Quantum leap in viral detection could impact ME/CFS & FM

Posted on 06/16/2015 by wames

Breakthrough findings in an individual disorder are special, but developing new technology that expands our ability to understand many diseases is something else entirely. It provides the potential to make a difference on a truly vast scale. Those types of breakthroughs are coming with increasing frequency.

  • Last month Mark Davis and his huge immune machine determined that exposures to herpesviruses, in particular, vastly altered the states of our immune system.
  • Just last week researchers uncovered a lymphatic network in the brain that provides a new window on neuro-immune disorders.
  • This week the journal Science published a breakthrough study that has major implications for understanding the role pathogens play in illness.

Each one could shed light on diseases like chronic fatigue syndrome and fibromaylgia
[See Medical Game Changer To Shed New Light on Neuroimmune Diseases]

The astonishing thing for us in the ME/CFS community is that two of the three researchers mentioned are also working on ME/CFS.

Steven Elledge, a Harvard researcher devised a cheap virus scan test:

Now that we can look at all viruses, it’s a complete game-changer.

I firmly believe that new technology drives science and generally has a much larger impact than individual basic science discoveries.

Read more by Cort Johnson on the Simmaron Research website:

Quantum Leap in Viral Detection Could Impact ME/CFS and Fibromyalgia, June 7, 2015

 

 

 

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Natural killer cytotoxicity in CFS

Posted on 06/15/2015 by wames

 Research abstract:

Natural killer (NK) cytotoxicity of chronic fatigue syndrome (CFS) patients is decreased, as reported by several laboratories. This observation led us to query whether the NK cells also lack antibody-dependent cell-mediated cytotoxicity (ADCC).

NK cells have the IgG Fc-receptor CD16A that mediates ADCC. To assess potential ADCC effectors, we examined the peripheral blood of 11 CFS patients from a Lake Tahoe cohort that met the Fukuda standards for CFS and had low SF36 scores.

Healthy controls were age- and gender-matched. We stained peripheral blood cells for CD16A with mAb clone 3G8 and for CD3, CD56, and perforin, then assessed the cells by flow cytometry. We found that the percentages of NK cells expressing CD16A were slightly lower for CFS patients 86.0+/-11.5% vs. controls 93.0+/-6.6% (P=0.08).

The median fluorescent indices (MFIs) of CD16A were lower,72% of the values for the CFS patients, 9342+/-3233 vs. control 12929+/-4425, though not statistically significant (P<0.17). Intracellular staining for perforin in the CD16Apos cells was similar for patients and controls.

Our data indicate that a larger sampling of CFS patients vs. controls is required to determine if the fractions of CD16Apos NK cells and the levels of CD16A on these cells differs. These two observations are both in the direction of compromising ADCC activity of patients. In addition, a bias in F over V allelic variants of CD16A might add to impairment, since the F allele confers reduced ADCC.

Assessment of the Fc receptor CD16A of NK cells of CFS patients for potential to mediate ADCC activity (HUM1P.303), by Isabel Silvestre, Daniel Peterson, Douglas Redelman, Stephen Anderson and Dorothy Hudig in The Journal of Immunology May 1, 2015 vol.194 (1 Supplement)

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The relationship between IBS, dyspepsia, chronic fatigue and overactive bladder syndrome

Posted on 06/15/2015 by wames

Research article abstract:

Background:

To investigate in a cohort with previous gastrointestinal infection and a control group the prevalence of overactive bladder syndrome (OAB), and how it was associated with three other functional disorders; irritable bowel syndrome (IBS), functional dyspepsia (FD) and chronic fatigue (CF).

Methods:

Controlled historic cohort study including 724 individuals with laboratory confirmed giardiasis six years earlier, and 847 controls matched by gender and age. Prevalence and odds ratios (OR) with 95 % confidence intervals (CI) were calculated.

Results:

The prevalence of OAB was 18.7 % (134/716) in the exposed group and 13.6 % (113/833) in the control group (p = 0.007). The association between OAB and IBS was strong in the control group (OR: 2.42; 95 % CI: 1.45 to 4.04), but insignificant in the Giardia exposed (OR: 1.29; 95 % CI: 0.88 to 1.88). The association between OAB and FD was weak in both groups. CF was strongly associated with OAB (OR: 2.73; 95 % CI: 1.85 to 4.02 in the exposed and OR: 2.79; 95 % CI: 1.69 to 4.62 in the controls), and this association remained when comorbid conditions were excluded.

Conclusions:

Sporadic IBS was associated with increased risk of OAB, whereas post-infectious IBS was not. An apparent association between OAB and previous Giardia infection can be ascribed to comorbid functional disorders.

Furthermore, our research demonstrates that CF conveys an increased and inherent risk for comorbidity with OAB.

The relationship between irritable bowel syndrome, functional dyspepsia, chronic fatigue and overactive bladder syndrome: a controlled study 6 years after acute gastrointestinal infection, by Robert Persson, Knut-Arne Wensaas, Kurt Hanevik, Geir Egil Eide, Nina Langeland, and Guri Rortveit, in BMC Gastroenterology 2015, 15:66 [Published online: 10 June 2015]

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Fatigue is prevalent and debilitating in patients with mitochondrial disease

Posted on 06/12/2015 by wames

Highlights

  • Perceived fatigue is a prominent and often debilitating symptom in patients with mitochondrial disease.
  • Perceived fatigue correlates with disease severity but not genotype.
  • Excessive sleepiness is prevalent but dissociated with perceived fatigue in patients with mitochondrial disease.
  • Perceived fatigue does not correlate with NMDAS muscle weakness scores.
  • Our findings have important implications for targeting of pharmacological therapies.

Research abstract

Perceived fatigue is a prominent symptom in patients with mitochondrial disease but to date its prevalence, impact and aetiology are poorly understood.

Our aim was to determine the prevalence and assess for comorbidities associated with clinically relevant fatigue in patients with mitochondrial disease. A cross-sectional postal survey of patients with mitochondrial disease was undertaken using a validated self-completion, patient-reported outcome measures (response rate: 60%; n = 132).

The prevalence and perceived functional impact of experienced fatigue were assessed using the Fatigue Impact Scale. Other putative biological mechanisms were evaluated using the Hospital Anxiety Depression scale and Epworth sleepiness scale.

Data were compared with those for healthy control subjects and patients with Myalgic Encephalopathy/Chronic Fatigue Syndrome matched for age and gender. Sixty-two per cent of patients with mitochondrial disease reported excessive symptomatic fatigue (Fatigue Impact Scale ≥ 40); whilst 32% reported severe, functionally limiting fatigue symptoms (Fatigue Impact Scale ≥ 80) comparable to perceived fatigue in patients with Myalgic Encephalopathy/Chronic Fatigue Syndrome.

Fatigue is common and often severe in patients with mitochondrial disease irrespective of age, gender or genotype. Future evaluation of causal factors in mitochondrial disease-associated fatigue is warranted with the potential to guide future treatment modalities.

Perceived fatigue is highly prevalent and debilitating in patients with mitochondrial disease, by Gráinne S. Gorman, Joanna L. Elson, Jane Newman, Brendan Payne, Robert McFarland, Julia L. Newton, Douglass M. Turnbull in Neuromuscul Disord,  July 2015 Volume 25, Issue 7, Pages 563–566

 

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Dysfunctional energy metabolism and oxidative stress pathways in CFS

Posted on 06/11/2015 by wames

Research abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating long-term multisystem disorder with a central and inexplicably persistent fatigue symptom that is unable to be relieved by rest.

Energy metabolism and oxidative stress have been recent focal points of ME/CFS research and in this study we were able to elucidate metabolic pathways that were indicative of their dysfunction.

Blood and urine samples were collected from 34 females with ME/CFS (34.9 ± 1.8 SE years old) and 25 non-ME/CFS female participants (33.0 ± 1.6 SE years old). All samples underwent metabolic profiling via 1D 1H Nuclear magnetic resonance spectroscopy and quantitated metabolites were assessed for significance.

Blood glucose was elevated while blood lactate, urine pyruvate, and urine alanine were reduced indicating an inhibition of glycolysis that may potentially reduce the provision of adequate acetyl-CoA for the citric acid cycle.

We propose that amino acids are being increasingly used to provide an adequate carbohydrate source for the citric acid cycle. We suggest that this is via glutamate forming 2-oxoglutarate through an enzyme that deaminates it and subsequently elevates blood aspartate.

Dysfunctional energy metabolism appears to have impacted creatinine and its elevation in urine suggests that it may be used as an alternative for anaerobic ATP production within muscle. A decrease in blood hypoxanthine and an increase in urine allantoin further suggest the elevation of reactive oxygen species in ME/CFS patients. These findings bring new information to the research of energy metabolism, chronic immune activation and oxidative stress issues within ME/CFS.

Metabolic profiling reveals anomalous energy metabolism and oxidative stress pathways in chronic fatigue syndrome patients, by Christopher W. Armstrong,
Neil R. McGregor,  Donald P. Lewis, Henry L. Butt, Paul R. Gooley in Metabolomics, 2015 May

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The effect of submaximal exercise tests in ME/CFS

Posted on 06/11/2015 by wames

Research abstract:

BACKGROUND

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness. Symptoms include profound fatigue and distinctive post-exertional malaise (PEM). We asked whether a submaximal exercise test would prove useful for identifying different patterns of tissue oxygen utilization in individuals with ME/CFS versus healthy subjects. Such a test has potential to aid with ME/CFS diagnosis, or to characterize patients’ illness.

METHODS

A case-control study of 16 patients with ME/CFS compared to 16 healthy controls completing a 3-min handgrip protocol was performed. Response was measured using near-infrared spectroscopy, resulting in measurements of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) over wrist extensors and flexors. Changes in O2Hb (delta (d)O2Hb) and HHb (dHHb) absorbance between the first and last contraction were calculated, as were the force-time product of all contractions, measured as tension-time index (TTI), and ratings of perceived exertion (RPE).

RESULTS

Individuals with ME/CFS demonstrated smaller dO2Hb and dHHb than controls. However, after adjusting for TTI and change in total hemoglobin (delta (d)tHb), differences in dO2Hb and dHHb were reduced, with large overlapping variances. RPE was significantly higher for cases than controls, particularly at rest.

CONCLUSIONS

Relative to controls, participants with ME/CFS demonstrated higher RPE, lower TTI, and reduced dO2Hb and dHHb during repetitive handgrip exercise, although considerable variance was observed. With further study, submaximal exercise testing may prove useful for stratifying patients with a lower propensity for inducing PEM, and have the ability to establish baseline intensities for exercise prescription.

Submaximal exercise testing with near-infrared spectroscopy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome patients compared to healthy controls: a case-control study, by Ruth R Miller, W Darlene Reid, Andre Mattman, Cristiane Yamabayashi, Theodore Steiner, Shoshana Parker, Jennifer Gardy, Patrick Tang, David M Patrick in the Journal of Translational Medicine, 20 May 2015 (e-published before print)

 

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Dysfunction found in innate and adaptive immune systems in CFS/ME

Posted on 06/10/2015 by wames

Research abstract:

Background:
Abnormal immune function is often an underlying component of illness pathophysiology and symptom presentation. Functional and phenotypic immune-related alterations may play a role in the obscure pathomechanism of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME).

The objective of this study was to investigate the functional ability of innate and adaptive immune cells in moderate and severe CFS/ME patients. The 1994 Fukuda criteria for CFS/ME were used to define CFS/ME patients.

CFS/ME participants were grouped based on illness severity with 15 moderately affected (moderate) and 12 severely affected (severe) CFS/ME patients who were age and sex matched with 18 healthy controls.

Flow cytometric protocols were used for immunological analysis of dendritic cells, monocytes and neutrophil function as well as measures of lytic proteins and T, natural killer (NK) and B cell receptors.

Results:
CFS/ME patients exhibited alterations in NK receptors and adhesion markers and receptors on CD4+T and CD8+T cells. Moderate CFS/ME patients had increased CD8+ CD45RA effector memory T cells, SLAM expression on NK cells, KIR2DL5+ on CD4+T cells and BTLA4+ on CD4+T central memory cells.

Moderate CFS/ME patients also had reduced CD8+T central memory LFA-1, total CD8+T KLRG1, naïve CD4+T KLRG1 and CD56dimCD16− NK cell CD2+ and CD18+CD2+. Severe CFS/ME patients had increased CD18+CD11c− in the CD56dimCD16− NK cell phenotype and reduced NKp46 in CD56brightCD16dim NK cells.

Conclusions
This research accentuated the presence of immunological abnormalities in CFS/ME and highlighted the importance of assessing functional parameters of both innate and adaptive immune systems in the illness.

Characterisation of cell functions and receptors in Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME), by Sharni Lee Hardcastle, Ekua Weba Brenu, Samantha Johnston, Thao Nguyen, Teilah Huth, Naomi Wong, Sandra Ramos, Donald Staines and Sonya Marshall-Gradisnik in BMC Immunology 2015, 16:3

 

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Computerised training improves verbal working memory in ME/CFS

Posted on 06/10/2015 by wames

Research abstract:

OBJECTIVE: Patients with myalgic encephalomyelitis/chronic fatigue syndrome experience cognitive difficulties. The aim of this study was to evaluate the effect of computerized training on working memory in this syndrome.

DESIGN: Non-randomized (quasi-experimental) study with no-treatment control group and non-equivalent dependent variable design in a myalgic encephalomyelitis/chronic fatigue syndrome-cohort.

SUBJECTS: Patients with myalgic encephalomyelitis/chronic fatigue syndrome who participated in a 6-month outpatient rehabilitation programme were included in the study. Eleven patients who showed signs of working memory deficit were recruited for additional memory training and 12 patients with no working memory deficit served as controls.

METHODS: Cognitive training with computerized working memory tasks of increasing difficulty was performed 30–45 min/day, 5 days/week over a 5-week period. Short-term and working memory tests (Digit Span – forward, backward, total) were used as primary outcome measures. Nine of the 11 patients were able to complete the training.

RESULTS: Cognitive training increased working memory (p = 0.003) and general attention (p = 0.004) to the mean level. Short-term memory was also improved, but the difference was not statistically significant (p = 0.052) vs prior training. The control group did not show any significant improvement in primary outcome measures.

CONCLUSION: Cognitive training may be a new treatment for patients with myalgic encephalomyelitis/chronic fatigue syndrome.

Computerized training improves verbal working memory in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a pilot study, by Daniel Maroti, Annika Fryxell Westerberg, Jean-Michel Saury, Indre Bileviciute-Ljungar in  J Rehabil Med, 2015 Jun 1

 

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Case study of yoga and CFS

Posted on 06/05/2015 by wames

Case study abstract:

BACKGROUND AND OBJECTIVE:

Chronic Fatigue Syndrome (CFS) is characterized by excessive fatigue after minimal physical or mental exertion, muscle and joint pain, poor concentration, dizziness, and sleep disturbances. We report here the effect of a yoga-based lifestyle intervention in a 30-year old male patient with a documented diagnosis of CFS with compromised quality of life (QoL) and altered personality.

METHODS:

The patient initially attended a short-term yoga-based lifestyle intervention program that consisted of yoga-postures, breathing exercises (pranayama), meditation, group discussions, and individualized advice on stress management, diet and physical activity besides group support. Thereafter, patient attended 5 more such programs.

RESULTS:

There was a notable and consistent improvement in his clinical profile, positive aspects of personality and subjective well-being, and reduction in anxiety following this yoga-based lifestyle intervention.

CONCLUSION:

Overall, the results suggest that lifestyle intervention may improve clinical condition and personality in patients with CFS.

A two-year follow-up case of chronic fatigue syndrome: substantial improvement in personality following a yoga-based lifestyle intervention by Yadav RK, Sarvottam K, Magan D, Yadav R. in J Altern Complement Med. 2015 Apr;21(4):246-9

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Variability in symptoms complicates usefulness of case definitions

Posted on 06/03/2015 by wames

Research abstract:

Background:
Ambiguities in case definitions have created difficulties in replicating findings and estimating the prevalence rates for chronic fatigue syndrome (CFS) and Myalgic Encephalomyelitis (ME).

Purpose:
The current study examined differences in occurrence rates for CFS and ME cardinal symptoms (i.e. post-exertional malaise, unrefreshing sleep, and neurocognitive deficits).

Results:
Findings indicated that there is a wide range of occurrence rates on critical symptoms of the case definition, suggesting that either the types of patients recruited differ in various settings or the questions assessing core symptoms vary in their wording or criteria among different researchers.

Conclusions:
The polythetic nature of the case definition may contribute to the wide ranges of symptom occurrence that was found. In order to increase assessed reliability of the symptoms and case definitions, there is a need to better standardize data collection methods and operationalization of symptoms. This solution would reduce the heterogeneity often seen in populations of CFS patients.

Variability in symptoms complicates utility of case definitions, by Stephanie L. McManimen, Leonard A. Jason & Yolonda J. Williams in Fatigue [Published online: 12 May 2015]

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