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I would very much like to have your office phone number or address, as I live

in New canaan,Ct,have had neuro Lyme Disease for over 5 years and have heard

of your success but forgot how to get in touch with you.

Thank You,serenabee

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In a message dated 6/13/99 10:53:06 PM Eastern Daylight Time,

frg@... writes:

<< This article was given to us by an " alternative health " person that we

know. It talks about a product called allicin which is apparently some

kind of garlic extract >>

allicin is in garlic...it is supposed to have anti-bacterial properties...I

started taking it last week...two a day...Bernadette

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In a message dated 6/14/99 5:31:58 AM Central Daylight Time, BratDet@...

writes:

<< << This article was given to us by an " alternative health " person that we

know. It talks about a product called allicin which is apparently some

kind of garlic extract >>

allicin is in garlic...it is supposed to have anti-bacterial properties...I

started taking it last week...two a day...Bernadette

>>

My LLMD has recommended garlic also for anti-bacterial properties and says

kyolic (?) is considered the best.

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  • 7 months later...

In a message dated 1/16/00 6:48:54 PM Eastern Standard Time,

moores@... writes:

<< The Mysteries of Chronic Fatigue Syndrome

Multiple Infections and Psychological Disorders May Create Complex Disease

By Jeanie Lerche

WebMD Medical News

Nov. 9, 1999 (Atlanta) -- Chronic fatigue syndrome -- a debilitating illness

that over the last decade has been called

Epstein-Barr virus, chronic mononucleosis, and yuppie flu -- may be an

illness caused by one or more infections, according to a

paper appearing in the current issue of ls of Behavioral Medicine.

Stress and depression may act to perpetuate the condition by disrupting

immune, neurological, and hormone functions

necessary to fight the infection, K. , PhD, a psychologist with

the University of North Carolina at Charlotte, tells

WebMD. " There very much is a mind-body connection, " she says.

Studies conducted at a Chronic Fatigue Research Center at the New Jersey

Medical School have looked at the role psychiatric

disease plays in CFS. They have identified two types of CFS patients. One

group had a gradual onset of physical symptoms,

accompanied by psychiatric problems, such as depression and anxiety. The

other group had a sudden onset of physical

symptoms with no psychiatric problems. Studies have shown that when CFS is

accompanied with depression or anxiety, the

chance for cure is dramatically reduced, says.

Several additional studies have shown CFS patients have a tendency to

minimize the psychological implications of their illness.

Other studies show many people with CFS tend to regard the disease as the

sole problem in their lives, and believe that it has a

biological origin. They are resistant to implications that the disease has a

psychological rather than biological basis, says

.

Chronic fatigue is an illness that impairs daily function and involves

numerous arthritis-related, infectious, neurological, and

psychiatric symptoms. Criteria for diagnosis once focused on infectious

symptoms, but in 1992 it was modified to include

depression and anxiety. Symptoms may include mild fever, muscle weakness,

sore throat, severe fatigue after mild exercise,

headaches, body aches, sleep problems, depression, and anxiety.

Fewer doctors today consider chronic fatigue to be a trivial complaint.

" It's taken much more seriously than it once was, "

tells WebMD.

The illness is difficult to diagnose, in part because fatigue is a very

common, subjective symptom found in many illnesses.

" Fatigue can denote problems with muscle weakness, exhaustion ... mental

tiredness ... or lack of motivation, " says .

Most doctors today establish a diagnosis by ruling out all the other

diseases, she adds.

While chronic fatigue primarily affects middle-aged women, it seems to be

most prevalent among black and Native American

women with incomes under $40,000. " The image of chronic fatigue syndrome as

an illness of the white professional class is

inaccurate, " says .

Because researchers have been unable to pinpoint any physical cause, a true

explanation of the illness' cause has eluded

researchers. There is an unresolved debate whether chronic fatigue is an

emotional disorder or an organic disease, says

. Also, the type of depression found in chronic fatigue patients can

be quite different from classical depression, with

significantly lower evidence of sadness in CFS patients.

Research to date has failed to provide convincing evidence that a single

infectious agent causes the illness. " It is likely that more

than one infectious agent is involved in producing CFS, " says .

Laboratory researchers are investigating cellular activity to better

understand how viral infection affects cell functions and the

immune function. As with all studies of CFS, findings have not proven

consistent, says . " To date, there are still no

useful viral or immune diagnostic markers for CFS, although there is

promising work being done. "

With the diverse symptoms shown by chronic fatigue sufferers, it is hardly

surprising that there is no firmly established treatment,

says . While many physicians recommend low-dosage antidepressant

therapy, at least one study showed that it had no

effect. A few drug treatments have been identified as important sources of

symptom relief and symptom management. But the

vast majority of antiviral medications, immune modifiers, antifungal agents,

vitamins, and minerals that chronic fatigue patients try

have not been tested.

While exercise and psychological counseling have been suggested to increase

activity levels and interrupt cycles of depression,

studies indicate that they are promising but high dropout rates show that

they do not fit all cases of chronic fatigue.

Researchers still don't understand why many who suffer from chronic fatigue

never are cured. But studies consistently show that

those who are less likely to have complete recovery tend to be older and

suffer from depression or anxiety disorder. " There's

been some pretty good physiological research, but it's been frustrating,

too, " says . " Findings look promising but tend

not to be replicated [in subsequent studies]. There's something there, but

we're having lot of trouble grasping it, pinning it

down. "

CFS is a multidimensional illness and challenges traditional perspectives on

illness, tells WebMD. " There's been

progress, but it's been incremental. There are still many unanswered

questions. "

>>

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Steve posted the article re CFS from WebMD re reserach by

, PhD.L

WebMD posted a summary of her research months ago citing the prevalence

statistics from CDC saying that CFS afflicts mainly white women. I e-mailed

with a summary of the epidemiological findings of Leonard

.

She responded to me that she was indeed in contact with Lenny and was

well aware of his findings but had agreed to not use his findings until after

Lenny published his data.

This article seems to portray as straddling the fence on the AIYH

issue. Perhaps it was all in the reporting of her findings. I have no

fundamental quarrel with studying the psychiatric aspects of illness, since

every illness has a psychiatric impact.

When the etiology or underlying mechanism of an illness is not understood, it

is frustrating to see that more reserachers prefer to study the psyche of

PWCs even though this will bring us to closer to getting better.

Bonnes

>

> > Stress and depression may act to perpetuate the condition by disrupting

> immune, neurological, and hormone functions

> necessary to fight the infection, K. , PhD, a psychologist

with

> the University of North Carolina at Charlotte, tells

> WebMD. " There very much is a mind-body connection, " she says.

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  • 2 months later...
Guest guest

--- robert harris <raharris@...> wrote:

> -- thought you might find this article

> interesting. Hope you are feeling better.

For the record, I'd meant to send this message to

, not to the list. Not that I mind this going

out to the list -- I mis-addressed it and that is no

big deal!

Drkoop.com is where and I are currently

running a chat session for psoriatic arthritis. Even

before news of drkoop.com's probable insolvency

and I had talked about migrating the chat

elsewhere, and, as PatB has noted, we now have our own

chat resources. Whatever happens, the PA community

will have an online chat --

Cheers all --

__________________________________________________

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  • 2 months later...
Guest guest

> ,

Thanks for the reference article. My family physician is convinced that my

achalasia is due to reflux, even though I was not aware of any heartburn or

acid. He wants to prescribe antacids to prevent further damage. I can't buy

his theory, so I don't take the antacids. I have gotten severe gas pains that

feel like a heart attack after the dilation procedure. They are controlled by

anti-gas pills (simethicon), but they have lessened with time.

>

>

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  • 1 year later...

What does CFS stand for?

Edie

Interesting article

> Treatment: CDC Pharmacological Treatments for CFS Pharmacologic Therapy

>

> Pharmacologic therapy is directed toward the relief of specific symptoms

> experienced by the individual patient. Patients with CFS appear

particularly

> sensitive to drugs, especially those that affect the central nervous

system.

> Thus, the usual treatment strategy is to begin with very low doses and to

> escalate the dosage gradually as necessary.

>

> Prescription medications

> Low-dose Tricyclic Agents: Tricyclic agents are sometimes prescribed for

CFS

> patients to improve sleep and to relieve mild, generalized pain. Examples

> include doxepin (Adapin, Sinequan), amitriptyline (Elavil, Etrafon,

> Limbitrol, Triavil), desipramine (Norpramin), and nortriptyline (Pamelor).

> Some adverse reactions include dry mouth, drowsiness, weight gain, and

> elevated heart rate.

>

> Antidepressants: Antidepressants have been used to treat depression in CFS

> patients, although non-depressed CFS patients receiving treatment with

> serotonin reuptake inhibitors have been found by some physicians to

benefit

> from this treatment as well or better than depressed patients. Examples of

> antidepressants used to treat CFS include serotonin reuptake inhibitors

such

> as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil);

> venlafaxine (Effexor); trazodone (Desyrel); and bupropion (Wellbutrin). A

> number of mild adverse reactions, varying with the specific drug, may be

> experienced.

>

> Anxiety or anxiolytic agents: Anxiolytic agents are used to treat panic

> disorder in CFS patients. Examples include alprazolam (Xanax), clonazepam

(

> Klonopin), and lorazepam (Ativan). Common adverse reactions include

> sedation, amnesia, and withdrawal symptoms (insomnia, abdominal and muscle

> cramps, vomiting, sweating, tremors, and convulsions).

>

> Nonsteroidal Antiinflammatory Drugs: These drugs may be used to relieve

pain

> and fever in CFS patients. Some are available as over-the-counter

> medications. Examples include naproxen (Aleve, Anaprox, Naprosen),

ibuprofen

> (Advil, Bayer Select, Motrin, Nuprin), and piroxicam (Feldene). These

> medications are generally safe when used as directed, but can cause a

> variety of adverse effects, including kidney damage, gastrointestinal

> bleeding, abdominal pain, nausea, and vomiting.

>

> Antimicrobials: An infectious cause for CFS has not been identified, and

> antimicrobial agents are not commonly prescribed for CFS, unless of course

> the patient has been diagnosed with a concurrent infection.. A controlled

> trial of the antiviral drug acyclovir found no benefit for the treatment

of

> patients with CFS.

>

> Antiallergy Therapy: Some CFS patients have histories of allergy, and

these

> symptoms may flare periodically. Non-sedating antihistamines may be

helpful

> for CFS patients. Examples include astemizole (Hismanal) and loratadine

> (Claritin). Some of the more common adverse reactions associated with

their

> use include drowsiness, fatigue, and headache. Sedating antihistimines can

> also be of benefit to patients at bedtime.

>

> Antihypotensive Therapy: Fludrocortisone (Florinef) has sometimes been

> prescribed for CFS patients who have had a positive tilt table test.

> Florinef is currently being tested in controlled studies for its efficacy

in

> the treatment of CFS patients. Beta blockers such as atenolol (Tenormin)

> have also been prescribed for patients with a positive tilt table test.

> Increased salt and water intake is also recommended for these patients.

> Adverse reactions include elevated blood pressure and fluid retention.

>

> Experimental drugs and treatments

> Ampligen is a synthetic nucleic acid product that stimulates the

production

> of interferons, a family of immune response modifiers that are also known

to

> have anti-viral activity. One report of a double-blinded,

placebo-controlled

> study of CFS patients documented modest improvements in cognition and

> performance among Ampligen recipients compared with the placebo group.

>

> These preliminary results will need to be confirmed by further study.

> Ampligen is not approved by the Food and Drug Administration (FDA) for

> widespread use, and the administration of this drug in CFS patients should

> be considered experimental. Although the recipients of Ampligen in this

> study tolerated the drug well, the adverse reactions of this material are

> still incompletely characterized, and some participants did experience

> reactions that might be attributable to Ampligen.

>

> Dehydroepiandrosterone (DHEA) was reported in preliminary studies to

improve

> symptoms in some patients; however, this finding has not been confirmed

and

> the use of DHEA in patients should be regarded as experimental. Gamma

> globulin (Gammar) is pooled human immune globulin. It contains antibody

> molecules directed against a broad range of common infectious agents and

is

> ordinarily used as a means for passively immunizing persons whose immune

> system has been compromised, or who have been exposed to an agent that

might

> cause more serious disease in the absence of immune globulin. Its use with

> CFS patients is experimental and based on the unsubstantiated hypothesis

> that CFS is characterized by an underlying immune disorder. Serious

adverse

> reactions are uncommon, although in rare instances gamma globulin may

> initiate anaphylactic shock. High colonic enemas have no demonstrated

value

> in the treatment of CFS. The procedure can promote intestinal disease.

> Kutapressin is a crude extract from pig's liver. Its use should be

regarded

> as experimental in any clinical circumstance, and there is no scientific

> evidence that it has any value in the treatment of CFS patients.

Kutapressin

> can elicit allergic reactions.

>

>

>

>

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What does CFS stand for?

Edie

Interesting article

> Treatment: CDC Pharmacological Treatments for CFS Pharmacologic Therapy

>

> Pharmacologic therapy is directed toward the relief of specific symptoms

> experienced by the individual patient. Patients with CFS appear

particularly

> sensitive to drugs, especially those that affect the central nervous

system.

> Thus, the usual treatment strategy is to begin with very low doses and to

> escalate the dosage gradually as necessary.

>

> Prescription medications

> Low-dose Tricyclic Agents: Tricyclic agents are sometimes prescribed for

CFS

> patients to improve sleep and to relieve mild, generalized pain. Examples

> include doxepin (Adapin, Sinequan), amitriptyline (Elavil, Etrafon,

> Limbitrol, Triavil), desipramine (Norpramin), and nortriptyline (Pamelor).

> Some adverse reactions include dry mouth, drowsiness, weight gain, and

> elevated heart rate.

>

> Antidepressants: Antidepressants have been used to treat depression in CFS

> patients, although non-depressed CFS patients receiving treatment with

> serotonin reuptake inhibitors have been found by some physicians to

benefit

> from this treatment as well or better than depressed patients. Examples of

> antidepressants used to treat CFS include serotonin reuptake inhibitors

such

> as fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil);

> venlafaxine (Effexor); trazodone (Desyrel); and bupropion (Wellbutrin). A

> number of mild adverse reactions, varying with the specific drug, may be

> experienced.

>

> Anxiety or anxiolytic agents: Anxiolytic agents are used to treat panic

> disorder in CFS patients. Examples include alprazolam (Xanax), clonazepam

(

> Klonopin), and lorazepam (Ativan). Common adverse reactions include

> sedation, amnesia, and withdrawal symptoms (insomnia, abdominal and muscle

> cramps, vomiting, sweating, tremors, and convulsions).

>

> Nonsteroidal Antiinflammatory Drugs: These drugs may be used to relieve

pain

> and fever in CFS patients. Some are available as over-the-counter

> medications. Examples include naproxen (Aleve, Anaprox, Naprosen),

ibuprofen

> (Advil, Bayer Select, Motrin, Nuprin), and piroxicam (Feldene). These

> medications are generally safe when used as directed, but can cause a

> variety of adverse effects, including kidney damage, gastrointestinal

> bleeding, abdominal pain, nausea, and vomiting.

>

> Antimicrobials: An infectious cause for CFS has not been identified, and

> antimicrobial agents are not commonly prescribed for CFS, unless of course

> the patient has been diagnosed with a concurrent infection.. A controlled

> trial of the antiviral drug acyclovir found no benefit for the treatment

of

> patients with CFS.

>

> Antiallergy Therapy: Some CFS patients have histories of allergy, and

these

> symptoms may flare periodically. Non-sedating antihistamines may be

helpful

> for CFS patients. Examples include astemizole (Hismanal) and loratadine

> (Claritin). Some of the more common adverse reactions associated with

their

> use include drowsiness, fatigue, and headache. Sedating antihistimines can

> also be of benefit to patients at bedtime.

>

> Antihypotensive Therapy: Fludrocortisone (Florinef) has sometimes been

> prescribed for CFS patients who have had a positive tilt table test.

> Florinef is currently being tested in controlled studies for its efficacy

in

> the treatment of CFS patients. Beta blockers such as atenolol (Tenormin)

> have also been prescribed for patients with a positive tilt table test.

> Increased salt and water intake is also recommended for these patients.

> Adverse reactions include elevated blood pressure and fluid retention.

>

> Experimental drugs and treatments

> Ampligen is a synthetic nucleic acid product that stimulates the

production

> of interferons, a family of immune response modifiers that are also known

to

> have anti-viral activity. One report of a double-blinded,

placebo-controlled

> study of CFS patients documented modest improvements in cognition and

> performance among Ampligen recipients compared with the placebo group.

>

> These preliminary results will need to be confirmed by further study.

> Ampligen is not approved by the Food and Drug Administration (FDA) for

> widespread use, and the administration of this drug in CFS patients should

> be considered experimental. Although the recipients of Ampligen in this

> study tolerated the drug well, the adverse reactions of this material are

> still incompletely characterized, and some participants did experience

> reactions that might be attributable to Ampligen.

>

> Dehydroepiandrosterone (DHEA) was reported in preliminary studies to

improve

> symptoms in some patients; however, this finding has not been confirmed

and

> the use of DHEA in patients should be regarded as experimental. Gamma

> globulin (Gammar) is pooled human immune globulin. It contains antibody

> molecules directed against a broad range of common infectious agents and

is

> ordinarily used as a means for passively immunizing persons whose immune

> system has been compromised, or who have been exposed to an agent that

might

> cause more serious disease in the absence of immune globulin. Its use with

> CFS patients is experimental and based on the unsubstantiated hypothesis

> that CFS is characterized by an underlying immune disorder. Serious

adverse

> reactions are uncommon, although in rare instances gamma globulin may

> initiate anaphylactic shock. High colonic enemas have no demonstrated

value

> in the treatment of CFS. The procedure can promote intestinal disease.

> Kutapressin is a crude extract from pig's liver. Its use should be

regarded

> as experimental in any clinical circumstance, and there is no scientific

> evidence that it has any value in the treatment of CFS patients.

Kutapressin

> can elicit allergic reactions.

>

>

>

>

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  • 2 months later...
  • 2 months later...

I liked the article but wished it had citations for his facts listed.

Whenever I look at saving an article to forward to friends who are unsure I

like to have well cited articles so it doesn't look like people are just

pulling facts randomly out of their a**.

L.

Proud mom to Autumn 1-13-97 & Zoe 8-8-00

>

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  • 5 months later...
Guest guest

Very, very interesting, from sources hard to refute. In my first 3

days of loading Synthevol2 (Creatine) and also tons of protein

(target 152 gms) I have to agree with the doctor that my kidneys and

system have been flushing everything.

However, its just starting to even out, now, today (after being quite

sick this morning) I am starting to feel much better and " flushing "

far less often that Sunday or Monday.

Research is based on fact, a lot of bodybuilding stuff can be hocos

pocos, I think. The proof is in the pudding, we've all seem the BFL

winners and know what they did to succeed. However, think of a

prison inmate, how do they get so ripped? Their food source is the

worst. Only possible answer....they have a lot of time on their

hands and all they do is lift and eat. They probably couldn't do it

in 12 weeks. :-)

> http://content.health.msn.com/content/article/1676.50058

>

> No wonder people are so confused about how/what to eat!! This

article

> completely villianizes protein!

>

> Betty

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Guest guest

hehehe - I know I have seen what works and I felt better when I

decreased the carbs and increased my protein. I am by NO means

agreeing with what is in that article.

I actually wonder some days if there isn't some kind of weird

conspiracy going on in the background between some of these

organizations that we are not aware of. MILLIONS have followed Bill's

plan with no reported/known ill effects and the protein/carb/fat

ratio is 40/40/20 - which flies in the face of what the American

Dietetic Assc, American Heart Assc, American Diabetes Assc & the food

Pyramid recommend which is 20/60/20 (roughly, this article said 15%

for protein). I have noticed in the last year that their has been

increased scrutiny for the BFL program and that medical professionals

almost seem to want to DISCOURAGE people from following a program

that cleans up peoples diets and gets them to exercise.

Anyone else ever notice this kind of thing, or am I just weird with

too much time on my hands???? I know - it is all those toxic ketones

building up along with the lactic acid and my decreasing body mass

making me delirious!!!

btw - don't give up this time !!! Can you back off the supps some

and then slowly add them back into your eating plan? Maybe that many

different & new things at once is contributing to your queasy

stomach?

Betty

> > http://content.health.msn.com/content/article/1676.50058

> >

> > No wonder people are so confused about how/what to eat!! This

> article

> > completely villianizes protein!

> >

> > Betty

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Guest guest

What is sad is that people are being mislead by wording such as this

into thinking that protein is evil.

" Adding more protein but not more calories or exercise to your diet

won't help you build more muscle mass, but it may put your other

bodily systems under stress. "

This is TRUE!!! If you want to build mass, you need to up your

calories, not push out your carbs with more protein.

" Eating more protein and increasing total caloric intake while

maintaining the same exercise level will build an equal amount of

additional fat and muscle mass, according to a study published in

1992 in the Journal of the American Geriatrics Society. "

This also is not saying anything that goes against what many fitness

gurus say. I don't know of anyone who goes into a " bulking " phase

WITHOUT changing their exercise level so it it a moot point. AND we

all know it is nearly impossible to gain muscle without gaining some

fat no matter what you do to increase your exercise level. And

furthermore, have there been no studies done on this in the past 10

years???

I hate when the media takes basically sound information and twists it

to say something it's not!

Lynda

*who seems to be gramatically challenged today!

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Guest guest

Some time when you have extra free time research who published a

certain article, who paid for the testing, lab results, etc. Most of

the time it is for example the dairy farmers promoting " milk is good

for you " ads and the chicken farmers promoting " eggs are healthy " ,

etc. I had a class in college that was a real eye opener on this!

I'm not saying the articles are necessarily biased, but the dairy

farmer is sure going to be looking for info to help his income or

position on things rather than info saying milk isn't good for you,

etc.

Personally I think what it boils down to is finding what works for us

as an individuals and sticking to it.

Colleen

-- In @y..., " daisyheads2000 "

<daisyheads2000@y...> wrote:

>

> I actually wonder some days if there isn't some kind of weird

> conspiracy going on in the background between some of these

> organizations that we are not aware of. MILLIONS have followed

Bill's

> plan with no reported/known ill effects and the protein/carb/fat

> ratio is 40/40/20 - which flies in the face of what the American

> Dietetic Assc, American Heart Assc, American Diabetes Assc & the

food

> Pyramid recommend which is 20/60/20 (roughly, this article said 15%

> for protein). I have noticed in the last year that their has been

> increased scrutiny for the BFL program and that medical

professionals

> almost seem to want to DISCOURAGE people from following a program

> that cleans up peoples diets and gets them to exercise.

>

> Anyone else ever notice this kind of thing, or am I just weird with

> too much time on my hands???? I know - it is all those toxic

ketones

> building up along with the lactic acid and my decreasing body mass

> making me delirious!!!

>

> btw - don't give up this time !!! Can you back off the supps

some

> and then slowly add them back into your eating plan? Maybe that

many

> different & new things at once is contributing to your queasy

> stomach?

>

> Betty

>

>

>

> > > http://content.health.msn.com/content/article/1676.50058

> > >

> > > No wonder people are so confused about how/what to eat!! This

> > article

> > > completely villianizes protein!

> > >

> > > Betty

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Guest guest

> .

>

> " However, think of a prison inmate, how do they get so ripped?

Their

> food source is the worst. "

>

> I've not been in prision, but I've been told that the prison diet

is

> heavily regulated as to it's quality so that prisoners often eat

> better on the inside than they did before going to jail. That

could

> be an exageration propigated by those who think we are too kind to

> our prisoners, however, so maybe they do get crappy food. Of

course,

> they probably don't have the option of six small meals a day.

>

Probably steroids. You can get drugs inside a prison just like you

can outside a prison although a bit more costly. The food is not

what the population believes it to be. It is mostly carbs and fat,

very little if any protein unless they buy their own food. They can

also in some states get food sent in so they could be using protein

powders, bars, etc. They can usually buy canned tuna and canned

chicken also. They are usually fed twice a day and given a sack

lunch. But if they've boughten food or had food sent in, they can eat

whenever they want.

Colleen

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  • 1 month later...

I thought this article was interesting although I hade to read it a

couple of times to absorb anyway I still found it interesting...Kathi

in OK

http://www.rheuma21st.com/cutting_index.html

THE CURRENT STATUS OF BIOLOGICS IN THE TREATMENT

OF SYSTEMIC RHEUMATIC DISEASES

Reported by Reichlin, M.D.

Vice President of Research & Scientific Director

Member,

Arthritis/Immunology Program

Oklahoma Medical Research Foundation

Lynn Cross Research Professor

Oklahoma University Health Sciences Center

published 11. February 2002

Download As A PDF File: To read and print PDF files,

you will need free Adobe Acrobat Reader

The age of biologics is upon us. The tumor necrosis

factor (TNFa) blockers

etanercept and infliximab which are soluble TNF

receptors and chimeric

(mouse-human) monoclonal anti-TNFa antibodies

respectively have taken their

place in the armamentarium of agents used by

rheumatologists to treat

rheumatoid arthritis. Over 200 abstracts at the

recent ACR Meeting were devoted

to studies involving these two agents attesting to

the widespread interest and

clinical investigations associated with these agents.

These two biologics reflect the two major methods now

available for the production

of materials active in treating disease. These are

first monoclonal antibody

production in mice followed by isolation of the

murine variable region heavy and

light chains which are then joined with human heavy

and light chain constant

region genes to produce a poorly immunogenic chimeric

antibody molecule which

can be produced by recombinant methods in bulk

culture. As will be discussed,

such chimeric antibodies directed to human complement

components, cytokines

and B cell markers, are being produced and studied

for their favorable effects on

disease activity in animal models and in human

systemic rheumatic diseases.

In the second method, recombinant methods are used to

produce crucial

receptors, costimulator molecules, and surface

regulatory molecules which in

soluble form can down regulate cellular activation by

engaging the natural ligands

which would otherwise stimulate immune cells. In what

follows, several examples

of ongoing work of this nature will be described.

Most of the information derives

from talks and published abstracts given at the

recent ACR Meeting, but some

studies are from the recent literature. There were

several abstracts published

about the treatment of RA with Anakinra which is a

recombinant form of the IL1

receptor antagonist. Anakinra represents another

biologic which has clinically

significant activity in the therapy of RA. Anakinra

increased productivity (Abstract

148) and had a favorable effect on functional status

(Abstract 1915). By itself, it

had a safety profile similar to other biologics in

the treatment or RA (Abstract 190)

as it did in combination therapy with etanercept

(Abstra ct 157). In the latter study

however, four serious infections (7%) requiring

hospitalization were noted. All

patients were successfully treated and discharged

from hospital. This observation

may signal some caution in the use of combination

therapy.

One of the more exciting factors to be described

recently is B lymphocyte

stimulator or BlyS. This is a 285 amino acid member

of the TNF ligand

superfamily (1). This material in a short time

interval has been discovered several

times and bears several different names including

TALL1 (TNF and Apol-related

leukocyte expressed ligand (1), BAFF (B cell

activator belonging to the TNF

family), THANK (TNF homologues that activates

apoptosis, NFKB, and JNK) and

zTNF4. (2)

There are at least three identified receptors for

BLyS protein: BCMA (B cell

maturation antigen); TAC1 (transmembrane activator

and calcium modulator and

cyclophilin ligand – interactor); and BAFF·R (BAFF

receptor). These receptors are

largely restricted to B cells. When BLyS which is

produced in macrophages,

monocytes, and dendritic cells engages its receptor

on B cells, the B cells

proliferate and become activated. Thus, BLyS

represents the molecule that

mediates monocyte driven B cell activation.

Administration of recombinant BLyS

to mice induces B cell lymphocytosis and polyclonal

hypergammaglobulinemia.

Each of these above receptors in soluble form

represent potential therapeutics if

excess BLyS plays a pathogenic role since they can

effectively bind and

neutralize BLyS. That excess BLyS contributes to

autoimmunity is suggested by

several lines of evidence. Firstly, mice made

transgenic for BLyS develop an

SLE-like disease with polyclonal

hypergammaglobulinemia, ANA, anti-dsDNA,

rheumatoid factor (RF), circulating immune complexes

and Ig deposits in the

kidneys (3-5). Secondly, BLyS plasma levels are

elevated in murine SLE (3), and

in three independent studies in human SLE (Abstract

278) (6,7). Finally, treatment

of SLE mice with TAC1-lg fusion protein suppresses

disease progression and

improves survival (3, Abstract 2060). There have been

as yet no therapeutic trials

of human SLE with soluble forms of BLyS receptors,

but soluble forms as TAC1-lg

and BCMA-lg are available and could be used. In

addition, a fully

human-antihuman BLyS monoclonal antibody that

neutralizes BLyS protein

activity has been developed (Abstract 1377) and could

be ready for phase 1

clinical trials.

In addition to SLE, BLyS levels are also elevated in

RA and in 7 of 7 instances

BLyS levels were much higher in RA synovial fluid

than in the plasma (7). It may

well be that therapeutic strategies directed at BLyS

would be appropriate in RA as

well as SLE. Interestingly, in the RA patients, BLyS

levels correlated far more

strongly with RF titers than with total IgG or total

IgM levels (7).

A final recognized role for BLyS may be in Sjögren's

Syndrome (Abstract 1205).

Serum levels of BLyS were greatly elevated in

patients with Sjögren's Syndrome

8.58 ng/ml versus 2.56 ng/ml (p<0.0001). The level of

BLyS was associated with

presence of anti-Ro/SSA anti-La/SSB 10.45 ng/ml

versus 5.6 ng/ml (p=.008); the

presence of rheumatoid factor; 10.76 ng/ml vs. 6.3

ng/ml (p=.03); the level of IgM

and the level of rheumatoid factor (p<0.0001). It may

be that BLyS plays an

important role in triggering activation of self Ag

driven B cells in Sjögren's

Syndrome.

Another agent that is being considered as a therapy

in autoimmune disease is

rituximab which is a chimeric murine-human monoclonal

antibody directed to the

B cell marker CD20. A phase 1/11 trial has been

conducted with 12 SLE patients

showing that rituximab was well tolerated and

significantly depleted B

lymphocytes (Abstract 2009). This favorable result

paves the way for a larger

placebo controlled trial aimed at assessing efficacy

in the therapy of SLE.

Interestingly, rituximab was used in a patient with

Wegener's granulomatosis who

could not be treated with cyclophosphamide because of

bone marrow toxicity

experienced with cyclophosphamide during treatment of

a relapse. Other

therapies such as azathioprine and mycophenolate

mofetil were ineffective and

methrotrexate was contraindicated. The patient

received four infusions of 375

mg/M2 of rituximab and high dose glucocorticoids.

Complete remission was

associated with the complete disappearance of cANCA

and B lymphocytes. The

glucocorticoids were discontinued and several months

later the cANCA recurred

and rituximab therapy was again given, this time

without glucocorticoids. After

eight months following the second course of retuximab

the patients disease has

remained in remission and the cANCA titer has

remained negative. This promising

result warrants closer study in a controlled clinical

trial of antibody mediated

vasculitis (8).

CTLA4 is found on activated T cells and binds B7 on

antigen presenting cells,

thereby enhancing cellular interactions and

proliferation. CTLA4 Ig is a soluble

form of CTLA4 which has had Ig Fc added as part of

its structure. By binding B7

and preventing this co-stimulatory interaction, T

cell activation and proliferation are

blunted. CTLA4 IgG has been used in active RA and was

found to be well

tolerated and to have favorable clinical effects and

activity (Abstract 1327). This

then is the fourth biologic with anti-inflammatory

effects toward RA.

Finally, two humanized monoclonal antibodies against

human complement

component 5 and IL6 were tested for their safety and

efficacy in RA. At the two

highest dosing schemes h561.1 (anti-C5) was safe and

efficacious over a

three-month period while the anti IL6 was effective

and well tolerated at a minimum

dose of 5mg/kg in a single dose with a measurable

clinical effect at two weeks.

Clearly, both regimens need to be tested for long-

term efficacy and safety

(Abstracts 1328, 1329).

The aim and aspiration of all this work is to find in

biologics more specific,

effective, and safer therapies for the systemic

rheumatic diseases than presently

exist. From the pace of work evident in this field it

would appear there is much to

anticipate and a solid basis for optimism.

.

References

1. PA, Belvedere O, Orr A, et al. BLyS: Member

of the tumor necrosis

factor family and B lymphocyte stimulator. Science

1999: 285:260-263.

2. Reviewed by Stohl. There is No Bliss in

Too Much BLyS (B lymphocyte

stimulator). In ACR Basic Science Symposium. Pp. 1-8,

Nov. 12, 2001.

3. Gross JA, ston J, Mudri, et al. TAC1 and BCMA

are receptors for a TNF

homologue implicated in B-cell autoimmune disease.

Nature 2000; 404:995-999.

4. Mackay F, Woodcock SA, Lawton P, et al. Mice

transgenic for BAFF develop

lymphocytic disorders along with autoimmune

manifestations. J. Exp. Med. 1999;

190:1697-1710.

5. Khare SD, Sarosi I., Xia X-Z, et al. Severe B cell

hyperplasia and autoimmune

disease in TALL-1 transgenic mice. Proc. Nat. Acad.

Sci. USA 2000;

97:3370-3375.

6. Zhang J, Roschke V, Baher KP, et al. Cutting Edge:

A role for B lymphocyte

stimulator in systemic lupus erythematosus. J.

Immunol. 2001; 166:6-10.

7. Cheema GS, Roschke V, Hilbert DM, Stohl W.

Elevated serum B lymphocyte

stimulator levels in patients with systemic immune-

based rheumatic diseases.

Arthritis Rheum. 2001; 44:1313-1319.

8. Specks U, Fernenza FC, Mc TJ, Hogan MC.

Response of Wegener's

granulomatosis to anti-CD20 chimeric monoclonal

antibody therapy. Arthritis

Rheum. 2001; 44:2836-2840.

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I think it's a very interesting article, too, Kathi! I really like that

site. Are you partial to this report because the author is from

Oklahoma?

http://www.rheuma21st.com/archives/cutting_reichlin_biologics.htm

[ ] RE: Interesting article

I thought this article was interesting although I hade to read it a

couple of times to absorb anyway I still found it interesting...Kathi

in OK

http://www.rheuma21st.com/cutting_index.html

THE CURRENT STATUS OF BIOLOGICS IN THE TREATMENT

OF SYSTEMIC RHEUMATIC DISEASES

Link to comment
Share on other sites

Thanks for the link. It is confusing at first blush. I've downloaded it to

print out in pdf. Maybe I can make more sense of it then.

Suzanne

[ ] RE: Interesting article

I thought this article was interesting although I hade to read it a

couple of times to absorb anyway I still found it interesting...Kathi

in OK

http://www.rheuma21st.com/cutting_index.html

THE CURRENT STATUS OF BIOLOGICS IN THE TREATMENT

OF SYSTEMIC RHEUMATIC DISEASES

Reported by Reichlin, M.D.

Vice President of Research & Scientific Director

Member,

Arthritis/Immunology Program

Oklahoma Medical Research Foundation

Lynn Cross Research Professor

Oklahoma University Health Sciences Center

published 11. February 2002

Download As A PDF File: To read and print PDF files,

you will need free Adobe Acrobat Reader

The age of biologics is upon us. The tumor necrosis

factor (TNFa) blockers

etanercept and infliximab which are soluble TNF

receptors and chimeric

(mouse-human) monoclonal anti-TNFa antibodies

respectively have taken their

place in the armamentarium of agents used by

rheumatologists to treat

rheumatoid arthritis. Over 200 abstracts at the

recent ACR Meeting were devoted

to studies involving these two agents attesting to

the widespread interest and

clinical investigations associated with these agents.

These two biologics reflect the two major methods now

available for the production

of materials active in treating disease. These are

first monoclonal antibody

production in mice followed by isolation of the

murine variable region heavy and

light chains which are then joined with human heavy

and light chain constant

region genes to produce a poorly immunogenic chimeric

antibody molecule which

can be produced by recombinant methods in bulk

culture. As will be discussed,

such chimeric antibodies directed to human complement

components, cytokines

and B cell markers, are being produced and studied

for their favorable effects on

disease activity in animal models and in human

systemic rheumatic diseases.

In the second method, recombinant methods are used to

produce crucial

receptors, costimulator molecules, and surface

regulatory molecules which in

soluble form can down regulate cellular activation by

engaging the natural ligands

which would otherwise stimulate immune cells. In what

follows, several examples

of ongoing work of this nature will be described.

Most of the information derives

from talks and published abstracts given at the

recent ACR Meeting, but some

studies are from the recent literature. There were

several abstracts published

about the treatment of RA with Anakinra which is a

recombinant form of the IL1

receptor antagonist. Anakinra represents another

biologic which has clinically

significant activity in the therapy of RA. Anakinra

increased productivity (Abstract

148) and had a favorable effect on functional status

(Abstract 1915). By itself, it

had a safety profile similar to other biologics in

the treatment or RA (Abstract 190)

as it did in combination therapy with etanercept

(Abstra ct 157). In the latter study

however, four serious infections (7%) requiring

hospitalization were noted. All

patients were successfully treated and discharged

from hospital. This observation

may signal some caution in the use of combination

therapy.

One of the more exciting factors to be described

recently is B lymphocyte

stimulator or BlyS. This is a 285 amino acid member

of the TNF ligand

superfamily (1). This material in a short time

interval has been discovered several

times and bears several different names including

TALL1 (TNF and Apol-related

leukocyte expressed ligand (1), BAFF (B cell

activator belonging to the TNF

family), THANK (TNF homologues that activates

apoptosis, NFKB, and JNK) and

zTNF4. (2)

There are at least three identified receptors for

BLyS protein: BCMA (B cell

maturation antigen); TAC1 (transmembrane activator

and calcium modulator and

cyclophilin ligand - interactor); and BAFF·R (BAFF

receptor). These receptors are

largely restricted to B cells. When BLyS which is

produced in macrophages,

monocytes, and dendritic cells engages its receptor

on B cells, the B cells

proliferate and become activated. Thus, BLyS

represents the molecule that

mediates monocyte driven B cell activation.

Administration of recombinant BLyS

to mice induces B cell lymphocytosis and polyclonal

hypergammaglobulinemia.

Each of these above receptors in soluble form

represent potential therapeutics if

excess BLyS plays a pathogenic role since they can

effectively bind and

neutralize BLyS. That excess BLyS contributes to

autoimmunity is suggested by

several lines of evidence. Firstly, mice made

transgenic for BLyS develop an

SLE-like disease with polyclonal

hypergammaglobulinemia, ANA, anti-dsDNA,

rheumatoid factor (RF), circulating immune complexes

and Ig deposits in the

kidneys (3-5). Secondly, BLyS plasma levels are

elevated in murine SLE (3), and

in three independent studies in human SLE (Abstract

278) (6,7). Finally, treatment

of SLE mice with TAC1-lg fusion protein suppresses

disease progression and

improves survival (3, Abstract 2060). There have been

as yet no therapeutic trials

of human SLE with soluble forms of BLyS receptors,

but soluble forms as TAC1-lg

and BCMA-lg are available and could be used. In

addition, a fully

human-antihuman BLyS monoclonal antibody that

neutralizes BLyS protein

activity has been developed (Abstract 1377) and could

be ready for phase 1

clinical trials.

In addition to SLE, BLyS levels are also elevated in

RA and in 7 of 7 instances

BLyS levels were much higher in RA synovial fluid

than in the plasma (7). It may

well be that therapeutic strategies directed at BLyS

would be appropriate in RA as

well as SLE. Interestingly, in the RA patients, BLyS

levels correlated far more

strongly with RF titers than with total IgG or total

IgM levels (7).

A final recognized role for BLyS may be in Sjögren's

Syndrome (Abstract 1205).

Serum levels of BLyS were greatly elevated in

patients with Sjögren's Syndrome

8.58 ng/ml versus 2.56 ng/ml (p<0.0001). The level of

BLyS was associated with

presence of anti-Ro/SSA anti-La/SSB 10.45 ng/ml

versus 5.6 ng/ml (p=.008); the

presence of rheumatoid factor; 10.76 ng/ml vs. 6.3

ng/ml (p=.03); the level of IgM

and the level of rheumatoid factor (p<0.0001). It may

be that BLyS plays an

important role in triggering activation of self Ag

driven B cells in Sjögren's

Syndrome.

Another agent that is being considered as a therapy

in autoimmune disease is

rituximab which is a chimeric murine-human monoclonal

antibody directed to the

B cell marker CD20. A phase 1/11 trial has been

conducted with 12 SLE patients

showing that rituximab was well tolerated and

significantly depleted B

lymphocytes (Abstract 2009). This favorable result

paves the way for a larger

placebo controlled trial aimed at assessing efficacy

in the therapy of SLE.

Interestingly, rituximab was used in a patient with

Wegener's granulomatosis who

could not be treated with cyclophosphamide because of

bone marrow toxicity

experienced with cyclophosphamide during treatment of

a relapse. Other

therapies such as azathioprine and mycophenolate

mofetil were ineffective and

methrotrexate was contraindicated. The patient

received four infusions of 375

mg/M2 of rituximab and high dose glucocorticoids.

Complete remission was

associated with the complete disappearance of cANCA

and B lymphocytes. The

glucocorticoids were discontinued and several months

later the cANCA recurred

and rituximab therapy was again given, this time

without glucocorticoids. After

eight months following the second course of retuximab

the patients disease has

remained in remission and the cANCA titer has

remained negative. This promising

result warrants closer study in a controlled clinical

trial of antibody mediated

vasculitis (8).

CTLA4 is found on activated T cells and binds B7 on

antigen presenting cells,

thereby enhancing cellular interactions and

proliferation. CTLA4 Ig is a soluble

form of CTLA4 which has had Ig Fc added as part of

its structure. By binding B7

and preventing this co-stimulatory interaction, T

cell activation and proliferation are

blunted. CTLA4 IgG has been used in active RA and was

found to be well

tolerated and to have favorable clinical effects and

activity (Abstract 1327). This

then is the fourth biologic with anti-inflammatory

effects toward RA.

Finally, two humanized monoclonal antibodies against

human complement

component 5 and IL6 were tested for their safety and

efficacy in RA. At the two

highest dosing schemes h561.1 (anti-C5) was safe and

efficacious over a

three-month period while the anti IL6 was effective

and well tolerated at a minimum

dose of 5mg/kg in a single dose with a measurable

clinical effect at two weeks.

Clearly, both regimens need to be tested for long-

term efficacy and safety

(Abstracts 1328, 1329).

The aim and aspiration of all this work is to find in

biologics more specific,

effective, and safer therapies for the systemic

rheumatic diseases than presently

exist. From the pace of work evident in this field it

would appear there is much to

anticipate and a solid basis for optimism.

.

References

1. PA, Belvedere O, Orr A, et al. BLyS: Member

of the tumor necrosis

factor family and B lymphocyte stimulator. Science

1999: 285:260-263.

2. Reviewed by Stohl. There is No Bliss in

Too Much BLyS (B lymphocyte

stimulator). In ACR Basic Science Symposium. Pp. 1-8,

Nov. 12, 2001.

3. Gross JA, ston J, Mudri, et al. TAC1 and BCMA

are receptors for a TNF

homologue implicated in B-cell autoimmune disease.

Nature 2000; 404:995-999.

4. Mackay F, Woodcock SA, Lawton P, et al. Mice

transgenic for BAFF develop

lymphocytic disorders along with autoimmune

manifestations. J. Exp. Med. 1999;

190:1697-1710.

5. Khare SD, Sarosi I., Xia X-Z, et al. Severe B cell

hyperplasia and autoimmune

disease in TALL-1 transgenic mice. Proc. Nat. Acad.

Sci. USA 2000;

97:3370-3375.

6. Zhang J, Roschke V, Baher KP, et al. Cutting Edge:

A role for B lymphocyte

stimulator in systemic lupus erythematosus. J.

Immunol. 2001; 166:6-10.

7. Cheema GS, Roschke V, Hilbert DM, Stohl W.

Elevated serum B lymphocyte

stimulator levels in patients with systemic immune-

based rheumatic diseases.

Arthritis Rheum. 2001; 44:1313-1319.

8. Specks U, Fernenza FC, Mc TJ, Hogan MC.

Response of Wegener's

granulomatosis to anti-CD20 chimeric monoclonal

antibody therapy. Arthritis

Rheum. 2001; 44:2836-2840.

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  • 1 month later...

Hi ,

You'll find a list of studies done at rheumatic.org/studies.htm, which

may help you.

Chris.

On Saturday, November 9, 2002, at 12:05 PM, Nicometo wrote:

> Hi everyone...I was looking on medline for articles to bring to my

> doc in hopes that they will be more likely to cooperate with my

> wanting to start antibiotics. Certain parts of this article are

> intersting...but a little outdated.

>

>

> DM

> Rochester

>

>

> Infection 1979;7 Suppl 6:584-8 Related Articles, Links

>

>

> [Positive side-effects of antibiotic and antimicrobial drugs in

> therapy (author's transl)]

>

> [Article in German]

>

> Illig L.

>

> Since about 1950 especially, dermatologists world-wide have been

> utilizing the positive side-effects, discovered by chance, of all

> groups of antibiotic and antimicrobial drugs. These drugs are used

> to treat certain non-microbially induced dermatoses, without any

> knowledge of the mechanisms involved. A short history is given and

> the most important drugs and the indications for their use are

> described. The following drugs are undoubtedly effective and

> sometimes even the therapy of choice: tetracyclines in acne vulgaris

> and rosacea (including rosacea keratitis); penicillin G in

> acrodermatitis atrophicans and cold urticaria; dapsone in dermatitis

> herpetiformis and - as a powerful adjuvant - in acne vulgaris and

> rosacea. Before the discovery of the socalled immunodepressive

> drugs, tetracycline was the only alternative to - or at least a

> highly effective adjuvant of - cortisone in dermatomyositis and

> chloroquine in localised and systemic lupus erythematosus. Finally,

> clioquinole was life-saving in acrodermatitis continua in children

> until this condition was recently identified as a zinc-deficiency

> syndrome. Therapeutical mechanisms have been found only in the case

> of acne, rosacea and dermatitis herpetiformis. In most other

> diseases the nature of the therapeutical effectiveness of antibiotic

> and antimicrobial drugs still remains a mystery.

>

> Publication Types:

> Review

>

> PMID: 162143 [PubMed - indexed for MEDLINE]

>

>

>

>

>

> To unsubscribe, email: rheumatic-unsubscribeegroups

>

>

>

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  • 2 months later...

Thanks SO very much for sending us that article Lou....very informative, I think I'm going to add that to our "links" section of our group.

Of course I couldn't disagree more with the section I copied & pasted below. GRRRRRRRR!!! "burden to the families" to travel...hmmm, since when is getting our children help a burden?????

Otherwise, quite educational....thanks again!

Debbie Abby's mom DOCGrad

MI

>>>Externally applied forces cause positional flattening, and externally applied forces can be utilized to correct the deformity. The "orthotic helmet" is a padded polypropylene band that is custom fabricated to fit snugly over the prominent aspects of the infant skull and to leave daylight over the flattened aspects. The infant wears the helmet continuously with interruptions only for bathing, and over the course of several months, as the brain grows, the head expands into the daylight and becomes more rounded. Minor adjustments in the fit of the helmet are required on a roughly bi-weekly basis to prevent pressure injuries to the scalp. Data suggest that orthotic helmet therapy is no more effective than positioning and exercises in the management of mild to moderate deformities, and the frequent visits to the orthotist are a burden to families from remote communities, so the author reserves this intervention for the most severely affected patients<<<

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Lou,

Thanks so much for sharing that great piece- very informative. I thought a few things sounded more like opinion, but its got a great description of everything- thanks so much for sharing and adding great information to the database!

' Mom

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Lou,

That was a really great article! Thanks for sharing it.

--- In Plagiocephaly , " Lou Callaway " <loucal@m...>

wrote:

> Hi,

> You guys may have already read this article but I thought it was

interesting. Check it out if you have not already read it. It helped

me understand a few things I was not sure about. Lou

> www.drexel.edu/med/neurosurgery/ped/heads.article.htm

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wow...that's the first time i've seen proof of my theory that my

carrying jordan around pretty much nonstop for the first three months

of her life (i would carry her in the crook of my left arm...forcing

her to look to the right) caused her torticollis & resulting plagio.

sigh, it's so frustrating... as a new parent, i relied on classes,

books, my pediatrician & relatives to help w/ advice and of course NO

WHERE did it say to vary the way you put a baby to sleep, let alone

vary the way you carry your baby...well at least i can prevent it

from happening to other people i know & to any future children i may

have. thanks for posting the article, i'd always theorized on my own

that my carrying her that specific way may have caused the problem,

but had never had it confirmed!!!

--- In Plagiocephaly , " Lou Callaway " <loucal@m...>

wrote:

> Hi,

> You guys may have already read this article but I thought it was

interesting. Check it out if you have not already read it. It helped

me understand a few things I was not sure about. Lou

> www.drexel.edu/med/neurosurgery/ped/heads.article.htm

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