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Medscape - physician's website - pnas study discussed

muffin

Senior Member
Messages
940
From Medscape Medical News http://www.medscape.com/viewarticle/727496
Highly Anticipated Study Is Second to Link Chronic Fatigue Syndrome and RetrovirusKathleen Louden

August 25, 2010 The authors of a new study that found a strong association between chronic fatigue syndrome (CFS) and a group of mouse retroviruses closely related to XMRV, or xenotropic murine leukemia virusrelated virus, offered possible explanations for the varying results among different research laboratories in Europe and the United States.

Published online August 23 in the Proceedings of the National Academy of Sciences, the study is the first to confirm the results of Lombardi and colleagues from last October (Science. 2009;326:585-589). That group reported finding XMRV in peripheral blood mononuclear cells from 67% of 101 patients with CFS compared with 3.7% of 218 healthy control patients. Four subsequent studies failed to find evidence of XMRV or related viruses in patients with CFS, including a study from the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, published online July 1 (Retrovirology. 2010;7:57).

The current study, conducted by researchers at the National Institutes of Health (NIH) and the US Food and Drug Administration (FDA), found a high rate of infection in CFS-affected patients with what the authors called murine leukemia virus (MLV)related viruses; 86.5% of 37 patients with CFS had MLV-like virus gene sequences in their peripheral blood mononuclear cells vs 6.8% of 44 healthy blood donors, the researchers reported.

Although the scientists did not find XMRV in their patient samples, XMRV is a type of MLV, according to study coauthor Harvey Alter, MD, chief of clinical studies for the NIH Department of Transfusion Medicine.
Their data, Dr. Alter said August 23 during a media briefing held by the NIH in Bethesda, Maryland, "are highly confirmatory" of the findings of the Science study, led by researchers at the Whittemore Peterson Institute in Reno, Nevada, and 2 other institutions.

Results Contrast With Other Studies
"A dilemma is how to reconcile why some labs find this association and others do not," Dr. Alter said.
Differences in test methods do not appear to explain the disparities between the results from the new study and those of the recent CDC study, Dr. Alter said in an interview with Medscape Medical News.
"We tested some of their [blood] samples and also found them negative," he said.
In addition, an NIH institute "determined both laboratories had equivalent sensitivities in their assays," the lead author of the other study, CDC microbiologist William Switzer, MPH, told Medscape Medical News.

The best method of collecting and testing blood samples for this class of retroviruses is not yet established, according to Dr. Alter. The NIH will convene a panel of experts September 7 to 8 to discuss this issue and others related to XMRV at the 1st International Workshop on XMRV. Some researchers also have linked XMRV to prostate cancer.

Dr. Alter said the most likely reason for the discrepancy in results is patient selection. Diagnosis of CFS is based on a symptom complex, not a specific disease marker. All patients in the NIH-FDA study met the accepted diagnostic criteria for the syndrome, and most blood samples were from the patient population of a single coauthor, who is a CFS expert, he said.
"There may be a geographic difference," Dr. Alter told Medscape Medical News. "In the Northeast, CFS may be due to MLV, and in the West, it may be due to XMRV."


However, he cautioned against interpreting their results as proving causation of CFS. "We haven't answered that question yet," Dr. Alter said, adding that the cause could be multifactorial.
It is also possible that the high frequency of MLV-related infections in their cohort with CFS indicates "an increased susceptibility to viral infections" because of immune dysfunction, rather than a causal role, the authors speculated in their article.

The research team did prove that MLV infection persists. As a follow-up to using frozen blood samples obtained from patients with CFS nearly 15 years ago, the investigators obtained fresh blood samples from 8 of the 32 MLV-positive patients, and 7 again tested positive for the retrovirus. "It was the same virus, but it had mutated, as a retrovirus does," Dr. Alter said.

Virus sequences seen in their patient samples were polytropic, not xenotropic, and were more diverse than those reported by the Nevada group, according to Dr. Alter. This variability is characteristic of a retrovirus and boosted the authors' confidence that laboratory contamination was not responsible for their findings, he said during the media briefing.

Indeed, the researchers were "very thorough" in showing there was no mice contamination, said a coauthor of an accompanying commentary in the Proceedings, Andrew Mason, MBBS, associate professor of medicine at the University of Alberta in Canada. "Taken together [with the research by Lombardi et al], these are 2 important studies that should not be ignored," Dr. Mason told Medscape Medical News.

Publication Delayed
Dr. Alter said his team went to extra lengths to rule out the possibility of laboratory contamination, even asking the journal editor to delay publication of their article after it was accepted so they could do more testing. The lay media reported in July that this action drew criticism from the CFS community, who feared suppression of the findings.

The decision came from the US Department of Health and Human Services, Steve Monroe, PhD, of the CDC, told Medscape Medical News. Officials wanted to find out why results of the 2 federal studies differed.

"I appreciate the frustration of the advocate community, but our goal was to ensure we were providing the best and most accurate data. Sending out an incorrect message would be detrimental," said Dr. Monroe, director of the CDC Division of High-Consequence Pathogens and Pathology.
Switzer said he and his coauthors also temporarily held up publication of their paper but ended up changing nothing.

"We felt it was the very best science we could do," he said.
They were unable to test patients' blood samples from Dr. Alter's group, Switzer said, because those scientists did not have sufficient stored specimens left.


Although the 2 teams could not explain their conflicting results, Dr. Alter said he and his coworkers also feel confident about their data. "We were able to add information that, I think, made the paper much stronger," he said regarding their efforts to retest some patients and to address concerns about potential laboratory contamination.

Dr. Alter said, "I thought all along: It's more important to be right than to be fast."


Dr. Alter, Dr. Mason, Dr. Monroe, and Mr. Switzer have disclosed no relevant financial relationships.
Proc Natl Acad Sci USA. Published online August 23, 2010.

Authors and Disclosures
Journalist
Kathleen Louden
Freelance writer, Gurnee, Illinois

Kathleen Louden is a freelance writer for Medscape.

Kathleen F. Louden has disclosed no relevant financial relationships.


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Medscape Medical News 2010 WebMD, LLC
Send press releases and comments to news@medscape.net.
 

V99

Senior Member
Messages
1,471
Location
UK
That last bit is not true, they could go back and retest the 8 again.
 

Sunshine

Senior Member
Messages
208
Location
UK
Or stop using stored specimen's and use fresh blood as they should do.

Think if we were having an HIV test and a doctor said, sure I'll see if you're infected let me go look in the freezer for a sample we took when you were a kid.

Alter/Lo were clever in exposing MULV in CFS but still didn't step up to the plate and deliver a true replication study on XMRV too which they should have done by following Lombardi's methods used in the SCIENCE paper.
 

V99

Senior Member
Messages
1,471
Location
UK
I would agree with that. Alter said so himself, the WPI study was better.
 

muffin

Senior Member
Messages
940
Switzer lied about not having enough samples. HOW does the CDC get away with bold face lying??? Medscape did a good job otherwise and it is read by Physicians!!! Medscape is actually a doctor/nurse website with CMEs' etc. Lots of good info but best of all- read by doctors!!!

Somehow the CDC has to be taken down. They blow my mind with their lies.
 

illsince1977

A shadow of my former self
Messages
356
Results Contrast With Other Studies
"A dilemma is how to reconcile why some labs find this association and others do not," Dr. Alter said.
Differences in test methods do not appear to explain the disparities between the results from the new study and those of the recent CDC study, Dr. Alter said in an interview with Medscape Medical News.
"We tested some of their [blood] samples and also found them negative," he said.
In addition, an NIH institute "determined both laboratories had equivalent sensitivities in their assays," the lead author of the other study, CDC microbiologist William Switzer, MPH, told Medscape Medical News.
Have I not been reading all the coverage carefully enough this week and missed this before? Doesn't the fact that Alter didn't find XMRV/MLV in the CDC samples either confirm that there was either selection bias in the CDC samples or the CDC processed the samples incorrectly by using the wrong collection tubes as Dr. Vernon said? If the assays are OK, it would have to be selection bias or faulty collection or storage methods. Of course Switzer's claim that there wasn't enough confirmed positive blood left for the CDC to test is more of the same dissembling/delaying tactics. Are we not supposed to notice? I guess I never quite understand how powerful the human need to be right is, except when I'm being humble and realizing I could admit I'm wrong more often! Could someone who is more on the ball than me enlighten me on this issue? Doesn't the fact that Alter couldn't find XMRV/MLV in the CDC samples make the CDCs negative study a non-issue?
:victory:
 

pictureofhealth

XMRV - L'Agent du Jour
Messages
534
Location
Europe
Great find, great post Muffin.

Now this is the kind of coverage I'm talking about - a really good medical write up for doctors where -
1. the scientists find something superb that
2. validates the illness
3. validates the WPI's retroviral finding,
4. is done by a top class scientist like Dr Alter with impeccable credentials, who other docs are likely to take v seriously which will encourage further real studies and who is therefore
5. likely to bring in further funding to discover the full mechanism behind our illness.

What's not to like? Alter gives a really good interview with a lot of meaty detail so the journalists will love him. And although some of the findings are not as firm yet as we would like them to be, he appears to fully support us and the WPI.

If the BBC science writers had done this kind of coverage for us I could almost have forgiven them for their previous disappointing charade.
 

SOC

Senior Member
Messages
7,849
Switzer said he and his coauthors also temporarily held up publication of their paper but ended up changing nothing.

"We felt it was the very best science we could do," he said.
[my bolding]

Don't think I'd be saying that at this stage of the game if I wanted to get anywhere in virology. If that's the best you can do....
 

Anika

Senior Member
Messages
148
Location
U.S.
Samples used in NIH/FDA paper and in CDC paper

On the issue of samples used for the PNAS study, and availability of samples to the CDC - Following up on quote from Medscape article:
Switzer said he and his coauthors also temporarily held up publication of their paper but ended up changing nothing.
"We felt it was the very best science we could do," he said.
They were unable to test patients' blood samples from Dr. Alter's group, Switzer said, because those scientists did not have sufficient stored specimens left.
(my boldface)

On the availability of material for CDC to test, which several people have questioned:
One of the things Alter's group did after they submitted the original paper was to go back and get fresh blood samples from 8 of the positive Komaroff patients and test those fresh samples. Those results are mentioned in the paper, but the actual study itself is on the 41 stored samples from 37 patients in the mycoplasma study (original 37 samples, plus repeat samples from 4 of the 37 patients obtained about 2 years later). So it is quite possible that of the 41 stored samples used for the PNAS study, there wasn’t sufficient material left for CDC to test. (At least not if Alter’s team kept whatever they needed for their own additional work – remember, the PNAS study didn’t include a number of the tests / analyses that WPI did, and I’m sure Alter's group has more work in progress). If Alter had provided material to the CDC to test, we’d hear about from Alter.

As for the 8 patients who gave fresh blood samples to Alter's group – 7 of 8 fresh sample were positive - thank you, patients! I hope all 8 of these patients are able to give enough samples for future testing by multiple labs – not just FDA/NIH but also CDC, WPI, etc. And we should remember, the 8th patient had tested positive before at least once, from the original frozen sample. I think I recall seeing a statement attributed to Alter or Lo that samples drawn at different times may give different results (which is something we’ve heard already from WPI - so another endorsement of WPI's views). The working group that is trying to come up with validated assays needs to address the issue of positive control samples from patient blood, not just spiked samples.

A note on the CDC samples that were used -
I think it’s also important to remember that in the CDC’s own study, they said they tested samples only from those CFS patients for whom they said had enough material to test – there were a good number of CDC CFS patients, over 20%, I think, for whom they did NOT have enough material to test. I have not to date seen any explanation for the type of “sample” bias that could have resulted from the limited availability of specimens for the CDC study. That is, samples from some patients were “selected out” because of insufficient material available. It’s not clear if some patients had never given enough sample material to begin with, or if material from some but not all patients had been used for certain testing, for example, leaving less material available for the XMRV test. (For example, I don't know if some of the CDC cohort's blood was tested for possible exclusionary infections, thus limiting sample material for future testing.)
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
That last bit is not true, they could go back and retest the 8 again.

Or stop using stored specimen's and use fresh blood as they should do.

Think if we were having an HIV test and a doctor said, sure I'll see if you're infected let me go look in the freezer for a sample we took when you were a kid.

Alter/Lo were clever in exposing MULV in CFS but still didn't step up to the plate and deliver a true replication study on XMRV too which they should have done by following Lombardi's methods used in the SCIENCE paper.

K99 and Sunshine- very true!
 

justinreilly

Senior Member
Messages
2,498
Location
NYC (& RI)
Switzer said he and his coauthors also temporarily held up publication of their paper but ended up changing nothing.

"We felt it was the very best science we could do," he said.
[my bolding]

Don't think I'd be saying that at this stage of the game if I wanted to get anywhere in virology. If that's the best you can do....

You're right. the hubris is shocking. CDC has no shame (as if we needed more proof). But going over the top like this like McClure did, is going to come back to haunt them.
 

SOC

Senior Member
Messages
7,849
Switzer lied about not having enough samples. HOW does the CDC get away with bold face lying??? Medscape did a good job otherwise and it is read by Physicians!!! Medscape is actually a doctor/nurse website with CMEs' etc. Lots of good info but best of all- read by doctors!!!

Somehow the CDC has to be taken down. They blow my mind with their lies.
[my bolding]

Do we know that this is a straight-out lie? I mean, the story says there were not enough stored samples left. Do we know there were remaining stored samples the CDC could have? Yes, they could have tested blood from the patients from whom Lo and Alter got fresh samples. I think Dr Switzer was being deliberately evasive, but unless we know he had access to the stored samples, we should be careful about saying he lied.

The CDC people are getting pretty disgusting in the way they play with words to deliberately miscommunicate.
 

Rrrr

Senior Member
Messages
1,591
You're right. the hubris is shocking. CDC has no shame (as if we needed more proof). But going over the top like this like McClure did, is going to come back to haunt them.

no it won't. no one will care. only us cfs folks.

i, too, can't believe how easily they lie. but it is exactly because no one will care except us cfs folks.

remember what happened when they were caught misappropriating congressionally mandated funds for cfs? exactly nothing happened. a hearing. and then nothing else.
 

Anika

Senior Member
Messages
148
Location
U.S.
Hi, sickof,

I also don't think Switzer was wrong in saying they weren't able to test the stored samples - probably got buried in my long-ish post above. I don't think Alter's group had enough stored material to share (especially if they kept enough for their own further studies).

CDC / Switzer may have published without even knowing (and maybe Alter didn't even know then) that the Alter group was going to get fresh blood from some of the original PNAS cohort.

Anika
 

SOC

Senior Member
Messages
7,849
Hi, sickof,

I also don't think Switzer was wrong in saying they weren't able to test the stored samples - probably got buried in my long-ish post above. I don't think Alter's group had enough stored material to share (especially if they kept enough for their own further studies).

CDC / Switzer may have published without even knowing (and maybe Alter didn't even know then) that the Alter group was going to get fresh blood from some of the original PNAS cohort.

Anika

Hi Anika,
Sounds like we're of one mind on this subject. You explained it all SO much better, though. :Retro smile:

I think you're right -- the CDC (and even Lo, Alter, et al) didn't know about the fresh samples when the CDC paper was published. I suspect those are the "new studies" that the team did after the PNAS paper was pulled.
 

illsince1977

A shadow of my former self
Messages
356
The point I was trying to make was the fact that Alter could not find XMRV/MLV in the samples from the CDC's study indicates the CDC did a terrible job with the methods they used, doesn't it? Doesn't that confirm all the complaints against the CDC paper? They could test the same patients Alter found positive, but if they use the wrong tubes or store those fresh samples incorrectly, they still won't find XMRV/MLV. Or did I miss something?
:confused:
 

SOC

Senior Member
Messages
7,849
The point I was trying to make was the fact that Alter could not find XMRV/MLV in the samples from the CDC's study indicates the CDC did a terrible job with the methods they used, doesn't it? Doesn't that confirm all the complaints against the CDC paper? They could test the same patients Alter found positive, but if they use the wrong tubes or store those fresh samples incorrectly, they still won't find XMRV/MLV. Or did I miss something?
:confused:

Good questions. Unfortunately, not so easy to answer. :Retro smile: There are a number of reasons why neither the CDC nor the FDA/NIH team found XMRV (Do we know they tried to find MLVs?)

One, of course, is that there were no true CFS patients and no one infected with XMRV in their cohort. Should they have seen at least 2% positive? Probably, but statistically they could have not had an XMRV+ person in their sample set. It's possible. We don't know much about geographic variation and their sets were very limited geographically.

Another is that the samples could have been effectively destroyed before the people doing the labwork received them. Poor collection techniques (wrong tubes, wrong prep), inappropriate storage, or deliberate sabotage.

The CDC sent 34 samples to Alter/Lo for testing. Statistically, it's possible there were no XMRV+ samples in that small of a group, especially if the CDC's "CFS"patients were not true ME/CFS patients. If the infection rate in the general population in Atlanta/Witchita is 2%, you could easily not find any positive samples in a random group of 34 people.

It's also possible that the 34 samples sent by the CDC were the 34 chosen to be the least likely to be positive. It would be inethical to do that, of course.

It would be unprofessional for a researcher to declare another researcher's methods were bad without considering all the scientifically possible alternatives. Whatever Drs Alter and Lo personally believe, they need to maintain a professional stance. Note that the CDC researchers were NOT professional in their attacks on WPI's research.

Do I think the CDC screwed up somehow? Yes. But I have to concede there are other possibilities that need to be investigated.

Yes, the CDC could test blood from the few "fresh sample" patients Alter and Lo tested. If it was properly collected and stored and the CDC didn't find MLVs, then one would definitely have to question the validity of their methods. The CDC hasn't done those tests. They don't have to, of course.

We'll know by the end of the year which of a number of labs (including the CDC) can accurately detect MLVs in blood. At this point we can only speculate about their failure.

That is probably way longer than it needs to be. *sigh* I hope it helps, though.
 

illsince1977

A shadow of my former self
Messages
356
Good questions. Unfortunately, not so easy to answer. :Retro smile: There are a number of reasons why neither the CDC nor the FDA/NIH team found XMRV (Do we know they tried to find MLVs?)

That is probably way longer than it needs to be. *sigh* I hope it helps, though.

Not too long. at all! Yes it does help, thank you, SickofCFS:Retro smile:!