News of replication of WPI XMRV study...

[kurt]

OT - discussion while we wait for news...

Hi, Kurt.

But what is disturbing the hypothalamus?

I think the problems with the hypothalamus in CFS can be accounted for by glutathione depletion there. We have good lab evidence for glutathione depletion in CFS, and it is known that the brain has a very meager ability to convert methionine to cysteine, so the brain is one of the organs that goes low in glutathione first when the body has a problem with it systemically.

Rich

Hi Rich,
Certainly that would make sense that GD is somewhere in the CFS brain pathologies. So following that logic, given that the hypothalamus is partly inside the BBB (the emitters and a few receptor neurons are outside), perhaps nature designed that system to expect fewer insults. Then when the BBB gets compromised (by co-infections perhaps), the hypothalamus loses GSH and becomes sluggish. Hmmm.

I like that model, very elegant. Simple yet could theoretically account for pretty much every major part of CFS. And if the Hypothalamus had low GSH and functioned sluggishly one would expect it to become easily overwhelmed by any type of ordinary input. Here is a nice summary of those inputs: http://thalamus.wustl.edu/course/hypoANS.html

So many top CFS researchers and practitioners seem to have danced around this type of model for CFS. And certainly multiple co-infections, including persistent retroviral forms, could be depleting GSH in the brain and thus altering functions of the hypothalamus. Wasn't there a study though that found GSH levels normal in the brains of PWC? I wonder if they looked at the hypothalamus, that organ is particularly susceptible probably, given it is both inside and outside the BBB.

 

[George]

Hi all, following some of the discussion on this thread, I am wondering if when the replication studies come out the most important thing for us to look at initially is the results are for the control groups.

I am thinking this because there seems to be so much controvery about how the CFS groups are selected and whether we all have the same illness or subgroups etc. that it may be differerent to interpret different results from different studies if they have selected their different cohorts differently.

. . .

I also have not seen anything released from WPI about antibodies in the control groups compared to CFS cases. This seems odd to me. Surely the level of exposure in controls measured by antibodies would have to be higher than PCR alone. It could reduce the argument for XMRV as a cause of CFS if positive antibodies were found at high rates in the healthy population.

Thoughts anyone?

Megan.

Hi Megan

In the original study they did not test for antibodies in either group.

In the second round of testing which is not published but is on the WPI web site they state;

that they set aside any XMRV sera positive healthy controls (meaning they tested positive in the regular test blood PCR test) Then using these rest of the controls and CFS samples they tested both for antibodies and found 0% in healthy controls and 30 of 33 in CFS samples (90 %). They went on to test for past antibody activity as well as something else my brain is having trouble remembering and that's the 95% and 98% numbers that they came up with. Again the controls were 0%. It worth pointing out again that they did remove the original 3.7% of positive samples from the healthy controls.

Hope that answers the question. You can find the exacts on the WPI web site.

 

[Cloud]

Infection.

I agree. After 6 months on Vistide, I not only had an improvement in symptoms and Immune lab values, but my hormone levels came back closer to normal as well. We believe that suppressing the CNS Virus('s), allowed the HPA to function more normally again. My testosterone levels actually rebound into high levels at first before dropping back into normal....Yikes, lol.

I agree also about the conversion of Methionine in the brain. I don't know much about this, but I can say that nothing straightens me out faster than SAMe, which has to do with this process. Problem is that I cannot keep taking it because after 2-3 days I get the same terrible reaction that I get with many meds.....people call it sensitvity, but I don't think that's what it is. It feels more like slamming into a wall.....or like a toxicity. Many things do this to me. Regardless, it does no good to change the dose or the frequency, so I get to feel great for 2 days and that's it. I can certainly tell that SAMe is affecting something that feels very much a core issue with my ME/CFS. I also think that if we were to identify this "wall", we would then be looking the dragon in the face.

 

[Eric Johnson from I&I]

> In the original study they did not test for antibodies in either group.

They did, in both. But it was 50% positive in CFS, not the 95% seropositivity they say they get now with a better assay. Also, I'm not sure if the healthy controls whose antibodies were studied were XMRV+ or -, though more likely they were -.

 

[Esther12]

I expect others have seen this before, but the online materials from science cleared up some points I was confused on (especially the patients selected as part of the science paper).

eg:

http://www.sciencemag.org/cgi/data/1179052/DC1/1

Patient samples. Banked samples were selected for this study from patients
fulfilling the 1994 CDC Fukuda Criteria for Chronic Fatigue Syndrome (S1) and
the 2003 Canadian Consensus Criteria for Chronic Fatigue Syndrome/myalgic
encephalomyelitis (CFS/ME) and presenting with severe disability. Samples
were selected from several regions of the United States where outbreaks of CFS
had been documented (S2). These are patients that have been seen in private
medical practices, and their diagnosis of CFS is based upon prolonged disabling
fatigue and the presence of cognitive deficits and reproducible immunological
abnormalities. These included but were not limited to perturbations of the 2-5A
synthetase/RNase L antiviral pathway, low natural killer cell cytotoxicity (as
measured by standard diagnostic assays), and elevated cytokines particularly
interleukin-6 and interleukin-8. In addition to these immunological abnormalities,
the patients characteristically demonstrated impaired exercise performance with
extremely low VO2 max measured on stress testing. The patients had been seen
over a prolonged period of time and multiple longitudinal observations of the
clinical and laboratory abnormalities had been documented.

 

[aquariusgirl]

ross..sam-e

Ross

Sam-e is a universal methyl donor, and your toxicity reaction makes me think you might get some mileage out of the rich van k or yasko protocols.

Part of the theory is that the methylation cycle gets blocked and by taking nutrients like sam-e and b12 you get it working again, which mobilises toxins...

just a thought

 

[Cloud]

Ross

Sam-e is a universal methyl donor, and your toxicity reaction makes me think you might get some mileage out of the rich van k or yasko protocols.

Part of the theory is that the methylation cycle gets blocked and by taking nutrients like sam-e and b12 you get it working again, which mobilises toxins...

just a thought

Thank you aquariusgirl....I think your absolutely right on. I have felt for a long time that it had to do with an impaired detox system...I was thinking P450. What little I have read about the methylation cycle, I agree it sounds like something I should look into. This "toxic" reaction I get to meds, is my oldest and most unchanging symptom.
I'm sure to find the links when I google your suggestions, but if you have any favorites handy, that would be great too.

Thanks again,

Ross

 

[Eric Johnson from I&I]

If SAMe fix it, why dont it stay fixed? Its probably firing up your monoamine neurotransmitters -- nothing bad is really that bad unless and until your brain says it is, and when its roiling with monoamines, a brain says that everything is good.

Does SAMe stop any symptoms that dont fundamentally consist of pain? Fatigue is pain, malaise is, depression, anxiety, a lot of stuff.

Actually, fatigue can sometimes not involve that much pain, though it usually does. But it always involves energy levels, and energy is also controlled by monoamines.

I used to have one or two-day unsustainable reactions like that to SAMe (I think), DLPA, adrafanil, some serotonergic antidepressants, T3 (dangerous to take if you dont have good knowledge of it), stuff like that. I also have mild bipolar disorder (caused by CFS), which probably helps me make a highly contrasting shift from terrible to great! to terrible when I take those monoaminergic substances.

 

[Eric Johnson from I&I]

Wildaisy, yea verily,

them dawgs mix it up like this

We next investigated whether XMRV stimulates an
immune response in CFS patients. For this purpose, we
developed a flow cytometry assay that allowed us to detect
antibodies to XMRV Env by exploiting its close homology to
SFFV Env (16). Plasma from 9 out of 18 CFS patients
infected with XMRV reacted with a mouse B cell line
expressing recombinant SFFV Env (BaF3ER-SFFV-Env) but
not to SFFV Env negative control cells (BaF3ER), analogous
to the binding of the SFFV Env mAb to these cells (Fig. 4D
and S6A). In contrast, plasma from seven healthy donors did
not react (Fig. 4D and fig. S6A). Furthermore, all nine
positive plasma samples from CFS patients but none of the
plasma samples from healthy donors blocked the binding of
the SFFV Env mAb to SFFV Env on the cell surface (fig.
S6B). These results are consistent with the hypothesis that
CFS patients mount a specific immune response to XMRV.

 

[Cloud]

"If SAMe fix it, why dont it stay fixed"? And that would be the million dollar question.

 

[perovyscus]

SAM-e reduces norepinephrine, which is the primary alertness chemical.

I wish I had more positive or even relevant things to say about XMRV scientifically speaking. HTLV is a retrovirus that has a proven causal link to cancer, and it isn't even tested for or treated. The timetable here is years, not months.

Guess I have to pull myself up by my bootstraps until then

 

[Cort]

Ross, my problem is that I respond well to many things but as my energy starts really getting going I basically fall apart; get really jittery, joints start aching and eventually fatigue, fluey feeling etc. Its as if my body is releasing something thats throwing a wrench into everything.

Anything similar to what you experience?

 

[usedtobeperkytina]

My latest

My latest theory is that we feel the fatigue when our immune system is working. Just as when we get a flu virus (by we, I mean humans), and the flu is doing its destruction for three days. But the sick feeling is from the immune response.

So, I think there is an ongoing see saw battle going on against XMRV in us, also against the reactivated viruses. So the virus is being destructive on our good days. We do too much and the cortisol, hormones or whatever turns on that virus. Then, our immune system kicks in to fight it. And that's when feel fatigue. But, for many of us, our immune system starts to win the battle, and so we feel better. And then we do stuff. And the virus starts replicating from all that cortisol or hormones. And we don't know it. And it is an endless cycle.

This is why we have push and crash. Unlike HIV that wins the battle and kills the host. We are in a constant Vietnam type battle in our bodies.

Call this Tina's #2 hypothesis.

Tina

 

[Martlet]

My latest theory is that we feel the fatigue when our immune system is working.

I've thought that for years. Since getting CFS, my doctor has recommended an annual flu shot. Stops me from getting the flu, but for a couple of weeks after it, I'm crashed. I'm sure that's because of an immune up-regulation.

 

[Eric Johnson from I&I]

Immune activation is often stated to be the cause of basically all symptoms of the flu, though I am not sure how this is demonstrated. Perhaps it is simply concluded from the results of injecting people with cytokines, which results are universally agreed in all published reports to be fluish fatigue, malaise, inactivity, and depression.

 

[Eric Johnson from I&I]

> T3 (dangerous to take if you dont have good knowledge of it)

I was asked about this. T3 can be risky for the heart under certain circumstances. A doctor would know all about this. What I meant is that one should not take it on one's own without knowing all about it, but I forgot to specify that.

 

[Jenny]

Tina's #2 hypo

Hi Tina

I like your hypothesis. It doesn't entirely fit my experience though.

Although my relapses are very occasionally linked to overdoing things, mostly they come completely out of the blue. I can be 95% for months, and not under any stress or in contact with anyone with an infection, and then suddenly one day I feel I have to sleep and that's it for 3-4 months -bedridden with severe flu-like symptoms, severe pain, can only walk a few steps, feeling desperately ill.

The pathogen(s) seem to have a life of their own.

Jenny

 

[duendeni]

Ross, my problem is that I respond well to many things but as my energy starts really getting going I basically fall apart; get really jittery, joints start aching and eventually fatigue, fluey feeling etc. Its as if my body is releasing something thats throwing a wrench into everything.

Anything similar to what you experience?

I sort of feel hyper-sensitive to any kind of stimulation. I don’t know what has gone wrong with my body, but I feel like some process has gone awry - like maybe I releases some kind of chemical, or maybe there is some sort of energy crisis, which pushes me into overdrive.

…………When I rest completely, I feel as though my systems are stabilising and recuperating. My energy level rises, the fatigue lifts, the muscle stiffness and pain abates, the skin sensations and feverishness wane and I feel stronger, calmly alert.

As soon as I start doing some physical exercise/activity, my muscles seize up - I feel as if the muscle stiffness I would experience after running a six hour marathon comes on in minutes. My whole body cramps up , I feel burning in my muscles. I get nauseous, I feel flooded with adrenaline. I get shaky, weak, a crushing headache (my whole scalp and face feels tight). My vision blurs, and I get after-vision. The noise becomes grating and the light gets glaring. My voice becomes hoarse. I get muscle twitches, numbness…now I can no longer concentrate…I feel dizzy, spacially disorientated and on the verge of collapse.

Later when I rest again, I feel poisoned, fluish. I have a sore throat when the stiffness starts to wear off in my throat, and these prickly, itchy, ‘creep crawley’ skin sensations over my body (but especially in my face and limbs) as my muscles start to loosen up again. My muscles now ache and hurt as the stiffnes wanes. I am left with a feeling of groginess and malaise that lasts for days.

I experience this to a lesser extent with mental activity. The more I work, the more my scalp feels tight, the less able I am to conentrate, the more I struggle to think. The more I push against it, the more drained I become and ultimately, my brain seizies up and I get the flushed-with-adrenaline feeling.

I have noticed this can also happen if I watch action films/ horror films, which I just don’t do anymore if can help it. I guess when you watch others engaging in stressful situations, you feel partly engaged in that stress yourself. So your body produces adrenaline or some knid of stress hormone, and it starts the whole cycle going. So emotional stress/anxiety is a no-no too, but the effect of that wares off much quicker for me than any physical activity.

 

[Lily]

That's me too.....

But for a couple of minor tweaks, you've described my experience. It always does me good when I see someone else put it in writing.

Linda

 

[Cloud]

Ross, my problem is that I respond well to many things but as my energy starts really getting going I basically fall apart; get really jittery, joints start aching and eventually fatigue, fluey feeling etc. Its as if my body is releasing something thats throwing a wrench into everything.

Anything similar to what you experience?

Yes, that sounds like the same thing Cort. "Throwing a wrench into everything", is a great way to put it. I have called it "Locking up", "Poisoned", and "getting toxic". Anything I take that "pushes" my system to function better works great for 2 days, then I crash. It feels like pushing the gas to the floor, and then after 2 days push the brake to the floor and hold both down. The same happens with SAMe, except that the initial good response is better than anything else I have ever taken, and it really feels like it's affecting a core problem.