TGI Friday! Our weekly round-up of recently published research abstracts and related items | 15 November 2013

November 15, 2013

From the Journal of Internal Medicine, 9 November 2013 [Epub ahead of print].

Comorbidity of postural orthostatic tachycardia syndrome (POTS) and chronic fatigue syndrome (CFS) in an Australian cohort.

Reynolds GK, Lewis DP, Richardson AM, Lidbury BA.
Department of Genome Biology, The John Curtin School of Medical
Research, The Australian National University, Canberra.



Patients with chronic fatigue syndrome (CFS) are frequently diagnosed with comorbid postural orthostatic tachycardia syndrome (POTS), suggesting a shared pathogenesis. The aim of this study was to examine the relationship between demographic characteristics,
autonomic functioning and fatigue levels amongst CFS patients with and without comorbid POTS.


All patients presenting to Melbourne CFS Discovery Clinic between 2009 and 2012 completed a 20-min standing task as part of their initial assessment.

Heart rate and pulse pressure were recorded at baseline, at 2 min intervals post-standing, at the end of the task and following a recovery period. Average heart rate and pulse pressure variability were calculated from this data. Age, gender,
length of illness and self-reported fatigue scores were also recorded.

POTS patients were diagnosed by an orthostatic increase in heart rate greater than 30 beats/min, concomitant symptoms of orthostatic intolerance and no orthostatic hypotension. Differences in autonomic
functioning between POTS and CFS patients were compared using independent-samples t-tests, while logistic and linear regressions were performed to examine the contribution of autonomic functioning to task completion and perceived fatigue, respectively.


Comorbidity of CFS and POTS (CFS-POTS) was observed in 11% (33/306) of patients. CFS-POTS patients were significantly younger (P < 0.001), had a shorter length of illness (P = 0.034), experienced greater task difficulty (P = 0.002) and were able to stand for significantly shorter periods compared to the CFS-only patients (P < 0.001).CFS-POTS patients experienced significantly lower baseline diastolic blood pressure (P = 0.002), and significantly higher heart rate and lower pulse pressures at each standing measurement. Early heart rate changes (P = 0.002) and overall heart rate change (P < 0.001) were significant predictors of completion status, whereas heart rate variability (P < 0.001) and female gender (P <0.001) were significant predictors of increased perceived task difficulty.CONCLUSIONSHaemodynamic and demographic differences between CFS-POTS and CFS-only patients suggest that the former group reflects a distinct subgroup of the CFS population. The findings highlight the utility of screening younger patients with fatigue for POTS, and identified heart rate variability as an important marker of fatigue for CFS patients in general.

From Brain, Behavior, and Immunity, published 7 November 2013.

Neurocognitive disturbances associated with acute infectious mononucleosis, Ross River fever and Q fever: A preliminary investigation of inflammatory and genetic correlates

Erin Cvejic(a), Jim Lemon(a), Ian B. Hickie(b), Andrew R. Lloyd©, Uté Vollmer-Conna(a),
a) School of Psychiatry, University of New South Wales, Australia
b) The Brain and Mind Research Institute, School of Psychiatry,
University of Sydney, Australia
c) Inflammation and Infection Research Centre, School of Medical
Sciences, University of New South Wales, Australia


Disturbances in neurocognitive performance are a core feature of the acute sickness response to infection; however the underlying mechanisms remain unclear. The current study used a computerised battery to assess neurocognitive functioning in subjects enrolled in the Dubbo Infection Outcomes Study (n = 107) – a prospective cohort of subjects followed from documented acute infection with Epstein Barr virus, Ross River virus, or Coxiella burnetii until recovery.

Subjects were assessed when ill, and a subset again after complete recovery. Associations between sickness-related cognitive disturbances and single nucleotide polymorphisms (SNPs) in cytokine (interleukin [IL]-6, IL-10, tumor necrosis factor-α and interferon-γ) and neurobehavioral genes (serotonin transporter and catechol-O-methyltransferase) were explored.

During acute infection, subjects exhibited slower matching-to-sample responses (p = 0.03), poorer working memory capacity (p = 0.014), mental planning (p = 0.045), and dual attention task performance (p = 0.02), and required longer to complete discordant Stroop trials (p = 0.01) compared to recovery. Objective impairments correlated significantly with self-reported symptoms (p < 0.05) as well as levels of the inflammation marker, C-reactive protein (p = 0.001). Linear regression analysis identified an association between neurocognitive disturbance during acute illness and functional polymorphisms in inflammatory cytokine genes. Specifically, the high cytokine producing G allele of the IL-6-174G/C SNP was associated with poorer neurocognitive performance when subjects were ill (p = 0.027).These findings confirm that acute infection impacts on neurocognitive performance, manifesting as slowed responses and impaired performance on complex tasks requiring higher-order functioning which has important real-world implications. The data provide the first preliminary evidence for a role of a genetic predisposition to more intense inflammatory responses in objective neurocognitive disturbances during acute infections. These associations require replication in a larger sample size.

From Rheumatology International, May 2013. Epub 28 September 2012.

The prevalence of fibromyalgia in patients with Behçet's disease and its relation with disease activity.

Melikoglu M, Melikoglu MA.
Department of Dermatology, Ministry of Health Erzurum Regional Training and Research Hospital, Erzurum, Turkey.


Behçet's disease (BD) is a chronic disorder characterized by mucocutaneous and multisystem manifestations. Fibromyalgia (FM) is characterized by widespread musculoskeletal pain and may be present concomitantly with several rheumatic diseases. Our aims were to investigate the prevalence of FM in patients with BD and to evaluate the possible relation of FM presence with BD disease activity.

A total of 104 Behçet patients were included in this study. Age, sex, disease durations and the BD Current Activity Form (BDCAF) scores as disease activity evaluation were recorded. Presence of FM and the Fibromyalgia Impact Questionnaire (FIQ) scores was investigated. Also, ESR and CRP concentrations were determined in all patients. Mann-Whitney U test and Pearson's correlation tests were used for the statistical analysis.

There were 60 female and 40 male patients with an age range of 19-51 years. Eighteen of 100 BD patients were diagnosed as FM. Although ages, disease duration and laboratory parameters did not differ between BD patients with and without FM, BD patients with FM were more frequently female (p < 0.000). The presence of FM did not differ significantly between patients with and without systemic manifestations. Also, oral-genital ulcers, erythema nodosum, thrombophlebitis, pustular lesions and doctor's impression of disease activity scores were not found to be different in BD patients with or without FM. However, there were significant differences in fatigue, headache, arthralgia and patient impression of disease activity (today and last 28 days) between these groups (p < 0.000; p < 0.01; p < 0.01; p = 0.021 and p = 0.027, respectively). Also, there were significant correlations between BDCAF and FIQ items that refer pain and fatigue (p < 0.01).FM is a common and important clinical problem that may represent an additional factor that worsens pain and physical limitations in patients with BD. The higher prevalence of FM in patients with BD seems to be affected by BD itself, rather than its severity.

From Food and Nutrition Sciences (Open Access), November 13.

The Role of Lactic Acid Bacteria in the Pathophysiology and Treatment of Irritable Bowel Syndrome (IBS)

Author(s) Julia König, Ignacio Rangel, Robert J. Brummer
School of Health and Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden. Email:


Irritable bowel syndrome (IBS) is a multifactorial chronic disorder characterized by various abdominal complaints and a worldwide prevalence of 10% – 20%. Although its etiology and pathophysiology are complex and still not completely understood, aberrations along the microbe-gut-brain axis are known to play a central role.

IBS is characterized by interrelated alterations in intestinal barrier function, gut microbe composition, immune activation, afferent sensory signaling and brain activity. Pharmaceutical treatment is generally ineffective and, hence, most therapeutic strategies are based on non-drug approaches.

A promising option is the administration of probiotics, in which lactic acid bacteria strains are considered specifically beneficial. This review aims to provide a concise, although comprehensive, overview of the role of lactic acid bacteria in the pathophysiology and treatment of IBS.

From the Journal of Virology, (open access), 13 November 2013. [Epub ahead of print, full text available].

Lack of evidence for retroviral infections formerly related to chronic fatigue in Spanish Fibromyalgia patients.

Elisa Oltra(2,*), María García-Escudero(2,†), Armando Vicente Mena-Durán(2,†), Vicente Monsalve(2), Germán Cerdá-Olmedo(1,2)
1) Cátedra Umivale en innovación e investigación en patologías del trabajo, C/Quevedo, 2, 46001 Valencia, Spain
2) Facultad de Medicina, C/Quevedo, 2, 46001 Valencia, Spain
†) Equal contributors
*) Corresponding author Email:



The etiology of fibromyalgia and chronic fatigue syndrome (FM/CFS) is currently unknown. A recurrent viral infection is an attractive hypothesis repeatedly found in the literature since it would explain the persistent pain and tiredness these patients suffer from.

The initial striking link of two distinct orphan retroviruses: the gamma retroviruses murine leukemia virus (MLV)-related virus and the delta retrovirus T-lymphotropic virus type 2 (HTLV-2) to chronic fatigue have not been confirmed to date.


Genomic DNA (gDNA) from 75 fibromyalgia patients suffering from chronic fatigue and 79 age-matched local healthy controls were screened for the presence of MLV-related and HTLV-2 related proviral sequences. The XMRV env gene was amplified in 20% of samples tested (24% patients/15% healthy controls).

Unexpectedly, no PCR amplifications from independent gDNA preparations of the same
individuals were obtained. None of the positive samples showed presence of contaminating murine sequences previously reported by other investigators, neither contained additional regions of the virus making us conclude that the initial env amplification came from spurious air-driven amplicon contaminants.

No specific HTLV-2 sequences were obtained at any time from any of the 154 quality-controlled gDNA preparations screened.


Previous associations between MLV-related or HTLV-2 retrovirus infection with chronic fatigue must be discarded. Thus, studies showing positive amplification of HTLV-2 sequences from chronic fatigue participants should be revised for possible undetected
technical problems.

To avoid false positives of viral infection, not only extreme precautions should be taken when nested-PCR reactions are prepared and exhaustive foreign DNA contamination controls performed, but also consistent amplification of diverse regions of the virus in independent preparations from the same individual must be demanded.

The fact that our cohort of patients did not present evidence of any of the two types of retroviral infection formerly associated to chronic fatigue does not rule out the possibility that other viruses ar involved in inciting or maintaining fibromyalgia and/or chronic fatigue conditions.

From the Journal of Family Medicine and Primary Care (official publication of the Acaedmy of Family Physicians on India), 29 October 2013.


Diagnosing chronic fatigue syndrome in south asians: Lessons from a secondary analysis of a UK qualitative study

R Erandie Ediriweera De Silva(1), Kerin Bayliss(2), Lisa Riste(2), Carolyn A Chew-Graham(3).
1) Primary Care Centre, Institute of Population Health, University of Manchester, Manchester, UK; Lecturer in Family Medicine, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka,
2) Primary Care Centre, Institute of Population Health, University of Manchester, Manchester, UK; National School for Primary Care Research, University of Manchester, Manchester, England,
3) National School for Primary Care Research, University of Manchester, Manchester, England; Research Institute, Primary Care and Health Sciences, Keele University, Staffordshire, UK.



Chronic fatigue syndrome/myalgic encephalitis (CFS/ME) is rarely diagnosed in South Asia (SA), although the symptoms of this condition are seen in the population. Lessons from UK based South Asian, Black and Minority Ethnic (BME) communities may be of value in identifying barriers to diagnosis of CFS/ME in SA.


To explore why CFS/ME may not be commonly diagnosed in SA. Settings and Design: A secondary analysis of qualitative data on the diagnosis and management of CFS/ME in BME people of predominantly South Asian origin in the UK using 27 semi-structured qualitative interviews with people with CFE/ME, carers, general practitioners (GPs), and community leaders.


CFS/ME is seen among the BME communities in the UK. People from BME communities in the UK can present to healthcare practitioners with vague physical complaints and they can hold a biomedical model of illness. Patients found it useful to have a label of CFS/ME although some GPs felt it to be a negative label. Access to healthcare can be limited by GPs reluctance to diagnose CFS/ME, their lack of knowledge and patients negative experiences. Cultural aspects among BME patients in the UK also act as a barrier to the diagnosis of CFS/ME.


Cultural values and practices influence the diagnosis of CFS/ME in BME communities. The variations in the perceptions around CFS/ME among patients, carers, and health professionals may pose challenges in diagnosing CFS/ME in SA as well. Raising awareness of CFS/ME would improve the diagnosis and management of patients with CFS/ME in SA.

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