Cheney lecture, Feb. 6, 1999, Orlando, Florida - part 1, pages 1 - 4

[Guest guest]

Lecture by Cheney, M.D.

Feb. 5-7, 1999

The Third International Congress of Bioenergetic Medicine, sponsored by the

Institute of Quantum and Molecular Medicine, National College of Oriental

Medicine and the Florida School of Acupuncture and Oriental Medicine,

Clarion Plaza Hotel, Orlando, Florida

This lecture precedes a workshop that was given by Dr. Cheney on the same

day. These are notes, and are not word for word. Dr. Cheney refers to

slides.

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INCIDENCE

......There's a 4-cities studies in the United States conducted by the

CDC--about 10 per 100,000; another study in Australia, 40 per 100,000. It

seemed like every study around the world began to see larger and larger

numbers. [There's] a question of whether the disease was more prevalent, or

more physician diagnosis. The incidence is now thought to lie between 200

and 600 per 100,000, approaching almost 1% of the population. It is very

common and extremely disabling.

The disability in this syndrome is truly impressive. The largest insurance

carrier in the U.S. reported huge increases from 1989 to 1993--in the case

of men a 365% increase, and for women a 557% increase. This is the highest

increase of any disease covered by this major disability carrier.

There seems to be [an increase] with each passing year, beginning in the

late 70s but especially in the 1980s. The data base in 1990 asked the date

patients became ill. It stopped in 1990 because that's when I asked the

computer [......?]. It peaked in 1987, and after a couple of years there

was a slow decline and then a rapid dropoff. It's probably fictitious. They

usually come after they've been sick 4 or 5 or 6 years down the road. And

then in 1994, I hit the button again and in each instance, the peak

production remained fixed. In 1987, suggesting that there might be a point

epidemic, peaking in 1987. Again the total number of cases continues to

rise. There are still new cases being produced all the time.

A group in england, Ramsay's group, saw a similar peak, again 1987. In

Minneapolis a group headed by , again 1987.

There may be something that began, almost at the same time HIV began. There

may be a link between this syndrome and HIV disease.

PHYSICAL FINDINGS

Physical findings are readily seen, and are a sort of basis for the belief

that it's a real disease in my mind. In the case control study that we did,

there's frequently lymphatic tenderness, not lymphomatic enlargement. By

placing your hands on the posterior cervical chain and the supraclavicular

node chain compressing these areas left to right, patients will commonly

complain that they are tender, left side more than right.

The reason it may be left-sided is the anatomy of the thoracic duct, the

left is the main terminal vessel, eventually emptying into the left

jugular. Immune activation states would be expected to back up and fill

these vessels.

If you just ask if it's tender they frequently produce tenderness. Tender

swollen areas can go up and down very rapidly

Another physical finding--the crimson crescent, sort of purple, found in

about 80%.

When you use a reflex hammer out, move away from these people as you tap.

About 80% are hypereflexive. Balance is always aberrant. Patients almost

always fall over. Test the Romberg, tandem stance and ? with eyes closed.

This particular one is so frequent, it was published in a Harvard

journal--a defect in vestibular apparatus.

About 10% progressively lose their fingerprints. There's disruption. This

generates interest with the FBI. People can't teach if they can't furnish

fingerprints. The pathophysiology--lymphocytic ..itis that penetrates the

vessels that engorge the areas around these vessels and may impair

nutritional flow. Also they have punched-out lesions within the fibroblasts

themselves. Fibroblasts make collagen, and it's necessary for the ground

substance.

IMMUNE ACTIVATION

What does it all mean? One category is something is wrong with the brain.

The hyperreflexia, these 2 particular findings are easiest to access in the

clinic. Second, they're immune activated. Even the loss of fingerprints is

immune activated.

I'll describe a particular case control study in the workshop this

afternoon. With regard to immune activation there is a great bulk of

published literature, all kinds of studies showing this. Here's a little

study we did on the interleukin receptor. It's just one measure of immune

activation. These people are without a doubt immune activated.

RNASE-L

This paper by Suhadolnik is important. It's the most important conceptual

idea in the field, interferon in a cytokine activated by a white cell,

typically in response to a viral infection, or perhaps an intracellular

pathogen. Interferon sits down on its receptor and on the cell membrane

around the body and ultimately activates the enzyme system within the cell.

That system's called the 2-5A synthetase pathway. It consumes a great deal

of ATP and it ultimately activates this enzyme called RNaseL . This enzyme

is present in essentially every cell in the body and has a very interesting

purpose. Under normal circumstances this enzyme regulates protein

synthesis so that when you're a little bit under a certain setpoint for

protein synthesis--we're talking about hormone or other enzymes that

operate the cell--if you're a little bit under this, the system

downregulates and you come back up. And if you're a little bit over this,

the system ramps up and you come back down. So it has a kind of regulatory

function for protein synthesis. It also has a supra-physiologic

function--namely when infected with a virus this system activates

significantly and tends to chew up messenger RNA encoded by viruses, and

that RNaseL then becomes a potent anti-viral weapon as it sits there and

chomps messenger RNA from the virus and that virus is decoupled from its

DNA or RNA and can no longer replicate. So it has a physiologic function of

regulating human protein synthesis and a supra-physiologic function when

ramped up of destroying RNA encoded by viruses.

The way you measure this is you take the patient's blood and you extract

the cytosalic (....?) of the lymphocytes and you put it in a test tube and

a target ribosomal RNA is used, and they'll measure how long it takes for

the RNA cell in that white cell cytosalt (?) to digest the ribosomal RNA

target. And typically human beings will digest some of this target in about

20 minutes and leave certain residual products that then migrate on these

gels. In the case of chronic fatigue syndrome, the rate of digestion is so

great that they will digest in 20 seconds ribosomal RNA target that a

normal human being cannot digest in 20 minutes. And when you digest

frequently or quickly these target molecules you end up with very digested

components that migrate off the gel and you end up with these blank strips.

And so in the Lake Tahoe region about two years ago, where we first saw

this disease, you would run this assay and all you would see would be blank

strips because they had huge activation of this enzyme system.

This is a quantitation of the RNaseL activity in the patient population

compared to the normal population. Interestingly, though, some CFIDS

patients have normal values. Perhaps in the workshop we'll go into them.

They're really quite interesting. They represent a different stage in the

illness.

A particular drug called Ampligen, which a piece of genetic material,

actually it's a piece of double-stranded RNA which regulates this RNaseL

pathway, was applied to patients in a double-blinded placebo-controlled

trial in the early 90s, of which I was a party. And this is the structure

of Ampligen, and it's mismatched in a couple of regions or RNA to make it

ephemeral. It only lasts about 8 minutes before it's destroyed by the body,

It's not very stable, but it has a biological life of much greater...

Since it regulates the RNaseL pathway, the thought was that if you could

regulate that back down to normal, the patients would... and indeed that's

essentially what we saw. This is the placebo, this is the treatment limb,

and in about 24 weeks they were clearly separated. They tend to get better

and better as time goes on and it appears now that treatment may have to

extend to even 18 months to get these patients to where they can return to

work.

(to be continued)