Abnormalities in pH handling by peripheral muscle and potential regulation by .......

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Tate Mitchell posted this to co-cure today.

[if: Thank goodness real science is continuing!]

'Abnormalities in pH handling by peripheral muscle and potential
regulation by the autonomic nervous system in chronic fatigue syndrome'


Jones, D. E. J.1; Hollingsworth, K. G.2; Taylor, R.2; Blamire, A. M.2;
Newton, J. L.

Journal of Internal Medicine, Volume 267, Number 4, April 2010 , pp. 394-401(8)

Affiliations: 1: From the Institute of Cellular Medicine 2: Newcastle
Magnetic Resonance Centre

Jones DEJ, Hollingsworth KG, Taylor R, Blamire AM, Newton JL (From the
Institute of Cellular Medicine, Newcastle Magnetic Resonance Centre,
and Institute for Ageing and Health, Newcastle University, UK).
Abnormalities in pH handling by peripheral muscle and potential
regulation by the autonomic nervous system in chronic fatigue
syndrome. J Intern Med 2010; 267: 394-401.

http://www.ingentaconnect.com/content/bsc/jint/2010/00000267/00000004/art00006


Abstract:

Objectives. To examine muscle acid handling following exercise in
chronic fatigue syndrome (CFS/ME) and the relationship with autonomic
dysfunction.


Design. Observational study.

Setting. Regional fatigue service.

Subjects & interventions. Chronic fatigue syndrome (n = 16) and age
and sex matched normal controls (n = 8) underwent phosphorus magnetic
resonance spectroscopy (MRS) to evaluate pH handling during exercise.
Subjects performed plantar flexion at fixed 35% load maximum voluntary
contraction. Heart rate variability was performed during 10 min supine
rest using digital photophlethysmography as a measure of autonomic
function.

Results. Compared to normal controls, the CFS/ME group had significant
suppression of proton efflux both immediately postexercise (CFS: 1.1 
0.5 mmol L−1 min−1 vs. normal: 3.6  1.5 mmol L−1 min−1, P < 0.001)
and maximally (CFS: 2.7  3.4 mmol L−1 min−1 vs. control: 3.8  1.6
mmol L−1 min−1, P < 0.05). Furthermore, the time taken to reach
maximum proton efflux was significantly prolonged in patients (CFS:
25.6  36.1 s vs. normal: 3.8  5.2 s, P < 0.05). In controls the rate
of maximum proton efflux showed a strong inverse correlation with
nadir muscle pH following exercise (r2 = 0.6; P < 0.01). In CFS
patients, in contrast, this significant normal relationship was lost
(r2 = 0.003; P = ns). In normal individuals, the maximum proton efflux
following exercise were closely correlated with total heart rate
variability (r2 = 0.7; P = 0.007) this relationship was lost in CFS/ME
patients (r2 < 0.001; P = ns).

Conclusion. Patients with CFS/ME have abnormalities in recovery of
intramuscular pH following standardised exercise degree of which is
related to autonomic dysfunction. This study identifies a novel
biological abnormality in patients with CFS/ME which is potentially
open to modification.


Keywords: autonomic dysfunction; chronic fatigue syndrome; magnetic
resonance spectroscopy; muscle bioenergetics

Document Type: Research article

DOI: 10.1111/j.1365-2796.2009.02160.x

Affiliations: 1: From the Institute of Cellular Medicine 2: Newcastle
Magnetic Resonance Centre
 
G

Gerwyn

Guest
Tate Mitchell posted this to co-cure today.

[if: Thank goodness real science is continuing!]

'Abnormalities in pH handling by peripheral muscle and potential
regulation by the autonomic nervous system in chronic fatigue syndrome'


Jones, D. E. J.1; Hollingsworth, K. G.2; Taylor, R.2; Blamire, A. M.2;
Newton, J. L.

Journal of Internal Medicine, Volume 267, Number 4, April 2010 , pp. 394-401(8)

Affiliations: 1: From the Institute of Cellular Medicine 2: Newcastle
Magnetic Resonance Centre

Jones DEJ, Hollingsworth KG, Taylor R, Blamire AM, Newton JL (From the
Institute of Cellular Medicine, Newcastle Magnetic Resonance Centre,
and Institute for Ageing and Health, Newcastle University, UK).
Abnormalities in pH handling by peripheral muscle and potential
regulation by the autonomic nervous system in chronic fatigue
syndrome. J Intern Med 2010; 267: 394-401.

http://www.ingentaconnect.com/content/bsc/jint/2010/00000267/00000004/art00006


Abstract:

Objectives. To examine muscle acid handling following exercise in
chronic fatigue syndrome (CFS/ME) and the relationship with autonomic
dysfunction.


Design. Observational study.

Setting. Regional fatigue service.

Subjects & interventions. Chronic fatigue syndrome (n = 16) and age
and sex matched normal controls (n = 8) underwent phosphorus magnetic
resonance spectroscopy (MRS) to evaluate pH handling during exercise.
Subjects performed plantar flexion at fixed 35% load maximum voluntary
contraction. Heart rate variability was performed during 10 min supine
rest using digital photophlethysmography as a measure of autonomic
function.

Results. Compared to normal controls, the CFS/ME group had significant
suppression of proton efflux both immediately postexercise (CFS: 1.1 
0.5 mmol L−1 min−1 vs. normal: 3.6  1.5 mmol L−1 min−1, P < 0.001)
and maximally (CFS: 2.7  3.4 mmol L−1 min−1 vs. control: 3.8  1.6
mmol L−1 min−1, P < 0.05). Furthermore, the time taken to reach
maximum proton efflux was significantly prolonged in patients (CFS:
25.6  36.1 s vs. normal: 3.8  5.2 s, P < 0.05). In controls the rate
of maximum proton efflux showed a strong inverse correlation with
nadir muscle pH following exercise (r2 = 0.6; P < 0.01). In CFS
patients, in contrast, this significant normal relationship was lost
(r2 = 0.003; P = ns). In normal individuals, the maximum proton efflux
following exercise were closely correlated with total heart rate
variability (r2 = 0.7; P = 0.007) this relationship was lost in CFS/ME
patients (r2 < 0.001; P = ns).

Conclusion. Patients with CFS/ME have abnormalities in recovery of
intramuscular pH following standardised exercise degree of which is
related to autonomic dysfunction. This study identifies a novel
biological abnormality in patients with CFS/ME which is potentially
open to modification.


Keywords: autonomic dysfunction; chronic fatigue syndrome; magnetic
resonance spectroscopy; muscle bioenergetics

Document Type: Research article

DOI: 10.1111/j.1365-2796.2009.02160.x

Affiliations: 1: From the Institute of Cellular Medicine 2: Newcastle
Magnetic Resonance Centre
Is there any way of finding out how these patients were diagnosed
 

lansbergen

Senior Member
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Abnormalities in pH handling by peripheral muscle

Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome

Abstract:. 

Jones DEJ, Hollingsworth KG, Taylor R, Blamire AM, Newton JL (From the Institute of Cellular Medicine, Newcastle Magnetic Resonance Centre, and Institute for Ageing and Health, Newcastle University, UK). Abnormalities in pH handling by peripheral muscle and potential regulation by the autonomic nervous system in chronic fatigue syndrome. J Intern Med 2010; 267: 394-401. Objectives. 

To examine muscle acid handling following exercise in chronic fatigue syndrome (CFS/ME) and the relationship with autonomic dysfunction. Design. 

Observational study. Setting. 

Regional fatigue service. Subjects & interventions. 

Chronic fatigue syndrome (n = 16) and age and sex matched normal controls (n = 8) underwent phosphorus magnetic resonance spectroscopy (MRS) to evaluate pH handling during exercise. Subjects performed plantar flexion at fixed 35% load maximum voluntary contraction. Heart rate variability was performed during 10 min supine rest using digital photophlethysmography as a measure of autonomic function. Results. 

Compared to normal controls, the CFS/ME group had significant suppression of proton efflux both immediately postexercise (CFS: 1.1  0.5 mmol L−1 min−1 vs. normal: 3.6  1.5 mmol L−1 min−1, P < 0.001) and maximally (CFS: 2.7  3.4 mmol L−1 min−1 vs. control: 3.8  1.6 mmol L−1 min−1, P < 0.05). Furthermore, the time taken to reach maximum proton efflux was significantly prolonged in patients (CFS: 25.6  36.1 s vs. normal: 3.8  5.2 s, P < 0.05). In controls the rate of maximum proton efflux showed a strong inverse correlation with nadir muscle pH following exercise (r2 = 0.6; P < 0.01). In CFS patients, in contrast, this significant normal relationship was lost (r2 = 0.003; P = ns). In normal individuals, the maximum proton efflux following exercise were closely correlated with total heart rate variability (r2 = 0.7; P = 0.007) this relationship was lost in CFS/ME patients (r2 < 0.001; P = ns). Conclusion. 

Patients with CFS/ME have abnormalities in recovery of intramuscular pH following standardised exercise degree of which is related to autonomic dysfunction. This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.
 

MEKoan

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Thank you, lansbergen, for this most interesting paper!

I am always happy to see the words: potentially open to modification!
 
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hi lansbergen & welcome to the forum

Thank you, lansbergen, for this most interesting paper!

I am always happy to see the words: potentially open to modification!
me too - and I especially like that "This study identifies a novel biological abnormality in patients with CFS/ME which is potentially open to modification.

ps - I'll let the admins know that there are 2 threads on this abstract now
 

MEKoan

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Whoa Nelly! What just happened?! A minute ago my post was the only reply.

Ahhh, thanks If and Gerwyn, too.

I gotta lie down.
 

Dolphin

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Is there any way of finding out how these patients were diagnosed
Patients with CFS ⁄ME (n = 16) were recruited through our local CFS⁄ME Clinical Service. All subjects fulfilled the Fukuda clinical diagnostic criteria for CFS[23].

23 Fukuda K, Straus SE, Hickie I et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med 1994; 121: 953–9.
Apart from the technical data, we are not given much info:
The CFS ⁄ME patients were substantially more fatigued than normal controls (median FIS scores 94 [range 48–137] vs. 2 [0–11], P < 0.0001).
A comparator group of age and sex matched
healthy sedentary controls recruited from the local
population (n = 8) underwent assessment. Sedentary
was defined as having a sedentary job and performing
<3 h of physical activity per week [24]. Subjects were
excluded, if they had potential secondary causes for
fatigue such as diabetes mellitus or hypothyroidism, or
were taking medications that could lead to fatigue or
interfere with muscle function. This included antihypertensives,
antianginals, diuretics and antidepressants.
Subjects refrained from caffeine or vigorous exercise
on the morning of the experiment.
 

Dolphin

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Thank you, lansbergen, for this most interesting paper!

I am always happy to see the words: potentially open to modification!
I'm not convinced:
The potential significance of our findings is that they
identify a clear potential approach to therapy. The
area of exercise based therapy in CFS ⁄ME is controversial
with many patient reports suggesting that exercise
can often make them feel worse [35, 38]. Our
findings would add further evidence to the suggestion
that unstructured approaches to exercise which led to
further proton efflux dysregulation would be expected
to exacerbate the symptoms experienced by patients
in the short term. There are clear data; however, to
suggest that modulated exercise can be associated
with substantial changes in the expression of proton
transporter proteins within muscle and increased functional
acid excretion [20, 21]. Taken together these
observations suggest that carefully structured exercise,
ideally using bio feedback and the information obtainable
by dynamic studies of the type described here,
can be expected lead to normalisation in proton excretion
which, we would postulate, would be associated
with symptomatic improvement. This hypothesis is
easily testable and the development of such regimes
would, if monitored against biological markers of the
acid exclusion pathway, be safe in this disease.
I like this idea:
We believe that this is the first study to quantify rates
of proton efflux in CFS ⁄ME and our findings would
suggest that this methodology has the potential to be
used as an end-point in clinical trials of targeted interventions
in this patient group.
Rubbish subject outcome measures particularly for recovery are used in many trials in the field.
 

WillowJ

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I'm not convinced:


I like this idea:

Rubbish subject outcome measures particularly for recovery are used in many trials in the field.
ugh to the biofeedback producing normalization. Don't they realize that serious chronic disease + lack of serious intervention = sophisticated independent biofeedback all on one's own? (othewise maligned as inappriate attention to symptoms)

If that were possible, we'd have done it already. Needs other intervention.

Sigh. That's what I get for putting articles on my list without having access to the full text. Thanks for the better info. :)
 

MeSci

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Great - thanks for that, Bob.

These bits are interesting:

Previous studies of CFS/ME patients using phosphorus spectroscopy have concentrated on mitochondrial oxidative function, which has been found to be comparable to that seen in matched controls in a number of different muscles [34–37]. Our study confirms that the same is observed in the soleus and gastrocnemius.
There was no significant differences in the postexercise recovery rate of PCr (CFS: 32.7 ± 9.0 s, controls: 27.2 ± 7.1 s), indicating no significant difference in mitochondrial oxidative function.
(Ouch - hope that bad grammar is a typo!)

Hmm...Myhill and some others reckon, and claim to have evidence that, there are mitochondrial oxidative abnormalities, and to have identified some. Hmmmmm....

Is one theory right and the other wrong, or is this an issue of subgroups? Or are the stats dodgy? (This study says no significant difference, but there is a difference.)
 
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Hmm...Myhill and some others reckon, and claim to have evidence that, there are mitochondrial oxidative abnormalities, and to have identified some. Hmmmmm....

Is one theory right and the other wrong, or is this an issue of subgroups?
Most evidence suggests that the oxidative function of the mitochondria themselves is in fact normal. Such deficiencies would also lead to different kinetics involved (particularly a lack of PEM, but rather a more constant fatigue instead).

Other evidence suggests that the problems are likely to be upstream of the mitochondria, with oxidative stress and issues with regulation of fatty acid metabolism before presentation across the mitochondrial membrane.
 

alex3619

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Its been a long time since I read Myhill's work. Wasn't the problem they were looking at something to do with transfer of substances across the mitochondrial membrane? So at rest or short activity it would look normal, but when stressed then critical deficiencies would start to appear?
 

MeSci

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Its been a long time since I read Myhill's work. Wasn't the problem they were looking at something to do with transfer of substances across the mitochondrial membrane? So at rest or short activity it would look normal, but when stressed then critical deficiencies would start to appear?
Here's one of the Myhill team's papers.