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Negative XMRV CFS study with Ila Singh's name on it (University of Utah)

Discussion in 'XMRV Research and Replication Studies' started by Jemal, May 4, 2011.

  1. Ember

    Ember Senior Member

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    Can we say Dr. Singhs study showed that they couldnt find XMRV with their own assay?

    Didnt they did detect mouse contaminant in 5% of their samples? Dr. Vernon quotes the study as saying: Using this assay, we found approximately 5 percent of our samples to be positive for products of the expected size, regardless of whether they were patients or healthy volunteers.

    Am I misunderstanding something here?

    Although the study failed to report this finding, Dr. Singh tells Mindy Kitei that they detected XMRV in their cultured positive controls as well. (All positive controls grew XMRV--as one would expect.) Mindy quotes the study: After weeks 2, 4, and 6, cultures were lysed and analyzed by Western blots...and by qPCR for XMRV.
  2. kurt

    kurt Senior Member

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    I agree, 1.5% seems way too high, there is just too much unfamiliarity with CFS in the general population for the number to be that high. Even 0.4% seems high to me but it might be right for the whole spectrum of CFS, based on more recent studies. That is about 1.2M CFS patients in the US, and if world population is going to reach 7B this year (which is what is predicted), then 0.4% is 28M CFS patients world-wide, not 17M. But where are all those patients?

    My guess is that the majority of international CFS patients are mis-diagnosed or un-diagnosed. How many cases of AIDS in Africa are actually post-infection CFS due to their variety of local co-infections? AIDS is often diagnosed symptomatically in Africa, not always with testing...so probably the real world-wide CFS patient number is in the 20-40M patient range... but that is hard to prove, without competent international surveys.

    When I first got sick with CFS I thought it was a rare disease, a few strange outbreaks, and not much information was available even though the illness had been diagnosed in patients for over 10 years (this was in the 90s). So it seemed there might be a few thousand cases in the US at that point. But since then CFS seems to have exploded, I personally have met many people with CFS in the course of ordinary working and living, even with my restricted activities. I suspect a new epidemiologic study would alarm even the denialists.
  3. Jemal

    Jemal Senior Member

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    Dr. Deckoff Jones has commented on the Singh study:
    http://treatingxmrv.blogspot.com/

    It's pretty harsh, but maybe not without cause. I don't think they are friends anymore :angel:

    Click the link above for more.
  4. Ronan

    Ronan Senior Member

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    Isint Dr. Deckoff Jones now working for the WPI? Is this then an unofficial response to the study from within the WPI? I could be totally wrong about this though!!!?
  5. Jemal

    Jemal Senior Member

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    It's her personal blog, so it shouldn't be seen as an (un)official response by the WPI. This has gotten her in trouble before though, as some people will see it as an (un)official response by the WPI. Ah well...
  6. Jemal

    Jemal Senior Member

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    And indeed, it will be seen as such. Take this quote from another blog for example:

  7. boomer

    boomer Senior Member

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    Dr. Deckoff-Jones has made it very clear that she does not speak for the WPI in any way. she posted this clearly on her blog.

    This appears at the top of her blog page.

    "In January 2011, I began to work for the WPI, but the content of this blog does not represent the institute. It is personal. Any opinions expressed are mine alone."
  8. Jemal

    Jemal Senior Member

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    Yeah, I know. However, she is clinical director at the WPI now and she is posting things that directly involve the WPI's research. So I can understand why some people have a hard time differentiating. Many companies would not allow this situation to exist.

    Anyway, I am glad that she responded to the Singh study.
  9. insearchof

    insearchof Senior Member

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    hi Megan

    I agree, it was disappointing for some.
    You raise some good questions.

    As for x reactivity......what is it that the antibodies might be reacting to? And how specific are the tests? Why the failure to find antibodies on this occasion?

    I was also confused about the following statement....and I am not sure what to make of it:


    http://news.sciencemag.org/scienceinsider/2011/05/more-bad-news-for-chronic-fatigue.html?ref=hp


    Is the suggestion here, that the strain found in prostrate cancer patients is different to that seen in CFS? Yet if this is indeed what is being suggested it does not make a lot of sense because Singhs clone for calibration purposes came from prostate tissue that I thought she said was for all intents and purposes the same as WPI samples because it was 99% the same. At least that is what thought I read. Maybe I am confused or have missed something.

    Maybe someone can set me straight here?

    If I am not mistaken, and that 1% difference is enough to support that statement above.....to distance XMRV in prostate cancer from that found in CFS, then how can she justify using a different strain as a means to calibrate findings in CFS patients?

    Alternatively, is she alluding to another virus ie MLVs or something else?
  10. In Vitro Infidelium

    In Vitro Infidelium Guest

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    The changes in diagnosed numbers, or in self describing numbers, have several possible explantions only one of which is increased prevalence. Even with increased prevalence, infectious causation need not be implied as social behavioural or even environmental changes can also impact upon prevalence for instance in the US it might be argued (Im not suggesting it is valid) that increased M.E/CFS diagnosis mirrors the increased obesity rate indicating either a direct connection (which I think was one of the implications of Reeves work ?) or some associated function of dietry change. The UK perspective certainly from 1987 was never really focussed on rarity or outbreak; heterogenaity and a National prevalence figure of 100,000 were the abiding descriptors, of course Royal Free Disease and Icelandic Flu were then still being used as co-names for M.E. M.E was only very rarely used at diagnosis PVFS/PVS etc being prefrerred by those specialists willing to give a physiological diagnosis - but by that stage it was clear that outbreaks alone werent able to explain the overall numbers. The increase from 100,000 to 250,00 as the agreed prevalence rate is pretty much unsubstantiated but as the 100,000 figure was never meaningfuly tested, the change is not of great significance.

    IVI
  11. In Vitro Infidelium

    In Vitro Infidelium Guest

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    That is not a secure report from which one can make useful deductions. Certainly Singh is saying that XMRV is definitively present in tissues associated with prostate tumours in some individuals, and that (with Shin el al) XMRV is defintively not present in the blood samples of people diagnosed with CFS, and that: "Given the lack of evidence for XMRV or XMRV-like viruses in our cohort of CFS patients, as well as the lack of these viruses in a set of patients previously tested positive, we feel that that XMRV is not associated with CFS".

    Shin et al go on to say: " It is also vital to state that there is still a wealth of prior data (2, 10) to encourage further research into the involvement of other infectious agents in CFS, and these efforts must continue." the refs are to Devanur, L. D., and J. R. Kerr. 2006. Chronic fatigue syndrome. J Clin Virol 37:139- 50. and Komaroff, A. L., and D. S. Buchwald. 1998. Chronic fatigue syndrome: an update. Annu Rev Med 49:1-13. Whether Singh has other evidence to support a belief that there are XMRV like infectious agents involved in CFS, I don't think she has specified anywhere.

    IVI
  12. eric_s

    eric_s Senior Member

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    Yes, but i don't have too much trust that there would be real change, significantly more funding and more and better research. To me it seems more like a pc thing to say, a nice way to retreat from ME/CFS. I would not want to depend on them following up on this promise. It's the same thing the Wellcome Trust press release said.

    I still believe the same thing, if you can't pay the reseach yourself or "force" them in one way or the other to give you more, they won't do it. They don't have money to give away and there are many other groups who want the same money and have strong lobbies and good support in the population.
  13. insearchof

    insearchof Senior Member

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    Thanks for that. However my main interest was not the speculative last sentence of my post really.....it was all of what came before it. Can you or others comment on that?

    Thanks
  14. currer

    currer Senior Member

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    Hi, similar issues which relate to this discussion are being discussed on the thread about Switzer's prostate cancer study.
  15. Jemal

    Jemal Senior Member

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    There is a very interesting comment on Dr. Deckoff Jones' latest blog entry by the way. A person has gotten replies from Dr. Ila Singh and a reaction to that from Dr. Mikovits. It talks about samples from 25 patients that have been sent from the WPI to Dr. Singh and now vice versa again. The WPI is going to retest them.

    [snip]I quoted both the reaction from Dr. Singh and Dr. Mikovits, but decided to cut it out of my message. I am not sure if those e-mails were meant to be published. The comment can still be read at Dr. Deckoff Joness blog though. It's Anonymous, May 9, 2011 8:47 AM

    I think I can quote this part from Dr. Mikovits e-mail:

  16. Megan

    Megan Senior Member

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    Insearchof,

    Yes the quote is confusing if it is correct, I guess its possible the journalist made a mistake, but given the other information it does seem cryptic. It would all be easier to let go of if these questions were answered. I hope Singh will answer some of these questions publicly, especially what she thinks her antibody tests referred to in her patent document were picking up.
  17. shannah

    shannah Senior Member

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    Coffin is quoted quite a bit in this particular article.

    Study Discounts Chronic Fatigue Link to Mouse Retrovirus



    "Tufts virologist Coffin said the research "looks like a very carefully done study" that is very close to replicating the original experiments, but with markedly different results.

    He noted that the evidence for XMRV infection "rests on five legs," specifically the detection of:
    Infected cells and integration junctions in vivo, which has only been shown in prostate cancer patients.
    Viral antigens on cells from patients.
    Antibodies against XMRV in samples from chronic fatigue syndrome patients.
    Virus-like sequences, again in samples from chronic fatigue syndrome patients.
    And isolation of infectious virus.


    Of those, he said, all but the first have been challenged, "in the almost complete absence of credible confirmatory findings."


    http://www.medpagetoday.com/InfectiousDisease/GeneralInfectiousDisease/26373
  18. eric_s

    eric_s Senior Member

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    I just very much hope what Judy Mikovits said is correct and we will get to see those studies not too long from now. Let's see what we hear on 20/5. And of course even if there are more positive studies they could still be wrong. But it would be good news.

    It's a shame Ila Singh did not add 25 samples of healthy controls to those she sends back. Everything coded and without cheating please :D
  19. eric_s

    eric_s Senior Member

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    Is it just a detail without much significance or does it mean something that Coffin now does not call the finding of XMRV integration in prostate cancer "challenged" anymore?
    I think they challenged that too, by saying at least some integration sites are exactly the same as in a cell line and therefore at least those must be from contamination. Have they now changed their opinion on this?
  20. In Vitro Infidelium

    In Vitro Infidelium Guest

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    http://www.retrovirology.com/content/7/1/108

    XMRV shares extensive sequence identity with known xenotropic, nonecotropic and polytropic murine viruses; the first of which is known to infect many common human tumour cell lines, a phenomenon that has confused retrovirologists looking for disease associations for over three decades. Most putative associations of new or old human retroviruses with diseases (including CFS and prostate cancer) have turned out to be laboratory artefacts [19]. The case of XMRV as a new human pathogen must be judged against this background [22]. It is true that we cannot formally rule out the possibility that the samples in question are infected with XMRV and simultaneously contaminated by mouse DNA, although this is unlikely since we found no IAP-negative samples from which we amplified MLV-specific sequences (data not shown). Also, the failure to detect XMRV sequences other than in association with mouse DNA contamination in our cohort does not mean that the virus is not present in other, unrelated, cohorts.

    It is difficult to explain how the contamination may have occurred, especially since the samples came from three unrelated centres in the UK, Korea and Thailand. As both our negative tissue and PBS controls treated in parallel with the FFPE were XMRV PCR-negative, it is unlikely that contamination was introduced via reagents. The UK FFPE tissue samples were stored boxed and stacked in a cupboard in the histopathology department for several years; and it is possible that contamination happened during that time, although why only a few samples (4.8%) were XMRV positive and the remainder not is difficult to explain. Nor does it explain the Thai and Korean results on tissue collected prospectively for the study. It does, however, demonstrate the necessity of controlling by highly specific and sensitive means for mouse contamination.


    IVI

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