TGI Friday! Our weekly roundup of research abstracts, 24 February 2012


This is our regular roundabout of research abstracts that may not yet have appeared on this website.


PLoS One. 2011;6(10):e24602. Epub 2011 Oct 12.

Murine gammaretrovirus group G3 was not found in Swedish patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.

Elfaitouri A, Shao X, Mattsson Ulfstedt J, Muradrasoli S, Bolin Wiener A, Golbob S, Ohrmalm C, Matousek M, Zachrisson O, Gottfries CG, Blomberg J.
Section of Clinical Virology, Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.

Abstract

BACKGROUND: The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans.

RESULTS: Three major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV.

Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden.

As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria.

CONCLUSIONS: XMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors.

PMCID: PMC3192035


Virol J. 2011 Sep 24;8:450.

Xenotropic murine leukemia virus-related virus is not associated with chronic fatigue syndrome in patients from different areas of the US in the 1990s.

Ali MA, Dale JK, Kozak CA, Goldbach-Mansky R, Miller FW, Straus SE, Cohen JI.
Medical Virology Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

BACKGROUND: In 2009, xenotropic murine leukemia virus-related virus (XMRV) was reported in 67% of patients with chronic fatigue syndrome (CFS) compared to 4% of controls. Since then numerous reports failed to detect XMRV in other cohorts of CFS patients, and some studies suggested that XMRV sequences in human samples might be due to contamination of these samples with mouse DNA.

RESULTS: We determined the prevalence of XMRV in patients with CFS from similar areas in the United States as the original 2009 study, along with patients with chronic inflammatory disorders and healthy persons.

Using quantitative PCR, we initially detected very low level signals for XMRV DNA in 15% of patients with CFS; however, the frequency of PCR positivity was no different between patients with CFS and controls. Repeated attempts to isolate PCR products from these reactions were unsuccessful.

These findings were supported by our observations that PHA and IL-2 stimulation of peripheral blood mononuclear cells from patients with apparently low levels of XMRV, which induced virus replication in the 2009 report, resulted in the disappearance of the signal for XMRV DNA in the cells.

Immunoprecipitation of XMRV-infected cell lysates using serum from patients from whom we initially detected low levels of XMRV DNA followed by immunoblotting with antibodies to XMRV gp70 protein failed to detect antibody in the patients, although one control had a weak level of reactivity.

Diverse murine leukemia virus (MLV) sequences were obtained by nested PCR with a similar frequency in CFS patients and controls. Finally, we did not detect XMRV sequences in patients with several chronic inflammatory disorders including rheumatoid arthritis, Bechet’s disease, and systemic lupus erythematosus.

CONCLUSIONS: We found no definitive evidence for XMRV DNA sequences or antibody in our cohort of CFS patients, which like the original 2009 study, included patients from diverse regions of the United States. In addition, XMRV was not detected in a cohort of patients with chronic inflammatory disorders.

PMCID: PMC3210120


BMC Health Serv Res. 2011 Sep 15;11:217.

The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database.

Collin SM, Crawley E, May MT, Sterne JA, Hollingworth W; UK CFS/ME National Outcomes Database.
Collaborators: O’Dowd H, Butt K, Dunn D, Pemberton S, White P, Murphy M, Mullick Y, Bansal A.
School of Social & Community Medicine, Centre for Child & Adolescent Health, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, UK.

Abstract

BACKGROUND: Few studies have investigated factors associated with discontinuation of employment in patients with CFS/ME or quantified its impact on productivity.

METHODS: We used patient-level data from five NHS CFS/ME services during the period 01/04/2006-31/03/2010 collated in the UK CFS/ME National Outcomes Database. We used logistic regression to identify factors associated with discontinuation of employment. We estimated UK-wide productivity costs using patient-level data on duration of illness before assessment by a CFS/ME service, duration of unemployment, age, sex and numbers of patients, in conjunction with Office for National Statistics income and population data.

RESULTS: Data were available for 2,170 patients, of whom 1,669 (76.9%) were women. Current employment status was recorded for 1,991 patients (91.8%), of whom 811 patients (40.7%) were currently employed and 998 (50.1%) had discontinued their employment “because of fatigue-related symptoms”. Older age, male sex, disability, fatigue, pain, and duration of illness were associated with cessation of employment. In a multivariable model, age, male sex, and disability remained as independent predictors.

Total productivity costs among the 2,170 patients due to discontinuation of employment in the years preceding assessment by a specialist CFS/ME service (median duration of illness=36 months) were £49.2 million. Our sample was equivalent to 4,424 UK adults accessing specialist services each year, representing productivity costs to the UK economy of £102.2 million. Sensitivity analyses suggested a range between £75.5-£128.9 million.

CONCLUSIONS: CFS/ME incurs huge productivity costs amongst the small fraction of adults with CFS/ME who access specialist services.

PMCID: PMC3184626


Gut. 2012 Feb;61(2):214-9. Epub 2011 Sep 12.

Irritable bowel syndrome and chronic fatigue 3 years after acute giardiasis: historic cohort study.

Wensaas KA, Langeland N, Hanevik K, Mørch K, Eide GE, Rortveit G.
Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway. knut-arne.wensaas@uni.no

Abstract

BACKGROUND: Giardia lamblia is a common cause of gastroenteritis worldwide, but there is limited knowledge about the long-term complications.

OBJECTIVE: To estimate the relative risk of irritable bowel syndrome (IBS) and chronic fatigue 3 years after acute giardiasis.

DESIGN: Controlled historic cohort study with 3 years’ follow-up. Data collected by mailed questionnaire.

SETTING: Waterborne outbreak of giardiasis in the city of Bergen, Norway.

PARTICIPANTS: 817 patients exposed to Giardia lamblia infection verified by detection of cysts in stool samples and 1128 matched controls.

MAIN OUTCOME MEASURES: IBS and chronic fatigue.

RESULTS: The prevalence of IBS in the exposed group was 46.1%, compared with 14.0% in the control group, and the adjusted RR=3.4 (95% CI 2.9 to 3.8). Chronic fatigue was reported by 46.1% of the exposed group and 12.0% of the controls, the adjusted RR was 4.0 (95% CI 3.5 to 4.5). IBS and chronic fatigue were associated and the RR for the exposed group of having a combination of the two outcomes was 6.8 (95% CI 5.3 to 8.5). The RR was also increased for having just one of the two syndromes, 1.8 for IBS (95% CI 1.4 to 2.3) and 2.2 for chronic fatigue (95% CI 1.7 to 2.8).

CONCLUSIONS: Infection with Giardia lamblia in a non-endemic area was associated with a high prevalence of IBS and chronic fatigue 3 years after acute illness, and the risk was significantly higher than in the control group. This shows that the potential consequences of giardiasis are more serious than previously known. Further studies are needed, especially in areas where giardiasis is endemic.


Psychother Psychosom. 2011;80(6):353-8. Epub 2011 Aug 6

Does the heterogeneity of chronic fatigue syndrome moderate the response to cognitive behaviour therapy? An exploratory study.

Cella M, Chalder T, White PD.
Department of Psychological Medicine, Institute of Psychiatry, King’s College London, UK. matteo.cella@kcl.ac.uk

Abstract

BACKGROUND: Chronic fatigue syndrome (CFS) is a heterogeneous condition. A few studies have shown that some independent factors predict outcomes after cognitive behaviour therapy (CBT). Two recent systematic reviews suggest that heterogeneity may moderate treatment outcomes. However, no study has explored whether subgroups of CFS predict response to treatment.

METHODS: We used both latent class analysis (LCA) and latent class regression (LCR) to clarify the relationship between subgroups of CFS patients (n = 236), diagnosed using the Oxford diagnostic criteria, and the response to CBT. We measured symptoms, demographics, mood, and cognitive and behavioural responses to illness to define subgroups.

RESULTS: We found 5 latent classes by LCA, which did not differ in the direction of their response to CBT, with all classes showing improvement. In contrast, an exploratory LCR identified 4 latent classes, 1 of which predicted a poor response to CBT, whereas the other 3 predicted a good outcome, accounting for more than 70% of the patients. The negative outcome class was defined by weight fluctuations and physical shakiness, anxiety, pain and being focused on symptoms.

CONCLUSIONS: CBT should be offered to all classes of patients with CFS, when defined by these measures. It may be possible to predict a minority group with a negative outcome, but this exploratory work needs replication.


J Intern Med. 2012 Jan;271(1):64-81. doi: 10.1111/j.1365-2796.2011.02405.x. Epub 2011 Jul 13.

Gene expression alterations at baseline and following moderate exercise in patients with Chronic Fatigue Syndrome and Fibromyalgia Syndrome.

Light AR, Bateman L, Jo D, Hughen RW, Vanhaitsma TA, White AT, Light KC.
Department of Anesthesiology The Brain Institute Department of Neurobiology and Anatomy Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT 84132, USA. alan.light@hsc.utah.edu

Abstract

OBJECTIVES: To determine mRNA expression differences in genes involved in signalling and modulating sensory fatigue, and muscle pain in patients with chronic fatigue syndrome (CFS) and fibromyalgia syndrome (FM) at baseline, and following moderate exercise.

DESIGN: Forty-eight patients with CFS only, or CFS with comorbid FM, 18 patients with FM that did not meet criteria for CFS, and 49 healthy controls underwent moderate exercise (25 min at 70% maximum age-predicted heart rate).

Visual-analogue measures of fatigue and pain were taken before, during and after exercise. Blood samples were taken before and 0.5, 8, 24 and 48 h after exercise. Leucocytes were immediately isolated from blood, number coded for blind processing and analyses and flash frozen.

Using real-time, quantitative PCR, the amount of mRNA for 13 genes (relative to control genes) involved in sensory, adrenergic and immune functions was compared between groups at baseline and following exercise. Changes in amounts of mRNA were correlated with behavioural measures and functional clinical assessments.

RESULTS: No gene expression changes occurred following exercise in controls. In 71% of patients with CFS, moderate exercise increased most sensory and adrenergic receptor’s and one cytokine gene’s transcription for 48 h. These postexercise increases correlated with behavioural measures of fatigue and pain.

In contrast, for the other 29% of patients with CFS, adrenergic α-2A receptor’s transcription was decreased at all time-points after exercise; other genes were not altered. History of orthostatic intolerance was significantly more common in the α-2A decrease subgroup. FM-only patients showed no postexercise alterations in gene expression, but their pre-exercise baseline mRNA for two sensory ion channels and one cytokine were significantly higher than controls.

CONCLUSIONS: At least two subgroups of patients with CFS can be identified by gene expression changes following exercise. The larger subgroup showed increases in mRNA for sensory and adrenergic receptors and a cytokine. The smaller subgroup contained most of the patients with CFS with orthostatic intolerance, showed no postexercise increases in any gene and was defined by decreases in mRNA for α-2A. FM-only patients can be identified by baseline increases in three genes. Postexercise increases for four genes meet published criteria as an objective biomarker for CFS and could be useful in guiding treatment selection for different subgroups.


BMC Fam Pract. 2010 Nov 15;11:89.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adults: a qualitative study of perspectives from professional practice.

Horton SM, Poland F, Kale S, Drachler Mde L, de Carvalho Leite JC, McArthur MA, Campion PD, Pheby D, Nacul L.
University of East Anglia, Norwich, UK. s.horton@uea.ac.uk

Abstract

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) can cause profound and prolonged illness and disability, and poses significant problems of uncertainty for healthcare professionals in its diagnosis and management. The aim of this qualitative study was to explore the nature of professional ‘best practice’ in working with people with CFS/ME.

METHODS: The views and experiences of health care practitioners (HCPs) were sought, who had been judged by people with CFS/ME themselves to have been particularly helpful and effective. Qualitative semi-structured interviews following a topic guide were carried out with six health care practitioners. Interviews were audio-recorded, transcribed and subject to thematic analysis.

RESULTS: Five main themes were developed: 1) Diagnosis; 2) Professional perspectives on living with CFS/ME; 3) Interventions for treatment and management; 4) Professional values and support for people with CFS/ME and their families; 5) Health professional roles and working practices.

Key findings related to: the diagnostic process, especially the degree of uncertainty which may be shared by primary care physicians and patients alike; the continued denial in some quarters of the existence of CFS/ME as a condition; the variability, complexity, and serious impact of the condition on life and living; the onus on the person with CFS/ME to manage their condition, supported by HCPs; the wealth of often conflicting and confusing information on the condition and options for treatment; and the vital role of extended listening and trustful relationships with patients.

CONCLUSIONS: While professional frustrations were clearly expressed about the variability of services both in primary and specialist care and continuing equivocal attitudes to CFS/ME as a condition, there were also strong positive messages for people with CFS/ME where the right services are in place.

Many of the findings from these practitioners seen by their patients as helping them more effectively, accord with the existing literature identifying the particular importance of listening skills, respect and trust for establishing a therapeutic relationship which recognises key features of the patient trajectory and promotes effective person-centred management of this complex condition.

These findings indicate the need to build such skills and knowledge more systematically into professional training informed by the experience of specialist services and those living with the condition.

PMCID: PMC2994803

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