While waiting for the chemical warfare on my brain conducted by a daily scopolamine analog (to prevent asthmatic bronchitis) and 2.5 mgm oxycodone at 3 AM (to stop the coughing so I can sleep) to be over; here are a few more thoughts on the subject. I’d love to be back reading Anslyn and Dougherty and retaining what’s in there, but not with what I’ve got on board. For what scopolamine does to memory see https://luysii.wordpress.com/2011/03/24/scopolamine-where-is-thy-sting/. Oxycodone is a narcotic — enough said.
There’s been a huge amount of controversy about the XMRV connection to chronic fatigue syndrome ever since the paper came out in October of 2009. People have had and continue to have huge difficulties reproducing each other’s results. For example, 4 papers reported 12/10 in Retrovirology implied that reports linking XMRV to CFS could be based on false positives (e.g. picking up mouse DNA or similar mouse viruses). At long last, the proper experiment is being performed. [ Science vol. 331 p. 17 ’11 ] Blood from 150 CFS patients and 150 controls from 6 geographically dispersed USA sites will be sent (blind) to several labs (to include the NIH, CDC and Mikovits) for testing. That should help explain the discrepancies (or further establish them).
While we’re all waiting with baited breath, suppose the work cited in the previous post is correct and that XMRV is a ‘new’ virus, created in the lab sometime in the 90s. It seems clear that it can infect man. Even if this is true it couldn’t possibly explain the cases I saw in the 70s and 80s. To which I say — So What ! ! It is most unlikely that chronic fatigue syndrome is one condition (more later). To get a flavor of how controversial the whole area (including whether the syndrome even exists as a nonpsychiatric entity) see http://pipeline.corante.com/archives/2011/01/11/xmrv_its_ugly_but_thats_science.php#comments along with 68 comments it brought forth.
First, a few unpleasant facts. No one who hasn’t worked in retail (say a supermarket) has any idea what the general public is like. Similarly, no one who who hasn’t worked in medicine has any idea of the clientele. Believe it or not, there are people who love being sick, or at least adopting the sick role. This behavior does not confine itself to workmen’s compensation or auto accidents where there is money involved. Much neurologic disease is obscure, with a variety of weird symptoms, so multiple sclerosis (MS) was a favorite refuge of some of these folks (in the pre-MRI era at least). For that reason, I actively discouraged my patients from attending MS support groups, because there was often someone there spewing medical garbage. “Should I have my teeth removed because fillings caused Mrs. Jones’ MS” etc. etc. Any disease for which diagnostic criteria are nebulous or undefined attracts these people. Chronic Lyme disease seems quite popular here in New England.
A true story: An ophthalmologist friend was trying to make some small talk with an octagenarian sent to him for a cataract. Opthalmologist: Well, Mrs. X. you must have done something right to be so hale and hearty at 87. Octagenarian: Young man, I’ve never had a well day in my life !
So I guarantee that in any group of of individuals claiming to have chronic fatigue syndrome, there are a few (probably around 5% but this is just a guess) who don’t have anything like it. That’s why any blood test which claims to be positive in 99% of patients with chronic fatigue syndrome simply has to be wrong. At some point a claim was made that 98% of patients with CFS had a positive test for XMRV. This doesn’t pass the smell test. To which I still say — So What ! !
If XMRV can cause only some CFS, this would still be worth knowing — particularly since antiretroviral drugs show some activity against XMRV (in cell culture, not (so far) in people). It would be the first time a viral cause has actually stuck. It’s certainly worth a look.
The last time you had the cold or flu you were probably fatigued. Fatigue is almost as common a symptom of infection as fever, and to look for a single cause of CFS is probably as quixotic as the pre-Pasteur physician looking for a single cause of fever. We know that multiple organisms can cause infections and fever, and it seems likely to me, that multiple organisms can cause chronic fatigue
This is somewhat reminiscent of the search for ‘the‘ schizophrenia gene. For details, see https://luysii.wordpress.com/2010/04/25/tolstoy-was-right-about-hereditary-diseases-imagine-that/. Schizophrenia has a myriad of genetic associations, each of which seems causative in a given family, but none of which are found in even 5% of cases. Well, schizophrenia is strongly hereditary and CFS is not, but the analogy holds.
Stay tuned.
Chemiotics II 
Comments
I can see you are trying to make sense of this situation but are missing the key bit of the puzzle and the history. Does this help? –
First, the difference between clinically diagnosed ME/CFS and “patients claiming to have chronic fatigue syndrome”. At the link here you will find the Canadian Consensus Criteria for ME/CFS http://www.cfids-cab.org/MESA/ccpc.html. This clinical definition is not focused on fatigue, is not vague, is not entirely subjective, does not easily allow overlap with other conditions; and is not something a person could “claim to have”. It represents the collective experience of hands-on clinicians.
You are correct that some CFS studies do indeed use “self report” or non-specific instruments to determine their study cohort. Here is a link to Prof. Jason’s study demonstrating how non-specific the CDC’s survey criteria are http://dps.sagepub.com/content/20/4/251.abstract.
Unfortunately the use of “self reported claims of having CFS” and non-specific survey instruments is not the domain of the patients. It is the domain of those research groups with a bloody-minded determination to define Chronic Fatigue Syndrome as general, vague condition with multiple causes. It is this issue that drives the rage of patients losing their lives to this condition. This issue predates XMRV by 20 years and the latter just happens to be the visible end of it right now.
So far all studies that have found murine derived viruses in CFS patients (eg. the original Science study, the FDA/NIH study, the Cornell University study) have looked at cohorts that reflect the clinical reality of the consensus criteria (or at least the Fukuda definition). One of the early negative studies (unbelievably) used patients “claiming to have CFS”, derived from a random telephone survey. And proclaimed this as “lack of association…of XMRV”
Hypothetical:- if a study of cancer and viral infections was published and you found out that the cancer patients were found from a telephone survey, would you take it seriously? And, would you trust a study looking for viruses that specifically excluded persons that showed signs of possible viral infection such as sore throat and tender lymph nodes would you take it seriously?
Neither do patients have confidence in the conclusions of research groups that make all sorts of technical claims, but can’t understand or deliberately ignore basic logic issues like the ones above.
Fortunately the quality of studies seems to be improving as you note. And fortunately there seems to be more involvement from researchers that demonstrate attention to detail by articulating the issues and seriousness of the illness. These are trusted.
“Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease
and CFS” http://www.cfids.org/research/proteome-analysis.pdf
http://news.stanford.edu/news/2007/january10/med-fatigue-011007.html
Peter W — thanks for taking the time to respond. A few thoughts.
Clinicians deal with the world as it presents itself to them. When did these criteria come out? Even if a patient didn’t meet a variety of criteria, but just said they felt tired all the time, no energy, the doc would never say anything like — “you don’t meet the criteria” and refuse to look at them or try to find what’s wrong (but presumably they wouldn’t write papers about the rejects). Hopefully the diagnostic criteria (met or not met) of all 150 individuals with CFS and controls are quite explicit and available to all.
Hopefully the criteria for CFS are like most diagnostic criteria — somewhat elastic, with inclusion if a just certain number of them are satisfied. People can have a condition so mild it escapes their notice. I recall one patient with myotonic dystrophy wheeled into the clinic by a cousin who had a very mild form and didn’t realize it.
Dear ???? (I’d settle for any name),
It’s been many weeks. And I’ve been *very* busy. I would like to respond to your reply. But first, is this on the radar or too old?
Peter W
As far as names go call me Luysii (or Ishmael). Not too old at all, but before doing so have a look at https://luysii.wordpress.com/2011/03/25/evil-scientists-create-virus-causing-chronic-fatigue-syndrome-in-lab/
XMRV was not created in the 90’s. The people that are claiming they think it was, do not have a sensitive enough assay, and the earlier generations of the cell line 22Rv1 are infected. The later ones were treated with hormones that increased the viral titre dramatically, so there assays could detect it. The biggest spanner for this odd belief is that 22rv1 actually does not contain XMRV. It contains a virus like it, but it is not XMRV. The env region is only 30% homologous.