Sept 10: CDC 'conference call' including Unger and Lipkin

[Ember]

I think Dr Snell has indicated that some other researchers have not managed to replicate his research...

Who has tried and failed to replicate Dr. Snell's research?

 

[vli]

That was a great post SOC, thank u.

 

[JT1024]

A lot of people are concerned about gut bacteria and the immune system. Its a hot topic in research.

Hi Alex!

Two years ago, I was fortunate to attend a conference on autoimmunity. One of the presenters was a pediatric gastroenterologist who was a fascinating speaker, researcher, and physician. At the time, he was at the University of Maryland and he started a Celiac Center. http://medschool.umaryland.edu/FACULTYRESEARCHPROFILE/viewprofile.aspx?id=1891

Since I saw him speak, he left the University of Maryland and is at Massachusetts General Hospital (MGH) : http://www.massgeneral.org/children/services/treatmentprograms.aspx?id=1723. I don't think MGH would have sought him if he wasn't on to something.

Since listening to his presentations a few years ago, I've become aware of 1) the huge impact our gut microbiome has on our health (it is the largest part of our immune system). , 2) the impact our food choices has on our health (gluten, GMO's, dairy, sugar, etc.), 3) how we have been "programmed" to eat foods with little to no nutritional value (fast food/processed foods), and 4) how our governments, pharmaceutical companies, food processing/agricultural companies have decided that large amounts of "food", regardless of it's nutritional value and contamination with pesticide/herbicide/genetic modification, have been allowed into our food supply without our knowledge of it's true safety.

I recently watched a documentary on (I think) youtube filmed by two college buddies. The video is named King Korn and can be viewed here:

It is another wake up call among so many others.
Not only is GMO the norm in the US for corn, the feeding of livestock (beef, pork, chicken, etc) of this corn doesn't help. High fructose corn syrup is another huge money maker for the industry. I had previously been aware of BT corn - but was previously unaware of other GMO products like Liberty Link corns: http://www.bayercropscience.us/products/herbicides/liberty/

IMHO, we've all been guinea pigs. Like everyone else, I just want my life back!

 

[heapsreal]

I dont understand how such a low percentage of people were found with hhv6 as its generally said that a high percentage of adults have hh 6??

 

[Daffodil]

is it the case that lipkin found no active pathogens (such as HHV6, EBV, etc), or is it the case that he did not find them in almost everyone with CFS? i think it is the latter, and indicates that these ubiquitous infections are not the root cause of CFS. this doesn't necessarily mean that it is not helpful to treat them

 

[SOC]

I dont understand how such a low percentage of people were found with hhv6 as its generally said that a high percentage of adults have hh 6??

I'm assuming he means no active hhv6, ebv, cmv. These viruses are ubiquitous, but latent in the vast majority of the population. HHV6, in particular, is tissue-based (I think) so active infections don't always show up in whole blood.

 

[Bob]

About one-day and two-day CPET testing. I can't imagine that one-day CPET testing, in itself, will give useful results. But if done on a large scale, who knows, it might bring us something useful.

The two-day CPET testing is a post-exertion exercise test. i.e. the second-day exercise test is carried out post-exertion (after the first-day test.) So the second-day CPET test is able to test for post-exertional symptomatic exacerbation (i.e. post exertional malaise or PENE.) The first-day test can't really test for post-exertional symptomatic exacerbation.

Unger is only doing a one-day CPET test, but she is carrying out online cognitive tests up to 48 hours after the exercise test. So she is carrying out a post-exertion cognition test. This, I think, may be an effective post-exertional symptomatic exacerbation (PEM/PENE) test, and I think perhaps it could bring us some very useful results. She has also indicated that she is considering carrying out post-exertion resting heart rate tests, with the theory that ME patients' heart rates don't follow a normal course after exertion.

I'm not making excuses for Unger not including a two-day CPET test, but just pointing out that she is including a post-exertional symptomatic exacerbation test, in the form of post-exertion cognition tests. That's my interpretation anyway.

 

[Otis]

I haven't been following this closely. I would fit into a group who wouldn't be able (or want) to do even a single test. However, I could see how the double test could still be useful: it could reduce heterogeneity in studies. If one then does further testing e.g. some sort of blood testing, on the group with the abnormal test results, hopefully results would be more consistent than if one didn't check them/stratify them in this way. The more severely affected could then have the blood test which had been developed, without having to do exercise test.
(perhaps I'm stating the obvious).

We're thinking alike, I believe. That should really worry you. I absolutely think we should be doing exercise testing and I strongly believe it should be two days.

Unger said:

We chose the one-day test so that more patients could be tested.
...
The two-day test would require an additional overnight stay for those patients who travel long distances to attend clinic and excludes those who are most severely affected because of the heavy physical toll.

I don't find this statement show insight into the most severely affected. The most severely affected can't travel. let alone take an exercise challenge.

As I've said before: I believe that the vast majority of people who can travel for a single day CPET can handle the second day on the bike. We really need the best data we can get and I think two day CPET test gets us there.

I just want all involved to think about the more severe all the way along. I think many, many opportunities have been wasted in not collecting symptom severity and attempting to correlate it to test results. You read many more papers than I (cognitive problems are catching up with the physical) so you're probably in a better position to comment on that supposition.

Hopefully a blood test will get developed, but I think we need to stop losing opportunities to collect symptom severity and that we need to get the best data possible from this CPET testing.

 

[Dolphin]

Thanks Otis.

I just want all involved to think about the more severe all the way along. I think many, many opportunities have been wasted in not collecting symptom severity and attempting to correlate it to test results.

I have a feeling there is some published evidence that symptom load (severity/number of symptoms) correlating with severity of functional impairment - it's past my bedtime so not going to try to think about this atm..

Also, we have evidence from a few studies that symptoms correlate with something physical e.g.

Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome.

Richards RS, Roberts TK, McGregor NR, Dunstan RH, Butt HL.

Redox Rep. 2000;5(1):35-41.

 

[Otis]

I had my testing done at Ithaca College by Dr. Betsy Keller. Ithaca is about a 4 to 5 hour drive from where I live. I can't drive anymore, so a family member took me up there. The next day I did Day 1 of the test. I did not feel rested going in, and used my wheelchair in order to save energy for the test itself. The following day was Day 2 of the test, and my "escort" drove us home after that test. I found it to be excruciating (for all my symptoms) and it took me 3 weeks to get back to baseline. It was worth every minute of hell.

I don't think that having the patient be well rested on day 1 is critical. The goal is to capture the drop in function on day 2. Although no one has published data on what a third test day would be, I suspect we would continue to drop in numbers every day we were tested until we were too sick to perform the test. Being in an all out crash on day 1 is not ideal, but being crashy (for lack of a better word) from travel may not skew results too badly. Day 1 is really an equalizer. The patient needs to be crashed on day 2. You ensure that through day 1.

Thanks for the insight.

Was the testing itself excruciating, or was it the PEM, or both?

I've been confounded by Klimas/Sol patients here making it sound like an AT bicycle test was wasn't very taxing and didn't seem come with much of a post-test price. "Excruciating" is much more what I would expect of an exercise challenge test.

 

[Daffodil]

in demeirleir's videos, he seems to imply that there is quite a bit of evidence gathered now, that implicates HERV. I hope he is right. and I hope drug companies take notice - quickly.

 

[Bob]

Who has tried and failed to replicate Dr. Snell's research?

Thanks for picking me up on that, Ember. It made me go back and look at the details of a presentation that Dr Snell made, and it seems that I may have misinterpreted a slide, and I think I was wrong to make that comment about other researchers not being able to replicate his research. It seems that he may have been referring to different types of research not being replicated. I'm not sure what he meant, and I don't know why he included it in his CPET testing presentation. (Apologies for the misinformation.)

If interested, see video at 83:54, and corresponding slide 177:
http://www.tvworldwide.com/events/f..._archive.cfm?gsid=2251&type=flv&test=0&live=0

But I think that Dr Snell hasn't exactly replicated his own research, although I can't be certain about the details of this without studying his literature in closer detail. He says in the video that he got 'slightly' different results in his most recent study from his previous study which had n=6. This isn't exactly surprising with only 6 participants in the previous study. (Watch at 82:50).

I think in the past he used to talk about VO2 max as being the test of choice, but the latest study found the most useful results were found when testing anaerobic threshold work-load, and not VO2 max. VO2 max was not such a useful test in the latest study. I'm not sure if the latest study found any significance in the VO2 max outcomes, but I need to study the results in closer details to be certain. Too tired to do that right now. Has anyone else studied the recent study enough to know the details for VO2 max?

We've explored some of the results previously in a discussion thread:
http://forums.phoenixrising.me/index.php?threads/new-dr-snell-paper-on-exercise-and-cfs.24050/

 

[Bob]

From the abstract of Snell's latest paper:

ConclusionsThe lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, results from the second test indicate the presence of a CFS related post-exertional fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in individuals with CFS. A second test may be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.

http://ptjournal.apta.org/content/early/2013/06/26/ptj.20110368.abstract

 

[Ember]

It made me go back and look at the details of a presentation that Dr Snell made, and it seems that I may have misinterpreted a slide, and I think I was wrong to make that comment about other researchers not being able to replicate his research. It seems that he may have been referring to different types of research not being replicated. I'm not sure what he meant, and I don't know why he included it in his CPET testing presentation. (Apologies for the misinformation.)

If interested, see video at 83:54, and corresponding slide 177:
http://www.tvworldwide.com/events/f..._archive.cfm?gsid=2251&type=flv&test=0&live=0

When Dr. Snell speaks here of "failure to reproduce," he's speaking of the patients' failure to reproduce on day two the CPET results that they achieved on day one. He isn't referring to other researchers' failure to replicate his research. In fact, he challenges other researchers to find out why patients can't reproduce their day one results. He suggests "lots of reasons" for his findings and lists on his accompanying slide (177) inflammatory cytokine elevation (Klimas et al., 2007), neuroendocrine dysfunction, cardiovascular abnormalities and mitochondrial abnormalities (Whistler et al., 2006, Wong et al., 1992).

 

[Otis]

I'm assuming he means no active hhv6, ebv, cmv. These viruses are ubiquitous, but latent in the vast majority of the population. HHV6, in particular, is tissue-based (I think) so active infections don't always show up in whole blood.

Yep, so far he's only looked in whole blood and CSF and mostly (exclusively?) using his high throughput sequencing. Since he found HHV-6 in a few instances and nothing else we consider common in M.E it makes me wonder about his testing. He hasn't done any serology (antibody) testing yet which is where my virus tests come back positive. I'm pretty sure they look for response to proteins and not complete viral sequences. As a result these tests can respond to something similar to "known" viruses, or perhaps to a mutated version of a known virus. Dr. Lipkin knows a billion times more than I but perhaps the "active" virus tests he's done are too specific. Viruses are always mutating. Or perhaps there's been a systematic issue with taking, shipping or storing of samples.

I've tested positive for EBV reactivation by serology and have multiple reasons to have faith in the results. That virus has had a looong time to mutate in me and it likes to hide as well.

He has a lot more testing to do but I have to ask. What would happen if the world famous Virus Hunter slammed the door on most or all viruses in M.E. prematurely. Talk about a setback.

 

[vli]

He has a lot more testing to do but I have to ask. What would happen if the world famous Virus Hunter slammed the door on most or all viruses in M.E. prematurely. Talk about a setback.

I am terrified of this.

 

[acer2000]

The issue is that the anaerobic threshold drops on the second test. Thats what's key. The way I understand it, other illnesses (and deconditioning) can show low V02 or low AT, but it's static. The fact that the AT drops the second day is the significant differentiator.

 

[Sasha]

if a single test is to substitute for a double test, we need to be sure its adequate.

Wasn't Dr Enlander doing a study of response to exercise? Was that a 2-day test? If we can get more data, that might help convince Dr Unger.

 

[Snow Leopard]

I dont understand how such a low percentage of people were found with hhv6 as its generally said that a high percentage of adults have hh 6??

I don't know, but I tested negative to hhv6/PCR when I was tested in the USA too...I don't remember seeing any large community based studies testing for HHV6 (I could be wrong). There are tales and then there is science.

 

[Firestormm]

I don't know, but I tested negative to hhv6/PCR when I was tested in the USA too...I don't remember seeing any large community based studies testing for HHV6 (I could be wrong). There are tales and then there is science.

Only wanted to add really, what has already been said earlier on the thread: that we are also individuals and therefore different.

We meet on forums such as this and occasionally share results and discover others have similar findings: what they don't mean is that the finding is significant to the disease ME/CFS.

Science and Lipkin's work does. We can and should critique it and it will need replication; but now we have the full transcript and Simon's review is now available.

I hope it helps to better explain some of the confusion being expressed due to the poor quality recordings that had been made available.

Hopefully we don't have to wait overly long for the publication of this research to appear.

Lipkin finds biomarkers not bugs