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Neuropsyche News: Spring 2012: XMRV Playing lost and found with the cause of CFS

Discussion in 'General ME/CFS News' started by Firestormm, Apr 17, 2012.

  1. Firestormm

    Firestormm

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    I think this was actually written at the end of October 2011 but I might be wrong. Still...

    Spring 2012 edition: http://www.mentalhealthglobal.com/pdf/SONspring 2012_final.pdf#page=3


    Playing lost and found with the cause of chronic fatigue syndrome

    Alex J. Mitchell

    University of Leicester, UK


    How often are truly ground-breaking discoveries made in medicine? The kind of discoveries that immediately convert a misunderstood psychiatric condition into an undeniable medical one? This may well have applied to chronic fatigue syndrome in 2009.

    Chronic fatigue syndrome is a condition with unclear definition, unclear cause, unclear treatment and unclear lines of medical responsibility, despite up-to-date National Institute for Health and Clinical Excellence (NICE) guidance (www.nice.org.uk/CG053).

    Chronic fatigue syndrome is characterised by 6 months or more of fatigue, sometimes with diffuse symptoms such as insomnia, difficulty with concentration and physical symptoms such as muscle weakness, sore throat and lymphadenopathy.

    There is no doubt it is a common and problematic condition, with currently no single clear-cut cause. However, this all looked to change in 2009.

    In 2009, US researchers from the Whittemore Peterson Institute (Nevada), Cleveland Clinic (Ohio), and National Cancer Institute-Frederic (Maryland) reported that a gammaretrovirus may explain the majority of chronic fatigue syndrome cases.

    The virus in question was xenotropic murine leukemia virus-related virus (XMRV), itself only described in 2006. In a paper in Science, the authors reported that XMRV DNA was present in 67% of 101 people with chronic fatigue syndrome but in only 3.7% of healthy controls.1

    This was really an incredible finding as most experts had considered chronic fatigue syndrome to be a syndrome with many possible underlying causes.2,3 The positive tests in the small but significant number of healthy controls also led to fears that XMRV could be present in the blood donor supply in many countries.

    This appears to have led the American Association of Blood Banks to immediately discourage patients with chronic fatigue syndrome from blood donation.4

    A lesser known paper from an independent group examined 41 peripheral blood mononuclear cell-derived DNA samples from 37 patients with chronic fatigue syndrome and found murine leukemia viruses-like virus (the parent family of XMRV) gene sequences in 32 of 37 patients (86.5%) compared with only 3 of 44 (6.8%) healthy volunteer blood donors.5

    Two conclusive results from two independent groups. Using the fail-safe meta-analysis number of three, only one more similar result was needed and the landscape of chronic fatigue syndrome would be changed forever.

    In the past year, about ten independent laboratories have looked but failed to replicate these findings, all finding no XMRV in patient groups with chronic fatigue syndrome (or control populations) using blood or cerebrospinal fluid.

    Even those using the same laboratory conditions (identical polymerase chain reaction primers) used in the first investigation failed.6 But if these replication failures were to be believed, where had the XMRV results come from?

    One possibility is a faulty test lacking specificity, but this seems unlikely as like-for-like replication failed. One group found that XMRV was probably created in laboratory experiments with mice that made an immortalised cell line to study prostate cancer.7

    To resolve this confusion, the US Department of Health and Human Services organised a nine-laboratory Blood Working Group (which included the original laboratory), and although their aim was to assess whether the donor blood supply was at risk from XMRV or related mouse retroviruses, it would also in effect illuminate the situation of chronic fatigue syndrome.

    Collectively, the Blood Working Group found that no one could reliably detect the virus, even in previously positive samples from patients. This caused a house of cards effect.

    In June 2011, Science published an expression of concern, then in September Science issued a partial retraction, followed by a full retraction in December. The PNAS article5 was also retracted.

    The authors of the Science paper apparently fell out with each other over what they had and had not originally found. But in an unfortunate turn of events, study author Dr Mikovits was dismissed for insubordination and misappropriating laboratory equipment leading to her arrest.

    However, in an equally remarkable recovery of fortunes, Dr Mikovits is now working again and is a co-author on a US$2.3 million multi-laboratory grant that will look for XMRV and related viruses in many more patients with chronic fatigue syndrome than were analysed in the Blood Working Group study.

    As we go to press, the American Red Cross has just analysed blood samples from over 17,249 donors and recipients across the USA. Three donors but no recipients tested weakly positive for one out of three possible antibodies, leading to the conclusion of no evidence of XMRV or related retroviruses in their blood banks.8

    The story is not yet concluded as some of the original authors clearly feel their findings are real and meaningful. They state in a new publication that this work clearly rules out any possibility of gross contamination and additionally, represents the first identification and isolation of naturally occurring infectious XMRV.9

    There are some important lessons for everyone here. Exciting new findings, particularly revolutionary ones, should be viewed with caution until replicated with sufficient scale and rigour.

    In my view, journals should be asking for scrutiny of the original data by peer reviewers and also asking for permission to publish these data online. Peer reviewers must be accountable for both unfair rejections and premature acceptance of articles and this will only happen if their identities are disclosed.

    Unfortunately, there may be a more immediate and negative connotation. I suspect that many patients with chronic fatigue syndrome will be even more likely to reject psychological help after reading how the medical profession nearly found the cause of chronic fatigue syndrome, only to lose it again.

    Author

    Alex J. Mitchell, Consultant in Liaison Psychiatry and Psycho-oncology, University of Leicester, UK. Email: ajm80@le.ac.uk


    References

    1. Lombardi VC, Ruscetti FW, Das Gupta J, et al. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 2009; 326: 5859.

    2. Hickie I, Davenport T, Vernon SD, et al. Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Aust N Z J Psychiatry 2009; 43: 2535.

    3. Kerr JR, Petty R, Burke B, et al. Gene expression subtypes in patients with chronic fatigue syndrome/myalgic encephalomyelitis. J Infect Dis 2008; 197: 117184.

    4. American Red Cross. American Red Cross statement on XMRV and chronic fatigue syndrome. December 3, 2010.
    5. Lo SC, Pripuzova N, Li B, et al. Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors. Proc Natl Acad Sci U S A 2010; 107: 158749.

    6. Groom HCT, Boucherit VC, Makinson K, et al. Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. Retrovirology 2010; 7: 10.

    7. Paprotka T, Delviks-Frankenberry KA, Cingz O, et al. Recombinant origin of the retrovirus XMRV. Science 2011; 333: 97101.

    8. Dockser Marcus A. Scientists say XMRV poses no risk to blood supply. The Wall Street Journal 2011; October 24 (http://blogs.wsj.com/health/2011/10/24/scientists-say-xmrvposes-no-risk-to-blood-supply/).

    9. Lombardi VC, Hagen KS, Hunter KW, et al. Xenotropic murine leukemia virus-related virus-associated chronic fatigue syndrome reveals a distinct inflammatory signature. In Vivo 2011; 25: 30714.
     
  2. Enid

    Enid Senior Member

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    I must admit Firestormm - Neuropsyche News is a real turn off - perhaps if a bath possible today I'll come back to it.
     
  3. Jarod

    Jarod Senior Member

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    I don't think any of the Lombardi studies were properly replicated....

    I think this may be a typo Firestormm. He probably meant to say until revised?
     
  4. justy

    justy Donate Advocate Demonstrate

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    Hmm, this stood out for me

     
  5. Enid

    Enid Senior Member

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    Hmm too - any psyche who thinks - now here's the answer.
     
  6. Firestormm

    Firestormm

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    It's a weird one and no mistake. Not really sure what the point of his message is - or even if their is a message.

    I thought the following was nonetheless interesting:

    'Funny' to think that I don't relate 'research' to 'medicine' and yet I suppose when the latter relates to disease it really is one and the same.

    What is perhaps interesting is his use of terminology in the next sentence - over and above any application of his thought to our condition. Are psychiatric conditions not medical ones? Does it then follow that psychiatric research is not inclusively part of medicine? Weird.

    I wonder what he's getting at here anyway. Pretty sure he means that 'XMRV' had the potential to shift a psychiatric condition into the realms of undeniability - but it's a silly thing to say...

    Perhaps the above provides more context and insight to his thinking? See I read that and thought, (as I said on the other forum), that whilst CFS/ME has been determined as a neurological condition with unknown cause - neurology have never picked up the ball.

    The ball is passed to and fro - hardly ever with neurology - more often than not in the court of Immunology; but most often in psychiatry/psychology.

    Of course you can I suppose include Neuropsychiatry - or rather it should include Neuropsychiatry - but seldom does.

    There are still no clear lines of medical responsibility. Why? Because Neurology have never been told 'Pick up and run with the ball.' Neither have Immunology come to that - although some CFS/ME specialists in the UK NHS are Immunologists.

    From what I can recall of the NICE Guidelines (can't be arsed to review) responsibility is laid at the feet of GP's. So NICE are at 'fault'. Again.

    And GP's (as well as other referring bodies) are not effective at diagnosing or managing patients with reported symptoms of CFS/ME. As demonstrated unequivocally by some recent research (e.g. 50% referrals determined to have an alternate diagnosis).

    So stop passing the buck and step up to the plate. Mixed sporting metaphors! Hell I have ME :angel:

    This is interesting. Anyone read the NYT yesterday? It was another piece by Carl Zimmer about, well have a look: http://www.nytimes.com/2012/04/17/s...orm.html?_r=2&pagewanted=1&ref=general&src=me

    Carl Zimmer's page in Discover (http://blogs.discovermagazine.com/l...e-boston-globe-make-science-more-transparent/) links to Retraction Watch and a recent article written by the authors: http://articles.boston.com/2012-04-17/opinion/31350524_1_retractions-journals-research-integrity

    Anyway, it looks like the huge increase in retractions is leading to the 'industry' taking a hard look at the way in which papers are so rapidly published.

    Couple all of this with the move towards 'free' publishing and no subscriptions... and I'm not really sure what we might be looking at. I mean on the one hand they want things tightened up and on the other for papers to be freely available.

    Someone somewhere will have to take responsibility and shoulder the additional cost. Can't have it every which way...
     
  7. alex3619

    alex3619 Senior Member

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    Papers are not published because they are right, or the truth. They are published because they look like making a contribution. Free papers with easy distribution means more review by a range of people after publication - and more bad papers will bet burned. Bye, Alex
     
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  8. Wildcat

    Wildcat

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    "Chronic fatigue syndrome is a condition with unclear definition, unclear cause, unclear treatment and unclear lines of medical responsibility, despite up-to-date National Institute for Health and Clinical Excellence (NICE) guidance (www.nice.org.uk/CG053)."
    .

    .
    Oh Please, Wake UP! NICE have been propagatng this BS for years now!

    Everyone who has followed the NICE/MRC Propaganda for more than a few years is no longer seduced by the NICE/MRC BS
    .
     
    Ember and justy like this.
  9. taniaaust1

    taniaaust1

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    Reading that whole thingtook me on a long strange journey. I must admit it was suspenseful with one not knowing what it was headed to next..

    .....

    That part sounds good. I do think peer reviewers should be named. (It would of been interesting just how many Wessely reviewed over the years.. him and buddies being the reviewers for each other time and time again)
    ....

    As a psych biased one.... I do think it could of been far worst then he put it (it made me aware of just how close XMRV was of becoming scientifically accepted etc) thou he certainly did kick a punch in that psych way at times.

    The think the biggest kicker was right at the start
    It got quite tame after that for a psych biased writing.

    There needs to be some authority to stop giving out such false medical isleading info, when it is medically accepted that CFS they dont know the cause. Medical deciet should be made illegal. He should be made to retract the above statement which would be seen as untrue in a court and issue appoligies.

    He cant deny he was refering to ME/CFS in that sentence as it was what the article was about.

    Could a patient group start sueing for medical discrimination? Being constantly hounded by things that is medical misinformation is surely a type of discrimination towards us? If not.. why not?

    The psych field should be forced to pull in their wayward members who present mistruth. These people who are lying in medical articles, misleading or lies which could be medically disputed, do have govering bodies which surely could be held responsible for leaving so many of their members out there telling lies?

    ME/CFS in NOT "a misunderstood psychiatric condition".
    It is a medical condition in which they just dont know the cause yet.

    Could a retraction of that unarguable statement be sought? If the publicatiion wont get their author to retract and appologise.. could things like this be taken further to those who oversee all publications like this?
     
  10. Googsta

    Googsta Doing Well

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    I never got my hopes up in the first place, they lost me waaay before that happened, lol.

    If I hadn't already had good psychological help, this comment would really put me off.
    :Retro mad:
     
    taniaaust1 likes this.

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