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XMRV CFS UK study #II

Discussion in 'XMRV Research and Replication Studies' started by Orla, Feb 15, 2010.

  1. Kati

    Kati Patient in training

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    What really bothers me is it's published in Retrovirology for the whole world to see. How do these studies then get discredited should there be grounds to?
     
  2. Alesh

    Alesh Senior Member

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    I remember Judy Mikovits was speaking about finding the proper reservoir of the virus. Perhaps I am naive from the point of virology and biology but I remember well that only the first 4 years I felt pathological symptoms outside of my neuraxis. The last 8 years all my symptoms are so to speak "located" in the brain. Perhaps the WPI study tested "fresh" patients :) and this one the patients with XMRV for long time well hidden against the immune system in brain tissue. I know everyone with ME/CFS has individual experience with his own symptoms and his own perspective but I would prefer if some study found something pathological in the tissue from brain biopsy or in cerebrospinal fluid.
     
  3. Alesh

    Alesh Senior Member

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    And perhaps Jonathan Kerr had to be mentioned as an author for completely different reason of the "publish or perish policy" kind.
     
  4. Gerwyn

    Gerwyn Guest

    hi Kurt The age of the blood is relevant because if extreme care is not taken at the point of sample collection cell lysis osmolarity changes etc release DNase which degrade the DNA so the older the blood the more degredation takes place.The older anticagulants inhibited tag polymerase and played havok with PCR so if the blood is say 15 years old the older anticoagulants were likely to be used.Now we know what happens when blood is collected in outpatients or in pathology cell lysis is very commonplace. The longer the blood is initially kept at ambient temperature the more chance of degredation processes starting.Rate of thawing also effects degredation-cryolysis.Dna in sera has even more problems due to deamination and hydrolytic cleavage.The age of blood also affects differnt types of RNA differently including viral RNA .These patients were in the NHS if the blood was taken by doctors probably juniors the situation could be even worse.
     
  5. kurt

    kurt Senior Member

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    Yes, they probably found something. And those high numbers are not unique, remember the ciguatera epitope? That was found in 96% of PWC. But if the XMRV validation studies continue to be negative, then likely they found something besides XMRV.

    I recently addressed this in the Cooperative test thread, and yes while most HERVs lack the pol gene required to replicate externally, it is conceivable that a HERV could be amplified through DNA activation if a culture study happens to use a cell line known to produce the target antigen, and a triggering protein as part of the amplification. And WPI used a prostate cancer cell line which is interesting. I don't know if their amplification included a triggering protein, so am not saying that happened, just that it is a possible alternate explanation that has to be evaluated experimentally.

    They had a real control from Silverman, but using spiked controls is a normal procedure. I would imagine at some point WPI did that as well, in fact a known positive control should probably be run with every batch.

    When a research line gets discredited usually the journals publishing the discredited studies will publish a retraction. But we are quite far off from that, there is not a sufficient body of studies yet.
     
  6. kurt

    kurt Senior Member

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    OK, so the original collection procedure might have been better in the 25 year-old blood taken by Peterson's office than the 15 year old UK blood? Yes, that certainly is an alternate explanation. Yet another variable that needs to be run down.
     
  7. Gerwyn

    Gerwyn Guest

    The last herv shown to be infective was about the time we diverged from chimps whatever the WPI found was infective and other workers have found exactly the same virus with the same base sequence. Even the opponents of xmrv as causative agent accept its existence.Everyone seems to forget that the WPI used a different patient cohort most british patients when diagnosed have idiopathic chronic fatigue.Feduka cant differentiate these from CFS and these guys pretend its feduka when in reality its oxford.you also cant get viruses from cells in 18 hours when it takes those cells two weeks to produce such virus When you say there are no powers that be in science I am afraid that you are being niave.You dont use a control group with ilnesses know to be related to endogenous gammas if you are seriously trying to find a very closely related endogenous one
     
  8. jspotila

    jspotila Senior Member

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    Several people have mentioned the NCI and other federal efforts to replicate the XMRV results, and develop a reliable blood test. From Dr. Suzanne Vernon's article on the January 6, 2010 PLoS One study:

     
  9. kurt

    kurt Senior Member

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    I did not say infective, rather that there are ways to activate a HERV with an amplification culture. A culture process might activate a HERV rather than culture an exogenous virus. But I am not doubting that XMRV exists, just trying to illustrate the types of issues that have to be addressed to reach a credible scientific consensus on the WPI study.

    True about patient criteria, but with that large of a sample they should have had many true CFS patients.

    Good point about 18 hours for amplification, how long did WPI amplify? I am assuming that was documented or stated somewhere, and that the Kerr study tried to replicate that. So that is the point. Also, how long does HERV activation take?

    Many competing labs have to weigh in on this, including some independent labs with no agendas. That is what I means by powers that be, there is no final arbitrator here, no authority figure. Maybe things look different in the UK, but here in the US things are usually a bit of a free-for-all.

    I agree about Kerr's control group, that made little sense except that it was probably a convenient sample available to them.
     
  10. Jimk

    Jimk

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    ukxmrv- yeah, that's what I mean. Nothing in this new study should be construed as a "replication study." This kind of thing will go on for a while, with various researchers using their own proprietary or favored method of PCR (different primers, different proteins, etc.) and finding different results, claiming that their test therefore proves it doesn't exist in CFS/ME. The headlines piss me off because most people don't go further than the headlines and look at the science, but that's "news" for you.
     
  11. Samuel

    Samuel Bedbound with NO DOCTOR

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    Hi Koan,

    Good point. These monster threads are hard to concentrate on for many of us.

    Please note that the forum software allows you to say how many posts show per page. So my page numbers do not match up with yours. :)

    Using article numbers is more bulletproof (though maybe not if you merge threads).
     
  12. Cort

    Cort Phoenix Rising Founder

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    %&^&%&! I was just starting to feel really good about all of this. No ulterior motives with Kerr and Gow. Kerr was very careful with his gene expression work - he crossed and dotted every T. Kerr is working closely with the WPI - he won that grant with them and he's doing that other study (apparently). I can't imagine he would lend his name to bad study. Ironically Gow was the other researcher that couldn't find De Freitas virus 25 years ago.

    Stil,l the most salient point of the Science Paper was the ability of the WPI researchers to put a clean cell next to a cell packed full of that XMRV (or whatever it is) and then watch that clean cell get infected and they were able to snap a picture of a virus budding out of that previously clean cell. If it wasn't XMRV it must have been something else - but something appeared to be growing in there. Until someone can explain to me that thats not the crux - or explain it away - I'm going to keep focused on that.

    If its an muLv virus fine. If its an endoretrovirus that's escaped and is infecting cells - that's probably fine too because I don't they've found one that can do that yet.

    Kerr HAS to make a statement about this - has he?
     
  13. Bob

    Bob

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    It's not all bad news! (Actually I think there may even be some really good news buried deeply in these results)....

    Like everyone else, I was disappointed when I heard the news of this study, but I'd been bracing myself for bad news... I was expecting more bad news along the way, and I'd already privately started thinking that XMRV might not be the answer we've all been hoping for... especially as the private blood tests are coming back at 'only' 50% positive.

    But, actually, this latest study has given me more encouragement than I had before it, not less!

    For a quick over-view of where we are right now:
    First of all, we know that about 50% of UK patients are getting tested positively when getting their blood tested privately. This is about the same figure as the USA results. (This is based on anecdotal reports from the patients themselves).
    So, even if the 'experts' can't find it, we know that this virus exists in the UK, no matter what the Wessely study found.

    Once the knowledge of this virus is out, as it is now, the genie can't be put back in the bottle. This virus is on our side now... we have real tangible proof of a new virus, which can't be disputed, even by Wessely. And it's now being investigated as a huge new phenomena, with huge amounts of funds going into it in the USA.

    The first UK study, The Imperial College study by Wessely & co, showed no sign of any XMRV virus in any of the healthy 'normal' UK population... zilch, nada, nothing, zero... And we are all confident to ignore that study because we know it was flawed.
    The second study, by Kerr & co, has found antibodies in the 'normal' controls, but not the ME patient blood (trust us in the UK to get it the wrong way round!)

    This latest finding has two major implications which is why I am encouraged by it:
    1. XMRV HAS BEEN DISCOVERED IN THE UK... They have now found the virus in the UK! Or at least antibodies to it! (I don't know why more of a fuss hasn't been made of this by the research team of by us lot!) I mean, this is really big news! XMRV is in the UK - why isn't this on the front page of all the newspapers in the morning, like the flawed Wessely study was! And another important point is that the percentage of the normal controls which tested positive for antibodies is exactly 4% - exactly the same as the WPI study - which is extraordinary, and i think significant! (26 out of 565 = 4.6%)
    2. The fact that no virus was found in the ME patient blood also seems to be significant to me. Significant because it suggests that the study was flawed. (We'd expect at least 4% positive testing - the same as the control group) There may have been many reasons why the ME patient blood may have been made useless e.g. storage, handling etc (Also, and I can't help feeling paranoid that the world is against me here, but if the ME patients are all from a certain type of clinic, then maybe all the Canadian definition ME patients - i.e. post exertional malaise - had dropped out of the clinics because they were using GET techniques which were making them more ill - so maybe the only patients left in the clinics did not experience any post exertional malaise - but this wouldn't explain the discrepancy with the normal population results)

    At least this team acknowledged that they had strange results and acknowledged that they need to more closely work with the WPI and standardize their tests.

    So this all seems like good news to me!
    So lets not be disheartened yet!

    One other things is that the WPI is creating better tests for the public testing, and is going to re-test all their past tests with the better quality test.
    This might mean that 60% or 70% of private blood testing ends up testing positive for XMRV (I'm being optimistic hear for the sake of discussion), in which case ME being associated with XMRV becomes a no brainer!

    Please could anyone pick up on any points that I may have got incorrect. (Much appreciated.)
     
  14. Kati

    Kati Patient in training

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    Here is a comment from the Virology blog author Vincent Racaniello:

    http://www.virology.ws/2010/02/15/x...log (virology blog)&utm_content=Google Reader

     
  15. anne_likes_red

    anne_likes_red Senior Member

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    http://www.retrovirology.com/content/pdf/1742-4690-7-10.pdf - is that what you're after?

    No statement that I'm aware of - perhaps we should ask him for one?

    Is a muLv fine as in less insidious? More easily treatable???

     
  16. gracenote

    gracenote All shall be well . . .

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    Cort, here is the provisional PDF of the Retrovirology 2010 paper.

    View attachment Absence of XMRV in UK patients with CFS.pdf

    --------------------

    ETA: Looks like anne likes red beat me to it. Thanks anne.
     
  17. Kati

    Kati Patient in training

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    Bob, thank you very much for your perspective. It is great that you could find some positive side to the study and I dig the fact that 4% of the control had some + XMRV material. Indeed it is a good sign. Why did the supposedly ME population didn't test +? Would it be wrong cohort- let's call it Wessley cohort, depressed patients and truly misdiagnosed patients, or perhaps patients that may have ME but their viral load is so low that it is not detectable.
    Could it be that the methodology was mishandled, for instance, primers, frozen samples, or samples that sat on the countertop for too long? (I am no scientist here so looking forward to hear Dr Vernon, Klimas and Mikovits' opinions.
     
  18. flex

    flex *****

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    So many good points here Bob. Straight to the point and explained in simple terms. Thank God someone here did explain it simply for the non scientists amongst us. One thing about no positives being found in the "CFS" group but 4% in the healthy controls is it makes me more suspicious about the cohorts and also makes me wonder whether the blood samples were pre screened before this study or indeed at any time in the past. It makes no sense that you wouldn't find 4% positive in the "CFS" patients but would find 4% in the healthy population. However there seemed to be a few different places providing the blood samples. This could explain the variance of results. They are reporting an overall result from a selection of different sample providers - is that true? Or did Kerr supply all the samples - I don't think that's how I read it.

    Anyway it is obvious that the main aim of this study is headlining. How they came to their conclusions will not affect the press reporting the "result". I really feel that some reputable people have been duped here and now have their names on this study in an attempt to poke a sword into the backs of the ME community.

    Like you say, at least it is confirmed to be present within these shores. I do worry about the June Kerr study going ahead though. It looks as though the plan is to rush out a load of flawed studies then pull the plug on any further ones going ahead. Hope the WPI/ Kerr study is a done deal.

    There were a lot of onside ME people in this study including Abhijit Chaudri and Kerr, I just cant understand how or why they got duped into this. Anyone got any suggestions.
     
  19. FernRhizome

    FernRhizome Senior Member

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    The thing about the WPI study is that didn't they have samples that tested positive not only at WPI but also at the Cleveland Clinic AND NIC? So that means three separate labs validated the WPI findings. I think we can be certain XMRV or something exists. It's another question as to whether it's in a different form in the UK.......I hope that WPI will put out a press release tomorrow and perhaps we'll learn more then. ~Fern
     
  20. Cort

    Cort Phoenix Rising Founder

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    That's true the Cleveland Clinic looked at a small # of samples - and they came up positive. These studies were much bigger but what a puzzle it is. The WPI is clearly doing a different test than these studies.

    I changed the title of the thread because I found it makes a big difference to search engine results - altho these results are nothing to be happy about. Dr. Vernon's response will be most instructive.
     

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