Saturday, March 20, 2010

Heartfelt Thank Yous!

There are so many who have done so much, and to each of you I say Thank You, it has not gone unnoticed.
I would love to name you all, but I won't, lest I inadvertantly omit someone from the list.  Needless to say, the list is long, and it encompasses people from all walks of life, who have contributed in all sorts of ways. 
Some of you have petitioned government entities.  Some of you have blogged tirelessly, hoping to bring awareness.  Some have testified in Washington, some have run support groups, and some have engaged in active dialog with researchers in hopes of getting their attention.  Some of you have shared your lives out loud for all of us to see and hopefully learn from.  Some of you have worked quietly behind the scenes, one-on-one, trying to help with individual support.
Some of you have watched Bill Reeves with hawk eyes, bringing communications to daylight.  Some have done the same with the CAA, with Wessely, White, and Sharpe, and with any other entity that has allowed psychologization of the disease. 
Some of you have kept history alive, despite all efforts to rewrite it.
Although many years and many lives have been devoted to grass roots advocacy for CFS, we are in as much danger, if not more, than ever.
Read more at:
Thanks all! ~ Khaly
[email protected]
[email protected]
* * *
I'll second that!

Friday, March 19, 2010

Another Health Insurance Option

Freelancers Insurance Co., a New York City-based nonprofit insurer that provides health coverage to self-employed individuals who are members of Freelancers Union, has seen its subscriber base balloon by 60% since November 2008, says Chief Executive Officer Sarah Horowitz.

Freelancer's monthly premiums for individual policies run from about $200 a month for basic coverage to around $500 a month for more comprehensive coverage -- about half of what an individual would pay on the open market.

See full article from DailyFinance:

Full Transcript of Dr. Bell's SoCal Lecture

Dr Bell's January 2010 XMRV lecture - full transcription
part 1 of 2
Published on January 31st, 2010 07:54 PM 0 Comments  Transcribed by 'thefreeprisoner'
January 15th 2010
Well thank you very much, it's a great pleasure to be here.
We always try to find some place to go in January and February from upstate New York. [laughter] This is a wonderful place.
Let's see if we can get our slides clicking here. So I have to turn this on... ahh there we are. It's always a bit of a mystery.
Review of XMRV in Chronic Fatigue Syndrome
David S. Bell MD, FAAP
Clinical Assistant Professor,
University of New York at Buffalo,
Buffalo, New York]
I'd like to keep this informal and then after about 50 minutes we're going to open it up for Questions and Answers, and any question is ok. There's no question that's silly or anything like that. I enjoy a huge variety of questions, but what I'm going to go through mainly is the new developments related to this virus XMRV.
Before I start I need to know is there anybody here who really doesn't have any experience with Chronic Fatigue Syndrome and needs some education about the basics? So everybody's a veteran, is that right? [laughter]
So that's really interesting because many of the patients with Chronic Fatigue Syndrome go into their doctor and they'll say "Well I've brought you this paper on the cytokines that's been published" and a family doctor has no idea what a cytokine is. So many people with Chronic Fatigue Syndrome are very sophisticated in what they already understand in terms of what this illness is. So I'm going to just touch very briefly on some of the basics because we'll be coming back to it.
Chronic Fatigue Syndrome Diagnostic Criteria: Centres for Disease
Activity-limiting fatigue
4 of 8 symptoms
1. Post-exertional malaise
2. Cognitive disturbance
3. Unrefreshing sleep
4. Recurrent sore throat
5. Lymph node pain
6. Recurrent muscle pain
7. Multi-joint pain
8. Headache
Absence of alternative explanation]
The current diagnostic criteria for CFS is really quite simple, even though on the internet people argue about it daily now for the past 25 years; it's really very simple. The simplicity is that this illness restricts your activity. They used to say you have to have only 50% of your normal activity. Some people now would say well how do you measure 50% of activity? It almost doesn't matter. In terms of what normal activity is, this illness restricts it. In addition, there are 8 very common symptoms, and you have to have 4 to meet the CDC criteria. And those symptoms are listed right up here.
And then the third part is that you have to have no obvious explanation for the fatigue and the other symptoms. So that it's really quite simple. If you have somebody who comes into the office and their chart is this thick [holds hands about a foot apart] and you have no clue of what's going on, they probably have Chronic Fatigue Syndrome. Those are the criteria that I put out 25 years ago, and I think that they're still quite accurate. A lot of people with Chronic Fatigue Syndrome get enormous numbers of tests, and those tests cost an enormous amount of money, and those tests in general, for the most part they're perfectly normal. This is interpreted by family physicians and specialists to mean that there is no disease present, and that's a misinterpretation, and we'll be coming back to that over and over again. Just because your standard laboratory tests are normal, does not mean that there's no disease present.
[Slide: The Fatigue of CFS, ME, FM
Described as Exhaustion weakness
Concept of Orthostatic Intolerance
Concept of Pre-Syncope
Not Simple Tiredness
Not Anhedonia]
Now the fatigue of Chronic Fatigue Syndrome - it's also called Myalgic Encephalomyelitis - the fatigue of Fibromyalgia as well - it not a true fatigue.
The fatigue as defined is a state of recovery. If you go out and run a marathon you will have fatigue. That is the process of recovery from that exertion. But that is exactly what does not happen in this illness. So fatigue is really the wrong word. This was misnamed right from the start. [you can virtually hear the nodding]
Whoopsie, I gave away my best slide there.
In fact, the fatigue is really described as an exhaustion or a weakness, but the true meaning of it is Orthostatic Intolerance. What that means is that people are not tolerating the ability to stand upright. So that when they're standing upright they're not able to maintain that position. Interestingly enough, most people with this illness when they're walking around, they feel much better than if they're standing still.
One of the tests that we very commonly do in our office is we have a person stand still next to the examining table for 5, 10, 15 minutes or half an hour. And this we call the orthostatic testing and it's been described by Dr David Streetman in great detail. Healthy people can stand for an hour. He did his normal values based on 90 healthy people. He had them stand for an hour without moving. After an hour many of them were somewhat tired and they would have some achiness in their legs and that's normal. Chronic Fatigue Syndrome patients very rarely make it past 20 minutes. The severity of the illness is almost predictable by how soon it will be before the symptoms become overwhelming and that person becomes pre-syncopal -- they have orthostatic intolerance and they have to lie down. Their pulse sometimes goes very high and their blood pressure goes through some changes, but this is in general called orthostatic intolerance, and it's different from the fatigue which is present in 50% of the population.
It's not simple tiredness and it's not Anhedonia. Anhedonia is a psychiatric term which means that you have no motivation to go out and do things. Persons with Chronic Fatigue Syndrome would love to go out and do things but they just physically feel that they can't do it. So in depression, because you're depressed, you really don't want to go out and go shopping at the mall but if you're pushed to do that, frequently you'll feel somewhat better. In Chronic Fatigue Syndrome if you try to go shopping at the mall, you actually don't feel better, you feel worse.
It's not a sleepiness. This is different from illnesses that are characterised by sleepiness, although a lot of patients will have hypersomnolance - they can sleep for 20 hours a day. In general the milder the illness, the more a person gets good or heavy sleep.
The psychiatric issue that's been going on for years looks like this is characterised in this slide... as I understand it the web will not be able to see this slide and I guess I will be able to get away with that [laughter] I showed this slide in a lecture I gave in 1987 at the University of Rochester School of Psychiatry. The University of Rochester has a world famous School of Psychiatry and the auditorium was filled with interns and residents and I showed this slide, and silence... just silence. [lots of laughter]
It's been a misperception that somehow this illness must be a psychiatric illness, and here's where modern medicine has made a big mistake. Doctors are under the gun. If you go into the doctor and the doctor has no idea what's going on with you, he's got to come up with a diagnosis. In the old days he could say [shrugs shoulders] 'I dunno what you got' but now they can't do that for some reason I don't understand quite why. They will say "Well, I can't find anything wrong. Your liver's normal size. Your blood tests are fine. Therefore you must be depressed."
And this is really quite unfortunate because psychiatric diagnoses have very strict criteria. If you're depressed, you usually know you're depressed. Depression has severe hopelessness; it has all these symptoms which are not part of Chronic Fatigue Syndrome. So for years there's been this ongoing controversy - is this illness due to a psychiatric basis, and doctors have been kind of mystified. "I dunno what you have, but I don't want to deal with you, so I want you to go to the psychiatrist." This has very unfortunate consequences for the patients. Because this is what's happening in the psychiatrist's office. [laughter]
And really, when you're trying to look at the specific... so in the University of Rochester they didn't like this slide at all. [laughter] They were very negative about this slide. I was trying to say -- you know, it's just a joke -- but psychiatrists really would have a difficult time explaining the theory of how a viral infection causes some inactivity and then that inactivity gets into a cycle which leads to orthostatic intolerance and these other things, because there is no model that explains it in the psychiatric literature.
Now that's not to say that psychiatric disease cannot coexist with Chronic Fatigue Syndrome. This is a very important point. For those people who have Chronic Fatigue Syndrome and are depressed, well you've got to address that. And it's actually fairly easy to address. The anti-depressants work very nicely on depression when it co-exists with Chronic Fatigue Syndrome. But it really doesn't help the symptoms of Chronic Fatigue Syndrome much at all. Many people are reluctant to admit their depression because they then say well maybe the psychiatrist will.... but that's a mistake, because if there's depression going on, you've got to address it. This is no different than if you had Multiple Sclerosis or HIV disease or any other organic illness. If you get depressed because of your organic illness, that becomes fairly easy to treat as a part of the illness but it doesn't remove the basic symptoms of Chronic Fatigue Syndrome.
[Slide: Definitions
XMRV - Xenotropic Murine Retro Virus
More accurately: Xenotropic Murine Leukaemia Related Virus
Retrovirus - an RNA virus able to change to DNA within the cell and insert itself into the human genome
Xenotropic - able to jump species lines
Oncogenic - causes cancer]
OK, tonight we're gonna be talking about XMRV. This was some of the interesting or exciting new information that's come out.
XMRV stands for Xenotropic Murine Retrovirus. More accurately it's Xenotropic Murine Leukaemia Related Virus. This is a fairly large family of retroviruses that XMRV is part of.
A retrovirus is a specific type of virus which is an RNA virus. Very small compared to other viruses. And it's able to insert itself into the human chromosome and from there, it replicates itself and causes damage.
Xenotropic means that it's able to jump species. Many years ago, back in the 1990s, this was thought to just never occurr among retroviruses and one of the big arguments in the HIV history was could this has come from the Simian Immonodeficiency Virus, or SIV. Did it actually jump species and become a human pathogen? Xenotropic means it definitely does. This was first described probably many years ago in the retrovirology in different animals and that's where doctors have been able to study this for many years and it's only recently become clear that this is a human pathogen.
Oncogenic means that it causes cancer. Now there are 3 human retroviruses, all of which cause cancer. HIV we know causes cancer. HTLV-1 clearly causes cancer. It used to be thought that HTLV-2 causes Cesary syndrome and leukaemias. That's been called into question at this point. But XMRV also is now related to human malignancies.
[Slide: Dong B, Kim S, Hong S, Das Gupta J, Malthi K, Klein EA, Ganem D, Derisl JL, Silverman RH. [not sure about spelling; slide is a bit fuzzy]
A new human retrovirus associated with prostate cancer.
Hpc1 families with RNAse L activity
RNAse L degrades mRNA
XMRV more accurately MLV-RV (Murine Leukaemia Virus-Related Virus)
MLV - several families of RV proviruses]
The first recent paper on this virus was by Dr Silverman's group in the Cleveland Clinic where he described families who had a specific immunologic abnormality called an RNAse L activity abnormality. He found in patients who had a very aggressive tuype of prostate cancer this virus. So there were a number of cases which he worked up and he published this about 5 years ago. And while there hasn't been a huge number of papers on this in the ensuing 5 years, most retro-virologists have said -- yes, this really looks like a human pathogen -- because it's present in prostate cancer.
[Slide: Schlaberg, R; Choe, DJ;
XMRV is present in malignant prostate epithelium and is associated with prostate cancer]
Here's a second paper, this was published in PNAS, again high grade prostate cancer. Now there have been 2 papers published, one from Germany, where they have been unable to replicate the presence of this virus in prostate cancer. So there's some discussion and debate going on, so the story's not over as it's regarding prostate cancer as well.
[Slide: Lombardi, VC; Ruscetti, FW; Gupta, JD; Plost, MA; Hagen, KS; Peterson, DL; Rusceni, SK; Bagni, RK; Petrow-Sadowski, C; Gold, B; Dean, M; Silverman, RH; Mikovits, JA
Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science, 8 October 2009; 10.1126/science.1179052]
This is the paper that came out 2 months ago. The first author Dr Vincent Lombardi, the second author Dr Frank Ruscetti, a very well known scientist who has worked for many years in this area, and then the final author is Dr Judy Mikovits who's in the WPI. They baiscally started studying this 2 years ago and began to approach it very quietly. Nobody really knew quite what they were up to.
I was fortunate to go to a conference in Reno in Feburary. From the audience, when Dr Mikovits was talking about cytokines, and she was obviously very excited about something but it wasn't the cytokines she was describing. And so I didn't find out what it was until October 8th when this paper appeared in Science.
Science as you know is an extremely reputable journal. They review these papers extremely carefully. Now, in the paper the first headline that most people take is that roughly 67% of patients had a test of their DNA done by what's called PCR - Polymerase Chain Reaction - which was able to detect the viral sequences of XMRV. So this was 2/3 of the patients had this sequences present. And when they do that test on healthy controls it's only 3 to 4%. So this represents one of the first ways of establishing whether or not an infection is important in the generation of an illness. You have a high percentage of people with the illness who have evidence of the virus and in healthy control people a very low incidence.
If you remember back in the days when this was thought to be due to Epstein-Barr Virus, well 95% of healthy people have antibodies to Epstein-Barr Virus, and yes if you're sick you've got a 95% chance of having those antibodies, but that doesn't mean that Epstein-Barr Virus virus caused the illness. In fact back in '85 we did a study on a bunch of children and only half the children had the antibodies to Epstein-Barr Virus. And half of our patients with Chronic Fatigue Syndrome who were children had those antibodies. So that meant that Epstein-Barr Virus clearly couldn't be the cause.
XMRV is in a totally different league. This is a disease that is pretty rare. In the Japanese literature, their healthy population of 1-2% has evidence of this virus, so in line with what the WPI found.
However, the PCR data by itself is not going to change the world. Many journals will not publish a paper based on just PCR data. The WPI realised that early, so they went ahead with several other technologies, one of which was to demonstrate that this virus was... they were able to infect other cells with it. And they were able to show under electron microscopy was budding viral particles that fit the description of XMRV and a number of other things they did, which made the paper extremely strong. This becomes very important, because people are quite ready to dismiss PCR data. But the other ancillary studies that the WPI did I think make this paper very strong.
[Slide: XMRV in CFS
Data Reported at CFSAC meeting
68/101 XMRV DNA positive
Of the other 33, 19 are XMRV antibody positive
30 of 33 had transmissible virus in the plasme
10 of the 33 had protein expression]
After the paper was published, they had 33 patients who were negative for the PCR. This data here was presented by Dr Dan Peterson at the Washington CFSAC meeting shortly after the publication of the Science paper. What they presented was that 19 of them had postiive antibodies to XMRV. What that means is that those patients have seen this virus and developed a resistance to it by the way of linking antibodies. 30 of the 33 had transmissible virus in the plasma. And this is extraordinary. If you take the plasma of these people with Chronic Fatigue Syndrome and then show that it can infect these tissue cultures, this is really quite extraordinary. Now there are a lot of questions here. How come they weren't PCR postiive? These are questions that are normal at the beginning of a scientific breakthrough and it's going to take the next 5 years to come up with all these answers. So quite legitimately you can say "How come these people have transmissible virus but they are PCR negative?" Let's give that a bit of time and we'll find out.
And then 10 of the 33 had protein expression. What that means is when you look in the cells, you can find that not only is the virus there, it is making copies of itself, it is actually replicating, it is doing things. We'll come to that a little bit later as well. When you add it all up, all of the people involved in this study, 99 out of the 101 patients had some evidence of XMRV infection and this is an extraordinary number. Is that going to hold up in the future? I have no idea. I think that it's quite possible that there are a number of people who will be negative for XMRV. We just don't know that yet. We need to be patient. We need to let the scientists do their work and we will come up with those answers eventually.
[Slide: XMRV in CFS
Data reported at CFSAC meeting - 2
no simple test now that will tell you if you have XRMV or if the virus is active in your system. And we need a good control study using all measures to accurately know control presence of the virus.
Viral infectivity
Detection of viral proteins
Antibody to the XMRV envelope]
Now there are a number of implications to these findings, and one is that there is no simple test which is a gold standard for XMRV infection. I guess if you had a culture assay which showed the growth of this virus in tissue culture, yes I would consider that a gold standard. If you were able to say that your laboratory has no sources of contamination and you can grow this virus in a tissue culture from your patient sample, yes I would say that's a gold standard but that's a very difficult and expensive set of tests to do. There's no way that the PCR is a gold standard at this point. Why is that? We don't know. Could it be that the primers are not the best primers? There are lots of technical reasons why there may be a better test down the road.
So, when people are saying "I want a test to see whether I've got XMRV" you know, I want that test too. But I think it's still a little bit early to say yes we have a test that is the right cost, the right specificity and that the clinicians will know how to interpret it. I think we are some time off from having those criteria met. Now if somebody wanted to go and get the test, it's quite expensive. I would say no insurance company is going to cover it. If you want it for your own intellectual curiosity to know about it, you can go ahead and get it. But for my patients I'm not encouraging them to do that, because I think that we need to know a little more about this virus and about the testing procedures before this becomes a standard part of medical care.
[Slide: A New Virus for Old Diseases?
John M Coffin, Tufts University
At the CFSAC meeting, I had the good fortune to meet a Dr John Coffin who wrote a little piece in the same issue of Science magazine that the original paper was published in. John is one of the great virologists. He's been there during all of the AIDS research. He is just about as knowledgeable as you can get on retroviral diseases and he has been speaking to the committee advising the Department of Health and Human Services and he was giving his comments as an outsider. He was not one of the authors of that original study. And he said something which is just the right perspective. What he said was that as a first paper; the paper by Lombardi and others, it's as good as it gets. You can't have a better first paper. But it's only a first paper. I think that's a perspective that we need to keep. It's very difficult because for people who have Chronic Fatigue Syndrome they lived for year after year after year of people disrespecting the illness itself. So patients are legitimately saying "I don't want to wait any more. I want this to be the end. I want this to be declared the cause of Chronic Fatigue Syndrome." Unfortunately it doesn't quite work that way and you're going to have to struggle through a little longer.
[Slide: Erlwein O, Kaye S, McClure M, Weber J, Will G, Collier D, Wessely S, Clear A.
Failure to detect the novel Retrovirus XMRV in Chronic Fatigue Syndrome.
E8519. doi: 10.1371/journal.pone.0008519]
Now just a few weeks ago there was a paper published in the journal PLOS which tested 186 stored samples from a group in London.
[Slide: Erlwein et al.
186 Patient stored samples
Nested PCR
XMRV or MLV not detected]
They used a technique called Nested PCR and they were not able to find XMRV in a single one of the patients. This has caused again a great stir. There has been a number of editorials that have come out saying 'Here we go again.' This is very difficult for patients because patients don't want to have to go through this controversy. However, science has to come up with the answer.
One of the things that's happened in Chronic Fatigue Syndrome is that historically, there have been a lot of theories, and a lot of the theories have been incorrect. So somebody will come out and they'll say "This illness is caused by a magnesium deficiency getting into the amygdala part of the brain" and it's a very nice theory, and then after a period of time that theory begins to fall away and then something else comes up. So there have been a lot of theories presented.
In my experience, I enjoy studing these theories for several reasons. One is that I learn a lot of medicine and the second is that I practise a technique which has been very useful to me. And that is I give the theory the benefit of the doubt. And I say ok, let's say that this theory is correct, then what means is this and this. And then I wait to see how long it is before that theory falls apart in my own set of reasoning. And in general the theories fall apart very quickly. Because this is a very complex disease. You have to be able to explain why children get it in equal sex ratios. Why do [in] adults more women than men get it? Why do some people get better without treatment, up to 80%? Why do some people get disastrous symptoms in this area? So when you look at all these symptoms, these theories tend to fall apart fairly soon.
[If you missed it, part 1 of this transcription is here]
When you look at XMRV at this point, it seems to me that this is a very good theorietical cause for the illness but that's gonna take some time before that's proven. And I'm happy to say that if it's proven to be the cause then we'll go from there. If it's disproved, then I'll say OK, but I want it to be disproven by science not politics. If it's put aside because of political inconveniences then I'm not going to be able to accept that. But if scientifically, it can be shown that this is not the cause, then ok, we'll go from there.
Something is the cause of Chronic Fatigue Syndrome. I have that as a certainty in my own mind. I have no question about that. What it's going to turn out to be? Well, we'll have to wait and see.
[slide not shown. Laughter.]
OK the doctor sits there [inaudible] and the patient says "I really look forward to your cheery little visits". This realates of course to the controversies about is it real, is it not real.
The WPI finds XMRV in lots of people and then this London group finds that out of 186 there's not a single sample was there. But this is what sicence is all about. We have to look at the methods. Did the London group use different methods? Did they use a different way of storing it? Did they use different PCR primaries and so on? And here's where over a period of time we'll come up with the answer. I'm quite optimistic that there will be about 10 groups that will try to replicate the WPI studies. So that if one or two groups can't find it that doesn't mean that all 10 or 15 groups are not going to find it. If all 10 or 15 groups can't find it then we have to come to some understanding about just what's going on and why they can't find it in those tissue cultures.
[slide shows virus picture]
So these slides that I'm going to show you are what a retrovirus is. These slides are coutresty of Dr Jones at the NIH. HIV is one of the retroviruses in the human population and as such it is a good model for us to use when we're talking about XMRV. Back in 1980 when AIDS first came on the scene, people were saying it was a type of psychosomatic illness and this went on for several years even with patients with HIV were dying, they were saying "Well, it's a real bad psychiatric disease." [laughter] I'm not kidding... there was a big controversy.
Then the virus was discovered and the research took off from there. It didn't take off right away, it actually took a couple of years for people to get the message that this was really important. The reason they got that message was because patients started getting HIV from blood transfusions. When that happened the politics started to change. But HIV as a retrovirus, a human retrovirus, is now somethng that can be treated quite well.
There have been 2 clinicians, Dr Mark Loveless and Dr Nancy Klimas who have large clinics, half of the whom have HIV and half of whom have Chronic Fatigue Syndrome. Recently somebody had said to Dr Klimas, "Well at least your patients aren't as sick as those with AIDS" and she said "What are you talking about?" Because of the anti-retroviral drugs, the patients with HIV Disease are hail and hearty, that was the term that she used -- and the patients with Chronic Fatigue Syndrome are bedridden, at least in her clinical practice.
What this means is that while HIV is still a terrible disease, the anti-retrovirals have changed the clinincal course so dramatically that patients can go out and do things and sometimes work full jobs. What this means for patients with Chronic Fatigue Syndrome - if XMRV is the cause of Chronic Fatigue Syndrome, I would anticipate that there will be good treatment in the near future; however, there are lots of steps to go through before that.
[Slide with diagram [undreadable - something about Free Virus, Binding and Fusion, CD4 receptors, CCR5 receptor, CXCR4 Receptor, Transcription, Integration]]
This is what happens in a retroviral infection. First of all the free virus attaches itself to the cell membrane and it chooses certain cells to attach to. For example, the HIV, it's the CD-4 primarily. Fusion proteins connect, and then, right at this stage, the HIV RNA goes into the cell and because of reverse transcriptase enzyme, it turns it into HIV DNA. This DNA goes and inserts itself in the human chromosome. This is the insertion or integation. And now the HIV DNA becomes a part of the normal human chromosome. And this is what defines a retrovirus.
When it is inserted or integrated into the DNA, it can use the normal cellular mechanisms and transcribe itself back into viral DNA, and then back into... er, it buds off from the cell and then becomes a mature infectious [barrier?]. How much of this is in your bloodstream is called the viral load, and that's one of the critical issues in the infectivity part of this illness.
So we'll skip this slide...
Also, we'll skip this slide which just shows the basic structural elements of the retrovirus.
[Slide: Protease
Cuts Gag polyprotein to MA, CA, NC
Exquisite cleavage specificity.
Major classif... [undreadable]... Inhibitors]
Now the Protease is an enzyme which cuts the Gag part of the gene into certain pieces which will then make it infective. The nucleus for HIV Disease are protease inhibitors. So what they do is they get into this enzyme and they change the confirmation of the enzyme so that the enzyme doesn't work. And as such, the HIV which is still integrated into the DNA now becomes kind of just a bystander or a passenger in the DNA. It will always stay there but it is not able to go out and make infections [varials?].
So this is the latest class of drugs for HIV disease. There are many different classes of drugs. There are fusion inhibitors. There are protease inhibitors. There's the reverse transcriptase inhibitors. So you can attack the virus at many different points and as a result you can render this virus much less pathogenic.
Now this has taken 20 years, well, 1985 to 2010, going on 25 years, but the scientists are pretty close to getting these treatments right. These drugs are incredibly expensive, they have significant side-effects, but if XMRV turns out to be a real cause of Chronic Fatigue Syndrome, we will be able to use the experience from the HIV community in formulating treatments that will work for Chronic Fatigue Syndrome.
[Slide: Diagram of 2 different T Cells
a) Latent infection
Shows CXCD4 coreceptors, CD4 receptors, Proviral DNA, T Cell, Chromosomal DNA
b) Active infection
Shows Viral DNA, Proviral DNA, mRNA, Envelope, Core with viral RNA, Virus budding from T cell and Progeny HIV]
2 seperate possibilities. Here you have a cell for the pro-viral DNA, again this is HIV but it could be the same for any retrovirus. Again it's just sitting in the cell, it's not doing anything. And then over on this cell you have an active infection where the pro-viral DNA comes out here, it's making the envelope and the other parts of the virus, it buds off here and becomes an infections [varia?].
So this is the difference between a latent infection and an active infection.
Now, why am I enthusiasitc about the possibility that XMRV is the cause of Chronic Fatigue Syndrome? Now first of all I can say that because I'm just a country doctor from way out in the rural countryside, so I'm not going to lose my job for saying something that's politically incorrect. Most of my regular patients have no clue that there's such a thing as Chronic Fatigue Syndrome. Every once in a while they say "Gee, have you heard that in the paper about Chronic Fatigue Syndrome?" They're as unfamiliar with it as everybody else in the country. So I can say what I want because I'm not an author of that paper and I have my own opinions.
[Slide: Chronic Fatigue Syndrome
70% of Lymphocytes activated
Abnormal RNAse L
Decrease NK cell number and function
Immune Activation
Activated T cells
Cytokines / Chemokines]
This is one of the reasons why I have the opinion that XMRV is a perfect candidate for the cause of CFS.
Studies for years have shown that the lymphocytes in this illness are activated. Nancy Klimas has said roughly 70% of the lymphocytes are in the activated state. What that means is they're doing something -- they're fighting something. Now everybody's saying "Well we can't find anything that they're fighting." That doesn't mean that it's not there, it means we can't find it. So the lymphocytes are active and they are trying to fight against something. Even though with every theory; well, it's EBV or mycoplasma or whatever it is; we haven't been able to prove that. But what we do know is that the lymphocytes are activated.
Secondly there's abnormal RNase-L. Now this is an enzyme which is very important in the anti-viral pathways. What it does is it's an RNA enzyme... it's a non-specific RNA destroyer. It breaks up RNA. The studies have been very complex but they've shown for probably at least 15, maybe 20 years that this enzyme is clearly an important factor in CFS. Why? Because there's clearly some retrovirus circulating around and this enzyme gets activated that way.
Thirdly there's a decreased Natural Killer Cell number and function. Natural Killer Cells are one of the arms of the immune system aand it's one of the areas that again over the years has proven to be a consistent abnormality in Chronic Fatigue Syndrome. Interestingly Natural Killer Cells have a role in keeping yeast suppressed. I remember reading about all the yeast studies. A lot of them were taking place right here in Southern California and I was saying "Well, who cares about yeast?" I see babies every day with thrush; that's yeast in their mouth; but adults shouldn't have thrush. But you find a lot of CFS patients with thrush. That's because the Natural Killer Cells are not working properly.
In addition Natural Killer Cells are one of the first natural lines of defence for herpes group viruses such as mono, EBV, cytomegalovirus, and these are exactly what we've been looking at for the past 25 years. Again Peterson at the CFSAC meeting said that the three types of cells that XMRV seems to have a preference for is the Natural Killer Cells, some B cells and some T cells. So we know that this is an illness that can affect Natural Killer Cells.
And then of course there's immune activation with activated T Cells and the cytokines.
So if you would put this together as a possible chain of events, what happens? And again this hypothesis is certainly not fixed; it's too early to know whether this is true. Dr Dan Peterson had mentioned this at the CFSAC meeting, so I'm happy to call it his particular theory on it, but it really makes a lot of sense.
First of all you may have an infection with XMRV. We don't know how people get it. People are going to say "Oh, how did you get it?" Don't know. That's something that there are a million theoretical possibilities. Right at this point it's best to say, "Just don't know." Then these B cells, T cells, get infected.
[Slide: Possible Chain of Events with XMRV
Step #2
NK Cell function impaired
NK Cell numbers decreased
[graph showing how viral load increases as these go down]]
Then the Natural Killer Cells function becomes impaired and the NK Cell numbers are decreased, and when that happens, the viral load can go up. In AIDS the same thing happens only this is CD4 cells and this is the viral load. As the CD4 cells go down, the viral load goes up. It's quite possible the same thing happens with XMRV.
[Slide: Possible Chain of Events with XMRV
Step #3
"Subtle" Immunodeficiency
Allows infection / persistence of:
Herpes group viruses
Numerous other agents]
So then the next thing that happens is that you have "subtle" immuno-deficiencies. I say "subtle" because it's nowhere near as drastic or as dramatic as HIV where you have these overwhelming infections that turn out to be lethal. So I would say in comparison the immuno-deficiency of CFS is subtle. But it's there. You do see patients with yeast. You do see patients with higher than normal viral loads of EBV or Cytomegalovirus. You do see patients with CFS who have difficulty with immunologic function. And there are numerous other agents that can be involved.
[Slide: Possible Chain of Events with XMRV
Step #4
Symptom Production from Secondary Infection
Cytokine release
chronic inflammatory changes
Inhibition of ATP production
Step four. You can have symptom production from the secondary infections. So what happens is you have increased release of the cytokines. You have chronic inflammatory changes. This leads to nitric oxide and inhibition of ATP production and loss of energy because of that, and the area that I've always been very fond of, which is the systemic vasoconstriction, which is probably due to the isoprostates which is related to oxidative stress. But it really doesn't matter quite exactly the mechanism is here, because whatever is the underlying cause of Chronic Fatigue Syndrome is causing these symptoms.
I think that XMRV makes an excellent candidate for that.
[Slide: Possible Chain of Events with XMRV
Treatment of secondary infections is of limited value
Treatment of secondary infections in AIDS patients causes symptomatic improvement
No-one dies of HIV, they die from secondary infections
Difference between NK cell immune defect and CD4 immune defect]
There's been a lot of hope in the past that if you treat one of the secondary infections then you will cure the illness, and that's been a great carrot dangling in front of us. 2 years ago there was tremendous hope in the Stanford Study that if you use Valcyte and treat the EBV and the Cytomegalovirus and other herpes viruses then people would have a dramatic recovery, and in their first trial they did have an extremely good result. Howeer, in the subsequent double-blind study the results were not all that good, so you can treat secondary infections and when you do that you will have some improvement of symptoms. But this also occurrs in AIDS. So in AIDS if you have secondary infections and you treat them, patients will feel better. However it doesn't make the disease go away. Nobody dies of HIV infection, they die of secondary infections.

The difference with XMRV -- if it turns out to be the cause of Chronic Fatigue Syndrome -- and HIV, is basically the cells that are being targetted are probably quite different.
[Slide: Results from Dr Paul Cheney as of 11/20/09
Of the 13 CFS cases tested to date by VIP, all were positive at least by one test.
7 out of 10 tested positive on whole blood PCR
5 out of 9 tested positive on serum PCR]
Dr Paul Cheney shared with me that he's had a number of patients that he's had tested, and he feels that this is quite likely to turn out to be true. So it's not just patients that are in the Western part of the United States. His patients are mostly in the Eastern part of the United States.
[Slide: Dr K DeMeirlier
Described 34 patients in Belgium who developed CFS (CDC criteria) within 2 to 7 days of a blood transfusion. In 9 of these patients, low molecular weight RNAseL assay was performed - all]
Kenny DeMeirlier presented a paper where he described 34 patients who developed CFS within a couple of days of having had a blood transfusion. Now this is the only reference to blood transfusion in Chronic Fatigue Syndrome in the current literature. Actually this paper is not part of the peer review literature but he had presented this.
I've seen patients who had got sick immediately after a blood transfusion, and if XMRV is the cause of Chronic Fatigue Syndrome and if it is in 3% of healthy persons, then the blood supply of the country is probably contaminated. This is an area that I think has the Red Cross quite nervous, obviously they are working quietly behind the scenes to see if this is what's going on. We don't have a simple test now to be able to exclude XMRV but I'm sure that will come up as quickly as possible.
Oh, of these patietns that he did, they had a low molecular weight fragment of RNase-L; let's not go into that [laughter]
I've never understood that paper very well [more laughter]
[Slide: Fletcher, MS, Klimas N; et al
Journal of Translational Medicine
Results: The following cytokines were elevated in CFS compared to controls: LT alpha, IL-1 alpha, IL-1 beta, IL-4, IL-5, IL-6 and IL-12.
The following cytokines were decreased in CFS: IL-8, IL-13 and IL-15.
The following cytokines were not different:]
Nancy Klimas recently published this paper. There's new technology which allows you to simultaneously measure 16 different cytokines all at the same time. In the past this has been very difficult to do. One group will measure IL-2 and one group will measure IL-6 and it's difficult to draw comparison because of different technologies and different days that the blood is drawn. In this study she was able to see that there were certain [inaudible] and cytokines were decreased in CFS and certain that were increased. And then there were a couple where it didn't seem to have any effects.
Her discussion said "The results imply a disorganised regulatory pattern of TH1 function, critical to antiviral defense."
The results from the study support a TH-2 shift, which is a pro-inflammatory cytokine up-regulation, and a down-regulation of important mediators of cytotoxic cell function. Essentially this means, this is not random. There's a method to these cytokine abnormalities. There's a pattern which emerges.
And she goes on to say "The observations of abnormal cytokine patterns in (ME)CFS patients support the reports of retrovirus infections."
So that she also seems to feel that XMRV makes a very good candidate as the etiologic agent. Now for the past 25 years we've been arguing like mad over the definitions of this illness. So there are 3 different criteria that you can use. Actually there are about 15 different criteria. My favourite is the one for the [Takinoue?] flu which nobody else seems to be interested in, but I got to visit Takinoue in Finland and I think that their criteria there are much better than anybody esle's. But the CDC has their criteria, the Canadian Consensus criteria and then the Myalgic Encephalomyelitis Ramsey criteria, so people have been arguing about this.
In my practise, I don't know where to draw the lines. I probably have 5 patients where they are so close to Multiple Sclerosis that it's very hard for me not to say they have MS. And then there are other patients that are very close to other illnesses; for example Fibromyalgia, Multiple Chemical Sensitivities and so on. So where we draw these lines in clinincal medicine has been very difficult to do, and it's part of the problem of studying this illness.
If in fact XMRV is the cause of Chronic Fatigue Syndrome, early reports from WPI have suggested that these other groups also look like they're positive, in which case, we won't actually be caring about the present criteria.
[Slide: XAND
Xmrv Associated Neuro-immune Disease]
There will be the disease called XAND - Xmrv Associated Neuro-immune Disease. And this is where AIDS went. Initially it was called Gay Cancer, then it was AIDS and now it's called HIV disease, and there are many different variations; there are malignancies, there are pneumonias, there are all sorts of different clinical variations, but it all traces back to an infection with one specific retrovirus.
[Slide: Conclusion
This new virus is a very big thing
It is a very hopefuly thing
The research necessary to bring treatments that are effective is already being mapped out
You can make a difference
Spread the word]
Now this is a slide courtesy of Dr Klimas. She knows that I'm stealing her material. But I think she's presented this so beautifully.
First of all this new virus is a very big thing. I was trying to figure out how to express this, but couldn't find the right word. This is it. It's a big thing. This is not just a casual detail. This is something that is very important.
It is a very hopeful thing. Now there are some people who have said "Oh my word. If there's a retrovirus that causes CFS then this is bad." Well, we know the illness is bad. That's not telling us anything we don't know already. We know what this illness does and it's a disaster even though the majority of physicians in this country still don't quite get it; they don't understand the seriousness of it; this is a disastrous illness from some people. Even though it's still a very mild illness for some people, in my original patients that got sick back in 85, 80% got better. Now why did they get better? I like to think it's because of the outstanding clinical care I gave them [laughter]. That actually wasn't it. I did a couple of sub-studies. Many of them had no health insurance, so I didn't do any tests on them; I didn't give them any medicine to speak of. I watched them and followed them and they got better at the same rate as those who got an enormous amount of testing and an enormous amount of treatment. I don't think I affected their course at all. However, 80% got better. We published that in a study in 1995.
We now studied that same group again and we found that unfortunately they are not staying well. Many of them are falling off the wagon and falling ill again. This is worrisome. So we ought to have that data in the near future.
So this is hopeful. If this virus is the cause, then we ought to have treatments in the near future. The research necessary to bring treatments that are effective is already being mapped out. Now this I'd like to emphasise. I have some patients in my office who have said "Hey Doc, can you slip me some AZT?" I said "No, no I can't do that. It's not that I don't like you" [laughter] "It's that I really really don't want to harm you." This is not the time to start experimenting with anti-retrovirals. When and if the time ever comes that anti-retrovirals are going to be used, they need to be used carefully by someone who really knows how to manage them.
I will never be able to do that because I'm in a rural area and if somebody's being treated with an anti-retroviral, they need somebody on call 24 hours a day who knows what they are doing with this. And so therefore I'm not going to be able to do it. However, there are lots of infectious disease clinicians who are supreme at treating retroviral infections, and if XMRV turns out to be for real, they will be able to treat Chronic Fatigue Syndrome.
Number 4 - you can make a difference. Volunteer, give and spread the word. This I think is very important. People with this illness have just been really stressed, but the enthusiasm has fallen off over the last 10 years because it looked like it was going to just never go anyplace. But it does appear at this point that there's something that is a very real lead.
This is a picture taken years ago of a C-type retrovirus and we'll know whether or not this is going to be the etiologic agent for Chronic Fatigue Syndrome and I would hope that within 6 months we will be able to say, you know what, the evidence is coming in, this is going to be for real or "Sorry it's just another a dead end" but I really don't think it's going to be a dead end.
OK, well I'd like to thank you, you've been very patient, and I wish you the best of luck in the future.
[video ends] Updated January 30th, 2010 at 12:18 PM by thefreeprisoner (Added a link to part 1)
Tags: bell, xmrv 
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Advocate - January 30th, 2010 07:28 PM
Freeprisoner, you did this all by yourself? Thank you!
Terri - January 31st, 2010 11:06 AM
Thank you for doing this. Like Cort, I would much rather read than watch a video since a lot of this is over my head and I need to read again and again to absorb and understand.
txfriend - January 31st, 2010 02:19 PM
Thank you, freeprisoner! Wonderful job of transcription for us. I'm so hopeful I can't stand myself!
ixchelkali - January 31st, 2010 06:34 PM
Wow, what a lot of effort that must have taken. Thank you! It's great to have this in written form.
thefreeprisoner - February 1st, 2010 01:38 PM
No problem, folks. I like to transcribe or take notes because I learn things a lot better that way. Helps me remember and concentrate on what is being said because I have gnosteria (wandering mind) 
JT1024 - February 5th, 2010 09:05 PM
Thanks for you hard work... again!
I love the word "gnosteria".... know I can use it when I get lost in a conversation or whatever I'm trying to do and someone makes fun of me!
Let them look it up... (And if you made the word up, so much the better) 
OverTheHills - February 8th, 2010 09:09 PM
Hi, I know this is late but the mysterious place in Finland... Is a place in New Zealand, Tapanui. An outbreak there meant it was known for a long time as Tapanui Flu in NZ.
Thanks for lovely transcription
fingers - February 11th, 2010 08:56 AM
An excellent overview, but frustrating that the view is this will take 5 years. Certainly if we continue to let the research proceed randomly, it will take at least that.
Surely there's a more systematic way of going about this to get some conclusions in a shorter timeframe?
If there are any researchers out there interested in a different approach (managing the science and adding some innovation, some knowledge and wisdom), then please let me know - write to my personal e-mail please.

Wednesday, March 17, 2010

Bumper Sticker

Dr. Bell on XMRV & ME/CFS – Sharing the Insights of 20 Years' Patie


Sleep Characteristics in Patients with CFS

'A Retrospective Review of the Sleep Characteristics in Patients with
Chronic Fatigue Syndrome and Fibromyalgia'

Spitzer AR, Broadman M.
Wayne State University School of Medicine, Detroit, Michigan.
Pain Pract. 2010 Mar 2. [Epub ahead of print]


This study characterizes findings on sleep testing and Human Leukocyte
Antigen (HLA) markers in a group of patients with fibromyalgia (FM)
and chronic fatigue syndrome (CFS). One hundred eighteen patients seen
in a general neurology practice over 5 years meeting standard clinical
criteria for FM or CFS were analyzed retrospectively. Cases of
untreated sleep apnea or restless legs syndrome were excluded prior to
inclusion in this study. Ninety-two patients had multiple sleep
latency testing (MSLT). Seventy-three (80%) were abnormal by standard
criteria. Of 57 females having positive MSLTs, 22 (39%) had one or
more periods of sleep onset rapid eye movement (SOREM), and 5 of 16
(31%) males with positive MSLTs had one or more SOREM. Highly
fragmented sleep, as previously described in FM, was seen but not
analyzed quantitatively. HLA DQB1*0602 was obtained in 74 patients,
and positive in 32 (43%), P < 0.0001 compared with published values in
228 populations. In our patients, who presented with neuromuscular
fatigue or generalized pain, we found a sleep disorder characterized
by objective hypersomnia. Some patients had characteristics of
narcolepsy. Objective assessment by sleep studies can assist the
diagnostic process, aid future research, and provide rationale for

* * *
I was reporting that I slept only 2 hours a night.  Unbeknownst to me, the doctors were writing down that because I spent 20 hours a day in bed, I spent all 20 hours sleeping, and therefore did not need a sleeping pill.
Had they ordered a sleep study, they would have found out why I was constantly exhausted.  Oh, wait ... if they'd ordered a sleep study, they would have found out WHY I was constantly exhausted, and could no longer attribute it to depression.  They might have had to admit I was right and they were wrong.


Severity of symptom flare after moderate exercise is linked to cytokine activity

'Severity of symptom flare after moderate exercise is linked to
cytokine activity in chronic fatigue syndrome'

White AT, Light AR, Hughen RW, Bateman L, Martins TB, Hill HR, Light KC.
Department of Exercise and Sport Science, University of Utah, Salt
Lake City, Utah, USA.
Psychophysiology. 2010 Mar 4. [Epub ahead of print]


Chronic fatigue syndrome (CFS) patients often report symptom flare
(SF) for >24 h after moderate exercise (post-ex). We hypothesized that
SF is linked to increases in circulating cytokines and CD40 Ligand
(CD40L). In 19 CFS patients and 17 controls, mental and physical
fatigue and pain symptom ratings were obtained together with serum for
11 cytokines and CD40L before and at 0.5, 8, 24, and 48 h post-ex.
Before exercise, CFS had lower CD40L (p<.05) but similar cytokines
versus controls. In subgroups based on SF at 48 h, high SF patients
(n=11) increased in IL-1beta, IL-12, IL-6, IL-8, IL-10, and IL-13
(p<.05) 8 h post-ex. Low SF patients (n=8) showed post-ex decreases in
IL-10, IL-13, and CD40L, and controls decreased in IL-10, CD40L, and
TNFalpha (p<.05). Thus, in CFS, cytokine activity may vary directly
with SF, which may explain prior inconsistent findings.

Tuesday, March 16, 2010


Due to the rain storms and flooding that occurred in Westchester County, NY this weekend, the NY Medical Center is without internet service for several days. Dr. Medow's webinar on Orthostatic Intolerance will be postponed until March 25 at 12:00 p.m. (Eastern time). Please watch for new registration info. Sorry for the inconvenience.

NEI Center Awaits Passage in NJ Senate


15 March 2010

Media Contact: Corin Ramos, APR
714-970-2268; [email protected]

NeuroEndocrineImmune (NEI) CenterT Resolution awaits passage in New Jersey
State Senate

Senate Resolution 20 will establish first research center dedicated to
chronic immune disorders

CORAL GABLES, Fl.-(13 MARCH 2010)-A resolution encouraging the establishment
of the NeuroEndocrineImmune (NEI) CenterT , the first research center in the
state of New Jersey dedicated to understanding and treating chronic
neuroendocrineimmune (NEI) illnesses which includes Chronic Fatigue Syndrome
and Fibromyalgia, is currently awaiting passage in the New Jersey State
Senate. Late last year, a similar resolution (Assembly Resolution 202)
unanimously passed the New Jersey State Assembly 78-0.

Senate Resolution (SR) 20, sponsored by Senator Christopher "Kip" Bateman
(R), Senate Deputy Conference Leader, and Senator Loretta Weinberg (D),
Chair of the Senate Health Committee, cites studies that an estimated 20
million American adults and children suffer with NEIDs.

The economic impact and loss of worker productivity in the United States due
to CFS/ME, alone, is estimated to be over $9 billion per year. Chronic
illness represents 75% of all the health care costs in the U.S.

From Senator Loretta Weinberg (D)

"It makes sense to locate the NEI center in New Jersey. As the nation's
medicine chest, New Jersey is home to research institutions and private
businesses that can cooperate to find a cure for these debilitating

From Senator Kip Bateman (R)

"I look forward to the passage of Senate Resolution 20, solidifying
legislative support for the research center, and have high hopes that this
will, in fact, be a great step forward toward finding answers for the
sufferers of these debilitating diseases."

From Marly Silverman, Founder, P.A.N.D.O.R.A.

"On behalf of P.A.N.D.O.R.A. and Sandi Lanford from the Lanford
Foundation-LifelymeT, Inc., we urge the New Jersey legislators to pass SR 20
and be part of an amazing and pivotal moment in the history of the
neuroendocrine immune disorders communities. Your vote would demonstrate a
caring commitment to a community of patients who for the first time can look
forward to a brighter future."

From Veny W. Musum, Chairman, NEI CenterT

"The passage of SR 20 would be a moral and political victory for millions of
individuals stricken with neuroendocrineimmune disorders who have been
living far too long without the compassionate support, research and
treatment options they deserve."

Read the entire press release here: or visit <> 


Corin Ramos, APR
Walson Communications
TEL: 714-970-2268
Cell: 714-865-4147

Monday, March 15, 2010

Pain and Pills

 Are Doctors Too Reluctant to Prescribe Opioids?
            Decisions about a patient's pain treatment are now made much more collaboratively, but even in modern times, the process is fraught with moral judgment, stemming largely from the nature of available pain treatments and an incomplete understanding of how to use them.

            APA Gets Opioid "Addiction" Sorted Out
            A review draft of the American Psychiatric Association's latest Diagnostic and Statistical Manual of Mental Disorders finally eliminates perplexing "Substance Abuse" and "Dependence" disease categories and suggests replacing them with a new "Addiction and Related Disorders" designation. The more appropriate language and definitions will help to dispel unfounded fears and accusations of addiction for those taking opioid medications for pain.
* * *
The simple fact is that fewer than 1% of patients become addicted to pain meds, and most of them can be identified in advance because they have addictive personalities.  Not just a history of drug or alcohol abuse but becoming addicted to computer games, etc.  Weed out those people and give appropriate medication to those who can be trusted.

Exercise: Cause and Effect

  Dangerous exercise: lessons learned from dysregulated inflammatory responses
  to physical activity

  Dan Michael Cooper, Shlomit Radom-Aizik, Christina Schwindt, and Frank
  Zaldivar, Jr.

  J Appl Physiol 103: 700-709, 2007.
  First published May 10, 2007;

  Pediatric Exercise Research Center, Department of Pediatrics, University of
  California, Irvine, California

  Exercise elicits an immunological "danger" type of stress and inflammatory
  response that, on occasion, becomes dysregulated and detrimental to health.
  Examples include anaphylaxis, exercise-induced asthma, overuse syndromes,
  and exacerbation of intercurrent illnesses. In dangerous exercise, the
  normal balance between pro- and anti-inflammatory responses is upset. A
  possible pathophysiological mechanism is characterized by the concept of
  exercise modulation of previously activated leukocytes. In this model,
  circulating leukocytes are rendered more responsive than normal to the
  immune stimulus of exercise. For example, in the case of exercise
  anaphylaxis, food-sensitized immune cells may be relatively innocuous until
  they are redistributed during exercise from gut-associated circulatory
  depots, like the spleen, into the central circulation. In the case of
  asthma, the prior activation of leukocytes may be the result of genetic or
  environmental factors. In the case of overuse syndromes, the normally
  short-lived neutrophil may, because of acidosis and hypoxia, inhibit
  apoptosis and play a role in prolongation of inflammation rather than
  healing. Dangerous exercise demonstrates that the stress/inflammatory
  response caused by physical activity is robust and sufficiently powerful,
  perhaps, to alter subsequent responses. These longer term effects may occur
  through as yet unexplored mechanisms of immune "tolerance" and/or by a
  training-associated reduction in the innate immune response to brief
  exercise. A better understanding of sometimes failed homeostatic
  physiological systems can lead to new insights with significant implication
  for clinical translation.

  inflammation; innate immunity; leukocyte; asthma


  Free full text at:  

  [Tom: Somebody summarised this to me with the following "take-home" points:
  - exercise is a major stimulus of the immune system
  - very little research done on exercise in chronic inflammatory states (p.
  705) (which CFS likely has some components of)]

  I just had this e-letter posted. It's not very exciting. I'm hoping that
  others interested in the issue might get interested in ME/CFS.

  Editor said:
  We have sent your commentary to the authors and invited them to submit a

  Numerous exercise abnormalities been found in Chronic Fatigue Syndrome (CFS)

  One curious omission from this interesting review[1] is Chronic Fatigue
  Syndrome (CFS), which is also sometimes known as Myalgic Encephalomyelitis
  (ME). An abnormal response to physical activity is an essential part of
  widely used ME/CFS clinical criteria for adults[2] and children[3]. The most
  frequently used research criteria for CFS [4] require that patients, along
  with suffering from chronic debilitating fatigue lasting at least 6 months,
  have at least 4 out of a list of 8 symptoms, one of which is "postexertional
  malaise lasting more than 24 hours."

  There is a growing body of research on abnormal responses to exercise in
  CFS. A recent review[5] covers the issue in a fairly comprehensive manner -
  here's a summary: "Exertion induces post-exertional malaise with a decreased
  physical performance/aerobic capacity, increased muscoskeletal pain,
  neurocognitive impairment, "fatigue", and weakness, and a long lasting
  "recovery" time. This can be explained by findings that exertion may amplify
  pre-existing pathophysiological abnormalities underpinning ME/CFS, such as
  inflammation, immune dysfunction, oxidative and nitrosative stress,
  channelopathy, defective stress response mechanisms and a hypoactive
  hypothalamic-pituitary-adrenal axis."

  High rates of adverse reactions to graded exercise programs have been
  reported in patients with CFS - sometimes 50% or greater[6].

  CFS remains a fairly poorly understood condition. There is increasing
  evidence that CFS is heterogeneous and this heterogeneity could be of
  relevance to therapeutic programs involving exercise [7,8]. Those interested
  in researching abnormal responses to physical activity, including
  dysregulated inflammatory responses, could find much of interest if they
  chose to study CFS.


  1) Cooper DM, Radom-Aizik S, Schwindt C, Zaldivar F Jr. Dangerous exercise:
  lessons learned from dysregulated inflammatory responses to physical
  activity. J Appl Physiol. 2007 Aug;103(2):700-9. Epub 2007 May 10.

  2) Carruthers BM, Jain AK, De Meirleir KL, Petersn DL, Klimas MD, Lerner AM,
  Bested AC, Flor-Henry P, Joshi P, Powles ACP, Sherkey JA, van de Sande MI
  (2003). "Myalgic encephalomyelitis.chronic fatigue syndrome: Clinical
  working definition, diagnostic and treatment protocols". Journal of Chronic
  Fatigue Syndrome 11 (1): 7-36.

  3) Jason LA, Porter N, Shelleby E, Bell DS, Lapp CW, Rowe K, & De Meirleir
  K. (2008). A case definition for children with Myalgic Encephalomyelitis/
  chronic fatigue syndrome. Clinical Medicine: Pediatrics, 1, 53-57.

  4) Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The
  chronic fatigue syndrome: a comprehensive approach to its definition and
  study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med.
  1994 Dec 15;121(12):953-9.

  5) Twisk FN, Maes M. A review on cognitive behavorial therapy (CBT) and
  graded exercise therapy (GET) in myalgic encephalomyelitis (ME) / chronic
  fatigue syndrome (CFS): CBT/GET is not only ineffective and not
  evidence-based, but also potentially harmful for many patients with ME/CFS.
  Neuro Endocrinol Lett. 2009;30(3):284-99.

  6) Kindlon T, Goudsmit EM. Graded exercise for chronic fatigue syndrome: too
  soon to dismiss reports of adverse reactions. J Rehabil Med. 2010
  Feb;42(2):184; author reply 184-6.

  7) Jason LA, Corradi K, Torres-Harding S, Taylor RR, & King C. Chronic
  fatigue syndrome: The need for subtypes. Neuropsychology Review 2005, 15,

  8) Kindlon T. Stratification using biological factors should be performed in
  more CFS studies. Psychol Med. 2010 Feb;40(2):352. Epub 2009 Oct 12.

Asking some crucial questions

 Invest in ME

  Letter to UK Secretary of State for Health

  Recently Mrs Ann Keen, Under-Secretary of
  State for Health, commented that people
  with Myalgic Encephalomyelitis were not
  able to donate blood. Invest in ME have
  written the following letter to the Secretary
  of State for Health, Mr Andy Burnham.


  Myalgic Encephalomyelitis
  and Blood Donations

  Rt Hon Andy Burnham MP
  Secretary of State for Health
  Department of Health
  Richmond House
  79 Whitehall
  London SW1A 2NS

  cc: Mrs Ann Keen MP

  14th May 2010

  Dear Mr. Burnham,

  Recently Mrs Ann Keen (in her capacity as
  Under-Secretary of State for Health) made the
  following comments in relation to Myalgic
  Encephalomyelitis and blood donations -

  "People with myalgic encephalomyelitis
  (ME), also known as chronic fatigue
  syndrome (CFS), are not able to donate
  blood until they have fully recovered.

  The reasons for this are: first, blood
  donors need to be in good health, and
  people with ME/CFS often experience a
  range of symptoms which could be made
  worse by donating blood; and second, as
  the causes of ME/CFS are not currently
  fully understood, people with the
  condition are deferred from donating
  blood as a precautionary measure to
  protect the safety of the blood supply for

  Mrs Keen's comments are, we assume,
  representative of the government and your

  Firstly it is good that your government recognises
  that people with ME are in poor health. This implies
  that all people with ME are therefore in need of
  proper healthcare provision which treats the disease

  Secondly it is good that you and your government
  recognise, by the implication from your statement,
  that blood supplies may be compromised by
  accepting people with ME as donors due to the
  organic nature of this disease.

  Thirdly it follows that an embargo on people with ME
  donating blood would mean that there is an
  infectious agent at work which could be passed on
  via blood.

  There follows several questions
  which lead on from this.

  It seems to be crucial to use the most stringent
  diagnostic criteria available for diagnosing ME (which
  even NICE acknowledge as being the Canadian
  Consensus Criteria). Yet your department, NICE and
  the MRC do not standardise on this internationally
  accepted standard for diagnosis of ME.

  When you state that people with ME are not able
  to donate blood are you employing the NICE
  guidelines for defining patients as having ME?

  If so then why does NICE proscribe serological
  testing unless there is an indicative history of

  If no initial indication of infection is present then
  no further blood tests are performed and a
  patient may receive a diagnosis of ME based on
  ongoing fatigue and one other symptom such as
  sleep disturbance.

  Why then would those patients be excluded from
  donating blood?

  As your government officially accepts ME as a
  neurological illness, as described by the World
  Health Organisation ICD-10 G93.3 code, and as
  the issue of blood contamination from an infectious
  agent demands the utmost care and attention, is it
  not of absolute necessity for your government to
  demand that a consistent set of up-to-date
  diagnostic criteria are used as standard by all

  Your department often states that the Medical
  Research Council is an independent body. Yet as it is
  apparent that the MRC only funds psychiatric studies
  which presume that ME is a behavioural illness why
  does your department refuse to comment on the
  MRC's usage of the Oxford criteria for research into
  ME which expressly excludes people with a
  neurological illness?

  Why does your department not criticise the MRC for
  funding purely psychiatric research into ME if you
  fully recognise that ME is a disease of organic and
  infectious nature?

  Since when did a psychiatric illness prevent blood
  donations? Does this not clearly show the MRC policy
  of research into ME for the last generation to be
  completely flawed and a waste of precious funding
  and patients' lives?

  When you state that people with ME are not able
  to donate until fully recovered please can you
  define what "fully recovered" means?

  Could you also provide a description of how a person
  with ME is defined as no longer having ME?

  What biomedical tests are available to determine
  that a person with ME is "fully recovered"?

  Could you inform of how and when clinicians perform
  such tests in order to ensure that a person is "fully
  recovered" from ME?

  Bearing in mind the seriousness of a possible
  contamination of blood supplies from people with ME
  please could you indicate what measures are in place
  to ensure that doctors do enforce testing to ensure
  that people with ME are "fully recovered" and will not
  therefore donate blood?

  If such a test exists then presumably people with ME
  who are not recovered are entitled to appropriate
  benefits due to incapacity and/or disability?

  As relapses are common with people with ME please
  could you explain if there is any minimum period
  which a person with ME needs to be "recovered" to
  be able to donate blood?

  Could you also provide information which your
  government has on the number of people with ME in
  this country, the proportion of patients who have had
  ME for longer than five years and how many people
  with ME have *fully recovered*?

  With regard to your statement that *the causes of
  ME/CFS are not currently fully understood* is it not
  inherent on the Chief Medical officer of the UK to
  attend the 5th Invest in ME International ME/CFS
  Conference 2010 on 24th May in Westminster, as
  guest of Invest in ME?

  As the foremost experts on ME in the world are
  presenting at the conference, along with the
  Whittemore-Peterson Institute *who have recently
  been involved in the discovery of the XMRV
  retro-virus which has possibly huge considerations
  for the blood supply of this country* would it not be
  sensible for anyone who is involved in healthcare and
  particularly in the treatment of people with ME to
  attend this event?

  Should not the government of this country also be
  sending a representative to the conference given
  that contamination of the blood supply by people
  with ME may be occurring and that education about
  the disease needs to be a pre-requisite for anyone
  involved in healthcare provision for people with ME?

  We would request that you provide a full and
  complete answer to every single one of the
  questions which we have asked in this letter
  and we look forward to your reply,

  Yours Sincerely,

  The Chairman and Trustees of Invest in ME

  Invest in ME
  Registered UK Charity Nr. 1114035
  PO BOX 561, Eastleigh SO50 0GQ

  Support ME Awareness - Invest in ME
* * *

Sunday, March 14, 2010

March Webinar: Blood flow

Going With the Flow -- Blood Flow That Is

Please join us for our third 2010 Webinar!
Thursday, March 18, 2010
12:00 p.m. - 1:00 p.m.  (Eastern Daylight Time)

Guest Speaker: Marvin Medow, PhD, New York Medical College

It has long been established that many people with CFS experience symptoms like
light-headedness, dizziness, shortness of breath and other symptoms associated with upright posture, broadly called orthostatic intolerance. Is it possible that these symptoms could be connected to impaired blood flow, ultimately
reducing the amount of blood that flows to the brain? That's what researcher Marvin
Medow, PhD, and his team at New York Medical College are investigating with their
grant from the CFIDS Association of America.

Dr. Medow is a physiologist and associate director of the Center for Hypotension at New York Medical College, where he works with Julian Stewart, MD, a longtime
CFS researcher.

At this webinar, Dr. Medow will describe his study and the techniques his team uses
to measure blood flow and chemical changes that may explain many of the symptoms experienced by CFS patients. You'll learn more about orthostatic intolerance, tilt
table testing, transcranial Doppler and microdialysis. Suzanne D. Vernon, PhD, scientific
director of the CFIDS Association of America, will moderate the program.

This program is the third in the CFIDS Association's 2010 webinar series. To learn
more about webinars in general, please visit Past Association webinars are described and archived at

Participation is limited to 1,000 people. Please register now at


Our Mission:
For CFS to be widely understood, diagnosable, curable and preventable.

Our Strategy:
To stimulate research aimed at the early detection, objective diagnosis and effective treatment of CFS through expanded public, private and commercial investment.

Our Core Values:
To lead with integrity, innovation and purpose.