Re: Comments on Dr. Cheney's June 18, 2005 talk in Irving, Texas

October 3, 2005

Thanks for the analysis, Rich. Part of Cheney's protocol is taking

ImmunePro, he is still recommending that. Whether that is enough to

address the glutathione problem is another question.

Helen

> Hi, all.

>

> A few weeks ago I received a copy of the video of Dr. Cheney's

> talk on June 18, 2005. I have now had a chance to view it, take

> notes, study them, and think about it in the context of other work

> on CFS. While I have not yet resolved all the questions the video

> raised in my mind, I am ready to comment on the main features.

>

> His talk was quite long and covered a lot of material, so I won't

> try to summarize it all here, but will only comment on certain

> issues.

>

> I think that Dr. Cheney has made a very important contribution by

> recognizing the significance of the work of Dr. Peckerman et al.

> indicating low cardiac output in PWCs and in building upon this

work

> in his measurements on his own patients.

>

> I also think that he is correct in concluding that PWCs exhibit

> diastolic cardiomyopathy, that it results from a mitochondrial

> dysfunction in the heart muscle cells that lowers the rate of

> production of ATP, and that it can explain many of the symptoms of

> CFS.

>

> I also think that he is correct in concluding that a rise in

> peroxynitrite is responsible for this mitochondrial dysfunction.

>

> I agree, in fact, with most of what he said in his talk.

>

> However, I think he is missing something very important: a correct

> understanding of the role of glutathione depletion in the

> pathogenesis of CFS. I think this is kind of ironic, since he is

> the person who first noted, back in 1999, that glutathione

depletion

> was almost a universal feature of his patients. His observation

was

> what first drew my attention to glutathione in CFS back then.

>

> My current view of the etiology, pathogenesis and pathophysiology

of

> CFS is that they can be synthesized in a fairly straightforward

> manner from (1) the genetic variations found in PWCs (which have

not

> yet been fully characterized and published, but which are clearly

> present, based on the recently published Swedish twin study and

> other work, and which I hope will be revealed soon by the ongoing

> work at the CDC and in other places), (2) the discussion I

presented

> in my poster paper a year ago

> http://www.cfsresearch.org/cfs/research/treatment/15.htm

> involving the variety of stressors that can lead to glutathione

> depletion and several of the subsequent effects of this depletion,

> including skeletal muscle fatigue, immune dysfunction, viral

> reactivation, and mercury buildup, and (3) the new diastolic

> cardiomyopathy piece, which I believe follows directly from the

> glutathione depletion.

>

> As I said above, I agree that the elevation of peroxynitrite is

what

> causes the mitochondrial dysfunction in the heart muscle cells,

> which in turn leads to the diastolic cardiomyopathy. However, it

> has been shown by others that glutathione depletion leads to the

> elevation of peroxynitrite. This apparently occurs by inhibition

of

> the glutathione peroxidase reaction, which in turn leads to buildup

> of hydrogen peroxide. The elevated hydrogen peroxide inhibits the

> superoxide dismutase reaction (by product inhibition), and this

> causes a rise in superoxide levels. The superoxide then reacts

with

> nitric oxide, as Dr. Cheney said, producing elevated

peroxynitrite.

> The elevated peroxynitrite reacts with aconitase and disables it,

> producing a partial blockade in the Krebs cycle that raises the

> level of citrate. I agree with what Dr. Cheney said about the

> subsequent effects of elevated citrate.

>

> I think that the reason why the effects of toxins do not show up

> until Dr. Cheney's phase 2 of CFS is that it takes some time for

the

> toxins to build up after the glutathione level drops below a level

> at which it is able to take the toxins out of the body as rapidly

as

> they come in.

>

> I think that the reason why the diastolic cardiomyopathy is delayed

> until Dr. Cheney's third phase of CFS is that the heart muscle

cells

> are known to express higher concentrations of glutamine cysteine

> ligase, the rate-limiting enzyme for the synthesis of glutathione,

> than do other organs. Thus, the heart is able to keep its

> glutathione level up longer than the skeletal muscles, for example,

> and the effects don't show up in the heart until the body's overall

> glutathione picture gets worse.

>

> I think it's important to make the role of glutathione depletion

> very clear, because I believe it will impact the success of the

> treatment for CFS. Dr. Cheney emphasized in his conclusions that

it

> is very important to deal with the elevated peroxynitrite before

> proceeding to treatments involving growth factors and stem cells,

> and I think that's right. I think that even if you put new cells

> into the heart muscle, they too will have elevated peroxynitrite

and

> will fail to correct the diastolic cardiomyopathy if they cannot

get

> their glutathione levels up because of a systematic glutathione

> depletion problem. I doubt that elevated peroxynitrite can be

> successfully corrected unless the glutathione depletion is

> corrected, since that is what I believe allows the peroxynitrite

> level to rise.

>

> I continue to be indebted to Dr. Cheney for stimulating most of my

> thinking about the pathogenesis of CFS, but I'm sorry to say that I

> think he is still missing the boat on the role of glutathione

> depletion. I mailed a copy of my paper to him nearly a year ago,

> but I don't know if he read it. I may try doing it again.

>

> Rich

October 3, 2005

Following Rich and Helen's comments, I recall years ago, that Dr. Cheney put

people on Immunopro because it " repairs the Glutathione pathway " . That any

" detox " would be pointless or harmful, until that was done. This is why I began

Immunopro, and still take it (and it's on Cheney protocol, as Helen said).

Rich, I am going blank and do not recall your suggestions for

repairing/elevating Glutathione. I cannot remember if I am taking anything else

for this.

Nor, what I am doing to lower peroxynitrite. We talked about it alot, and I'm

sure my tapes and diagrams explain.

Rich, what all can lower Peroxynitrite? All the antioxidants?

Thanks a bunch for your preliminary review and comments on Dr. Cheney's work!

KatrinaM

> > Hi, all.

> >

> > A few weeks ago I received a copy of the video of Dr. Cheney's

> > talk on June 18, 2005. I have now had a chance to view it, take

> > notes, study them, and think about it in the context of other work

> > on CFS. While I have not yet resolved all the questions the video

> > raised in my mind, I am ready to comment on the main features.

> >

> > His talk was quite long and covered a lot of material, so I won't

> > try to summarize it all here, but will only comment on certain

> > issues.

> >

> > I think that Dr. Cheney has made a very important contribution by

> > recognizing the significance of the work of Dr. Peckerman et al.

> > indicating low cardiac output in PWCs and in building upon this

> work

> > in his measurements on his own patients.

> >

> > I also think that he is correct in concluding that PWCs exhibit

> > diastolic cardiomyopathy, that it results from a mitochondrial

> > dysfunction in the heart muscle cells that lowers the rate of

> > production of ATP, and that it can explain many of the symptoms of

> > CFS.

> >

> > I also think that he is correct in concluding that a rise in

> > peroxynitrite is responsible for this mitochondrial dysfunction.

> >

> > I agree, in fact, with most of what he said in his talk.

> >

> > However, I think he is missing something very important: a correct

> > understanding of the role of glutathione depletion in the

> > pathogenesis of CFS. I think this is kind of ironic, since he is

> > the person who first noted, back in 1999, that glutathione

> depletion

> > was almost a universal feature of his patients. His observation

> was

> > what first drew my attention to glutathione in CFS back then.

> >

> > My current view of the etiology, pathogenesis and pathophysiology

> of

> > CFS is that they can be synthesized in a fairly straightforward

> > manner from (1) the genetic variations found in PWCs (which have

> not

> > yet been fully characterized and published, but which are clearly

> > present, based on the recently published Swedish twin study and

> > other work, and which I hope will be revealed soon by the ongoing

> > work at the CDC and in other places), (2) the discussion I

> presented

> > in my poster paper a year ago

> > http://www.cfsresearch.org/cfs/research/treatment/15.htm

> > involving the variety of stressors that can lead to glutathione

> > depletion and several of the subsequent effects of this depletion,

> > including skeletal muscle fatigue, immune dysfunction, viral

> > reactivation, and mercury buildup, and (3) the new diastolic

> > cardiomyopathy piece, which I believe follows directly from the

> > glutathione depletion.

> >

> > As I said above, I agree that the elevation of peroxynitrite is

> what

> > causes the mitochondrial dysfunction in the heart muscle cells,

> > which in turn leads to the diastolic cardiomyopathy. However, it

> > has been shown by others that glutathione depletion leads to the

> > elevation of peroxynitrite. This apparently occurs by inhibition

> of

> > the glutathione peroxidase reaction, which in turn leads to buildup

> > of hydrogen peroxide. The elevated hydrogen peroxide inhibits the

> > superoxide dismutase reaction (by product inhibition), and this

> > causes a rise in superoxide levels. The superoxide then reacts

> with

> > nitric oxide, as Dr. Cheney said, producing elevated

> peroxynitrite.

> > The elevated peroxynitrite reacts with aconitase and disables it,

> > producing a partial blockade in the Krebs cycle that raises the

> > level of citrate. I agree with what Dr. Cheney said about the

> > subsequent effects of elevated citrate.

> >

> > I think that the reason why the effects of toxins do not show up

> > until Dr. Cheney's phase 2 of CFS is that it takes some time for

> the

> > toxins to build up after the glutathione level drops below a level

> > at which it is able to take the toxins out of the body as rapidly

> as

> > they come in.

> >

> > I think that the reason why the diastolic cardiomyopathy is delayed

> > until Dr. Cheney's third phase of CFS is that the heart muscle

> cells

> > are known to express higher concentrations of glutamine cysteine

> > ligase, the rate-limiting enzyme for the synthesis of glutathione,

> > than do other organs. Thus, the heart is able to keep its

> > glutathione level up longer than the skeletal muscles, for example,

> > and the effects don't show up in the heart until the body's overall

> > glutathione picture gets worse.

> >

> > I think it's important to make the role of glutathione depletion

> > very clear, because I believe it will impact the success of the

> > treatment for CFS. Dr. Cheney emphasized in his conclusions that

> it

> > is very important to deal with the elevated peroxynitrite before

> > proceeding to treatments involving growth factors and stem cells,

> > and I think that's right. I think that even if you put new cells

> > into the heart muscle, they too will have elevated peroxynitrite

> and

> > will fail to correct the diastolic cardiomyopathy if they cannot

> get

> > their glutathione levels up because of a systematic glutathione

> > depletion problem. I doubt that elevated peroxynitrite can be

> > successfully corrected unless the glutathione depletion is

> > corrected, since that is what I believe allows the peroxynitrite

> > level to rise.

> >

> > I continue to be indebted to Dr. Cheney for stimulating most of my

> > thinking about the pathogenesis of CFS, but I'm sorry to say that I

> > think he is still missing the boat on the role of glutathione

> > depletion. I mailed a copy of my paper to him nearly a year ago,

> > but I don't know if he read it. I may try doing it again.

> >

> > Rich

October 3, 2005

Rich,

thanks so much for this report. This sure bears true with my personal ION

profile results from Metametrix, everything you said here seems to be linked. I

agree with you totally. I think this is why people get into trouble with detox

and dieoff, if the glutathione is low, it could be causing more harm than good

to try and detox or even kill bugs.

I have been wondering for some time Rich and scared to ask, but how is your

friend you were working with on the pancreatic cancer doing?

I've seen some significant improvement in many ways from getting that leaking

merc filling out of the base of the root of that tooth some weeks ago. Its

amazing! Less brain fog, more relaxed, brain feels so much less tortured, less

joint and muscle pain and stiffness. Skin and hair are getting a little softer.

Still have the fatigue tho and I'm not 'well' yet. Waiting on more funds to

continue the work, still have the temp bridge in my mouth to try and let my jaw

heal a little, MUCH less pain in my mouth and jaw now since this bridge, even

tho temporary and of rough materials, fits so much better. Still have to restore

the damage done to the upper 4 front teeth same time the new bridge goes on

(which requires a lot more $$$ and waiting on that) before I can do the cracked

merc filling on top and then the rest of the old mercury that needs to come out.

I think it will be about a year and 1/2 before the merc is all out, but in some

ways I'm not sorry it has to go so slow, I doubt I could handle it much faster

anyway as overloaded as my system is being sick so long.

I can now tolerate almost 3/4 tsp of ImmuneproRx about 5 days a week now, before

was only able to take about 1/4 tsp maybe 4 times a week, so am working up

slowly. I'm about to order the Lipo GSH, altho I'm almost sure I can't tolerate

it because its lecithin based and lecithin (choline) has made me seriously

dizzy for the last 15 or more years, but I feel I need to try it. I'm wondering

if you have any reports yet on whether the LipoFlow is going to be a comparable

product in efficiency? Is it lecithin based as well?

I'm also tolerating the coq10 now too that I couldn't before. MSM isn't going

well, I rarely take it as it gives me headaches and some nausea the next day, so

holding off on that.

My preference would be to get the glut IV's but its just too expensive, this ND

is just milking people's need for it, what a shame, so no way I can afford to go

that route except to get them on days I have dental work done.

Thanks again for all your work on this!

Marcia

Comments on Dr. Cheney's June 18, 2005 talk in

Irving, Texas

Hi, all.

A few weeks ago I received a copy of the video of Dr. Cheney's

talk on June 18, 2005. I have now had a chance to view it, take

notes, study them, and think about it in the context of other work

on CFS. While I have not yet resolved all the questions the video

raised in my mind, I am ready to comment on the main features.

His talk was quite long and covered a lot of material, so I won't

try to summarize it all here, but will only comment on certain

issues.

I think that Dr. Cheney has made a very important contribution by

recognizing the significance of the work of Dr. Peckerman et al.

indicating low cardiac output in PWCs and in building upon this work

in his measurements on his own patients.

I also think that he is correct in concluding that PWCs exhibit

diastolic cardiomyopathy, that it results from a mitochondrial

dysfunction in the heart muscle cells that lowers the rate of

production of ATP, and that it can explain many of the symptoms of

CFS.

I also think that he is correct in concluding that a rise in

peroxynitrite is responsible for this mitochondrial dysfunction.

I agree, in fact, with most of what he said in his talk.

However, I think he is missing something very important: a correct

understanding of the role of glutathione depletion in the

pathogenesis of CFS. I think this is kind of ironic, since he is

the person who first noted, back in 1999, that glutathione depletion

was almost a universal feature of his patients. His observation was

what first drew my attention to glutathione in CFS back then.

My current view of the etiology, pathogenesis and pathophysiology of

CFS is that they can be synthesized in a fairly straightforward

manner from (1) the genetic variations found in PWCs (which have not

yet been fully characterized and published, but which are clearly

present, based on the recently published Swedish twin study and

other work, and which I hope will be revealed soon by the ongoing

work at the CDC and in other places), (2) the discussion I presented

in my poster paper a year ago

http://www.cfsresearch.org/cfs/research/treatment/15.htm

involving the variety of stressors that can lead to glutathione

depletion and several of the subsequent effects of this depletion,

including skeletal muscle fatigue, immune dysfunction, viral

reactivation, and mercury buildup, and (3) the new diastolic

cardiomyopathy piece, which I believe follows directly from the

glutathione depletion.

As I said above, I agree that the elevation of peroxynitrite is what

causes the mitochondrial dysfunction in the heart muscle cells,

which in turn leads to the diastolic cardiomyopathy. However, it

has been shown by others that glutathione depletion leads to the

elevation of peroxynitrite. This apparently occurs by inhibition of

the glutathione peroxidase reaction, which in turn leads to buildup

of hydrogen peroxide. The elevated hydrogen peroxide inhibits the

superoxide dismutase reaction (by product inhibition), and this

causes a rise in superoxide levels. The superoxide then reacts with

nitric oxide, as Dr. Cheney said, producing elevated peroxynitrite.

The elevated peroxynitrite reacts with aconitase and disables it,

producing a partial blockade in the Krebs cycle that raises the

level of citrate. I agree with what Dr. Cheney said about the

subsequent effects of elevated citrate.

I think that the reason why the effects of toxins do not show up

until Dr. Cheney's phase 2 of CFS is that it takes some time for the

toxins to build up after the glutathione level drops below a level

at which it is able to take the toxins out of the body as rapidly as

they come in.

I think that the reason why the diastolic cardiomyopathy is delayed

until Dr. Cheney's third phase of CFS is that the heart muscle cells

are known to express higher concentrations of glutamine cysteine

ligase, the rate-limiting enzyme for the synthesis of glutathione,

than do other organs. Thus, the heart is able to keep its

glutathione level up longer than the skeletal muscles, for example,

and the effects don't show up in the heart until the body's overall

glutathione picture gets worse.

I think it's important to make the role of glutathione depletion

very clear, because I believe it will impact the success of the

treatment for CFS. Dr. Cheney emphasized in his conclusions that it

is very important to deal with the elevated peroxynitrite before

proceeding to treatments involving growth factors and stem cells,

and I think that's right. I think that even if you put new cells

into the heart muscle, they too will have elevated peroxynitrite and

will fail to correct the diastolic cardiomyopathy if they cannot get

their glutathione levels up because of a systematic glutathione

depletion problem. I doubt that elevated peroxynitrite can be

successfully corrected unless the glutathione depletion is

corrected, since that is what I believe allows the peroxynitrite

level to rise.

I continue to be indebted to Dr. Cheney for stimulating most of my

thinking about the pathogenesis of CFS, but I'm sorry to say that I

think he is still missing the boat on the role of glutathione

depletion. I mailed a copy of my paper to him nearly a year ago,

but I don't know if he read it. I may try doing it again.

Rich

October 3, 2005

Do you mean you think this is correct in all PWC's, or just a subset?

Thanks

Doris

----- Original Message -----

From: rvankonynen

I also think that he is correct in concluding that PWCs exhibit

diastolic cardiomyopathy, that it results from a mitochondrial

dysfunction in the heart muscle cells that lowers the rate of

production of ATP, and that it can explain many of the symptoms of

CFS.

I also think that he is correct in concluding that a rise in

peroxynitrite is responsible for this mitochondrial dysfunction.

October 3, 2005

Hi, Helen.

I'm glad Dr. Cheney still has ImmunoPro Rx in his protocol. I

continue to work on ways to better address glutathione depletion. I

suspect that genetic polymorphisms in the genes coding for enzymes

that affect the ability to maintain normal levels of glutathione and

to utilize it may be involved in many cases of CFS. This weekend I

wrote to the researchers at the CDC who are looking into DNA

polymorphisms in CFS and suggested that they include the above genes

in their study. I hope they will.

I also think that toxins and especially infections can act as

impediments to building glutathione back to normal levels, and that

these may need to be dealt with directly in order to allow the

glutathione level to be brought up to normal in many cases.

Rich

> Thanks for the analysis, Rich. Part of Cheney's protocol is taking

> ImmunePro, he is still recommending that. Whether that is enough

to

> address the glutathione problem is another question.

>

> Helen

October 3, 2005

Hi, Katrina.

I think that Dr. Cheney still believes in building up glutathione,

and I'm glad he does.

I still don't think I have figured out the absolute optimum way to

get glutathione back up to normal in PWCs.

I suspect that there are genetic polymorphisms that predispose a

person to glutathione depletion, but these have not yet been

studied, as far as I know. If they do in fact exist and can be

identified, it may be possible to compensate for them with targeted

supplements, and I'm hopeful that this will be done.

I think that the infections and toxins (especially mercury) that

have built up over the time during which the glutathione has been

low also act as impediments to building glutathione, so these will

probably have to be attacked directly in order to be able to build

glutathione.

Finally, I think that a combination of approaches that give the

liver the raw materials for making its own glutathione, together

with a method that puts glutathione per se directly into the blood,

it probably the best way to go. I favor RenewPro or ImmunoPro Rx

for the first purpose. For the second purpose, the glutathione

rectal suppositories may be the least expensive way to do it. If

one can afford the I.V. glutathione injections and can get to a

clinic to get them regularly, that is a good way to go for the

second purpose, also.

Concerning peroxynitrite, I think that the best way to lower it is

to build glutathione, because that normally holds peroxynitrite

under control. Beyond that, there are some antioxidants that are

particularly effective against peroxynitrite itself. Pynogenol

(oligomeric proanthocyanidins or OPCs, also found in grape seeds) is

one of them. Another is ginkgo biloba. Another is the gamma

tocopherol form of vitamin E. One can also take the antioxidants

that are effective against nitric oxide and superoxide, which are

the substances that react to form peroxynitrite. Coenzyme Q-10 and

alpha lipoic acid are two of them. I actually favor taking a

combination antioxidants, including vitamin C as well as the others

mentioned above.

Rich

> Following Rich and Helen's comments, I recall years ago, that Dr.

Cheney put people on Immunopro because it " repairs the Glutathione

pathway " . That any " detox " would be pointless or harmful, until that

was done. This is why I began Immunopro, and still take it (and it's

on Cheney protocol, as Helen said).

>

> Rich, I am going blank and do not recall your suggestions for

repairing/elevating Glutathione. I cannot remember if I am taking

anything else for this.

>

> Nor, what I am doing to lower peroxynitrite. We talked about it

alot, and I'm sure my tapes and diagrams explain.

>

> Rich, what all can lower Peroxynitrite? All the antioxidants?

>

> Thanks a bunch for your preliminary review and comments on Dr.

Cheney's work!

>

> KatrinaM

October 3, 2005

Hi, Cort.

There are some details of things he said that I don't believe are

actually correct, but the main point I want to make is that I think

he covered many of the pieces of the pathogenesis in his talk, but

that I don't think he has them put together properly, in terms of

the cause and effect sequence, and the early part is not there at

all. Although he mentioned glutathione, I don't think he views its

depletion as the immediate cause of the rise in peroxynitrite, as I

do.

In his talk, Dr. Cheney presented the latest modification of his

pathogenesis model for CFS. The first thing it starts with is his

Phase 1, with a viral infection and elevated RNase-L activity.

However, I think the disease process in CFS actually has to start

earlier than that. Most everyone in the general population is

carrying (in the latent state) the viruses that show up producing

infections in people who get CFS. There has to be an explanation

for why some people experience viral reactivation, RNase-L

dysfunction, and CFS, while most people do not, even though they are

carrying these same viruses in their bodies.

I believe it starts in many people with certain genetic

polymorphisms. These have not yet been identified for CFS, but they

have to be there, based on the evidence of the twin studies and the

familial occurrence of CFS. I hope these will be studied and

identified soon. The CDC has this in their current research plan.

After that, there has to be exposure to what have been

called " environmental factors, " which include not just toxins from

the environment, but also the whole range of long-term physical,

chemical, biological and psychological/emotional stressors that

people have reported in the studies, which I reviewed in my paper,

and the combination differs for each person. Some of these do

result from lifestyle choices that people make, but many result from

circumstances that people do not choose, but are thrust upon them.

From the standpoint of the body's nonspecific stress response

systems, they are all treated together.

This combination of genetics plus exposure to some combination of

long-term stressors is the only way I know of to explain all the

observations. It explains the twin and familial study results, and

it also explains why PWCs aren't born with CFS, but develop it after

undergoing some combination of long-term stressors.

The body responds to the long-term stressors with long-term elevated

cortisol and adrenaline. In people with the right (or maybe I

should say wrong) genetic makeup, this results in severe glutathione

depletion. That suppresses cell-mediated immunity, and also

reactivates the latent viruses in the body, and I have reviewed the

evidence for both these effects in my paper.

I believe that all these pieces must precede the first thing Dr.

Cheney mentioned in his model, which was viral infection.

The second thing he mentioned was RNase-L activity. But in CFS, it

is not normal RNase-L activity. Rather, the normal RNase-L gets

cleaved to form the low-molecular-weight, unregulated version. How

does this happen? Dr. Cheney's model doesn't explain this. I think

it is caused by glutathione depletion, which removes the inhibition

from calpain, and that cleaves the RNase-L molecules. I have

literature support for this process.

So I guess my first general comment about Dr. Cheney's model is that

it is missing a good " front end, " and I think the combination of

genetic polymorphisms (yet to be elucidated) and what I wrote in my

paper would supply that.

Dr. Cheney did not explain why PWCs go through the three phases he

has identified. His second phase involves toxicity, and his third

phase involves diastolic cardiomyopathy. I believe that the ongoing

depletion of glutathione naturally produces these phases. The immune

system and the skeletal muscles are the first to go low in

glutathione (as was described by Bounous and Molson several years

ago), and that's what produces the immune dysfunction, persisting

flu-like symptoms, and fatigue of Phase 1. After glutathione drops,

it takes some time for the toxins to build up that glutathione would

have taken out of the body, and that's why it takes some time for

Phase 2, the toxic phase, to develop. Because the heart does not

drop in glutathione level until later on, because of its known

higher gene expression for glutamate cysteine ligase, the rate-

limiting enzyme for synthesizing glutathione, Phase 3 takes even

longer to appear. But glutathione depletion explains why this

sequence occurs.

Dr. Cheney is right on, in my view, about the mitochondrial

dysfunction being central to CFS, and about peroxynitrite's role in

causing it. However, I don't sense that he sees glutathione

depletion as being the cause of the peroxynitrite elevation, as I do.

Some of the things Dr. Cheney said about the biochemistry of

glutathione are unfortunately not correct. He suggested that the

issue with glutathione may be that because of the energy problem,

not enough of it is kept in the chemically reduced state. I think

he has the cart before the horse here. ATP is not needed to reduce

glutathione. This reaction is powered by NADPH, which is produced

by the pentose phosphate shunt on the glycolysis pathway. On the

other hand, glutathione is needed to maintain the production of ATP

by the Krebs cycle, because without enough glutathione, the level of

peroxynitrite rises and blocks aconitase in the Krebs cycle, slowing

the production of ATP. So the energy problem is due to the

glutathione depletion, not vice versa.

Dr. Cheney also said that glutathione may not be depleted in CFS,

but may just be in the oxidized state to a higher degree than

normal. He also said that building glutathione may not be a good

idea, because you might actually build the oxidized form, which

would be detrimental. He seems not to be aware that cells export

the oxidized form of glutathione if it rises too high relative to

the reduced form. When they do that, they go low in glutathione,

and it really isn't possible to build the oxidized form of

glutathione very high within the cells.

Concerning the cardiomyopathy, Dr. Cheney clearly recognizes that

the diastolic cardiomyopathy most common in CFS is not the same as

the type that he had himself, and that most people with heart

failure (but not CFS) have. He seems to recognize that they arise

from different causes, with mitochondrial dysfunction (resulting

from elevated peroxynitrite) being the immediate cause of type most

common in CFS. But I don't think he has a clear idea of what causes

the elevated peroxynitrite, because he advocates treatments that

work for the other type of cardiomyopathy. He seems to think that

bringing in new stem cells, or using cardiac growth factors will

correct the mitochondrial dysfunction in CFS. My concern about this

is that I think the elevated peroxynitrite arises from glutathione

depletion, and if this is true, the new or rejuvenated cells will

have the same problem that the old ones had: they won't be able to

get their glutathione level high enough to keep peroxynitrite from

rising and producing mitochondrial dysfunction in the new cells,

too, because the glutathione depletion is a systemic problem, not

confined to the heart. The raw materials for making glutathione, as

well as the levels of glutathione itself, are low in the blood,

because the entire body has a glutathione depletion problem by the

time it begins to affect the heart function.

Dr. Cheney discussed the viral cardiomyopathy work of Dr. A.

Lerner and the Italian paper showing elevated mercury in the hearts

of people who had died of heart failure. As I understand it, these

represent a different type of cardiomyopathy from the diastolic

cardiomyopathy that Dr. Cheney is commonly seeing in his patients.

I think these cardiomyopathies occur in CFS as well (certainly Dr.

Lerner has shown that the viral type does), but they are not the

same as what he is seeing in the majority of his patients. Again,

we are dealing with subsets, I think. I hasten to add, though, that

the common denominator is that you can't have an active herpes

family virus infection or a big buildup of mercury unless

glutathione is either not there to do its jobs, or one of the

enzymes that makes use of glutathione to do its jobs (the

glutathione peroxidases or the glutathione transferases) is not

functioning properly. So I maintain that glutathione depletion (or

a glutathione enzyme deficiency) is behind all the forms of

cardiomyopathy that have been found to occur in CFS.

A smaller point concerns contraction alkalosis. Dr. Cheney still

seems to have this backward, as he did in his last talk. Alkalosis

does not produce a contraction in the blood volume. It's the other

way around. A contraction in the blood volume, such as caused by a

hemorrhage, will result in the blood pH moving in the alkaline

direction, because of the response of the kidneys. In CFS, I

believe that the blood alkalosis results from too low a production

of carbon dioxide as a result of partial blockades in the oxidative

metabolism produced by elevated peroxynitrite in response to

glutathione depletion. The decrease in blood volume is most likely

due to decreased secretion of arginine vasopressin (antidiuretic

hormone) by the hypothalamus/pituitary. This amounts to diabetes

insipidus. I still don't know why the hypothalamus sustains such a

heavy hit in CFS. It could be due to toxins, infections, low

glutathione in the cells of the hypothalamus, or low blood flow

there.

I guess these are the main issues on which I have some disagreement

with Dr. Cheney's talk. I want to emphasize again, though, that I

am deeply indebted to him for stimulating most of my thinking on

CFS. His new emphasis on cardiomyopathy is very important, in my

view, and I think cardiomyopathy and the resulting low cardiac

output explain a great deal of what goes on in CFS. I think that

this is a major advance in our understanding.

Rich

> Thanks for comments. I dont see in there , though, exactly how

you disagree with Dr. Cheney. I see the parts of his talk that you

agree with and what you believe is occurring but I'm missing what he

said that you disagree with. What was that?

>

October 3, 2005

Hi, Marcia.

> Rich,

>

> thanks so much for this report. This sure bears true with my

personal ION profile results from Metametrix, everything you said

here seems to be linked. I agree with you totally. I think this is

why people get into trouble with detox and dieoff, if the

glutathione is low, it could be causing more harm than good to try

and detox or even kill bugs.

***I'm glad this all seems to fit together in your case.

>

> I have been wondering for some time Rich and scared to ask, but

how is your friend you were working with on the pancreatic cancer

doing?

***Thanks for asking. He's still on the cesium chloride treatment.

His second MRI seemed to indicate that the tumor had not grown, and

that's pretty good news, since pancreatic cancers can move pretty

fast. He's not out of the woods, though. He now has gallstones,

which make eating anything with fat pretty painful. His pancreatic

duct seems to be blocked also, so that makes eating protein

painful. He's lost weight, but still has some reserve. On top of

this, his doctor started making noises about cutting off his pain

medication if he was not willing to do biopsy, chemo and radiation.

So this week he is seeking a new doctor who will keep up the pain

medication, because it's pretty miserable without it. We're still

hopeful that the cesium will get the best of the cancer cells before

he starves to death. A tough situation to be in. His name is Jack,

if you want to pray for him.

>

> I've seen some significant improvement in many ways from getting

that leaking merc filling out of the base of the root of that tooth

some weeks ago. Its amazing! Less brain fog, more relaxed, brain

feels so much less tortured, less joint and muscle pain and

stiffness. Skin and hair are getting a little softer.

***That's really great to hear, Marcia!

Still have the fatigue tho and I'm not 'well' yet. Waiting on more

funds to continue the work, still have the temp bridge in my mouth

to try and let my jaw heal a little, MUCH less pain in my mouth and

jaw now since this bridge, even tho temporary and of rough

materials, fits so much better. Still have to restore the damage

done to the upper 4 front teeth same time the new bridge goes on

(which requires a lot more $$$ and waiting on that) before I can do

the cracked merc filling on top and then the rest of the old mercury

that needs to come out. I think it will be about a year and 1/2

before the merc is all out, but in some ways I'm not sorry it has to

go so slow, I doubt I could handle it much faster anyway as

overloaded as my system is being sick so long.

***It sounds as though you're making the best of it. It's really

nice to know that you're going in a helpful direction.

>

> I can now tolerate almost 3/4 tsp of ImmuneproRx about 5 days a

week now, before was only able to take about 1/4 tsp maybe 4 times a

week, so am working up slowly. I'm about to order the Lipo GSH,

altho I'm almost sure I can't tolerate it because its lecithin based

and lecithin (choline) has made me seriously dizzy for the last 15

or more years, but I feel I need to try it. I'm wondering if you

have any reports yet on whether the LipoFlow is going to be a

comparable product in efficiency? Is it lecithin based as well?

***Sorry, I don't know any more about the LipoFlow GSH. I gather

from other postings on the list that the producers don't give out

much information about it.

>

> I'm also tolerating the coq10 now too that I couldn't before. MSM

isn't going well, I rarely take it as it gives me headaches and some

nausea the next day, so holding off on that.

***O.K.

>

> My preference would be to get the glut IV's but its just too

expensive, this ND is just milking people's need for it, what a

shame, so no way I can afford to go that route except to get them on

days I have dental work done.

>

> Thanks again for all your work on this!

***You're very welcome. I hope this trend continues for you.

>

> Marcia

***Rich

October 3, 2005

Hi, Doris.

Since CFS is defined in a way that produces such a heterogeneous

population, I should probably preface everything I say with the

qualification that there are subsets.

Dr. Cheney reported that as of June 2005, he has found low cardiac

output due to cardiomyopathy in 82% of the patients he has tested. He

noted that his patients tend to be " sicker " patients than those tested

by Peckerman et al., because he does not require them to stop their

medications to be tested, and he treats them, while Peckerman et al.

did require stopping meds and they didn't offer treatment. As a

result, the sicker patients would not have chosen to go to Peckerman

et al to participate in their study, in Cheney's opinion. I don't

think we know what fraction of PWCs overall have cardiomyopathy. I

don't think it usually shows up until the later phases of the disorder.

Among the PWCs who have cardiomyopathy, some have a viral infection in

their heart, as shown by Dr. Lerner. Some may have elevated mercury,

similar to the heart attack patients studied in the Italian study. I

think most have the peroxynitrite problem, based on Cheney's work.

I think we have a lot to learn about what fraction of PWCs has what.

Thanks for raising this point. I get a little carried away and

oversimplify sometimes.

Rich

> Do you mean you think this is correct in all PWC's, or just a subset?

> Thanks

> Doris

> ----- Original Message -----

> From: rvankonynen

> I also think that he is correct in concluding that PWCs exhibit

> diastolic cardiomyopathy, that it results from a mitochondrial

> dysfunction in the heart muscle cells that lowers the rate of

> production of ATP, and that it can explain many of the symptoms of

> CFS.

>

> I also think that he is correct in concluding that a rise in

> peroxynitrite is responsible for this mitochondrial dysfunction.

>

October 4, 2005

Hi, Rich,

Thank you for your comments on Dr. Cheney's talk. I am still watching it

and trying to just remember what he said.

I trace the beginning of my illness back to being exposed to (1) natural

gas cooking and heating stoves and the sulfur compounds added to natural

gas and (2) gasoline fumes and exhaust -- when I was a child. I think

that was when I developed a sensitivity to sulfur compounds, including

glutathione. I wonder if there was an immune system cross reaction

between endogenous sulfur compounds and toxic environmental sulfur

compounds, if that makes sense. My sulfur and glutathione

hypersensitivity may be due to impaired sulfur and glutathione metabolism

( inherited abnormality), OR my impaired sulfur and glutathione

metabolism ( or gene expression abnormality ?) may be due to sulfur and

glutathione hypersensitivity, if that makes any sense. I guess the same

can be said for my sensitivities to petrochemicals. They may have

produced other metabolic problems.

My chemical sensitivities and other allergies were relatively mild until

I had a chemical exposure that dramatically worsened my MCS. After that

my other allergies worsened over time (foods, dust, mold, weeds, trees,

etc.). I developed many hormonal problems, viral reactivations, mitral

valve prolapse and chronic fatigue. Any infections I came down with

tended to become chronic.

I hope you can make sense of some of that. I'm too brainfogged to think

through it today, but I think there may be some truth to my impressions.

If I didn't care about my kids and other CFS sufferers, I wouldn't even

try to figure it out. Today I feel like crawling in bed and never

getting out. But tomorrow is another day.

Thanks for being such a caring person.

Vickie

October 4, 2005

Hi, again, Rich. I would be interested in your comments on the following

(partial) article by Pall on MCS. (You probably have already read

it.)

In my mind there is definitely an immune system, hypersensitivity,

inflammatory reaction to chemicals that he is missing in his theory. He

hints at a genetic component because a certain percentage of people are

more susceptible to MCS.

Vickie

------------------------------

03-05-2003

By L. Pall

Source: http://molecular.biosciences.wsu.edu/Faculty/pall.html

Elevated Nitric Oxide/Peroxynitrite/NMDA Model of MCS:

My own interest in MCS stems from the reported overlaps among MCS and

chronic fatigue syndrome (CFS), fibromyalgia (FM) and posttraumatic

stress disorder (PTSD). These have overlapping symptoms, many people are

diagnosed as having more than one of these and cases of each of these are

reported to be preceded by and presumably induced by a short term

stressor such as infection in CFS and chemical exposure in MCS. The

overlaps among these have led others to suggest that they may share a

common causal (etiologic) mechanism.

Having proposed that elevated levels of nitric oxide and its oxidant

product, peroxynitrite are central to the cause of CFS, it was obvious to

raise the question of whether these might be involved in MCS. We proposed

such a role in a paper published in the ls of the New York Academy of

Sciences (4) and in a subsequent paper, I list 10 different types of

experimental observations that provide support for the view that elevated

levels of these two compounds have an important role in MCS (5). These 10

observations are listed in the table below (from ref. 5).

Types of Evidence Implicating Nitric Oxide/Peroxynitrite in MCS:

1. Several organic solvents thought to be able to induce MCS,

formaldehyde, benzene, carbon tetrachloride and certain organochlorine

pesticides all induce increases in nitric oxide levels.

2. A sequence of action of organophosphate and carbamate insecticides is

suggested, whereby they may induce MCS by inactivating

acetylcholinesterase and thus produce increased stimulation of muscarinic

receptors which are known to produce increases in nitric oxide.

3. Evidence for induction of inflammatory cytokines by organic solvents,

which induce the inducible nitric oxide synthase (iNOS). Elevated

cytokines are an integral part of a proposed feedback mechanism of the

elevated nitric oxide/peroxynitrite theory.

4. Neopterin, a marker of the induction of the iNOS, is reported to be

elevated in MCS.

5. Increased oxidative stress has been reported in MCS and also

antioxidant therapy may produce improvements in symptoms, as expected if

the levels of the oxidant peroxynitrite are elevated.

6. In a series of studies of a mouse model of MCS, involving partial

kindling and kindling, both excessive NMDA activity and excessive nitric

oxide synthesis were convincingly shown to be required to produce the

characteristic biological response.

7. The symptoms exacerbated on chemical exposure are very similar to the

chronic symptoms of CFS (1) and these may be explained by several known

properties of nitric oxide, peroxynitrite and inflammatory cytokines,

each of which have a role in the proposed mechanism.

8. These conditions (CFS, MCS, FM and PTSD) are often treated through

intramuscular injections of vitamin B-12 and B-12 in the form of

hydroxocobalamin is a potent nitric oxide scavenger, both in vitro and in

vivo.

9. Peroxynitrite is known to induce increased permeabilization of the

blood brain barrier and such increased permeabilization is reported in a

rat model of MCS.

10. 5 types of evidence implicate excessive NMDA activity in MCS, an

activity known to increase nitric oxide and peroxynitrite levels.

However, although one can make a substantial case for this theory for an

elevated nitric oxide/peroxynitrite etiology (cause) in MCS, this does

not explain how the exquisite chemical sensitivity may be produced -

which has to be viewed as the most central puzzle of MCS. By what

mechanism or set of mechanisms can such exquisite sensitivity to organic

chemicals be generated?

Another theory of MCS was proposed earlier by Iris Bell (6,7) and

coworkers and adopted with modifications by numerous other research

groups. This was the neural sensitization theory of MCS. What this theory

says is that the synapses in the brain, the connections between nerve

cells by which one nerve cell stimulates (or in some cases inhibits)

another become hypersensitive in MCS.

This neural sensitization theory is supported by observations that many

of the symptoms of MCS relate directly to brain function and that a

number of studies have shown that scans of the brains of MCS people,

performed by techniques known as PET scanning or SPECT scanning are

abnormal. There is also evidence that electrical activity in the brains

of MCS people, measured by EEG's, is also abnormal. Neural sensitization

is produced by a mechanism known as long term potentiation, a mechanism

that has a role in learning and memory. Long term potentiation produces

neural sensitization but in the normal nervous system, it does so very

selectively - increasing the sensitivity of certain selected synapses.

In MCS, it may be suggested, that a widespread sensitization may be

involved that is somehow triggered by chemical or pesticide exposure.

This leaves open the question as to why specifically [petrochemicals],

hydrophobic organic solvents or certain pesticides [or other chemicals

such as aldehydes] are involved and, most importantly, how these can lead

to such exquisite chemical sensitivity as is seen in MCS. So the neural

sensitization theory is a promising one but it leaves unanswered the

central puzzles of MCS.

The question that I raised in my key paper (5), published in the

prestigious publication of the Federation of American Societies for

Experimental Biology, The FASEB Journal, is what happens if both of these

theories are correct? The answer is that you get a fusion theory that,

for the first time, answers all of the most puzzling questions about MCS.

The fusion theory is supported by all of the observations supporting the

nitric oxide/peroxynitrite theory, all of the observations supporting the

neural sensitization theory plus several additional observations that

relate specifically to the fusion.

How can we understand this fusion theory? When you look at the two

precursor theories together, you immediately see ways in which they

interact with each other. Long term potentiation, the mechanism behind

neural sensitization, involves certain receptors at the synapses of nerve

cells called NMDA receptors. These are receptors that are stimulated by

glutamate and aspartate and when these receptors are stimulated to be

active, they produce in turn, increases in nitric oxide and its oxidant

product, peroxynitrite. So immediately you can see a possible interaction

between the two theories.

Furthermore, nitric oxide can act in long term potentiation, serving as

what is known as a retrograde messenger, diffusing from the cell

containing the NMDA receptors (the post-synaptic cell) to the cell that

can stimulate it (the pre-synaptic cell), making the pre-synaptic cell

more active in releasing neurotransmitter (glutamate and aspartate). In

this way, NMDA stimulation increases the activity to the pre-synaptic

cell to stimulate more NMDA activity. Thus we have the potential for a

vicious cycle in the brain, with too much NMDA activity leading to too

much nitric oxide leading to too much NMDA activity, etc.

There is also a mechanism by which peroxynitrite may act to exacerbate

this potential vicious cycle. Peroxynitrite is known to act to deplete

energy (ATP) pools in cells by two different mechanisms and it is known

that when cells containing NMDA receptors are energy depleted, the

receptors become hypersensitive to stimulation. Consequently nitric oxide

may act to increase NMDA stimulation and peroxynitrite may act to

increase the sensitivity to such stimulation. With both nitric oxide and

peroxynitrite levels increased by NMDA receptor activity, an overall

increase in these activities may lead to a major, sustained increase in

neural sensitivity and activity. The only thing left is to explain how

hydrophobic organic chemicals or pesticides can stimulate this whole

response. I'll discuss that below.

I have also proposed two additional, accessory mechanisms in MCS. One is

that peroxynitrite is known to act to break down the blood brain barrier

- the barrier that minimizes the access of chemicals to the brain. By

breaking down this barrier, more chemicals may accumulate in the brain,

thus producing more chemical sensitivity. It has been reported that an

animal model of MCS shows substantial breakdown of the blood brain

barrier. Nitric oxide is also known to inhibit the activity of certain

enzymes that degrade hydrophobic organic solvents, known as cytochrome

P-450's.

By inhibiting these enzymes, nitric oxide will cause more accumulation of

these compounds because they are broken down much more slowly.

Consequently there are four distinct mechanisms proposed to directly lead

to chemical sensitivity:

• Nitric oxide acting as a retrograde messenger, increasing release of

neurotransmitters (glutamate and aspartate) that stimulate the NMDA

receptors.

• Peroxynitrite depleted energy (ATP) pools, thus making the NMDA

receptors more sensitive to stimulation.

• Peroxynitrite acts to break down the blood brain barrier, thus allowing

greater chemical access to the brain.

• Nitric oxide inhibits cytochrome P-450 activity, thus slowing

degradation of hydrophobic organic chemicals.

It is proposed to be the combination of all four of these mechanisms,

each acting at a different level and therefore expected to act

synergistically with each other that produces the exquisite chemical

sensitivity reported in MCS.

So how do organophosphate pesticides or hydrophobic organic chemicals

initiate this sensitivity and trigger symptoms of MCS? Both are proposed

to stimulate the potential vicious cycle involving too much nitric

oxide/peroxynitrite and too much NMDA activity (figure 1).

Organophosphates and carbamate pesticides, often reported to be involved

in inducing cases of MCS, are both acetylcholinesterase inhibitors,

acting to increase acetylcholine levels which stimulate muscarinic

receptors in the brain.

It is known that stimulating of certain muscarinic receptors produces

increases in nitric oxide! Thus, these two pesticides should be able to

act to stimulate the proposed nitric oxide/peroxynitrite/NMDA vicious

cycle mechanism. Hydrophobic organic solvents are proposed to act by

three possible mechanisms, two producing increases in nitric oxide and

one producing energy depletion and therefore NMDA stimulation.

These three mechanisms are documented in the scientific literature but

none have been tested yet for involvement in MCS. So both the pesticides,

organophosphates and carbamates, and the hydrophobic organic solvents

have known mechanisms which should be able to initiate the proposed

vicious cycle centered on excessive NMDA/nitric oxide/peroxynitrite and

thus initiate MCS. Once MCS has been initiated, by simulating this same

cycle, they are predicted to produce the symptoms of chemical

sensitivity.

Explanations for the most puzzling features reported for MCS:

If this theory is correct, it provides answers to all of the most

difficult questions about MCS.

1. How do pesticides (organophosphates and carbamates) and hydrophobic

organic solvents act to induce cases of MCS? Each acts to initiate a

vicious cycle mechanism involving NMDA receptors, nitric oxide and

peroxynitrite in the brain, with organophosphates/carbamates acting via

one known mechanism and hydrophobic organic solvents acting by another

mechanism.

2. How do hydrophobic organic solvents act to trigger the symptoms of

MCS? They act by the same mechanism proposed for such solvents in #1

above.

3. Why is MCS chronic? Presumably for two reasons: Because of the several

positive feedback loops that maintain the elevated nitric

oxide/peroxynitrite/NMDA activity and also because changes in the

synapses of the brain may be long term.

4. How can MCS victims be so exquisitely sensitive to organic solvents?

Because there are four different mechanisms by which nitric oxide or

peroxynitrite act to produce the response, with the combination of all

four acting synergistically to produce such exquisite sensitivity. The

mechanisms of all four are well documented although their relevance to

MCS can be questioned.

5. How are the symptoms of MCS generated? Possibly by the same mechanisms

proposed earlier for the symptoms of chronic fatigue syndrome.

6. How can we explain the overlaps of MCS with chronic fatigue syndrome,

fibromyalgia, posttraumatic stress disorder and Gulf War syndrome? All of

these are proposed to involve excessive nitric oxide and peroxynitrite

and all may also involved excessive NMDA activity.

October 4, 2005

rvankonynen <richvank@...> wrote:

Hi, Doris.

Since CFS is defined in a way that produces such a heterogeneous

population, I should probably preface everything I say with the

qualification that there are subsets.

Dr. Cheney reported that as of June 2005, he has found low cardiac

output due to cardiomyopathy in 82% of the patients he has tested.

He

noted that his patients tend to be " sicker " patients than those tested

by Peckerman et al., because he does not require them to stop their

medications to be tested, and he treats them, while Peckerman et al.

did require stopping meds and they didn't offer treatment. As a

result, the sicker patients would not have chosen to go to Peckerman

et al to participate in their study, in Cheney's opinion.

***It drives me nuts that he's saying this. All you have to do is read that

Peckerman paper to the end and see where he states and I quote " Another

limitation of this study is that many of our patients were on medications,

including SSRI's. This is the most important paper in CFS history, right? Didn't

he give it thorough going over???

Peckerman doesn't necessarily offer treatment - thats true. He maintains a

large database of potential CFS research subjects. I would think the really sick

patients wouldn't be amenable to being a research subject - that certainly seems

true.

On the other hand I saw Dr. Cheney and I am not a sicker CFS patient but I still

found it a great burden, given my MCS, to have to fly across the country to

Charlotte and then drive an hour and a half to Asheville. Dr. Cheney's

requirement that you do at least one office visit a year only makes it more

difficult. He's hardly easy to access - this I would think would restrict his

load of sicker patients. On the other hand, who knows, maybe his high expenses

might cause not so sick people to hold off from seeing him. They sure didnt

stop me - even not so sick is still pretty bad.

I don't

think we know what fraction of PWCs overall have cardiomyopathy. I

don't think it usually shows up until the later phases of the disorder.

Among the PWCs who have cardiomyopathy, some have a viral infection in

their heart, as shown by Dr. Lerner. Some may have elevated mercury,

similar to the heart attack patients studied in the Italian study. I

think most have the peroxynitrite problem, based on Cheney's work.

I just want to remind everyone that no studies have found increased

peroxynitrite levels in the blood of CFS patients let alone their heart cells.

There is one study that implies peroxynitrite may be increased in the blood. Its

all SOOOO theoretical at this point. Pall's theory is still just that and so in

Cheney's. A breakdown at any point in this rather fragile, as least so far as I

see it, theory, could invalidate either much of it or all of it. I really think

we're in for alot more twists and turns before this thing will be finally

decided. There are times I just cannot believe it when I hear researchers or

doctors say they KNOW what is going on in CFS.

I think we have a lot to learn about what fraction of PWCs has what.

Thanks for raising this point. I get a little carried away and

oversimplify sometimes.

Rich

> Do you mean you think this is correct in all PWC's, or just a subset?

> Thanks

> Doris

> ----- Original Message -----

> From: rvankonynen

> I also think that he is correct in concluding that PWCs exhibit

> diastolic cardiomyopathy, that it results from a mitochondrial

> dysfunction in the heart muscle cells that lowers the rate of

> production of ATP, and that it can explain many of the symptoms of

> CFS.

>

> I also think that he is correct in concluding that a rise in

> peroxynitrite is responsible for this mitochondrial dysfunction.

>

October 5, 2005

As always thanks for the complete response. While I may at times disagree with

your conclusions I always appreciate your probing analysis of the situation and

your very clear way of expressing it.

rvankonynen <richvank@...> wrote:

Hi, Cort.

In his talk, Dr. Cheney presented the latest modification of his

pathogenesis model for CFS. The first thing it starts with is his

Phase 1, with a viral infection and elevated RNase-L activity.

However, I think the disease process in CFS actually has to start

earlier than that. Most everyone in the general population is

carrying (in the latent state) the viruses that show up producing

infections in people who get CFS. There has to be an explanation

for why some people experience viral reactivation, RNase-L

dysfunction, and CFS, while most people do not, even though they are

carrying these same viruses in their bodies.

I believe it starts in many people with certain genetic

polymorphisms. These have not yet been identified for CFS, but they

have to be there, based on the evidence of the twin studies and the

familial occurrence of CFS. I hope these will be studied and

identified soon. The CDC has this in their current research plan.

***My understanding of the genetic component to CFS is that it is there and it

is real and it is important but that it cannot account for most of risk one has

for getting CFS.