CDC Gene Expression Paper

[Guest guest]

Hi, all.

Some time ago I posted a review of Suzanne Vernon's talk at the NIH

CFS workshop last June. At that time she reported that a paper had

been submitted to a journal on the latest results of the CDC's CFS

gene expression work. It appears that this paper has now been

published in electronic form. Fred Springfield posted the link to

the full paper on Co-Cure yesterday:

http://www.translational-medicine.com/content/pdf/1479-5876-1-10.pdf

I would like to make a few comments about the paper.

First, I think it continues to show the promise of gene expression

measurements in elucidating the pathophysiology of CFS. I expect

that we will be hearing a lot more about this in the future, and I

think it will be very helpful.

Second, I think it is important to keep in mind that this study was

conducted on peripheral blood mononuclear cells from PWCs, i.e. T

and B lymphocytes, monocytes (which can later become macrophages)

and natural killer cells. While it's possible that the results may

reflect on the gene expression of other types of cells in the body,

I think it is best to focus the interpretation of the results on

these particular white blood cells unless or until this

corresponsence is established. Therefore, right now this study is

really telling us most directly about gene expression in certain

cells of the immune system in CFS. The fact that differences are

found is consistent with the fact that dysfunction of the immune

system is known to be a characteristic of CFS, and that the

dysfunction appears to vary between different PWCs.

Third, the work reported in this particular paper does not compare

the gene expression in PWCs to that in normal, healthy controls.

Rather, it seeks to identify subsets within the PWC population by

means of the simultaneous application of clinical and

epidemiological characteristics and gene expression results. It is

successful in distinguishing gene expression differences between

those with sudden and gradual onset of CFS. I think this is an

important result, in that it shows that there are significant

differences in the behavior of immune system cells between these two

groups. At a minimum, I think it points out that the immune system

is not operating in the same way in these two groups of PWCs. Since

sudden onset of CFS is usually accompanied by a viral-type

infection, whereas gradual onset may not be, this seems to make some

sense. This result also gives more support to the need that many

researchers have expressed to identify the various subsets in CFS in

order to make headway (divide and conquer).

Fourth, this paper does not list the particular genes that were

found to have significantly different expression in the two groups.

However, it does present the categories of genes that were found to

be most differently expressed. Primary among these were the genes

associated with metabolism, and in particular those involved with

glucose metabolism, glycolysis, and oxidative phosphoryation. These

genes were found to be downregulated in the group with gradual onset

as compared to those with sudden onset of CFS. (One could also say

that these genes were upregulated in the sudden onset group relative

to the gradual onset group. Since no comparison is given to normal

controls, it isn't possible to say which of these is the better way

to view this result.) What does this mean? I think it's difficult

to say much until we have more details, but as a minimum it says

that these immune cells are exhibiting important differences in

their intermediary metabolism between the sudden and gradual onset

groups. Intermediary metabolism is the means by which the cells

burn fuel and obtain usable energy in the form of ATP to operate

biochemical reactions to carry on the business of the cell. I think

that this result suggests that these immune cells are trying much

harder to ramp up their metabolism in the sudden onset cases than in

the gradual onset cases. Whether or not they are succeeding in

doing so will depend on other factors that have not yet been

measured and reported, such as the populations of the enzymes that

these genes code for, i.e. the so-called proteomics. Just because

the genes are expressed at a higher rate does not mean that this is

successfully translated into production of the enzymes. More

information will be needed to determine this.

Fifth, I think this paper shines a spotlight on the importance of

dysfunction of intermediary metabolism in CFS. While a few

researchers and clinicians have been focusing on intermediary

metabolism, I think that this area has heretofore been too much of a

backwater in CFS research. More attention has been given to other

aspects, which, I have suspected, occur farther on in the

pathogenesis than the metabolic dysfunction, though they are

undeniably important. I'm hopeful that these results will cause

more attention to be drawn to the intermediary metabolism in CFS

research.

Sixth, for those who have heretofore remained unconvinced that there

are biochemical aspects involving organic body systems in CFS (as

opposed to solely psychological aspects), this study should help

them to consider a major paradigm shift.

Finally, I think this work is very tantalizing, and is just a

start. It will be very interesting to see a detailed comparison

between the gene expression of PWCs and normal controls. It will

also be nice to know specifically which genes are being expressed

differently. And it will be even more interesting to see what the

proteomics are, corresponding to the relevant genes. When we know

which enzymes are up or downregulated in which cases, we will be in

a better position to understand the pathophysiology, particularly as

it involves the immune system. The paper also discusses possible

isolation of the different types of peripheral blood mononuclear

cells for study of their individual gene expression, which will also

be interesting.

Rich Van Konynenburg, Ph.D.

[Guest guest]

Rich,

I have read your comments with interest, but also only with partial

understanding. I am afraid I have lost sight of the forest for the trees.

Does all this mean that genetic factors are the likely " cause " of the disease or

just that the best we can ultimately do is look at and try to fix deranged

processes and that the cause is really still unknown? Or that learning the cause

is still way down the line?

(I understand the importance of demonstrating that there is a patholgy going on

other than " all-in-your head. " )

I suppose one can at least conclude that if one's immune cells are doing

" porely, " it makes sense to try to boost them in some way?

Thanks,

Adrienne

CDC Gene Expression Paper

Hi, all.

Some time ago I posted a review of Suzanne Vernon's talk at the NIH

CFS workshop last June. At that time she reported that a paper had

been submitted to a journal on the latest results of the CDC's CFS

gene expression work. It appears that this paper has now been

published in electronic form. Fred Springfield posted the link to

the full paper on Co-Cure yesterday:

http://www.translational-medicine.com/content/pdf/1479-5876-1-10.pdf

I would like to make a few comments about the paper.

[Guest guest]

Hi, Adrienne.

Gene expression study in CFS is probably best viewed as a way to try

to get a better understanding of the inner workings of the disease

process.

Looking at gene expression gives a snapshot of the rates at which

the cells are using their genetic code to try to make various

enzymes, which form the machinery of the cell's factory, so to

speak. Unfortunately, this is quite a few steps removed from

understanding the cause (or causes) or figuring out the best

treatment, let alone cure, for CFS.

It must be extremely frustrating to have been suffering from such a

debilitating disease for so many years, and to have the scientists

still puzzling over trying to understand the basic things about it.

However, we have to start where we are, and I hope that it's at

least somewhat encouraging that there are some people working on it

and that they are using some of the latest methods to study it.

There is evidence of genetic predisposition in at least some cases

of CFS. Gene expression work does not study this, however. The

Genovations tests offerred by Great Smokies Diagnostic lab

(www.gsdl.com) does look at the genetic variations in individual

PWCs.

I do think there is benefit in boosting the immune system in many

cases of CFS, but until we understand the whole picture, it doesn't

seem that this alone will usually solve the problem completely.

My reading of the available information continues to be that both

genetic factors and environmental (or lifestyle) factors together

are involved in bringing about the onset of CFS.

Rich

> Rich,

> I have read your comments with interest, but also only with

partial understanding. I am afraid I have lost sight of the forest

for the trees.

>

> Does all this mean that genetic factors are the likely " cause " of

the disease or just that the best we can ultimately do is look at

and try to fix deranged processes and that the cause is really still

unknown? Or that learning the cause is still way down the line?

>

> (I understand the importance of demonstrating that there is a

patholgy going on other than " all-in-your head. " )

> I suppose one can at least conclude that if one's immune cells are

doing " porely, " it makes sense to try to boost them in some way?

> Thanks,

> Adrienne

[Guest guest]

rich

thanks for this posting. i ahven't had a chance to give a close

reading of the paper yet, but i was wondering about something you

mentioned in your assessment.

you said that this paper does not give results of a control group (ie

healthy subjects). in the study, did they have a control group and

they decided to not publish the results, or did they not do a control

group?

i'm assuming that it is the former because it would be absurd to do

this study without considering the results of healthy subjects.

that leads me to the question of why they did not include the results

of the control group in this paper. it seems that that is the only

way to really gain anything from this type of investigation.

thanks

bill

> > Rich,

> > I have read your comments with interest, but also only with

> partial understanding. I am afraid I have lost sight of the forest

> for the trees.

> >

> > Does all this mean that genetic factors are the likely " cause " of

> the disease or just that the best we can ultimately do is look at

> and try to fix deranged processes and that the cause is really

still

> unknown? Or that learning the cause is still way down the line?

> >

> > (I understand the importance of demonstrating that there is a

> patholgy going on other than " all-in-your head. " )

> > I suppose one can at least conclude that if one's immune cells

are

> doing " porely, " it makes sense to try to boost them in some way?

> > Thanks,

> > Adrienne

[Guest guest]

>

I like I suspect everyone in this group feel lucky to have Rich's

knowledge and his dedication to explicating some issues and

evaluating them in ways that I for one couldn't myself do.

And the postre this paper is no exception. I of course,with Rich,feel

it's very important to want to see Vernon's work use a matched sample

group of healthy people.

That said, Rich's comments (below), which come up often and always

raise a similar question in me,is something I'd like to comment and

raise questions about.

Though for years I've read the clinical experience with this disease

from my colleague patients, it's of course my own case that I'm most

familiar with. And my case, no matter how many times I revisit it, I

come out wondering if the division into gradual and sudden onset is

either a sufficiently delineated subgrouping (i.e., are graduals

sufficiently similar to be considered a group or do they represent

several groups). And is the distinction between gradual and sudden

onset possibly one more of life circumstances and perception and even

personality than metabolic.

I will use my case to explicate these potential problems.

The day before the day I got so sick and that though unbeknownst to

me would be the first day of not a week's flu but years of illness

followed a day in which I worked l2 hours, and l2 very difficult

hours at a very demanding job.

My symptoms were viral like. I awakened with severe vertigo, a low

fever,aches, a heavyness in the chest, etc. And the first and second

doc I saw called it " post-viral benign positional vertigo. "

No treatment besides trying meclazine (for motion sickness) was felt

to be appropriate, and meclazine didn't help.

YET, while for about 6 years prior I somehow managed to raise a

child, go thru a marital separation, run a three-story house, be

responsible for my car and my sweet dog in addition to my child, and

take classes as part of doctoral studies, upon looking back I realize

that while I was able to pull it off, my health had in fact gone down

hill for a while, though I managedto do it all.

Over those 6 years many things happened to support my saying that

there were inroads to my health ,and in fact some of them prefigured

what I experienced at " sudden onset " .

I've listed them in the past and I'm falling asleep as I write this,

so I won't enumerate them,but have and could and they felt and

seemed, in retrospect, very much like,even the pictures of what I

frankly now believe was, which , this same illness " fighting to

express itself " and me being able to resist it's full takeover,

though even when the episodes ended I defintly experienced that my

health was deteriorating and it worried me big time. My life demands

were a budding career that I felt could not be interupted; a child I

was raising though he was my stepson; the house, my dog, my

doctorate, and no one to support me. . .

So I wonder if gradual onset might not often be a very defensive

denial of how damn sick one is, which then of course makes you sicker.

I can't go on now and maybe don't have to,but I wonder how many

gradual onsets take place among folks who claim to be sudden onsets

and whether thus the differences they might have found are

differences that reflect biological issues that emanate from that

pushing from denial.

Rich, I snipped your report till it talk about these two distinctive

groups but I'm raising the question whether the distinction is

between gradual and sudden onset, and also whether your comments

about the more viral nature of the latter might not be the case.

I so wish that this didn't have to be answered without the missing

excellent epidemiological data we've never been given.

And I don't think my suggestion isn't compatable with what you

characterize as the immune system operating differently.

I'm curious to have your response and thos of others..

I better end this before I forget to erase the jibberish I write as I

fall asleep midsentence!!!!!

Again thanks. How I'd love to connect with S. Vernon about this.

Thanks again, Rich. Getting these reports and then your further

thoughts puts us so much further ahead.

Judith Wisdom

*******

[after snipping the beginning the following is the part of Rich's

comments that are related to my comments above.]

> the work reported in this particular paper does not compare

> the gene expression in PWCs to that in normal, healthy controls.

> Rather, it seeks to identify subsets within the PWC population by

> means of the simultaneous application of clinical and

> epidemiological characteristics and gene expression results. It is

> successful in distinguishing gene expression differences between

> those with sudden and gradual onset of CFS. I think this is an

> important result, in that it shows that there are significant

> differences in the behavior of immune system cells between these

two

> groups. At a minimum, I think it points out that the immune system

> is not operating in the same way in these two groups of PWCs.

Since

> sudden onset of CFS is usually accompanied by a viral-type

> infection, whereas gradual onset may not be, this seems to make

some

> sense. This result also gives more support to the need that many

> researchers have expressed to identify the various subsets in CFS

in

> order to make headway (divide and conquer).

>

> Fourth, this paper does not list the particular genes that were

> found to have significantly different expression in the two

groups.

> However, it does present the categories of genes that were found to

> be most differently expressed. Primary among these were the genes

> associated with metabolism, and in particular those involved with

> glucose metabolism, glycolysis, and oxidative phosphoryation.

These

> genes were found to be downregulated in the group with gradual

onset

> as compared to those with sudden onset of CFS. (One could also say

> that these genes were upregulated in the sudden onset group

relative

> to the gradual onset group. Since no comparison is given to normal

> controls, it isn't possible to say which of these is the better way

> to view this result.) What does this mean? I think it's difficult

> to say much until we have more details, but as a minimum it says

> that these immune cells are exhibiting important differences in

> their intermediary metabolism between the sudden and gradual onset

> groups. Intermediary metabolism is the means by which the cells

> burn fuel and obtain usable energy in the form of ATP to operate

> biochemical reactions to carry on the business of the cell. I

think

> that this result suggests that these immune cells are trying much

> harder to ramp up their metabolism in the sudden onset cases than

in

> the gradual onset cases. Whether or not they are succeeding in

> doing so will depend on other factors that have not yet been

> measured and reported, such as the populations of the enzymes that

> these genes code for, i.e. the so-called proteomics. Just because

> the genes are expressed at a higher rate does not mean that this is

> successfully translated into production of the enzymes. More

> information will be needed to determine this.

>

> Fifth, I think this paper shines a spotlight on the importance of

> dysfunction of intermediary metabolism in CFS. While a few

> researchers and clinicians have been focusing on intermediary

> metabolism, I think that this area has heretofore been too much of

a

> backwater in CFS research. More attention has been given to other

> aspects, which, I have suspected, occur farther on in the

> pathogenesis than the metabolic dysfunction, though they are

> undeniably important. I'm hopeful that these results will cause

> more attention to be drawn to the intermediary metabolism in CFS

> research.

[snipped again]

>

> Rich Van Konynenburg, Ph.D.

[Guest guest]

I was surprised at a lack of a control group as well. It made me wonder

if there is another study out there waiting to published. There is no

indication of that in the CDC web site. They do mention interestingly

enough two moreo ongoing studies involving gene expression in CFS patients

(and I think controls) before and after an allergic challenge and one

involving protein expression. Linking the protein expression and gene

expression studies would be interesting because the protein expression study

would indicate if the genes expressed actually resulted in protein

synthesis. Since proteins do do the work in cells I would think it would

tell more than the gene expression study.

I can only assume that they felt that their prior study involving

controls -as small as it was - was sufficient to demonstrate the differences

did exist.

In regard to another question of gradual vs onset I think the terms

obscure, at least I hope they do, fundamental differences in symptoms

between the two groups. I believe the sudden onset is characterized by

flulike symptoms that, no matter how they may have waxed and waned prior to

the actual 'onset', present themselves in a dramatic fashion such that the

patient never recovers from the 'flu' they caught. As such they the onset

is memorable. Gradual cases - of which I am one - do not, I believe,

present flulike symptoms. My symptoms at onset included incredible fatigue,

muscle pain, accelerated heartbeat, difficulty standing, etc. No flulike

symptoms at all. In fact no colds at all for quite awhile.

Cort

>From: " winsomme " <winsomme@...>

>Reply-

>

>Subject: Re: CDC Gene Expression Paper

>Date: Fri, 05 Dec 2003 22:16:43 -0000

>

>rich

>

>thanks for this posting. i ahven't had a chance to give a close

>reading of the paper yet, but i was wondering about something you

>mentioned in your assessment.

>

>you said that this paper does not give results of a control group (ie

>healthy subjects). in the study, did they have a control group and

>they decided to not publish the results, or did they not do a control

>group?

>

>i'm assuming that it is the former because it would be absurd to do

>this study without considering the results of healthy subjects.

>

>that leads me to the question of why they did not include the results

>of the control group in this paper. it seems that that is the only

>way to really gain anything from this type of investigation.

>

>thanks

>bill

>

>

> > > Rich,

> > > I have read your comments with interest, but also only with

> > partial understanding. I am afraid I have lost sight of the forest

> > for the trees.

> > >

> > > Does all this mean that genetic factors are the likely " cause " of

> > the disease or just that the best we can ultimately do is look at

> > and try to fix deranged processes and that the cause is really

>still

> > unknown? Or that learning the cause is still way down the line?

> > >

> > > (I understand the importance of demonstrating that there is a

> > patholgy going on other than " all-in-your head. " )

> > > I suppose one can at least conclude that if one's immune cells

>are

> > doing " porely, " it makes sense to try to boost them in some way?

> > > Thanks,

> > > Adrienne

>

_________________________________________________________________

Shop online for kids’ toys by age group, price range, and toy category at

MSN Shopping. No waiting for a clerk to help you! http://shopping.msn.com

[Guest guest]

I completely agree. I had the same situation as you. " Sudden onset " , but then

on the other hand there were things wrong with me in the years leading up that

time that probably wouldn't have happened to a person who was " well " . I wonder

how many people truly are " sudden onset " in the sense that they were perfectly

healthy for many years, then had sudden onset. I agree with you that people's

perceptions are probably to minimize the things that happened before onset,

write them off as minor, inconsequential, or unrelated or even forget them.

Doris

[Guest guest]

Is this true? Did the researchers use this definition (flu-lie=rapid onset)?

I also read your other post and found your thoughts interesting. The " flu-like "

description certainly seems easier to determine than whether one is fast or slow

onset. However, flu-like is variable. For me " flu-like " comes and goes with

the viruses and bacterias I have at the time. So maybe it has more to do with

the secondary infections than anything else. Which could point basically to a

problem in the immune system where you cannot fight normal pathogens. Maybe

those without " flu-like " symptoms have better immune function.

Doris

----- Original Message ----- > tell more than the gene expression study.

I believe the sudden onset is characterized by

> flulike symptoms that, no matter how they may have waxed and waned prior

to

> the actual 'onset', present themselves in a dramatic fashion such that the

> patient never recovers from the 'flu' they caught. As such they the onset

> is memorable. Gradual cases - of which I am one - do not, I believe,

> present flulike symptoms. My symptoms at onset included incredible

fatigue,

> muscle pain, accelerated heartbeat, difficulty standing, etc. No flulike

> symptoms at all. In fact no colds at all for quite awhile.

[Guest guest]

Hey guys, I remember reading something released by the CDC several

months ago that they were able to use the gene expression test to

identify the ones with CFS and the healthy people. I cannot remember

where I read that but I will think on it and maybe it will come to

me. When I read that I was wondering if they could do that, why

wouldn't that be a marker for CFS? Also since every PWC's gene

expressions were the same, would this indicate that there are not

subsets?? I don't know much about gene's but wouldn't a PWC's with a

different subset produe different gene expressions?

Bob

[Guest guest]

Bill,

In an earlier paper, the CDC group did do a comparison with a

control group, but it was a relatively small, preliminary study,

without a lot of details. I expect that they will be publishing a

more detailed comparison with controls as they are able to. Since

this type of analysis is fairly new, I would expect that they are

being pretty cautious about publishing results until they are sure

they have checked everything over. No scientist wants to have to

publish a retraction and acknowledge that they made mistakes. I

think we will just have to be patient.

Rich

> rich

>

> thanks for this posting. i ahven't had a chance to give a close

> reading of the paper yet, but i was wondering about something you

> mentioned in your assessment.

>

> you said that this paper does not give results of a control group

(ie

> healthy subjects). in the study, did they have a control group and

> they decided to not publish the results, or did they not do a

control

> group?

>

> i'm assuming that it is the former because it would be absurd to

do

> this study without considering the results of healthy subjects.

>

> that leads me to the question of why they did not include the

results

> of the control group in this paper. it seems that that is the only

> way to really gain anything from this type of investigation.

>

> thanks

> bill

[Guest guest]

Cort, Judith W. and the group,

I agree that the distinction between sudden and gradual onset needs

to be more carefully studied. I think that the fact that the CDC

group was able to find significant differences in gene expression

between these two rather roughly defined groups suggests that there

is something significant there, and it needs to be further studied.

Perhaps sudden onset implies a certain type or types of viral

infection, and the immune system responds differently in this case

than it does when there is a more gradual buildup of stressors. And

yes, it isn't easy to clearly delineate whether or not a person with

sudden onset might have had some gradual things going on before

that. I view this result as an indicator that this needs to be

looked at more carefully, rather than a final conclusion in itself.

It's said that the wheels of justice grind slowly. I think the

wheels of science often do, too, although sometimes they make a big

surge, as in Kuhn's concept of scientific revolutions. We

can hope for some of those in CFS, and I think the gene expression

work is a place where big jumps could happen.

Rich

> > > > Rich,

> > > > I have read your comments with interest, but also only with

> > > partial understanding. I am afraid I have lost sight of the

forest

> > > for the trees.

> > > >

> > > > Does all this mean that genetic factors are the

likely " cause " of

> > > the disease or just that the best we can ultimately do is look

at

> > > and try to fix deranged processes and that the cause is really

> >still

> > > unknown? Or that learning the cause is still way down the line?

> > > >

> > > > (I understand the importance of demonstrating that there is a

> > > patholgy going on other than " all-in-your head. " )

> > > > I suppose one can at least conclude that if one's immune

cells

> >are

> > > doing " porely, " it makes sense to try to boost them in some

way?

> > > > Thanks,

> > > > Adrienne

> >

>

> _________________________________________________________________

> Shop online for kids' toys by age group, price range, and toy

category at

> MSN Shopping. No waiting for a clerk to help you!

http://shopping.msn.com

[Guest guest]

My experience was somewhat like Judith Wisdom's experience in terms of sudden

vs. gradual, but I strongly identify with the sudden onset camp. At one

point, I saw activist Schweitzer use the term " prodrome " to describe the

shadowy symptoms that happen for many CFIDS patients in the years before they

REALLY get sick with the flu-like sudden onset. To me, sudden onset

characterizes

those who may or may not have had prodrome symptoms, but who have that

practically-overnight disruption of health. I went from being a very active,

young,

full-time college student who spent most evenings cycling or doing weight

training to having trouble walking up one flight of stairs -- all with the

change

of that " flu-like " illness. Also, I don't think anyone who has experienced

the " flu-like " illness would really call it flu-like. As Hillenbrand

said about CFIDS fatigue, this is like comparing a nuclear bomb to a match. The

" flu-like " illness was so UNlike any flu I had ever experienced -- even though

it had the fevers, sore throats, headaches, malaise, and other symptoms --

that I was acutely aware, at the time, that I wasn't having something exactly

" flu-like. " Along with the typical flu-like symptoms, I was experiencing severe

cognitive problems, disorientation, light sensitivity, bizarre new allergies,

vertigo, etc.

I wonder how many sudden onset patients, though, have marked prodrome

symptoms. I did. A good four years before I got sick, I began to have strange

visual problems and trouble reading, symptoms I now know to be very CFIDS-like

--

they were severe enough to be a big part of why I dropped out of school for a

semester. My first english papers were so confusing and nonsensical that my

professor called me in for a conference. Then again, I somehow managed to pull

it together and major in Creative Writing. I never caught the typical college

colds and flu that passed around the dorms and classrooms, and in general I

was extremely high-functioning before I got sick. But there were shades of

CFIDS in my daily life, like the sore throat and difficulty swallowing that I

had

for almost a year before the actual CFIDS " flu. " However, I never would have

considered those symptoms in the years before CFIDS to be anything like

full-blown CFIDS. They were there, but my level of functioning was so

dramatically

different once I got the sudden-onset " flu. "

I know I had pesticide exposures in the time before I got sick, but they

weren't unusual ones -- they were the type of spraying that people do in

households all the time (plus I was living in an agricultural area for most of

my life

-- but so are many people). When I look at CFIDS, I often look to

environmental causes in my case, but there are other things that throw a wrench

in that

theory. Like, I was dating someone with chronic Lyme symptoms when I got sick.

And, the semester I took off from college I lived in Berkeley, CA, where (if

I remember correctly) that same year hundreds of CFIDS cases were noted in

the East Bay.

Maybe there is actually a third category -- sudden onset with prodrome.

Peggy

<<Though for years I've read the clinical experience with this disease

from my colleague patients, it's of course my own case that I'm most

familiar with. And my case, no matter how many times I revisit it, I

come out wondering if the division into gradual and sudden onset is

either a sufficiently delineated subgrouping (i.e., are graduals

sufficiently similar to be considered a group or do they represent

several groups). And is the distinction between gradual and sudden

onset possibly one more of life circumstances and perception and even

personality than metabolic.>>

[Guest guest]

Well, definitely they need better definitions of rapid onset vs gradual onset,

like everything else in researching this illness.

I have to disagree with you on flu-like however. I definitely have often had

flu-like symptoms and I have no problem calling them flu-like. In fact, it

seems to pretty well describe those symptoms. That is not to say I didn't have

other symptoms on top of those, such as severe cognitive problems and other

issues. But to me flu-like perfectly describes the sore throats, general

malaise/crappy feeling, inability to do much but lie around, headaches, etc.

And I find most people can related to it because they have all had the flu.

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

From: Peggomatic@...

Also, I don't think anyone who has experienced

the " flu-like " illness would really call it flu-like. As Hillenbrand

said about CFIDS fatigue, this is like comparing a nuclear bomb to a match.