Discussion in 'XMRV Research and Replication Studies' started by Orla, Feb 25, 2010.
I'm back to playing it cool now!
67% had xmrv 4% controls . more people who are healthy will have xmrv because there are more of them but pwcs nhave much higher titres.A retrovirus can cause the symptoms of ME I dont know of anything else that can.I have had this conversation with court Oxford focuses on chronic fatigue in the absence of neurological signs.There is a quote from one of its creators above .it doesnt diagnose ME/CFS even the uk authorities state that.The fact that the dutch study didnt show xmrv even in "healthy" controls makes their results highly suspect considering that other researchers even groom
It could be another 25 years depending on what you mean by "decent". If the history is any indication, WPI will continue to find faults with any negative study.
One way to quickly end this controversy without wasting more resource is to take WPI's own samples, code them, and see if WPI can pick out the positives using their own method. I think they should resort to that if CDC also fails to confirm and controversy remains. It is utterly important for patients to get clean closure on this, so that they won't have to hang on to the viral theory and keep waiting. We don't want to repeat the history, after all.
Here is Dr. Vernon's analysis of the Dutch study. The Association's website is experiencing problems at the moment, so the article has only been posted to Facebook so far. Once the website is back up, this article will be posted there and linked from our XMRV info page.
Sometimes I get the feeling Dr. V wants more info on the cohort.
Some Levity! Great Anne.
Yea, this response feels a lot like her earlier response-- hopefully she didn't just copy-paste-- JK =) . Apparently she thinks there were minor things wrong with the study but nothing that should prohibit them from finding XMRV at all. I'm getting the feeling she really doesn't have an idea why everything is turning out the way it is though. Even if there are variants they used the same primers WPI used (with WPI claiming to detect XMRV internationally with those primers). I'm wondering what Mikovit's response will be, hers might be more informative than Vernon's this time around.
Something isn't right here. From Dr. Vernon's analysis above:
From the WPI website ():
ETA - The Science paper, Dr. Peterson's CFSAC cancer slide, and the WPI website are in conflict. This is something they need to explain.
There are plenty of other conditions that can cause symptoms of ME and CFS. Including brain damage, chronic herpes infections, various bacterial infections, ciguatera type toxins (which may include toxins from mitochondria damage as their envelope is a ciguatoxin epitope), many different parasitic infections, particularly the protozoans, glutathione insufficiency from various causes, and organic mitochondria disease. Also add to that HPA damage or malfunction due to prolonged trauma or stress, post-polio type syndromes, and the list goes on. Of course combinations of these and other factors also can create ME/CFS type symptoms.
Also, the only reason the Dutch study used Oxford is that was all there was at that time. These were very sick patients evaluated in other CFS studies.
That is a great idea but I doubt WPI would go for that, they have too much at stake and any number of factors could cause that type of test to fail. But I agree patients need closure. We will get that eventually, when enough confirmation studies have been reported.
I know that is how things look in the UK, but don't forget that things are not rosy in the US either. Our problem often is not the lack of treatment options but the lack of insurance coverage for those treatments. Then there is the small problem of effectiveness, people in the UK may be better off in some ways because the drug treatments used here can be dangerous. Yes, people in the UK have been killed with GET but people in the US have been killed by the supposedly 'better' biological therapies. A friend of mine with CFS died from effects of a drug given for CFS, and I nearly died from the same drug and have had other severe reactions to therapies doctors insisted were perfectly safe. That is one of the reasons I believe we have to be very careful about research claims and proposed drug therapies, we need a very competent scientific consensus process and serious debate and review of every CFS research finding.
I agree, it's happened at least once on one of the CFIDS groups I used... I'm talking more about the continual cranking out of subpar studies that divert attention from biomedical research and appear to have authority because they are repeated and there are so many of them.
I agree, Lesley. Dr Peterson's presentation to the CFSAC does not match the info on WPI's website. I don't know why the two do not match, and it won't serve any of us well to speculate. It would be appropriate for Dr. Peterson and/or Dr. Mikovits and/or WPI to clarify.
I don't know if this is getting of track but I ran across an article in the Journal of Virology Mar. 2010 p. 2556-2562. I have no idea what they are talking about or whether it is germane to CFIDS but I'll put it out there for anyone who can decipher the info.
Xenotropic Murine Leukemia Virus-Related Virus Establishes an Efficient Spreading Infection and Exhibits Enhanced Transcriptional Activity in Prostate Carcinoma Cells
Columbia University, Howard Huges Medical Institute Jason Rodriguez and Stephen Goff
Xenotropic murine leukemia virus-related virus (XMRV) is a novel human gammaretrovirus discovered in association with human prostate tumors. XMRV was first identified in prostate stromal cells surrounding the tumors of patients carrying a mutation in the HPC1 gene locus. To determine the tropism of XMRV in cell culture, we tested the ability of XMRV to spread and replicate in various prostate and nonprostate cell lines. We found that although the expression of XMRV viral proteins and the spread of infectious virus were minimal in a variety of cell lines, XMRV displayed robust expression and infection in LNCaP prostate tumor cells. The transcriptional activity of the XMRV long terminal repeat (LTR) was found to be higher than the Moloney murine leukemia virus LTRs in both LNCaP and WPMY-1 (simian virus 40-transformed prostate stromal cells). The U3 promoter of XMRV and a glucocorticoid response element (GRE) within the U3 were required for the transcriptional activity in LNCaP cells. Coexpression of the androgen receptor and stimulation with dihydrotestosterone stimulated XMRV-LTR-dependent transcription in 293T cells, and the GRE was required for this activity. These data suggest that XMRV may replicate more efficiently in LNCaP cells in part due to the transcriptional environment in LNCaP cells.
These conditions can cause some of the symptoms of CFS but not all necessairily. Yes, you do have extreme cases which could cause all but the average case, I would have to disagree based on my experience. Although we've all been thrown for a loop with CFS, medicine isn't so primative and disease patterns so similar that we can't separate some of these from the others.
Great list Kurt. I'm quite brain-fogged lately, but I would add pesticide and other chemical exposures (which are almost never tested for), hidden mold exposure (as was the case with Erik 'Mold Warrior' from the Tahoe outbreak), chronic fungal infections, chemicals in our food supply, heavy metals, methylation problems, etc..
And that (in my opinion) is why ME/CFS has been so difficult to treat, whether or not XMRV is involved. People have actually recovered, before XMRV was discovered, even though recovery is rare. Dr. Klimas will testify to that, and she's seen the worst of the worst.
Insurance coverage...don't get me started. Just think...if they would pay for some of the tests that we know can direct treatment (try getting even a stool test for parasites), rather than deny, deny, deny, perhaps some of us could've returned to being productive citizens long ago. My heart breaks for patients in the UK and elsewhere, where the only option is CBT and GET. Just shameful...
Drug intolerance: That I think is one of the reasons why people just don't understand CFS. For the most part, we can't handle drugs...(with perhaps the exception of some antibiotics). We can't pop a pill and get back to work, despite all the ads on tv claming otherwise. People I've talked to during the last 12 years of this look at me googly-eyed when I tell them I can't tolerate drugs, even some mild over-the-counter drugs. Frust-rating.
okay...I'll shut up.
I agree in part, if these causes or 'conditions' are taken separately...on their own...but if one has many, multiple 'triggers', they can or may certainly be the things that lead one to develop CFS. Just my two cents.
The tone of the CAA press release is so critical of the Science study and so supportive of the other studies that it appears to be a biased and self-serving review. In the press release I received, there were direct links to the studies that failed to find XMRV, but no link to the Science study.
The following statement by Dr. Vernon, expressing phony concern for other people's resources, felt to me like an attack on the Whittemore-Peterson Institute.
This press release does not serve patients well. The CAA missed a good opportunity to show that they are on our side.
I agree, Advocate. Vernon is soundling like a broken record. As if it's WPI's fault that this study used the Oxford criteria. It's really quite ridiculous.
Here here Mithriel.
Thank you Bettine for the above information. It looks to me like this has highlighted some important information has been ignored in the general discussion of the cohorts. I agree with many others that there is an overlap between the Canadian Consensus Criteria and other definitions, so on the face of it you would expect something to show up in the other studies. However:
1) Forgetting the definitions they use, isn't there a problem with the clinics many of the European study patients have been selected from? Aren't they are coming from clinics or doctors basing their treatments on the use of GET and CBT (I dont know whether this is true of the Kerr study but sounds like it is in the other two)? I can't think of a better way to 'deselect' anyone with post exertional milaise than to offer a treatment such as GET! Speaking for myself I would not show up to one, or if I did stick around long enough become part of one of their studies. Surely this would be minimising the attendance of patients fitting Canadian criteria at these places. I have myself avoided going to a similar type clinic after seeing their philosophy on their website.
Likewise with CBT. While I can see that CBT may be helpful to us in managing with our illness, I can get this from any sympathetic psychologist, or read a book, without having to go to some specialist clinic that informs me that it is all in my head (this would be a source of added stress). On ths basis I would consiously not go to such a place.
I know many people may be mislead or sometimes have no choice in going to such places if they need to do so for benefits etc. I am in Australia so I do not fully understand the situation in Europe. But my observation here is that if the exercise is not helpful then people tend to avoid or get out of these places if they can. It is therefore imperative to me that, regardless of the definitions used, that any replication or validation study should be selecting patients from clinics that believe patients have an organic illness and do not push GET as these are where the highest concentration of true CFS patients are most likely to be.
2) Secondly much of the discussion has focussed on the level of overlap with the different CFS definitions. It seems to me that yes, there is overlap between Canadian criteria, the Fekuda and Oxford definitions. But maybe this doesn't tell you anything unless you also consider the prevalence of conditions in our community that can mimic CFS. If they are very prevalent, such as depression, then even a small percentage of such people getting accidentally diagnosed as CFS could mean that CFS studies get 'swamped' by such cases in studies. My understanding is that CFS makes up only as small percentage of our population (well below 1%). If you take a high prevalence illness such as depression and add number of other things mentioned on this thread that could also be misdiagnosed, then marry that to the more vague definitions, then it's easy to see how CFS patients could be left as a very tiny proportion of a sample selected for study. Add to this the 'self selection' bias that might be taking place on the part of patients with respect to different treatments/clinics (point one) and the cohort problem still seems alive and well to me.
Having said the above points, I still agree with many others that there must also be a difference in the testing between these studies and the WPI, as a finding of complete zero on all patients and controls (even the Kerr study said their antibody positive cases were due to cross reacting antibodies) is hard to believe if the WPI study got the 4% figure right on the healthy controls. As pointed out by someone earlier on this thread, the collective zero findings of the European CFS studies and their prostate ones seem to be challenging the very notion of XMRV itself! I think this is the more important observation at this point.
When the Kerr study came out, I remember that one observer noted:
Given what we're hearing about how XMRV may work, both from the retrovirology conference last week, as well as Dr. Judy's comments about the slow replication rate and the difficulties with finding XMRV using PCR at the ProHealth talk, it sounds like XMRV may work quite differently than what everybody is used to. Thus I can see how it's possible that everybody really is doing everything "right" based on current virological knowledge but still coming up with contradictory results. The fact that the Kerr study and this new Dutch one didn't find XMRV in anybody shows that the problem here goes beyond just the connection to ME/CFS but to how much of a role XMRV plays in humans altogether, something neither study commented on because both were focusing so much on ME/CFS (one for good reason, one malicious).
Dr Vernon does mention the tissue depository issue, suggesting that she too has been reading about the findings at that retrovirology conference (as are people here in this forum) but isn't sure what to make of it yet. Indeed from the way the article summarizing the retrovirology conference ended, it sounds like everybody is still scratching their heads.
Or, I'd add, haven't been looking for it in the right place(s).
Clearly something big is going on with XMRV because there is so much money, so much excitement surrounding it at the moment -- more than anything I've ever seen connected with ME/CFS, even if it's more likely generating the money and excitement because of the cancer connection. The fact that someone like John Coffin, who has been studying retroviruses similar to XMRV for 35 years, is saying "there is no question I think that the virus is real and that the virus is infecting some numbers of people. And it’s VERY important to figure out where it is going as far as all of its disease associations are concerned…" outweighs these three speedy, fairly conventional studies in my mind. The IC and Dutch studies just seem like attempts -- if effective among the general public in the short term -- to shift momentum away from an XMRV-ME/CFS connection in the vain hope that will stop further study (i.e. "waste of valuable resources" B.S.). But as Robin pointed out in the thread about Coffin and Goff, these guys don't know really anything about ME/CFS and don't seem to have a bias about it one way or another. They just see a new human retrovirus to study and people who may well have it. And they seem to be really interested in really looking for it, as do a lot of their friends and competitors (Dr Mikovits said the guy who did the German prostate cancer XMRV study that was negative wants to try again with her techniques to see if then he can find it), especially if it takes them and the field of retrovirology into new places they've never been before. It looks like XMRV may just well be doing that.
Don't forget that it's only been 3 1/2 months since the Lombardi, et. al. paper. It took a few years for the scientific community to reach a consensus about HIV (the fact that so many of these retrovirologists are comparing it to the early days of HIV also feels very promising!). There's going to be a lot of back and forth for awhile.
But many of us are used to vertigo, right?
Isn't that sort of like what happened with the Witchita study where, at the end of it, they really only ended up including something like 6 CFS-Fukuda patients in a study of well over a 200?
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