Published on January 31st, 2010 07:54 PM 0 Comments Transcribed by 'thefreeprisoner'
Review of XMRV in Chronic Fatigue Syndrome
David S. Bell MD, FAAP
Clinical Assistant Professor,
University of New York at Buffalo,
Buffalo, New York]
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
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
Absence of alternative explanation]
Described as Exhaustion weakness
Concept of Orthostatic Intolerance
Concept of Pre-Syncope
Not Simple Tiredness
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.
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.
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]
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]
XMRV is present in malignant prostate epithelium and is associated with prostate cancer]
Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science, 8 October 2009; 10.1126/science.1179052]
Data Reported at CFSAC meeting
68/101 XMRV DNA positive
30 of 33 had transmissible virus in the plasme
10 of the 33 had protein expression]
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.
DNA by PCR
Detection of viral proteins
Antibody to the XMRV envelope]
John M Coffin, Tufts University
Failure to detect the novel Retrovirus XMRV in Chronic Fatigue Syndrome.
E8519. doi: 10.1371/journal.pone.0008519]
186 Patient stored samples
XMRV or MLV not detected]
[If you missed it, part 1 of this transcription is here]
Also, we'll skip this slide which just shows the basic structural elements of the retrovirus.
Cuts Gag polyprotein to MA, CA, NC
Exquisite cleavage specificity.
Major classif... [undreadable]... Inhibitors]
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]
70% of Lymphocytes activated
Abnormal RNAse L
Decrease NK cell number and function
Activated T cells
Cytokines / Chemokines]
NK Cell function impaired
NK Cell numbers decreased
[graph showing how viral load increases as these go down]]
Allows infection / persistence of:
Herpes group viruses
Numerous other agents]
Symptom Production from Secondary Infection
chronic inflammatory changes
Inhibition of ATP production
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]
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.
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]
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]
I've never understood that paper very well [more laughter]
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:]
Xmrv Associated Neuro-immune Disease]
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.
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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!
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.
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.