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OI encompasses any symptoms you get when upright. Fainting upon immediate standing or some sort of localized pain when upright is by definition OI. But I think we agree that when we refer to the syndrome of POTS we are not referring to those things. We are referring to things like getting more...

Yes, I don't know if all the controls are like that or just this study. My understanding is they get referrals for all sorts of exercise intolerance not just ME/CFS. And out of the group that doesn't meet the criteria for ME/CFS they use some of them for controls. So I don't think it is as bad...

I think that is a very good point. I wonder if the bodies response to low cardiac output and low RAP are different. But I find it hard to produce a single story too. I do think the results of low RAP during exercise are so pronounced that if they hold up they must be somehow related to ME/CFS.

I know there are multiple discussions going on on more than one paper but I thought I'd add some comments because I think it is worth discussing. Systrom used controls who had some exercise intolerance but who didn't have ME/CFS or another condition is known to alter those parameters. So I...

The low right atrial pressure only occurs when upright and undergoing the exercise challenge. Whatever is going on it seems like gravity is a critical factor in driving the lower RAPs. If there is increased venous compliance couldn't that cause a larger drop off in venous pressure back to the...

I think the shunting is a different category to the low right atrial filling pressures not the cause. Most have low RAP but some seem to have a peripheral limitation of oxygen reaching or being used by the muscles.

Agreed, it does feels like there are treatments for OI/POTS that do frequently help people even if they didn't work for me. Here is a small trial of Ivabradine that seems to provide positive results. https://www.sciencedirect.com/science/article/pii/S0735109720381316

This doesn't make much sense to me. Of course there is some part of the brain that processes orthostatic symptoms otherwise they wouldn't be experienced. Since these symptoms are different from those experienced from heat or pain they are unlikely to be produced by the same areas/neurons that...

If there is a protein that is more frequently expressed by microglia in people who have conditions effecting the brain, would it not be useful to know if that increased expression occurs in ME/CFS? There seems to be good evidence that TSPO is elevated in certain conditions and after brain...

If the data set featured many healthy individuals without ME, you'd expect the data to look more like the control cohort. The genes they identified are different from a random sample, so would be unlikely to occur if no one had a disease. If a handful of healthy controls were added into the...

Agreed that number of symptoms is a strange way to gauge OI. I might have 6-8 symptoms after standing for 10 minuets but of those only dizziness, palpitations and my feet getting very red and itchy are significantly uncomfortable. Perhaps they should have measured the self reported difference...

Appreciate the explanation and I agree with you on the definition of inflammation and its lack of presence in ME/CFS. I think it is useful to have the evidence for inflammation spelled out at those different levels. It would be interesting to see what reasons advocates of inflammation would give...

It isn't a matter of brute fact, the conclusion one draws depends entirely on how the evidence is intrepretated. Evidence is not some objective entity that points towards one true conclusion, evidence means something because a mind interprets it as changing a point of view. If these...

My conclusion is that there is no universal standard of evidence that makes something convincing. What conclusion you draw is based on how the evidence fits with your prior experiences and beliefs. I think people can disagree on pretty much any issue and still be reasonable, it is just hard to...

I doubt it, I think the vast majority of people that meet IOM criteria would also meet the CCC criteria. Perhaps there is a difference in the cohorts but it wouldn't be a result of using CCC or CCC and/or IOM. These diagnostic categories allow differences between ME/CFS patients even if they...

One of my first symptoms was strong palpitations after trying to exercise. My fitness at the time was very good so something definitely changed in a short amount of time. Do you think the autonomic nervous system "sensitized" into sending PEM signals when the heart is being used. Or is the...

The biopsychosocial people might disagree, but false sensation is non-sensical. If you are having the sensation it must be real, regardless of its cause. The difference between the pain of losing a limb and neural hypervigilance (if such a thing exists) might be that pushing through the pain of...

Thank you Jonathan for putting this together. Even for patients and researchers who don't have the necessary understanding to grasp the intricacies of the immune mechanisms, the summary of the available evidence is quite useful. I could imagine it being used as a sort of framework for...

I actually really like this idea. It fits well with my understanding of truth as the degree to which some perception meshes with our other interpretations of reality. If we take a simple case like a banana is yellow, if we take the idea of the banana and remove all the yellow what we are left...

The thing that I disagree with is that good/bad is fundamentally different than any other indivisible event. When we think about good and bad it is something that feels completely different than blue/red or hot/cold. But why not think that this difference isn't a result of something about...