Abstracts from six research papers that have been published or brought to our attention this week and not already appeared on the MEA website.
1. CARNITINE DEFICIENCY IN ME/CFS
Reuter SE, Evans AM.
J Intern Med. 2011 Jul;270(1):76-84. doi: 10.1111/j.1365-2796.2010.02341.x. Epub 2011 Jan 19.
From the School of Pharmacy & Medical Sciences, University of South Australia, Adelaide, SA, Australia. stephanie.reuter@unisa.edu.au
Abstract
OBJECTIVE:
The underlying aetiology of chronic fatigue syndrome is currently unknown; however, in the light of carnitine's critical role in mitochondrial energy production, it has been suggested that chronic fatigue syndrome may be associated with altered carnitine homeostasis. This study was conducted to comparatively examine full endogenous carnitine profiles in patients with chronic fatigue syndrome and healthy controls.
DESIGN:
A cross-sectional, observational study.
SETTING AND SUBJECTS:
Forty-four patients with chronic fatigue syndrome and 49 age- and gender-matched healthy controls were recruited from the community and studied at the School of Pharmacy & Medical Sciences, University of South Australia.
MAIN OUTCOME MEASURES:
All participants completed a fatigue severity scale questionnaire and had a single fasting blood sample collected which was analysed for l-carnitine and 35 individual acylcarnitine concentrations in plasma by LC-MS/MS.
RESULTS:
Patients with chronic fatigue syndrome exhibited significantly altered concentrations of C8:1, C12DC, C14, C16:1, C18, C18:1, C18:2 and C18:1-OH acylcarnitines; of particular note, oleyl-L-carnitine (C18:1) and linoleyl-L-carnitine (C18:2) were, on average, 30-40% lower in patients than controls (P < 0.0001). Significant correlations between acylcarnitine concentrations and clinical symptomology were also demonstrated.CONCLUSIONS:It is proposed that this disturbance in carnitine homeostasis is reflective of a reduction in carnitine palmitoyltransferase-I (CPT-I) activity, possibly a result of the accumulation of omega-6 fatty acids previously observed in this patient population. It is hypothesized that the administration of omega-3 fatty acids in combination with l-carnitine would increase CPT-I activity and improve chronic fatigue syndrome symptomology.
2. IRRITABLE BOWEL SYMPTOMS & DYSPEPSIA
Van Oudenhove L, Vandenberghe J, Vos R, Holvoet L, Tack J.
Neurogastroenterol Motil. 2011 Jun;23(6):524-e202. doi: 10.1111/j.1365-2982.2010.01667.x. Epub 2011 Jan 24.
Department of Pathophysiology, Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium. lukas.vanoudenhove@med.kuleuven.be
BACKGROUND:
It is unclear which factors explain the high co-morbidity between functional dyspepsia (FD) and other functional somatic syndromes. The aim of this study is to investigate the association between gastric sensorimotor function, psychosocial factors and ‘somatization' on the one hand, and co-morbid irritable bowel syndrome (IBS) and chronic fatigue (CF)-like symptoms on the other, in FD.
METHODS:
In 259 tertiary care FD patients, we studied gastric sensorimotor function with barostat (sensitivity, accommodation). We measured psychosocial factors (abuse history, alexithymia, trait anxiety, depression, panic disorder) and ‘somatization' using self-report questionnaires, and presence of IBS and CF-like symptoms. Hierarchical multiple logistic regression was used to determine which of these factors were independently associated with co-morbid IBS and CF-like symptoms, including testing of potential mediator effects.
KEY RESULTS:
Co-morbid IBS or CF-like symptoms respectively were found in 142 (56.8%) and 102 (39.4%) patients; both co-morbidities were not significantly associated (P=0.27). Gastric accommodation (β=0.003, P=0.04) and ‘somatization' (β=0.17, P= 0.0003) were independent risk factors for IBS (c=0.74, P<0.0001); the effect of adult abuse (β=0.72, P=0.20) was mediated by 'somatization'. Depression (β=0.16, P=0.008) and 'somatization' (β=0.18, P=0.004) were overlapping risk factors for CF-like symptoms (c=0.83, P<0.0001); the effects of alexithymia and lifetime abuse were mediated by depression and 'somatization', respectively.CONCLUSIONS & INFERENCES:'Somatization' is a common risk factor for co-morbid IBS and CF-like symptoms in FD and mediates the effect of abuse. Gastric sensorimotor function and depression are specific risk factors for co-morbid IBS and CF-like symptoms, respectively.
3. SLEEP DISTURBANCE IN ME/CFS
Sleep-wake behavior in chronic fatigue syndrome.
Rahman K, Burton A, Galbraith S, Lloyd A, Vollmer-Conna U.
Sleep. 2011 May 1;34(5):671-8.
School of Psychiatry, University of NSW, Sydney, Australia.
Abstract
STUDY OBJECTIVES:
Disturbances of the internal biological clock manifest as fatigue, poor concentration, and sleep disturbances-symptoms reminiscent of chronic fatigue syndrome (CFS) and suggestive of a role for circadian rhythm disturbance in CFS. We examined circadian patterns of activity, sleep, and cortisol secretion in patients with CFS.
DESIGN:
Case-control study, 5-day behavioral observation.
SETTING:
Natural setting/home environment
PARTICIPANTS:
15 patients with CFS and 15 healthy subjects of similar age, sex, body mass index (BMI), and activity levels.
INTERVENTIONS:
N/A MEASUREMENTS: Self-report questionnaires were used to obtain medical history and demographic information and to assess health behaviors, somatic and psychological symptoms, and sleep quality. An actiwatch accelerometer recorded activity and sleep patterns over 5 days with concurrent activity and symptom logs. Diurnal salivary cortisol secretion was measured. Additionally, overnight heart rate monitoring and pain sensitivity assessment was undertaken.
RESULTS:
Ratings of symptoms, disability, sleep disturbance, and pain sensitivity were greater in patients with CFS. No between-group differences were found in the pattern or amount of sleep, activity, or cortisol secretion. Afternoon activity levels significantly increased evening fatigue in patients but not control subjects. Low nocturnal heart rate variability was identified as a biological correlate of unrefreshing sleep.
CONCLUSIONS:
We found no evidence of circadian rhythm disturbance in CFS. However, the role of autonomic activity in the experience of unrefreshing sleep warrants further assessment. The activity symptom-relationship modelled here is of clinical significance in the approach to activity and symptom management in the treatment of CFS.
4. PSYCHOLOGY: CHRONIC FATIGUE & BURNOUT
Two sides of the same coin? On the history and phenomenology of chronic fatigue and burnout.
Leone SS, Wessely S, Huibers MJ, Knottnerus JA, Kant I.
Psychol Health. 2011 Apr;26(4):449-64. Epub 2010 Apr 29.
Source
Department of Epidemiology, Maastricht University, Maastricht, The Netherlands. Stephanie.Leone@epid.unimaas.nl
Abstract
BACKGROUND:
Burnout and chronic fatigue syndrome (CFS) are two fatigue syndromes which have developed largely independently from each other, yet whose similarities in symptoms can be a source of confusion. We aim to explore the phenomenology of burnout and CFS in a historical context as this may provide some insight into the links and relationship between these conditions.
METHOD:
A narrative review based on literature in the fields of history, social science and medicine.
RESULTS:
The origins of CFS lie within medicine, whereas burnout developed in a psychological setting. As well as symptoms, burnout and CFS also share similar themes such as an overload process triggering illness onset, the need for restoration of depleted energy, external causal attributions and the characteristics of people suffering from these illnesses. However, these themes are expressed in either psychological or medical terms according to the historical background.
CONCLUSION:
Despite their similarities, there have been few direct comparisons of the two concepts. Culture, illness perceptions and accountability are important issues in both conditions and could contribute to their differences. Comparing burnout and CFS within one sample frame, thus looking beyond the psychology/medicine divide, could be a useful first step towards understanding their relationship.
5. XMRV & ME/CFS
Lombardi VC, Hagen KS, Hunter KW, Diamond JW, Smith-Gagen J, Yang W, Mikovits JA.
In Vivo. 2011 May-Jun;25(3):307-14.
Whittemore Peterson Institute, University of Nevada, Reno MS 0552, 1664 N. Virginia St. Reno, NV 89557-0552, USA. vclombardi@wpinstitute.org
Abstract
BACKGROUND:
The recent identification of xenotropic murine leukemia virus-related virus (XMRV) in the blood of patients with chronic fatigue syndrome (CFS) establishes that a retrovirus may play a role in the pathology in this disease. Knowledge of the immune response might lead to a better understanding of the role XMRV plays in this syndrome. Our objective was to investigate the cytokine and chemokine response in XMRV-associated CFS.
MATERIALS AND METHODS:
Using Luminex multi-analyte profiling technology, we measured cytokine and chemokine values in the plasma of XMRV-infected CFS patients and compared these data to those of healthy controls. Analysis was performed using the Gene Expression Pattern Analysis Suite and the Random Forest tree classification algorithm.
RESULTS:
This study identifies a signature of 10 cytokines and chemokines which correctly identifies XMRV/CFS patients with 93% specificity and 96% sensitivity.
CONCLUSION:
These data show, for the first time, an immunological pattern associated with XMRV/CFS.
6. XMRV, PROSTATE CANCER & ME/CFS
XMRV, prostate cancer and chronic fatigue syndrome.
Kenyon JC, Lever AM.
Br Med Bull. 2011;98:61-74. Epub 2011 May 6.
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Abstract
BACKGROUND:
A new retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), was identified in 2006 and an association was claimed between it and a genetic polymorphism predisposing to cancer of the prostate. In 2009 the same virus was identified in a cohort of patients with chronic fatigue syndrome (CFS). In 2010 a second related virus was identified in a separate group of CFS patients. A series of studies from disparate geographical areas have failed to substantiate this work. Most recently several papers have suggested that the detection of these viruses was explained by laboratory contamination.
SOURCES OF DATA:
All papers including the wording XMRV were abstracted from the NIH library of medicine database and included in the analysis.
AREAS OF AGREEMENT:
XMRV is a newly described retrovirus whose nucleic acid has been identified in samples from patients with both prostate cancer and CFS.
AREAS OF CONTROVERSY:
Opinions differ as to whether the detected nucleic acid indicates infection with this virus in this disease or whether laboratory contamination of samples accounts for its presence.
GROWING POINTS:
An increasing number of papers now refute the association of XMRV with human disease in humans although there is some evidence of serological reactivity to the virus. While it is unlikely that XMRV is a major cause of either prostate cancer or CFS, it can infect human cells and might yet have a role in human disease.
AREAS TIMELY FOR DEVELOPING RESEARCH:
Further studies to either prove or disprove the disease association of the virus are ongoing.
John Coffin’s last two papers on human gamma retroviruses were positive. The authors have decided to change the rules on what counts as a positive. No longer is a result positive or negative. This would never been allowed with assays used for the other two human retroviruses.
In these two new papers John Coffin agrees that multiple assays are needed due to having no gold standard assay. But he has then decided that a person must test positive on all the assays and multiple times. This is despite the fact that we know some people are not mounting an immune response to the virus and will be negative by serology. The results of the ELISA assays are also subjective and are being compared not to controls samples from humans but monkeys. Monkey are known to not respond to HGRVs the same way a human does. This is why monkeys are no longer used for HIV research. With assays that are able to measure the viral load he now requires a minimum amount of virus. Again, if you have the virus you are infected. The level is not relevant. Again, if this was HIV it would not be allowed.
The HIV study was 3% positive and the prostate cancer study was 12% positive.
Prevalence of XMRV Nucleic Acid and Antibody in HIV-1 Infected Men and in Men at Risk for HIV-1 Infection
http://www.hindawi.com/journals/av/aip/268214/
Nucleic Acid, Antibody, and Virus Culture Methods to Detect Xenotropic MLV-Related Virus (XMRV) in Macaque and Human Blood Samples
http://www.hindawi.com/journals/av/aip/272193/
“Comparing burnout and CFS within one sample frame, thus looking beyond the psychology/medicine divide, could be a useful first step towards understanding their relationship.”
The divide is there for a reason.
Show me the paper that demonstrates Burnout suffers have irregular cytokine profiles. Show me the acidosis correlations. Tell me about the scores of outbreaks of Burnout associated with a viral outbreak. Show me the autopsies with spinal inflammation.
If ‘fatigue’ can be said to unify differentials, then wheel out all of your sick for their next paper. Seriously, this isn’t even GCSE science surely?
Nothing good can come from giving the slightest publicity to this quackery.