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German study finds xmrv

Discussion in 'XMRV Research and Replication Studies' started by bel canto, May 18, 2010.

  1. Gerwyn

    Gerwyn Guest

    Hi nice to have you back.The cytokine study in the klimas study is consistent with immunomodulation rather than overt suppression.The problem in my opinion lies more with the Oxford and fukuda definitions who produce to many patients with depression with push cytokine patterns the other way.the population as a whole would display no abnormalities.
  2. Gerwyn

    Gerwyn Guest

  3. bel canto

    bel canto Senior Member

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    My comments were aimed at improving clarity. Instead, since you are dismissing my comments as opinions to be ignored, I think it is not helpful any longer. Sorry to have bothered.[/QUOTE]


    Please don't let one person's dismissive remarks make any difference to you. I, and I am sure many others, appreciate your efforts to clarify these terms. Particularly as they relate to the German study. The more clarification on scientific terms, the better for all of us in understanding some of these complicated discussions.

    Thank you for your efforts and contributions, awol!
  4. awol

    awol *****

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    and thanks for your encouragement. I am actually really not that upset. ;)

    I don't think dismissiveness was intended.
  5. usedtobeperkytina

    usedtobeperkytina Senior Member

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    Well, I have missed a lot. Have been preoccupied, so I just came into this conversation. I love debates like this that try to figure out mysteries. I like seeing the proposed theories, many of which I would not have thought of.

    I think we need to all write down our theories, mail it to the sock person (Creek) and two years later, or whenever the answer is found, we see which one of us is right. The winner will be tapped as CFSer King or Queen in a ceremony, with socks hanging around the room.

    I stopped reading posts at number 186. Not feeling well today, but just have to throw in my thoughts.

    First, I don't buy the 3-4% healthy are positive. I think it is much higher, at least 10%. No matter how you look for it, it is hard to find, even in sick people. So how much harder will it be to find it in healthy people, with likely no virus floating around in the blood and very few cells with it? I think this study might actually be showing that when a person's immune system is compromised, they are more likely to have active XMRV and more cells with it, because of their immune system compromise. But, had they not had immune system compromise, they would have XmRV but may not have shown up on current testing methods. So I don't think the rate of infection is different from healthy to immune system compromised people. Just immune system isn't keeping virus numbers down as it is in healthy people, making it more likely to show up on the tests.

    It is possible there is more exposure to XMRV in immune compromised folks, but with just 6% difference, it seems more likely the virus just shows up more in them using current tests.

    Secondly, I doubt it is transmissible through air. I don't think any previously discovered retrovirus is. I think it might could pass through saliva, but unlikely. Conditions would have to be just perfect in both people. Although, someone said XMRV is very stable, so it survives outside longer than other retroviruses. I think it was Mikovits that said that. Something caused outbreaks in schools and hospitals and the symphony in North Carolina. It is more than sex, but I doubt it is in the air. I am thinking this may be like FeLV which can be passed through saliva, but even then, it isn't common. Think of this, if just being in close contacts through schools is how it is spread, we would see more of it. My fear is that 10% of my friends and relatives will show positive, but since I am the one sick, they will think they all got it from me.

    Also, remember, as has been said, as with all viruses, not everyone exposed gets infection. And some get infection but immune system controls it so it doesn't cause disease. This is true of flu, and many, many other viruses, including the retros. I've been reading some on FeLV. This is what I read about FeLV: "Most cats that get exposed to the virus develop antibodies and are able to fight it off. This is especially true for cats that are free of parasites, are current on their routine vaccines, and are fed a good diet."

    Based on Mikovits' statements, I am leaning away from genetics playing a part. It seems to me the studies showing abnormal gene expression is likely a result of a retrovirus messing things up in the cell. Seems we get the virus, I say most of us through our parents, but some from sex, others from blood transfusion, some from other ways. Then, we keep the virus for a while with our immune system fighting it. And maybe for many months, years, even decades, the viral load is low and the immune system is doing its job and we aren't sick.

    Now, some without a strong immune system (possibly from not enough exposure to stuff) who have the virus may get sick earlier in life. Some get sick after numerous infections, which Mikovits says activates virus replication. Some may get sick after high stress lifestyle, which Mikovits says can activate virus replication because of cortisol levels. Some may get sick when they go through a hormonal change, with androgens turning on virus replication. Some of us have the virus and it is mold or bacteria or something else that turns on virus replication. Remember, the virus is in the Natural Killer cells, so anything that turns on NK Cell replication also turns on XMRV replication.

    Maybe for some, their immune system would keep it in check with just one of the trigger factors, but if we have one or two together, or one or two or three in succession, then maybe the immune system just can't get it under control. My point is, I think the triggers are more important in determining which XMRV+ people come down with an illness, rather than predisposition. I remember Mikovits showing this with hand gestures of level of virus in relation to immune system ability to respond.

    Remember, XMRV attacks natural killer cells (among others). And with each trigger, more natural killer cells are diseased. This then would start a cascading downward spiral of reactivation of latent viruses (secondary infections), high cytokine levels, more natural killer cell replication and more XMRV replication, then back to more infected and diseased Natural killer cells, etc.

    All of this fits with previous immune system studies in us and it fits our good days and bad days experiences. Mikovits spoke about that too. She said the cytokine response to the infection can be big and quick. This is why we can be walking in the grocery store and the fatigue come over us as though someone pulled a plug and all our energy drains out.

    i don't think this German study resolves anything but to say it is in Europe and is either higher in number or easier to find in immuno suppressed people. This doesn't say it happens in higher rates of CFSers. The previous studies, the three negative, I think some of them found the virus, but they didn't find it in CFSers or they didn't find it in higher rate in CFSers. If I remember right, I think one said they found it in a healthy person (just one) but didn't find it in any of the CFS samples. But the new German study doesn't dispute any of the three negative study results. The previous studies weren't saying XMRV isn't in Europe, they were saying it doesn't cause ME / CFS in Europe.

    First UK study only looked at ME / CFS people. They found none.
    I am sorry, too sick to remember or find the others.

    Also, folks, I think the reason US blood people have not decided to defer CFS people or XMRV+ people is that once they announce that is is in blood supply or can be transmitted by blood and their concern for causing disease makes them stop accepting donations from these groups, then you will have a whole bunch of people crying out for tests, and yet there is no standardized test. You will have people refusing to accept blood and that is bad for business, which blood transfusions are.... they are a business, lots of money involved if the blood spicket stops on either end. Until they can say they can test that blood they are giving a patient and can assure it is not XmRV+ you won't see them ban these people. Their out is that there is not enough evidence to show it causes disease. Besides, they have the "are you feeling well today" question in place, enough until they know more. And, this scenario of announcement of stopping may never happen. I just saw where WPi and a company have found a way to kill the virus in the blood. So, blood folks may be able to announce "yes it is in blood, yes it causes disease, yes there is a test, but we can kill it so all blood from this point on is safe." All in one, nice and neat, no public outcry, blood orders keep coming in.

    Tina
  6. slayadragon

    slayadragon Senior Member

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    Is this something that's known, or is it a hypothesis?

    Is there somewhere that I can find a list of all the things that we know that XMRV does, or that people who know a lot about the virus (e.g. Dr. Judy) have said that they think that maybe it does?

    There's so much material on this board and elsewhere about the virus that the really important info can get lost in the shuffle.

    Thanks very much for your help, to anyone willing to provide it.

    Best, Lisa
  7. Gerwyn

    Gerwyn Guest

  8. Gerwyn

    Gerwyn Guest

    Hi Tina If it helps Mulvs in mammals can exist in moist conditions(grass etc) for up to 7 weeks.Other Mulvs can be transmitted by saliva.I dont know about XMRV.There is a direct link between the lymph where all Mulvs replicate and the saliva
  9. usedtobeperkytina

    usedtobeperkytina Senior Member

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    yes, and I remember Osler's Web saying there was higher rate of cancer in that area, taste buds was it? Or was it lymph in the jaw? It was in the saliva glands, maybe. Boy, my mind is toast today.

    Gerwyn and Slay, I added a few paragraphs to my earlier post. If you have interest, go back and see addition.

    Gerwyn, you're talking science speak again. I don't know all those terms. Somewhere in all that is relationship of NK Cells and cytokines. Are you saying my theory is wrong or right?

    And by the way, the triggers and viral load part is from Mikovits.

    Tina
  10. Otis

    Otis SeƱor Mumbler

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    That thread is back here: http://www.forums.aboutmecfs.org/showthread.php?5073-Dr-Klimas-Recent-Lecture-ME-Awareness-Day-(-ve-XMRV-paper-coming)
  11. slayadragon

    slayadragon Senior Member

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  12. Gerwyn

    Gerwyn Guest

  13. lululowry

    lululowry Senior Member

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    I just want to thank all of you - and I do mean ALL of you - for your questions and explanations as I seek to understand this. I was diagnosed maybe 6 weeks ago (time? what is it?), I just finished Osler's Web yesterday, , I have been trying, trying, trying to understand what is happening to me and in the world with xmrv and I am grateful beyond words that I somehow landed here among you at PR.
  14. alex3619

    alex3619 Senior Member

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    Hi Awol,

    I stand by my conundrum. However, it doesn't necessarily mean what you think it does, it is designed as a conundrum to invoke thought - all science requires interpretation, even hard statistics and hard mathematical modelling. Statistics are used to lie all the time by all sorts of groups, including the biopsychosocial researchers. Everything has to be interpreted, even math. This is why the conundrum is a loop, and applies only to the scientific domain of arguement. From a social/pragmatic perspective, interprentation (and hence opinion) is absolutely essential to achieving goals. You can't work with just facts, which is why the conundrum emphasises that facts have to be interpreted. This condundrum specifically relates to scientific scepticism, something that all scientists need a good dose of.

    The solution to the conundrum is not that you shouldn't have opinions. It is that opinions alone are probelematic and have to be grounded in the facts, and that few people have a strong enough background to be sure of their interpretations, including me or anyone else in most cases. To really understand something, you not only have to listen to other's interpretations, you have to keep going back to the facts, but this is very hard work for those of us with ME or CFS. So a simpler answer is to question everything - which you are doing, and so I am not saying that you are wrong. I am only saying that the issues are imprecise enough that a very detailed interpretation is problematical.

    Suppression can indeed be pathological. The difference between suppression and deficiency, however, is that if you remove suppression there will be an instant return to full functionality (ignoring for this arguement the problem that many systems become highly unstable for a time after suppression is removed). Deficiency more accurately describes an absence, such as a loss of cells. Dysfunction is more a perterbation of the system, and includes both supression and deficiency, it is a more general term. These terms are rarely used precisely except in very specific contexts - and EVERYONE does this, it is a function of language and not a criticism. An example of suppression is the inhibition of the immune system via cortisol released during exercise in healthy people. Deficiency occurs in the loss of T cells in HIV AIDS, while dysfunction occurs in all cancers.

    Immune suppressed transplant patients have specific anti-immune drugs prescribed to them to prevent rejection. I do not understand enough of the mechanisms of any of these drugs to be sure of what they do, and with different drugs there will be different effects. Most of these drugs target specific immune systems, and are optimized to suppress those mechanisms which cause rejection, and not to suppress the entire immune system. The point is that these topics are very very complicated, and so it is possible to over-interpret the science, when in fact it is just poorly characterized for a general audience, as the target audience is retroviroligists and immuniologists, (of which I am neither). This German paper could really use a review by a competant retrovirologist who is good at communicating to nonretrovirologists.

    In fact I agree with your analysis in the second last paragraph, except that immune deficiency does not always imply disease, only most of the time.

    I think I sm waxing too philosophical, which is my bad.

    Bye
    Alex


  15. alex3619

    alex3619 Senior Member

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    Hi Gerwyn, I respectfully disagree. Interpretation is required for all aspects of science, ESPECIALLY statistics. Many of the biopsychosocial researchers have moderate to strong statistical results to back up their claims, but it doesn't make them right. These statistical results are misleading, and can only be interpreted with an understanding of the study they are for, its assumptions and methodogies, and where it fits with overall research. Statistics can be used to lie, objuscate and spin results to support arguements, which is why the UK health and social support system is so toxic to ME patients - the authorities have tons of statistics to back up their actions. Without accurate interpretation, statistics have no value at all. Statistical methods are simply a very valuable mathematical tool to assist analysis. The question at the back of you mind when you see statistical analysis should always be: does this make sense? If it doens't, it is possible the statistical results are misleading, ambiguous or wrong.

    Bye
    Alex



  16. alex3619

    alex3619 Senior Member

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    Hi Awol,

    Sorry if I seem to be dismissing you or your arguements, I am simply trying to provide a broader context for understanding. My scientific and philosophical/systems background is rooted in socratic debate, thesis and antithesis, and it is how I think about everything even making coffee in the morning. No disrespect is intended, and I appreciate that you realize that I was not trying to dismiss you. Debate is good, in my opinion, but then that is part of the Socratic viewpoint.

  17. alex3619

    alex3619 Senior Member

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    the biggest mystery of our time

    Hi Tina,

    This is the biggest mystery of our time, I think it is bigger than global warming. I have used the 10% figure before, even used it in a letter to the Australian Minister for Health, but it requires some extreme assumptions. Using a correction factor for underdiagnosis based upon the original prevalence figure in CFS and the new one (not necessarily valid, just the best I could do) I calculated prevalence at 9.72%. This ignored several disesases that are implicated because there were too many uncertainties for me to make a calculation, so there is room for this to go above 10%. In particular I am worried about posttransplant and postcancer fatigue patients.

    If the worst case assumption turns out to be correct, then there could be (roughly, I wont do the math, these are just rouph examples) 700 million people in the world with XMRV, including 30 million Americans and 2 million Australians. This is not a small problem. Even if this figure is double the real prevalence, we still have 350/15/1 million people are who are XMRV positive. Since the virus is transmissable, and so many people are infected, and it is hard to detect, the ONLY solution the world has is to find answers, and there appear to be three approaches, all of which are necessary: diagnostic testing, a vaccine, and active treatment which may include antiretrovirals. These approaches need to be pursued worldwide, even in countries where nobody can afford them. This will be a tough sell in these economically turbullent times.

    The other problem, as you surmise, is that the testing is still very inaccurate. With so little virus present, and probable immune suppression, no test can be considered completely accurate, and may not be for some years. This actually has a silver lining, as any CFS patient who tests negative to XMRV might be able to get a positive test when the technology improves. Taken in this light, the nearly 10% prevalence of the transplant patients in the German study may be a more accurate result, and reflect their inability to fight the infection. Similarly, the 10% figure fits with the risk of getting CFS after a severe infection.

    The airborne arguement you use is correct in my view, but the point of the speculations is that the possibility has been raised. This is very much a worst case scenario. If it is present in saliva, we know from influenza research that particles from a caugh or sneeze can travel up to nine metres, or roughly the lengh of an average bus. If there is enough protection from the saliva, this would make it transmissable via air, but I have to agree that it doesnt appear likely as yet.

    I like the "submit your theory" idea, it may have great value in promoting public awareness and debate.

    Bye
    Alex

  18. alex3619

    alex3619 Senior Member

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    Hi Lisa,

    I could be wrong, but I think the affect of XMRV on NK cells is an hypothesis. It is certainly consistent with current models of XMRV action, but is far from proven. What we do know (and may be what the original poster intended) is that it is thought to be infecting NK cells, but it is not known known if this pathological. Maybe someone else could comment on this some more?

    Bye
    Alex


  19. Mark

    Mark Acting CEO

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    So much to catch up on, on this thread; so much I'd like to respond to...I'll have to just pick out a couple of points...

    I absolutely agree alex. Phrases like 'global pandemic' and 'biological weapon of mass destruction' have been used, and to anyone who's actually read about what we're dealing with here, that doesn't sound overblown to me at all. Unfortunately we have to remember that the vast majority of people have heard nothing about any of this from their media, so we're in a difficult position as usual. If we tell it like it is, we look like complete nutters to most 'reasonable' people. To get any kind of sense of how such a massively significant phenomenon can be known to us and yet not be in the papers...explaining that takes a long time, individuals need a whole lot of information before they can be brought to that point. Very frustrating.

    But anyway, I agree with many posters here who are talking about figures of up to 10%. A lot of people have been talking about their pet theories lately, and I think that's all good. So for me I'll restate once again that my strong feeling is that retrovirology will be the key linchpin to understanding MS, IBS, CFS, GWI, and a whole range of 'medically unexplained' phenomena. Anybody with neuro-immune problems who it turns out hasn't got XMRV, I would be looking for other retroviruses.

    The point has been made that it is immune dysregulation that we're talking about here. That seems right to me, and to fit with (for just one example) Gupta's amygdala training; Gerwyn has also confirmed some pieces of the puzzle relating to upregulation or downregulation of immune responses. Failure of regulation of immune responses seems to me to be quite a key point to latch on to.

    Tina: I enjoyed your posts, as always, but there's one para I disagree with:

    Having followed the UK and Dutch studies in some detail at the time they came out, I don't think it is relevant that they only looked at ME/CFS people. We did a lot of analysis at the time, and the key point is this: none of those 3 studies found any XMRV at all. You're right that Kerr's study mentioned it may have found one or two possible positives in one batch, but they then backtracked and said they could actually be something different anyway. (It was a bit weird, because they effectively said it turns out that with their test, even their handful of positives aren't necessarily positives, but there you go!).

    We crunched the numbers and considered the angles, and the firm conclusion was: the only way they could all get 0% (remembering that Kerr's study tested on a lot of samples) was if there was either no XMRV in the UK, or if their tests weren't good enough.

    The detailed inadequacy of the testing methodology has been identified by Gerwyn and others, and it turns out that the people who are finding XMRV are using the right procedures that one would expect to be more likely to work. It's turning out to be a lot harder to detect XMRV than expected, which has confounded things quite a bit.

    So anyway: given that the Germans have now found a background level of 3% or so, consistent with US and Japanese findings, the probability of the UK studies testing hundreds of samples - ME/CFS or otherwise - and finding no XMRV, is infinitesimally small.

    If 3% of the population have XMRV, then at least 3% of ME/CFS patients should have it. Even if it's not associated with ME/CFS, they should still have found some XMRV in some of the samples. Even at 3%, with a few hundred samples, the chances of finding none at all are very, very small.

    McClure actually did try to suggest, in the press, that there might be no XMRV in Europe at all. They won't take samples from the WPI on the basis that they're afraid of introducing XMRV to Europe by doing so. So actually, that quite ludicrous proposition is what has been suggested, and that's why it's so important that the German study has debunked it.

    The only way you could hold out any other interpretation of the failed UK studies - other than that they simply failed as in FAIL - would be to suggest that ME/CFS patients, for some reason, uniquely have no XMRV - ie we're resistant to it somehow. Just not credible given what WPI found in the first place.

    Of course, what you said is exactly what the Wessely school and the cautious scientific world will continue to say; they will continue to urge caution as always, and they will say that ME/CFS association with XMRV remains unproven in Europe. Even after there have been studies that do find that association in Europe, I'm sure they will produce further negative studies and then do studies of studies that attempt to balance it all out and make a case that the association is 'unproven'. My expectation is that as the game draws to a close, they will make themselves look more and more foolish and come out with some truly ridiculous stuff that exposes their whole modus operandi. They will carry on, on auto-pilot, right up until they crash into the cliff. So every little step will have to be made one by one, and until it's all conclusively proven, nobody will be allowed to believe anything.

    Won't stop me believing though...:Retro smile:
  20. Robyn

    Robyn *****

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    They didn't find it because I believe they didn't want to find it. That and theydidn't replicate the original study. Wessely Simon is a psychologist not a retrovirologist. Why is his name even associated with any papers. And why was he allowed to hand pick the patients. I think that England has too much to lose if people go on diablility so they are treated horribly to prevent having to pay benefits. In the US we are looked at as nuts but we aren't sectioned and forced to exercise. There cannot be this many of us imagining this disease at once. If we all had mental illness I would think some of the antidepressants would have helped some of us over the last 25 years. I myself believe we have found the answer in xmrv. I think it is just a matter of time before it is revealed as such. They need to dot the I's and cross the t's before it goes out to the public.

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