1. Patients launch a $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
ME/CFS and Beating the Clock
For Jody Smith, the ticking of a clock was enough at one time to chase her back to her bed. But with the passage of time, she has been able to reclaim her living room ...
Discuss the article on the Forums.

EBV, Candida, Dorsal Root Ganglionitis and Dorsal Defects - putting pieces of the puzzle in place

Discussion in 'General Treatment' started by John H Wolfe, Sep 10, 2012.

?

Do you think there may be something to this analysis?

  1. Yes

    4 vote(s)
    57.1%
  2. Didn't read it

    0 vote(s)
    0.0%
  3. No

    3 vote(s)
    42.9%
  1. In Vitro Infidelium

    In Vitro Infidelium Guest

    Messages:
    646
    Likes:
    280
    An hypothesis for an autoimmune role in M.E/CFS is certainly attractive, in the sense it offers a model of disease that fairly well describes what we all (all too painfully) observe. But at this stage we also have to allow that there may be more than one autoimmune process or set of processes to be found across the global M.E/CFS patient population (genetic variation might be expected to produce different autoimmune responses), as well as allowing that the symptomology produced by an autoimmune response could also be produced by multiple pathogens, either acting singly or in combination. However from a purely personal viewpoint, if I had to choose where to put the research £s/$s/Es for the purposes of quickest/biggest returns, I think I'd plump for anything connected with auto-immunity in M.E/CFS.

    IVI
  2. user9876

    user9876 Senior Member

    Messages:
    684
    Likes:
    1,548
    One of the things I was trying to argue is that there is probably more than one auto immune process hence only some people responding to Rutuximab. I like the way you put it in terms of the best bet of where to put research dollars. I think not only do we need ME research looking at auto immunity but there seems to be a fair bit of basic biological research into the immune system which will hopefully help.

    I think the thread started by Currer http://forums.phoenixrising.me/inde...to-put-the-puzzle-together.19326/#post-295708 is interesting in that it points to a paper talking about different things that in combination may trigger auto immune reactions inc genetic predisposition.
  3. justy

    justy Senior Member

    Messages:
    2,350
    Likes:
    1,984
    U.K
    I was actually under the impression that a substantial number of PWME had biological aberrations that were similar - not that we all had wildly different things showing up. If you look at the work of Myhill et al it is striking how similar the results are across the patient population. I think the same is broadly true for immune system problems whihc seem to let all sorts of nasty bugs and viruses get in and take root. The main difference i see in PWME is wehter they have marked autonomic dysfunction such as severe POTS and NMH or wehter they are in the category (like myself) who doesnt have this particular issue.

    All the best, Justy
  4. John H Wolfe

    John H Wolfe Senior Member

    Messages:
    220
    Likes:
    36
    London
    I’m not at all stubborn, I’m very open minded (have tried everything anyone’s ever put in front of me, and investigated various leads some of which have accorded with my own inklings, others of which have caused me to question them

    Curing a complex, chronic, multi-system illness with ‘a bit of massage’ doesn’t look very likely at all. However the theory does make sense and the clinical trials are encouraging, hence I wasn’t too quick to write it off, have been giving it a go and trying to fathom how it could fit into ‘the bigger picture’

    Neither am I. However what do we know about the illness? We know it’s multi-system, we know it commonly involves IBS, fatigue, some environmental and/or emotional stressor(s), and some level of chronic systemic inflammation, we also know that many of those who have healed have done so through an integral approach.. these are the sorts of themes that have directed my own approach

    There is always that possibility yes, however one may end up with forming the basis of these separate pictures, which may, in time, form the basis for understanding a group of illnesses with common factors – that can’t hurt now can it!? :)

    I would love to only I am not from the right background/don’t have the expertise (or the energy). I would love to see others who have both to engage in related work however, as they are indeed doing e.g. investigating whether mitochondria is a reliable biomarker for M.E. and the likely processes involved in associated dysfunction

    Thanks, that’s interesting

    Working backwards is indeed perhaps the best hope we’ve got until some crazy scientist somewhere has his eureka moment!

    Interesting, will have to include further this detail in my page, thanks for your input! :)

    Indeed it is subject to limitations, but that is not to say that it is a simple story or work of fiction, that’s a very black and white (and unhelpful) attitude

    I think perhaps you ought to revisit their literature, they are not devoid of any science at all

    Perhaps the greatest scientific/medical breakthrough in modern times? The identification of DNA, and sequencing.. where did that journey start? Dreamy Darwinian notions of chromosomes containing hereditary information in the 19th century - later provided spot on when the technology became available/expertise was developed in order to be able to follow up ‘scientifically’ on what amounted to a hunch
    If people like myself had allowed themselves to be dissuaded by monochromatic/defeatist thinkers back then, well.. imagine what state modern medicine would be in today..

    This is not really a matter of contention

    Again, I would not disagree, but I would say that it would be nice to see visiting fans of the Man Utd/Cities of this world not turning their backs on/throwing chips at the home fans, and celebrating their assumed defeat before the full 90 mins are up![/quote][/quote]
  5. In Vitro Infidelium

    In Vitro Infidelium Guest

    Messages:
    646
    Likes:
    280
    If you look at the list I linked to (list ) you’ll see that there is evidence for biomarkers, but these are not consistent across the different studies. Also it really isn’t possible to say anything substantive about a single study, and while I know that there is a lot of loyalty toward Myhill, her environmental medicine isn’t scientific, there’s no way to go from what she’s produced as research to arrive at something meaningful, at least outside of the paradigm under which Myhill practices. Folks can decide for themselves whether Myhill offers beneficial treatment, but that’s a different order of things from being able to equate research.
    There appears to be no body of published evidence supporting immune dysfunction in M.E/CFS, the research actually seems to militate against chronic infection with known pathogens, and against a dysfunction of the immune system that leads cycling of identifiable infection. POTS and NMH could be associative with the underlying pathology of M.E/CFS, or could be co-morbidities which are especially noticeable because of mutual reinforcement of debility between the clinically separate conditions. Where there is association of pathology, then that may have application across the global patient population (meaning the notional 17 million representing the whole gamut of human genetic variation and variations in pathogen and environmental exposure) , or be limited to discrete sub populations, limited by genetics and or pathogen exposure etc.
    IVI
  6. John H Wolfe

    John H Wolfe Senior Member

    Messages:
    220
    Likes:
    36
    London
    Thanks for the welcome :)

    Noted – a number of other folks were concerned about this, I didn’t write it very well – have now fully elucidated what I meant by this menu of exercise types

    I’m inclined to agree, although I know that for mild-moderate PWME like myself, activity beyond available energy doesn’t necessarily worsen the condition, although it always worsens symptoms for several days

    I know what you mean..
    ..but I suppose these modalities are fundamentally a process of finding out whether the kid in the shed used just the hammer, or the hammer, pliers, vice, etc, and with different manifestations of damage, how best to approach trying to fix the vehicles (different measures will have differing efficacy given differential damage)

    Indeed it may not, however being a bystander in certain cases does not preclude its role as a trigger, or propagator given other, complementary vulnerabilities (as per my hypothesis)

    Precisely, if the immune system knocks the mono on the head fairly swiftly/robustly then we may expect the patient to recover normally

    Yes, I believe that its severity/recurrence is indeed an indication that all is not well systemically

    Interesting, that's exactly what I've speculated in my blog!- do you happen to know the paper?

    I included this too in my analysis, and suggested that it could be infection-linked inflammation, toxicity-linked, or both

    ..and this

    ..but not this, thanks for the link

    Will have to take a look, thanks for the link!

    Thanks for your thoughts/comments folks :)
    justy likes this.
  7. user9876

    user9876 Senior Member

    Messages:
    684
    Likes:
    1,548
    Paper is here. http://rheumatology.oxfordjournals.org/content/40/2/205.full Most of it is about treating RA with Rituximab but there is speculation about mechanism in the discussion section. If I had time I would use google scholar to look at papers that reference this work to see if any have developed more of an explanation.
  8. user9876

    user9876 Senior Member

    Messages:
    684
    Likes:
    1,548
    You make a few errors in how you describe Rituximab - I don't think they affect your argument though.

    In your analysis is that you say Rituximab is used to treat leukemia. I believe its used to treat lymphoma which is cancer in the lymph nodes rather than leukemia which is cancer in the bone marrow. More interestingly its used to treat a number of auto immune conditions including RA, AIHA, Lupus.

    Also you say Rituximab is
    Rituximab is in wide spread use just not for ME where it is in early stages of trials - I think Fluge and Mella are currently carrying out an open label trial to try to understand dosing. There is quite an important point here in that Rituximab is already licenced and used for other purposes.


  9. Enid

    Enid Senior Member

    Messages:
    3,309
    Likes:
    838
    UK
    Since we are still in the dark as patholgy findings flood in - go with it John. (IVI any better ideas). Actually no one has a the real picture yet (oh lots of pathology findings - so why and what sets in motion - any better ideas IVI as to etiology - break it and find a Nobel prize).
    justy likes this.
  10. user9876

    user9876 Senior Member

    Messages:
    684
    Likes:
    1,548
    You talk a bit about the reactivation of viruses such as EBV. Personally I don't think ME is associated with virus reactivation as I think that would have been found. However a while ago I found this paper http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1065340/pdf/ar1691.pdf which talks of localised infections targetting sites of imflamation such as that produced by an auto immune mechanism.

    Alex gave a good explanation see:
    http://forums.phoenixrising.me/inde...une-model-of-me-cfs.18083/page-10#post-281763
    heapsreal likes this.
  11. user9876

    user9876 Senior Member

    Messages:
    684
    Likes:
    1,548
    Its good to discuss various ideas and try to join up various peices of research. I think discussion is important in developing ideas and making sure they cover a wide range of research.
    justy likes this.
  12. Enid

    Enid Senior Member

    Messages:
    3,309
    Likes:
    838
    UK
    I think for whatever reason the immune system crashes (overloaded most likely) - WHY ??
    justy likes this.
  13. John H Wolfe

    John H Wolfe Senior Member

    Messages:
    220
    Likes:
    36
    London
    My analysis page is a little more detailed/developed and I've also begun to flesh out how I believe the elements could be interconnected [Link]
    Many thanks
    Oh, it’s described in some of the literature as being used to treat Lymphocytic/Lymphoblastic Leukemia?


    I should include something about this too, you’re right that’s much more easily understood as relevant, thanks


    Ok, I’ll be more specific about what I meant by that aye


    Yes indeed, but I’m unaware of anyone having been prescribed it for M.E., and it appears to be very expensive, hence “for most”


    This tallies with my comments towards the end pertaining to local toxic/viral stress on inflamed regions (those in contact with/close proximity to the CSF)
    Thanks for the links :)
  14. In Vitro Infidelium

    In Vitro Infidelium Guest

    Messages:
    646
    Likes:
    280
    What evidence is there for all these claimed 'knowns' ? What evidence is there that there is a single 'it' ? And what is meant by healed and where is the evidence that it has happened ?
    Whether it 'can hurt' or not depends upon the presentation - one only needs to look at the case of XMRV to see the harm of an hypothesis tested inadequately against a judgement of plausibility, which when crowd endorsed led to many hundreds of people who could ill afford it, spending $100s on useless tests, and developing unnecessary concern about non existent retroviral infection.
    The eureka myth is one of most unhelpful nostrums of scientific history - not even supported by Archimedes own writings, its translation to modern science merely invokes numerous cases of narrative embellishment and the inherent unreliability of memory.
    I didn't use the word 'fiction', the use of which tends to imply knowing creation of an inexact presentation of a truth. Science is a black and white endeavour, its application in human life is necessarily limited but if your reference is to science then that has to be kept to, otherwise it stops being science, and merely becomes a narrative part of life.
    So something can be a 'little bit' scientific ? How precisely does one seperate out the science from the nonsense in such Curate's Eggs ? Neither 'environmental medicine' nor osteopathy meet the requisites of scientific rigour and both are wanting in a test of prior plausibilty.
    That is an argument of false equivalence. We are not in the 19thC, no one here is a Darwin and no one (hopefully)here is arguing in support of Bishop Usher. The limitations imposed by the accummulation of knowledge (there is a reducing ammount of what is imaginable relative to what is known) and the limitations imposed by the sophistication of scientific practice (Darwin would likely have been strongly - and positively -challenged by Popper should they have been contemporaries) mean that context of scientific thinking is necessarily different 150 years on.
    Further false equivalences - this place is not old Trafford, but just a public park with hoodie tops for goal posts, the best we can hope to achieve is a broad acknowledgement of the Off Side Rule and have an informed discussion about how the game may be played at a professional level, while indulging in a kick about.

    IVI
  15. In Vitro Infidelium

    In Vitro Infidelium Guest

    Messages:
    646
    Likes:
    280
    My proposition is that the whole notion of 'resolving the puzzle' is axiomatically flawed. That approach leads (as it has done for thirty years) down a route that sees patients invest in a belief and expectation of science that simply can not be delivered. Science works by breaking things down into small chunks - resolving small questions each in a very thorough way. The kind of thing envisage at the begining of this thread involves multiple hypotheses each heaped on upon the other in a Jenga like construction - that's exactly the kind of structure that science avoids for the obvious reason that a single failure can bring the whole ediface down.

    I can give a fairly simple aetiology that fits with what most readers here would agree are the key features of what they uderstand as M.E/CFS:

    the condition is an hormonally mediated neurological dysfunction, affecting a small area of the brain's communication/perception network such that sufferers do not actually have any persistent infection, have no other organic dysfunctions (other than unconnected comorbities), have no (other than unconnected comorbities) psychiatric illnesses, but because of this one discrete dysfunction in the brain - experience themselves as being perpetually ill, to the extent that the illness is to all intents, as disabling as though those affected by it were suffering a chronic infection:

    the hormonal mediation involves those hormones differentially expressed by gender, and which are subject to change by age. The dysfunction in the brain is primarily congential (allowing that damage to the brain may arise rarely at other times in life) and only becomes symptomatic under the influence of hormal expression or supression. So in conclusion - we are not 'actually' ill, but our brains are telling us we are ill. Do I like this hypothesis ? No! Do I expect any reader here to like this hypothesis ? Certainly not ! But as far as I can see it is very difficult to argue against it having a logical validity:

    whether it could have scientific validity is another matter. On the face of it the hypothesis appears to be falsifiable (though that's probably arguable), what it lacks though is evidence pointing to a location of the brain dysfunction - that is the hypothesis is reliant upon a further hypothesis - this is a fatal failing in terms of scientific validity, what appears to be a simple hypothesis is in fact a stack (albeit a stack of just a few) of hypotheses.

    IVI
  16. user9876

    user9876 Senior Member

    Messages:
    684
    Likes:
    1,548
    One of the problems I have with a lot of the papers I read about ME is the lack of a clear hypothysis (which would ideally be stated in a formal or semi formal way). The lack of clarity around what hypothesis is being stated makes it hard to see what supporting evidence there is, what unsupported assumptions are being made and which patients this may apply to. Also it is hard to give a counter example to invalidate or refine a hypothesis.Having a clear hypothesis also helps in designing experiments, choosing what measures to look at to try to disprove the hypothesis.

    Some papers such as Wessely's papers on FSS seem to lack an internal logical consistancy but this is glossed over with vague language.
  17. snowathlete

    snowathlete

    Messages:
    2,001
    Likes:
    1,994
    UK
    As a side note: Darwin is an interesting example. A scientist who understood evolution and breeding then married his first cousin and had many children with genetic problems most of whom died in infancy as a result. His surviving son went on to marry his first cousin too...
  18. In Vitro Infidelium

    In Vitro Infidelium Guest

    Messages:
    646
    Likes:
    280
    I entirely agree. I think source of the problem is a lower level of rigour associated with clinical setting research as opposed to laboratory setting research, this is something for which the Evidence Based Medicine culture has not provided a proper challenge. The Science Based Medicine critique of EBM offers some way forward, in particular the demand for a test of prior plausibility requires a formal test of hypothesis in advance of research proceeding.

    Psychiatry is highly problematic and when neurosurgery, neurochemistry and (less certainly) behavioural psychology are removed, what remains of psychiatry can not easily meet any test of prior plausibility. Personally however I’m not willing to go down the route advocated by Szaz which seems to me to leave deeply distressed people who don’t fit the known physical models of illness, with no medical or social support. What I do believe though is that mental health should not be allowed to become a convenient dustbin where other medical specialisms can dump ‘difficult to treat’ conditions and that the overweening ambitions of the APA and its supporters, in seeking to psychologise all medicine, should be challenged. Where psychiatric intervention is to be applied to conditions which are not of certain psychiatric purview, then there should be an absolute requirement for research to meet a test of prior plausibility, and for the founding hypotheses that are to be tested by research, to be explicitly stated within both the research bid and the final publication.

    IVI
    user9876 likes this.
  19. John H Wolfe

    John H Wolfe Senior Member

    Messages:
    220
    Likes:
    36
    London
    There’s evidence for multi-system effects in the symptomatology, hence M.E. relates to inflammation of the CNS and muscular pain (CNS + SNS = two systems)
    Many experience symptoms across two or more systemic process groups: neurological, psychological, immunological and gastrointestinal
    When referring to ‘it’ I am referring to M.E., we use the term to group together people with the above qualification, in the absence of more detailed, irrevocable, knowledge of related aetiology/ies
    Healed is not used in an exhaustitive, scientific sense here, it’s a proxy for the qualitative reporting of remission of symptoms particularly disruptive or detrimental in nature
    Then we must ensure that all such theories are adequately tested/debated then mustn’t we?.. whilst remaining respectful of individuals who have gone to considerable effort to further their understanding of the illness/earnestly contribute to related discussion/research/exploration thereof
    Where in my piece do I claim to have solved M.E.? God you're so hyperbolic/condescending; for someone with demonstrably high intelligence you have a funny way of showing it in the context of social interaction!
    ”relying on Myhill, Shapiro and Perrin would as far as I’m concerned produce more a work of fiction than of science”
    Through literature review, discussion, critical analysis, and hypothesis testing
    On the contrary, it’s a very apt paradigmatic analogy given where we are with understanding M.E.
    With respect, your role here appears to be that of an even worse pariah, at least he didn’t just concern himself with haughty condescention from the sidelines and actually motioned an alternative proposition (beyond the basics) – feel free to bring something to the party my friend
    Oh come on! Revisit the page, which I’ve now expanded considerably, if not yet exhaustively (other than in the sense that it’s fried my puny science-brain), and tell me that there are no nuggets in there at all!
    P.S. You don’t have to link the offside rule for me mate, I’m a player
    Science would never get to that stage until we first conceive of wider composite systems/processes: "99%" =/= 100%


    So we stop at that? What could be causing hormonal dysfunction? Aren’t you interested in exploring the possibilities/finding out?


    Where is yourevidence” that it is a discrete function?


    Hang on a minute.. where’s the science-nazi gone? :p


    Until we have more definitive scientific knowledge of/irrevocable findings concerning associated dysfunctional processes stacking hypotheses is perhaps the best hope we’ve got of understanding more about what could be behind the condition


    You see ‘quitting the game’ as a necessary corollary, I see an opportunity to use the information we do have, my intuition as a PWME, and my imagination, to think outside the box. End of story

    Totally in agreement, refinement is key (what I have posted is definitely not final, hence the format – a blog page, which I am constantly updating), never mind narrowed to a single, exclusive hypothesis, never mind exhaustive in terms of my exploration of its constituent elements


    What it is, from my point of view at least, however, is a step in the right direction

    Thank you for that compelling insight :)


    Amen.

See more popular forum discussions.

Share This Page