"No evidence for XMRV association in pediatric idiopathic diseases in France" aug 2

Frickly

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http://www.retrovirology.com/content/7/1/63
Eric Jeziorski , Vincent Foulongne , Catherine Ludwig , Djamel Louhaem , Gilles Chiocchia , Michel Segondy , Michel Rodiere , Marc Sitbon and Valerie Courgnaud

Retrovirology 2010, 7:63doi:10.1186/1742-4690-7-63


Published: 2 August 2010

Abstract (provisional)
Retroviruses have been linked to a variety of diseases such as neoplastic and immunodeficiency disorders and neurologic and respiratory diseases. Recently, a novel infectious human retrovirus, the xenotropic murine leukemia virus-related virus (XMRV), has been identified in cohorts of patients with either a familial type of prostate cancer or chronic fatigue syndrome. The apparent unrelatedness of these diseases raised the question of the potential involvement of XMRV in other diseases. Here, we investigated the presence of XMRV in a selection of pediatric idiopathic infectious diseases with symptoms that are suggestive of a retroviral infection, as well as in children with respiratory diseases and adult patients with spondyloarthritis (SpA). Using a XMRV env-nested PCR, we screened 72 DNA samples obtained from 62 children hospitalized in the Montpellier university hospital (France) for hematological, neurological or inflammatory pathologies, 80 DNA samples from nasopharyngeal aspirates from children with respiratory diseases and 19 DNA samples from SpA. None of the samples tested was positive for XMRV or MLV-like env sequences, indicating that XMRV is not involved in these pathologies.
 

Esther12

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Hmmm... zero positives.

Either they're not able to detect XMRV in patients, or those finding 3-6% in the general population are getting false positives.

Where's the NIH paper!!>!
 

Jemal

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Another negative study... need more positive studies.
Or maybe XMRV can't swim ;)

Therefore, differences in the worldwide distribution of XMRV may rather result from an infection that would have recently occurred in North America and that is not yet widespread in other parts of the world, or at least in Western Europe.
 

taniaaust1

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Only 19 of the study participants were adults. Even if they were testing properly during this study... it wouldnt be unreasonable to think that no XMRV may be found, with those numbers if it is only about 3% in those kinds of populations. One would think it would be at a rate of far less in children due to less time to have been exposured to it at some point.... and on top of that, maybe many of the transmissions of it is happening sexually, so hence it could be much rarer in children..
 

Esther12

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Some have speculated that XMRV infection occurs primarily from parents to children...

but you're right. We don't really know what's going on, and it's possible the prevalence is much lower in children than adults.
 

Jemal

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One would think it would be at a rate of far less in children due to less time to have been exposured to it at some point.... and on top of that, maybe many of the transmittions of it is happening sexually..
This makes sense.
Also I am wondering what kind of symptoms these children were displaying. I don't think they belong to the typical CFS cohort:

The present study included 72 samples obtained from 62 children who exhibited hematological, neurological or inflammatory pathologies.
 

thegodofpleasure

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Blood samples were not collected correctly in order to preserve XMRV

I note that the blood samples used in this study were not collected (& the RNA preserved) in Heparin tubes - which I understand is an important part of any testing protocol which has so far managed to isolate the XMRV retrovirus.

Again, I don't think that this negative paper will stand up to close scrutiny.

TGOP
 

Cort

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It was certainly an interesting try...they were looking for it in children with mysterious flu-like illnesses "idiopathic infectious diseases' - which sounds like it could be close to CFS as well as a group with respiratory problems. Until a test is validated, though, I wonder if anyone should expect to find the bug - it doesn't seem to be happening. If they are all doing the normal PCR stuff they are wasting their money.
 

George

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XMRV displays more than 90%
sequence identity with MLV and harbors distinct amino acid substitutions and a short
deletion in the gag leader region. Strikingly, these combined features lead to a
putative absence of glycoGag, an alternative open reading frame of the gag gene
that has been shown to play a role in MLV replication and pathogenesis.
They came to this conclusion based on a 1994 MLV study.

Corbin A, Prats AC, Darlix JL, Sitbon M: A nonstructural gag-encoded
glycoprotein precursor is necessary for efficient spreading and
pathogenesis of murine leukemia viruses. J Virol 1994, 68:3857-3867.
If you notice they used nested PCR for the env gene which according to the Dr.'s Ruscetti is where the deletion is in XMRV. I haven't seen anything that indicates a deletion in the gag gene. I think this may be where many of the negative papers are making their mistakes. XMRV may share a <90% likeness to MLV's but it is not an MLV and considering that it is closer to SFFV MLV than say MoMLV you have to pick the right MLV.

The association of XMRV with these two pathologies remains debated in part due to
the fact that several studies by European teams and a more recent one in the United
States did not detect XMRV by PCR in either types of patients [16-22]. When
detected, XMRV prevalence in the United States appears to be up to 40% and 67%
in prostate cancer patients and CFS patients, respectively, while in Northern Europe,
the prevalence is virtually zero. Furthermore, Lombardi et al., found a 4% prevalence
of XMRV in control patients from the same geographic region [15]. In view of the
striking conservation of XMRV sequences, the lack of detection of XMRV is unlikely
due to potential differences in PCR sensitivity. Therefore, differences in the
worldwide distribution of XMRV may rather result from an infection that would have
recently occurred in North America and that is not yet widespread in other parts of
the world, or at least in Western Europe.
Then you have this lovely prognostication. (grins) Me thinks they are going to be a bit surprised about the coming realities. (grins)

Blood samples were drawn by venipuncture using standard phlebotomy procedures
into 2 ml sterile microtubes containing EDTA, and synovial fluids were obtained by
needle puncture and transferred in special collection tubes. For each samples, at
least 2 aliquots were prepared and stored at -80 C for later use. Total DNA was
isolated from whole blood or synovial fluid cells using the QIAamp blood kit (Qiagen,
Courtaboeuf, France) according to the manufacturer's instructions. DNA
concentrations were determined by Nanodrop ND-1000 spectrophotometer. To
ensure quality of the DNA extracts, all samples were subjected to a single-round
PCR reaction using GAPDH primers (Figure 1A). Bacterial exploration with direct
examination and culture was performed in all synovial fluid samples with no bacterial
agent found.
Correct no heprin tubes and the lab work does not meet the WPI standards for detecting XMRV anyway.

We designed primers to specifically target XMRV-like sequences. A 600-bp region of
the SU env gene, spanning the receptor binding domain (RBD) was amplified with
the following primers with positions indicated according to the XMRV VP35 sequence
[10] : XenvS1 : 5’-ATGGAAAGTCCAGCGTTCTCAAA-3’ (5754 to 5776) and
XenvAS1 : 5’-ATGGGGACGCGGGGCCCTACATTG-3’ (6443 to 6466) for the first
round, while primers for the second round were XenvS2 : 5’-
Wrong sequences, they did not have controls and excuse me but there doesn't even seem to be a spiked copy to go on to make sure they could find it!

Fischer et al. found a significant proportion of XMRV gag sequences in
all of their respiratory disease patient and donor groups (between 2 to 10%). They
found the highest incidence of gag XMRV detection in the group of
immunosuppressed patients (adults conditioned before transplant) [27]. Although,
this confirms that XMRV is more likely to emerge in the context of altered immune
response, it remains perplexing that no other report found XMRV in Europe.
Well, sweety I'll tell ya why cause you guys need to go back and learn to read!!!!!!!!!

I mean this has got to be the sloppiest study of them all. Woof, This one get's NO PAWS
 

Otis

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Yup. Not another negative study, just another bad one.

They looked in a good combination of places (blood, lung, CSF) but you gotta know how to find it.
 

SOC

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http://www.retrovirology.com/content/7/1/63
Eric Jeziorski , Vincent Foulongne , Catherine Ludwig , Djamel Louhaem , Gilles Chiocchia , Michel Segondy , Michel Rodiere , Marc Sitbon and Valerie Courgnaud

Retrovirology 2010, 7:63doi:10.1186/1742-4690-7-63
Here's another lousy paper full of problems that should have been caught in peer-review. What kind of peer reviewers let this sort of garbage through? Why was this even published? Who published this?

Retrovirology

This is the 4th lousy paper in Retrovirology refuting the connection between XMRV and ME/CFS, I believe. Shouldn't we be asking ourselves, "Why so many in one journal?" Is it possible that no one else will publish this garbage? What's Retrovirology got invested in this?

We may have found a confederate of our detractors that we might be able to take on much more easily than we can the CDC.
 

thegodofpleasure

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Yup. Not another negative study, just another bad one.

They looked in a good combination of places (blood, lung, CSF) but you gotta know how to find it.
It is a particularly undesirable / unwelcome study because it will have the effect of disuading other groups from looking for an XMRV association with these diseases - at least for the time being.

A real spoiler of a study
 

xrayspex

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sickofcfs and godofpleasure you make 2 good dif points,
first of all should someone make a concerted effort to find out if retrvirology is somehow invested in helping cover up?
this is what someone more knowledgable than I just pointed out:

What's interesting is that CDC and NIAID have a vested interest in keeping us buried, because otherwise they have some serious 'splainin' to do.

But National Cancer Institute (NCI), is ALSO part of NIH, and is in general more highly respected in the scientific community. They are the ones who said they found XMRV in an even larger patient cohort.

And they are joined by the blood products division of FDA.

So it is two divisions within NIH pitched against each other - NCI v. NIAID - and then CDC v. FDA.

------
and 2ndly gop you say "spoiler of a study"--but if its true it was poor protocol wouldnt real scientists and institutions see thru that? what can we do to expose this?

oh so regarding the blurb I shared about the politics if NIAID has reason to cover up perhaps that journal is in bed with them, retrovirology.
I know it happens for example, at least in the 60s, JAMA gave special preference to east coast med research over midwest, I know this for a fact
 

thegodofpleasure

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Questionable Peer Review

--but if its true it was poor protocol wouldnt real scientists and institutions see thru that? what can we do to expose this?
As others have already commented, the quality of peer review in this journal has to be questioned. If, by a bit of judicious background reading, complete amateurs like myself can pick out the deficiencies in a paper such as this one (wrong sampling tubes, wrong protein targets etc.) then why aren't the peer reviewers doing so? :eek:

Given our evident superior skills, perhaps we could tap into a new source of income as freelance peer reviewers for "Retrovirology"

TGOP :D