A reference supporting Dr. Marshall's model of pathogenesis

[Guest guest]

FYI,

The model of pathogenesis seems to be coming together quite nicely

for those of us PWCs. These are exciting times...we can hope,

Am J Med. 1993 Oct;95(4):407-12. Related Articles, Links

Serum angiotensin-converting enzyme as a marker for the chronic

fatigue-immune dysfunction syndrome: a comparison to serum

angiotensin-converting enzyme in sarcoidosis.

Lieberman J, Bell DS.

Department of Medicine, Veterans Affairs Medical Center/UCLA,

Sepulveda 91343.

PURPOSE: To study the reliability of a serum angiotensin-converting

enzyme (ACE) assay as a marker for the chronic fatigue-immune

dysfunction syndrome (CFIDS), and to compare some enzyme

characteristics of ACE in CFIDS with that in sarcoidosis. PATIENTS

AND METHODS: Forty-nine patients with CFIDS and 56 endemic control

subjects from Lyndonville, New York, and Charlotte, North Carolina;

plus 23 untreated patients with active sarcoidosis, 24 with

sarcoidosis receiving corticosteroid therapy, and 32 patient controls

without sarcoidosis from California. Serum ACE levels were determined

with a spectrophotometric method. The effect of freezing and thawing

and the effect of storage at 4 degrees C were compared between CFIDS

and sarcoidosis samples. RESULTS: Serum ACE levels were elevated in

80% of patients with CFIDS and 30% of endemic control subjects as

compared with 9.4% of nonendemic California control subjects. The ACE

activity in CFIDS differed from that in sarcoidosis because of its

lability with storage at 4 degrees C in CFIDS and its partial

activation with freezing and thawing. Thus, ACE activity was elevated

in the majority of CFIDS patients either upon initial assay or upon a

subsequent assay after refreezing. ACE activity was elevated in 87%

of patients with active sarcoidosis and was not affected by storage

or freezing and thawing. CONCLUSIONS: Serum ACE elevations may be a

useful marker for CFIDS, especially if a method can be developed to

distinguish ACE in CFIDS from that in sarcoidosis. The sensitivity

for CFIDS was 80%, with 68% specificity in an endemic area. The

increased prevalence of serum ACE elevations in endemic controls as

compared with nonendemic controls suggests that an ACE increase may

be an early manifestation of CFIDS and supports the concept that

CFIDS is a definite disease state.

TABLE 1 Group No. Mean serum ACE(u/l) No. +

ACE

Lyndonville CFIDS* 20 49.1 18 (90%)

Controls (same area) 33 30.9 9 (27%)

Charlotte, NC CFIDS 29 39.6 21 (72.4%)

Controls 23 34.8 9 (39.2%)

Southern California

Controls 32 26.1 3 (9.4%)

Sarcoidosis (untreated) 23 51.9 20 (87%)

Sarcoidosis

(treated with steroids) 24 33.4 9 (38%)

[Guest guest]

Dear , I have read every single post on the lymenet threads and

have tried to digest as much as my simple mind can in regards to

using Benicar to block angiotensin II receptors and stop the

inflammation cascade. In this study that you referenced what

exactly does high ACE mean? When high ACE levels are lowered does

that mean inflammation has subsequently lowered too? Does Benicar

lower ACE and if so does lowering ACE levels result in inactivation

of the angiotensin II receptors or is it the other way around? This

is all confusing to me. I did do some studying and read that in

humans inhibition of angiotensin II activity has been associated

with improved cognition, so it seems we are on the right track.

Only thing is I told you of how 5 years ago following a surgery I

took dexamethasone for 13 days along with Zithromax for a few days.

Even though this was before the later deep stage CFS that I went

into and I never really knew I had CFS before this, once on the

dexamethasone I noticed I could think clearly for the first time in

my life. , would you mind doing some research into any

similarities b/t what dexamethasone does and what Benicar may do.

If Benicar can do similar to what dexamethasone did it will truly be

a savior and I could get back the powerful mind that I only had for

a couple weeks in my whole life while on dexamethasone.

Interestingly my cognition, memory and focus kept dramatically

increasing even after I stopped dexamethasone and seemed to peak a

week after I got off of it. It's not just me that this had an

effect on b/c another person told me of how he came out of surgery

and was also given abx and dexamethasone and was able to think

clearly for the first time he could remember. So I think we have

certainly hit on a key issue here. Thing is I reported on this to

many doctors and people in this group and of course no one really

cares or could ever describe why dexamethasone (and perhaps coupling

it with abx is irrelevant or could be important as well?) had this

effect or worried about investigating it further, so it is no wonder

we don't have our cure yet as one can stumble on a key part of cure

but since it hasn't happened to others yet no one bothers to check

it out why such and such is happening so that we can hopefully

extrapolate from that and move forward on improving results through

another similar method or means and going from there. I did google

search here:

http://www.google.com/search?hl=en & ie=ISO-8859-1 & oe=ISO-8859-1 & q=%

22angiotensin+II%22+dexamethasone

but again, my understanding is limited as I am a layman. One thing

I did note is dexamethasone increases ACE. But if CFSers already

have increased ACE then how would that be a good thing? Even when

on abx and feeling physically near cured I still did not have total

absense of brain fog like I did when on dexamethasone. Thanks for

your time.

> FYI,

>

> The model of pathogenesis seems to be coming together quite nicely

> for those of us PWCs. These are exciting times...we can hope,

>

>

>

>

> Am J Med. 1993 Oct;95(4):407-12. Related Articles, Links

>

> Serum angiotensin-converting enzyme as a marker for the chronic

> fatigue-immune dysfunction syndrome: a comparison to serum

> angiotensin-converting enzyme in sarcoidosis.

>

> Lieberman J, Bell DS.

>

> Department of Medicine, Veterans Affairs Medical Center/UCLA,

> Sepulveda 91343.

>

> PURPOSE: To study the reliability of a serum angiotensin-converting

> enzyme (ACE) assay as a marker for the chronic fatigue-immune

> dysfunction syndrome (CFIDS), and to compare some enzyme

> characteristics of ACE in CFIDS with that in sarcoidosis. PATIENTS

> AND METHODS: Forty-nine patients with CFIDS and 56 endemic control

> subjects from Lyndonville, New York, and Charlotte, North Carolina;

> plus 23 untreated patients with active sarcoidosis, 24 with

> sarcoidosis receiving corticosteroid therapy, and 32 patient

controls

> without sarcoidosis from California. Serum ACE levels were

determined

> with a spectrophotometric method. The effect of freezing and

thawing

> and the effect of storage at 4 degrees C were compared between

CFIDS

> and sarcoidosis samples. RESULTS: Serum ACE levels were elevated in

> 80% of patients with CFIDS and 30% of endemic control subjects as

> compared with 9.4% of nonendemic California control subjects. The

ACE

> activity in CFIDS differed from that in sarcoidosis because of its

> lability with storage at 4 degrees C in CFIDS and its partial

> activation with freezing and thawing. Thus, ACE activity was

elevated

> in the majority of CFIDS patients either upon initial assay or

upon a

> subsequent assay after refreezing. ACE activity was elevated in 87%

> of patients with active sarcoidosis and was not affected by storage

> or freezing and thawing. CONCLUSIONS: Serum ACE elevations may be a

> useful marker for CFIDS, especially if a method can be developed to

> distinguish ACE in CFIDS from that in sarcoidosis. The sensitivity

> for CFIDS was 80%, with 68% specificity in an endemic area. The

> increased prevalence of serum ACE elevations in endemic controls as

> compared with nonendemic controls suggests that an ACE increase may

> be an early manifestation of CFIDS and supports the concept that

> CFIDS is a definite disease state.

>

> TABLE 1 Group No. Mean serum ACE(u/l) No. +

> ACE

>

> Lyndonville CFIDS* 20 49.1 18 (90%)

>

> Controls (same area) 33 30.9 9 (27%)

>

> Charlotte, NC CFIDS 29 39.6 21 (72.4%)

>

> Controls 23 34.8 9 (39.2%)

>

> Southern California

> Controls 32 26.1 3 (9.4%)

>

> Sarcoidosis (untreated) 23 51.9 20 (87%)

>

> Sarcoidosis

> (treated with steroids) 24 33.4 9 (38%)

[Guest guest]

,

ACE, stands for angiotensin converting enzyme (ACE). It is the

enzyme that converts the inactive form of angiotensin into the

active form, angiotensin II. Angiotensin II (AT-II) is what

triggers the inflammatory cascade we are discussing in PWCs.

Activated macrophages (a primary Th1 cells) produces a lot of ACE.

Reducing ACE can inhibit some of this Th1 inflammatory

cascade...however, the best way to block the perpetual inflammatory

cycle is to block the angiotensin II type 1 receptors found on the

macrophages...that's what Benicar does.

It doesn't take much ACE to produce significant amounts of AT-II

from angiotensin. So, it's much more effective to block the AT-II

receptors instead.

Benicar can lower ACE...but it's indirectly related to it's specific

ability to antagonize AT-II type 1 receptors.

You'll be glad to know that Benicar has the same benefits of

dexamethasone in regards to extinguishing inflammation, however it

is very fortunate for us that it does this without the immuno-

suppressive effects that steroids have.

In fact, Benicar has the ability to modulate the immune system so

that it actually enhances it's ability to deal with the pathogens

triggering the initial Th1 inflammation. It also seems to encourage

the Th1 inflammatory response to shift to a Th2 immune response.

The reason no one was interested about the dexamethasone is because

they didn't understand the angiotensin connection and the knew you

couldn't stay on dexamethasone as a long term therapy.

Our knowledge regarding the cause and cure for the pathogenesis of

PWCs is rapidly accelerating.

Sincerely,

> > FYI,

> >

> > The model of pathogenesis seems to be coming together quite

nicely

> > for those of us PWCs. These are exciting times...we can hope,

> >

> >

> >

> >

> > Am J Med. 1993 Oct;95(4):407-12. Related Articles, Links

> >

> > Serum angiotensin-converting enzyme as a marker for the chronic

> > fatigue-immune dysfunction syndrome: a comparison to serum

> > angiotensin-converting enzyme in sarcoidosis.

> >

> > Lieberman J, Bell DS.

> >

> > Department of Medicine, Veterans Affairs Medical Center/UCLA,

> > Sepulveda 91343.

> >

> > PURPOSE: To study the reliability of a serum angiotensin-

converting

> > enzyme (ACE) assay as a marker for the chronic fatigue-immune

> > dysfunction syndrome (CFIDS), and to compare some enzyme

> > characteristics of ACE in CFIDS with that in sarcoidosis.

PATIENTS

> > AND METHODS: Forty-nine patients with CFIDS and 56 endemic

control

> > subjects from Lyndonville, New York, and Charlotte, North

Carolina;

> > plus 23 untreated patients with active sarcoidosis, 24 with

> > sarcoidosis receiving corticosteroid therapy, and 32 patient

> controls

> > without sarcoidosis from California. Serum ACE levels were

> determined

> > with a spectrophotometric method. The effect of freezing and

> thawing

> > and the effect of storage at 4 degrees C were compared between

> CFIDS

> > and sarcoidosis samples. RESULTS: Serum ACE levels were elevated

in

> > 80% of patients with CFIDS and 30% of endemic control subjects as

> > compared with 9.4% of nonendemic California control subjects.

The

> ACE

> > activity in CFIDS differed from that in sarcoidosis because of

its

> > lability with storage at 4 degrees C in CFIDS and its partial

> > activation with freezing and thawing. Thus, ACE activity was

> elevated

> > in the majority of CFIDS patients either upon initial assay or

> upon a

> > subsequent assay after refreezing. ACE activity was elevated in

87%

> > of patients with active sarcoidosis and was not affected by

storage

> > or freezing and thawing. CONCLUSIONS: Serum ACE elevations may

be a

> > useful marker for CFIDS, especially if a method can be developed

to

> > distinguish ACE in CFIDS from that in sarcoidosis. The

sensitivity

> > for CFIDS was 80%, with 68% specificity in an endemic area. The

> > increased prevalence of serum ACE elevations in endemic controls

as

> > compared with nonendemic controls suggests that an ACE increase

may

> > be an early manifestation of CFIDS and supports the concept that

> > CFIDS is a definite disease state.

> >

> > TABLE 1 Group No. Mean serum ACE(u/l) No. +

> > ACE

> >

> > Lyndonville CFIDS* 20 49.1 18 (90%)

> >

> > Controls (same area) 33 30.9 9 (27%)

> >

> > Charlotte, NC CFIDS 29 39.6 21 (72.4%)

> >

> > Controls 23 34.8 9 (39.2%)

> >

> > Southern California

> > Controls 32 26.1 3 (9.4%)

> >

> > Sarcoidosis (untreated) 23 51.9 20 (87%)

> >

> > Sarcoidosis

> > (treated with steroids) 24 33.4 9 (38%)