR positivity for B. burgdorferi DNA in the absence of culture positivity. In mice that

were treated with antibiotic therapy, residual spirochetes could be taken up by ticks during a blood

meal and could be transmitted to SCID mice. These spirochetes are attenuated; their presence is not

associated with either inflammation or disease. In this review the methodology and findings of these

studies are critically analyzed, and the significance of the results with regard to human Lyme disease

is evaluated, with special emphasis on whether these studies provide useful insights into post‐Lyme

disease syndrome. A serious methodological concern is the failure to consider the pharmacokinetic‐

pharmacodynamic properties of the antibiotic in choosing the dosage regimen used. We conclude

that there is no scientific evidence to support the hypothesis that such spirochetes, should they exist

in humans, are the cause of post‐Lyme disease syndrome.

BACKGROUND: "Post‐Lyme disease syndrome" refers to prolonged subjective symptoms after

antibiotic treatment and resolution of an objective manifestation of Borrelia burgdorferi infection

(Lyme disease). "Chronic Lyme disease" is a vaguely defined term that has been applied to patients

with unexplained prolonged subjective symptoms, whether or not there was or is evidence of B.

burgdorferi infection. OBJECTIVE: To determine if the population of patients with chronic Lyme

disease differs from the populations of patients with either Lyme disease or post‐Lyme disease

syndrome by examining the gender of patients with these diagnoses. Methods: Data on gender were

compiled in this cross‐sectional study based on a systematic review of published studies of antibiotic

treatment in United States patients with post‐Lyme disease syndrome (n = 184) or chronic Lyme

disease (n = 490), and on cases of adults with Lyme disease reported to the Centers for Disease

Control and Prevention from 2003 to 2005 (n = 43,282). RESULTS: Patients with chronic Lyme disease

were significantly more likely to be female than were patients diagnosed with either Lyme disease

(odds ratio [OR] 2.42, 95% confidence interval [CI] 1.98‐2.94, p < 0.0001) or with post‐Lyme disease

syndrome (OR 2.32, 95% CI 1.62‐3.34, p < 0.0001). CONCLUSIONS: Patients with chronic Lyme disease

differ with regard to gender from those with either B. burgdorferi infection or post‐Lyme disease

syndrome. This finding suggests that illnesses with a female preponderance, such as fibromyalgia,

chronic fatigue syndrome, or depression, may be misdiagnosed as chronic Lyme disease.

Currently, chronic fatigue syndrome (CFS) seriously affects people's normal living and work. In the

present paper, the physiological parameters, such as tissue oxygenation saturation and heart rate,

were used to evaluate the subjects' fatigue degree, and the fatigue resistance capsule and coffee

were taken as a measure to adjust the fatigue. Human tissue oxygen saturation (rSO2) can be

monitored noninvasively and in real time by near infrared spectroscopy (NIRS) based on spatially‐

resolved spectroscopy. Aiming at those brainworkers who need to work in an office for a long time;

two static experiments were designed to evaluate the fatigue degree of the subjects who either take

the fatigue resistance capsules/coffee or not. The rSO2 and heart rate (HR) of the subjects in the

ME Research UK — Database of Research Publications 2009

Wyller VB, Eriksen

HR, Malterud K.

Yan S, Li HZ, Zhang

XY, Li HJ.

Zhang L, Goudh J,

Christmas D,

Division of




Hospital, Oslo,




Department of

Urology, Peking

Union Medical

College Hospital,

Peking Union

Medical College,

Chinese Academy

of Medical Science,

Beijing 100730,


St George's

University of

Can sustained

arousal explain the