EVEN MORE PROBLEMS WITH THE VAN KUPPEVELD STUDY
Consider the failed XMRV/CFS studies. An analysis of the British Medical Journal’s van Kuppeveld paper on XMRV, presented as the "trump card" in negative XMRV/CFS research, reveals that their 20 year old blood samples were not from Chronic Fatigue Syndrome (ME/CFS) patients, and not remotely comparable to the Science CFS cohort. The BMJ (Nijmegen team) represented their (Vercoulen et al) cohort as CFS, when in fact they were largely studying the blood of tired, depressed patients. Here's the evidence:
Some shocking quotes from the study where the BMJ and Nijmegen’s 20 year old blood came from:
• “Information on physical abnormalities and treatment relied on self-reportâ€.
• “Using a score of 16 or more, 36% of patients could be considered as having a clinical depression.â€
• “To test generalizability, the present study sample was compared with a recently tested group of 68 patients with Unexplained Fatigue†(not CFS).
• And the clincher: the source of the blood came from a study where they, “Minimalized the risk of including patients with delayed convalescence of a viral infectionâ€.
For a detailed analysis of the BMJ article's flaws, complete with meticulous references, see:
http://www.forums.aboutmecfs.org/showth ... S-Research the 5-part article Scandal in BMJ’s XMRV/CFS Research, posts #1,2,4,6,7. The BMJ stated their XMRV research was on a “well-defined cohort†of CFS patients, when it was on a group of depressed patients with Unexplained Fatigue – which had been explicitly screened to remove patients with “delayed convalescence of a viral infectionâ€. Not much chance of finding XMRV in that cohort. How strong are the BMJ’s conclusions that XMRV isn’t in the UK – and that it isn’t associated with CFS!
GLAXO SMITH KLINE FOLLOWING THE SCIENCE METHODOLOGY
Pharma giant Glaxo Smith Kline just announced their own study into XMRV and ME/CFS and are so confident in the Science results that they are using positive XMRV samples from patients studied by the Science researchers (See:
http://www.forums.aboutmecfs.org/showth ... undertaken ). In other words, GSK “gets†the difference between research on cohorts of depressed, tired patients; versus patients with rigorously defined Canadian/Fukuda criteria ME/CFS, reproducible immune abnormalities, and severe, disabling fatigue. Further, by using positive samples from actual CFS patients with XMRV in the Science study, GSK is in effect saying:
1) We believe that XMRV exists; and
2) We believe that you found XMRV in CFS patients.
3) Further, we believe that it is necessary to look for XMRV in rigorously defined cohorts of ME/CFS patients, particularly those with a viral onset - rather than 20-year old samples of tired, depressed patients. Now, can we please use your samples as a positive control?
PROSTATE CANCER RESEARCHERS JUMPING INTO CFS/XMRV RESEARCH
What is perhaps most compelling about the XMRV/CFS linkage is that renowned prostate cancer researchers are crossing over to the “dark sideâ€: namely ME/CFS research. It appears that some (not all) patients with the most malignant prostate cancer Gleason Grades (and XMRV infection) share a genetic defect that is also found in many XMRV-positive ME/CFS patients: namely a defect in the RNase-L antiviral pathway. If you remember high-school chemistry, the suffix “ase†describes an enzyme, or a chemical that breaks down things. RNase breaks down RNA – and (you guessed it), XMRV, and indeed all retroviruses are made up of RNA. In short, some prostate cancer and ME/CFS patients share a genetic susceptibility to viral infection.
Dr Robert Silverman, prostate cancer expert, was in fact one of the authors of the Science paper on XMRV and ME/CFS. His organization, the renowned Cleveland Clinic has drawn an interesting line in the sand. Just recently, the Cleveland Clinic very publicly announced an award to Dr Silverman and his colleague Dr Klein for discovering the linkage between XMRV, prostate cancer, ME/CFS, and RNase-L (See 2-minute video @ the Cleveland Clinic's YouTube site:
http://www.youtube.com/watch?v=RWOWvdiXiSE ). Drs Silverman and Klein are being compared to the likes of Dr Sones, who pioneered the use of injectable dye imaging in cardiac surgery.
Similarly, Dr Ila Singh, another eminent prostate cancer researcher, has been forging full-speed ahead in XMRV research on prostate cancer AND ME/CFS. She has wasted no time, testing 45 compounds and 28 drugs on XMRV “in vitro†(or in the test tube)- and being reported widely in media such as USA Today and Scientific American. Not the behavior one would expect from someone who thinks XMRV is benign. Dr Singh clearly "gets" the plausability of the potential link with ME/CFS. As her team commented in their source article:
http://www.plosone.org/article/fetchArt ... ne.0009948
"... the notion that a retrovirus might be involved in both cancer and a neuroimmune illness in humans is not without precedence. Human T-cell lymphotrophic virus, type 1 (HTLV-1), another retrovirus, causes both T-cell lymphoma/leukemia as well as tropical spastic paraparesis, a myelopathy due to immune defects resulting from the viral infection."
THE PSYCHIATRY ANGLE
And now for the psychiatry angle: psychiatrists studying this viral neuro-immune disease have been stating for years that the most rigorous Canadian Criteria (2003) for ME/CFS (Summary here:
http://www.cfids-cab.org/MESA/me_overview.pdf ) are just too difficult to apply in research. They have also advantageously expanded their market for exercise and feel-good clinics, by including out-of-shape patients, depressed patients, patients with Unexplained Fatigue, together with patients with classical Canadian-Criteria ME/CFS. In fact in the UK, patients with a diagnosis of ME/CFS are routinely denied biological diagnostics, such as lab-work or immunological workups. This creates a self-fulfilling prophesy, a delusion on the part of psychiatrists that ME/CFS has no physicial findings. Eschewing the rigorous Canadian Criteria is a little like saying one should abandon speed limits because no one likes to follow them. Or lumping together appendicitis patients with diffuse stomach ache patients to "simplify" research. Like appendicitis, which has right-sided abdominal pain as a cardinal sign, ME/CFS's hallmark is Post-Exertional Malaise - something the 3 failed XMRV studies have not fastidiously observed. A helpful primer on the importance of CFS criteria has just been made available this week by noted CFS psychologist, Dr Leonard Jason. His slides on how CFS cohort selection can bias research outcomes, can be seen at:
www.cfids.org/webinar/jason-slides041410.pdf
These are fascinating times, as retrovirologists and politically-motivated psychiatrists jockey for position. After all, psychiatrists have built an entire industry of exercise and "positive attitude" clinics for patients who are known in the biomedical literature to have persistent opportunistic infections - and who may also have a cancer-causing retrovirus: XMRV. And the psychs won’t give up their fiefdoms without a fight. But it is nothing short of earth-shaking that the BMJ's XMRV research team committed such an enormous research blunder – while the "big boys" in immunology, molecular biology, retrovirology and oncology take over the exploration of what may indeed be the next AIDS.
Science Based - 18-04-2010 | 11:44