• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

The Fight is on...Imperial College XMRV Study

fresh_eyes

happy to be here
Messages
900
Location
mountains of north carolina
The more I think about it, all cohort questions aside, this has to be a methodology issue - not one person tests positive. It almost seems like they're taking a stand against the existence of XMRV itself, or at least its presence in any population.

It seems like they're doubling down on the lab contamination theory. Which I might buy if the Science paper was just one lab, but contamination in 3 labs??
 

Cort

Phoenix Rising Founder
I agree but also consider the problems with the German replication studies of XMRV. There's something strange about XMRV itself. Interesting that several US studies can find it but no studies outside of the US have found it - AT ALL!

Several US studies from different labs have found it- could they all be contaminated? You wouldn't think so.

I don't know if VIPDx did the testing or if it was done at NCI but I can't imagine that VIPDx - a small lab - has many laboratory mice running around. They're a commercial lab - not a research lab.
 
K

_Kim_

Guest
2. They had one positive XMRV "sample". Where did the sample come from? Is this sample from the WPI or Cleveland Clinic or NCI? They don't say. Only that with each run they ran their positive sample and all other samples came up negative.

Found in the section: PCR detection of XMRV and MLV sequences.

PCR amplicons were visualised on a 1% agarose gel stained with ethidium bromide. Each PCR run consisted of test samples, six negative (water) and two positive controls. The positive control was a dilution of a plasmid with a full-length XMRV (isolate VP62) insert, generously gifted by Dr R. Silverman.
 
K

_Kim_

Guest
http://www.cfids.org/cfidslink/2010/010603.asp

"Can this study be considered comparable to the results published by Lombardi et al., in Science? In short, no."

Hey hvs!!!

Looks like the CAA heard you. At least their timing was right on. I'm heading back over to read the rest of SV's comments.

XMRV Negative Results Emphasize Need for Robust Replication Study by Suzanne D. Vernon, PhD

The new report, published Jan. 6, 2010, in the open access online journal PLoS ONE, failed to detect XMRV in CFS, but should not be considered a valid attempt to replicate the findings described by Lombardi et al., in the Oct. 8, 2009 Science article.

(Thanks JayS for posting this - we're all very interested in how the CAA will handle the replication studies)
 

fresh_eyes

happy to be here
Messages
900
Location
mountains of north carolina
Can this study be considered comparable to the results published by Lombardi et al., in Science? In short, no. It very well could be true that XMRV is not present in the U.K. as Erlwein, et al. suggest in their discussion, but it is also possible that the technique used in the PLoS ONE paper was suboptimal due to the different methods employed, when compared to the original experiments conducted by Lombardi, et al....Once XMRV detection methods are optimized and made widely available, we encourage this group of researchers to take another look at XMRV as a possible explanation for the organic basis of CFS in the U.K.

Hey, do I hear fightin' words from Suzanne V?

ps Good dog, George! (pat, pat, pat)
 

Cort

Phoenix Rising Founder
CFIDS Association says the study 'is not a valid attempt to replicate the WPI study.

http://www.cfids.org/cfidslink/2010/010603.asp

The new report, published Jan. 6, 2010, in the open access online journal PLoS ONE, failed to detect XMRV in CFS, but should not be considered a valid attempt to replicate the findings described by Lombardi et al., in the Oct. 8, 2009 Science article.

Why?

  • The blood was collected from CFS patients in different types of blood collection tubes.
  • The genomic DNA was extracted and purified using different techniques.
  • The amount of genomic DNA included in the amplification assay was different.
  • Different primer sequences were used that amplified different regions of the XMRV proviral DNA.
  • The conditions of the PCR amplification assay were different – from the numbers of cycles, to the type of polymerase used.
 

Alice Band

PWME - ME by Ramsay
Messages
175
Location
UK
The reference to a 9am cortisol test in the patient cohort is interesting. It's not normal in the UK for doctors to run a test like this.

Is it possible that Wessley supplied the same blood samples for XMRV testing that he had already used for his earlier paper on cortisol?

The reason that this may be signifigent/interesting is that he finds high cortisol in his patients (when others find low)
 

Dr. Yes

Shame on You
Messages
868
George and I keep barking up the same trees. :Retro wink:

I think cohort selection is extremely significant in this (and all) studies, and still find this statement puzzling:

"All patients had undergone medical screening to exclude detectable organic illness, including a minimum of physical examination, urinalysis, full blood count, urea and electrolytes, thyroid function tests, liver function tests, 9 a.m. cortisol and ESR."

That is a very unclear statement, even if we were to look at this without knowledge of the criteria controversies in CFS. Excluding "detectable organic illness" sounds like the old Wessely, and not just a poorly-worded sentence. At the very least, it is a mistake, as it should read "to exclude other organic illness considered exclusionary by the Fukuda criteria", etc.. I really want to emphasize that this is BAD scientific paper writing, folks; they're usually much more careful in the methodology section than this, as nothing embarasses (real) scientists more. Very rare to see those kind of mistakes unless they are NOT mistakes, but actually DO describe the real selection criteria they used.

Note that they only list some of the tests they ran (along with not making clear if these alone, or complete differential diagnoses, were necessary for exclusion from the study).
If XMRV is more difficult to detect in less severely ill patients, as the WPI surmised, and the more severely ill ones also had numerous laboratory or physical abnormalities (what about having HHV6 or EBV positive titers, for instance? Or just lymphocytosis?), then it may be that using their protocols and at this stage in the game it is difficult to detect XMRV in all but those with other positive physical findings. So if that group was excluded, then it's understandable that no XMRV positives would be found.

So we really DO need to find out what exclusionary criteria were used for this study (whether we can ever get an honest answer is another question...).

As for the lack of corroboration in European studies.. there have been only two. One was of CFS patients selected by Wessely, a lousy scientist who favors lousy selection criteria. The other focused on prostate XMRV and was not a CFS study of any kind, to my understanding. So, so far I don't see any valid contradiction of the WPI study until I hear more about the criteria, etc. used by this new study.

ETA: I guess it would be more accurate to say that George keeps barking up the same trees I'm swinging from... Gibbons don't bark...
 
Messages
13,774
The reference to a 9am cortisol test in the patient cohort is interesting. It's not normal in the UK for doctors to run a test like this.

Is it possible that Wessley supplied the same blood samples for XMRV testing that he had already used for his earlier paper on cortisol?

The reason that this may be signifigent/interesting is that he finds high cortisol in his patients (when others find low)

I'm really confused by this. Surely he can't be excluding patients with abnormal cortisol levels from his definition of CFS... but I don't know why he'd mention cortisol levels otherwise. I've not been reading any of his recent papers, so have no idea about his own beliefs as to how CFS and cortisol could be related.
 
K

_Kim_

Guest
"I agree but also consider the problems with the German replication studies of XMRV. There's something strange about XMRV itself. Interesting that several US studies can find it but no studies outside of the US have found it - AT ALL!"

Sorry to be a pest but everyone keeps saying that XMRV has not been found in Europe. Even Wessley's truly pathetic "paper" claims this. Yet it actually cites the 2008 Fischer study, which found XMRV in one German prostate cancer patient and one healthy control.

J Clin Virol. 2008 Nov;43(3):277-83. Epub 2008 Sep 27.

Prevalence of human gammaretrovirus XMRV in sporadic prostate cancer.
Fischer N, Hellwinkel O, Schulz C, Chun FK, Huland H, Aepfelbacher M, Schlomm T.

Good point KFG!! I'm glad to see a new member or two decide to chime in on this discussion.

Welcome to the Forums:D
 

rebecca1995

Apple, anyone?
Messages
380
Location
Northeastern US
Wow, the CAA went to bat for us! That's encouraging and hopefully a sign of things to come.

Can't wait to see what Dr. Mikovits has to say about the Wessely paper at her presentation 1/22.
 

fresh_eyes

happy to be here
Messages
900
Location
mountains of north carolina
@ Dr Yes: You're absolutely right about the cohort. AND if the methodology was the same, they'd be finding a higher indidence even in a random sample, unless, as they imply, it's all about lab contamination.

The more I look at it, with the help of all you fine science minds, the more I think they've overplayed their hand here.

George and I keep barking up the same trees.

Is THAT what that racket is?
 
K

_Kim_

Guest
Wow, the CAA went to bat for us! That's encouraging and hopefully a sign of things to come.

Can't wait to see what Dr. Mikovits has to say about the Wessely paper at her presentation 1/22.

I can't help but think that SV's quick response was due, in part or in whole, to the brilliant suggestions that hvs made in The Big Talk Part II.