The State of Play ?

[KFG]

"In conclusion, the fundamental question of whether XMRV is really an infectious agentcirculating in the human population is still unresolved. This question will not be settled until reproducible assays for the virus are established and validated; in turn this will require exchange of samples and testing of well-characterized standards, followed by cross-comparison of results obtained in different laboratories."

from
Cancer Res. 2010 Oct 21.
XMRV: A New Virus in Prostate Cancer?
Aloia AL, Sfanos KS, Isaacs WB, Zheng Q, Maldarelli F, De Marzo AM, Rein A.
HIV Drug Resistance Program, National Cancer Institute.
--------------------------------------------------------------------------------------------------------------------

I think it would be a good idea to remember that XMRV research is not the only ME/CFS research taking place in the world today. A number of good research teams continue to look at non-viral aspects of the illness, as well as other immunology. The fact that researchers in the NCI who aren't affiliated to WPI are willing to consider the possibility that XMRV isn't even a proper infectious virus in humans is saying a huge amount. And please don't misinterpret or misrepresent what I'm saying - this in no way casts any aspersions whatsoever on the NCI people working with WPI, or WPI themselves for that matter.

The key point to remember is that there is other good quality non-XMRV research taking place around the world. If XMRV proves not to play any role in ME/CFS then we can hope that the publicity it has garnered brings enough new good quality researchers into the field to see breakthroughs occur.
This story has some way to run but if you read the quote above then it seems sensible to be cautious about the XMRV story, but not think there are no alternatives if it doesn't pan out.

Unfortunately my illness isn't about to go away. Neither am I. I want my life back and I want the research done. If it isn't XMRV it's sure as hell something else. And for the benefit of anyone who might be in any doubt - it doesn't, didn't, and never will have, anything to do with Psychiatry either.
This nonsense will end, whether it's XMRV or not.

 

[usedtobeperkytina]

I think the Light study is a breakthrough. It was put in the shadows by the WPI study. But, it would have been and still is a breakthrough. It is measurable, objective test showing the post-exertional malaise.

I was also impressed with Snell's research, that shows similar, objective abnormalities in oxygen absorption and heart rate in CFS patients 24 hours after exercise.

I think Dr. Klimas is looking at immune system abnormalities as a part of post-exertional malaise.

The question is, would this be distinctive to CFS. Nancy Klimas said that from symptom reporting, the only other illness she is aware of with post-exertional malaise is MS. I note that the Light study compared the gene expression between CFS folks and MS. And CFS was much more pronounced in their abnormal readings.

So, if you combine the Light study with Snell's study with possibly Klimas' research that might come out soon, I think you see a distinctive, objective, biological picture of CFS.

Now, two questions: will this translate into tests that can be done in the clinical setting? What specialist?

Also, what good is this if it is not known by clinicians?

But, from a standpoint of getting us closer to a biomarker, even for research purposes, these different studies are showing the same thing. The biological picture is becoming more clear.

If the virus holds up, it will take precedence as it will be as easy a test as the HIV test. Send it off, get results. These other tests would require one day of stress test and then another day of tests.

Some CFS experts are also expressing concern as to what it does to CFS people to create the post-exertional malaise. It does raise an ethical question if the test does not bring benefit, just diagnostic purposes. Can you accurately diagnose without this test that will do harm if you have the disease?

Thank you, from me personally, to all the patients who are willing to be harmed for the purpose of furthering research.

Tina

 

[Glynis Steele]

Hi KFG and Diesel,

This research is following up on the Sheedy/de Meirleir paper on CFS/D-lactic acidosis, which states that stool samples of patients with CFS had higher than usual bacteria that are d-lactic producers, and that the 2 conditions are strikingly similar. You've probably read the original, but here it is again.

http://www.ncbi.nlm.nih.gov/pubmed/19567398

This is the follow up application to measure biomarkers in CFS

http://sacfs.asn.au/download/Lactic acid study 2008 - Ethics Application.pdf

Here is the Information for Participants

http://sacfs.asn.au/download/Lactic acid study 2008 - Information for participants.pdf


I'm not sure it they are any where near completing this study though. I have put some d-lactic stuff on the Reseach Thread, if you want more info, though most of it applies to short bowel patients. The thing is d-lactic acidosis is only seen by gastro's, who see it in patients with a shortened bowel. I think outside their field the importance of the original study is not understood. Dla is a serious condition, needing urgent treatment.

Dla causes neurological changes, one of the main symptoms is extreme lethargy. It also causes confusion, a change in gait, slurred speech, & difficulty in speaking. It requires a special blood test, & does not show up in routine testing. A d-lactic (lactate) assay kit is required, & most path labs cannot test for it, which I find very worrying. In the UK Birmingham Children's Hospital can test for it. Treatments include minimally absorbed antibiotics, IV sodium bicarbonate & a low carb diet, but would require a GI to oversee testing, interpret the results and treatment, which they MUST give in the event of a positive test, as dla should not be seen in a healthy person.

Dla occurs when unabsorbed carbohydrates become fermented by gut bacteria. This lowers the pH of the bowel, and acid loving bacteria become dominant, and dla is produced to an extent that overwhelms the body's capacity to clear it. It is then absorbed into the bloodstream, and is capable of crossing the blood brain barrier.

I think it is unacceptable for people with CFS to have to wait for research to be developed in this regard, after all if a short bowel patient develops dla, either a blood or urine test is performed, and treatment is given. Nowhere have I found any evidence to show that these patients had to wait until a large enough study was undertaken to enable them to be treated, this being the "gold standard, evidence based scientifically proven method". Short bowel patients who develop dla are treated urgently, certainly not ignored, this would be extremely negligent.

In all I think mainstream medicine is shockingly ignorant regarding dla, it is not part of their training, unless they become gastro's, and why would a gastro think a person with CFS has dla? After all they have an intact bowel. The gastro would not see a CFS patient BEFORE they developed CFS, so would have no reference of what that person would present as, if they were healthy. Does this make sense? Sometime I waffle, and my typing can become confusing, sorry!

Please write if you want some dla papers. I have loads!

BW

Glynis

 

[Sasha]

Some CFS experts are also expressing concern as to what it does to CFS people to create the post-exertional malaise. It does raise an ethical question if the test does not bring benefit, just diagnostic purposes. Can you accurately diagnose without this test that will do harm if you have the disease?

Lots of interesting stuff in your post, Tina, but I just wanted to comment on this bit - I'm concerned too about the possibility of "destructive testing" to demonstrate PEM. It would be great if there were another objective measure of disease severity without an exercise challenge, such as viral load.

 

[BEG]

Maybe the test results of the (unwitting) patients who've already had the cardiopulminary stress test can be used so others don't have to be tested. We can't ignore this aspect of the illness, however. It's widely known as the hallmark of this disease. When the CDC expressly states (at the CFSAC meeting) that they won't use post-exertional malaise in their (yet again) new definition, patients and clinicians must push for it in more ways than one.

Regarding XMRV, IMO this is the first exciting news to come out in 25+ years of research. This, more than anything, has propelled us into the spotlight and hopefully the light will get brighter. So whether we test positive or not, keep your fingers crossed, the discovery of XMRV will bring about many treatments. Speculation, I know. But I am very hopeful that all will be helped, the positives and the negatives.

 

[Sasha]

Maybe the test results of the (unwitting) patients who've already had the cardiopulminary stress test can be used so others don't have to be tested. We can't ignore this aspect of the illness, however. It's widely known as the hallmark of this disease. When the CDC expressly states (at the CFSAC meeting) that they won't use post-exertional malaise in their (yet again) new definition, patients and clinicians must push for it in more ways than one.

Hi BEG - I completely agree that PEM is a cardinal symptom and in terms of diagnosis, very important, but I think that in everyday life PWC experience enough evidence of PEM just in doing (or trying to do) their everyday activities that they can tell their diagnosing physician about it. My impression is that a stress test isn't therefore necessary for diagnosis and is being used in research because there isn't anything better to measure outcomes. The Lights' study is the exception, of course, because they are studying PEM specifically and there's no getting around using a stress test there.

Actually, now that I've written that para, I'm questioning my basis for it! Can PWC go through everyday life without realising that their fatigue is delayed? Does that feature only show up later in the illness? Or only with higher levels of exceeding a certain baseline of activity?

I do think PEM is very interesting - the Lights' graph comparing ME, MS & healthies post-exercise is jaw-dropping.

 

[urbantravels]

Self-reporting of symptoms is where we are now, and we all know how far that gets most of us with most of our doctors. It's hard to objectively measure what's going on in PEM without having something concrete to measure.

That said, I do hope standard diagnostic tests do not end up relying on an exercise challenge. It's simply too expensive and cumbersome to be used as routine screening. As a research tool, though, it's going to be fundamental to furthering our understanding of the disease.

Suffering the PEM afterward would be nasty, but I doubt it would represent a permanent setback for most of us.

It's extremely hard to figure out the patterns of PEM just by observing yourself, especially since it seems to me that sometimes flareups occur when there has been no unusual exertion....and the level of exertion that will bring on a PEM varies from day to day.

 

[Glynis Steele]

Hi Diesel,

Thanks for the reply, I think that if dla was in part or wholly responsible for CFS, then each case found would have to be urgently referred to a GI. If the symptoms of dla were not corrected by antibiotics alone, then an IV containing sodium bicarbonate would be used. From what I have read about dla this seems common practise. Also of course they would need to use the correct antibiotics to kill off the bacterial overgrowth, as each person's gut bacteria are different, and some strains are resistant. I think it can be a bit hit and miss, until the right treatment for that particular patient is found. Here is a good link, which explains the (sometime) complexities of dla, including a theory that insulin might also help.

Antibiotics used are vancomycin, metronidazole, neomycin, kanamycin, co-trimoxazole and others.

Of course dla in CFS has still yet to be proven, it might not be the case at all, I'm just a dla nutcase!!

http://www.ccjm.org/site/misc/Jun07_Bakhru.pdf

Best

Glynis

 

[shannah]

Suffering the PEM afterward would be nasty, but I doubt it would represent a permanent setback for most of us.

I know for me that after every major PEM, I never return up to baseline but lose more ground, become sicker, weaker and less and less functional all the time. It's like it kicks up the pathogens and wears down the immune system another notch. I wonder if there is a subset of others this happens to. Anyone else?

 

[Sasha]

Suffering the PEM afterward would be nasty, but I doubt it would represent a permanent setback for most of us.

This is the big question, I think - I'd honestly be scared to do an exercise challenge for fear I might suffer a permanent setback. Beyond a certain point, I think at least some of us can't recover. I'm in what has turned out to be a sustained relapse now following overdoing it four months ago.

That's true that maybe PEM isn't as obvious as I had been thinking. Complicated...

 

[Otis]

Some CFS experts are also expressing concern as to what it does to CFS people to create the post-exertional malaise. It does raise an ethical question if the test does not bring benefit, just diagnostic purposes. Can you accurately diagnose without this test that will do harm if you have the disease?

I *think* I heard (from a video I watched maybe 2 years ago) Dr. Bateman indicate that @ some point in the future exercise tests in ME/CFS will be considered ethical. Tough question.

I'm not able to even attempt a test like this right now so I, too, want to thank those who are doing this for the common good!

 

[Otis]

Hi BEG - I completely agree that PEM is a cardinal symptom and in terms of diagnosis, very important, but I think that in everyday life PWC experience enough evidence of PEM just in doing (or trying to do) their everyday activities that they can tell their diagnosing physician about it. My impression is that a stress test isn't therefore necessary for diagnosis and is being used in research because there isn't anything better to measure outcomes. The Lights' study is the exception, of course, because they are studying PEM specifically and there's no getting around using a stress test there.

Actually, now that I've written that para, I'm questioning my basis for it! Can PWC go through everyday life without realising that their fatigue is delayed? Does that feature only show up later in the illness? Or only with higher levels of exceeding a certain baseline of activity?

I do think PEM is very interesting - the Lights' graph comparing ME, MS & healthies post-exercise is jaw-dropping.

I'm not in favor of fishing for any and all biomarkers (*ahem*) but I think this PEM work is very important because it's the hallmark symptom.

I was happy to see some data from Dr. (Alan) Light's study as presented at the CFSAC using gabapentin or Lyrica showing some promising effects on cytokine dampening during PEM. Good to know someone is trying things out there.

On the gene expression side I think Dr. Klimas and her collaborator (can't recall his name - from Ottawa I think) are collecting more data, using common sample times for comparison with the Light study. They want to backtrack and see if they can get closer to the beginning of the cascade and hopefully find interventions. This is a case where we're benefiting from the GWI money Klimas has been able to pull in. Just tack on some CFS patients. Brilliant.

On the question of PEM and who notices it early in the illness and when (obviously not applicable to the large number of people who get blasted with horrible sudden onset) given that at least 80% go undiagnosed I'm sure there's lots of PEMed people out there who have no idea what the symptoms represent or correlate them to anything given the typical delay of onset.

Looking back I can pinpoint one very bad case of PEM that I wrote off as some kind of bug because it was 5 years prior to a Dx despite being symptomatic.

So I think PEM hides pretty well early on and even when one understands the PEM price to be paid can even miss it if they are constantly pushing.

 

[George]

I have a nutty question about the current "state of play", two actually. First does anyone have an inkling of what the Dr. Light(s) are trying to patent?? Or if the "legal quite period" is even about a patent??? If they are going to so much trouble then I hope that this will be "the biomarker" ya know. (grin)

Second Dr. LeGrice referred to a study which would rule out contamination completely (or not) that would be available shortly like by the end of November in his monologue on CFSAC science day. Does anyone know anything about that study?? Who's doing it and how it's designed, things of that nature???

I know it's not the Dr. Lipkin study which will be finished up in time for the NIH conference on the "State of Research on XMRV" scheduled for next April. But I'm confused if it's part of the Phase II portion of the NHLBI Study which I understand will be completed the first week of November and should be reported on before Thanksgiving.

Any information would be appreciated on that.

 

[George]

Oh and Otis
I'm confused about the XMRV in Mice thing. The PNAS commentary, states that they it's been found in the 129 lab mouse strain and a close cousin has been found in BL6, Dr. LeGrice mentions that it's been part of the artifacts found in lab mice for decades and I do remember Dr. Coffin talking about that last year as well. It's an artifact that pops up when you run human cells through mice. I'm not clear if its' in the human cells or in the mice and the human cells pick it up.

However, a recent statement by Dr. Mikovits indicates that XMRV (does that include the PLMV's???) has NOT been found in mice despite a search for it???? I doubt either statement is incorrect but there seems to be a lack of context does anybody have any more information.?????

If XMRV is indeed in mice then ruling out contamination would be a must before going public about the virus itself, not ruling it out would just leave all the research that came after open to debate and create a lot of problems. That would be best to avoid I think.

 

[Glynis Steele]

Hi Diesel,

I started looking online to see if I could find anything linking dla and CFS. I came across this link, and though it's in connection with fibro and lactic acidosis (does not state dla), I wondered whether it was relevant. I don't know if MELAS has been discussed on this forum, so forgive me if I am repeating older studies/already known anomalies in CFS.

http://www.solacenutrition.com/pdfs...-Encephalomyopathy-Lactic-Acidosis-Stroke.pdf

Regards

Glynis

 

[Otis]

I know for me that after every major PEM, I never return up to baseline but lose more ground, become sicker, weaker and less and less functional all the time. It's like it kicks up the pathogens and wears down the immune system another notch. I wonder if there is a subset of others this happens to. Anyone else?

Shannah,

Yes, I too have a patten like this.

 

[*GG*]

I know for me that after every major PEM, I never return up to baseline but lose more ground, become sicker, weaker and less and less functional all the time. It's like it kicks up the pathogens and wears down the immune system another notch. I wonder if there is a subset of others this happens to. Anyone else?

Probaby is a subset that happens to, I can recover from exercise, but now I chose not to exercise to any great extent, I walk 1 mile to 3, depending upon how I feel and what I need to do the next day, work etc. I went thru a Major flare up last fall, and I don't feel like missing work/income for months and leave me wondering what the consequences will be next time!

I would do more studies if I knew that it would further the science, (participated in a NIH study if XMRV turns up in my blood, over 2 months, and still no news!), and if I had the support that I might need to recover or to ensure that I would be taken care of if I needed it, just don't have that apparatus in position now, so not sure how far I would push my body to help the science along?!

GG

PS I was biking on a fairly regular basis up until the end of summer of 2009, but I don't bike anymore, and have gained 30 pounds in the last year!

 

[waiting]

Self-reporting of symptoms is where we are now, and we all know how far that gets most of us with most of our doctors. It's hard to objectively measure what's going on in PEM without having something concrete to measure.

That said, I do hope standard diagnostic tests do not end up relying on an exercise challenge. It's simply too expensive and cumbersome to be used as routine screening. As a research tool, though, it's going to be fundamental to furthering our understanding of the disease.

Suffering the PEM afterward would be nasty, but I doubt it would represent a permanent setback for most of us.

It's extremely hard to figure out the patterns of PEM just by observing yourself, especially since it seems to me that sometimes flareups occur when there has been no unusual exertion....and the level of exertion that will bring on a PEM varies from day to day.

I also hope that there will be another test (like measuring titres) that will one day be available, and I'm sure many PWC's could be harmed by the test -- if not forever, then at least for weeks to months. However, the CPET (cardio-pulmonary exercise test) is very important because it is objective and it measures *severity* of ME/CFS.

 

[Frankie Dene]

I know for me that after every major PEM, I never return up to baseline but lose more ground, become sicker, weaker and less and less functional all the time. It's like it kicks up the pathogens and wears down the immune system another notch. I wonder if there is a subset of others this happens to. Anyone else?

Yes that is definitely true for me too. I did a little bit too much 4 months ago and here I am still not as good as I was then. I am very careful to not do too much and wonder too about those brave people who will exercise for research - I certainly couldn't.

 

[valentinelynx]

D-Lactic Acidosis: Wouldn't that be easy to rule out?

Not an expert on this disorder (d-lactic acidosis), but it being a form of lactic acidosis, which is a form of metabolic acidosis, I would suppose it would be easy to test for, that is, easy to "rule out." A simple basic chemistry blood test (done in almost all basic lab testing) would show anion gap acidosis. A blood test for lactate would be elevated. Given that "normal" basic labs are the "norm" in CFS, I've got to think this disorder is pretty unlikely.