Re: 's experience/conclusions...

[Guest guest]

said:

> That's where I thought my experience would have been useful to

> CFSers.

> 1. is a CFS survivor.

> 2. tried mold avoidance

> 3. is on top of mountain

>

> Since a CFS survivor should not be on top of a mountain, maybe the

> mold avoidance did something - especially since he says so.

>

> But instead, the alternate conclusions are that:

> 1. could not possibly have " real CFS " .

> 2. Everyone knows that mold avoidance isn't that helpful, so that

> can't be it.

> 3. If is on top of any mountain, it is just a fluke that he

> wrongly attributes to something he was trying at the time he just

> happened to get better.

,

My conclusions are that your CFS was due to a different cause than many others

on this

board and around the world, and that your remedy worked for you, where it may or

may

not work for others. Just as others suggestions regarding mold may not work for

some,

but they might be working for them.

d.

d.

[Guest guest]

" kdrbrill " <kdrbrill@...> wrote:

> ,

>

> My conclusions are that your CFS was due to a different cause than

many others on this board and around the world, and that your remedy

worked for you, where it may or may not work for others. Just as

others suggestions regarding mold may not work for some,

> but they might be working for them.

>

> d.

Could be. But since my CFS is the one that the syndrome was

originally based on, you'd think that people might want to check it

out as a possibility.

Especially seeing as I've got mold stories about an awful lot of

pretty well known CFSers.

As per mold, the problem is, just as Dr Myhill explains, you don't

know until AFTER you give it a try.

Most don't, so they don't know.

From my perspective, it's like throwing someone a life preserver and

having them swim away, saying " It's not government certified, you

can't prove that it floats " .

-

[Guest guest]

Yes, , I absolutely agree that everyone should check mold out

as a possibilty. For example, my house had a water leak in a pipe

in the attic that got into the ceiling and the walls. That is

why I have kept asking you questions. I just don't get symptoms

when I go into any particular area or building that might be

mold infested.

In my case, I was dx'd w/ CFS by 5 docs, 3 of which were infectious

disease docs. However, without mold avoidance as a 'treatment', I

have been snow skiing at 12-13,000 feet for the last seven years.

My main problem is post exertional fatigue, and it doesn't matter

where I am. So I think that whatever hit me was something other

than mold-I think a virus but I don't know. Best regards,

Mike C (CFS since May, 1993)

>

> > ,

> >

> > My conclusions are that your CFS was due to a different cause

than

> many others on this board and around the world, and that your

remedy

> worked for you, where it may or may not work for others. Just as

> others suggestions regarding mold may not work for some,

> > but they might be working for them.

> >

> > d.

>

>

> Could be. But since my CFS is the one that the syndrome was

> originally based on, you'd think that people might want to check it

> out as a possibility.

> Especially seeing as I've got mold stories about an awful lot of

> pretty well known CFSers.

> As per mold, the problem is, just as Dr Myhill explains, you don't

> know until AFTER you give it a try.

> Most don't, so they don't know.

> From my perspective, it's like throwing someone a life preserver

and

> having them swim away, saying " It's not government certified, you

> can't prove that it floats " .

> -

>

[Guest guest]

" yakcamp22 " <yakcamp22@...> wrote:

>

> Yes, , I absolutely agree that everyone should check mold out

> as a possibilty. For example, my house had a water leak in a pipe

> in the attic that got into the ceiling and the walls. That is

> why I have kept asking you questions. I just don't get symptoms

> when I go into any particular area or building that might be

> mold infested.

>

> In my case, I was dx'd w/ CFS by 5 docs, 3 of which were infectious

> disease docs. However, without mold avoidance as a 'treatment', I

> have been snow skiing at 12-13,000 feet for the last seven years.

> My main problem is post exertional fatigue, and it doesn't matter

> where I am. So I think that whatever hit me was something other

> than mold-I think a virus but I don't know. Best regards,

>

> Mike C (CFS since May, 1993)

In our cohort, Dr Cheney and Dr say it was something that

was initially named " Human B Cell Lymphotropic Virus " when it was

first discovered, later to be changed to HHV6, and then again to

HHV6A when the less pathogenic and far more prevalent HHV6B " Roseola "

variant was discovered.

So, we're pretty sure we know which virus it was that slamdunked

our little geographic area.

-

Brain Physiology

Buchwald D, Cheney PR, DL, Henry B, Wormsley SB, Geiger A,

Ablashi DV, Salahuddin SZ, Saxinger C, Biddle R, et al. A chronic

illness characterized by fatigue, neurologic and immunologic

disorders, and active human herpesvirus type 6 infection. ls of

Internal Medicine 1992; 116(2): 103-13.

Abstract: OBJECTIVE: To conduct neurologic, immunologic, and

virologic studies in patients with a chronic debilitating illness of

acute onset. DESIGN: Cohort study with comparison to matched, healthy

control subjects. PATIENTS: We studied 259 patients who sought care

in one medical practice; 29% of the patients were regularly bedridden

or shut-in. MAIN OUTCOME MEASURES: Detailed medical history, physical

examination, conventional hematologic and chemistry testing, magnetic

resonance imaging (MRI) studies, lymphocyte phenotyping studies, and

assays for active infection of patients' lymphocytes with human

herpesvirus type 6 (HHV-6). MAIN RESULTS: Patients had a higher mean

(± SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 ± 1.5

compared with 2.3 ± 1.0, respectively; P less than 0.003). Magnetic

resonance scans of the brain showed punctate, subcortical areas of

high signal intensity consistent with edema or demyelination in 78%

of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to

36%) (P less than 10(-9)). Primary cell culture of lymphocytes showed

active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to

78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P less than 10(-

8], a finding confirmed by assays using monoclonal antibodies

specific for HHV-6 proteins and by polymerase chain reaction assays

specific for HHV-6 DNA. CONCLUSIONS: Neurologic symptoms, MRI

findings, and lymphocyte phenotyping studies suggest that the

patients may have been experiencing a chronic, immunologically

mediated inflammatory process of the central nervous system. The

active replication of HHV-6 most likely represents reactivation of

latent infection, perhaps due to immunologic dysfunction. Our study

did not directly address whether HHV-6, a lymphotropic and gliotropic

virus, plays a role in producing the symptoms or the immunologic and

neurologic dysfunction seen in this illness. Whether the findings in

our patients, who came from a relatively small geographic area, will

be generalizable to other patients with a similar syndrome remains to

be seen.

[Guest guest]

Almost every self-described CFS patient that I have ever spoken to,

when asked if they had spent time in a moldy building

around the time that they first fell ill, has told me yes. I went to a

CFS sufferers coffee meetup last year and almost everybody there had

been exposed to mold. I didn't ask them, I just told them my own

story. They volunteered the information.

Thats pretty striking -

Plus you have some huge and powerful business and corporate medical

interests stating publically that it would be a financial disaster for

them if mold was officially admitted to be causing all the sickness

people are telling us it is, and I think we have a recipe for a public

health disaster of denial.

So, its not just (as you changed the subject to) " 's " experience,

its lots of people's experience..

On Jan 2, 2008 3:40 PM, kdrbrill <kdrbrill@...> wrote:

> said:

>

>

[Guest guest]

This includes Dr h Ryll.

Although years ago when I interviewed him, he was unaware of Stachy,

he still described the " mold clues " perfectly.

-

http://www.med-help.net/ME-CFIDS.html

SICK BUILDING SYNDROME

I have examined many of those labeled as having this. I find the

disease identical to the chronic fatigue syndrome. There is no

difference - it is the same disease. Also, these people without

exception show the same laboratory features. I will comment later on

its causes.

There are those who believe that CFS can be caused different things

such as stress including injuries, operations, childbirth, and

exposure to toxins (here is where the sick building syndrome comes

in). I myself believe that there is always a virus in residence. I

believe that these various stresses can precipitate the virus to

cause CFS in individuals who are already carrying it or are exposed

to it at the same time as the given stress.

..

FIBROMYALGIA CFIDS

MYALGIC ENCEPHALOMYELITIS

IVN & Fibromyalgia

By Doctor h Ryll

DISCUSSED BY: ERICH D. RYLL, M.D.

Assistant Clinical Professor of Medicine

Division of infectious & Immunologic Diseases

Department of International Medicine

University of California

, California

..

..

..

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

----------

..

..

HISTORY

In the spring and summer of 1975, there was a major,

severe epidemic of a communical, apparent viral disease at the Mercy

San Hospital in Carmicheal, a suburb of Sacramento, California.

It occurred in February, and the bulk of the disease happened between

July and November of 1975. Cases continued to occur, although few,

until 1978

The epidemic involved all departments of the

hospital. It was equally severe in all departments.

I was appointed chairmen of a committee to

investigate the outbreak. At the time, I feared that there might be

fatalities and so Asked that the CDC (Communicable Disease Center,

Atlanta, Georgia) become involved. An epidemiologist fro there spent

a week at the hospital. Another epidemiologist from the State came

for the day.

Cultures were obtained for all known viruses,

bacteria, and rickettsiae, and all were negative. The disease was

apparently due to a new agent of disease.

At the time, we did a literature search and found

three reports of outbreaks that were called EPIDERMIC PHLEBODYNIA

(meaning painful veins). While the disease at Mercy San was

somewhat similar, it included many more features that were subscribed

in epidermic phlebodynia and so at the time, I believed it was not

the same disease. Later , additional literature search showed that

the disease was very similar to epidermic neuromyasthenia/ myalgic

encephalomyelitis. But toublingly, very few if any, vascular features

were mentioned.

Since the very beginning, I have followed these

patients on a virtual daily basis-in 1992, now for 17 years. This

continuos observation and study is perhaps the longest interval that

anyone has ever studied such an disease. I have, throughout the

years, learned all the nuances of the disease. Because the symptoms

are so many and often seemingly bizarre, I often attempted to

disclaim them as being real. But I learned that the patience were

always right and that I had to have an open mind. This disease is

humbling.

One must remember what a famous French physician said

a year ago, Charcot:

" DISEASE IS VERY OLD AND NOTHING ABOUT IT HAS

CHANGED. IT IS WE WHO CHANGE AS WE LEARN TO RECOGNIZE WHAT FORMERLY

HAS BEEN IMPERCEPTIBLE. "

Infectious Venulitis

Infectious venulitis (IVN) is a disease caused by an as

yet unidentified virus. This disease begins by an in fluenza-like

onset with headaches, sore throat, fever, dizziness, runny nose,

congested head, nausea, vomiting, muscle aching, extremity pain, and

other features. Unlike ordinary flu, however, this initial phase of

IVN can last as long as a year and longer without let up. During this

initial flu state, that I call a flu-storm because it lasts so long

in many patients, sufferers are very drowsy at times - almost in a

light coma. The extremity discomfort is often described as a burning,

searing sensation. Joint pains can be sever cases, patients have

frequent bruises for unexplained reasons and swollen, painful veins.

After the initial flu state leaves, the patients

are still not well. They have a constant plateau of illness

punctuated by unpredictable relapses. In a menstruating woman,

relapses are apt to occur during menses or during menses, the disease

is worse with increased pain and disability. During relapses they may

have resumption of the many flu-like symptoms including drowsiness,

headaches, fever and other features. Some patients have a relatively

mild flu onset, only to have years later a relapse that is much more

severe than the initial illness.

The disease is frightening to patients because of the

severity and many features. Physicians are not trained to diagnose an

illness that encompasses so many signs and symptoms. Two common

statements by patients during the initial illness are: " I HURT ALL

OVER " and " I AM GOING TO DIE " .

Patients suffering from IVN have the following

features:

SEVERE EXHAUSTION AND WEAKNESS

The exhaustion that occurs in this disease is profound and

unusual. Patients often are not even able to hold up their heads.

They have a compelling need to sleep. During relapses, patients have

been known to sleep around the clock for days on end. The usual sleep

pattern requires many more hours than usual. The sleep pattern is

disturbed and is not restful. And yet, during waking hours, patients

feel sleepy much of the time. A common statement is: " I LIVE IN A

FOG " . Strength is greatest for most early in the morning. After a

short time, endurance fades and patients find that performing the

slightest tasks requiring little effort formerly, now can not be

done. Some patients find that they can do small tasks in spurts,

resting between times. During relapses, many patients can be totally

helpless and unable to even care for themselves. Walking at all can

become impossible and patients have been known to crawl to the

bathroom on hands and knees.

Most women love to shop, but for a woman with IVN, it may

be next to impossible to do. I have suggested that they obtain

wheelchairs for activities such as shopping and other social events.

They can then tolerate more extended activity. Many patients find

that they can think more clearly when lying down and are able to do a

limited amount of work while in the prone position. One patient who

was desperately trying to hang onto her job would dash down to her

car on her breaks in order to rest and restore her energy in an

effort to keep on working. Patients have been known to fall asleep

inappropriately, at times in mid conversation One severely ill

patient reported that at time her head would drop onto her chest

while she was standing and she would be asleep.

DISTURBANCE OF COGNITION/MENTATION

Short term memory can be severely impaired. Patients

cannot remember where they place items or store them in inappropriate

sites, such as putting a book in the refrigerator, etc. Calculating

numbers is difficult. In the severely ill, checkbook cannot be

balanced or even the most simple arithmetic accomplished. They cannot

take care of their own financial affairs. Filling out forms can be

impossible. Mental work of any kind becomes difficult or impossible.

Patients cannot put their mind to words - it is as though the brain

is no longer connected to the tongue. Concentration can be severely

impaired. Directions are difficult to follow. Women often cannot

follow cookbook recipes. Reading is difficult. Patients must read

again and again to comprehend meaning and to retain.

Over confusion is common. Many have great difficulty

in driving and often get lost in familiar neighborhoods. Street signs

are difficult to follow and patients cannot decides at times which

way to turn. Some have gotten lost on their way to my office, finding

themselves in a different part of town. They had to call spouses or

family members to get them. Cars cannot be found in parking lots.

Others often report that when driving they suddenly realize that they

don't know where they are going and others have stated that upon

arrival at a destination, they did not know how to find their way

home. There are frequent mental lapses.

Because of a frightening new disease that physicians

cannot recognize, diagnose or understand and because it seems never

to go away, patients become depressed. Upon visiting physicians, this

depressions recognized and blamed for the entire illness. This of

course is not true. Further, the viral disease itself is also in the

brain and there may be an element of organic depression due to the

virus.

Panic is common and can be severe. Rarely, patients

can become psychotic and have hallucinations. But patients realize

usually that these occur. They know that their minds are not working

properly unlike in Alzheimer's syndrome when patients do not seem to

have an awareness of their true state.

NERVOUS SYSTEM ABNORMALITIES

Patients are usually dizzy on an intermittent basis.

Rarely, some are dizzy all the time. They are incoordinate and lurch

about. Attempting to go through a doorway, they will hit the door

jamb instead. They can have difficulty in performing fine movements

such as writing. They have difficulty in judging distances - lack of

spatial perception. Some are totally unable to drive; most others

learn that there are days when they cannot safely drive an

automobile.

Falls are common. Patients often relate that their

legs simply give way and they fall. Others state that severe

dizziness has caused them to fall. Many do not know what happens.

Patients have injured themselves severely at times by falling.

Fainting episodes are not unusual; patients usually do not have

insight into the reasons. Patients have occasionally experienced

sudden fainting while driving and awakened to find themselves in

ditches, etc. Epileptic like seizures are seen rarely. Small strokes

are not unusual. Many patients have definite weakness, sometimes of a

given extremity, other times in general. There have been no major

strokes to date, although some patients have persistent weakness of

extremities after small strokes. Some have had to use canes, walkers,

wheelchairs and been bed confined.

Patients usually drop items unexpectedly from their

hands. Women often burn themselves inadvertently in the kitchen.

Blurred vision is common and ringing of the ears as well. Some

patients experience such a roaring or fluttering sound in their ears

that it is most difficult to tolerate. Numbness and tingling of

extremities is common.

The autonomic nervous system is usually deranged in

this disease the portion that controls sweating, blushing and so on.

Patients thus have episodes of flushing and sweating. Hands are often

hot and wet with sweat; often they are bright red or mottled. At

times hands and feet can be cold and very clammy. Some have been

known to have deep purple and extremely cold hands. When patients are

in relapse, others can immediately notice that they are not well as

they are often pale. Family members and close associates are usually

able to tell when a patient is feeling worse than usual by their

appearance.

PAIN

Pain can be very severe in this disease. Muscles are

painful and tire easily. Joint exhibit a peculiar type of arthritis.

The areas around the joints becomes inflamed. At times, although this

is much more unusual, there can be swelling of joints. While joints

are uncomfortable, they are not destroyed by this disease. The

arthritis in this disease is migratory - it seems to travel around.

Patients at times relate that they feel as though a hot poker is

being pushed through their veins, notably those of the legs. They

sting and burn. A majority of patients have ulcer like symptoms and

some, more rarely, have ulcers. In addition properly and that the

gastrointestinal tract is sluggish.

Of all the areas of pain, headache is often the worst.

It is often accompanied by nausea, dizziness and vomiting. Light

bothers their eyes most of the time, worse at the time of headache.

At their most severe, headaches are worse than migraine and difficult

to control with medications.

Pain and all symptoms of this disease are made worse

by exercise. A patient during a better period might try to exercise

normally and the find he or she must spend days in bed as a result to

recuperate. A common statement is " I PAY FOR EVERYTHING THAT I DO " .

The discomfort of these patients is made much worse by

the hostility that they encounter from family, friends and many

physicians. Spouses have been known to be disbelieving and totally

unsupportive. This has led to severe martial stress or dissolution.

Children become burned out and friends do not always want to hear

that a patient doesn't feel well. As a result, many patients finally

remain quiet. Panic and depression occur when the patient realizes he

is not improving. Because he or she has been told so often that

nothing is physically wrong with them, they begin to believe that

they are " crazy "

Vascular Features

At the onset of their disease, many patients have

unexplained bruises (without any trauma) . These often sting and

burn. More severe cases can exhibit swollen veins, painful in nature.

At times, clots have formed in veins, but usually not in the deep

circulation. Small veins can suddenly break, with a stinging

sensation leaving a bruise. Veins can be inflamed even when they are

not visible on the surface.

A RELAPSING COURSE

Except for the mildest cases - those who have symptoms

only during a relapse - patients have a constant plateau of illness

during which they are never entirely well. One cannot during these

times gauge their illness because appearances can be deceiving. Bear

in mind that many patients with cancer, heart disease, diabetes and

other severe illnesses often appear to be normal to the casual

observer as one encounters them at the grocery store, church and

other places. During relapses anyone can tell that a patient is not

well.

Relapses can be induced by physical, emotional or

environmental stress. Again, in the menstruating woman, the disease

is worse at this time and a relapse is apt to occur at this time.

Relapses can last for indefinite periods from weeks to months.

LABORATORY STUDIES

To this date, there is no conclusive test or tests that

can tell one with certainty that they have this disease. There are

many, however that can be abnormal, many of them involving the immune

system.

An elecrtomyogram is frequently abnormal, showing

damage to nerves. A magnetic resonance brain image often reveals

evidence of demyelination. We find this in multiple sclerosis, as

well and probably in other virus diseases. (Multiple sclerosis is not

known at this time to be caused by virus.) A specialized SPECT scan

shows evidence of impaired brain circulation in nearly all of the

patients, confirming the vascular nature of this disease. Tests for

muscle often show abnormalities and damage, although muscles do not

visibly shrink.

TREATMENT

There is currently no treatment that cures the disease.

Gamma globulin is useful in a majority of patients to improve

function. A new drug called Ampligen is being studied and may be

available within a year. These two treatment, however, are expensive

and insurance carriers are loathe to pay for them.

Beyond this, there are many things that can be done to

improved better function. One must always remain positive it aids

the immune system in holding the disease in check. You must

restructure your life. Accept that you have this disease and live

with it's limitation. Be as normal as you can but do less of

everything, rest is essential and restorative. Gentle exercises are

advised so as to maintain muscle tone.

OUTLOOK

The general tendency is to slowly improve and the

majority of you will recover much of your function. Many of you will

recover virtually completely and will be able to live entirely normal

lives. Mild cases recover quickly and in all probability are not

diagnosed. (They do not even fit the diagnostic criteria for the

disease). A smaller percentage will remain ill.

ADDENDUM

I failed to mention one last entity that is currently very

popular and about which you may have heard something. It is

fibromyalgia or fibrositis or fibromyositis.

What is fibromyalgia? It is an inflammation of joints

and musculoligamentous connections - where muscles attach to joints

and bones.

Early on, investigators in this field said that in

fibromyalgia, if one exercise one feels much better - now they do not

say this. It is a term used by rheumatologists chiefly, although

others now are using it too. They used to say it was a disease of

women who are anxious and depressed - now they say this less and

less.

If you were to see a rheumatologist, many specialists

in internal medicine and others these days, you would be labeled as

having fibromyalgia . Researchers in this area - at least some of

them - now may also say that it comes from a viral disease.

Now I have known for 17 years that you have a form

of fibromaygia - it is due to IVN. But you have much more - It is

just one facet of your disease. Fibromyalgia can occur with many

conditions. To mention a few: systemic lupus, erythematosis, collagen

vascular diseases of all kinds, rheumatoid arthritis, Lyme disease

and many others. I have found in examining people that other viral

diseases can cause this - but it does not persist as it does in IVN.

Furthermore, in Fibromalgia, vascular features are not mentioned

and the crucial features of my physical diagnosis are not mentioned

and the crucial features of my physical diagnosis are not included.

I am afraid that investigators working in this area are including

fibromyalgia due to many causes, including that due to IVN. This

further beclouds the issue and confuses those working in this area.

SUMMARY

IVN may be the same or closely related to a disease

that is in the United Kingdom called MYALGIC ENCEPHALOMYELITIS and

in this country, EPIDEMIC NEUROMYASTHENIA. These two are the same

disease and were first described in an epidemic that took place in

Los Angeles. This epidemic was reported by the National Institute of

Health in the form of a very thick public health report. Since then,

ME and ENM have been reported worldwide, usually in closed, contained

populations such as monasteries, convents, schools, military barracks

and especially hospitals. IVN is identical to ME/ENM with the

exception of the vascular features. There were several references to

vascular involvement but it was not striking. Vascular features were

perhaps more prominent in the epidemic at the Mercy San Hospital

in 1975, or they were simply not recognized in other outbreaks around

the world. In 1955, two researchers studying an epidemic of ME

performed studies on monkeys, some of whom died. Definite vascular

features were reported by them.

In 1984 I visited New Zealand and found many people

there suffering from a milder form of IVN (called ME by them). I

spoke to large groups of people and appeared on National Radio and

TV. I examined patients with Dr. Murdoch, a leading researcher there

and showed him my method of examination that he has since used.

Also in 1984, I presented a paper at the Interscience

Conference for Antibiotics and Chemotherapy, and arm of the American

Society for Microbiology, where much original research in infectious

diseases is aired for the first time. This was in Washington, D.C. An

abstract of this presentation is published in their Proceedings of

that year.

In the 50's and 60's, three different epidemics of a

painful vein disease occurred and were published in the medical

literature's. I believe that EPIDEMIC PHLEBODYNIA, the term that was

given this disease, is probably a milder form of IVN It too had

severe pain, headaches, but not nearly as many features as in IVN

and ME/ENM. It has not been reported since the 1960's.

In 1985 two scientific papers were published on so-

called Chronic Epstein-Barr virus disease. At the same time, an

epidemic of a strange, viral like disease took place at north Lake

Tahoe and the researchers there promptly named it chronic EB virus

disease. When this occurred, I had misgivings and did not believe

this was the case. EB virus disease is manifested in infectious

mononucleosis, the most common form of EB virus disease (other types

exist, but they occur in severely immune deficient people). The

reason I did not believe it was because my patients with IVN, whom I

had followed daily since 1975 - some of them developed infectious

mono well after the onset of IVN. I witnessed the infectious mono to

come and go, but the IVN remained the same unto this day. So I

reasoned that the outbreak at Lake Tahoe was probably a variant of

IVN or the same identical disease, and if this be so, the disease

could not be due to Epstein-Barr Virus.

Finally, all experts in the field across the country

came also to realize that so-called chronic EB virus disease was not

due to EB virus at all.

In 1986, the National Cancer Institute discovered a

new human virus that they first named HBLV and then renamed HHV6 or

HUMAN HERPES VIRUS NO.6. Then the opinion prevailed that HHV6 was the

cause of the Lake Tahoe outbreak. But this did not prove to be the

case epidemiologically and this theory has been largely discarded at

this time.

In 1988 the Communicable Disease Center of Atlanta,

Georgia convened a symposium of many prominent researchers on this

disease, across the country. The name Chronic Fatigue Syndrome was

coined and criteria were established to diagnose this disease.

How is the CHRONIC FATIGUE SYNDROME different from

IVN? I believe it is the same disease, although no vascular features

are mentioned in the scientific writings thus far published. Yet many

of you who are examined by me exhibit the same features as my

original patients from 1975 with with evident vascular features. In

all of you I find evidence of inflammation of deep veins.

My original 1975 cases, as time has elapsed - years -

have less evidence of superficial venous involvement and now resemble

most of you whom I see for the first time. Aside from that, you

fulfill all the criteria for those who are labeled " CHRONIC FATIGUE

SYNDROME " . But I make my diagnosis on physical examination as well as

history, unlike others working in this area.

The viral agent responsible has not yet been

identified. In 1975 cultures of all kinds were submitted, to test for

all known viruses, bacteria and rickettsiae and they were all

negative. It is a difficult agent to culture. There are some who

believe that this disease could be caused by a partial or incomplete

virus. The truth at this time is not known.

The description of the disease above describes the

more severe cases. There are those of you who have milder cases and

expressions of this disease. Some of you for instance, have only mild

exhaustion and extremity discomfort. There are those of you who have

mild disease and when you have a remission, feel virtually normal. At

least in the more severe types, IVN appears to be a lifelong disease.

The general tendency is for patients to gradually improve.

While there is presently no cure for IVN, a great

deal can be done to help patients cope with the distress caused by

this disease. It is also very useful for you to know what you have,

for if you know what you are up against, it is HALF THE BATTLE WON!

There are medicine's that do help.

..

..

..

UPDATE, SEPTEMBER 1990

It has been my contention since 1975 that, a new and

difficult to cultivate virus causes this disease. In 1975, we

attempted to isolate a virus from human sources, throat swabs, mouth

washes and stool samples. We checked for evidence of all known

living agents and viruses that might cause such a disease. Nothing

grew in tissue cultures, suckling mice and no antibodies were found

against all possible known viruses, including EBV (Ebstein-Barr

virus), sackie virus and many others. I further have consistently

stated that this virus is communicable person-to-person and that

close family members and associates could harbor the virus, but not

be ill. My guess was that this might be a new retrovirus. Recently

at the Wistar Institute of Philadelphia, Dr. Elaine DeFreitas was

able to show a virus that most closely resembles HTLV-2 in 10 of 12

Chronic Fatigue Syndrome patients who were adults and 14 out of 19

children studied. Bear in mind, however, that she did not actually

isolate the virus. She also used in situ ybridization of find DNA

sequences complementary to viral messenger RNA probes in lymphocytes,

the white cells infected by HTLV-2. But this is not proof positive

that this virus causes the chronic fatique syndrome (infectious

venulitis) . Additional work must be done to prove it. Nevertheless,

it is the most exciting lead as yet and HTLV-2 may indeed be the

virus we have been looking for. What is HTLV-2, or human T cell

lymphotrophic virus? It is a retrovirus, a peculiarly formidable

family of viruses. Now, Herpes viruses (Chicken pox-shingles, Herpes

simplex (or cold sore virus), Cytomegalo virus, EBV virus (Epstein-

Barr or infectious mono virus ), HHV6 (human herpes virus No. 6 ) and

HHV7 appear to infect all of us and that is why it is so difficult

to grow retroviruses. The Herpes groups rapidly destroy the cells

and one can't see what the retrovirus effect is doing. So, a direct

approach to grow retroviruses does not work. HTLV-1

causes a type of leukemia (hairy cell leukemia) and tropical spastic

paraparesis, a chronic neurological disease. As you know, HTLV-3 or

HIV causes AIDS. But thus far, HTLV-2 has been associated with no

disease, unless this new association with the chronic fatique

syndrome holds up. It is interesting that DdFrietas found HTLV-2 in

family members and associates who were not ill. I have said for many

years that the unknown virus was carried latently, that is, without

disease in family and close associates. My studies have indicated

this for a long time. Many researchers believe that perhaps more than

one virus is involved including EBV and HHV6. The British believe

that sackie are not involved. Only time and further studies will

reveal whether HHV6 plays any causal role in an ancillary manner.

!992

The exact identity of this retrovirus is unknown. It is

unidentified. Four teams around the world are studying it. It shows

up in my 1975 Mercy San patients as well as recent cases,

indicating that the 1975 epidemic was indeed a variant of the chronic

fatique syndrome. While HHV6 is shown to be actively replicating in

patients with CFS, there is nothing to suggest it is the cause of the

disease. High titers can be found in normal people.

Retype with permission given by DR. ERICH D. RYLL

BY Jocelyn N. --

LVN

GO TO NEXT PAGE

..

FOR MORE ON FIBROMYALGIA,

CFIDS, & MYALGIC ENCEPHALOMYELITIS

GO TO PAGE 20 (CLICK)

.

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

----------

HISTORY

In the spring and summer of 1975 there occurred a major, severe

epidemic of a communicable, apparent viral disease at the Mercy San

Hospital in Carmichael, a suburb of Sacramento, California. The

first two cases became ill in February; the bulk of he cases fell ill

between July and November of 1975. Several cases tailed out to 1978.

The epidemic spread to all departments of the Hospital. It was

equally severe in all departments.

I was appointed chairman of a committee to investigate the

outbreak. Fearing that some people might die, I asked that the CDC

(Communicable Disease Center of Atlanta, Georgia) to become involved.

An epidemic intelligence officer of the CDC spent one week in

residence, and an epidemiologist from the California State Department

of Health, Berkeley, came for a day.

Cultures were obtained for all known viruses, bacteria, mycoplasma,

and rickettsiae, and all were found to be negative. The disease was

apparently due to an unknown agent, presumably a virus.

At the time we did a literature search and found three reports of

outbreaks that were called EPIDEMIC PHLEBODYNIA(EP), meaning painful

veins. While the disease at the Mercy San Hospital (MSJ) was

somewhat similar, it included many more features that were described

in EP and so at the time I did not believe it was the same disease.

Additional literature search showed that the disease was very similar

to EPIDEMIC NEUROMYASTHENIA/MYALGIC ENCEPHALOMYELITIS (ENM/ME). But

troublingly, very few vascular features were mentioned.

I have followed these patients on a daily basis since 1975. This is

the longest continual study of this type of disease that has ever

been made. Because of this, I have learned all the nuances, all the

signs and symptoms of the disease. Because the complaints of patients

are so many and often seemingly bizarre, I often attempted to

disclaim them as being real. But I learned that you patients were

always right and I was always wrong. In studying this disease, one

must always have an open mind. This disease teaches the physician to

be humble.

One must remember what a famous French physician,

Charcot, said many years ago : " DISEASE IS VERY OLD AND NOTHING ABOUT

IT HAS CHANGED. IT IS WE WHO CHANGE AS WE LEARN TO RECOGNIZE WHAT

FORMERLY HAS BEEN IMPERCEPTIBLE. "

INFECTIOUS VENULITIS

Infectious venulitis (IVN) is a disease caused by an as yet

unidentified virus or perhaps a combination of more than one virus.

It begins with an influenza like onset, often so severe in nature

that I call it a flu-storm, with headaches, sore throat, fever,

dizziness, runny nose, nausea and vomiting, muscle aching, extremity

pain, and other features. Unlike ordinary flu, the flu-storm can last

from weeks to over a year. Sufferers are very drowsy at times,

especially during relapse that almost resembles a light coma. The

extremity discomfort is often described as a burning, searing

sensation. Joint pain can be severe. Numbness and tingling of the

extremities is common. The cases that occur in an epidemic have

spontaneous bruises that occur without any injury, and painfully

swollen veins. Those who become ill from the epidemic cases might not

show this - these cases are often milder, or the bruises and painful

veins might have only been at the beginning and went unnoticed.

After the initial flu state leaves, the patients are still not

well. They have a constant plateau of illness punctuated by

unpredictable relapses. In women who menstruate, the disease is worse

at this time and relapse is apt to occur. Some patients have a

relatively mild flu onset, only years later to suffer a relapse that

is worse than the initial illness.

Patients who suffer from IVN have the following features:

1. Severe exhaustion and weakness

The exhaustion that occurs in this disease is profound and unusual.

Patients often are not even able to hold up their heads. They have a

compelling need to sleep. During relapse, patients have been known to

sleep around the clock for days on end. The usual sleep pattern

requires many more hours than usual. Yet patients do not sleep

restfully and do not awaken refreshed. In the day time they

state : " I live in a fog. " Strength is greatest for most early in the

morning. After a short time, endurance fades and patients must obtain

bed rest. Energy is at a low ebb all of the time. Patients find that

can do small tasks in spurts, resting between times. During relapse,

many can be totally helpless and unable to care for themselves.

Walking at all can become impossible and patients have been forced to

crawl on their hands and knees.

Most women love to shop, but for a woman with IVN, it may be next

to impossible to do so. I often suggest a wheelchair for activities

such as extended shopping and other social events. Many find that

they can think more clearly lying down and are able to do a limited

amount of work this way - it apparently improves their brain

circulation. One patient who was desperately trying to hang onto her

job would dash down to her car on her breaks in order to rest lying

down, to continue working.

Patients have been known to fall asleep inappropriately, at times

in mid-conversation. One severely ill patient reported that at times

her head would drop onto her chest while she was standing up and she

would be fast asleep.

2. Disturbance of Congnition/mentation

Short term memory can be severely impaired. Patients cannot

remember where they place items, or store them in inappropriate

sites, such as putting a book in the refrigerator, etc.. Calculating

is difficult ; checkbooks cannot be balanced. They often cannot take

care of their own financial affairs. Directions are difficult to

follow ; road signs cannot be read. Filling out forms may be

impossible. Mental work of any sort becomes difficult or impossible.

Patients can't find the right words to say- it is as though the brain

is no longer connected to the tongue. At times patients have told me

that their brain does not send proper signals to their arms or legs

and they cannot function. Women have difficulty in following cookbook

recipes. Reading becomes difficult or impossible. Patients must read

again and again in order to comprehend.

Overt confusion is common. Many have great difficulty in driving

and get lost, even in familiar neighborhoods. Some have gotten lost

on their way to my office and had to call family to come and get

them. Others often report that when they are driving they suddenly

realize that they don't know where they are or where they are going

and can't find their way home. There are frequent mental lapses.

Panic is common and can be severe. Rarely, patients become

psychotic and have hallucinations. But this is usually not a true

psychosis - they know it is not real. It is unlike Alzheimer's

syndrome in which patients do not seem to have an awareness of their

true state.

Because of a frightening new disease that physicians cannot

recognize, diagnose, or understand, and because it never seems to go

away, patients become depressed. Upon visiting physicians, this

depression is recognized and blamed for the entire illness. This of

course is not true - the depression is as a result of the disease and

does not cause the disease.

Nervous system abnormalities

Dizziness often occurs and for some patients, it is constant. They

are incoordinate and lurch about. They do not know where they are in

space, often hitting door jambs and at times have falling episodes.

They state that their legs just give way causing them to fall. At

times falls result in severe injury. Some have fainting episodes.

Small strokes are not uncommon and can be very alarming. Seizures can

occur. Many are only able to drive to a limited extent ; at times,

not at all. Others can never drive. Patients at times have fainted

while driving and awakened to find themselves in ditches, etc. Some

have had definite nerve damage such as not being able to lift a leg,

etc...Some have had to use canes, walkers and wheelchairs. At the

worst, patients are bed-confined.

Patients droop items unexpectedly from their hands. Women often

burn themselves in the kitchen. There is difficulty in performing

fine movements such as writing. Blurred vision and double vision are

common. Eye muscles do not work properly. Ears ring and at times

there is an extremely annoying fluttering or roaring. Numbness and

tingling of extremities is common. This interferes with feeling and

handling objects.

The autonomic nervous system that results in flushing, blushing

etc., that controls blood vessels is deranged in this disease.

Sweating, flushing, icy and blue hands and feet, hot sweaty hands,

red and blotchy hands are common. When patients are in relapse it is

easy to tell that they are ill : pallor of the face and dark areas

under the eyes, etc. But when they are in relapse, but still sick,

they are mistakenly thought to be well. One cannot place reliance

upon looks.

Pain

Pain can be the most severe aspect of this disease. It affects all

areas of the body; headache is usually the most severe pain and is

difficult to control, even with the most potent opioids at times.

With the more severe headaches, there is nausea and vomiting that at

times can leak to dehydration and hospital admission. Joint pain can

be severe, but the disease does not cause a destructive form of

arthritis. Mild swelling of joints is common ; rarely, it is severe.

The joint pain is migratory - travels around. Ulcer symptoms and

ulcer disease is common. Patients relate that their food doesn't

digest - it just sits in the stomach. There is partial paralysis of

the stomach and gastrointestinal tract - this can result in nausea.

Pain and all aspects of this disease are made worse by exercise or

attempting to behave normally. A patient during a better period might

attempt to act normally and then find herself or himself in bed for

days. A common statement is : " I pay for everything that I do. "

The discomfort of these patients is made worse by the hostility

that they encounter from family, friends, associated, and physicians.

Disbelieving and unsupportive spouses lead to marital stress or

dissolution. Children become burned out and friends do not always

want to hear that a patient does not feel well. Because patients have

so often been told that nothing is physically wrong with them, they

begin to believe they are 'crazy'.

Vascular features

At the onset of their disease, many patients have unexplained

bruises (without any trauma). These often sting and burn. More severe

cases exhibit swollen veins, painful in nature. At times, clots have

formed veins, but usually not in the deep circulation. Small veins

can suddenly rupture, with a tingling sensation, and leaving a

bruise. Deep veins can remain inflamed and are not visible on the

surface.

A relapsing course

Except for the mildest cases - or those who have symptoms only

during a relapse- patients have a constant plateau of illness during

which they are still not well, but do not appear that ill. Appearance

can be deceiving. Bear in mind that many patients with cancer, heart

disease, diabetes, and other severe illnesses often appear to look

normal to the casual observer as they are encountered at the grocery

store, church, and other sites. During relapse, however, patients

look unmistakable ill. Relapses can be caused by physical, emotional,

or environmental stress. Again, in the menstruating woman, relapses

can occur at this time and the disease is worse in general at the

time of menses. Relapses can for indefinite periods from weeks to

months to years.

Laboratory studies

To this date there is/are no conclusive test or tests that can tell

with certainty that the disease exists. There are, however, many

tests with abnormal findings that are in keeping with this disease,

most of them involving the immune system.

An electromyogram is frequently abnormal, showing damage to nerves.

The magnetic resonance brain image (MRI) often reveals evidence of

demyelination - damage to the myelin sheath covering the brain. The

MRI can show the same findings in other diseases as well, including

multiple sclerosis. A specialized SPECT scan invariably shows

impairment of brain blood circulation. A PET scan can be abnormal,

indicating that the physiology, or function of the brain is impaired.

Cytokines, produced by lymphocytes, are substances we all need but

in this disease, there is often an excess that causes damage or the

production of some that are damaging by nature. Some cytokines are

protective, and perhaps they are deficient in this disease.

Some tests commonly found are keeping with, and support the idea of

an active viral infection. Muscle biopsies are often abnormal as well

as other tests for muscle disease. Muscles, however, may be damaged

but do not visibly shrink or waste away.

Treatment

There is currently no treatment that can cure this disease.

Treatments are geared to treating symptoms and making life more

bearable and functional, as well as to modulate, or change the immune

system so that it can better combat the disease. Immune modulating

therapies, however, are usually expensive and insurance carriers are

loathe to pay for them.

Beyond this, however, there are many things that can be done to

improve comfort and well-being. One must always have a positive

outlook - have a mind set that the disease will get better. This aids

the immune system - and indeed, it is possible. You must re-structure

your life. Accept that you have this disease and live within its

limitations. It takes some experimenting to find out how much you can

get by with. Be as normal as you can, but do less of everything. Rest

is essential and restorative. Gentle aerobic exercise are advised to

maintain muscle tone.

OUTLOOK

The general tendency is to slowly improve and the majority of you

will recover much of your function, but all things are possible. Very

mild cases often recover entirely. Many of you will have residual

symptoms, for a long time. Beyond the mild cases, most of you will

continue to have some symptoms, at least intermittently.

There a number of confusing entities (conditions) that need to be

discussed:

FIBROMYALGIA

Fibromyalgia is an inflammation of joints and musculoligamentous

connections. The diagnosis rest upon finding so-called trigger points

over various joints. Early on investigators stated that if one has

fibromyalgia, one should exercise - it makes you feel better. Now

they do not say this. It is a term that is used by rheumatologists

chiefly although now other physicians are beginning to use the term.

Generally, if you are seen by a rheumatologist or internist, he or

she may say that you have fibromyalgia. And indeed you have

fibromyalgia. But it is one facet, one part of your illness, the

chronic fatigue syndrome. I have examined 5000 of you at this time

and all but 8 have had the chronic fatigue syndrome (infectious

venulitis). The eight I mentioned had fibromyalgia that I could not

categorize. It was caused by something else. The remainder of the

5000 all had your disease.

In other words, fibromyalgia is just one part of your disease. Some

of you have it mildly, some of you, severely. Generally I believe

that those who label this disease fibromyalgia are akin to the seven

blind men with the elephant : they only see the trunk or the tail-

and miss all the rest that is going on with you. Many of you fulfill

all of the criteria for fibromyalgia in addition to the chronic

fatigue syndrome and/or infectious venulitis.

Fibromyalgia can also occur with many other illnesses including

cancer, Lyme disease, rheumatoid arthritis, lupus erythematoses,

cancer, to mention just a few. Other viral diseases can cause

fibromyalgia, but unlike your disease, it does not last very long,

nor does it keep coming back.

SICK BUILDING SYNDROME

I have examined many of those labeled as having this. I find the

disease identical to the chronic fatigue syndrome. There is no

difference - it is the same disease. Also, these people without

exception show the same laboratory features. I will comment later on

its causes.

GULF WAR SYNDROME

At this writing, I have examined two patients with this label and

also, find them to have the chronic fatigue syndrome. From the

histories that they gave, it also is a communicable disease, as is

the chronic fatigue syndrome. They are already carrying, or had been

simultaneously exposed to viral agent that caused disease when they

were exposed to an environmental toxin or pollutant.

EPSTEIN-BARR VIRUS DISEASE (EBV)

This is an outmoded term, but one that physicians who are not up to

date (and they are many) still cling to. No expert, including me,

believes that chronic fatigue syndrome (CFS) is caused by EBV.

Whether it plays a lesser role, along with other viruses, cannot now

be determined. But it is not the cause of your disease. It is

reactivated by CFS, along with other common viruses.

SUMMARY

The chronic fatigue syndrome first occurred in modern times at the

Los Angeles County Hospital in 1934. It occurred in the midst of a

poliomyelitis epidemic. Several astute physicians recognized that

there was a new disease present. Gilliam, who wrote a large research

paper accurately described CFS but did not name it. In the fifties

there was an epidemic in Iceland, also associated with a polio

outbreak - but again, recognized to be a new disease. It was found

that patients who developed CFS became immune to polio. CFS has

occurred more or less world-wide. Epidemics have been described in

closed, contained populations such as schools, military barracks,

convents, monasteries, and especially hospitals.

What I call infectious venulitis, that occurred in sever epidemic

form in 1975 in suburban Sacramento, is a variant of the chronic

fatigue syndrome. Until 1988, it was called epidemic neuromyasthenia

(ENM). Those in the United Kingdom call it myalgic encephalomyelitis

(ME), a term that is still in vogue, although chronic fatigue

syndrome is starting to be used their interchangeable. I believe that

the pathophysiology - the damage - is to the vascular system. Gilliam

and others found involvement of the vascular system in the Los

Angeles outbreak also. I find evidence of involvement of the vascular

system in the chronic fatigue syndrome, although generally not so

striking as in infectious venulitis.

In the 50's and 60's, three different epidemics of a painful vein

disease occurred in this country and were published in the medical

literature. It was called epidemic phlebodynia (painful veins). It

had many features of what I call infectious venulitis and the chronic

fatigue syndrome. I believe it was a milder form of infectious

venulitis. (Infectious venulitis has a more complete expression.) It

has not been reported since the 1960's.

In 1984 I visited New Zealand at the request of medical staff at

the University of Otago in Dunedin, the South Island because of a

widespread epidemic in both North and South islands of New Zealand.

It was called myalgic encephalomyelitis (ME) or Tapanui Flu, after

the small area where it was first discovered. I spoke to large groups

of people and appeared on national radio and TV. I was able to

examine patients there and showed medical staff my methods of

examination. It was then I found that what I was calling infectious

venulitis (IVN) was the same as ME, and thus also, ENM.

Also in 1984 I presented a research paper at the INTERSCIENCE

CONFERENCE FOR ANTIBIOTICS AND CHEMOTHERAPY, a forum where much

original research is aired world-wide. This was in Washington, D.C.

An abstract of this presentation is published in their proceedings of

that year.

In 1985 two scientific papers were published on so-called Epstein-

Barr virus disease. At the same time, an epidemic of a strange, viral-

like disease took place at north Lake Tahoe in Incline Village.

Researchers there, who had read these two papers promptly called it

chronic EB virus disease. When this occurred I had misgiving and did

not believe that this was the case. Virtually the only manifestation

EB virus is infectious mononucleosis with rare exception. Other types

exist but they occur in severely immune deficient individuals. The

reason I did not believe it because among my patients with IVN, whom

I had followed daily since 1975 - some had developed infectious

mononucleosis well after the onset of IVN. I witnessed the infectious

mononucleosis to come and go, but IVN remained and remains the same

to this day. I had reasoned that the disease at Lake Tahoe was either

the same disease as IVN or a variant of the same disease. And if this

was so, it could not be due to the Epstein-Barr virus. Finally, all

experts in the field across the country came to the same realization -

the disease was not due to EB virus.

In 1986, the National Cancer Institute of the NIH discovered a new

human virus that they first named HBLV and then renamed HHV6 for

human herpes virus number 6. There was an immediate flurry of

activity and claims that this was the cause of the Incline Village

outbreak and the cause of CFS. But this did not proveto be the case

epidemiologically and this theory has been largely discarded at this

time. It is possible that HHV6 plays some ancillary role, along with

other viruses. Since then HHV7 and HHV8 have been discovered - two

human viruses without a disease discovered thus far at. There are now

thus 8 Herpes viruses : chicken pox/shingles (the same virus), Herpes

simplex - fever blisters & genital herpes, cytomegalo virus (CMV),

Epstein-Barr virus (infectious mononucleosis), HHV6, HHV7, and HHV8.

In 1988 the Centers for Disease Control (CDC) of Atlanta, Georgia

(formerly called the Communicable Disease Center), convened a

symposium featuring many prominent researchers of this disease from

across the country. The name chronic fatigue syndrome was coined and

criteria were established to diagnose CFs. In December of 1994 the

criteria were changed and simplified somewhat.

How is chronic fatigue syndrome/myalgic encephalomyelitis different

from IVN? I believe it is the same disease. Although no vascular

features are mentioned in CFS, there are allusions to vascular

involvement in ME. I believe thus far researchers on CFS have failed

to note them - they are there. Many of you whom I have examined

exhibit the same features as my original patients of 1975 with very

evident vascular features. In all of you I find inflammation of deep

veins.

My original 1975 cases, with the passage of time, have less

evidence of superficial vascular involvement and now resemble most of

you. Aside from that, you fulfill all the criteria for CFS. But

unlike the official diagnosis of CFS, I also use a very specific

physical exam to make the diagnosis.

So what causes IVN/CFS/ME ? A specific viral agent has not yet been

identified. It does not appear to be anything common. It could be a

viral agent very difficult to cultivate. It could be what is called

a partial virus. Could it be due to two viruses? As yet there has

been no association with a retrovirus that has been proven. The

previous finding of a retrovirus has not been able to be repeated by

experiments and is invalid. But suppose that all, or nearly all of

us, carry an unknown retrovirus in our genes. And then another viral

agent infects and the two in combination produce the disease? Or

could this illness be due to a virus that escapes immune

surveillance. That is, our immune system is unable to detect it as a

foreign invader?

There is very interesting illness called the post-polio syndrome.

Patients who have had polio 20-30 years before acquire an illness

that closely resembles CFS. I have examined some of these people and

cannot tell the difference. Could this syndrome be due to a mutant

polio virus that escapes immune detection? Earlier I said that the

early epidemics of ME/ENM/CFS were immune to polio.

There are those who believe that CFS can be caused different things

such as stress including injuries, operations, childbirth, and

exposure to toxins (here is where the sick building syndrome comes

in). I myself believe that there is always a virus in residence. I

believe that these various stresses can precipitate the virus to

cause CFS in individuals who are already carrying it or are exposed

to it at the same time as the given stress.

The general tendency in this disease is for gradual improvement but

anything is possible. Beyond the mild cases who might totally

recover, most of you will have some symptoms lifelong.

It is very important for you to have a firm diagnosis. If you know

what you are up against, it is half the battle won.

Retyped & Posted With Permission

From: DR. h Ryll

By Jocelyn N.

..

[Guest guest]

So it must be that the reason that everyone in the building didn't

get sick was either, 1)genetics, or 2)a pre-existing (viral/other)

infection that made the mold able to cause serious illness?? Or am

I missing something (like 3,4,5)?

Mike C

>

> Almost every self-described CFS patient that I have ever spoken to,

> when asked if they had spent time in a moldy building

> around the time that they first fell ill, has told me yes. I went

to a

> CFS sufferers coffee meetup last year and almost everybody there had

> been exposed to mold. I didn't ask them, I just told them my own

> story. They volunteered the information.

>

> Thats pretty striking -

>

> Plus you have some huge and powerful business and corporate medical

> interests stating publically that it would be a financial disaster

for

> them if mold was officially admitted to be causing all the sickness

> people are telling us it is, and I think we have a recipe for a

public

> health disaster of denial.

>

> So, its not just (as you changed the subject to) " 's "

experience,

> its lots of people's experience..

[Guest guest]

Huh? I don't follow you at all.

I was at a cafe with a bunch of people who had CFS, most who had had

it for years. This wasn't some random group

of workers in a building. It was a group of CFSers. Not all of them

attributed their CFS to mold, but some did, including

the president of the local CFS organization. But as I remember a very

great many did say that they had been exposed to mold

around when they got CFS and that mold makes them sick.

Mold has to be very bad to smell it. And 'new' - Toxins like

trichothecenes can persist for decades in buildings.

We need better tools to test for mold because the current set of tools

that 'mold inspectors' use are WOEFULLY INADEQUATE.

I have had conversations about this with some of the most

knowledgeable professionals in the field and the bottom line is that

the kind of mold tests (spore tests) that they do in most testing

situations (because they are cheap) CONSISTANTLY show false negatives

with regard to stachybotrys. (the one that lasts decades)

There are other methods.. toxi testing for specific toxins and

something called " QPCR " but they are expensive and the typical

customers of mold inspectors are NOT usually looking for the truth,

they just want legal deniability.

On Jan 6, 2008 11:02 AM, yakcamp22 <yakcamp22@...> wrote:

>

> So it must be that the reason that everyone in the building didn't

> get sick was either, 1)genetics, or 2)a pre-existing (viral/other)

> infection that made the mold able to cause serious illness?? Or am

> I missing something (like 3,4,5)?

>

> Mike C

>

>

> >

> > Almost every self-described CFS patient that I have ever spoken to,

> > when asked if they had spent time in a moldy building

> > around the time that they first fell ill, has told me yes. I went

> to a

> > CFS sufferers coffee meetup last year and almost everybody there had

> > been exposed to mold. I didn't ask them, I just told them my own

> > story. They volunteered the information.

> >

> > Thats pretty striking -

> >

> > Plus you have some huge and powerful business and corporate medical

> > interests stating publically that it would be a financial disaster

> for

> > them if mold was officially admitted to be causing all the sickness

> > people are telling us it is, and I think we have a recipe for a

> public

> > health disaster of denial.

> >

> > So, its not just (as you changed the subject to) " 's "

> experience,

> > its lots of people's experience..

>

>

[Guest guest]

I cannot change the history of CFS.

I can only tell people how CFS came about.

It's all written down in Osler's Web.

And whether they believe it or not still doesn't change how it happened.

-

[Guest guest]

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Re: Dr Enlander - MOLD? Jan 10 2006

When Dr Cheney asked me to volunteer for the 1988 CFS CDC definition

study group, I tried to refuse, because I had told them from the

first day that mold was killing me - and I thought my " mold illness "

would obfuscate the viral concepts of " Yuppie Flu " " CEBV " - soon to

be " CFS " .

But Dr Cheney didn't seem to care, and then I thought that this

would work out great - because as a prototype for CFS, this would

FORCE them to identify the reason for my mold reactivity.

As I met more and more CFSers, I found that they too shared this

same strange reactivity to mold.

Remember how the CFS epidemic got started?

Half the girls basketball team and nine teachers all using the

teachers lounge all became ill - as told in Osler's Web?

(That tenth teacher didn't really use the teachers lounge - he ate

all his lunches out in his truck parked at Donner Lake)

I'm a graduate of Truckee HS and those were my teachers, and yes,

Truckee is a slammer! Still is.

I told Dr Cheney, " If whatever happened to us keeps happening, we

are going to see an epidemic of people just like me " .

I thought that doctors might be interested to know that an epidemic

of mold reactivity was coming their way. I contacted hundreds of

doctors and researchers, and told my story to various CFS groups,

and even though I consistently felt " mold hits " in these groups,

with many people complaining of the identical clues to mold

reactivity, nobody believed it.

In fact, you can go back in this group and CFSresearch and see that

I've posted all this before, and it just disappeared into the void.

Nobody thought much of it in these groups, either.

One would think that finding a common neurotoxic denominator at the

site of so many CFS clusters, especially the cohort that initiated

the Incline Village epidemic, might at least be worth a second look.

Dr Shoemaker was the only doctor who responded with the interest

that I thought all doctors would have, if given the chance to hear

this story.

These researchers uncovered the Truckee HS / SBS connection, but

didn't make it so far as to discover the T2 Trichothecene

contamination from Stachybotrys.

They could have just asked.

-

SICK-BUILDING-SYNDROME

CONCURRENT SICK BUILDING SYNDROME AND CHRONIC FATIGUE SYNDROME:

EPIDEMIC NEUROMYASTHENIS REVISITED

Cases of sick building syndrome (SBS) associated with the

development of chronic fatigue syndrome (CFS) were described. Three

apparent outbreaks of SBS were investigated: high school teachers in

Elk Grove, California in 1989; federal government workers in

Washington, D.C. in 1986; and high school teachers in Truckee,

California in the 1980s. Reported symptoms included cough, headache,

sore throat, fatigue, colds, sinusitis, dizziness, memory loss, and

weakness. Illness deemed more serious than SBS was observed in nine

of the 10 teachers who frequently used a single conference room in

Truckee, five of the 22 responding teachers in Elk Grove, and nine

of the 93 responding office workers in Washington, D.C. Individuals

with severe fatigue tended to have symptoms of mucous membrane

irritation characteristic of SBS; in addition, however, they

frequently had neurological complaints not typical of SBS but

characteristic of CFS. The authors conclude that CFS can apparently

occur in the setting of SBS and may occur in predisposed individuals

after exposure to noninfectious agents.

Clinical Infectious Diseases; 18(Suppl 1):S43-S48, 1994. (45

references)

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

>

Sick buildings can create great problems in the immune system,

how the mold acts on immunity we do not know, but obviously it is

toxic. I have a number of patients with mold problems and CFS.

<

Amazing.

After twenty years of being called crazy for asking CFS researchers

and doctors to investigate mold, suddenly mold is " obviously toxic " .

Yet they never asked the people at " ground zero " for the CFS

epidemic.

It was half the girls basketball team and the Truckee teachers that

caught the attention of Dr Cheney and Dr and got " CFS "

going.

This has been posted a number of times.

Maybe it will finally " Click " now.

-

[Guest guest]

And before anyone starts squawking at me about the girls basketball

team being at Incline instead of Truckee, that is part of the story.

I figured that once I got my foot in the door, then I could explain.

Twenty years on - and they don't see anything of interest.

They just slammed the door closed.

-

[Guest guest]

And contrary to the widespread belief that " If anyone found anything

that helps, we would know because everyone would be RIGHT ON IT -

faster than a fly on a cow-pie " ...

the reality is that I can go into ANY CFS group and say " I'm a member

of the original CFS cohort who found something crazy that seemed to

help " and instantly clear the room faster than a rasty beer fart.

You'd swear that people were deadset determined NOT to find clues.

-

[Guest guest]

Dear

See http://en.wikipedia.org/wiki/Blind_Men_and_an_Elephant

R

Re: 's experience/conclusions...

> I cannot change the history of CFS.

> I can only tell people how CFS came about.

> It's all written down in Osler's Web.

>

> And whether they believe it or not still doesn't change how it happened.

> -

>

>

>

> This list is intended for patients to share personal experiences with each

> other, not to give medical advice. If you are interested in any treatment

> discussed here, please consult your doctor.

>

[Guest guest]

" Windsor " <rwindsor@...> wrote:

>

> Dear

> See http://en.wikipedia.org/wiki/Blind_Men_and_an_Elephant

The point, being?

-

[Guest guest]

Every person perceives the elephant from ther personal experience and

perspective.

Re: 's experience/conclusions...

" Windsor " <rwindsor@...> wrote:

>

> Dear

> See http://en.wikipedia.org/wiki/Blind_Men_and_an_Elephant

The point, being?

-

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11:46 AM

[Guest guest]

Here's what I get out of that. Different people have different perspectives,

depending on what they are exposed to.

Ok, I get that, but the fact remains, it's still an elephant.

erikmoldwarrior <erikmoldwarrior@...> wrote:

" Windsor " wrote:

>

> Dear

> See http://en.wikipedia.org/wiki/Blind_Men_and_an_Elephant

The point, being?

-

This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

[Guest guest]

And CFS is ecperiences/ caused by different things in different people. It

ain't all mold dear

Re: Re: 's experience/conclusions...

Here's what I get out of that. Different people have different perspectives,

depending on what they are exposed to.

Ok, I get that, but the fact remains, it's still an elephant.

erikmoldwarrior <erikmoldwarrior@...> wrote:

" Windsor " wrote:

>

> Dear

> See http://en.wikipedia.org/wiki/Blind_Men_and_an_Elephant

The point, being?

-

This list is intended for patients to share personal experiences with each

other, not to give medical advice. If you are interested in any treatment

discussed here, please consult your doctor.

[Guest guest]

" Diane " <dphf@...> wrote:

>

> And CFS is ecperiences/ caused by different things in different

people. It ain't all mold dear

>

And what would lead you to believe that " " , a member of the

cohort listed below in which HBLV/HHV6a was discovered, would think

that everything is due to just mold?

-

A Chronic Illness Characterized by Fatigue, Neurologic

and Immunologic Disorders, and Active Human

Herpesvirus Type 6 Infection

Dedra Buchwald, MD; R. Cheney, MD, PhD; L. ,

MD;

Berch Henry, PhD; B. Wormsley, BS; Ann Geiger, BA;

Dharam V. Ablashi, DVM; S. Zaki Salahuddin, MS; Carl Saxinger,

PhD;

Royce Biddle, MD; Ron Kikinis, MD; Ferenc A. Jolesz, MD;

Folks, PhD;

N. Balachandran, PhD; B. , MD, PhD; C. Gallo, MD;

and L. Komaroff, MD

ls of Internal Medicine

15 January 1992; Vol 116 (2):103-13

____________________________________________________________________

¨ Objective: To conduct neurologic, immunologic, and virologic

studies in patients with a chronic debilitating illness of acute

onset.

¨ Design: Cohort study with comparison to matched, healthy control

subjects.

¨ Patients: We studied 259 patients who sought care in one medical

practice; 29% of the patients were regularly bedridden or shut-in.

¨ Main Outcome Measures: Detailed medical history, physical

examination, conventional hematologic and chemistry testing, magnetic

resonance imaging (MRI) studies, lymphocyte phenotyping studies, and

assays for active infection of patients' lymphocytes with human

herpesvirus type 6 (HHV-6).

¨ Main Results: Patients had a higher mean (± SD) CD4/CD8 T-cell

ratio than matched healthy controls (3.16 ± 1.5 compared with 2.3 ±

1.0, respectively; P < 0.003). Magnetic resonance scans of the brain

showed punctate, subcortical areas of high signal intensity

consistent with edema or demyelination in 78% of patients (95% Cl,

72% to 86%) and in 21% of controls (Cl, 11% to 36%) (P < 10-9).

Primary cell culture of lymphocytes showed active replication of HHV-

6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls

(20%; Cl, 9% to 36%) (P < 10-8), a finding confirmed by assays using

monoclonal antibodies specific for HHV-6 proteins and by polymerase

chain reaction assays specific for HHV-6 DNA.

¨ Conclusions: Neurologic symptoms, MRI findings, and lymphocyte

phenotyping studies suggest that the patients may have been

experiencing a chronic, immunologically mediated inflammatory process

of the central nervous system. The active replication of HHV-6 most

likely represents reactivation of latent infection, perhaps due to

immunologic dysfunction. Our study did not directly address whether

HHV-6, a lymphotropic and gliotropic virus, plays a role in producing

the symptoms or the immunologic and neurologic dysfunction seen in

this illness. Whether the findings in our patients, who came from a

relatively small geographic area, will be generalizable to other

patients with a similar syndrome remains to be seen.

ls of Internal Medicine. 1992: 116:103-113

American College of Physicians

For current author affiliations and addresses, see end of text.

We studied 259 patients who had an illness that was typically of

abrupt onset, beginning with a " flu-like " syndrome that was followed

by months or years of sometimes disabling chronic fatigue and

impaired cognition. Enough cases occurred among family members,

coworkers, and other close contacts to suggest the possibility of an

infectious agent transmissible by casual contact. A few patients

developed transient periods of apparent encephalitis, characterized

by confusion, ataxia, paresis, and primary seizure disorders.

Several unusual features have been revealed by immunologic testing,

magnetic resonance imaging (MRI) studies of the brain, and virologic

studies.

__________________________________________________________________

Methods

Initiation of the Study

In late 1984, two of us (DLP and PRC) who had a general medicine

practice in Incline Village, Nevada, on the north shore of Lake

Tahoe, began to see several patients with an unusual illness. By mid-

1985, we were concerned that an epidemic might be unfolding. Two of

us who were studying a similar illness in an academic general

medicine practice in Boston (DB and ALK) heard of the events in

Nevada. Together, the four of us began a formal study in January

1986. A team from Boston traveled to Nevada on several occasions.

Many additional collaborators became involved. Research assistants in

Lake Tahoe and Boston gathered detailed clinical and laboratory data

and collected blood specimens, and all data were entered into a

computerized database in Boston. Because a formal study was initiated

a year after events unfolded, we were unfortunately not able to

determine exactly how many patients were seen in this practice who

had the symptoms of this unusual illness but were not entered into

the study. However, we estimate that 85% of the patients seen in the

practice who had this illness were enrolled.

Patients

One hundred and eighty-three patients lived in one of several

communities near the California-Nevada border, in the vicinity of

Lake Tahoe, and sought medical care between 1984 and 1987 for chronic

fatigue at the internal medicine practice. The mean (± SD) age of

this " Tahoe " group was 38.9 ± 12.3 years: 67% were female and 41%

were college graduates.

Seventy-six other patients with chronic, debilitating fatigue came to

the same practice during the same time period. These patients were

from outside the Lake Tahoe area, typically from urban areas of

California and Nevada. The mean age of this " non-Tahoe " group was

38.6 ± 11.4 years: 70% were female and 36% were college graduates.

The mean age of all patients, including both the Tahoe and non-Tahoe

groups, was 38.8 ± 12.0 years: 68% of patients were female, and 39%

were college graduates.

The Tahoe group may have represented part of an epidemic, because

most of these patients became ill within a 2-year period and many had

close contacts who became ill. Hence, they are also referred to as

the " epidemic " group; however, the design of our study did not allow

us to establish that a true epidemic had occurred. The non-Tahoe

group is referred to as the " endemic " group because the patients did

not know many other persons who were similarly affected: however,

many patients knew at least one close contact who was allegedly

affected.

The 259 patients enrolled in the study were asked to complete a

detailed questionnaire, and data from each patient's medical record

were abstracted. To be included in our study, a patient had to have

chronic, debilitating fatigue of at least 3 months duration that was

associated with at least two of the following symptoms (also of at

least 3 months duration): fever, headache, sore throat, earache,

rhinorrhea, cough, diarrhea, or myalgias. At the time of enrollment

in the study, the median duration of illness had already reached 1.3

years.

Data were obtained from several different groups of healthy control

subjects. These control groups are described in the following

sections and in Table 1, with reference to the diagnostic testing for

which they served as controls.

Measurements

Standard Laboratory Tests

Complete blood counts, erythrocyte sedimentation rates, standard

serum chemistry tests, various tests for collagen vascular diseases,

and thyroid function tests were ordered when indicated clinically and

not according to a study protocol.

Cerebrospinal Fluid Examination

Analysis of cerebrospinal fluid obtained by lumbar puncture was done

in six patients who had developed acute neurologic changes

(confusion, marked cognitive deficits, delirium, ataxia, transient

paresis, or primary seizure).

Magnetic Resonance Imaging of the Brain

Magnetic resonance imaging studies were done by one of us (RB) at

Reno Diagnostics Center. One hundred and forty-four patients had at

least one MRI study. These patients had somewhat greater debility but

were otherwise generally similar to the 115 patients in whom MRI

studies were not done (Table 2). The MRI findings in patients were

compared with those in 47 control subjects who did not have chronic

fatigue and who were similar to the patients in mean age and gender

distribution (see Table 1). Forty-two of these controls had been

asked to undergo scanning as part of a study to assess the resolution

of a new machine with a larger magnet; four patients had sustained

head trauma and one patient had a suspected cervical herniated disk.

The images from the controls were obtained on the same brand of

machine, with the same size magnet, by Dr. Victor Haughton of

Milwaukee, Wisconsin. The images from patients could be distinguished

from those of control subjects by the logos of the two radiology

departments (Reno and Milwaukee); thus, blind interpretation was not

possible. However, the images were interpreted independently by two

of us (RB and FAJ), and inter-rater reliability was determined.

The patient studies were done using a 1.5-tesla superconducting Signa

magnetic resonance imager (General Electric Medical, Milwaukee,

Wisconsin). Images included a T1- weighted sagittal scan followed by

T2-weighted transaxial spin echo scans of the brain. These axial

scans were obtained at 5-mm intervals from the foramen magnum to the

vertex, with a skip of 1 to 2 mm. The repetition time was between

2000 and 2500 ms and the echo delay time was between 20 and 30 ms for

the first echo and between 50 and 80 ms for the second echo.

Table 1. Characteristics of Patients and Control Subjects by

Individual Test*

Test Patients Control

Subjects P Value †

HHV-6 replication assay

Number 113 40

Mean age. y 39.5 ±11.2 37.5

± 10.7 > 0.2

Female, % 70

53 0.07

HHV-6 serologic testing

Number 134 27

Mean age, y 38.4 ± 12.3 47.5

± 11.9 < 0.01

Female, % 63

48 0.23

Lymphocyte phenotyping

Number 121 54

Mean age. y 41.2 ± 11.7 32.4

± 9.1 ‡ < 0.01

Female, % 70

60 ‡ 0.21

MRI study

Number 144 47

Mean age. y 38.8 ± 10.8 36.9

± 13.2 > 0.2

Female. % 72

68 > 0.2 .

* HHV-6 = human herpesvirus-6: MRI = magnetic resonance imaging.

Mean values are expressed +/- SD.

† P < 0.05 was considered statistically significant.

‡ Data on age and sex were available from only 35 of the 54

control subjects.

Lymphocyte Phenotyping

Two of us (SBW and JBP) did the phenotyping studies. Two hundred and

thirty-nine measurements were done in 121 patients who were slightly

older but were otherwise generally similar to the 139 patients not

tested (Table 2). Studies were also done on 270 occasions in 54

healthy control subjects (laboratory personnel) who were somewhat

younger but similar in gender distribution to the patients (see Table

1). Phenotyping of coded specimens was done concurrently and in

blinded fashion by the same technicians using the same reagents and

flow cytometer.

Mononuclear cells were separated by Ficoll-Hypaque centrifugation

from 20 to 40 ml. of heparinized venous blood and were then washed

and stained with the T-cell monoclonal antibodies CD2, CD4, CD8

(Ortho Pharmaceuticals, Raritan, New Jersey), and CD5 (Boehringer

Mannheim, Chicago, Illinois) and the B-cell monoclonal antibody CD20

(Coulter Immunology, Hialeah, Florida), using standard indirect

immunofluorescence techniques. Isotype-matched myeloma protein was

used in place of these monoclonal antibodies as a staining control:

fluorescein isothiocyanate-conjugated goat anti-mouse immunoglobulin

(Tago, Inc., Burlingame, California) was the secondary reagent.

Assay for Active Replication of Human Herpesvirus Type 6

An assay was conducted by one of us (BH) to detect active replication

of HHV-6 in peripheral mononuclear cells. Assays were done on at

least one occasion in 113 patients. These patients were similar to

the 146 patients not tested (see Table 2). The only criterion in

selecting patients for these studies was the availability of the

virology technician to receive and process the blood sample

immediately.

Heparinized blood samples were obtained from 40 healthy blood donors

and laboratory personnel who served as controls and were similar to

the patients in mean age and in gender distribution (see Table 1).

The control samples were tested according to identical techniques in

two laboratories (those of BH and DVA). The control samples were

tested late in the study, when initial results from patients had

suggested a high frequency of active replication. Control samples

were then intermixed with patient samples, and the testing was done

in blinded fashion by the same technicians using the same reagents.

The method used to detect the presence of HHV-6 in human peripheral

blood lymphocytes was similar to that previously described by one of

us (SZS) (1). Briefly, peripheral mononuclear cells were separated by

Ficoll-Hypaque centrifugation at 1200 g for 45 minutes. The cells

were collected, washed once in RPMI 1640 medium, placed in RPMI 1640

medium supplemented with 10% heat inactivated fetal calf serum and

penicillin-streptomycin, and incubated at 37 degrees C for 24 hours

under 5% CO2. Cells were then washed, exposed to phytohemagglutinin

(5 ug/mL) for 48 hours, collected by centrifugation, and resuspended

in media containing dexamethasone (5 ug/mL). The cell cultures were

then observed daily.

We used modification of the standard immunofluorescence technique to

confirm infection with HHV-6. Briefly, the patients' cells were fixed

in ethanol, then centrifuged and resuspended in RPMI 1640 medium

containing 50% fetal calf serum. The desired number of cells was

placed on a slide, fixed for 30 minutes in cold methanol, and air-

dried. The fixed cells were then exposed to the desired dilution of

test and control sera, followed by exposure to a fluorescein-labeled

secondary human antibody (Chemicon International Inc., Temecula,

California). Test sera contained high levels of antibody to HHV-6

and no detectable antibody to Epstein-Barr virus or human

cytomegalovirus. Control sera had no detectable antibody to HHV-6 but

did have antibody to Epstein-Barr virus or human cytomegalovirus, or

both, as determined by standard immunofluorescence assays. The

presence of infected cells was determined by the degree of

fluorescence relative to that seen in cell lines infected with

Epstein-Barr virus (B95-8 and Raji) and a cell line infected with

human cytomegalovirus (HEL).

A " positive bioassay " for active HHV-6 infection was defined by the

following findings (1): 1) After 4 to 8 days in culture,

refractive " giant cells " developed that increased in number and then

underwent cytolysis, the cytopathic effect typical of HHV-6; 2)

these giant cells showed diffuse fluorescence (typically not limited

to either the nucleus or the membrane) when incubated with HHV-6-

positive serum and then with fluorescein-labeled antibody; 3) the

giant cells did not demonstrate fluorescence when incubated with

control sera (as defined above); and 4) normal-sized cells that did

not exhibit the characteristic cytopathic effect also did not show

fluorescence when incubated with HHV-6-positive serum. When multiple

longitudinal samples were obtained, a patient was considered to have

a " positive bioassay " if the number of positive results (as defined

above) was equal to or greater than the number of negative results.

Additional studies were done in patients with positive bioassays to

confirm the presence of active HHV-6 infection. First, cord-blood

lymphocytes were co-cultivated with supernatant from six randomly

selected patients who had a positive bioassay. For purposes of

control, cord-blood lymphocytes were also co-cultivated with

supernatant from three persons who had a negative bioassay, and with

supernatant from mock-infected HSB-2 cells, from Epstein-Barr-virus-

infected producer (P3HR-1) and nonproducer (Raji) cell lines, and

from cell-free human cytomegalovirus. Second, fluorescein-labeled

monoclonal antibodies developed by one of us (NB) were used to stain

cells from seven randomly selected patients who had a positive

bioassay; for purposes of control, three samples from patients with a

negative bioassay and uninfected HSB-2 cells were stained with the

same monoclonal antibodies in the laboratory of three of us (DVA,

SZS, and RCG). Three different monoclonal antibodies specific for

different HHV-6 (GS isolate) epitopes were used in the

immunofluorescence assay: 12B3G4, which recognizes a protein of 135

kDa; 6A5G3, which recognizes three glycoproteins of 54, 64 and 116

kDa; and 945D12, which recognizes proteins of 41 and 110 kDa (2).

Third, polymerase chain reaction was used to detect HHV-6-specific

DNA concurrently in cells from six randomly selected patients who had

a positive bioassay; for purposes of control, the study was also done

in cells from eight persons who had a negative bioassay. The

specificity of the HHV-6 probe was also tested by determining whether

it hybridized to cell DNAs (VERO and HEL) and other virus DNAs (human

cytomegalovirus, herpes simplex virus types 1 and 2, varicella-zoster

virus, and Epstein-Barr virus); and whether it produced a positive

signal with a reaction involving the HHV-6 oligonucleotide primers,

buffer, and Taq polymerase, but without a DNA template. The

polymerase chain reaction assays were done according to the method of

Saiki and colleagues (3). Briefly, reactions were conducted using an

annealing temperature of 56 degrees C for 2.5 min, an extension

temperature of 72 degrees C for 1.7 min, and a denaturation

temperature of 94 degrees C for 1.7 min. A series of 40 amplification

cycles was used for each reaction.

Table 2. Characteristics of Tested and Untested Patients *

Test

Patients Patients

Tested Not Tested P Value †

HHV-6 replication assay

Number

113 146

Mean age. y 39.5 ±

11.2 38.3 ± 12.6 > 0.2

Female. %

70 67 > 0.2

College graduates, %

37 42 > 0.2

Bedridden or shut-in ‡. %

40 20 < 0.01

Chronic headaches ‡, %

93 79 < 0.01

Difficulty in sleeping ‡. %

44 56 < 0.01

Paresthesias ‡. %

44 56 < 0.01

HHV-6 serologic testing

Number

134 125

Mean age, y 38.4 ±

12.3 39.2 ± 11.2 > 0 2

Female, %

63 73 0.11

College graduates. %

41 36 > 0.2

Bedridden or shut-in ‡. %

21 29 < 0.01

Paresthesias ‡, %

30 48 < 0.01

Lymphocyte phenotyping

Number

121 139

Mean age, y 41.2 ±

11.7 36.7 ± 12.0 0.01

Female, %

70 65 > 0.2

College graduates, %

43 36 > 0.2

MRI study

Number

144 115

Mean age, y 38.8 ±

10.8 38.7 ± 13.4 > 0.2

Female, %

72 62 0.10

College graduates, %

43 35 0.22

Unable to work full-time ‡, %

67 37 < 0.01

Chronic headaches ‡, %

91 78 < 0.01

Chronic nausea ‡, %

63 38 < 0.01

Arthralgias ‡, %

80 61 < 0.01

Paresthesias ‡, %

75 47 <

0.01 .

* HHV-6 = human herpesvirus type 6. MRI = magnetic resonance

imaging. Mean values are expressed ± SD.

† Alpha = 0.01 (see Tukey [9]).

‡ Symptom or descriptor (out of a total of 190 evaluated) for which a

statistically significant difference was found between the patients

tested and those not tested.

Serologic Testing

Coded sera from 134 patients were tested for IgG antibody reactivity

against HHV-6-associated antigens by end-point dilution enzyme-linked

immunosorbent assay (ELISA) in the laboratory of two of us (CS and

RCG), according to previously described techniques (4). These 134

patients were similar to the remaining 125 patients not tested (see

Table 2). Coded sera from 27 healthy control subjects from the same

community who were somewhat older but similar in gender distribution

to the patients (see Table l) were also tested.

Serologic test panels for Epstein-Barr virus were done at least once

in 249 of 259 patients (96%) at Nichols Institute Immunology

Reference Laboratory, San Capistrano, California, according to

standard techniques (5, 6). (Specimens from 29 patients and control

subjects were tested in the laboratory of the late Dr. Werner Henle

at the Children's Hospital of Philadelphia, and values were within

one tube dilution of those observed at the Nichols Institute.) Coded

sera from 36 healthy control subjects (mean age, 47.4 ± 11.4 years:

56% female) from the same community were also tested for antibodies

to Epstein-Barr virus.

Testing for human cytomegalovirus and Toxoplasma gondii was also done

by standard immunofluorescence assay at Nichols Institute.

Human Retrovirus Studies

Testing for antibodies to human T lymphotropic virus type 1 (HTLV-I)

was done using a conventional ELISA (DuPont, Wilmington, Delaware).

Testing for HTLV-I was done in 49 patients whose mean age (38.1 ±

13.7 years), gender distribution (69% female), and education (39%

college graduates) were not significantly different from those of

patients not tested. Testing for antibodies to human immunodeficiency

virus (HIV) was done in 39 patients whose mean age (39.5 ± 11.0

years), gender distribution (51% female), and education (44% college

graduates) were not significantly different from those of patients

not tested. These serologic retroviral studies were done in the

laboratory of L. Sullivan at the University of Massachusetts

Medical Center, as well as at Nichols Institute.

One of us (TF) attempted to find evidence of a human retrovirus using

heparinized blood from 14 patients. Peripheral mononuclear cells from

the patients and from normal persons (laboratory personnel) were

isolated and stimulated using a previously described method (7).

After stimulation, patients' peripheral mononuclear cells were either

cultured in media alone or co-cultured with normal stimulated

peripheral mononuclear cells according to a previously described

method (8). Supernatants from these cultures were tested for reverse

transcriptase activity (7) over a 30-day period. The primer used for

the reverse transcriptase assay was oligo dT; the template was poly

rA. Both Mg++ and Mn++ were used as divalent cations, because the

reverse transcriptase from different known human retroviruses has

different cation dependency. The patients' cells were established in

culture only once. The supernatants were tested at 3-day intervals

for 1 month (approximately 10 tests for reverse-transcriptase

activity per patient over the 1-month culture period).

Statistics

When percentages of patients and controls with a certain clinical or

laboratory finding were compared, we used the chi-square or Fisher

exact test. Intergroup comparisons of the distributions of continuous

variables were done using either t-tests or Wilcoxon rank-sum tests

(when distributions were non-normal). When a large number of similar

comparisons was made between two groups (such as comparing the

frequency of multiple symptoms), a P value for detecting type I

errors was chosen according to the method of Tukey (9). When

distributions were non-normal, we normalized them by log-

transformation (base 10). When multiple values for a variable were

obtained for an individual at different points in time, we calculated

a mean value for the variable after first normalizing the

distribution (if necessary). For example, a geometric mean titer for

Epstein-Barr virus antibody was calculated for each patient, as

described previously (10).

__________________________________________________________________

Results

Onset of Illness

Most patients experienced the onset of illness between 1984 and 1986

(Figure 1), although in some cases the illness had begun years

before. No seasonal preponderance of cases was observed.

" Clustering " of Cases

In the Tahoe group, several groups of patients who had frequent close

contact became ill within several months of each other: 10 of 31

teachers at one local high school (at least one student from the same

school was similarly affected, but this student chose not to

participate in the study); 5 of 28 teachers and 3 students at another

local high school; 3 students and 1 teacher at a third high school;

and 11 employees at a casino. The spouses or sexual contacts of six

patients were similarly afflicted, and there were eight instances in

which at least one parent and one child both had the illness.

Clinical and laboratory findings in the " clustered " patients did not

differ from those of the larger patient group. Altogether, 101 of 183

patients (55%) in the Tahoe group and 39 of 76 patients (51%) in the

non-Tahoe group stated that a close contact was similarly affected.

Symptoms and Signs

The two groups were generally similar regarding symptoms and signs.

In most patients, the chronic, debilitating illness was of sudden

onset, beginning with a " flu-like " syndrome; 29% of the patients were

regularly bedridden or shut-in. The symptoms (Table 3) were chronic

and were experienced on a nearly daily basis in the months and years

after the typically sudden onset of the illness. These chronic

symptoms constituted a new experience for most patients: Very few of

the patients reported these chronic symptoms in the years before

illness onset. For example, difficulty in concentrating was

experienced chronically by 3% of patients before the onset of the

illness but by 82% of patients after the onset of illness; depression

(as reported by patients) was experienced chronically in 6% of

patients before onset but by 68% after onset. Patients in the non-

Tahoe group were more frequently shut-in and had a slightly higher

frequency of headaches, adenopathy, arthralgias, paresthesias, and

rash, but generally the two groups were similar (Table 3). No

statistically significant differences were found when patients who

experienced the onset of illness before 1984 were compared with those

who had a later onset of illness. No statistically significant

differences were found between patients whose illness began abruptly

with " flu-like " symptoms and the few patients who experienced a more

insidious onset, except that abdominal pain was more frequent in the

former group.

Twenty-two patients (8%) had evidence of an acute neuropathic

process, which generally occurred within several weeks of the acute

onset. Acute neurologic symptoms included primary seizure disorder (7

patients); profound, transient ataxia of acute onset (10 patients);

and transient paresis (8 patients). Ataxia and paresis were confirmed

by neurologic examination (done by PRC and DLP) and typically lasted

1 to 4 weeks; none of the patients sustained a permanent deficit. The

frequency of acute neurologic events was similar in the Tahoe and non-

Tahoe groups (see Table 3).

Measurements

Standard Laboratory Tests

Laboratory tests generally yielded unremarkable results. However, 31

of 172 patients (18%) had atypical lymphocytosis (mean percentage of

atypical cells, 6.5%). In addition, 21 of 81 patients (27%) tested

had an antinuclear antibody titer of 1:20 (only 1 patient had a titer

as high as 1:320); no patient had clinical evidence of systemic lupus

erythematosus. The frequency of these laboratory abnormalities was

similar in the Tahoe and non-Tahoe groups.

Cerebrospinal Fluid Examination

Of the six patients whose cerebrospinal fluid was studied, one had

pleocytosis (leukocyte count, 8 x 106/ L). Glucose and protein levels

were unremarkable in all cases. Oligoclonal bands were absent. No

bacterial organisms were cultured from any patient. In one instance,

Epstein-Barr virus antibodies were measured: Neither viral capsid

antigen IgG nor viral capsid antigen IgM was detected. Unfortunately,

no cerebrospinal fluid was available for HHV-6 isolation or serologic

studies.

Magnetic Resonance Imaging of the Brain

Foci of high signal intensity on T2-weighted images, typically

punctate and occasionally larger patchy areas, were seen in 113 of

144 patients (78%) but in only 10 of 47 matched healthy controls

(21%) (P < 10-9) (Table 4). The films were interpreted independently

by two neuroradiologists (RB and FAL), who agreed about the presence

or absence of abnormal signal in 97% of the patients. Representative

images are shown in Figure 2. The subcortical white matter was

affected most often, but white matter elsewhere in the central

nervous system was also affected. A relation was seen between the

anatomic area affected and the clinical presentation: One patient

with ataxia had high signal intensity areas involving the cerebellum

(Figure 2, panel D), seven patients with visual symptoms had high

signal intensity areas involving the occipital cortex, and one

patient with paresis had a high signal intensity area involving the

contralateral internal capsule. In several cases, MRI studies were

repeated, and the scans showed that areas of high signal intensity

persisted even after symptoms resolved.

Table 3. Clinical Findings

Findings Tahoe

Group Non-Tahoe Group

(N

= 183) (N = 76)

.. [

n (%) ] [ n (%) ] .

History of fatigue

Severity of the fatigue

Bedridden (can do virtually nothing) 11

(6) 3 (4)

Shut-in (cannot do even light housework

or its equivalent or carry out

family responsibilities) 32 (17)

* 28 (37)*

Can work on only a part-time basis 51

(28) 22 (29)

Can fulfill all home or work

responsibilities but is much more

easily fatigued from such activities

(no energy left for anything else) 89 (49)

* 23 (30)*

Chronic fatigue started suddenly with

a " flu, " " cold, " or virus † 156

(85) 69 (91)

Associated symptoms

Myalgias 151

(83) 69 (91)

Headaches 149

(81) 71 (93)

Difficulty in concentrating 144

(79) 67 (88)

Recurrent pharyngitis 134

(73) 63 (83)

Swollen lymph glands 130

(71) 65 (86)

Difficulty in sleeping 121

(66) 42 (55)

Anxiety 129

(70) 54 (71)

Depression or unusual mood changes 122

(67) 55 (72)

Joint pain 122

(67) 62 (82)

Cough 99

(54) 38 (50)

Recurrent fevers at home 79

(43) 41 (54)

Nausea 88

(48) 47 (62)

Stomach ache 83

(45) 39 (51)

Loss of appetite 70

(38) 27 (36)

Odd sensations in the skin 73 (40)

* 52 (68)*

Intermittent swelling of the fingers 81

(44) 42 (55)

Diarrhea 60

(33) 32 (42)

Weight gain of more than 4.54 kg (10 Lb) 44

(24) 26 (34)

Eczema 37

(20)* 30 (39)*

Other rash 54

(30) 33 (43)

Vomiting 29

(16) 9 (12)

Weight loss of more than 4.54 kg (10 Ib) 23

(13) 12 (16)

Neurologic events

Primary seizure disorder 4

(2) 3 (4)

Transient ataxia 7

(4) 3 (4)

Transient paresis 3

(2) 5 (7)

Physical examination

Anterior cervical adenopathy

(enlarged or tender nodes) 118

(66) 44 (64)

Posterior cervical adenopathy

(enlarged or tender nodes) 91

(51) 36 (52)

Temperature more than 37.6 degrees C 10

(6) 2 (3) .

* P < 0.01; threshold for significance given that more than 20

comparisons were made (see Tukey [9]).

† Characterized by at least two of the following symptoms: fever,

headache, myalgias, sore throat, earache, congestion, runny nose,

cough, diarrhea, and fatigue.

Lymphocyte Phenotyping Studies

The CD4/CD8 ratio was higher in each of the two patient groups when

compared with the control group (Tahoe group, 3.11 ± 1.6; non-Tahoe

group, 3.19 ± 1.40; control group, 2.30 ± 1.00 [P < 0.003]). The

higher CD4/CD8 ratios in the patient groups were accounted for by

both higher numbers of CD4+ cells (934.4 ± 319.6 cells/mm3 for the

patients and 871.9 ± 389.0 cells/mm3 for the control subjects; P =

0.07) and lower numbers of CD8+ cells (370.2 ± 215.1 cells/mm3 for

the patients and 452.0 ± 257.6 cells/mm3 for the control subjects; P

= 0.01). No significant differences were noted in the total T-cell or

B-cell number.

Assays for Active Replication of Human Herpesvirus Type 6

Two hundred and thirty-five specimens were obtained from 113

patients. A positive bioassay for HHV-6 (Figure 3) was seen in 70% of

the patients and 20% of the control subjects (P < 10-8) (see Table

4). Most of the assays in 27 of the 34 patients (79%) who had serial

testing for HHV-6 indicated active replication of HHV-6. When, later

in the study, samples from control subjects were intermixed with

those from patients, the rate of positivity among patients was as

high as it had been before control samples were intermixed,

indicating that the earlier reading of patient samples was accurate.

Confirmatory studies for HHV-6 replication were also done. Co-

cultivation of cord-blood lymphocytes with supernatant from primary

cultures yielded a positive cytopathic effect in each of the six

patients tested; no cytopathic effect was seen in any of the

controls. In two patients showing a positive cytopathic effect in the

primary co-cultivation study, secondary co-cultivation studies using

supernatant from the presumably infected cord-blood lymphocyte

cultures were done. The characteristic cytopathic effect was seen in

the new cord-blood lymphocyte cultures in each of the two patients

tested. Monoclonal antibody studies were positive with all three

monoclonal antibodies in all seven patients studied, confirming that

HHV-6-specific antigens were present in patients who had a positive

bioassay. Monoclonal antibody staining was not observed in the

controls. Polymerase chain reaction studies were shown to be specific

for HHV-6, as described in the Methods section; the studies were

positive in all six patients who had a positive bioassay and in none

of the controls, confirming that HHV-6-specific nucleic acid

sequences were also present in patients with a positive bioassay. As

reported elsewhere, Southern blot examination was also done in three

patients (11), which confirmed the presence of HHV-6 in all three

instances.

Of the 113 patients studied for HHV-6 replication, 84 (74%) underwent

MRI study; 68 of these 84 patients (81%) had MRI abnormalities, a

proportion similar to that observed for all patients who had MRI

study (79%). Patients with abnormalities were not more likely to have

evidence of actively replicating HHV-6 (P = 0.6).

Serologic Testing

Median optical density values for the HHV-6 IgG ELISA in patients and

control subjects were 1905 and 1288, respectively (P = 0.08, one-

tail). Ninety-three percent of patients were seropositive for Epstein-

Barr virus; only two patients had serologic evidence of primary

Epstein-Barr virus infection. The reciprocal geometric mean titers (±

SD) for the Tahoe and non-Tahoe groups were significantly higher than

those of the control group for Epstein-Barr virus viral capsid

antigen IgG (138.0 ± 2.6 for the Tahoe group, 154.9 ± 3.0 for the non-

Tahoe group, and 67.6 ± 4.4 for the control group; P < 0.0001); and

for early-antigen R antibody (40.7 ± 2.6 for the Tahoe group, 30.9 ±

2.2 for the non-Tahoe group, and 12.6 ± 6.0 for the control subjects,

P < 0.0001); there were no statistically significant differences in

values for viral capsid antigen IgM, early-antigen D antibody, and

Epstein-Barr nuclear-antigen antibody.

Of 92 patients tested, 45 (49%) had cytomegalovirus IgG antibody

levels of more than 1:20 and 10 had low levels of cytomegalovirus IgM

antibody. Low levels of IgG and IgM antibody to Toxoplasma gondii

were found in 7 of 29 (24%) and in 1 of 11 (9%) patients tested,

respectively.

Human Retrovirus Studies

Serologic test results for antibodies to HTLV-I and antibodies to HIV

were negative in the patients tested. The 14 culture supernatants

tested were negative for reverse transcriptase activity by both

assays (Mg++ and Mn++).

Table 4. Results of the Magnetic Resonance Imaging Studies of the

Brain and of the Bioassay for Replication of Human Herpesvirus Type 6

in the Tahoe Group, the non-Tahoe Group, and the Control Group*

Finding Tahoe Group Non-

Tahoe Gp. Control Gp. P Value †

[ ----------------

( n/n (%) ) -------------- ]

Hyperintense signal in

white matter on MRI

study of the brain 71/91 (78) 42/53

(79) 10/47 (21) <10-9

Positive bioassay 45/71 (63) 34/42

(81) 8/40 (20) <10-8

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

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

* The Tahoe group comprised patients from the Lake Tahoe area near

the Nevada-California border: this patient group was also referred to

as the " epidemic " group because most of the patients had many

contacts who also became ill. The non-Tahoe group comprised patients

from outside the Lake Tahoe area: this patient group was also

referred to as the " endemic group " because patients did not have many

contacts who became ill. The control group comprised healthy

persons. MRI = magnetic resonance imaging.

† P value for the comparison of two patient groups with the control

group.

____________________________________________________________________

Discussion

The illness we have observed shares many features with the entities

variably called " postinfectious " or " postviral " fatigue syndrome

(12); myalgic encephalomyelitis, Royal Free disease, or Icelandic

disease (13-19); primary fibromyalgia (or fibrositis) (20-22);

chronic mononucleosis (23-25); chronic active Epstein-Barr virus

infection syndrome (26-28); and the chronic fatigue syndrome (29,

30). Perhaps these differently named entities are the same illness

and share a common etiologic agent; perhaps they are clinically

similar but separate illnesses, with each triggered by a particular

and different etiologic agent; or perhaps these entities represent

one illness that can be triggered by various factors and that

manifests different clinical features in different patients (perhaps

because of host factors) but causes chronic fatigue and certain

common pathophysiologic features in all patients. We are more

inclined to the last view.

We cannot say precisely if the illness we witnessed from 1984 to 1986

meets criteria for chronic fatigue syndrome because the case

definition for that illness developed in 1988 (30) includes some

symptoms (for example, a greater than 50% reduction in function) that

we did not explicitly ask the patients about, using the same

language. Nevertheless, most patients probably would have met the

case definition for chronic fatigue syndrome because the illness

began suddenly in 87% of patients, the median duration of the illness

at time of study entry was 1.3 years, 57% of patients were bedridden,

shut-in, or unable to work full-time, and most had the key symptoms

required by the case definition (see Table 3).

For most patients in our study, the illness consisted largely of

subjective and nonspecific symptoms, and the results of common

laboratory tests were often normal. Initially, it was unclear to us

whether the patients were experiencing an organic illness or the

somatic manifestations of a psychological illness. The several

objective neurologic, immunologic, and virologic findings make a

diagnosis of purely psychological illness unlikely, although it

remains possible that these findings are biologic concomitants of

primary psychiatric illness. Studies of that possibility are in

progress.

We frequently saw areas of abnormal signal intensity in the white

matter of the central nervous system. Without studies of central

nervous system tissue, we cannot be certain about the meaning of

these findings. Progress in characterizing white matter abnormalities

using magnetic resonance imaging has been severely inhibited by the

absence of tissue. In normal persons, for example, hyperintense

signal on T2-weighted images is seen anterior to the frontal horns

(31). Similar signal characteristics are seen in the periventricular

white matter lesions of patients with multiple sclerosis; because no

signal feature can be used to differentiate these MRI signal

abnormalities, only their spatial distribution identifies them. Many

different diseases in addition to multiple sclerosis are associated

with areas of high signal intensity caused by white matter edema or

demyelination, or both: Alzheimer's disease; vascular dementia

(Binswanger disease, lacunar state, multi-infarct dementia); normal

pressure hydrocephalus; metastatic disease; trauma; leukodystrophies;

secondary Wallerian degeneration from any brain damage; and post-

irradiation, post-chemotherapy, toxic, or metabolic

leukoencephalopathies. Viral infection (for example, with the retro-

viruses HIV [32] or HTLV-I [33]) also commonly produces similar white

matter changes. As was the case in our study, such punctate areas of

high signal intensity can also be seen in apparently healthy persons

of all ages.

The clinical significance of these " incidental " areas of high signal

intensity in the white matter is not known (34-37); their prevalence

appears to rise with age and with the presence of cerebrovascular

risk factors. Particularly ambiguous is the interpretation of

punctate areas of high signal intensity seen mostly in the

subcortical white matter. The distribution of this finding

corresponds anatomically to the cerebrospinal-fluid-filled

perivascular (Virchow-Robin) spaces that can be seen on high-

resolution magnetic resonance images. The enlarged Virchow-Robin

spaces may be a normal variant or may be the result of either

cerebrospinal fluid penetration into ischemic white matter or

cellular infiltration within the dilated perivascular spaces as part

of an inflammatory process (38, 39). The areas of high signal

intensity seen in our patients and control subjects varied in size

and location and may arise from different causes. The much greater

frequency of high signal intensity in the white matter of both the

Tahoe and non-Tahoe groups than in the control group (P < 10-9), the

presence in some patients of larger and deeper white matter lesions,

and the correlation between the anatomic area of involvement and

clinical symptoms all suggest that the patients were experiencing a

genuine but as yet undefined pathologic process.

We cannot judge how generalizable the MRI findings might be to other

patients with a similar syndrome. In our preliminary studies of

patients with chronic fatigue syndrome from New England, MRI

abnormalities were seen less commonly (40% to 50% of patients) than

in this patient group. We do not recommend routine use of MRI studies

in patients with suspected chronic fatigue syndrome; the value of the

test first needs to be assessed in other populations. We and others

are currently evaluating magnetic resonance imaging and other

neuroimaging techniques in chronic fatigue syndrome.

Immunologic (lymphocyte phenotyping) studies revealed a significantly

increased CD4/CD8 ratio in each of the two patient groups when

compared with the control group (P < 0.003), because patients had

both a higher number of CD4+ T cells and a reduced number of

circulating CD8+ T cells. Landay and colleagues (40) have also found

a reduced number of CD8+ cells in clinically similar patients,

although some studies of clinically similar patients have not found a

similar increase in the CD4/CD8 ratio (22, 40, 41). We did not

examine T-cell subsets, but Gupta and colleagues (41) as well as

Straus and Strober (Unpublished data) studied patients with an

apparently similar syndrome and reported elevated numbers of

activated CD4+ cells. Klimas and coworkers (22) and Landay and

coworkers (40) have found an elevated number of activated CD8+ cells,

decreased numbers of CD4+ CD45RA+ " suppressor-inducer " cells (22),

and decreased numbers of CD8+ 11b+ " suppressor " cells (40). We did

not measure T-cell function, but Klimas and colleagues (22), Murdoch

(42), and Lloyd and colleagues (43) have found evidence of cutaneous

anergy or T-cell dysfunction, or both, as reflected by conventional

mitogen stimulation assays, in patients with a similar chronic

illness. Gupta and colleagues (41) found T-cell dysfunction in

response to challenge with soluble antigens. Increased B-cell numbers

have been reported in some patients with chronic fatigue syndrome

(22, 44) but not in others (40, 41). An increase in the B-cell subset

(CD20+ CD5+) that may be dedicated to the production of

autoantibodies (45) has been reported by Klimas and colleagues (22).

Increased numbers of activated monocytes have been observed (41). We

have reported previously that natural killer cell phenotypic and

functional abnormalities are also present in patients with chronic

fatigue syndrome: Such patients show reduced numbers of the NKH1+ T3-

subset, and their natural killer cells demonstrate defective

cytolytic activity against target cell lines (46). Other

investigators have also found defective natural killer cell function

(22, 47-49). Indeed, defective natural killer cell function may be

the most commonly reported abnormality in patients with chronic

fatigue syndrome. Taken together, the controlled studies cited above

and many others summarized elsewhere (50) seem to indicate an immune

system chronically responding to a " perceived " antigenic challenge.

The virologic studies we have done thus far indicate that two human

herpesviruses may be actively replicating more often in patients than

in control subjects. The first is Epstein-Barr virus, and the

indirect evidence for its active replication in patients with chronic

fatigue syndrome comes from the Epstein-Barr virus antibody profiles,

which are characterized by higher levels of IgG antibody to both

viral capsid antigens and early antigens. The second such virus is

HHV-6, which was recently discovered in one of our laboratories (RCG)

(1, 51, 52). With HHV-6, the evidence of active viral replication is

direct: When lymphocytes from the two patient groups were placed in

primary cell culture, a cytopathic effect typical of HHV-6 was seen

in 70% of patients but in only 20% of control subjects (P < 10-8)

(see Table 2 and Figure 3). The use of three different monoclonal

antibodies specific for HHV-6 epitopes confirmed that HHV-6 protein

was present in cells exhibiting cytopathic effect, and the

application of polymerase chain reaction using probes specific for

HHV-6 nucleic acid sequences also confirmed the presence of HHV-6.

The only other known human virus that might also have been detected

with these assays was the closely related, recently discovered human

herpesvirus type 7 (53). Finally, in every instance, supernatant from

the primary cell culture produced the same cytopathic effect in cord-

blood lymphocytes, demonstrating that a transmissible agent was

indeed present in the patients' lymphocytes and that this agent was

HHV-6.

We do not know how generalizable these findings may be. Several other

groups have found elevated antibodies to Epstein-Barr virus (23, 26-

28). After our first report (54), several groups reported elevated

antibody levels to HHV-6 (40, 55-57) in patients with a similar

illness. As for our finding of active HHV-6 replication in patients'

lymphocytes, although one group has been unable to induce active

replication of HHV-6 in the lymphocytes of healthy persons (57),

others (58, 59; Gillespie D. Personal communication; Yamanishi K.

Personal communication) have been able to do so with a frequency

similar to that which we report. Like us, some investigators (59;

Gillespie D. Personal communication) also have found evidence of

inducible active HHV-6 replication in patients with chronic fatigue

syndrome. At this time, because the assays are difficult to do and

because their value has yet to be tested in other populations, we do

not recommend the routine use of HHV-6 testing in patients with

suspected chronic fatigue syndrome.

It appears that most patients acquire primary infection with HHV-6

early in life (4). Therefore, the active replication of HHV-6 seen in

most patients probably represents reactivation of an old, latent

infection rather than a new, primary infection with the virus. This

reactivation of HHV-6 could be nothing more than an epiphenomenon,

secondary to immune dysfunction or transactivation by another

unrecognized virus, and could have no relation to patients' symptoms.

Alternatively, whatever the mechanism of reactivation, HHV-6 might

contribute to producing the morbidity associated with this illness.

Such a hypothesis is plausible because HHV-6 is tropic for T cells; B

cells; and glial, neuroblastoma, and intestinal cell lines (60, 61).

Our study had several limitations. We could not systematically survey

a random sample of the denominator population in the community;

hence, we could not assess disease prevalence nor could we examine

more closely the possible clustering of cases. Magnetic resonance

imaging lymphocyte phenotyping, and the assays for HHV-6 replication

were not done in all 259 study patients; nevertheless, the large

samples tested were sufficiently similar to the total group (see

Table 2 and the Results section) that the striking differences

between patients and healthy control subjects are unlikely to be

explained by a sampling bias. The MRI findings were interpreted

independently by two neuroradiologists, with very high agreement.

However, because films from patients could be distinguished from

those of control subjects by the logos on each image, interpretation

was non-blinded.

We do not argue that these observations identify the cause of this

illness, nor can we be sure our findings will be confirmed in other

populations of patients with apparently similar illnesses. Indeed, as

stated earlier, we think that this probably is a heterogeneous

illness that can be triggered by multiple different genetic and

environmental factors (including stress, toxins, and exogenous

infectious agents), all of which can lead to immune dysfunction and

the consequent reactivation of latent viruses (29). Several different

exogenous and endogenous infectious agents may be involved in this

illness, acting singly in some cases and collaboratively in others.

In addition to HHV-6 and Epstein-Barr virus, the enteroviruses (62-

65), Borrelia burgdorferi (66), and other infectious agents (67) may

be involved in some cases. Preliminary evidence suggests that a novel

retrovirus may be involved in this illness (68); at least one other

retrovirus, HIV, is known to act synergistically with HHV-6 (69, 70).

In our study, the apparently " epidemic " Tahoe cases may have been

triggered by different agents than the apparently " endemic " non-Tahoe

cases; however, the remarkably similar clinical and laboratory

findings in the two patient groups suggest a final common

pathogenetic pathway involving immune dysregulation. We hope that

further investigation generated by these observations may lead to a

better understanding of this often devastating illness.

Acknowledgments:

The authors thank S. Baker, E. F. Cook, K. Cullen, K. Dibvig, S.

DeLaFerriere, N. Fiebach, E. Gebhardt, V. Haughton, D. Holt, M.

, A. Kinter, E. Keiff; J. Kornish, C. Lawyer, J. Lee, P. Levine,

R. Lissner, C. , R. Schmidt, H. Streicher, J. L. Sullivan, D.

Swain, R. S. , D. , R. A. Weinberg, and D. Willitts for

their help with the study or their advice: and R. Honess for

provision of HHV-6-specific oligonucleotide primers and the HHV-6 DNA

plasmid, pHD5.

Grant Support: By the National Institutes of Health (grants R01A1

26788, R01A127314. U01A132246. 2P01CA41167 and SK04NS01083); and by

funds from M. Palevsky. S. , the S. Sydney DeYoung Foundation,

the Minann Foundation, the Pioneer Foundation, the Rowland

Foundation, and Sierra Research Institute. Dr. Buchwald was supported

by a fellowship from the Henry J. Kaiser Family Foundation and by a

Young Investigator Award from the National Alliance for Research on

Schizophrenia and Depression.

Requests for Reprints: L. Komaroff, Division of General

Medicine, Department of Medicine, Brigham and Women's Hospital, 75

Francis Street, Boston MA 02115.

[Guest guest]

perhaps they all had mercury fillings too. or root canals.?

and mold just tipped thier already streesses systems , perhaps not the

only or main cause

amy

> > > when asked if they had spent time in a moldy building

> > > around the time that they first fell ill, has told me yes. I went

> >

[Guest guest]

Everyone's mercury levels have risen recently for many reasons. The

use of coal is a big one. Fish from fresh water sources have it, as

well as ocean fish. Now there is mercury in rain and it builds up in

the soil so anyone who lives near farms gets exposed to lots of it.

Vaccines are another.

Lead in gas and paint exposed a whole generation to more *lead* than

is considered safe now.

We really should start a national dialogue on toxics because they are

probably responsible for a LOT of illness.

Maybe that is why they are covering up CFS? They don't want to accept

blame. Sort of like whats going on now with Katrina.