Results: Participants hoped referral to a specialist service
would clarify diagnosis, give guidance and support, assist in
understanding the complexity of the illness and provide hope for the
Thank god someone did a peer-reviewed study for this! Imagine we would have to guess what a patient wants and expects, when he is being referred to a specialist!
While participants hoped that the service would be able to provide
information and guidance, many expressed the view that more information
earlier in their illness would make the waiting period less stressful
and make it possible for them to do more to help themselves.
Conclusions: GP referral to a specialist service appeared to be
highly valued by the participants in this study. The levels of
uncertainty expressed by many patients about the nature of CFS/ME raises
the issue of the role of information on CFS/ME during the early stages
of the illness and suggests a need for more reassurance and positive
advice during the waiting period.
So patients want to know what's wrong with them? They want to get some form of help, any form of help actually, when they go to their doctor? Even if it only is information, reassurance and "positive advice"? What a strange world we live in.
Herpes Zoster Preeruptive Phase This phase is characterized by unusual skin sensations or pain within the affected dermatome that heralds the onset of lesions by 48-72 hours. During this time, patients may also experience other symptoms, such as malaise, myalgia, headache, photophobia, and, uncommonly, fever.
Dr Nancy Klimas said: “The most compelling finding was that natural killer cell cytotoxicity in chronic fatigue syndrome was as low as we have ever seen in any disease. This is very, very significant data with very, very low levels of lymphocyte response to mitogens….The actual function was very,very low – 9% cytotoxicity; the mean for the controls was 25. In early HIV and even well into ARC (AIDS-related complex) NK cytotoxicity might be around 13 or 14 percent….Chronic fatigue syndrome patients represent the lowest cytotoxicity of all populations we’ve studied”
CFS Central: In your prostate-cancer study, “XMRV is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors,” you found 4 percent of healthy controls with evidence of XMRV. If you’re finding a background rate in controls in your prostate-cancer studies, why do you think you didn’t find a background rate in CFS patients and controls?
Singh: Not entirely sure, but there were different assays (e.g. immunohistochemistry) and different sample types (blood vs prostate tissue).
CFS Central: Will you revisit your prostate-cancer XMRV findings in light of this XMRV negative CFS study? From what you’ve learned in this latest CFS study, do you now believe that the XMRV that you found in prostate cancer is a human infection or just contamination?
Dr. Ila Singh: Prostate cancer and chronic fatigue syndrome are completely different illnesses. I recognize that recent studies have cast doubts on the prostate cancer association as well, but there is still considerable data supporting the link to prostate cancer that cannot be easily explained by contamination. We will present some of this work at the Cold Spring Harbor meeting later this month. But clearly more work needs to be done before that question can be settled.
CFS Central: Did you test the new assays/methods used in the new study against any XMRV positive samples from your prostate-cancer study?
Singh: Our prostate cancer study was entirely on prostate tissues. These were archived in tissue banks in a de-identified manner, so there was no way to go back to those patients and obtain blood samples. So, we could not test some of the new tests we developed on our material from prostate cancer patients.
CFS Central: Do you believe scientists should be looking for XMRV in CFS patients’ tissues instead of blood?
Singh: The original study by Mikovits' group reported finding XMRV only from blood. They did not examine other tissues. So blood is where the focus should be. Now if one found it in blood, then of course you'd be interested in finding out where else the virus is. And then it would be interesting to look at tissues. But looking at tissues is not trivial and not something to be attempted without good evidence of the virus being present in the body first.
On the tissue question is where I disagree a bit with Singh. Yes, it's difficult, but both Mowbray and Chia found entereoviruses in the tissue, with Chia emphasizing that you can make only reasonable findings in tissue.
So, how ubiquitous are those endogenous mouse retroviruses? OK, I think I am confident that there is no trace of XMRV in the peripherial blood (and that most, and maybe all of WPI studies are actually at some point contaminated). But I am not completely confident that retroviruses other than HIV are not present in the general population. What about XMRV and prostate cancer? What about MMTV and human mammary cancer? And are there other (mouse) retroviruses? What about vaccines grown in animal tissues, do/did they contain endogenous retroviruses that could infect humans? What about the macaque studies, that show that XMRV goes in the tissue and hides in lymphocytes? Does XMRV stay there, or gets it cleared over time?
In his Medical
Address at the AGM of the ME Association on 25th April 1987, James
Mowbray, Professor of Immunopathology, St Mary’s Hospital Medical School, London,
said: “When we meet a new infection…the first thing we do is to make IgM
antibodies and then in a matter of a few weeks we switch over and make IgG
antibodies (which) last for a long time and protect us. If someone has IgM
antibodies they have either been recently infected or they are still
infected….We developed a technique using a specialised antibody…which detects a
protein in enteroviruses which is the same in all 72 enteroviruses (and) we can
use that antibody to look for the virus protein in the blood. Doing that, we
have been able to find a very large fraction of the ME patients have got an
enterovirus antigen….Just because you find virus proteins in the blood, does
that mean they are infected? Yes, it does….The virus is present in the
intestine. It is also shown to be present in the muscle….Here is a muscle
biopsy where you see the dark brown infective muscle cells, where the probe has
bound to the virus genes in the muscle cell. (There are) two ways which
demonstrate that in the muscle (in) a patient with ME, there is an
enterovirus….What does it do in the muscle?….(It) does the thing that viruses
usually do, they infect the cell and take over…saying ‘You must switch off all
your genes and read only my genes’. So (the virus) switches off all the genes
that produce energy to the cells….The virus is being made and is switching
off host genes stopping the cells’ own energy production. If you now exercise,
you rapidly run out of energy in the muscle and that has been shown by
sophisticated techniques….Whilst (the virus) is there, it severely
limits the ability of the muscle to work….The thing that seems to make it worse
is exhausting the muscle….Sufferers know, they have a kind of feeling for
it, especially as time goes on, about what is going to be too much….When you
have got the disease it is a good basis for saying do not use up all the muscle
energy, do not get to that stage. It may lead to more virus affecting that
muscle….It is clear that it is not only exhaustion in the muscle but also in
the brain….Either muscle or brain overdoing it is the same….if you live
within the limits of the disease while you have got the disease, I think you
will do much better and we have now got some good scientific background”.
So it's either another virus in CFS, or it's protein that is produced in CFS patients (and not in healthy controls), as a result of some disease process. ASFAIK, the WPI uses different antibodies than Singh does. We'll see where this goes.
First Dr. Singh tested 36 uninfected LnCaP cells used for culturing and found two of them were positive for XMRV using the WPI’s nested PCR but not with her qPCR or the IAP test. (Since they had not been infected with XMRV all should have been negative). Then she began to test different components of the actual test itself and found that two enzymes (Taq polymerase and Platinum Taq polymerase from Invitrogen) tested positive for mouse DNA. When she began testing different batches of the polymerases she found that four different batches were contaminated. Repeated testing of another polymerase from Amplitaq, on the other hand, indicated that it was clean. … Except for handling (ie testing) samples more frequently they were unable, however, to come up with a good explanation for the strikingly different PCR results between the healthy controls and the patients in the original study.
That is my biggest fear, that the serology tests at the WPI have the same testing bias, that CFS patients are tested until something is found while controls are tested only once.
The "worst case" scenario for me is at the moment: Most of the WPI and Redlabs research (mainly PCR and culture) is based on contamination at some point (not necessary in the lab). With a low false positive rate and maybe a testing bias towards CFS patients (are CFS patients tested until they find it? Does this explain the waxing and waning? Do they test the controls the same way until they find something?). But what irks me is the WPI serology/antibodies work: Is there crossreactivity to some other retrovirus? Be it endogenous or exogenous?