Medicinal cannabis and ME

Posted on 04/09/2015 by wames

Sittingbourne-based Netflix documentary producer Jason Reed speaks out: online article at  Kent online, 24 March 2015

Jason Reed, who suffers from M.E. has spoken extensively on the uses of medicinal cannabis.

“To feel the literal definition of exhaustion, to have pain course through your body like a derailed freight train, to be so sensitive you cannot touch your own skin, or to be unable to look at the dimmest of lights.

Well, these problems are not conducive to leading a ‘normal’ life.

“It doesn’t take much for a prescribed drug to knock me off my axis. Knowing how badly I react to most substances, I was always exceedingly wary of taking any drug.

“When I hit my mid-20s, with health forcing me to give up music, I reluctantly relented and took the advice of fraught onlookers to try cannabis.

“It’s funny, if you say to a stranger you use lavender for therapeutic purposes, it’s instantly understood.

“If you say the same about cannabis, that has actual evidence to support its efficiency, you may well be the recipient of a sceptical and stigmatising glare.

“So now, I seek to promote the voices of others with multiple sclerosis, Crohn’s, ME, fibromyalgia, to name a few.

“A by-product of our current drug laws are that they create an underclass. It predicates stigma and a deep sense of societal and individual shame.

“To seek relief is a basic human necessity, and the time has come to end judgement and end the barbaric criminalisation practices that serve no other use that political profiteering.”

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Post-exertional muscle abnormalities in CFS

Posted on 04/09/2015 by wames

Research abstract

Background:

Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK) activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects.

Methods:

Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS) for up to 24h and examined for changes associated with exercise.

Results:

In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured.

Conclusion:

EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.

Abnormalities of AMPK Activation and Glucose Uptake in Cultured Skeletal Muscle Cells from Individuals with Chronic Fatigue Syndrome, by  Audrey E. Brown, David E. Jones, Mark Walker, Julia L. Newton in PLOSone 10(4): e0122982 [Published: April 2, 2015]

 

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Cognitive dysfunction in adolescents with chronic fatigue

Posted on 04/08/2015 by wames

Research abstract:

OBJECTIVE: To compare cognitive function in adolescents with chronic fatigue with cognitive function in healthy controls (HC).

STUDY DESIGN: Cross-sectional study.

SETTING: Paediatric department at Oslo University Hospital, Norway.

PARTICIPANTS: 120 adolescents with chronic fatigue (average age 15.4 years; range 12-18) and 39 HC (average age 15.2 years; range 12-18).

METHODS: The adolescents completed a neurocognitive test battery measuring processing speed, working memory, cognitive inhibition, cognitive flexibility, verbal learning and verbal memory, and questionnaires addressing demographic data, depression symptoms, anxiety traits, fatigue and sleep problems. Parents completed the Behaviour Rating Inventory of Executive Function (BRIEF), which measures the everyday executive functions of children.

RESULTS: Adolescents with chronic fatigue had impaired cognitive function compared to HC regarding processing speed (mean difference 3.3, 95% CI 1.1 to 5.5, p=0.003), working memory (-2.4, -3.7 to -1.1, p<0.001), cognitive inhibition response time (6.2, 0.8 to 11.7,  p=0.025) and verbal learning (-1.7, -3.2 to -0.3, p=0.022). The BRIEF results indicated that everyday executive functions were significantly worse in the chronic fatigue group compared to the HC (11.2, 8.2 to 14.3, p<0.001). Group differences remained largely unaffected when adjusted for symptoms of depression, anxiety traits and sleep problems.

CONCLUSIONS: Adolescents with chronic fatigue had impaired cognitive function of clinical relevance, measured by objective cognitive tests, in comparison to HC. Working memory and processing speed may represent core difficulties.

Cognitive dysfunction in adolescents with chronic fatigue: a cross-sectional study,  D Sulheim, E Fagermoen, ØS Sivertsen, A Winger, VB Wyller, MG Øie in Arch Dis Child. 2015 Mar 19. [Epub ahead of print]

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CFS subgroup found to have low level inflammation

Posted on 04/08/2015 by wames

CFS is characterized by profound levels of persistent/recurrent fatigue. It is proposed that chronic, low level inflammation may play a role in this fatigue.

We recruited 100 untreated patients with CFS (average age 33±12) and 100 age and sex matched healthy controls (HCs). Serum levels of TNF-α were assessed using ELISA. Subjective fatigue was determined by questionnaire and muscle function tests were undertaken in subgroups in which maximal voluntary contraction (MVC), electrically stimulated muscle force generation and rate of fatigue were assessed in the quadriceps muscle.

Subjective fatigue was higher in patients with CFS compared with HCs. Preliminary analyses showed that serum TNF-α was undetectable in 97% of HCs, whereas 15% of patients with CFS had detectable (4.4+/-0.18pg/ml) serum TNF-α. MVC was significantly reduced in subjects with CFS compared with HCs. No difference was seen in stimulated muscle fatigue between groups.

This preliminary data suggests that a sub-group of patients with CFS may have low level inflammation and analyses are underway to further characterise other inflammatory markers in serum and muscle of these patients and to determine whether such changes could affect indices of muscle function or central fatigue. Funded by MRC, BBSRC and the ME Association.

The role of cytokines in muscle fatigue in patients with Chronic Fatigue Syndrome (CFS), by Kate Earl, Giorgos Sakellariou, Daniel Owens, Melanie Sinclair, Manuel Fenech, Graeme Close, Clare Lawton, Louise Dye, Micheal Beadsworth and Anne McArdle in The FASEB journal vol. 29 no. 1 Supplement 1055.34

Comment by Dr Charles Shepherd: Mitochondrial dysfunction and the role of cytokines in ME/CFS

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A review of grey matter volume research in CFS

Posted on 04/07/2015 by wames

Review article abstract:

Chronic fatigue syndrome (CFS) is a debilitating and complex disorder characterized by profound fatigue with uncertain pathologic mechanism.

Neuroimage may be an important key to unveil the central nervous system (CNS) mechanism in CFS. Although most of the studies found gray matter (GM) volumes reduced in some brain regions in CFS, there are many factors that could affect GM volumes in CFS, including chronic pain, stress, psychiatric disorder, physical activity, and insomnia, which may bias the results. In this paper, through reviewing recent literatures, we discussed these interferential factors, which overlap with the symptoms of CFS.

Gray Matter Volumes in Patients with Chronic Fatigue Syndrome, by Le-wei Tang, Hui Zheng, Liang Chen, Si-yuan Zhou, Wen-jing Huang, Ying Li, and Xi Wu in Evidence-Based Complementary and Alternative Medicine, Volume 2015, Article ID 380615, 7 pages  [Accepted 26 August 2014]
http://dx.doi.org/10.1155/2015/380615

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Assessing fatigue in children

Posted on 04/07/2015 by wames

Research abstract

BACKGROUND AND OBJECTIVE:

Fatigue is common in chronic health conditions in childhood, associated with decreased quality of life and functioning, yet there are limited data to compare assessment instruments across conditions and childhood development. Our objective was to describe fatigue assessment instruments used in children with chronic health conditions and critically appraise the evidence for the measurement properties of identified instruments.

METHODS:

Data sources included Medline, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO (using the EBSCOhost platform). Study selection included quantitative assessment of fatigue in children with health conditions. Data extraction was as follows: (1) study design, participant and fatigue instruments, (2) measurement properties of fatigue instruments, (3) methodological quality of included studies, and (4) synthesis of the quality of evidence across studies for the measurement properties of fatigue instruments.

RESULTS:

Twenty fatigue assessment instruments were identified (12 child reports, 7 parent reports, 1 staff report), used in 89 studies. Fatigue was assessed in over 14 health conditions, most commonly in children with cancer and chronic fatigue syndrome. Evidence for the measurement properties of instruments varied, and overall quality was low. Two fatigue instruments demonstrated strong measurement properties for use in children with diverse health conditions and children with cancer.

CONCLUSIONS:

The review is limited to children younger than 18 years and results are specific to health conditions described, limiting generalizability of findings to other populations. Evidence for the measurement properties of fatigue instruments varied according to the population in which instruments were used and informant. Further evidence is required for assessment of fatigue in younger children, and children with particular health conditions.

Fatigue in child chronic health conditions: a systematic review of assessment instruments, by A Crichton, S Knight, E Oakley, FE Babl, V Anderson in Pediatrics 2015 Mar 23. pii: peds.2014-2440. [Epub ahead of print].

 

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Personality disorders in CFS

Posted on 04/04/2015 by wames

Comorbid personality disorders in Chronic Fatigue Syndrome patients: a marker of psychopathological severity, by Calvo N, Saez-Francas N, Valero S, Alegre J, Casas M.
Actas Esp Psiquiatr. 2015 Mar;43(2):58-65.

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Police recruiters told that CFS is psychological condition

Posted on 04/02/2015 by wames

Dr Shepherd of the ME Association wrote to the Home Office in March to challenge the advice to Chief Police Officers that, when assessing recruits for the service, they should regard Chronic Fatigue Syndrome as akin to somatoform, factitious and dissociative disorders. The illness is listed in the circular as among “Conditions affecting mental and psychiatric health”.

Elementary, my dear Home Office… your classification is wrong!

 

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Fluge & Mella’s patent application for a CFS treatment

Posted on 04/02/2015 by wames

Excerpt from patent application:

Inventors: Øystein Fluge & Olav Mella

Date of publication 26 11 2014

Nitric oxide donor for the treatment of chronic fatigue syndrome.

Description
[0001] The present invention relates in a first aspect to a nitric oxide donor for use in the treatment of chronic fatigue syndrome also known as myalgic encyphalomyelitis.

In particular, the present invention relates to the use of a pharmaceutical composition containing a nitric oxide donor for the treatment of chronic fatigue syndrome/myalgic encyphalomyelitis in a subject afflicted with said disease.

In a further aspect, the present invention relates to a combination of a nitric oxide donor with a B-cell depleting agent for use in the treatment of chronic fatigue syndrome.

Said combination may be provided in form of a kit comprising pharmaceutically effective dosages of said compounds. Further, the present invention relates to a method for treating chronic fatigue syndrome comprising the step of administering a nitric oxide donor to a subject afflicted therewith.

Brief description of the present invention
[0018] In a first aspect, the present invention relates to the use of a nitric oxide donor (NO donor) for use in the treatment of chronic fatigue syndrome (CFS).

[0019] That is, the present inventors recognized that administration of a NO donor relieve the symptoms of CFS and, thus, may be useful in the treatment of chronic fatigue syndrome.

[0020] In particular, the present inventors recognized that an immediate relief after administration of an NO donor can  be observed. In contrast to medication administered so far for treatment of CFS, which are characterized by a  remarkable lag time of treatment success, as described for example for the treatment with Rituximab or Methotrexate, see e.g. WO  2009/083602. Thus, the administration of a NO donor surprisingly allow a treatment of CFS patients for immediate relief of symptoms without any delay as described for e.g. a B-cell depleting agent, like Rituximab, before.

An alternative strategy was applied, using supplement with relatively high doses of L-Arginine 5 g twice daily combined with L-Citrulline 200 mg twice daily. L-Arginine is the sole substrate of Nitric Oxide Synthases (NOS), thus this approach aims to overcome the dysregulated nitric oxide system in CFS/ME patients by providing relatively high doses of the substrate.

[0021] Further, the skilled person is well aware of other compounds suitable to influence the NO level, e.g. by influencing the amount or level of available substrate for NO production. Examples thereof include compounds inhibiting arginase, e.g. arginase II, a competitor of the NO synthase (NOS). Other examples comprise compounds stimulating the activity of NO synthase, in particular, of the eNOS, either by increasing the amount or level of NOS or the turn over rate of the enzyme. These compounds may act directly or indirectly through affecting the level of natural eNOS stimulators, like
sphinogine 1-phospate.

[0022] Hence, in another aspect, the present invention relates to a pharmaceutical composition comprising a NO donor optionally in combination with a pharmaceutically acceptable diluents, excipient or carrier for use in the treatment a chronic fatigue syndrome.

[0023] Moreover a composition is provided containing a combination of a nitric oxide donor and a B-cell depleting agent. Said composition is particular useful in form of a pharmaceutical composition for use in the treatment of chronic
fatigue syndrome. That is, while an immediate relief is obtained with the first component, the NO donor, a delayed response is obtained by the treatment with the B-cell depleting agent, as described in the art. Hence, it is desired to
administer the pharmaceutical composition containing the combination of NO donor and B-cell depleting agent in a combination, either simultaneously, separately, or sequentially.

[0024] Furthermore, the present invention provides a kit comprising as a first component a NO donor and as a second component a B-cell depleting agent. Said kit is useful in the treatment of chronic fatigue syndrome.

[0025] Finally, the present invention provides methods for treating chronic fatigue syndrome comprising the step of administering daily a nitric oxide donor. Preferably, said method of treatment includes the combinatorial treatment with
a B-cell depleting agent.

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Comparison of consensus & empirical ME/CFS definitions & criteria

Posted on 04/01/2015 by wames

Research abstract:

Background:  Since the publication of

  • the CFS case definition [Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A.
  • The chronic fatigue  syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994;121:953-959],

there have been a number of other criteria proposed including

  • the Canadian Consensus Criteria [Carruthers BM, Jain AK, De Meirleir KL, Peterson DL, Klimas NG, Lerner AM, Bested AC, Flor-Henry P, Joshi P, Peter Powles AC, Sherkey JA, van de Sande MI.
  • Encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatments protocols.  J Chronic Fatigue Syndr. 2003;11:7-115] and
  • Myalgic  Encephalomyelitis: International Consensus Criteria [Carruthers BM, van de Sande MI, De Meirleir KL, Klimas NG, Broderick G, Mitchell T, Staines D, Powels AC, Speight N, Vallings R, Bateman L, Baumgarten-Austrheim B, Bell DS, Carlo-Stella N, Chia J, Darragh A, Jo D, Lewis D, Light AR, Marshall-Gradisbik S, Mena I, Mikovits JA, Miwa K, Murovska M, Pall ML, Stevens S.
  • Myalgic encephalomyelitis: international consensus criteria. J Internal Med. 2011;270(4):327-338; Jason LA, Evans M, Brown M, Porter N, Brown A, Hunnell J, Anderson V, Lerch A.
  • Fatigue scales and chronic fatigue syndrome: issues of sensitivity and specificity. Disabil Stud Q. 2011;31:PMCID:  PMC3181109; Jason LA, Jessen T, Porter N, Boulton A, Njoku MG, Friedberg F.
  • Examining types of fatigue among individuals with ME/CFS.
    Disabil Stud Q. 2009;29:4-11].

Purpose
The current study compared these domains that were developed through consensus methods to one obtained through more empirical approaches using factor analysis.

Methods: using data mining, we compared and contrasted fundamental features of consensus-based criteria versus empirical latent factors. In general, these approaches found the domain of fatigue/post-exertional malaise as best differentiating patients from controls.

Results
Findings indicated that the Fukuda et al. criteria had the worst sensitivity and specificity.

Conclusions
These outcomes might help both theorists and researchers better determine which fundamental domains to be used for the case definition.

Comparing and contrasting consensus versus empirical domains, by Leonard A. Jason, Bobby Kot, Madison Sunnquist, Abigail Brown, Jordan Reed, Jacob Furst, Julia L. Newton, Elin Bolle Strand & Suzanne D. Vernon in Fatigue: Biomedicine, Health & Behavior [Published online: 26 Mar 2015]
URL:

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