fingers2022
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So as a group do we think it's te selection criteria or the testing methods/protocols?
I vote for the latter, but many posts seem to focussing on the former.
Any thoughts on this?
So as a group do we think it's te selection criteria or the testing methods/protocols?
I vote for the latter, but many posts seem to focussing on the former.
any thoughts on this?
Dr. Vernon is working on an analysis of this study. I don't have an exact publication time, but it will appear on the Association's XMRV webpage. I'll also post it here as soon as I can.
So as a group do we think it's te selection criteria or the testing methods/protocols?
I vote for the latter, but many posts seem to focussing on the former.
Thanks, jspotila - do you know if she is planning to write to the BMJ?
No way patient selection would lead to the difference between the WPI's results and the others: unless the others were being intentionally fraudulent, or the WPI were being way more selective than they've claimed.
It seems to me that either XMRV is surprisingly difficult to detect (which seems like it could well be the case), or there's some problem with the WPI's work, or both.
Spiking experiments showed that we were able to detect at least 10 copies of XMRV sequences per 105 peripheral blood mononuclear cells by real time as well as by nested polymerase chain reaction, demonstrating high sensitivity of both assays.
In our study, we used the same primer sets as used by Lombardi et al.
However, the [Lombardi] paper fell short in the description of the patients: what was the nature of the cohort, what was the age and sex distribution, how well were the controls matched?
Unfortunately, the paper of Lombardi and colleagues lacked a clear description of their patient cohort. Recently, at the Tri-Society Annual Conference 2009 in Lisbon, a presentation reported that the peripheral blood mononuclear cells were derived from patients from the outbreak of chronic fatigue syndrome at Incline village at the northern border of Lake Tahoe, United States (1984-5).
No way patient selection would lead to the difference between the WPI's results and the others: unless the others were being intentionally fraudulent, or the WPI were being way more selective than they've claimed.
It seems to me that either XMRV is surprisingly difficult to detect (which seems like it could well be the case), or there's some problem with the WPI's work, or both.
XMRV was found not only in the WPI's healthy controls, but also in Japanese healthy community. So if this study could actually find XMRV in every sample if it were there - How come there was not one XMRV positive blood sample from the 43 healthy controls, and actually, from the 75 blood samples altoghether, assuming that there is no reason for ME/CFS patients to be less susciptble to XMRV than the healthy population?).
Patient samples. Banked samples were selected for this study from patients
fulfilling the 1994 CDC Fukuda Criteria for Chronic Fatigue Syndrome (S1) and
the 2003 Canadian Consensus Criteria for Chronic Fatigue Syndrome/myalgic
encephalomyelitis (CFS/ME) and presenting with severe disability. Samples
were selected from several regions of the United States where outbreaks of CFS
had been documented (S2). These are patients that have been seen in private
medical practices, and their diagnosis of CFS is based upon prolonged disabling
fatigue and the presence of cognitive deficits and reproducible immunological
abnormalities. These included but were not limited to perturbations of the 2-5A
synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as
measured by standard diagnostic assays), and elevated cytokines particularly
interleukin-6 and interleukin-8. In addition to these immunological abnormalities,
the patients characteristically demonstrated impaired exercise performance with
extremely low VO2 max measured on stress testing. The patients had been seen
over a prolonged period of time and multiple longitudinal observations of the
clinical and laboratory abnormalities had been documented.
DNA and RNA isolation. Whole blood was drawn from subjects
Where did the samples come from for the XMRV study?
The WPI repository samples came from patients who live in many different locations around the US. Physicians who contributed patient samples include: Dr. David Bell, Dr. Paul Cheney, Dr. Daniel Peterson, and Dr. Eric Gordon. Other individual patient samples came from individuals who became ill while living in California, Wisconsin, South Dakota, etc.
What about Dr. Peterson's private repository? [view answer...]
Dr. Peterson has a repository of samples from the original out break in Incline Village, Nevada which also includes longitudinal samples taken from patients from the 1980's through 2005. None of these samples were used in the XMRV study.
I,m Afraid that patient selection is absolutely critical
I
Will researchers give more weight to publications than oral presentations of unpublished data? I assume that it is similar to being on or off the record in journalism. If Dr Mikovits said on the record in the above reference that the positives came from Incline Village, then researchers will treat that statement as true and make the criticism we see in this paper - that XMRV might be related to the Incline outbreak only. But if there are conflicting statements out there, especially if those statements are from Dr. Peterson and Mikovits, then what will researchers believe? The publication? The press releases? Presentations at conferences? Presentations to patients?
We need a meticulous replication study. We need the federal data (CDC, NCI, NIH). We need it now. I am really concerned that the negative studies are building momentum. The real danger, in my personal opinion, is that pharma and academia will lose interest in this work, or decide it is easier to study XMRV in prostate cancer instead. This would be a problem, because apart from the federal government the big money resources are with pharma and high-profile academia. If the big money walks away, it might have a chilling effect on the whole field.
I think the quote from Dr. Goff is spot on: "His answer: everyone needs to exchange samples, and they are not doing it." The greatest service anyone can render to the CFS community would be to throw open the doors on information. Everybody needs to exchange primers, assays, samples, cohort data. Exchange everything. I know there must be intellectual property and other issues at stake, etc. but we need free exchange of ideas and information so we can unravel this puzzle.
Sorry Gerwyn, but surely, if the testing's not right, the selection is irrelevant?
Well as a CFS/ME patient this really worries me even with the Oxford Criteria... I find it hard to believe the psychiatric people would out and out LIE in a scientific journal like BMJ. I do think they might do a sort of half-***ed study and hope it doesn't find anything but I can't believe scientists would be actively malevolent.
So what is the reason? The oxford criteria? Even if not one of those patients had the real CFS/ME which is unlikely (imo) some of the controls should have tested positive. The prostate cancer studies have never found XMRV in Europe either to my knowledge.
So what do you guys think it is? Is XMRV just not in Europe or they have a substantially different variant? Maybe retroviruses in human beings are common and there are a subset that can trigger CFS/ME such as XMRV and Defrietas's Virus? Those explanations fail at explaining why the WPI *IS* finding XMRV in other countries and in Europe though which (I believe, please correct if wrong) was mentioned in one of the Mikovits Lectures.
So what do you all think the reason is? To back up my assertion that scientists wouldn't outright lie to other scientists (or that it is rare) even Wessely has done studies where there were some biological abnormalities which he promptly proceeded to dismiss, *but* he didn't deny they were there when his study found them. Right now I am thinking, for whatever good it will do, how to explain finding XMRV by WPI and by Cleveland Clinic (in Prostate Cancer) but not by others.
Especially if WPI is finding it internationally... I can't see how the "undetectable variant hypothesis" would still work to explain everything.
Does anyone have any ideas? Is it just that the replication studies are so sloppy? The one with Kerr presumably was not so that not explain away everything( you'd think).
I have no doubt XMRV will be important but I am having a hard time making sense of all this right now.