Astounding Norwegian research breakthrough with Rituximab can solve CFS mystery!!!

[Esther12]

I don't have time to check the paper now to see what is the more likely meaning. Although maximum variations of 11% in the control group makes me think that one is talking about numerical changes i.e. a change of 11% equals 11 points; otherwise the maximum changes for the control group look small.

That is a very good point.

Too often with data, I just see the numbers, and stop thinking about what it actually means, or considering if it makes sense. I keep trying noticing this error of mine, but continue making it anyway!

 

[Esther12]

I don't have time to check the paper now to see what is the more likely meaning. Although maximum variations of 11% in the control group makes me think that one is talking about numerical changes i.e. a change of 11% equals 11 points; otherwise the maximum changes for the control group look small.

That is a very good point.

Too often with data, I just see the numbers, and stop thinking about what it actually means, or considering if it makes sense. I keep trying noticing this error of mine, but continue making it anyway!

 

[redo]

This study is only of 30 people and of the 15 that received the drug, only 10 saw major improvements. Some patients have come out saying their experience was anything but good. This is also the case with Ampligen, which has good results in some, but detrimental to others.

Hi Tina,
Which patients have come out saying their experience was anything but good? I find that hard to believe. I'd really like to read/hear more about that.

 

[redo]

Redo your post 20 - in case someone pops in ahead

Just how is the big question now I think. Most ME information is already out on all the major Charity sites, and each as we know (not inexhaustable time and energies) is working with different emphases/aspects/promotions in addition to providing support and guidance for sufferers. W through his position at the Science Media Centre influences the Media (that's what it's for) and from the latest orchestrated attack on ME suffers has solely gained the ears of certain journalists and publications. Not difficult to spot partisanship with the constant ignoring of eg. Prof Hooper's writings revealing the science in ME.

Any thoughts about the way forward ?

(Apologies off-thread - back to Norwegian breakthrough !)

I haven't the health do much reading lately. Thanks for the tip about the Science Media Centre, I haven't heard about them. As for thoughts on the way forward, I think the media could be worked very well with patient stories. Someone getting better from one therapy. Someone getting worse from the CBT stuff. Someone writing Op Eds about the W stuff. How they don't get a representative group of ME patients, as most would reject going to the CBT stuff. And when they sit with this selected group whom think CBT may be a thing for them, they still don't get any impressive results... Getting the message out.

 

[redo]

We have the problem of reconciling these two facts, - ME can occur in epidemics, and it responds to immunomodulation.

Are autoimmune diseases epidemic? Do we see outbreaks of rheumatoid arthritis?
(Rituximab is also used for RA)

Obviously HGRVs are not proven. But we need to look further than an "autoimmune" answer.

If ME is autoimmune something is priming the immune system to malfunction, which is latent in large numbers of the population.

Now this may not be a retrovirus. But you need to look for a widespread agent which relies on a trigger of some kind.
It could be that many people have an underlying immune abnormality, which did not exist a couple of generations ago.

What could that be? And why?

Those are some excellent questions currer. Personally I think that there is some pathogen which is latent (exogenous or endogenous), and gets triggered in ME patients. But, when there is such a strong overlap between ME and RA, why doesn't it happen also in RA, if they share some of the same etiology. I think there are close variations of the same pathogen, with differences in symptoms they produce, and how they're triggered.

About why it's not been here to such an extent generations ago, I think that's also vital to understanding the disease. I got a thread going here about it, weigh in if you'd like. At the moment, I am thinking that a endogenous RV is likely, and that the reason it breaks out now, and not generations ago, is altered immune function due to drastic chances in diet.

 

[Dolphin]

I've edited a post I wrote late last night - I said I wanted to check how they used the SF-36. As the correction might get missed, I thought I'd post it here also:
They use normalised SF-36 scores not just for PCS and MCS but also the 8 SF-36 subscales. So one can't make direct comparisons with the PACE Trial straight away - 10 points is 1 SD so if one gets the SDs for the scales that are not normalised, one can then make the comparison.
The population norms for the Norway can be got from: http://www.sf-36.org/nbscalc/index.shtml .

PF RP BP GH VT SF RE MH PCS MCS oblique Phys oblique
Ment
Score 50.0 50.0 50.0 50.0 50.0 50.0 50.0 50.0
Mean 90.7 84.3 76.4 80.0 70.0 86.4 85.7 78.6 50.0 50.0 50.0 50.0
S.D. 19.2 35.5 25.9 22.4 29.8 22.3 32.8 16.0 10.0 10.0 10.0 10.0
NBS 28.8 40.3 39.8 36.6 43.3 33.7 39.1 32.1 37.0 37.9 34.2 34.8

So divide any of the SDs above by 10 and multiply the result the scores given to convert to the SF-36 subscale scores as more commonly used (although PCS and MCS are generally given normalised). (Ignore first line - I just put a number into the boxes to get there results table).

I presume they used the Norwegian data. The US figures are in Table 1 at: http://www.sf-36.org/tools/SF36.shtml - the SD is bigger for SF-36 PF anyway (23.3). (UK scores are at: http://jpubhealth.oxfordjournals.org/content/21/3/255.full.pdf ).

However, I imagine they used Norwegian or US norms.

 

[Tristen]

Personally I think that there is some pathogen which is latent (exogenous or endogenous), and gets triggered in ME patients. But, when there is such a strong overlap between ME and RA, why doesn't it happen also in RA, if they share some of the same etiology. I think there are close variations of the same pathogen, with differences in symptoms they produce, and how they're triggered.

I agree with you that our symptoms suggest a latent infection, triggered by any number of different possibilities. But I can also say that, at least in my family, there is an overlap with RA. Some people with RA do have me/cfs like symptoms, especially with exertion/stress.

I also know that RA is one of the exclusionary diseases listed in the CCC. And that's what, 12-15 years old now?

 

[snowathlete]

According to Klimas another possibility is that the B-cell is a reservoir for a virus that really matters. The B-cells are the major reservoir for Epstein Barr Virus, a virus that has been linked to ME/CFS several times in the research literature. It is well established in research that mononucleosis trigger ME/CFS in many cases.

- Let us just pretend its EBV for a moment. When were done with our EBV, when you and I had our mono, we are left with roughly one million latent EBV-infected cells. And our immune system handles that. One of the questions that have never been answered in chronic fatigue syndrome patients is, do they have a bigger reservoir than that? Was their primary infection so intense that they have ten million or a hundred million latently infected cells? Because theres going to be a threshold where a normal immune system cant contain latency and cant maintain that virus under control. () Maybe Rituximab simply knocked down the reservoir so intensely so that we got it down under the threshold, and then the immune system could handle it. And that would make sense to me, Klimas said. She stressed that this is just a hypothetical construct without data to back it up, and then adds that she would love to see some before and after cells and serum plasma be sent off from the Norwegian freezers to EBV-wizards like Ron Glasers group.

Personally, I think Klimas is spot on with her second theory, quoted above. Im absolutely convinced that the origin of ME/CFS is EBV. I know that not everyone will agree with me, but i think the facts will prove me right, years down the line.

 

[FancyMyBlood]

Personally, I think Klimas is spot on with her second theory, quoted above. Im absolutely convinced that the origin of ME/CFS is EBV. I know that not everyone will agree with me, but i think the facts will prove me right, years down the line.

Whatjustifications do you have to be absolutely convinced about that? I partly ask this question because I don't believe there are justifications to make that claim. Afterall, if it was that clear-cut the pathophysiology of ME/CFS would be well-known and treatment options would be available or in progress.

For the other part, I'm interested in data about a possible connection of EBV-ME/CFS that I'm not aware of.

 

[Andrew]

Personally, I think Klimas is spot on with her second theory, quoted above. Im absolutely convinced that the origin of ME/CFS is EBV. I know that not everyone will agree with me, but i think the facts will prove me right, years down the line.

If it's in the B cells, it should findable with blood tests. But so far, not luck.

 

[richvank]

Personally, I think Klimas is spot on with her second theory, quoted above. Im absolutely convinced that the origin of ME/CFS is EBV. I know that not everyone will agree with me, but i think the facts will prove me right, years down the line.

Hi, snowathlete.

Active EBV is definitely found in quite a few PWMEs. It does reside in its latent state in immortalized B cells. Rituximab does knock out B cells.

Based on the work of Palamara et al. at the University of Rome, a healthy ratio of reduced to oxidized glutathione is able to prevent proliferation of herpex simplex type 1 by preventing the formation of disulfide bonds in glycoprotein B. The other herpes family viruses, including EBV, also have glycoprotein B. I conclude from this that a healthy ratio of reduced to oxidized glutathione also suppresses proliferation of EBV.

As I've posted before, I suspect that the Rituximab treatment overcomes the inflammation that is being produced by the overactive B cells (due to the known Th2 shift in ME/CFS), and this allowed glutathione to normalize in the patients who experienced recovery from this treatment. Recovery of glutathione would suppress not only the herpes family viruses, but would also restore cell-mediated immunity, which is necessary to defeat other viruses as well as intracellular bacterial infections (mycoplasma, chlamydia and rickettsia) and fungi, including yeasts. All of these are found in various ME/CFS patients. EBV is not the only pathogen found.

Best regards,

Rich

 

[Tristen]

Maybe it's more about virulence rather than type of pathogen hiding out in the B cells. I thought several bugs liked that particular hiding place. Two I know have been found in B cells and cause pathology are Lyme and HCV. I'm only going on recall with the Lyme, but here's a link on the HCV. New Japanese study. They discuss using Rituximab with the Standard of Care for treatment.

http://www.hindawi.com/journals/ah/2011/835314/

Something like 5% of the HCV community have me/cfs. Obviously HCV alone doesn't cause me/cfs in everyone, but 5% is extremely high compared to the general population.

 

[serg1942]

Dear Rich,

Its been very long since I dont read or write here. I have experienced a HUGE improvement with GcMAF, that has allowed me to enroll at the medicine school, and I am devoting all my energy to my new life of student. I estimate I am at my 60%, but I feel a bit better after every weekly injection, so I think I still have a good margin of improvement ahead of me time will tell!

The thing is that I am just trying to catch up with this new study of Rituximab on CFS, and I wanted to thank you for having, as always, given a step back to see the whole elephant, and as a result, having given in a so scientifically way a convincing explanation for the Rituximab study results, again, matching them with your GD-MCB theory.

As Sushi and others have asked you, Id really like you to try to give a similar possible explanation for the so good results GcMAF is showing Unlike Rituximab, this is a non-toxic natural protein our immune system work with, and its results seem to be impressive for many of us, and seem to be permanent so far

I cannot find an explanation for the so good results of GcMAF if we think of CFS as an autoimmune disease, unless some exogenous or even endogenous retroviruses are actually the real cause behind the autoimmunity, as some researchers have speculated May I ask whats your take on this?

Well, thanks in advance for your always wholehearted and priceless help,
Best wishes,
Sergio.

 

[mellster]

The immune system is hard to fool and it could very well be that they will find the reason for why it is shifting towards Th2, but if it stays imbalanced for too long and the dial has turned too much, it weakens Th1 and increasingly causes opportunistic viral infections and what is seen as auto-immune reactions to stressors. Also, the fact that a lot of people experience at least temporal improvement from taking ABx (and I am no fan of ABx) could hint to involvement of bacteria as well as well as an immune deficiency as a lot of ABx have immune modulating properties.

Dear Rich,

Its been very long since I dont read or write here. I have experienced a HUGE improvement with GcMAF, that has allowed me to enroll at the medicine school, and I am devoting all my energy to my new life of student. I estimate I am at my 60%, but I feel a bit better after every weekly injection, so I think I still have a good margin of improvement ahead of me time will tell!

The thing is that I am just trying to catch up with this new study of Rituximab on CFS, and I wanted to thank you for having, as always, given a step back to see the whole elephant, and as a result, having given in a so scientifically way a convincing explanation for the Rituximab study results, again, matching them with your GD-MCB theory.

As Sushi and others have asked you, Id really like you to try to give a similar possible explanation for the so good results GcMAF is showing Unlike Rituximab, this is a non-toxic natural protein our immune system work with, and its results seem to be impressive for many of us, and seem to be permanent so far

I cannot find an explanation for the so good results of GcMAF if we think of CFS as an autoimmune disease, unless some exogenous or even endogenous retroviruses are actually the real cause behind the autoimmunity, as some researchers have speculated May I ask whats your take on this?

Well, thanks in advance for your always wholehearted and priceless help,
Best wishes,
Sergio.

 

[redo]

Richvank, according to your theory can you perform a thought experiment of giving Rituximab to autism patients?

I think that's a great idea Fla. The numbers of autism patients are so great, that they could simply try to harvest some data when someone goes in for lymphoma treatment (with Rituximab). It's just a shame that it wont be done... If it'd work, it would bring some valuable clues.

 

[redo]

Multiple Sclerosis has occurred in cluster outbreaks that are the same or similar to infectious outbreaks. One was on the Danish Faroes Islands between 1943 and 1949 when British troops arrived there in that previously isolated place.
Also some researchers speculate that there M.S might have an infectious cause because it's epidemicology and the numbers of people getting ill over the years with it is more similar to that of infectious deseases rather than a non infectious illness *

So here you've got a autoimmune illness that is possibly infectious.

The CFIDS Foundation has also said in it's newsletters that it thinks M.E is an autoimmune illness.

*Citations: John Kurtzke 1986 paper and a couple of things I read in a book called "The Rise and Fall of of Modern Medicine"

I'm more optimistic about this than I was about the XMRV virus.

This was fascinating redrachel. Both the latter, about the CFIDS position, but also the outbreaks of MS. Do you have any links to where I could get more info on this?

 

[oceanblue]

They use normalised SF-36 scores not just for PCS and MCS but also the 8 SF-36 subscales. So one can't make direct comparisons with the PACE Trial straight away - 10 points is 1 SD so if one gets the SDs for the scales that are not normalised, one can then make the comparison.
The population norms for the Norway can be got from: http://www.sf-36.org/nbscalc/index.shtml .

My brain is addled right now so I shouldn't really be trying to read posts anyway, but this looks important.
2 Qs
1. where does it say they used norm-based scoring? I missed that. Obviously it negates all my conclusions, but thanks for pointing it out!
2. can you check my estimates conversion of baseline and max change SF36 scores for the rituximab group to the 0-100 scoring method?
I made the baselines PF score around 60, which seems quite high for a clinical trial patient group. 28% net improvement would give a very impressive +17points on the PF scores, assuming the percentage applies to 0-100 scores.
thanks

 

[Dolphin]

They use normalised SF-36 scores not just for PCS and MCS but also the 8 SF-36 subscales. So one can't make direct comparisons with the PACE Trial straight away - 10 points is 1 SD so if one gets the SDs for the scales that are not normalised, one can then make the comparison.
The population norms for the Norway can be got from: http://www.sf-36.org/nbscalc/index.shtml .

My brain is addled right now so I shouldn't really be trying to read posts anyway, but this looks important.
2 Qs
1. where does it say they used norm-based scoring? I missed that. Obviously it negates all my conclusions, but thanks for pointing it out!

I should perhaps have been a little less definite. It looks to me like they used norm based scoring.
For example, they say:

The SF-36 short form analyses before intervention confirmed a
low quality of life particularly for the dimensions related to
physical health, while the subdimensions mental health and
role emotional showed higher baseline values.

The scores for mental health and role emotional aren't particularly good unless one uses norm based scoring.
Generally role physical will be the lowest on raw scores for people with CFS but because it is has a large SD it won't be so low on norm based scoring.
It seems a big coincidence that none are over 50 or below 20. It just looks like norm based scores.
Maximum variations look quite small e.g. PF, MH, etc.

A question has now been asked on this.

2. can you check my estimates conversion of baseline and max change SF36 scores for the rituximab group to the 0-100 scoring method?
I made the baselines PF score around 60, which seems quite high for a clinical trial patient group. 28% net improvement would give a very impressive +17points on the PF scores, assuming the percentage applies to 0-100 scores.
thanks

If they used those particular Norwegian norms, it would be 60 (=90.7-30.72).
I think there's a good chance they used US norms - the norms that were given with the package say. I think that is not uncommon e.g. I remember reading that a Scandinavian country had a PCS or MCS of 54 which couldn't happen if they used their own population.
If they did that, the baseline scores for physical functioning would be (approx.) 46.92 and 49.25.
Hopefully the authors will answer the question and we will get the answers to these questions.

 

[kheopz]

Derek Enlander and David Bell is attempting to replicate the retuximab study in the us.
Very good news.
Here is Bells comment on the initial study
http://www.youtube.com/watch?feature=player_embedded&v=petcvu53S0w

 

[sensing progress]

Derek Enlander and David Bell is attempting to replicate the retuximab study in the us.

Source please?