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Prof Trevor Marshall
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Our new paper, "Immunostimulation in the treatment for chronic
fatigue syndrome/myalgic encephalomyelitis", has been peer-reviewed and published by Springer's 'Immunologic Research.'

You can download a preprint of the paper from our website:

http://AutoimmunityResearch.org/preprints/2013-Lindseth-ImmunologicResearch.pdf

Links to the PubMed and Springer pages:

http://www.ncbi.nlm.nih.gov/pubmed/23576059
http://link.springer.com/article/10.1007%2Fs12026-013-8413-z

Don't forget the Transcript of Inge's presentation at the International Congress on Autoimmunity, which formed the basis for this publication, but makes a more patient-friendly read:

http://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf

And Inge's YouTube presentation:

http://www.youtube.com/watch?v=2IMdAV6SIMU

Thanks to all who helped us get our efforts to this point, for helping us build a solid basis for moving forward into mainstream consciousness.

..Trevor..

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I am working my way through the 22 pages! I'm on page 7. Congratulations on the paper.

Deb

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Awesome! Congrats!

jezzer
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And from me too:)

mvanwink5
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Dr. Marshall,
Two points:
1. From my recent 25D serum level drop to 12 ng/ml it feels like 25D is not a mild immune suppressor. I can see at higher dosing, after the VDR is blocked or significantly disabled, that it would appear as a mild immune suppressor, but at the onset of engaging as an antagonist it would seem to be as powerful as any immune suppressing drug. Also given the very high affinity 25D has for the VDR, how can it not be seen as a dangerous drug?

2. It would seem to me that perhaps there are two elephants in the VDR room with stem cell proliferation and differentiation being the second elephant to the innate immune function of pathogen detection and destruction. With that in mind, perhaps the stem cell flow on effect is the more deadly and diabolical consequence of the intracellular pathogen survival tactic of shutting down the VDR. So, given that, auto immune disease perhaps should be viewed as a stem cell disease as well as an innate immune dysbiosis. In future papers, would it be possible to bring out the dangerous stem cell connection?

I realize from a treatment point of view, the restoration of the innate immune system efficacy is the spear tip, but a clear redirection of palliation regimen mind set from "feel good" to the danger to stem cell viability should finish off the discussion of suppression vs stimulation. That is just my thinking though.

Prof Trevor Marshall
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Mike,
Yes, as I said in the webconference yesterday, supplementation with Vitamin D may finally allow the world to see the stupidity of running evidence based experiments while lacking the underpinning scientific knowledge of what to measure. I fear that supplementation with Vitamin D will prove the biggest mistake that Medicine has ever made. Fortunately, I do see some pulling back of enthusiasm for high dose supplementation at this moment, and we must hope that not too much damage has been done. Additionally, the moves in Europe and Russia toward preventative and predictive medicine has  given us the tools needed to deal with a population potentially made very ill by the supplementation fad.

And yes, it is a very effective immunosuppressant. We can see that in many of the study results.

Medicine routinely uses immune suppression to try and help patients with idiopathic inflammatory disease. It is regarded as a "good thing" by physicians who have been given nothing else (by PhRMA) to help chronically ill patients. To try and completely wipe out that mode of thinking at this time is beyond our reach. I want to put in place the understanding of what to do next, and that is the reason for my PPPM efforts. You will see that coming through clearly in the Chapter we have just written for PPPM textbook which will be presented in Brussels in September.

..Trevor..

mvanwink5
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Dr. Marshall,
I fully realize I am re-preaching from the choir. The point is that it is the initial 25D dietary inclusion that does the damage. Afterwards, 25D looks like a mild or "safe" palliator. The second point will likely require published results on the stem cell issue, but disabling stem cells is not a small consequence of disabling the VDR from a disease, patient consequence point of view. Again, you are the one that mentioned in passing that the VDR expresses the Lrg4 and Lrg6 genes, crucial to stem cell viability. Is there a paper that shows this connection of the VDR to expression of Lrg4 and Lrg6, that you could point to (that is not pay walled) as I would like to read it?
As always, thanks!

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Just finished reading the paper.  Well that sure turns mainstream medical thinking on its head!  :) :) :)

Hope it garners a lot of attention and engenders a ton of discussion and further research by others.  :cool:

Congratulations on putting together such a well-researched and eminently readable paper! :D

Paisleykilt
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Are we allowed to forward this paper to others?  I'd like to send it to Dr. Alison Bested who is in charge of a new chronic diseases clinic opening in British Columbia very shortly.

Prof Trevor Marshall
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Yes, the preprint can be sent to anybody, that is its big advantage compared to a copy bought from the journal.

I am not sure Alison will be so keen to find out she has a CFS expert (Greg) in her back yard. But I guess she will find out eventually :) By all means send it around.

Also, Inge's presentation transcript is available here:
http://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf

..Trevor..

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Congrats to all!  Thanks so much for the time and effort you all put in to this paper.
:):):)

Marysue

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I am so proud and glad for all of us!! Thanks for the hardwork!!! You all deserve a standing ovation and more!!!!!! :dude::dude::dude::dude:

I would like a hardcopy of this journal article. How do I obtain one?

Thanks, Jeannine

Last edited on Sun Apr 14th, 2013 14:12 by Bella

Prof Trevor Marshall
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Check your email, Jeannine :)

Malcolm Jackson
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Firstly congratulations and thanks to all for the hard work in putting this paper together.

Secondly there a typo on page 6?

Cathelicidin possesses antibacterial, antiviral, and
antifungal activity. Human beta-defensin plays a key
role in allowing the immune system to target both
gram-positive and gram-negative bacteria [57]. It also
mitigates viral virulence [57]. Human beta-defensins
HBD-1, HDB-2, and HBD-3 have also been shown to
target the opportunistic yeast species Candida albicans
[58], which has been detected in patients with CFS/ME.
In addition the AMPs play an essential role in the
protection of skin and other organs [59]. They not only
kill microbes but also regulate host physiologic
functions such as in!ammation, angiogenesis, and
wound healing [59].

Should HDB-2 be HBD-2?

Finally. I understand the meaning of peer reviewed but will that convince my Doctor to prescribe Olmesartan? I am one of the many who are self funded in this.

GillyB
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Malcolm, I'm self-funded too, but not because I can't get a prescription.  My &#*%^*$ health insurance won't pay for it at the dosage required, or at all.  For you, the problem is probably the British Health Service.  Your doc is probably leery of getting hammered by the BHS for prescribing off-label.

Malcolm Jackson
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Hi Gilly. You're right. My doctor will prescribe it but has been told not to over prescribe. I have to wait until it's an accepted treatment, till then I have the lottery of whatever turns up from India via Hong Kong paid through a German bank.

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1. For the first time I feel I really understand this, thank you for your excellent work and dedication to find answers for an otherwise "orphaned" group. Could I also get a copy of the journal publication?

2. It is clear, as you say, that conventional medicine only offers immunosuppressive symptomatic treatment which limits the body's ability to eliminate the microbes causing the inflammation in the first place. While immunostimulation may worsen symptoms short-term, positive treatment helps the body eliminate the microbes and actually cure the disease.

2. Could VDR be the only regulator of innate immunity?

3. Why was the article limited to CFS/ME when many other chronic inflammatory diseases share the same symptoms and processes?

4. Many scientists believe that dinosaurs became extinct in response to migrating herds that brought new diseases and microbiomes to existing herds (and vice-versa). When Europeans first came to America, they brought many diseases that had existed for hundreds of years in Europe giving the Europeans a relative immunity, while Native Americans were decimated by these diseases (i.e. smallpox). As there is increased global travel and MacDonald's are springing up around the world, are we taking obesity, diabetes and heart disease to the third world?

5. What about the tendency of Benicar to increase blood levels of potassium, sometimes to dangerous levels? Is this more of a problem when taking more than one 40 mg dose each day as recommended for hypertension? When are we going to get a Benicar generic that's not as expensive?

6. Can probiotics or customized microbial treatment help you acquire a healthier microbiome?

Prof Trevor Marshall
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uvbogden, I am attending a conference today, will respond this evening.

..Trevor..

paulalbert
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Yes, Malcolm, that is a typo. :(

Oh well.

Paul

uvbogden
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I had additional questions that I'll add here:

7. I have Sarcoidosis with many of the symptoms of CFS/ME. However, my calcium, ACE, 25-D and 1,25-D levels are all low. Does this mean VDR does not play a significant role in my chronic inflammation? Or do blood levels not always
represent what's going on in the cells?

8. I'm trying to convince my health insurance company to help pay for my immunostimulation. One thing they will refuse to pay for is anything "experimental". Looking on your websites for details (including the use of multiple doses of Benicar per day) to send them I ran across a number of key words that suggest, even though I know this has been a part of medical practice for decades, that the MP might be experimental: "research foundation", "study site", and "cohort".

Do you have or could you create literature that omits these words and clearly states that the MP is no longer "experimental". It might help others as well to get insurance coverage for the MP.

Last edited on Thu Apr 18th, 2013 19:09 by uvbogden

GillyB
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If you figure out how to convince your health insurer to pay for your olmesartan, please let us all know.  I was turned down flat by mine.

Cynthia S
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Buying thru Canadian on-line companies was about the same price as my copay, without the enormous hassle.  Cynthia

Sallie Q
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uvbogden wrote: .....................key words that suggest, even though I know this has been a part of medical practice for decades, that the MP might be experimental: "research foundation", "study site", and "cohort".
............

Off the top of my head, but in  keeping with the intention to close the Support Forum on curemy
perhaps change MPSS to Marshall Protocol Support Site :?

Prof Trevor Marshall
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@uvbogden

Q2. Could VDR be the only regulator of innate immunity?

No, but it is a primary target of the microbes. They cannot persist while Cathelicidin is expressed. Thus VDR is always knocked down in chronic disease, but by a variety of mechanisms.

Q3. Why was the article limited to CFS/ME when many other chronic inflammatory diseases share the same symptoms and processes?

Because Medicine still likes to think in terms of diagnoses, and we are required to write papers so that they are accepted by peer-reviewers from the Medical community :)

Q4a. Many scientists believe that dinosaurs became extinct in response to migrating herds that brought new diseases and microbiomes to existing herds (and vice-versa)


None, that i have spoken with

Q4b. As there is increased global travel and MacDonald's are springing up around the world, are we taking obesity, diabetes and heart disease to the third world?

In all of my recent presentations I have a slide pointing to this as a pathogenic factor:

http://www.youtube.com/DrTrevorMarshall

Q5a. What about the tendency of Benicar to increase blood levels of potassium, sometimes to dangerous levels?

What makes you say they are dangerous. Oh - you mean they would be dangerous if the patient was not taking benicar - the two sets of 'dangerous' levels are different, of course... See Figure 3 of this paper for a discussion of creatinine (which is similar):

http://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf

Q5b. When are we going to get a Benicar generic that's not as expensive?

Quite good if you are living in Europe, but if you are living in the USA, never. The FDA has no incentive to approve one, and PhRMA has no incentive to provide one. See, for example, my recent presentation at the FDA public hearing:

http://www.youtube.com/watch?v=sZUF-GvBplo

q6. Can probiotics or customized microbial treatment help you acquire a healthier microbiome?

Not that I have seen. In fact, they seem to just primarily overload the immune system.

Q7a. I have Sarcoidosis with many of the symptoms of CFS/ME. However, my calcium, ACE, 25-D and 1,25-D levels are all low. Does this mean VDR does not play a significant role in my chronic inflammation?

Well, if the VDR is not playing a role, how do you rationalize all those changes? :) Most of my recent presentations talk about the "Interactome" and how the body sets up homeostasis. Hopefully that will help you fit the puzzle together

Q7b. Or do blood levels not always represent what's going on in the cells?

The cell membrane, a lipid bilayer, exists to stop the insides of a cell 'merging' with the bloodstream (dissolving into the bloodstream would be an apt description :) ) Clearly there are some things which will not penetrate this membrane, and stay inside the cell.

Q8. I'm trying to convince my health insurance company to help pay for my immunostimulation. One thing they will refuse to pay for is anything "experimental". Looking on your websites for details (including the use of multiple doses of Benicar per day) to send them I ran across a number of key words that suggest, even though I know this has been a part of medical practice for decades, that the MP might be experimental: "research foundation", "study site", and "cohort".

Insurance companies in the USA don't listen to science or reason. They will seize any opportunity to deny a claim. The words we use are immaterial. You might have a chat with them about needing to go on a highly expensive biologic, like Rituximab, if they won't approve olmesartan.

Q9. Do you have or could you create literature that omits these words and clearly states that the MP is no longer "experimental". It might help others as well to get insurance coverage for the MP.

If we did that we would have the FDA and every US State Medical Board breathing down our necks. They regard the MP as experimental, so it is them that you need to discuss this issue with, I think :)

Hope that helps,
Trevor


eClaire
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I could not find the general thread on ME/CFS (if someone can link me, I will save it for future reference) regardless of forum. (I was looking in the forum closed to the general public, as I think it is best to discuss things like what I'm about to post there.) If someone wants to move this post to the appropriate place, I'd appreciate it.

I came across this, which I do not think is incompatible with the MP in terms of the causes of ME/CFS. And I wanted to know people's thoughts. (It wouldn't change my reasons for being on the MP, as I want my body to knock out whatever is setting off the cascade of symptoms.)

http://www.pdf-archive.com/2013/06/23/vanelzakker-vnih-cfs-in-press/

Prof Trevor Marshall
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Claire, the "Medical Hypotheses" paper is just a small subset of what is actually happening, a small subset of what we have described? Looking at individual pathogens and only the vagus nerve cannot describe a terrible systemic disease process like CFS/ME :) :)
 

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I noticed some patterns with that nerve and th1 pshychological symptoms a few years ago.

I have not read the paper yet but I think there are some interesting things going on with that nerve.

My hypothesis was that nerve was being manipulated by the infectious process to achieve specific bahaviour patterns that would further the disease process... somewhat like the stories about rats being dangerously attracted to cats in the presence of certain microbes.

Last edited on Sun Jun 23rd, 2013 05:09 by Markt9452

Prof Trevor Marshall
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Sure, its just that a lot more is happening than just the vagus nerve :)

eClaire
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Thank you Doctor Marshall. That's my thought even though the vagus nerve's role helps explain some of the more troubling symptoms for patients. I see the paper as just one more step to understanding the sickness response more fully, but like most, the author hopes to prove that THIS is the whole story even as he acknowledges that THAT can be triggered by a host of pathogens.

Lee
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Would this mean that the studies about neck injuries and CFS are on the same page with the vagus nerve studies?  TIA!  Lee

Prof Trevor Marshall
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There are a lot of neural lymph nodes in the neck area, Lee. They typically are inflamed in Th1 disease.

Malcolm Jackson
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Is this a sign that science is getting the right idea?

http://www.sciencedirect.com/science/article/pii/S1075996413000929

Prof Trevor Marshall
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They still haven't got three main issues

1. The human innate immune response is suppressed in disease
2. Changes in the endogenous antimicrobials may well be causative for the flora change, and not the other way around
3. The intra-phagocytic microbiota is key

If a probiotics could help disease, then Danone would have found it during all their testing in France these last five years :) But they reported (at the Paris HMC conference last year) that they were not close to any therapy which worked in any disease :)
 
 
ps: Thanks for this paper - it will help me write the abstract I am composing for the next HMC :)
 

Rico
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And Vitamin D supplementation contributing to chronic disease?

Prof Trevor Marshall
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Oh, Rico, that will the very last thing they understand...

Verena
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eClaire wrote
I came across this, which I do not think is incompatible with the MP in terms of the causes of ME/CFS. And I wanted to know people's thoughts. (It wouldn't change my reasons for being on the MP, as I want my body to knock out whatever is setting off the cascade of symptoms.)

http://www.pdf-archive.com/2013/06/23/vanelzakker-vnih-cfs-in-press/

 
Claire, I have no "thoughts" about the paper but an anecdote to tell. Three months before I had the first MS attac, I had an operation on my throad and a tumor removed. They needed to scratch that tumor off some nerves and one of those nerves was the left nervus vagus. That left side is the side, where I had most of the problems, the spastic cramps etc.

Might still be coincidence :?



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