One of these things is not like the others. One of these things just doesnt belong. Can you tell which thing is not like the others, by the time I finish my blag post?

#1– Chronic Fatigue Sufferers Find Vindication in a Virus
News that chronic fatigue syndrome may be linked to a virus has been met with excitement by many sufferers whose symptoms and sanity have been doubted over the years.

#2– Is a Virus the Cause of Fatigue Syndrome?
The new report has intrigued scientists, been seen as vindication by some patients and inspired hope for a treatment.

“I just feel like the whole future has changed for us,” said Anne Ursu, 36, a writer living in Cleveland who has had the syndrome in the past.

#3– We have been vindicated by this breakthrough, say ME sufferers
Peoplw who have suffered from Chronic Fatigue Syndrome say they have been “vindicated” after it was discovered the condition may be linked to a virus.

Ian Logan, chairman of the Worcestershire ME Support Group, said the findings would be important to all people affected by the debilitating condition, after years of being told it was depression or even that the condition was all in their head.

#4– On the track of an elusive disease
Patient advocate groups seized on DeFreitas’ work as the ultimate proof that CFS was not a psychiatric illness but one with a known cause.


Did you guess #4?

If you did, youre right!

In 1991, researchers at the Wistar Institute (lol, Wistar), found a retrovirus like HTLV-II in the blood of patients with CFS, adults and children.

They got a PNAS paper out of the deal.

CDC/NIH totally freaked they were so excited.

… And no one has been able to replicate the 1991 results, including Jay Levy (retrovirus GAWD).

What was the ultimate conclusion of “OMFG HTLV-II–>CFS!!!AAAHHH!!!”?

It now seems clear that the media’s enthusiasm was, at the very least, premature. Even DeFreitas doesn’t claim to have pinned down HTLV-II as the cause of the puzzling syndrome. And among other virologists, her team’s findings are meeting a markedly cool reception, both because they are so sketchy and because several other viruses have been proposed as the cause of CFS only to fall by the wayside under closer scrutiny.

Im not saying XMRV doesnt cause CFS. Im saying that XMRV–>CFS might be more snipe hunting, not vindication.

Comments

  1. #1 Optimus Primate
    October 20, 2009

    And to think, I can’t recall ever having heard of XMRV before a week or so ago. Now it’s everywhere. XMRV has gone viral! :P

  2. #2 Eric Johnson
    October 20, 2009

    It’s certainly more than fair to point this out. Vindication-themed stories have also been seen in the media, in recent years, upon publication of gene expression data – whose broad repeatability probably remains to be seen. It’s just an emotional angle the media likes.

    Disconfirmation happens, heaven knows. It’s worth noting that the XMRV results were already repeated by the Cleveland Clinic as a part of the Mikovits publication, which I don’t think was true for the DeFreitas paper (I have only skimmed it).

    I don’t know of any other apparently-false alarms in the past that had about the same salience, or higher, as the DeFreitas paper. If someone can correct me on that I will fess up that I have been duly convinced and edified.

    Obviously, we won’t know for, I donno… eight to twenty months (wild guess)… just what is going to happen when other labs take this Mikovits thing for a spin.

  3. #3 gf1
    October 20, 2009

    It’s sad that for many people, unless there’s evidence of a physical illness, CFS patients should be condemned. That so many ill people feel the need to be vindicated of the arguments from ignorance that are normally imposed upon them is a testament to the medical profession’s failure to live up to the philosophical underpinnings of science in this case.

    I’d be surprised if a single virus was the cause of all cases of CFS, but that doesn’t make it reasonable to conclude that those without a known physical cause must be psychologically ill. We should expect those arguing for a psychological cause to present their own evidence, rather than accept it as the default position in the absence of compelling evidence either way.

  4. #4 Eric Johnson
    October 20, 2009

    gf1,
    Yup. Just look at the history of the perception of migraine, look at the history of the perception of narcolepsy.

    The destruction of 500,000 hypocretin-secreting neurons in narcolepsy is a minute event. It does not change your blood chemistry. It doesn’t really do much of anything except make you fall asleep all the time. Narcolepy has an extremely robust association with an MHC allele, but serological MHC typing was not used in man until the 1950s. Before that, the disease had no physical correlate and a psychogenic school was prominant.

    And yet, decades before the hypocretin basis of narcolepsy was even discovered c. 2000, lots of people already “knew” that a disease with no known physical explanation had to be fake. Apparently they just knew it all when it came to fairly simple human organs like the brain and the immune system.

  5. #5 daedalus2u
    October 20, 2009

    I think the association with virus is likely to be real but non-causal. I don’t think the virus causes CFS, I think what causes CFS is a persistent low NO state which then allows for virus to persist at higher levels in PBMCs. I think this is very similar to the increased levels of mycoplasmas also found in PBMCs of CFS patients. The clearance of intracellular debris (including mycoplasmas) is by autophagy, and this is triggered in PBMCs by increased ATP levels. The ATP level is controlled (in part) by the NO level (NO and ATP co-modulate sGC). Low NO levels will reduce clearance of intracellular infectious agents including mycoplasmas (and likely viruses too).

    There is plenty of evidence to show that CFS is a real condition and not psychosomatic. I subscribe to the low NO hypothesis which I have described here.

    http://www.chronicfatiguetreatments.com/wordpress/treatments/chronic-fatigue-syndrome-nitric-oxide/

    In the brain during neuroinflammation, the low NO causes low ATP and reduces intracellular transport by ATP powered motors (i.e. transport down the axons). This shows up as reduced proton diffusion on MRI, as “white matter hyperintensities”. The cargo being moved up and down the axons entrains water and that shows up as anisotropic proton diffusion. White matter is mostly axons, so with less ATP, the movement is slowed so there is less apparent proton diffusion. This is non-linear and pretty complicated too. NO is the link between low O2 consumption, low blood flow, low ATP, neuroinflammation and white matter hyperintensities observed in essentially all neurodegenerative diseases (including neurosyphilis). Fever therapy resolved the symptoms of neurosyphilis by resolving the neuroinflammation.

    I discuss the physiology of that in some detail.

    http://daedalus2u.blogspot.com/2008/01/resolution-of-asd-symptoms-with-fever.html

    NO is a neurotransmitter, and also mediates vasodilation. The prompt vasodilation observed in the BOLD fMRI imaging is undoubtedly due to neurogenic NO release. NO is unique as a neurotransmitter, in that it is freely diffusible through lipid membranes. All NO sensors only “sense” the sum of NO from all sources, including the basal level. When the basal level is changed, that changes the range, onset time and duration of all NO mediated signals. In the case of the vasodilation observed with BOLD fMRI and which is considered to be a precise measure of functional connectivity, the range, onset time and duration would change with the basal NO level too.

    It is my hypothesis that changes to the basal NO level that occur with neuroinflammation (inflammation lowers NO levels) or fever (fever raises NO levels) changes the functional connectivity and so changes the properties of the brain producing the characteristic symptoms. This is non-linear and quite complicated. The brain fog that often accompanies CFS is likely due to this.

  6. #6 Sili
    October 20, 2009

    It works both ways, though, Eric.

    My depression is treated with medication that alter my brain chemistry. But that only deals with a symptom of my illness, and its primary function has been to make me well enough to focus of on therapy. The sessions with the psychologist has been the real cure.

  7. #7 HvS
    October 20, 2009

    Not analogous. Cleveland Clinic has already replicated the Mikovits results and Silverman at CCF had no horse in the race whatsoever.

  8. #8 RobRed9
    October 20, 2009

    i read with some fascination the comments on this story on the New York Times website. People who ID as CFS patients are simply ecstatic about this latest virus claim. One wrote, “I’ve been dancing about for days.”
    If you’re a CFS patient and you’ve been dancing about for days as the result of a reported scientific discovery, that should give you a clue that your condition may be caused by more than a polytropic mouse retrovirus. Something in your brain. After all, the virus should be in your blood, sapping your energy by unexplained mechanisms, before during and after the discovery.
    It’s obvious what doctors should do. Make a new report about a CFS virus or bacterium or fungus every few months, giving CFS patients a burst of energy. Let excited patients demand expensive tests and treatments and indulge them. Act surprised when shit doesn’t work out. Announce a new discovery before they can sink back into malaise.
    Like ERV i don’t say the retrovirus has no relation with CFS, but i’m also skeptical. First because how the heck do you diagnose CFS? By exclusion. Just like how many similar conditions? It’s not a distinct diagnostic entity, you can pretend it is but it is not. Second because when an author publishes 67% in Science and then says over 98% in interviews, i think hype. Third because this discovery is from an institute with a tiny little stake in finding an infectious cause. Fourth because i think PLoS Pathogen reviewers obviously thought Silverman’s stuff about prostate cancer could be contamination, and the largest latest study didn’t find one example of the virus in prostate cancer. Fifth because the only reason why they tested for the retrovirus was a controversial connection to an IFN pathway enzyme and all articles on the enzyme in CFS are from one lab.
    i wanna see a lot more independent confirmation of this stuff.

  9. #9 Felix
    October 20, 2009

    RobRed9, Get a grip! Not everything people say is meant in literal terms. Being a young person who has CFS I have also been “dancing about for days”. Listen….until now the only people who knew the gravity of this disease were the people that had it. Thats because it is invisable to the outside world. We have fevers, swollen lymph nodes and a great deal of pain. Personally, I don’t go around telling everyone this as I do have some dignity. It is very hard for people to understand the gravity of this disease without feeling it. We are sick and it is not in the head. I was in the best shape of my life with lots of plans when this thing hit me hard. I am only 39 years old. I am also waiting for more independent confirmation. Until then I think people should stop talking and have a little respect for those of us who are suffering.

  10. #10 Sili
    October 20, 2009

    Some people obviously go a bit overboard, but I think it’s fair to say that most of us do understand that you’re suffering.

    But we still reserve the right to be highly skeptical of this syndrome being 1) having the same cause for all sufferers, 2) being due to any sort of infection.

    That is not to say that it shouldn’t be investigated, of course.

    (And if anyone refuses psychological treatment and therapy upfront, because “there’s nothing fucking wrong with my head”, I’ll reserve the right to being rather disdainful of their commitment to discovering what’s wrong with them. Again I’m not saying that it is psychosomatic in all cases, but if the patient refuses to even let it be investigated whether it is in their case, then fuck ‘em.)

  11. #11 anonymic
    October 21, 2009

    These CFS blogs are so much better if you see Chicken Fried Steak instead of Chronic Fatigue Syndrome.

  12. #12 Eric Johnson
    October 21, 2009

    Rob, be serious. By your logic, emaciated AIDS patients should not have experienced any elation when the effectiveness of new treatments was published.

    Sili, do you have actual data on Chicken Fried Steak patients rejecting talk therapy? If not, then whose assurances are you relying on? I wonder whether you are prepared to actually defend, with data and strict scientific inference, your basis for saying “fuck you” to a bunch of people. A lot of patients have undergone talk therapy. I don’t dispute that some have resisted it, though without numbers we don’t know the salience of the phenomenon.

    Are you considering that people have limited money and ability to travel, and are used to seeing doctors that offer them nothing helpful, or completely reject them? Suppose you had severe flu-like feelings for three months on end. What would you think of being referred for talk therapy focused on cycles of negative thinking? Would you think that would be effective? Suppose you have no choice but to attempt to get a disability pension, do you think receiving a psychogenic diagnosis made without strict scientific inference would be helpful for your future? Suppose you are engaged in social conflicts with an employer or family member about whether you are really sick? You need not accept the decision of /some/ patients to reject talk therapy (nor do I demand that you shed tears for them), but you should probably admit that their reaction to an ineffective therapy does have some logical coherence if you assume the patient really does feel flu-like.

    Where’s your evidence that talk therapy is effective for CFS? That is a highly controversial proposition. A number of studies showed the contrary. The objective evidence that it is even effective for depression is limited:
    http://neurocritic.blogspot.com/search?q=cbt

  13. #13 Eric Johnson
    October 21, 2009

    ‘Scuse me, I meant to indicate only the first of the two Neurocritic posts seen at the above-linked page. That is, I meant to indicate this post.

  14. #14 gf1
    October 21, 2009

    sili,

    I think you’ve been misled about the way CFS patients tend to respond. There was a very misleading piece on ‘Science Based Medicine’, which lied about what the CDC says about CFS, and seemed entirely driven by the writer’s personal prejudices – I think I’ve seen you mention that before. Every claim made in that article should be checked, and not taken on faith. Please look at the CDC website rather than trust that quackery.

    That piece, and the deceptions contained within, may help you understand why many CFS patients do respond poorly to their Drs. It seems sadly acceptable within western medicine for doctors to rely on their prejudices when it comes to poorly understood illnesses like CFS, and then pretend they have the weight of ‘science’ behind them. It is not fair to blame seriously ill patients for responding badly to this.

  15. #15 Eric Johnson
    October 21, 2009

    The “Science Based Medicine” article was not referenced. Something that isn’t referenced to real data can certainly be worthwhile; what it can never be is authoritative.

    In a lot of ways, though, I have to sort of respect the author of that piece, overall. He put some quantitation where his mouth was (if not money), giving 20% odds to the XMRV thing being replicated, which basically amounts to admitting he thinks there is a 20% chance the disease is bona fide. At least sometimes, he used evidence and strict inference. He was fairly clear about his logic.

    He did say a few things that I do not have any respect for.

    the [emphasis added] current opinion on the nature of CFS and its other forms – somatization” – not true. Somatization is not a majority opinion.

    “the century-long identified history of mood disorder” – false. There is not conclusive evidence for any common disease such as depression being psychogenic.

    “the sudden epidemic-like spread acted as much like a mass psychogenic illness as it did an infectious disease” – there is no scientifically proven case of mass psychogenic illness, proven to the extent that it is a scientific “fact” in the common usage of the term.

    There were a few more objections but I’m not gonna go on. It seems like this guy is used to spiking lousy BS medicine and promoting evidence-based medicine. That’s cool. But he almost treats research as if it were medical practice, suggesting researchers should stop studying CFS physiology since they haven’t found all that much over 20 years. Well, there is no such thing as evidence-based research or research-based research; research is the search for evidence. You do use prior research to make a case that your research is worth doing – but obviously you don’t “prove” that your hypothesis will be proven true if you can just get funding.

  16. #16 gf1
    October 21, 2009

    The SBM piece doesn’t source much, but does say: “CFS uniformly spontaneously resolves over time. According to CDC, almost all cases are resolved by three years, although there are many of longer record.”

    The CDC website says:

    Recovery from CFS

    •CFS affects each individual differently. Some people with CFS remain homebound and others improve to the point that they can resume work and other activities, even though they continue to experience symptoms.
    •Recovery rates for CFS are unclear. Improvement rates varied from 8% to 63% in a 2005 review of published studies, with a median of 40% of patients improving during follow-up. However, full recovery from CFS may be rare, with an average of only 5% to 10% sustaining total remission.

    So the one sourced piece of information turns out to be bullshit.

    He may not source his other assertions, but the fact he goes on to present controversial and minority viewpoints without any supporting evidence as if they were part of an accepted medical consensus is not to his or SBM’s credit imo. The logical development of prejudices and instinctive beliefs does not serve to make them any more respectable or evidence based.

    I think CFS patients would be better off visiting a crystal healer than Wallace Simpson, and that surely serves to discredit SBM’s fight against nonsense. Doctors like this are as much to fault for the rise of nonsense treatments as those who peddle them.

  17. #17 Eric Johnson
    October 21, 2009

    > I think CFS patients would be better off visiting a crystal healer than Wallace Simpson

    Probably. It’s kind of interesting that no psychogenic approach has ever been radically effective or even moderately effective in treating any non-rare disease when studied rigorously against placebo; at best it has been quite mildly effective. Also interesting is the two-part Rosenhan experiment(s). The second experiment is really a fairer deal than the first, and is immune to the complaints from Spitzen quoted in that article.

    Psychology – and the “conversion disorder” idea coming from that fantastic scientist Sigmund Freud – sure is some evidence-based medicine.

    As for the other thing, bullshit would be fair. Many of those natural history studies were based on the CDC surveillance criteria. Surveillance criteria are necessarily strict. Many people are totally incapacitated without meeting those criteria, which require certain minor symptoms such as sore throat. Assuming the nature of the disease is rather invariant, there is no need for surveillance definitions to capture every case or even a majority: even if they identify only 10% of cases, comparisons of the incidence of the disease at various places and times will still be valid, relative to one another.

    In fact, only a small minority of patients get 90% better or more, and 90% is certainly a rather broad definition for “complete recovery” or “resolution of disease.”

  18. #18 daedalus2u
    October 21, 2009

    The piece on CFS in SBM was unfortunate. There really is quite a lot of data in the literature suggesting that CFS is a real syndrome. My research suggests that it is due to a changed setpoint; that is that there is nothing “wrong” with the various control systems that are regulating physiology, just that they are operating at the “wrong” setpoint.

    In particular, the “setpoint” for how many mitochondria you have is something that is pretty important. We know that the mitochondria number setpoint changes, essentially the only difference between someone in excellent aerobic condition and someone who gets fatigued walking up stairs is their capacity for aerobic ATP production. That aerobic ATP production is only produced by mitochondria, and the number of mitochondria in each cell is regulated by that cell. If the number is too low, the cell can’t make enough ATP to keep up with what physiology calls on it to do; when that cell is a muscle cell, not enough mitochondria results in exercise intolerance. The muscle is just as strong (it doesn’t take much ATP for static strength), but there is no endurance (because it is ATP production rate that is impaired).

    If the “setpoint” for the number of mitochondria was reduced, the resulting mitochondria depletion would mimic the symptoms of CFS if the tissue compartment was skeletal muscle. If the tissue compartment was the liver, it would mimic the symptoms of HAART liver failure. HAART reduces mitochondria biogenesis by interfering with mitochondria DNA replication.

    Once you get into a state of insufficient mitochondria, it can become self-sustaining because fewer mitochondria produce the same ATP but at a higher mitochondrial potential with more “slip”, while generating more superoxide and at reduced efficiency. The superoxide destroys NO and reduces the basal NO level. NO is what triggers mitochondrial biogenesis, so this ends up being self-sustaining. The reduced efficiency in ATP production shows up as a “hypermetabolic state”, where it takes greater O2 plus substrate to maintain basal metabolism. The amount of ATP needed is the same (or even less), the efficiency of that ATP generation is reduced, and it is only substrate consumption that is measured.

    The hypermetabolic state of HIV lipodystrophy is due to this same mechanism too. There are not enough mitochondria to generate ATP via oxidative phosphorylation, so the body uses glycolysis. There are not enough mitochondria in the liver to recycle the lactate via the Cori cycle, so the body disposes of it where ever there are mitochondria by making ectopic fat, in the liver, in the skeletal muscle, where ever there are mitochondria to consume the reducing equivalents of lactate.

    “Stress” makes CFS and HIV lipodystrophy worse because “stress” lowers the NO level and reduces mitochondria biogenesis even more. Stress reduction might make CFS and HIV lipodystrophy a little better, but unless the mitochondria number is high enough, the hypermetabolic state will persist and so will the exercise intolerance.

  19. #19 bonafide
    October 21, 2009

    Whittemore Peterson Institute: October 17,2009
    Facebook

    “XMRV is strongly linked to patients with ME/CFS. This initial finding was confirmed in three different laboratories, the National Cancer Institute, the Cleveland Clinic and the Whittemore Peterson Institute.
    Patient samples were donated from different locations around the US. This was not one cohort. All patients met the Fakuda and Canadian definitions for CFS and the study included age and sex matched controls with zip codes but Science did not feel that information was important to this publication. Not all patient samples that were positive had the biological markers of low NK cell function and RNase L defect.
    The importance of this finding is two fold. One that XMRV is an infectious retrovirus found in significant numbers in the blood of people who are ill with CFS and only in a very few without symptoms of ME/CFS. Number two is that it was found in 4% of healthy controls which means that 10 million Americans may be infected with this retrovirus.
    What you ultimately call this disease is not important. We must now try to understand how this virus is acquired and how that relates to disease and immune deficiencies. Human infectious retroviruses are not ubiquitous or benign. This virus should not be confused with benign endogenous retroviral particles that we all have in our genome. This is only the third human infectious retrovirus found to be replicating in the blood of humans to date, the other two are HIV and HTLV-1 & 2. It is a gamma retrovirus not a lenti retrovirus which means it is a simple vs. a complex retrovirus.”

  20. #20 XenoBiotic
    October 21, 2009

    Can someone explain to me why do many people on CFS have T4 cell count drop while others have T8 count drop??
    Also is it possible to have CFS with normal NK cell counts?? I have known many sufferers who display low NK cell count. Also others display other immune parameters being affected, most seem to have low sIGA (salivary IGA) and low IgMs.

    How is this immune response and findings so variable?? I really would like an experts voice here (someone who not only studies but also likes immunology coz i dont haha)

    Last but not least, is l-RNAse THE MOST important finding in CFS sufferers or can one have viral CFS without it?

    DO these variable immune responses i stated above have anything to do with potential differend viral strains affecting an already XMRV positive individual? Say for example someone is superimposed with CMV + XMRV while next one is CMV+EBV+XMRV or Coxsackie+Parvovirus+XMRV, does this alter the immune counts in different ways or is it more related to the individuals immune response??

  21. #21 daedalus2u
    October 21, 2009

    bonafide, so far there is only an association. A causal connection has not been demonstrated. A causal pathway has not been suggested. There have been similar findings of an association of mycoplasmas infections with CFS and fibromyalgia compared to controls.

    http ://www.ncbi.nlm.nih.gov/pubmed/12879275

    This paper shows multiple infections by a larger diversity of bacteria and HSV6.

    http ://www.ncbi.nlm.nih.gov/pubmed/12887507

    I suspect that the CFS state simply allows for greater persistence of viruses and bacteria in the blood. I suspect that if you look hard enough at a CFS cohort you will find an excess of just about every kind of blood borne infectious agent.

    I think Abbie’s comments on how leukemia is not observed in CFS, and that infection with XMRV does tend to cause leukemia is significant. I think it is way to early to be jumping on this as a path to a cure.

  22. #22 XenoBiotic
    October 21, 2009

    Also can someone just with a single virus or combos (without XMRV however) like a single herpesvirus HHV6,EBV or enterovirus display such an ongoing suppression in his immune profile like a CFS patient?? Since 90% of individuals test positive for EBV antibodies does that mean that XMRV is the key that opens the door to all the rest of viral agents to do their damage??

    How is it possible for EBV affected individuals to have reactivation of the viral symptoms after exercise. Is it only EBV+ patients who suffer like this. I know CFS patients with CMV+enteroviruses who can exercise and feel better afterwards yet they suffer from DOMS (delayed onset muscle soreness). However they can still exercise but display all the rest of findings, IBS, cognitive impairement, recurrent infections, headaches, slight metabolic problems and others.

  23. #23 Eric Johnson
    October 21, 2009

    Well, we don’t necessarily know yet that viral CFS, as you put it, exists. But the WPI says at their Facebook page that some of the XMRV+ subjects in their study had normal RNase L and normal NK cell /function/ (not counts). I don’t know if any subjects were normal for /both/ those parameters.

    I have my doubts about the other immune abnormalities you mention. Do you have any refs for that stuff? It’s all fun and games until the refs come out and disconfirming refs are searched for.

  24. #24 bonafide
    October 21, 2009

    daedalus2u, I just pasted a WPI Facebook entry, without comment. It’s interesting that Science thought that independent replication at three sites and matched controls were not important.

  25. #25 HalfMooner
    October 21, 2009

    Isn’t it wonderful that sometimes all it takes to save a life is a goofy good nature?

  26. #26 RobRed9
    October 21, 2009

    What’s interesting is that WPI is publishing their research in that famous center of scrupulous peer review, Facebook.

  27. #27 Eric Johnson
    October 22, 2009

    Yeah, I guess they just couldn’t get a rigorous enough grilling from that scoffed-at little bullshit tabloid, Science magazine, and naturally had to turn elsewhere. Happens a lot.

    Anyway, I heard the National Academy of Scientologists didn’t hang onto your most recent manuscript very long, and Playgirl also wasn’t into running it, even though you tried adding some extra figures from your private stash. I was really glad to hear that your paper finally got the OK from some crust punks who run an anarchist photocopy ‘zine in Seattle.

  28. #28 kg
    October 24, 2009

    “…the MLV coat protein can disrupt red blood cells in mice, leading to low blood oxygen levels…”
    http://www.bioedonline.org/news/news.cfm?art=5704
    I’ve been looking for the paper containing the above data and it’s driving me nuts. Any virologists out there know the reference? Any help much appreciated….

  29. #29 SL
    October 24, 2009

    Glad to know that research on this illness has picked up again. As a person with this illness (who has a child with this illness)— and all documented objectively—forget any subjectivity. CFIDS is very complex and if XMRV has a part in this, then I’d like to see serious research exploring that. I’d like to see serious research in this illness, period.
    I once worked in the mental health field and I think I might be the only CFIDS patient who wished to have clinical depression, for I was very familiar with treatment for that—clinical depression is so very treatable. Alas, clinical depression doesn’t cause the kind of immune dysfunction seen in the illness I have. I knew my immune system was messed up after the third episode of mono within 5 years (with positive lab work and fever of 102), and after recurring C. Difficile infections in the absence of antibiotic use. Postural orthostatic syndrome, I only would stand up to get a heart rate of 150. Try to do anything with that—“graded exercise”? To create heart damage or a stroke. Stupid. So stupid. Beta-blockers help some.
    I don’t want vindication. I just want good science.
    My mother was prescribed DES when pregnant with me as happened with millions of women in this country between the late 40’s through the late 60s. If taken at the first of pregnancy (when it was most often given) the animal studies show gyn and urological problems and oh, screwed up immune systems for life. But we wouldn’t want to look at something like THAT now would we? Nah, might find some connection that would explode the DES debacle further. Studies are on-going now re: effects of 3rd generation DES “grandchildren.” But let’s continue with non-integrated science. So wise, isn’t it?

  30. #30 Eric Johnson
    October 24, 2009

    I would think ordinary broad surveillance on those estrogen mimetics, which I assume probably exists, would pick up excess CFS if there was any? After all, CFS is about as common as any disease other than depression and anxiety – with a point prevalence around 0.6%. Only a rare disease should have an inconclusive sample size in general surveillance, and thus fly under the radar unless examined in a specific study.

  31. #31 SL
    October 24, 2009

    Eric,

    What are you talking about? “which I assume probably exists, would pick up excess CFS”—how would it “pick up” CFS? What would it actually “pick up”? Immune dysfunction, perhaps? Screwed up immune systems that open one up to various viral and bacterial infections?
    From descancer.org

    Since 1971, the devastating effects of DES exposure discovered include:
    Structural damages in reproductive organs of DES sons and daughters;
    High risk pregnancies and miscarriage for DES daughters;
    Increased risk of clear cell cancer of the vagina and/or cervix in DES daughters;
    Increased risk for infertility in DES sons and daughters;
    Increased risk of breast cancer in DES mothers and DES daughters over 40 years of age;
    Possible immune system impairment in mothers and children exposed to DES.
    There are an estimated 10 million DES mothers and children in the United States today. Current statistics indicate that one in a thousand DES-exposed daughters will get CCA, the clear cell cancer originally linked to DES in 1971.
    To this day, none of the 267 pharmaceutical companies who produced and distributed DES has accepted any responsibility for the DES tragedy, and all continue to claim that DES causes no health problems. Eli Lilly, the largest manufacturer, has been a defendant in the majority of lawsuits brought by victims of DES-related cancer, infertility, and birth defects.

    Researchers are still uncovering the long-term effect of exposure to DES, including higher rates of breast cancer in DES mothers, reproductive abnormalities in daughters and sons, higher rates of ectopic pregnancy in daughters, and damage to the endocrine and immune systems. Effects on the third generation – DES grandchildren – are as yet unknown.

  32. #32 SL
    October 24, 2009

    Only by “further scientific research” (see below) which is pretty much stalled.
    But maybe very important, eh? Considering the millions and millions of people in the US population alone who were exposed? Heck, I’d certainly look at XMRV but I’d most certainly be looking here (and the research has not been done):

    “In April 1992 the National Institutes of Health sponsored the first research conference to identify the medical questions about DES that can be answered only by further scientific research. Preliminary studies presented at the 1992 conference indicated that when DES crossed the mother’s placenta it not only harmed the reproductive system of the fetus, but the endocrine, immune, cardiovascular and skeletal systems as well. Also cited were animal studies indicating that DES-exposed offspring manifest adverse health effects throughout the entirety of their lifespan.”

  33. #33 Eric Johnson
    October 24, 2009

    What I mean is, has there been a study where you take maybe 2,000 people who are gestationally DES-exposed, trying hard to get a random sample, and examine whether they have the same rate of CFS (and other diseases) as the rest of the population.

    Actually, my description of how this works was incomplete. It would be easy to detect if the rate of CFS were elevated 10-fold, and such a finding would be hard to explain except by drug effects. If it were elevated 2.5-fold, this would be statistically easy to detect, but it would be really tough to rule out other causes like sampling bias, ascertainment bias, direct effects of the condition for which the mother took the estrogen mimetic, or a combination of all three, etc. If it were elevated only 20%, this would be nearly impossible to detect, and surely impossible to attribute to the estrogen mimetic with good confidence.

  34. #34 SL
    October 24, 2009

    Eric,
    The research simply hasn’t been done. That’s my point. Except for the mice studies that show a definite coorelation between DES given to pregnant mice early-on and totally screwed up immune systems. Have the studies moved past this? No. I supposed someone is waiting for all us DES exposed folks to die off and then the problem will disappear (DES is no longer given to pregnant women—that ended in 1971.) Then just take a look (for the heck of it) when you start seeing CFS turn up (as well as some other neur-immune illnesses). CFS is a relatively vague diagnosis except in hard-core objective cases and in those cases you see undeniable immune system dysfunction—and it doesn’t have to be all the same thing either.) One problem in CFS research (which has been pitifully meager) is the lack of sorting out sub-groups. If that is done and done in a truly scientific way (not bio-political, although you might say you can’t separate the two) then you’d start seeing something. Otherwise, it’s just a big mess that’s shoved under the rug like a huge pile of dust.
    Put it this way: the gyn-oncologist that I see bi-annually at a major medical center and have seen him since I was 19 years old (it’s been over 20 years that I’ve seen him)—when I first got sick with the viral and bacterial infections (that you aren’t supposed to get over and over), then he referred me to an infectious disease specialist (world-renowned) who looked over my chart, checked me out and without hesitation said, “you have what is presently called “chronic mononuleosis.” Lovely, huh? There was never (with me) any doubt that what I had was a dysfunctional immune system and it fit in with CFS (for lack of another diagnosis for it.) The gyn-oncologist I still see is also a DES reseacher and is aware of the immune system issues with DES exposed sons and daughters. When I asked him “What kind of things do they have? What are their illnesses like?” He said—“Like yours, very much” But, of course—it’s all anecdotal (has to be if research isn’t being done and it’s not.)

  35. #35 SL
    October 24, 2009

    Also, when 267 pharma companies were involved in the DES tragedy, there is much incentive put forth for research to NOT be done.

  36. #36 shmerls
    October 25, 2009

    RedRob, your point, while entertaining to even this CFS sufferer, did bring on a grin and chuckle. Lord knows we can use them. But what your comments seem to miss is that there is a indeed an emotional aspect to CFS. Some believe it is all a form of depression, others purely physical. But whatever, when you have it, chicken/egg, it is depressing and, if in fact a physical illness, complicates matters and makes us worse. So when good news hits, we get a boost and do lift out of the malaise. Some more than others. I’m 58. I’ve had this since 35, so I don’t jump for joy much. A smirk is about as much as I allow. For your new sufferers reading this, here’s some advise. Take care of yourself. Get a few tests (maybe), but don’t tell too many people. Non-sufferers don’t get it. Won’t get it. What I found was that I started losing friends back in my 30’s. One because I would commit to plans on Mon when feeling better, for Wed and cancel just before Wed when I was feeling bad again. Plus non-CFS’rs are helpless and many just don’t want their emotional pain/issues to surface around you. If you’re out of their mind, so is their pain about whatever it is they think about CFS and us. Like life. One day at time. When there’s a cure or more probably a management regine, like with AIDS, and you can go to the Rx store and buy it, then you can dance. Until then, hold the fort, do what makes you feel best, sadly sleep never worked for me. I think the most upsetting aspect of this, for me, is the non-restorative sleep aspect. I hate waking up exhausted. But then I don’t have some of the other symptoms others complain about like FMS and my memory, while not great, is better than it was 20 years ago when first hit. But I’ll leave you with this. 20ish years ago when it was Epstein-Barr disease, here in the States, I read as much as I could. I tried and took every thing. I even did a friggin’ exorcism and I’m Jewish! Ever hear of the psychic surgeons from the Philippines? Did that too. Then saw Penn & Teller debunk it. Didn’t matter to me. It was still the coolest hand/eye I had done on my belly ever :) But in those years, I was looking for control. I finally came to the point where I gave that up. But I didn’t give up on hope. I started to just get on with life as best I could. I am from what I see and read, one of the luckier ones. I can now have full days. I can even exercise. When I first got it, I was in bed for 8 months. Those days are long gone, thank God. So… do the most of what you can. Don’t fret what you can’t. When there’s a cure or management, we’ll know. We’ll get/try it and hopefully we’ll be relieved and God-willing, cured…

  37. #37 Sl
    October 26, 2009

    shmerls,

    You describe some things very well about this illness and your experience.Your advice to your sufferers is critical–stay as subclinical as possible and choose carefully whom you tell of your medical situation; your advice to those who are healthy but could very well be knocked flat medically by an acute case of whatever causes CFS is well put. Little do they know. And to those of us who have waited decades for proper research, though, we have been done wrong for some reason. Sub-groupings have not been delineated for research (so of course the results are confusing)–the research has been abysmal.
    For those of you on this blog who are scientists or who are PhD students in the hard sciences, the researcher/clinician who diagnosed me (and quickly in light of the strong objective evidence he saw) is Director of an HIV/AIDS Clinical Trials Division of a major research university. Obviously he sees other patients too, but he’s tested me for HIV several times and the results are always negative, plus I do not fit that profile either. Immunologically it’s clear something is badly awry, strong enough to take away career, something that has allowed vertical passage of illness to my child, etc.
    I recall this reacher/doctor saying to me, “You know how hypoglycemia was all the rage in the 70s? Everyone who didn’t have a clear diagnosis was labeled with this? Well, does that mean that hypogylcemia doesn’t exist? Hell, no, true hypoglycemia is a serious medical problem. No different with the illness you have. Research will bear this out in time. It’s just taking too long because too many people have blown off the whole illness (the real illness) and made jokes, done horrible research, and caused lives to be both diminished and shortened. I agree with you that you make of your life what you can, given your circumstances, but the way “CFS” patients have in general been treated, the lack of proper funding, the sloppy research that has gone on is a travesty. The jokes and arrogance about this illness is in poor taste and shows a lack of knowledge and care.

  38. #38 Dr. Matthew
    October 27, 2009

    Just to set the record straight, the review of CBT on the neurocritic blog was a review of a single meta-analysis with a questionable selection of studies. That said, CBT is one of the best researched interventions for the treatment of depression, and in many studies has surpassed the effectiveness of medication. The best intervention for CFS to date? CBT with graduated exercise. More research is needed, but here’s the deal – to suggest that CFS sufferers would benefit from psychotherapy and behavioral research makes no claim on the etiology. Most integrated health care systems strongly promote chronic pain group or individual treatment (often CBT based) because a) it works, and b) it reduces reliance on medications that might have further longterm consequences. This has nothing to do with the origin of the pain, and many chronic pain patients have clear physical causes for their pain. That doesn’t mitigate the usefulness of psychological intervention because.. ::drumroll::.. pain perception occurs in the brain. As does the perception of fatigue. Does that mean that CFS is cured by CBT, or pain, for that matter? No, though the possibility of ameliorating symptoms is typically motivation enough. I think what frustrates providers, friends, and loved ones of those with CFS is often the resistance to non-physiological interventions (this occurs among families of those with chronic pain as well, for that matter). Why is it so frustrating/infuriating for others? Because of what some psychologists call “sickness behaviors” – when we’re sick, we call on our resources, we complain, we visit doctors, we ask for favors… all given freely and with empathy in hopes we’re well soon, and it’s functional for a short term malady. Every system – from doctors to family – gets taxed when those sickness behaviors never alleviate. Sometimes working on the shift to living with a chronic illness is all that psychotherapy can offer, but still successfully improves social functioning.

  39. #39 Eric Johnson
    October 27, 2009

    I concede that I’m not expert on that meta-analysis or criticisms of it – and even that it was rather disingenuous of me to quasi-imply that I knew that work well. In a similar vein, it’s hard to believe you are not aware that your claims about CBT and graded exercise are highly controversial at best. Indeed, a review to the contrary was published yesterday by M Maes, though it is not necessary the best such opinion ever written – other expert opinions with the same viewpoint exist.

    I would not dispute that in depression CBT shows effectiveness comparable to that of medications, but I think good evidence for the power of those medications is limited. You are probably aware that unblinding due to side effects is a major point of controversy there.

    I do not dispute you on the nature or effects of sickness behaviors, or your statement that it is possible CBT could effect a disease regardless of a physical etiology. Of course sickness behaviors are easily and robustly induced in mice by injecting cytokines or immunogenic substances, not that you have suggested otherwise. It’s also easy to google evidence that tuberculosis patients were noted for crabbiness and selfishness.

    Is there high-quality evidence for CBT affecting function, well-being, or other variables other than treatment-seeking, or answers given on a questionnaire such as the Beck Inventory or Ham-D? Quite modest changes in answers on the latter – which I think is all that is indisputably well-evidenced – might to my mind simply be caused by CBT teaching people to bias their thinking and output positively. That would not improve function or well-being eo ipso. I wonder if exposure to superior literature, film, and philosophy with appropriate themes might not be equally effective. Particularly stoicism and existentialism. I wonder how eager you would be to see CBT for people with physical illness face off against such conventional sources of wisdom, or conversation with longer-term patients not trained in any professional modality.

  40. #40 Dr. Matthew
    October 28, 2009

    Thanks for replying, Eric – I don’t have citations off the top of my head where I would know the outcome measure used, but this is pretty debated in the field – i.e., the importance of clinical change over statistical change. I would definitely agree with your comment about more traditional pursuits of literature, film, or philosophy for consolation and cognitive reframing being potentially equally effective. In fact, I think many CBT researchers would like to think that all they’re doing is the same thing (Zindel & Teasdale’s Mindfulness-Based Cognitive Therapy, which incorporates mindfulness-based meditation and cognitive techniques, is particularly short-changed by the aforementioned meta-analysis b/c, for all depression sufferers pooled, it sucked, and they don’t recommend it for everyone – but for individuals with 3+ episodes of Major Depressive Disorder, the effect of the intervention suddenly skyrockets; along with compliance by participants, implying that some of the effect is that of suffering individuals being more interested in engaging in new ways of thinking that would reduce suffering). I’m an empiricist at heart – there are a number of well-defined existential therapies (Yalom wrote a great book on them) that focus on issues of pain and death, and that I don’t think have been rigorously compared to other interventions, but merit the effort. I think it would be very helpful for clients to do so, and just b/c CBT therapists are more hooked on finding evidence for effect, that doesn’t mean alternatives aren’t equally or even more effective. There are many associations, though I’m most familiar just with those re: ALS or MS, that work to bring early sufferers in contact with late sufferers, to have those candid discussions about how life changes that you can’t have with a provider. So far as I know, that hasn’t happened yet for CFS, and might provide some benefit.

  41. #41 gf1
    October 28, 2009

    “Why is it so frustrating/infuriating for others? Because of what some psychologists call “sickness behaviors” – when we’re sick, we call on our resources, we complain, we visit doctors, we ask for favors… all given freely and with empathy in hopes we’re well soon, and it’s functional for a short term malady. Every system – from doctors to family – gets taxed when those sickness behaviors never alleviate.”

    Maybe those others would benefit from some CBT, to help them understand the nature and injustice and chronic illnesses? Sounds like they might be falling prey to the Just World Hypothesis, or some similar disturbed thought pattern.

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