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What might remissions mean?

Kyla

ᴀɴɴɪᴇ ɢꜱᴀᴍᴩᴇʟ
Messages
721
Location
Canada
Not much. I think the evidence for gut barrier function having anything to do with human autoimmunity is close to zero. Unfortunately this sort of speculative idea that would once be had over a glass of beer is now being used to make money by review journals and they don't mind how little evidence there is.

As far as I know the gut barrier has nothing to do with self tolerance at all.

The zonulin research seems to be pretty well respected in regards to Celiac disease.
 

Jonathan Edwards

"Gibberish"
Messages
5,256

That's the same guy going on about his idea. In Coeliac the mucosa gets damaged by the autoimmune reaction and then becomes permeable as far as I know. So the zonulin has nothing to do with the autoimmunity to tissue transglutaminase - which never crosses the epithelium anyway because it is a self antigen. I am not sure what he is trying to say but it doesn't look to me to make much sense.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
That's the same guy going on about his idea. In Coeliac the mucosa gets damaged by the autoimmune reaction and then becomes permeable as far as I know. So the zonulin has nothing to do with the autoimmunity to tissue transglutaminase - which never crosses the epithelium anyway because it is a self antigen. I am not sure what he is trying to say but it doesn't look to me to make much sense.

So if leaky-gut treatment improves at least some symptoms for some people with ME, this may just be due to tackling a downstream effect of autoimmunity?

Alternatively, leaky gut may produce (all) ME symptoms via a non-autoimmune mechanism?

For myself, I don't favour an infectious cause for my illness. Like so many others, I have a low body temperature, and would normally expect an infection to cause a high temperature (but there are probably exceptions). OTOH, a chronically low body temperature might partly explain the persistence of an infection - perhaps we can't clear the infection due to inability to raise our temperature via autonomic means, in which case deliberately raising our temperature could combat it...hmm.

Discussion perhaps more suited to the 'Do MEs cause CFS' thread, but maybe just about relevant here!
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
There are several reasons why treatments lose their effect. Common ones involve adjusting of receptor sensitivity or hormonal balance - like loss of effect of airway dilators in asthma or steroids for inflammation. But I think what you are interested in here relates to diseases where there is a 'survival of the fittest' process going on in either host cells or microbes. For antibiotic resistance the few resistant microbes survive and take over. For cancer the few cancer cells that have mutated a bit more and so similarly become resistant to control take over. In autoimmunity B cells that are resistant to particular therapies may take over. however, fortunately there is not much evidence for rituximab resistance. The annoying thing is that there are some resistant cells right from the start.

When it comes to benefit from treatments in ME there may be all sorts of reasons of these different types I guess.

Have you come across any examples of resistance developing after a single dose of a drug, or of a combination of drugs taken or administered simultaneously?
 

Sea

Senior Member
Messages
1,286
Location
NSW Australia
  • What could remissions, whether lasting an hour, a day, a week, a month or several years, tell us about our illness - an illness that has proven so resistant to permanent recovery for most of us?
By remission I mean something more than improvement - I mean substantially-increased cognitive and physical function, plus improvement in sleep and mood, and decrease in or disappearance of pain, for those who suffer from these. The improvement must include significantly or completely improved resilience to exertion and other things that usually make things worse. The person should feel near-normal again. There should be no PEM.

Individual experiences will also be useful, including what might have led to remission.

In 28 years of illness I've had one remission lasting 4 years. During that time I was near normal. I was working 3 days a week, added 2 children to our family, had energy for hobbies, exercise and family life. My deterioration was slow over several months following a flu-type virus when my youngest was around 1 yr old.

What led to the remission? I can't say for sure if any/all/none of the following caused the remission but it happened soon after:
- I had all my mercury amalgams removed
- I had a root canal filled tooth removed, another tooth that was beyond saving without a root canal therapy removed and wisdom teeth removed.
- I was given an iv infusion of Vitamin C
- I was given a detox protocol to follow which included fasting and use of a product called Ultraclear.

Since relapsing I've tried Ultraclear again and it made no difference.

Another interesting piece of the puzzle (which doesn't happen any more but did for many years) is that I would be able to think clearly, remember things properly, feel normal energy and be able to do more things without payback for several days whenever I had a cold. It didn't make a difference whether I did lots of stuff while the energy was there or rested throughout, a few days into the cold I would return to my usual ME/CFS state.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
In 28 years of illness I've had one remission lasting 4 years. During that time I was near normal. I was working 3 days a week, added 2 children to our family, had energy for hobbies, exercise and family life. My deterioration was slow over several months following a flu-type virus when my youngest was around 1 yr old.

What led to the remission? I can't say for sure if any/all/none of the following caused the remission but it happened soon after:
- I had all my mercury amalgams removed
- I had a root canal filled tooth removed, another tooth that was beyond saving without a root canal therapy removed and wisdom teeth removed.
- I was given an iv infusion of Vitamin C
- I was given a detox protocol to follow which included fasting and use of a product called Ultraclear.

Since relapsing I've tried Ultraclear again and it made no difference.

Another interesting piece of the puzzle (which doesn't happen any more but did for many years) is that I would be able to think clearly, remember things properly, feel normal energy and be able to do more things without payback for several days whenever I had a cold. It didn't make a difference whether I did lots of stuff while the energy was there or rested throughout, a few days into the cold I would return to my usual ME/CFS state.

I used to feel much better in the early days if I had a cold or flu. But then I stopped getting them. I am guessing that I only got them in the first 3 years, as the 3-year mark is when cytokine levels change, notably many going from high to low, according to Lipkin and Hornig's research. When I finally find the time to digitise my health diaries I may find out.
 

greeneagledown

Senior Member
Messages
213
@deleder2k --
Here's what I envision might be a good strategy for an ME patient once we know that Rituximab is effective:

1) Get a year's worth of Rituximab using the same schedule as is being used in the big phase 3 trial. That year of infusions is probably enough -- if it weren't, they wouldn't be pursuing it.

2) After the 6th infusion (the one at the 12-month mark), stop getting any infusions and wait for a relapse to see how long you can go without more Rituximab.

3) Once you start relapsing, repeat the 12-month Rituximab cycle (assuming your first response was large enough and long enough to make Rituximab a viable long-term treatment for you).

4) Now you know how long a year's worth of Rituximab lasts you, and in the future, you can start new 12-month cycles right before you know you would start relapsing. That way, you go as long as possible without getting more Rituximab but you never relapse. That allows your good antibodies to recover and reduces the risk of major infection. I believe this is done in RA, and that the amount of time before relapse tends to be the same for an individual patient after each course of Rituximab.

The only layer of complexity I might add is that if your symptoms are still improving at the time of the 6th infusion at 12 months -- in other words, if your response hasn't stabilized -- maybe it might make sense to get one or two more infusions at 15 and 18 months. In RA, I believe the experience has been that the longer you keep the patient without b-cells, the greater the chances of long-term remission. Unfortunately, it also increases the risk of major infection.

Goes without saying that I'm not a doctor, this isn't medical advice, wait for the phase 3 results, insert legal disclaimer here, please don't sue me.
 
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Hip

Senior Member
Messages
17,820
There have been lots of studies of starving people with RA or feeding them elemental diets of glucose and amino acids and suchlike - which is about as much exclusion as you can get - and not much happened. People tend to feel better to begin with but the disease itself does not seem to change.

Would you know how the results of these studies were statistically processed?

Could it be the case that dietary interventions many have improved symptoms in some RA patients, and worsened them in others, so that when in a study you average over all patients, no overall improvements would be seen, even though such interventions may have helped certain individual patients?


I also wonder whether such statistical averaging over all patients within an ME/CFS study might mask the actual benefits of a drug or supplement tested on ME/CFS patients. You often see on these forums that the same medication which leads to marked improvements in some patients may significantly worsen others. So again, if you just took the average result, you would conclude that the drug does not benefit ME/CFS, even though it may do for certain patients.
 

MeSci

ME/CFS since 1995; activity level 6?
Messages
8,231
Location
Cornwall, UK
Thanks to @Hip for this post in another thread, which describes Dr Goldstein's views on mechanisms of tolerance to drugs (maybe they could also apply to failure of other types of treatment after initial success).

The thought of brain hypoperfusion sounds a little worrying though.