Interesting first appointment with Dr. KDM

[Research 1st]

Yes, I would concur. I think he is genuinely working hard to unravel this, but sometimes he is overly enthusiastic about findings that do not pan out.

Other than XMRV I honestly cannot remember an idea of his that didn't work out, at least in myself.

Can you name any? I don't mean this rudely or as a challenge. I'm just genuinely interested and accept I may have forgotten.

 

[Sushi]

Can you name any? I don't mean this rudely or as a challenge. I'm just genuinely interested and accept I may have forgotten.

I don't want to divert the thread too far from the topic of @SamB's first appointment, so I'll just comment that by "pan out" I mean that a number of times during the course of my treatment he has shifted as to what he thought was the "core causation"--which leads to the focus of treatment shifting as well. Not that each aspect of hypothesized causation didn't have merit, but none so far proved to be the core causative factor.

 

[Research 1st]

I like KDM. We had a brief chat in 1999 at a conference in Sydney, and I have had a chat with him (online or phone, I don't recall now) at least once since. I think he is genuine. I think that history also shows he gets too enthusiastic too fast.

Its funny about PGE2, that hypothesis is what drew me into ME research in 1993. In fact I was on a modified diet to limit it. This had side effects. There was short term gain, but long term decline.

PGE2 is derived from arachidonic acid, which also leads to many other series 2 eicosanoids. However its an essential fatty acid.

Previously it has been postulated that we over release free arachidonic acid (alcohol does this for example) via oxidative stress and other mechanisms, leading to inappropriate eicosanoid synthesis. It most likely is not just PGE2 either.

However this research has languished for two decades and not much has been done. You cannot just cut arachidonic acid out of the diet either, as being an essential nutrient you will die without it.

Those of us who are salicylate sensitive will also not make enough of it.

However as you will see from the chart these paths are inhibited by NSAIDs so you would think they would have more impact on ME. If there is a problem here, and its a big IF, then its about fine scale regulation of arachidonic acid, not blanket inhibition. This does however become more of an issue in anyone with low cortisol, as the normal function of cortisol is to lower arachidonic acid use.

So I am going to say I think its unlikely the issue they are alluding to is PGE2. Whatever it is, there is a need for ongoing research. Promising leads are not validated and replicated hypotheses until after the science is done.

Interesting you posted that diagram Alex.

Looking at it in relation to myself: I tested PGE2 and it was high and also I tested my Arachidonic Acid (AA) and it was very high. I saw the word Mast Cells there. I also have MCAS and have become allergic to nearly all foods so have lost 5 stone (31.75Kg) in weight.

If this is related to ME or Lyme disease or both, I have no idea.

 

[adelheid55]

I think it's important for doctors to be enthusiastic. How will you proceed without enthusiasm? Trial and error...
And it's really great that Dr. de Meirleir ist still enthusiastic after so many years and so many patients.
There are not many doctors in Europe who treat ME/CFS patients

 

[halcyon]

Its funny about PGE2, that hypothesis is what drew me into ME research in 1993. In fact I was on a modified diet to limit it. This had side effects. There was short term gain, but long term decline.

I've been worried about PGE2 as well recently, but I'm really not sure it's a problem. There is a controlled trial with high dose EFAs that showed clear benefit, and personally the times I've improved the most have been when I've been taking high dose EFAs.

 

[Research 1st]

Reminds me of all the media hype that followed the 'discovery' of a urine test for ME/CFS several years ago >>

After more than 20 years of investigation, and having assessed and treated thousands of patients in Europe and America, Prof De Meirleir, who is an internist at the Himmunitas Foundation in Brussels (a non-profit organisation specialising in chronic immune disorders), believes he has identified a mechanism to explain the development of ME that opens up new treatment options.

In addition, he and his fellow Belgian, Dr Chris Roelant, Chief Operating Officer of the diagnostics company Protea biopharma, have developed a self-diagnosing urine test for ME.

This 'discovery' was given uncritical coverage in the UK Daily Telegraph and several other papers and created a lot of false hope in the patient community at the time...

http://www.telegraph.co.uk/news/health/5407749/ME-Proof-that-it-isnt-all-in-the-mind.html

With respect, the H2S Urine test worked for me, I tested for it.

The experimental assay claims the more darker the urine, the more H2S you have in your body which implies bacterial overgrowth. I got multiple test kits. Mine is the worst result of all family members and I am the most severely affected (the test kit doesn't have bias).

Is it validated? No. It's just experimental, an 'idea', but his ideas work at least for me.
From ideas you dig deeper.

KDM claims the H2S comes from bacteria in your stomach, the wrong type.
So I tested for that and he's correct. And he claims this can cause things like D-Lactate to go very high. So I tested for that and he's correct.

Without the DIY urine test, I'd never now realise this idea of stomach bacteria in ME is really a 'thing'. I am glad I used the urine test as it made me explore other avenues I had no idea of.

 

[Research 1st]

When taken together, these data suggest that lipopolysaccharide (LPS), likely from gut bacteria, plays an important role in the pathophysiology of CFS/ME.

In 2013 he published

Plasmacytoid Dendritic Cells in the Duodenum of Individuals Diagnosed with Myalgic Encephalomyelitis Are Uniquely Immunoreactive to Antibodies to Human Endogenous Retroviral Proteins
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776582/

Recently he published

Humoral Immunity Profiling of Subjects with Myalgic Encephalomyelitis Using a Random Peptide Microarray Differentiates Cases from Controls with High Specificity and Sensitivity

Cort wrote that


https://www.healthrising.org/blog/2017/03/21/immunosignature-biomarker-chronic-fatigue-syndrome/

So it'a going to involve the immune system, the gut, and a human endogenous retrovirus.

Hi there.

I found some LPS and CFS research that might possibly interest you and others.

2016

''We observed elevated levels of some blood markers for microbial translocation in ME/CFS patients; levels of LPS, LBP, and sCD14 were elevated in ME/CFS subjects''

Source:
Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.
Giloteaux L1, Goodrich JK1,2, Walters WA1,2, Levine SM3, Ley RE1,2, Hanson MR4.
Microbiome. 2016 Jun 23;4(1):30. doi: 10.1186/s40168-016-0171-4.

2013

''The incidence of positive autoimmune activity against 5-HT was significantly higher (p<0.001) in ME/CFS (61.5%) than in patients with CF (13.9%) and controls (5.7%). ME/CFS patients with 5-HT autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise.''

Source:
In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.
Maes M1, Ringel K, Kubera M, Anderson G, Morris G, Galecki P, Geffard M.
J Affect Disord. 2013 Sep 5;150(2):223-30. doi: 10.1016/j.jad.2013.03.029. Epub 2013 May 10.

2007:

''Serum IgA levels were significantly correlated to the severity of illness, as measured by the FibroFatigue scale and to symptoms, such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory. The results show that enterobacteria are involved in the etiology of CFS and that an increased gut-intestinal permeability has caused an immune response to the LPS of gram-negative enterobacteria. It is suggested that all patients with CFS should be checked by means of the IgA panel used in the present study and accordingly should be treated for increased gut permeability''.

Source:
Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. Maes M, Mihaylova I, Leunis JC (2007)
J Affect Disord 99: 237-240. doi:10.1016/j.jad.2006.08.021. PubMed: 17007934.

2005:

''CFS patients showed an inverse stress-induced response pattern of LPS-stimulated cytokines responses in comparison to healthy controls, i.e. stimulated cytokine production decreased shortly after stress in CFS patients, while it increased in controls. Fatigue scores and basal LPS-induced cytokine levels were significantly associated for TNF-alpha in controls and for both cytokines in CFS patients. Stress-induced changes in stimulated cytokine production were not associated with general fatigue scores in the control group, whereas in the CFS group, fatigue scores were significantly correlated with integrated levels of LPS-induced cytokines. However, partial correlations revealed that these results were due to the high correlations with basal LPS-induced cytokine levels''.

Source:
Stress-induced changes in LPS-induced pro-inflammatory cytokine production in chronic fatigue syndrome.
Gaab J1, Rohleder N, Heitz V, Engert V, Schad T, Schürmeyer TH, Ehlert U.
Psychoneuroendocrinology. 2005 Feb;30(2):188-98.

2001:

''Several causes have been held responsible for the chronic fatigue syndrome (CFS), including an altered hypothalamus-pituitary-adrenal gland (HPA)-axis activity, viral infections and a reduced Th1 activity. Therefore, it was investigated whether the regulation of IL-10 is different in CFS. LPS-induced cytokine secretion in whole blood cultures showed a significant increase in IL-10 and a trend towards a decrease in IL-12 as compared with healthy controls. In patients and controls, IL-12 secretion was equally sensitive to suppression by dexamethasone, whereas IL-10 secretion appeared more sensitive in CFS-patients. In controls, IL-10 and IL-12 secretion were inversely correlated with free serum cortisol (r=-0.492, p<0.02 and r=-0.434, p<0.05, respectively). In CFS, such an inverse correlation was found for IL-12 (r=-0.611, p<0.02) but not for IL-10 (r=-0.341, ns). These data are suggestive for a disturbed glucocorticoid regulation of IL-10 in CFS''.

Source:
LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone.
Visser J1, Graffelman W, Blauw B, Haspels I, Lentjes E, de Kloet ER, Nagelkerken L.
J Neuroimmunol. 2001 Oct 1;119(2):343-9.

 

[Gingergrrl]

Its funny about PGE2, that hypothesis is what drew me into ME research in 1993.

Sorry for my confusion but is PGE2, the same as prostaglandins which are elevated in MCAS (or at least they were for me) or is this something different?

 

[alex3619]

I've been worried about PGE2 as well recently, but I'm really not sure it's a problem. There is a controlled trial with high dose EFAs that showed clear benefit, and personally the times I've improved the most have been when I've been taking high dose EFAs.

Hi have short term improvement on EFAs but long term decline. High AA is probably from a diet high in polyunsaturated fat, or from lots of animal sources high in AA such. High AA is not itself a problem unless its being released to make hormones in too high an amount.

 

[alex3619]

Sorry for my confusion but is PGE2, the same as prostaglandins which are elevated in MCAS (or at least they were for me) or is this something different?

PG = prostaglandin, E is a type, and 2 refers to the arachiconate synthesis path, there are two others named 1 and 3. Path 3 does come from omega 3 fats, but path 1 is a side branch of polyunsaturates.

PGE2 is an inflammatory prostaglandin that is implicated in a lot of things. I think it has a little to do with mast cells but I am not sure if its a major player. I think its PGD2 that is important in mast cells. Maybe somebody who follows mast cell research can comment. You can see mast cells are listed under PGD2 in the diagram I posted above.

 

[alex3619]

I started writing a blog on LPS and ME some years back but my temporary brain improvement ended and so did my technical blogs. LPS is one interesting candidate. If its high in blood you only have two choices, bacterial infection (even if undetected) or translocation. Its important to note that bacteria are not what is being translocated for the most part, that leads to sepsis, but their cell surface products, including the superantigen LPS or lipopolysaccharide.

 

[Gingergrrl]

PGE2 is an inflammatory prostaglandin that is implicated in a lot of things. I think it has a little to do with mast cells but I am not sure if its a major player. I think its PGD2 that is important in mast cells. Maybe somebody who follows mast cell research can comment. You can see mast cells are listed under PGD2 in the diagram I posted above.

Thank you for clarifying and I appreciate it!

 

[justy]

Sorry for my confusion but is PGE2, the same as prostaglandins which are elevated in MCAS (or at least they were for me) or is this something different?

No, its a different one, PGD2 I think....

 

[ryan31337]

24hr urine collection for PGD2 is indeed a test for MCAS, championed by Dr Afrin and others I believe. Like most its contentious, notoriously difficult to do properly and very expensive...

 

[Daffodil]

I just found out there are no publications in the works right now

 

[Thinktank]

PG = prostaglandin, E is a type, and 2 refers to the arachiconate synthesis path, there are two others named 1 and 3. Path 3 does come from omega 3 fats, but path 1 is a side branch of polyunsaturates.

Wouldn't it be better to increase PGE1 and PGE3 to offset PGE2? Like you mentioned, it's critical for normal function.
But then, aren't all PGE series actually inflammatory? One less than the other.

 

[Snow Leopard]

Reminds me of all the media hype that followed the 'discovery' of a urine test for ME/CFS several years ago >>

Yeah, many of us have heard all this before.

I trust data before hype...

 

[Thinktank]

I like the fact that he's so devoted to our cause, but we were already told a few times in the past that "the" cause of ME was found, which turned out not to be so.
First it was XMRV, then H2S, then it was chronic lyme, now it's something in the gut.

This time i need to see it validated and proven before i get enthusiastic.

 

[Dechi]

I like the fact that he's so devoted to our cause, but we were already told a few times in the past that "the" cause of ME was found, which turned out not to be so.
First it was XMRV, then H2S, then it was chronic lyme, now it's something in the gut.

This time i need to see it validated and proven before i get enthusiastic.

@Thinktank Dr Hyde has been saying it's in the gut for 30 years. This is not a new thing. He diagnoses his patients with ME by doing 2 tests (apart from the patient having a specific history) : SPECT scan that must show cerebral hypoperfusion and gastric biopsy which must reveal the presence of enterovirus or parvovirus.

https://liberationislife.files.wordpress.com/2017/03/definitionofme_nrf_print.pdf

 

[trishrhymes]

Thinktank Dr Hyde has been saying it's in the gut for 30 years. This is not a new thing. He diagnoses his patients with ME by doing 2 tests (apart from the patient having a specific history) : SPECT scan that must show cerebral hypoperfusion and gastric biopsy which must reveal the presence of enterovirus or parvovirus.

It seems to me possible that by using these 2 specific tests, Dr Hyde may be diagnosing correctly a subset of ME sufferers. It also seems possible to me that there may be other people who do not meet these specific criteria, but still have Internationally defined ME/CFS. For example there may be other viruses or other infectious agents that can set off and/or maintain ME symptoms.

I have not looked in depth into Dr Hyde's work - I have glanced through the paper you link to, which looks impressive - has he published any studies on this that show, for example that a very high proportion of ME sufferers meet these criteria, and also that healthy controls and people with other fatigue conditions do not?

This is not a criticism of Dr Hyde - I am genuinely both ignorant and interested.