Science Express - einde XMRV?

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magnetronnie
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Even samenvattend, voor degene die wat meer moeite hebben met medische teksten in het Engels..

In december 2009 hebben het Amerikaanse ministerie van Volksgezondheid en de National Heart, Lung, and Blood Institute een werkgroep opgericht om te onderzoeken of XMRV een gevaar is voor de bloedvoorziening.

Het onderzoek bestond uit verschillende fasen en gisteren heeft de werkgroep een studie van Phase III gepubliceerd in het vakblad Science Express. Phase III was bedoeld om de klinische sensitiviteit en selectiviteit te bepalen van de XMRV bepalingsmethoden van de deelnemende laboratoria. Met andere woorden, in welke mate zijn de laboratoria in staat om XMRV aan te tonen in positieve monsters en juist niet aan te tonen in negatieve monsters.

In totaal deden negen laboratoria mee aan deze studie en gebruikten daarbij gezamelijk 19 bepalingsmethoden (PCR, antistoffen, cell-culture). Er is een panel gemaakt met daarin 5 monsters die eerder in de Lo/Alter studie positief waren bevonden, 10 monsters die eerder door het WPI positief waren bevonden (waaronder 6 uit de originele studie van Lombardi et al.), 3 negatieve monsters van laboratoriummedewerkers en 12 negatieve monsters van gezonde bloeddonoren. In totaal dus 15 positieve en 15 negatieve monsters. Bovendien werden drie monsters toegevoegd die men positief had gemaakt door ze te besmetten met XMRV uit een besmette cellijn. Deze monsters diende als positieve controle, dus om vast te stellen of de bepalingsmethoden überhaupt wel in staat waren om XMRV te detecteren. Alle monsters zijn centraal verzameld en verwerkt en vervolgens blind naar de deelnemende laboratoria verstuurd.

De resultaten liegen er niet om. Slechts twee laboratoria waren in staat XMRV/MLV aan te tonen in patiëntenmonsters en monsters van gezonde bloeddonoren; het WPI en het laboratorium van Ruscetti (NCI). Alle andere laboratoria, inclusief die van Alter/Lo wist XMRV/MLV alleen aan te tonen in de positieve controlemonsters. Het WPI en het NCI laboratorium toonde XMRV/MLV in gelijke mate aan in patiëntenmonsters en monsters van gezonde bloeddonoren. Bovendien zijn alle monsters meerdere keren gemeten en kon het resultaat niet worden gedupliceerd; monsters die positief testten waren bij herhaalde meting negatief en andersom. Daar komt nog eens bij dat het XMRV uit de positieve monsters grote gelijkenis vertoonde met XMRV uit de cellijn. Met andere woorden, de resultaten waren een rommeltje en men kon niet met zekerheid zeggen welk monster ook echt positief was.

Door deze ontwikkelingen zal de werkgroep geen Phase IV uitvoeren. De conclusie luidt dat XMRV geen gevaar is voor de bloedvoorziening.

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poppetje
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Vandaag spreekt Mikovits op het congres in ottawa, Ben benieuwd wat daarvan naar buiten komt en hoe zij hiernaar kijkt. Hoe nu verder voor de toekomst.
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marlène
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Dank je wel magnetronnie voor deze toelichting!
http://opstaanmetmecvs.blogspot.com

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nokkos
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Kan het wel zijn dat XMRV niet schadelijk is voor bloed, maar wel voor het lichaam"?
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tanto
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Hoewel ik zelf nooit echt overtuigd ben geraakt over het bestaan van xmrv, vind ik de conclusie in deze toch wel wonderlijk: de resultaten zijn een zooitje: dus er is geen gevaar voor de bloedvoorziening/volksgezondheid? Ontbreekt hier niet iets? Dat je uitzoekt wat er precies misgaat bijvoorbeeld?

Magnetronnie dank voor je samenvatting!
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poppetje
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http://www.nytimes.com/2011/09/23/healt ... .html?_r=3


‘Viral Theory Is Set Back in Chronic Fatigue Study’, New York Times, 22 September 2011
by Tony Britton on September 23, 2011
From the New York Times, 22 September 2011 (story by David Tuller)

Dashing the hopes of many people with chronic fatigue syndrome, an eagerly awaited study coordinated by government health agencies has not confirmed a link between the illness and a virus called XMRV or others from the same class of mouse leukemia viruses.

Two research groups had earlier reported an association between chronic fatigue syndrome and the group of viruses, known as murine leukemia viruses, or M.L.V.’s, raising hopes that a treatment or cure could be found. But later studies did not substantiate the link, and many researchers suggested that that the initial findings were the result of contamination of laboratory samples or equipment.

The new multilab study, published online Thursday in the journal Science, was designed to answer some of the questions about these unusual viruses and determine whether they posed a risk to the blood supply.

Results from another government-sponsored study of M.L.V.’s, with a much larger sample size, are expected early next year. But Thursday’s report appeared to leave little room for continued optimism.

Of the nine labs that received blinded blood samples from 15 people previously reported to have been infected with M.L.V.’s and 15 healthy controls, only two reported finding evidence of the viruses in any of the samples. And the results from those two labs — which were the only two to find positive results in the original studies — contradicted not only each other this time, but some of their own earlier findings as well.

“These results indicate that current assays do not reproducibly detect XMRV/M.L.V. in blood samples and that blood donor screening is not warranted,” reported the new study, written by researchers participating the Blood XMRV Scientific Working Group.

But the scientists also said they could not “definitively exclude” the possibility that levels of viral markers in the blood might fluctuate over time and become undetectable at certain periods.

Also on Thursday, researchers from the original study linking XMRV to chronic fatigue syndrome, which was published in Science in October 2009, retracted a portion of their data — but not their conclusions — because of evidence of contamination in one lab involved in the study.

Vincent Racaniello, a microbiology professor at Columbia University who has covered the controversy on his popular virology blog, said the XMRV/M.L.V. hypothesis was now dead. “It’s clearly time to move on in the study for the origin of this disease,” he wrote in an e-mail message.

An estimated one million Americans suffer from chronic fatigue syndrome. Countless studies have documented immunological, neurological and other physiological abnormalities. Despite the name of the illness, patients have long reported that simple fatigue is not their cardinal symptom but rather what researchers call postexertional exhaustion — a profound depletion of energy after even minimal exercise or activity.

Recently, a panel of top researchers proposed a new definition of the illness that requires the presence of postexertional exhaustion, rather than the six months of unexplained fatigue required under the standard definition.

The group also recommended changing the name to myalgic encephalomyelitis, a virtually identical illness long recognized by the World Health Organization.

Dr. Nancy Klimas, an immunologist at the University of Miami, said that the two-year debate over M.L.V.’s had raised the profile of the disease and brought attention to the likely role of infectious agents in chronic fatigue syndrome.

“Internationally recognized experts have looked at the immune data and concluded that there very well may be a pathogen or pathogens involved in the persistence of this illness,” Dr. Klimas wrote in an e-mail message.


The new findings will also be presented Friday in Ottawa at the annual conference of the International Association for Chronic Fatigue Syndrome/ME, a leading scientific organization.
Laatst gewijzigd door poppetje op 23 sep 2011, 14:10, 1 keer totaal gewijzigd.
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poppetje
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http://www.latimes.com/health/boostersh ... 0217.story


By Karen Kaplan, Los Angeles Times/For the Booster Shots blog
September 22, 2011, 2:28 p.m.
At first, it looked like a breakthrough in the fight against chronic fatigue syndrome. Researchers said they found a mouse retrovirus called XMRV in the 68% of blood samples collected from 101 patients with chronic fatigue syndrome, while only 4% of blood samples from 218 healthy controls had evidence of the same virus. The research team said it was strong evidence that XMRV had something to do with causing chronic fatigue syndrome (CFS). The report had added credibility because it was published in the prestigious journal Science.

But the XMRV-CFS theory began unraveling just a few weeks after the study was published in October 2009. The tale reads like a whodunit and is summarized nicely in Friday’s edition of Science. That article is accompanied online by a partial retraction of the controversial paper and a multi-lab study that failed to turn up any convincing evidence linking XMRV to chronic fatigue syndrome.

When the initial report was published, virology experts were skeptical that a mouse virus could be responsible for chronic fatigue syndrome, a debilitating condition characterized by extreme fatigue, chronic pain and depression. One of the early criticisms was that the strains of the XMRV virus found in patients were unusually similar, suggesting that contamination was responsible for their presence in so many of the blood samples.

In addition, the genetic technique used to look for XMRV – called “nested PCR” – has a known tendency to produce false positives, critics said.

Still others noted that all the CFS patients in the study were from Nevada, but the controls were from all over the country. Perhaps there was something in the Nevada environment that made XMRV more prevalent there but had nothing to do with chronic fatigue.

There was also the fact that when the researchers tested the blood samples, they knew whether those samples were from patients with CFS or from healthy controls. That knowledge may have biased their results.

After the report came out, many other labs looked for XMRV in the blood of other patients with CFS and couldn’t find it. Those that did find it also turned up evidence of mouse DNA, lending support to the theory that XMRV got into the blood samples through contaminated laboratory chemicals.

In March, scientists from the National Cancer Institute and Tufts University presented strong evidence that the strain of XMRV identified in the initial Science report had been created inadvertently in the 1990s by researchers who were studying prostate cancer in mice. If that were the true origin of XMRV, it couldn’t possibly be responsible for cases of chronic fatigue syndrome, which was recognized in the 1980s. (Similar ailments were described decades earlier.)

For many, the NCI-Tufts report was the final blow. The new study in Science, published online Thursday, simply piles on.

It involved nine different laboratories, including ones at the National Institutes of Health, the Centers for Disease Control and Prevention, the Food and Drug Administration and the two labs that published the initial paper. Each lab got a collection of blood samples to test. Some of those samples were from chronic fatigue syndrome patients who had previously been found to be infected with XMRV (or a related virus), and some were from healthy controls. There were no labels that might tip off the testers about which were which.

Overall, only two of the labs were able to detect XMRV in any of the blood samples – the same two labs that worked on the original study. But this time around, these labs found XMRV in blood samples from healthy people just as often as they found it in blood taken from people with CFS. Also troubling was the fact that when the same blood sample was divided up and tested separately, the results didn’t always agree.

Ostensibly, the purpose of this study was to determine whether there was any reason to screen donated blood for XMRV, in case the virus might be spreading and causing new cases of CFS. “Blood donor screening is not warranted,” the research team concluded.

But the driving force behind the 2009 study, Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease in Reno, continues to believe in a connection between XMRV and CFS. As she told Science, the new study shows only that there’s no reliable way to find XMRV in blood samples, but the virus could still be lurking in patients’ tissues or be circulating in the bloodstream at levels that are too small to detect using ordinary methods. She accused one particular naysayer of trying to play God and offered a conspiracy theory in which the U.S. government is trying to undermine her research because it fears an outbreak of XMRV.

In the partial retraction published online Thursday, Mikovits and her colleagues on the original study acknowledge that two of the researchers used blood samples that were contaminated with XMRV DNA. Two figures and a table were affected. But the retraction says nothing about the study’s overall conclusions.
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‘Virus link to ME called into question’, BBC News, 22 September 2011
by Tony Britton on September 23, 2011
From BBC News, 22 September 2011 (story by health reporter James Gallagher)

Scientists who first linked chronic fatigue syndrome, also known as ME, to a virus have withdrawn some of their findings.

They have said some of their findings were based on “contaminated data”.

Meanwhile, a study in Science claimed the virus could not be reliably detected in ME patients, even in the labs which originally made the link.

Understanding of chronic fatigue syndrome is poor. It may be many diseases and the causes are uncertain.

There was a sense of hope for many patients when a study published in Science in 2009 showed that DNA from a mouse virus, XMRV, was present in 67% of patients with the illness, but only 4% of the general population.

Yet other scientists around the world could not find evidence of the virus. Many researchers began to argue that the most likely explanation was contamination of the laboratory samples.

It led to Science asking the authors to withdraw their findings and it published an editorial “expression of concern” saying that the validity of the study was “seriously in question”.

The authors have now issued a partial retraction after some of the scientists involved reported contamination, but this only calls into question the information in one table and two diagrams, not the rest of the paper and not the final conclusion.

One of the labs involved, the Whittemore Peterson Institute in Nevada, is standing by the conclusion. One of its lead researchers, Dr Vincent Lombardi, said it was “participating” in the retraction but: “We want to make it very clear that we are continuing the important work of studying retroviruses in association with ME/CFS and other similarly complex illnesses.

“WPI’s more recent retroviral work, although still in the early stages of discovery, continues to warrant additional investigations.”


Dr Jonathan Stoye, virologist at the Medical Research Council National Institute of Medical Research in the UK, said: “I don’t think this partial retraction has any meaning, it would have been nice to have a complete rather than a partial retraction.

“They’re saying the rest of the paper still stands, but that is becoming increasingly difficult for them to maintain.”

A fresh study on XMRV published in Science, which the researchers behind the original study participated in, again questioned the link.

Samples of blood were collected from 15 patients who had previously tested positive for XMRV, 14 of whom also had chronic fatigue syndrome, and from 15 patients without XMRV.

These samples were sent to nine laboratories, including two which had found the link previously. No lab knew which samples were from which patients.

Only two laboratories, the two which initially proposed the link, detected any cases of XMRV. However, the virus was detected at “similar rates” in both groups of patients, the study said.

The results from the two laboratories were also “inconsistent” even when testing blood from the same patient.

Dr Charles Shepherd, medical adviser to the ME Association said: “These are very emphatic negative or inconsistent findings from the Blood Working Group study, along with the retraction of some of the original supporting data that was published in Science.

“So it is now looking extremely unlikely that XMRV is either linked to ME/CFS or that it has a disease-causing role.

“Having had their hopes raised that a treatable component to ME/CFS had been identified, it’s not surprising that people are becoming increasingly disappointed at the way things are turning out.

“But it’s too early to send out the scientific jury to make a final definitive decision on XMRV and ME/CFS – we still need the results from the other major multi-centre study on XMRV and ME/CFS being carried out in America by Prof Ian Lipkin.”


http://www.meassociation.org.uk/?p=8169
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tanto
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Bericht door tanto »

Dank je Poppetje!

Verwarrend allemaal, ik vind zelf dat WPI er niet zo heel goed voor staat nu (wel heel toevallig dat er een paar staten gecontamineerd blijken te zijn met xmrv). Ik ben benieuwd naar de resultaten van Lipkin.
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nijntje
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ontzettend bedankt voor alle leerzame info!!!
magnetronnie
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Ik weet even niet meer waar ik het heb gelezen, maar de monsters die gecontamineerd zijn in de originele studie zijn afkomstig van het lab van Urisman van de prostaatkanker studie, en waarschijnlijk afkomstig van de bekende besmette cellijn. Dat is denk ik ook de reden waarom men niet de hele studie heeft ingetrokken.
tanto schreef:Hoewel ik zelf nooit echt overtuigd ben geraakt over het bestaan van xmrv, vind ik de conclusie in deze toch wel wonderlijk: de resultaten zijn een zooitje: dus er is geen gevaar voor de bloedvoorziening/volksgezondheid? Ontbreekt hier niet iets? Dat je uitzoekt wat er precies misgaat bijvoorbeeld?

Magnetronnie dank voor je samenvatting!
Dat staat er inderdaad niet duidelijk bij, maar er is nog een andere studie die laat zien dat het menselijk lichaam heel erg snel en efficiënt XMRV kan opruimen, dus zelfs als dit virus uit het lab zou ontsnappen, dan nog is de kans dat er mensen geïnfecteerd raken én elkaar infecteren heel erg klein. Ik denk dat dát de uiteindelijke reden is geweest waarom de bloedvoorziening het risico op besmetting niet groot acht.
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tanto
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oh ok, dank je.

Goed dat jullie het allemaal zo bijhouden!
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nijntje
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@Magetronnie : in jouw samenvatting gaat het niet over ME/CVS, maar de artikes in "science" gingen dacht ik wel over het feit dat XMRV niet bepaald kon gedetecteerd worden bij ME/CVS-patiënten, en dat de oorspronkelijke studie in 2009 zelfs gedeeltelijk zou teruggetrokken worden....
kan je dat even linken of ben ik zo suf dat ik het niet snap?
magnetronnie
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nijntje schreef:@Magetronnie : in jouw samenvatting gaat het niet over ME/CVS, maar de artikes in "science" gingen dacht ik wel over het feit dat XMRV niet bepaald kon gedetecteerd worden bij ME/CVS-patiënten, en dat de oorspronkelijke studie in 2009 zelfs gedeeltelijk zou teruggetrokken worden....
kan je dat even linken of ben ik zo suf dat ik het niet snap?
Er lopen twee verhalen door elkaar hier, dus dat is misschien wat verwarrend. :)

Het gaat hier in dit topic eigenlijk de hele tijd over de resultaten van de Blood Working Group. Dat is dus het hele verhaal wat ik daarboven typte, dat de testen waarmee ze XMRV aantonen (in ME/CVS patiënten en gezonde personen) niet betrouwbaar zijn.

En daarnaast is er gisteren in hetzelfde vakblad, ook in Science Express, een "partial retraction" gekomen, dus een gedeeltelijke intrekking, van de originele studie van Lombardi uit 2009. En daarin wordt gezegd dat ze nu direct bewijs hebben dat in ieder geval een aantal monsters in die studie besmet zijn geweest en dat deel is dan ook ingetrokken. En zoals ik het begrijp kwam dat door materiaal dat ze van Silverman, van de prostaatkanker studie, hebben gekregen.
Het is wel vreemd dat die studie nog niet is ingetrokken overigens.

Beide verhalen staan wel los van elkaar volgens mij.
magnetronnie
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Ohja en de linken..

De partial retraction: http://www.sciencemag.org/content/early ... ce.1212182

De resultaten van de BWG: http://www.sciencemag.org/content/early ... 1.abstract


En eigenlijk was er ook nog een derde "studie" geplaatst in Science Express gisteren, maar da tis eigenlijk meer een artikel/interview over het hele XMRV verhaal tot nu toe, met alle betrokkenen. Wel erg interessant om te lezen trouwens.
http://www.sciencemag.org/content/333/6050/1694.summary
(gratis, maar je moet wel registreren en dat ging niet heel makkelijk)
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