Recovery In Neverland

Even though the last blog was the least controversial I’ve ever written, it managed to ruffle a few feathers. On the one hand, it couldn’t possibly be as simple as a diet cure and, on the other, it is too hard to implement, especially if you are sick and short of money. And what about retroviruses?

I am not cured. It is a relapsing, remitting illness and I am experiencing a remission. I am not asymptomatic, but much, much better. My husband and I have ridden our tandem 180 miles so far this month. Our rides are quickly getting longer, faster and more challenging. My husband said I have never worked harder. I don’t know if that’s because I want it more, or because I finally fixed my rubidium deficiency;-). No doubt a real doctor would say I finally decided to get off my ass;-). But anyone with real knowledge of the disease knows what a profound change has to occur for an ME patient to return to exercise after nine years.

Ali also has noticed improvement with respect to her physical abilities. She went to an hour long yoga class a few days ago with no PEM and expects to continue. She is living away from me, something neither of us thought possible just a few short years ago.

It isn’t just the diet. The diet happened to us in the context of a slow recovery over a number of years during which several treatments were contributory, all documented on this blog. Antiretrovirals, oxygen, Deplin, at one time Actos, at another modified Meyer’s cocktail IVs, metformin and Prometrium for Ali, prior dietary modifications and ever more awareness of the importance of biotoxin avoidance. I believe all of these things have helped to tip the balance towards recovery. When you are treating an incurable disease, it is necessary to look for therapeutic synergy.

As to the diet being hard, some of the biggest things aren’t too hard. A daily smoothie, big plates of organic greens, bone broth from clean grass fed animals. Buy organic. Try your local CSA (community sponsored agriculture) who sometimes deliver. Try eliminating gluten and dairy for three months. Consider nutrient density before eating something. Don’t try to change everything at once. Pick one thing and do that, then add to it. It is more expensive to eat this way. If it is too expensive, I am thinking the food is more important than supplements, on which most patients spend a lot of money. I am increasingly suspicious of things that come in pill form, including supplements.

One of the really interesting things that has happened to me on the Wahls diet is I am not tolerating B vitamins at all, finding them overactivating and sleep disrupting, after taking Deplin for years. I presume this is because I am getting what I need from my food. Can we infer from this that my methylation status has improved? Take a look at the numbers midway through this article by Dr. Wahls: Maximizing Nutrient Density for the Modern Day Hunter-Gatherer.

In addition to a relatively small number of known required nutrients, whole food contains thousands of compounds which work together in ways we do not begin to understand. Supplements supply an excess of a single nutrient. In the case of L-methylfolate, the idea is to overcome an enzyme deficiency by supplying the activated form of the nutrient folic acid to prime the pump of essential metabolic pathways. The deficiency occurs more often in the presence of certain genetic mutations, or SNPs, but remember, the problem is most often not caused by the genetic make-up of the individual, who was healthy once, but by epigenetic changes that have occurred. Also remember that methylation silences retroviruses.

I still think retroviruses are at the bottom of it, endogenous and/or exogenous. I will prevail upon Dr. Snyderman, who has lots to say on this subject, to give us an update in the near future. There is a growing body of literature to support the association of activated HERVs with various diseases. There are even a few intrepid researchers still pursuing novel retroviruses in chronic disease, working at the edge of our current understanding. Andrew Mason‘s betaretrovirus associated with primary billiary cirrhosis, clinical trials with antiretrovirals ongoing, Sidney Grossberg‘s JHK gammaretrovirus which he has identified in CFS patients, and Hervé Perron‘s MSRV, particles from HERV-W transcripts, with an immunopathogenic envelope protein, severity of illness correlates to viral load, replication competence still unknown. “Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients.” from The DNA copy number of human endogenous retrovirus-W (MSRV-type) is increased in multiple sclerosis patients and is influenced by gender and disease severity.

The possibility that animal retroviruses are the root cause of the enormous increase in chronic neuroinflammatory illnesses, autoimmunity and cancer in our modern world has not been ruled out, just because the particular sequence called XMRV has been put to bed. In fact, in figuring out where XMRV came from, created in a lab using techniques in use every day all over the world, a can of worms has been opened. How many times have similar organisms been created? How many cell lines commonly in use produce infectious virus that can spread airborne through a clean lab, as XMRV does.

Given that retroviruses recombine and rescue each other, that under certain conditions HERVs activate to produce viral product, that the environment is full of the very toxins used to amplify retroviruses in the lab and that high risk biotechnologies have offered up so many chances for new retroviruses to infect humans, it seems more likely than unlikely that it has happened, and more than once. After all, we have been injecting adventitious retroviruses into people for 80 plus years in combination with other live viruses. We think nothing of fusing human and mouse genetic material to produce monoclonal antibodies that are given to immunocompromised people. Passaging human tumor tissue through immunodeficient mice, gene vector technology, genetically modifying animals to produce human proteins for IV administration (Atryn) are all very high risk things to do. Lots and lots of chances. Hubris allowed it. Money drives it. How could the legacy of all that science be that half of everybody has a chronic illness, including children? Who wants to know that?

Injected into monkeys, XMRV causes a low level latent infection, which isn’t communicated by transfusion. However, Dr. Mikovits found other sequences in patients besides XMRV. Here is a slide from her recent lecture at Dr. Enlander’s conference showing just that.

The Exotic Biology of XMRVsfinal slide 10

Of course, she doesn’t have her notes, so all of the unpublished work she did is lost to us. Meanwhile, the WPI continues to suck up a big chunk of the government dollars spent on our disease, while their co-founder awaits jail for his felony convictions.

$450,000 of taxpayer money was spent on the specimens collected for the Lipkin study, which was negative, as expected. The good news was that Dr. Lipkin was going to use those specimens to answer some questions. I guess he couldn’t get funding. Instead those specimens have gone to Dr. Peterson, who is raising money to look for evidence of arthropod borne disease, even though the collection criteria for the specimens specifically excluded Lyme Disease. How’s that for looking under the streetlight?

Meanwhile, as a patient community, we are back to case definitions, an obfuscation if there ever was one. A case definition is an exercise in futility, because the disease isn’t one thing. ME/CFS is a garbage pail diagnosis, somewhere to put all those patients who feel awful, have non-specific immune dysfunction and secondary mitochondrial failure, with nothing else to define their illnesses. Many roads lead to Rome. The question of causation is simply too complex for our current scientific methods. The ability to analyze huge amounts of genetic material cost effectively is coming, but it isn’t here yet. It may turn out that the specific retroviral sequences involved are found in particular families or groups of people with certain environmental exposures, e.g. certain chemicals or vaccines.

With the burying of XMRV has come a resurgence of Lyme Disease as The Cause. The CDC recently admitted that they were low on the number of annual cases by a factor of ten, right on time for the release of Baxter’s new vaccine and Lyme test. The CDC’s admission is unfortunately a boon to ILADS, a renegade medical society based on an incestuous relationship with a private lab, to which they refer and then use the unvalidated results to perpetuate their mythology: Patients congratulated for “herx” reactions to antibiotics, rather than recognizing it for the damaging cytokine storm that it is. Then there’s the one about how enough antibiotics in the right combination for the right duration can eradicate it, despite all evidence to the contrary. And the one about how chronic Lyme Disease is a distinct entity from ME/CFS, despite the fact that the two groups are clinically indistinguishable without test results from this one particular cash only lab whose results no other lab can duplicate. And then, if they happen to get a negative test, which is a rare event, the most imaginative of all, seronegative Lyme can be diagnosed clinically, even in people with no risk factors. It’s a scam and a dangerous one. I saw this yesterday: Is Lyme Disease Contagious? Clues Hint That It May Be A Sexually Transmitted Disease, quoting no other than Dr. Raphael Stricker, the most published of the so called LLMDs. Here is what the Office of Research Integrity at the NIH has to say about him (link):

Raphael B. Stricker, M.D., University of California at San Francisco. An investigation conducted by the University found that Dr. Stricker falsified data for a manuscript and a PHS-supported publication reporting research on AIDS. In the manuscript, Dr. Stricker selectively suppressed data that did not support his hypothesis, and reported consistently positive data whereas only one of four experiments had produced positive results. In the publication, Dr. Stricker reported that an antibody was found in 29 of 30 homosexuals, but not found in non-homosexuals. However, Dr. Stricker”s control data, which he suppressed, showed the antibody in 33 of 65 non- homosexuals. The falsified data was used as the basis for a grant application to the National Institutes of Health. The ORI concurred in the University”s finding. Dr. Stricker executed a Voluntary Exclusion and Settlement Agreement in which he has agreed not to apply for Federal grant or contract funds and will not serve on PHS advisory committees, boards or peer review groups for a three year period beginning April 1, 1993. The publication “Target platelet antigen in homosexual men with immune thrombocytopenia” in the New England Journal of Medicine, 313: 1315-1380, 1985 has been retracted (New England Journal of Medicine, 325: 1487,1991).

ME/CFS, Chronic Lyme Disease, mold illness, MCS, fibromyalgia, GWI, all have pretty much the same symptoms. Lots of tunnel vision going on in each group. A retroviral hypothesis is the most parsimonious explanation for all of these diseases, which didn’t exist or were very rare when I went to medical school 35 years ago. Dysautonomia, now common, wasn’t seen then except rarely in advanced diabetes. A retroviral hypothesis fits for ASD also. This very brief distillation is all referenced elsewhere on this blog. However, even when one turns to the literature for answers, you have to figure that a very large proportion of it is wrong due to mistakes, contamination and fraud (lots of that going around). Why Scientific Studies Are So Often Wrong: The Streetlight Effect. So whatever cohort you fall into, which may depend more upon which doctor you go to than anything else, you get to choose between neglect by conventional doctors and expensive overtreatment by the “experts”. My advice is avoid doctors and eat your vegetables.

Tonight’s song: We Shall Overcome by Pete Seeger

Healing In A Toxic World

My health has been slowly improving for four and a half years. Even so, I have been unable to exercise without payback, but that changed three months ago. I attribute this breakthrough to “minding my mitochondria” per Dr. Terry Wahls. Six months ago I watched her TED Talk. I had written a blog entitled MS Light? a few months earlier, suggesting that MS and ME are two branches of the same tree and I thought, if it worked for her, maybe it will work for me.

We jumped into the diet as a family in July. In a nutshell, 3 cups each of greens, sulfur containing foods and colored fruits & veggies each day, bone broth, grass fed grass finished meat,  organ meat and seaweed. No grains or simple sugars. Olive oil, coconut oil, butter, animal fat. Every bite needs to be nutritionally dense. In addition, we cleaned up our act, went all organic, non-GMO, almost all locally sourced food, no cans containing BPA, no teflon or plastic in the kitchen. In addition, we emphasized a variety of mushrooms, ginger, turmeric, garlic, cilantro and fermented foods. We all noticed some improvement after a month, sick and healthy people alike.

Then I got distracted, sucked up in a negative energy vortex involving my family of origin, the kind of stuff that makes me nuts, and then sick. I didn’t particularly notice what I was eating for a while, but ate what my daughter, Julie, put in front of me. Historically, I can adhere to a regimen for about a month, before losing track, but Julie kept me on the diet.

One day, after about three months of eating this way, I was feeling particularly stressed, sick and discouraged. My husband said, “Let’s go for a ride on the tandem.” I quipped, “OK, maybe I’ll die.” I’ve ridden a few times before in the last few years, and the aftermath wasn’t pretty. But this time, it was only good- the ride itself, afterwards and the next day. I was shocked. After nine years, I didn’t really expect it to ever change. We went again the day after and have kept on going, trying to ride at least three times a week. We started with 4.5 miles in 25 minutes and have worked up to 17 miles in an hour and a quarter. Also, I can now hike a couple of miles again, even though walking was really tough before. When I stand, I don’t feel like somebody turned up the gravity anymore. My arms no longer feel heavy. No more wheel chairs through airports for this girl.

I am putting on muscle quickly. I have much less resistance to exercising than when I was younger and healthy. Maybe it’s because I couldn’t do it for so long or maybe it’s because exercise requires a willingness to suffer and my illness has taught me how to accept physical suffering. I am so motivated, we have continued to ride in freezing weather. We even tried off road for the first time a couple of days ago when it was 30 degrees out. 7 miles of dirt with mud and ice here and there, plus a fierce wind. Pretty hardcore for a 60 year old sick woman;).

We have been learning about food and improving our family’s diet since our kids were little, but even so, I must have been nutritionally deficient and/or being harmed from ongoing toxin exposure in my food to have experienced such a fundamental improvement in physical function. Here’s an interesting one. I have been taking Deplin 7.5 mg for years but in the last month, I’ve stopped tolerating more than a tiny dose, which is good, because the pharmaceutical preparation contains coating and additives that a quality OTC supplement doesn’t. So methylation status is much more complex than MTHFR genetics. It is possible to get enough folate from food, even for someone who needed to take it before in high dose pill form.

As I am using food as medicine, I am ever more suspicious of anything that looks like a pill or was made in a plant. I am taking Vitamin D3, methyl B-12 and OTC 5-MTHF in the form of Metafolin, B-complex, fish oil, UBQH, magnesium and chlorella. I am still taking antihypertensives and bioidentical HRT. I stopped Viread and Isentress a couple of months ago, once I knew my improvement was solid. A year ago, I had a hypertensive crisis when I stopped Viread monotherapy and restarted. This time my BP only went up a little for a short time and returned to better than prior baseline. I wanted to get off, because it is not going to be studied and there is no way to monitor what the drugs are doing. I was pretty sure they were helping in the first year, and we had clear laboratory evidence of improvement from the WPI, but after that, it was less clear. Both Ali and I did very well during the years we took them, but when we started, I thought we’d have viral load measures in a year and it didn’t happen.

Ali likes the diet, but hasn’t experienced the clear cut benefit that I have. She has continued her slow uphill climb, excelling in college at U Mass Lowell online, going out and being much more physically active, MCS improved, but still experiencing post exertional malaise if she pushes it. As she says, she has gotten very good at managing her spoons. She is living with her boyfriend in Albuquerque, something I wouldn’t have thought possible a couple of years ago. She has made huge progress, but it has not been clearly related to the diet. She wants to continue nevertheless. She stopped Actos about 6 months ago, continuing on metformin and luteal phase Prometrium with good control of PCOS symptoms. She came off arv’s in the last month and has been having a bit of a hard time since, but not so bad as to force her to restart at this point. With no support from the medical or scientific communities, it is time for us to stop if possible.

All of this is triggering my survivor’s guilt or whatever it is. Maybe that’s why it’s been so hard to write lately. Or maybe it’s just that my anger has been diluted by endorphins and anger has been the driving force behind many of the blogs I have written. I feel guilty reporting that this is what is working for me, because I couldn’t do it without lots of support. My daughter keeps me on the diet and exercise is dependent upon my husband’s skill and encouragement. My advice is find a friend to support you and, if you can exercise, pick an activity you have done before. I have muscle memory for the tandem; we rode for many years before I got too sick to do it.

Besides patients with neuroimmune disorders there is growing anecdotal evidence that a paleo diet is beneficial for patients with autoimmune disorders, in particular rheumatoid arthritis. Many ME patients have evidence of autoimmunity. Phoenix Helix is a good blog with lots of useful information, in particular how to do a strict elimination diet, cutting out the most allergenic foods that might be contributing to the problem, dairy, eggs, nuts, nightshades, legumes, and then adding them back in one at a time. Ali is planning to do this when she has a clear space to see if a particular food is keeping her from realizing gains.

So, since I was already on a good diet, what’s my guess for what is making the difference? The big changes for me were force feeding leaves, bone broth, seaweed, no grains, sugar or vegetable oils besides olive and a little sesame, almond and avocado oil. All organic. Toxin avoidance. Organ meats are a bit of a stumbling block for me, but I am eating some liver.

I am a small woman and can only eat 6 or 7 cups of vegetables and fruit per day. It falls off quickly if I don’t focus on getting in my cups. Once I eat what I’m supposed to there is no room for anything else. I have not been scientific about it at all. 3 cups is a heaping dinner plate, raw, where you can’t see the bottom. I just work on getting down as much as I can. I have a daily smoothie with leaves, berries and probiotics which helps me get down more greens.

A couple of my patients crashed themselves at the beginning trying to do the diet. Others have said up front, I can’t do it. I could never have done it without Julie. I think I could do it now, but I’m six months in and my daughter is now an inspired paleo cook, so if I stay home, I’m covered:). But I keep thinking about how to make it possible for sick patients. In a perfect world, share a cook. Otherwise, baby steps! Massive dietary change is hard on the body. Eat more leaves. Eat from the rainbow. Make bone broth once you have sourced clean animal marrow or knuckle bones. Put in some lemon or apple cider vinegar to help extract the minerals. It is kind of gross if you cook it on the stove top for a long time, but Julie makes it in a pressure cooker, which as far as I can tell, preserves the nutrients well. It is quick and wonderful. Healing. She makes it with garlic, ginger, fresh turmeric root and seaweed, then uses it to cook everything. I enjoy it plain or with spinach or kale.

There is so much to learn about food. Eating for health is a lifestyle, not a diet. Take a look at Eating On The Wild Side. It will inform your decisions about what to buy in the supermarket, farmer’s market and seed catalog, as well as how to store and prepare your food to maximize it’s nutritional value. It isn’t really possible to eat an ancestral diet since the foods that paleo people ate are no longer readily available. I really looking forward to gardening and foraging in the spring. My daughters and I started a Facebook community page called Healing In A Toxic World. Please join us. We are sharing what we are learning including how to source your food and lots of recipes.

 

Van Morrison – Days Like This

Bats In The Belfry

I missed Dr. Lipkin’s dog and pony show a few days ago, but thank you to ME/CFS Forums for posting a transcript. Here again, it appears he has dismissed the only finding that actually adds to the discussion. It is just like last time when he dismissed the only positive finding in the XMRV study, that 6% of the people tested were positive for an antibody to a nasty mouse retrovirus, significance unknown. This time:

We found retroviruses in 85 percent of the samples. Again, it is very difficult at this point to know whether or not this is clinically significant, and given the previous experience with retroviruses in Chronic Fatigue I am going to be very clear in telling you, although I am reporting this at present in Prof. Montoya’s samples, neither he nor we have concluded that there is a relationship to disease. I’ll repeat that one more time. We found retroviral sequences, but their relationship, at this time, to Chronic Fatigue Syndrome is unclear and, in fact, if I were to place bets and speculate, I would say that they are not going to pan out.

In addition to this astonishingly unscientific statement, in the same week, he announced other recent findings. From the BBC News: “They found nearly 60 different types of viruses, most of which had never been seen before”, in one species of bat. He extrapolated this to suggest that there are 320,000 new viruses in mammals still to be discovered. However, he could find nothing at all in hundreds of sick humans. Presumably using the same techniques. Or is that the problem? Doesn’t it seem unlikely that there would be nothing to find in sick humans with low NK function and a propensity for opportunistic infections of all kinds? We are mammals after all. Here is the paper: A Strategy To Estimate Unknown Viral Diversity in Mammals. He wants to spend billions of dollars in an attempt to avert a pandemic, when he has several existing pandemics staring him in the face. I guess existing diseases aren’t as much fun as teaching Gwyneth Paltrow how to have a seizure. Then again, maybe we all really do need to be vaccinated for the next bat virus we might encounter.

But, he did give the nod that we are sick, not just crazy, so I guess that’s a good thing coming from such a high profile scientist. We have elevated levels of proinflammatory cytokines and chemokines. Completely nonspecific, all downstream effects, but abnormal numbers nevertheless, something measurable. In my experience however, the commercially available tests (Labcorp and ARUP via Quest) don’t show the abnormalities he describes (and which have been previously described by others), so we need more sensitive assays commercially. I’m not sure why the difficulty, but the clinical reality is that the doctors who are actually treating the patients have almost nothing to follow, except for a very few nonspecific inflammatory markers in some patients, e.g. hsCRP, C4a and TGF beta-1.

So that leaves us exactly nowhere, as usual. We are not going to be saved anytime soon by the medical model. Look how much the scientific method has accomplished for us in the last few years:-). As a doctor, I have a small bag of tricks to fight a terrible, incurable disease. However, it is an inherently unstable disease, relapsing and remitting all on its own. Look for a way to get a foot in the door. It is possible to tip the balance in favor of better health with global strategies that support the body, mind and spirit. Find synergy. Ali and I continue to be committed to the Wahls paleo diet. Less suffering for sure, after only a couple of months. Just like oxygen, methylation supplements, hormone balancing, we feel better from this intervention. Not expecting a cure, but we are both experiencing a bit more uphill movement, even though our diets were already pretty good. Please take a hard look at this diet, most likely beneficial for all neurodegenerative and inflammatory diseases.

Ali has all but moved out, her symptoms so manageable that she is mostly living with her boyfriend in Albuquerque, despite nearly new construction that once triggered her MCS so badly, she almost couldn’t be there. There was a time when I didn’t think she would ever be able to live away from me. Bittersweet…

She Blinded Me With Science (Live) by Thomas Dolby

Opting Out

My thoughts keep coming back to this paragraph on the CFS Patient Advocate blog:

Mady Horning gave a fine talk, echoing the one she gave in Florida in January. That talk can be accessed here. She spoke of the terrain and genetic defects leading to ME/CFS – what variables contribute to getting ME/CFS. In a follow-up question she was asked what we all want to know. What information can she give about the ongoing CFI Lipkin study? She said that 80% of the blood work is done, but that much additional work needs to be done on saliva, feces and urine. She said that they had identified several promising pathogen “candidates” including a “novel pathogen” – but the work was still early and no conclusions can be drawn. I have heard the term “novel pathogen” somewhere before.

A novel pathogen from Dr. Lipkin’s lab… Hard not to speculate on what it could be. An attenuated poliovirus perhaps? That would put us back into the doomsday scenario, life imitating science fiction again. My illness is consistent with a post-polio syndrome. I received the very first round of the oral polio vaccine from my pediatrician father. I have a vivid memory of lining up with the kids in his practice to get my sugar cube. I remember impressive pain from IBS for some time after that. My father told me it was normal, but I wonder if he wondered. He knew the state of the technology. My father’s office was attached to our house. He had rats in the toolshed on which he did research.  I also remember getting called into his office to get a gamma globulin shot followed by a kiss from a patient with measles, so I would get a “modified” case. He was on the frontier. Rockefeller Institute was nearby.  Lots of women exactly my age (59) are sick. Too high a percentage of the patient group. It was a wave. Something went out horizontally. There were other waves, the first outbreak of Epidemic Neuromyasthenia at LA County Hospital happened two years after the Yellow Fever vaccine was released, a live attenuated vaccine passaged through mouse brains, mouse brains that express viruses like XMRV. Maybe it’s a persistent enterovirus, as Dr. Chia has long thought. Maybe it lies dormant, and with an appropriate trigger, say organophosphate exposure, mold, infection, trauma, vaccination, what have you, it fires up and activates HERV’s, probably different sequences in different people and families. Doesn’t fit as well as the retroviral hypothesis, but it could be right.

Yes, I find myself hoping against hope that “the world’s most celebrated virus hunter” will find our pathogen(s). We need new treatment strategies. We are becoming visible as a patient group and there is more acceptance that there is a biological basis for our illness. ME patients are demanding the big guns. We are going to get what other patient groups get, to be guinea pigs. This is what can happen: PML Case Seen in Patient on Gilenya. This was an MS patient. PML or progressive multifocal leukoencephalopathy is a complication of drugs like Rituxan, trials currently being sought by ME advocate groups. That’s what modern medicine has to offer you, if you have a real disease.

Not to mention how monoclonal antibodies are produced… Hybridoma technology involves producing cells that are a fusion of another mammal’s B cells and human cancer cells and the resultant product is introduced into humans. Revolting when you think about it. Probably just the sort of thing that got us into this mess. Splicing and dicing viruses and growing them in the cells of various animals. That’s where XMRV came from. How many more? Here’s another scary one: from Modelling the long-term persistence of neutralizing antibody in adults after one dose of live attenuated Japanese encephalitis chimeric virus vaccine, which says, “One such new vaccine is a Japanese encephalitis chimeric virus vaccine (JE-CV; Imojev™; sanofi-pasteur), a live, attenuated product grown in Vero cells.” Vero cells are monkey kidney cells. So viruses spliced together in the lab and grown in monkey cells, which can express viral particles, are injected live into people. “Attenuated”, meaning reduced virulence, which doesn’t tell us anything about whether a virus persists or not. They look for persistence of antibodies, but not for persistence of the live virus they intentionally infect people with. Look how much they knew about the dangers of using monkey cells in 1960: Notes on viruses likely to be encountered in vaccine production using monkey kidney tissue. The government acknowledges that 30 million people were accidentally innoculated with a monkey virus, SV40. Not so surprising given the crude techniques they used at the time. It Only Took 50 Years: CDC Admits Polio Vaccine Tainted with Cancer Causing Virus.

It is out of control. Biotechnology run amok. We don’t have the wisdom, individually or collectively. It is all built on a faulty premise, that Big Pharma is going to save us. It isn’t going to happen. These are the folks that brought us Viox, Avandia and Fen-Phen. Fraud is rampant in the pharmaceutial industry. Huge multibillion dollar settlements happen all the time. Our world is becoming populated with sick people. In the US, 55% of children have a medical condition, 20% of the population have a rheumatologic disorder, 2% of children fall on the autistic spectrum. 1% of the US population has ME/CFS. MS, cancer, neurodegenerative diseases. The disease burden is enormous and completely out of balance with nature. It is no doubt multifactorial, but the parenteral use of engineered biologicals must be high on the list of stupid things we have done. All of this interspecies tinkering and regular introductions of foreign DNA and RNA into people who are chronically inflamed from their environments anyway, has offered innumerable opportunities for the creation of new infectious viruses. It is ridiculous to think that the creation of XMRV was a unique event.

The older I get, the clearer I am that pharmaceuticals are a very poor answer to chronic illness. All drugs are poisons, which doesn’t mean that you might not choose to take one, but they are almost never truly health enhancing. In particular, drugs which are akin to shooting a bazooka at the immune system are a bad idea. I know, I know, I am taking antiretrovirals. However, I have every reason to believe they are not going to kill me. I do not know if they are helping or not, but I tried to stop them and got worse. I had a prolonged hypertensive crisis when I came off Viread, requiring the addition of more drugs, now getting back to my baseline after on again for 6 months. Thus, I think I am better back on Viread and Isentress, but how can I know for sure? The disease waxes and wanes all on its own and life happens, making it very difficult to evaluate the effect of any one intervention. Antiretrovirals are not the only thing Ali and I do for our illness. We use oxygen and methylation supplements. We are always working on our diet and supplements. We get ever cleaner about food and the products we buy. Life does not imitate science in any way. Real life is always multifactorial.

At any rate, almost 3 1/2 years in, despite huge stress in the last 2 years, Ali and I are still beating the odds. We are not well by any stretch, but it’s a good life. Still improving glacially, not all the time, but overall, better function. Able to do more with less payback. Minimal suffering compared to our years as chronic Lyme patients. I have never said that anyone should take antiretrovirals, but it is still unfathomable to me that it has not been studied at all. Enough people experienced initial improvement, though it was rarely dramatic, and often didn’t last beyond a year, but it is a clue. These drugs are supposed to have specific activity and weren’t designed for what we have and yet, they can have a positive effect. There has still been no experience at all with protease inhibitors, except as reported to us by Dr. Snyderman. I don’t understand what it is about this particular class of drugs that freaks everybody out so much. Patients get  much more dangerous drugs for much flimsier reasons every day. Why? What’s the big deal about a trial of drugs which inhibit retroviral proteins, especially since they might have an impact on activated HERVs or other retroelements. I don’t understand why the drug companies aren’t more interested. There are more of us than AIDS patients. Throw in ASD and MS, we are talking about a lot of people.

My first day of medical school, in 1975, a wise professor told us, “Half of everything you learn here will turn out to be wrong.” Well, it was much more than half. Just recently there have been papers reporting Zithromax can cause sudden death. Statins and beta blockers are bad for old people. All those CYA  head CT’s we did on little kids that we knew would be normal gave some of them brain cancer. Mammograms are bad for you. When it came to nutrition, they didn’t teach us much of anything, but what we did learn was wrong. Turns out diabetics don’t need to limit fruit, only refined carbohydrates. Vegetable oils are mostly bad for you. Salt, coffee, bacon and eggs are good for you, if properly sourced. “They” were wrong about almost everything. What is bad for you is to eat processed foods that contain genetically engineered plants that tolerate RoundUp, but have almost no nutritional value.

What is bad for you is to take drugs for symptomatic relief of chronic symptoms. Sleep and pain meds are a trap. They commit patients to a kind of purgatory. They cause poor quality sleep, depression and cognitive decline. Deadeners. They lead to physical dependence and tolerance is an ongoing struggle. I am not judging anyone. I did it. I call them my lost years. Everything improved when I discontinued antibiotics and medication for symptom relief. I wish the drugs really helped, but they don’t, and they make it worse over time. Don’t kill the messenger. I prescribe them if I have to, but my patients know going in that my agenda is to wean them if at all possible. When patients give up unnecessary drugs, they come out improved on the other end, pretty much without fail, because the body works better without the toxic assault. I know up close and personal what it is like to sit there on pain meds, not tolerating the pain, wondering how it is possible to survive without dulling it, but the brain has been sensitized to the pain and in fact, can’t adjust to the reality of the pain while the drug is there.

Sleep is such a fragile thing. There is no way to reach deep restorative sleep through artificial means. Insomnia is perhaps the hardest symptom to address, inflammatory in nature. Insomnia goes hand in hand with better or worse, in a chicken or egg fashion. Melatonin and herbal concoctions can help. Neurofeedback may help, though sleep disruption is a stubborn symptom. Sleep hygiene is crucial. Sleep returns with wellerness. It is important not to go more than one night with no sleep, but sometimes some sleeplessness may have to be endured to get the body used to not being knocked out with drugs. There is a payoff at the end of that tunnel. Please note, it is dangerous to stop benzodiazepines without weaning.

Our family is trying hard not to comply with Big Ag’s agenda. We are a big family. Four generations under one roof, and I am blessed to be living with young adults who share the work. Ali and I are following the Wahls Paleo Diet, the rest of the family also, plus some rice, potatoes and gluten free bread. We both really like it, though Ali just discontinued Actos, after a slow wean. It was kind of tough every time she went down, so she hasn’t realized a tangible benefit from the diet yet the way that I have. She was already on the best diet of all of us. She plans and prepares many of our meals, for up to 9 people, a clear sign of how far she has come. I’ve been much less symptomatic since I started the diet. I was away for 5 days of wilderness camping with my husband for our 25th anniversary, didn’t have my daily smoothie or as many veggies as at home, cheated with a little gluten free bread, and my gut noticed. Now home again for 4 days, I again realize how important this diet is for me. What surprises me is, our diet was already really good. The differences are a huge increase in fruits and vegetables, no grains (we had already eliminated gluten), grass fed/grass finished animals, more fish, seaweed, marrow bone soup, nut milks, no cheese (we were already non-dairy except cheese), all organic, completely non-GMO (we were mostly there already). We are also emphasizing fermented foods, including brewing our own kombucha. Today’s smoothie was spinach, kale, purslane, frozen berries, hemp seeds, coconut milk, glutamine and water in the Blendtec. I used to be anorexic until noon. If I drink a veggie berry smoothie in the morning, my appetite is improved for the whole day and I can eat lots of green things.

Please read the comment by Celia Harrison in the last blog. There are other testimonials on the internet by ME patients who are finding this diet beneficial. It is likely useful for all neurodegenerative diseases. I heard from people who took exception with my use of the nickname MS Light in previous blogs, feeling that it trivializes our illness. That was certainly not my intent, rather I think the comparison of ME to MS is a useful one conceptually, but sister illnesses is a better way to put it.

It is more than a diet for us. It is a complete lifestyle. We are buying our food from local sources. No convenience foods. We are gardening and planning to expand next year. CSAs (community supported agriculture) are a wonderful way to go. Organic produce, in season. Instead of shopping for what you want, eat what you get. Big Ag considers the food we are eating specialty crops, because they don’t generate big profits. They don’t get made into GM corn syrup, which is what they make their money on. They have been feeding us their insane ideas, e.g. food containing BT toxin. Our illness is part of a bigger problem. The bees are dying. They are canaries in the coalmine, just like we are. The ways in which food is being mass produced in the modern world is making our planet sick also. What a strange world that growing your own vegetables and supporting local farmers is revolutionary.

Opt Out

 

Today’s song: As Time Goes By

Status Post XMRV

I have been in the doldrums, but since blogging is my hedge against powerlessness…

This is how deep in it I have been; my inner blogger didn’t even twitch for this: Partial molecular cloning of the JHK retrovirus using gammaretrovirus consensus PCR primers. Grossberg SE, …, Sun HY

 “Unlike earlier reports, in which MLV-like sequences were identified in human source material, which may have been due to murine contamination, budding retrovirions were demonstrated repeatedly by electron microscopy in uncultivated lymphocytes of the index patient that were morphologically identical in their development to the virions in the JHK-3 cells, and immunological evidence was obtained that the index patient produced IgG antibodies that bound to the budding viral particles in patient PBMCs and in the JHK-3 cells. “

It’s tough to keep writing about it when the medical and scientific communities aren’t interested. This group has been publishing about their retrovirus since 1995. Andrew Mason and Hervé Perron have been publishing about their respective retroviruses for over a decade and nobody is interested:

I haven’t heard or seen anything that makes me feel hopeful of meaningful treatment since the demise of XMRV. The only perhaps promising development was Dr. Hornig saying publicly that they have isolated a novel pathogen. Cruel to have said so without more information, but let’s hope it is true and they publish soon. Otherwise, it is pretty much the same ole, same ole.

Chronic Lyme Disease seems to be experiencing a horrifying resurgence as the explanation for what ails us. A wise doctor, one of the few, once told me that antibiotics are the surest path to worse. Wish I had listened to him. ILADS hasn’t updated their guidelines since 2006, even though lots and lots of people have been made worse by their protocols. They are stumped because in all these years they still can’t show that what they do is a good idea.

Borrelia burgdorferi is obviously one of the things that can happen to the microbiome if one is bitten by deer ticks. The problem is that it can’t be eradicated  with antibiotics once it is established and the antibiotics are harmful. Weigh these papers:

This is as positive as it gets in the literature:

Nevermind that we can’t really tell who has it or whether it is what is making them sick. They could tell that a man from 5000 years ago, found frozen in the Aps had Bb, but he died of trauma. However, they can’t really tell if we have it. The Iceman’s Genome Reveals Evidence Of Lyme Disease, Lactose Intolerance And Distant Relatives.

But what about the people who do get better from antibiotics? My daughter got several remissions in the early years. Did it even have anything to do with Lyme? Broad spectrum antibiotics kill in a broad spectrum way.

So who should get antibiotics? That is the million dollar question. I keep listening and it seems to me the people who are better off for having taken antibiotics know it pretty quickly when they go on. When it works, it works. This idea that a prolonged “herx” is a good thing is lunacy. As bad as blood letting with leeches. It is a cytokine storm, not a good thing and if it lasts a long time, it is damaging.

Two suicides in the Facebook ME/Lyme community yesterday. Both beautiful young women. This should not be happening! And the response is, we understand why they did it. How can that be? When is it going to change? Not soon. Nobody is going to save us. We have to help ourselves. The disease is treatable. Not curable, but treatable. Read the last blog. K is not an anomaly. She has come a huge distance by finding synergy in gentle therapies, none of which would have done it alone. But those therapies aren’t even on the table for discussion.

Ali and I have been on the Wahls diet for 2 weeks. Terry Wahls is a physician with secondary progressive MS who got herself out of a reclining wheelchair with diet. She was already on a paleo diet which had slowed her progression, but modified it to get reversal. Since my working hypothesis is that we have MS Light, I decided to give it a try. I already know it is helping me. My chronic nausea is almost gone and my gut function is much improved. Ali is less sure, but likes it and plans to continue. Only two weeks. We were already on a good gluten free, mostly dairy free, whole food diet. Changing diet is a process, but we have taken it to the next level. Force feeding vegetables:). 9 cups daily, or as much as we can stuff in. Lots of leaf and berry smoothies. We have eliminated grains and added sea vegetables. Working on organ meats and bone soup.

There is no one right diet for everybody. Nor do I expect it to be curative. Like everything I do, it is about quality of life. In particular, getting our food from local CSA’s and learning about the source of what we are eating is feeling really good. Learning about food is fascinating. Focusing on making each bite nutrient dense is working for me. Yes, it is a lot of prep work and yes, it is more expensive. I couldn’t have started without Ali, but now I could do it alone. I posted something about the diet on Facebook and the comments that it is impossible are heartbreaking. Why do these patients have no help?

Dr. Wahls has a book on Amazon Minding My Mitochondria in print and kindle editions. Here are her recent papers:

She is doing the work. The Wahls Foundation is working to further her research and is on Facebook. She found something that helps and she is putting it out there. Here are the videos that inspired me: 

Guest Blog: K Update

I am in no way suggesting by posting this that what has worked for K works for everyone. However, the treatments we have used are very low risk and non-invasive. In my opinion, supervised trials of these safe, gentle therapies should be widely available to ME/CFS patients. Val’s account of K’s remarkable progress contains many clues about how to improve. The credit is all K’s. She did the work. I am so proud of her for taking control of her health and finding her own path to wellerness. She is a most remarkable young woman. Now, for some good news from Val. (Here is the link to her original guest blog in March 2012: Seeing Jamie.)

 

K skiing

K skiing

 

It’s been just over a year since I first posted here about my daughter’s (K) experiences with Dr. Jamie’s treatment, so I wanted to do an update to share the really fabulous news about K’s progress.  In preparation, I’ve been re-reading old posts and correspondence, and it’s sure been a lesson in how effective our minds can be at suppressing bad memories — at least the memories that don’t generate PTSD — although some of those 3 a.m. trips to the ER had the potential.

K has continued to improve beyond our wildest dreams over this past year.  These are the symptoms that have improved:

Pain

Her pain has decreased so much that she’s basically off any prescription pain meds. She’ll take a very small piece (e.g., 1/8th) of a 5 mg Percocet tablet for pain in the evenings, but often goes without it now.  This is compared to what she was taking when she first saw Dr. Jamie, when she was using a 25 mcg fentanyl pain patch supplemented with 15 mg oxycodone tablets 4 times/day.  K will still have pain that puts her on the couch with her heating pad some evenings.  But it’s nothing compared to how excruciating and unremitting it previously was.  She also went off Lyrica a few months ago, and this time the withdrawal was barely noticeable.

Sleep

A big shock is that her sleep/wake cycle has straightened out!  She still takes tizanidine at night for sleep, but she can go without it and often substitutes Benadryl instead, believe it or not.  She actually has a REGULAR bedtime now, after all of these years.  She is still a bit of a night owl – bedtime is midnight or 1 a.m. and she usually sleeps until 10 a.m. – but she’s not just endlessly cycling around the clock, and is reliably awake during the daytime.  What a difference being reliably awake during the daytime has made in her quality of life!  As I described in my post a year ago, she’s had terrible sleep since she was born, so I never thought we’d see this.

OI/POTS

One of K’s scariest symptoms was fainting without warning.  That stopped happening over a year ago.  When Dr. Jamie did the 5-minute standing mini-tilt test with K last October, K’s vital signs did what they were supposed to do and the test didn’t bother at all.  The first time Dr. Jamie did this test, we had to stand right next to K to make sure we could catch her if fell, and it was very painful for her. Now she can stand up long enough to take a really looonggg shower (annoys the heck out of my husband) without all the blood pooling in her feet and ankles and no dizziness.  She can even stand up in the kitchen long enough to help with dinner!

Cognition

She is able to be on the internet again finally!  Her cognitive limitations that made it impossible for her to do much more than watch tv and read romance novels a few hours a day are gone.  Having an iPad also helps.  Now she’s once again voraciously reading the news and the kinds of complex political and economic analyses she used to love, posting on facebook and in forums, handling twitter, and even doing some writing.

Gut

This, too, has straightened out.  No more terrible cramping and it all works normally for the first time in her life.  Interestingly, she’s just discovered that she does much better by avoiding gluten.  She was tested for celiac when she was having extreme gut problems in her early 20’s, but was negative.  And she’d tried a low-carb diet in the past, which seemed to make no difference at all previously.  But now, also at Dr. Jamie’s recommendation, she’s finding that avoiding gluten and just about all processed foods is helping a lot.

Exertion

The most amazing thing of all is that she’s now capable of vigorous physical exercise with no PENE!!!  The background on this is that we’ve relocated to Hawaii – just in time for Dr. Jamie to move her practice to Arizona…  But we fell in love with it here and moved this past year.  Hubby and I got to Hawaii on September 1st.  K wasn’t able to get here until early October because of complications from bringing her dog into Hawaii, but then had a full month of treatment with Dr. Jamie and basically finished detoxing off the prescription pain meds.  She spent December and January in Seattle and handled it really well, despite it being cold, dark and damp, which formerly made Christmases there a really bad time for her – not to mention how difficult it was for her to handle the flights.

But here is the big news:  She was well enough by late January to go SKIING!!!  It’s something she has always loved, but she had to stop when she was about 16.  We hadn’t even kept her equipment.  So, she used one afternoon’s worth of energy to go get the rentals she needed.  Then the next day, she was able to ski two runs in the afternoon, with no PENE.  AND, she did it again the next day!!!  (Apologies for all of the exclamation marks, but I really can’t help it.)

When she got back to Hawaii at the beginning of February, she started swimming.  Vigorously.  For increasing lengths of time and over increasing distances.  In the ocean, with waves and sharks (seriously) and currents.  Doing the crawl – you know, that swim stroke that has you lifting your arms over your head and uses the muscles in your neck, shoulders and back, where her worst pain has always been located???  And she says it feels wonderful – no PENE from this either!  In fact, she craves the exercise now and goes at least every other day and often daily.

Oh, and Fatigue

I’ve never known what this is supposed to be about.  She felt like shit all the time.  She was in so much pain and misery she could never sleep well and any kind of exertion made everything worse.  Or, she could never sleep well and so was in constant incredible pain and misery, and any kind of exertion made it all much worse, as well as making her feel fatigued.  She desperately tried to sleep as much as she possibly could to escape the conscious experience of how unremittingly miserable she was, but it didn’t alleviate the misery, no matter how much she kind-of slept, and being constantly “fatigued” was a by-product of the entire mess.  She was completely incapacitated and felt horrible all the time, awake, asleep or in between.  She could barely move on most days.  Is that “chronic fatigue?”  “Feeling dead tired all the time” is the least of the categories of misery this disease imposes.

But, anyway, she still gets pooped out and has to lie down a good part of every day.  She still has nightmares that interrupt her sleep from pain and misery some nights. She isn’t close to having the energy we see that her friends are able to expend in a day.  She doesn’t faint, can get out of bed, dress herself, exercise, drive, stand, shower, shop a little, cook a little, talk on the phone or in-person for longer periods, chat online or text more and for longer periods, read and comprehend intellectually challenging stuff, and doesn’t pay for it.  When she overdoes, the payback is limited to the next day and she’s not flayed by it for the next week or weeks or for months.  She can travel on airplanes without being destroyed for weeks afterwards.  She’s not in bed 24/7 with her eyeshade on and earplugs in, and doesn’t have to crawl to the bathroom.  Is she less “chronically fatigued?” Yes, she feels less “fatigued,” but focusing on fatigue as the major symptom of this disease is ludicrous.

Summary

Taken together, this all adds up to much more of a real life than she’s had in 10 years.  She’s not even close to being able to work or sustain a social life yet.   But it seems like in a few more months…?

Next Challenges

The next big step is resuming her education.  Not only has it always been near and dear to her heart, but it’s also looking like she may be able to do paid work eventually and even possibly in a profession.  It’s been 7 years since she finished the last online college course that she was able to complete.  She tried for three more semesters, each of which ended abysmally.  As any young person who has this disease has experienced, dealing with our educational systems’ rigidity and lack of comprehension has left lasting scars, not only to her self-esteem but also in response to the plain old distrust, insults and abuse that are visited on our very ill young people by so much ignorance.  Speaking of PTSD, we’ve labeled all of that as Post-Traumatic-Student-Disorder.  We’re not only dealing with the residue of bad educational experiences, but there is the additional discomfort now associated with being an older student. As we move through the processes required to get her enrolled in online classes again, I’m realizing that she’s not the only one with this version of PTSD!

Attributions

In looking back at my blog post from 14 months ago, I see that I said, “I’m pretty sure that if we only stopped here with oxygen, hyperbaric and Deplin, all these gains would fade over the next 2 years.”  Well, we’re only just a couple months past a year out from that self-protective prediction – we didn’t want to let ourselves have too much hope.  After all, there are stories around of PwME who go into remission for years at a time, attributing it to some combination of treatments or other, only to have it fade away over time or end with another crash.  So, it’s possible this past 20 months of improvements may be another example of the relapsing/remitting nature of this disease. There may not actually be a link between the improvements and the high-flow oxygen, Deplin, the mild HBOT Dr. Jamie provided over a month in March 2012, and then again between October and December this year, dietary tweaks and getting her off all of the prescription meds.

But K has inadvertently done her own within-subject research on whether it’s these treatments that are actually responsible for the improvements.  For example, there have been occasions over the past year when we were unable to arrange for her O2 in the midst of our moving and travels.  She reports that within 2-3 days of being off the O2, her energy starts decreasing, then her pain level starts increasing, then the brain fog starts returning.  She hasn’t had to go without it longer than 2 weeks, but she REALLY noticed the difference.  The effects of going without Deplin are milder.  Its absence also increases her fatigue and brain fog, but doesn’t have as much of an effect on her pain as the absence of O2 does.  For a former treatment-resister of the youthful “if it’s not a magic bullet that makes me feel better immediately, I’m not going to do it” type, she’s become very dedicated to making sure, herself, that she has her O2 and Deplin now.

And now there is this happy little study from Turkey that came out the other day:  “The efficacy of hyperbaric oxygen therapy in the management of chronic fatigue syndrome”.  In a very preliminary way, it supports what K and some of Dr. Jamie’s other patients are experiencing.  That is, if you pulse the patients with high dose oxygen, their symptoms abate.  And, based only on K’s really positive, immediate happy experiences with HBOT vs. the slower, but continuing improvements from daily high-flow O2, I’m betting there’s a dose-response relationship that wouldn’t be hard to demonstrate at all, if there were researchers who had the funding to look into it.  Of course, there is absolutely no money to be made by Big Pharma on this, so we can be sure that the NIH, CDC, the CAA, etc. won’t ever fund research on such a simple, inexpensive, accessible thing as high-flow oxygen from a tank or concentrator, which insurance and Medicaid/care in the US cover and can be delivered to the bedsides of even the sickest patients.  But, I sure do hope these lovely guys in Turkey continue looking into it.

Once again, I apologize for the excessively long post, but I have two more things to report/say.

A Step Back

K went back on Lexapro last fall.  In the Oct-Dec timeframe when K was upset about moving to Hawaii and was going through the rapid withdrawal, her mood tanked.  Going back on it helped, even at the much lower dose she is now taking.  I think she’s ready to go off it again, but I’m just an observer these days.  With all of these improvements, she’s really able to be in charge of managing her own treatment. Yay!!!  Dr. Jamie wasn’t in favor of K going back on Lexapro last fall, but K was sure she needed it then, and Jamie was so good about supporting K’s decision. They’ll figure it out.  As a Mom who spent years in pure panic mode, it so is nice to have K able to evaluate these things for herself.  It’s even nicer that K has a Dr. who puts her ego aside, understands how complicated and interesting it is for K to be emerging from the horrible prison of this illness, and knows how to support K as she begins catching up in life.

Rate of Improvement, New Benefits from Old Ideas, and New Sensitivities

The strangest thing about all of this is that K’s rate of improvement has massively accelerated since she got past the opiate and other prescription med withdrawals in January (except Lexapro, as above).  Whereas the first year or so on Dr. Jamie’s treatments gave her slow, but steady improvements, over this past 3-4 months, the pace has accelerated.  Was all that garbage interfering with and slowing down the rate of her improvements?  Probably.

Or, what if there are thresholds in this disease where old hat treatments/changes actually can make a difference, if we could somehow stop the cascade of failures?  I don’t discount the beneficial effects of K getting off the dozen or more prescription meds her previous physicians had thrown at her (and I permitted in desperation – Mom guilt).  But, beyond that, over the past 20 months, it’s as if every system that failed sequentially as her disease progressed has been coming back online.

As she was getting sicker and sicker, it was like this disease attacked one system at a time.  As I wrote in my post last year, she had sleep and gut problems from birth, and those have been the most recent improvements.  The OI/POTS and migraines came next at puberty.  Then, the excruciating pain and fatigue/PENE soon after, but distinctly later by a year.  Then the complete hormonal failures.  Then a wild and crazy exacerbation of her gut problems that had her in the hospital numerous times for a year.  And finally, the complete cognitive shutdown.  Over the past 20 months, it’s as if the systems that control those symptoms at first stuttered into occasional action, then have eventually kicked in to functioning somewhat close to normally again.  I’m reminded of Paul St. Amand’s claims about how “reversal” works on his guaifenesin protocol.  It has been interesting how the symptom sets have improved in the reverse order from how they initially shut down.

It is also so strange how things that made no difference at all or made her WORSE while she was getting sicker and sicker are now making a positive difference.  I mean, really, how weird is it that she’s now dedicated to vigorous exercise to control her pain and it actually makes her feel better overall with no PENE?  How can that be?  And how strange is it that she’s suddenly discovered she is gluten intolerant?  Another small change is that arnica actually works for her now to give a little pain relief now and then, when it was one of the first treatments we tried and did nothing at all to help her back then. What’s with that?

Wishes, not Conclusions

I wish we knew why Dr. Jamie’s treatments have been so good for K.  I wish we knew what has been making these treatments work so well for her, but not some others.  I especially wish we knew whether K’s upward trajectory will continue and the improvements will last.

I’ll continue to post updates as this evolves.  A little more wellerness as every month goes by has been unbelievably wonderful.

Hate this disease, but I sure do love Dr. Jamie.  Thanks so much, dearest friend.

 

K after swimming

K after swimming

 

The Doomsday Scenario

An important new paper has been published: Xenotropic MLV envelope proteins induce tumor cells to secrete factors that promote the formation of immature blood vessels. Muegai et al. The et al includes Pathak who published the paper with Coffin which identified XMRV as a virus created in the lab. From the title you might think it is about cancer and blood vessels; however, look at the last sentence of the conclusion:

… the results suggest that xenograft approaches commonly used in the study of human cancer promote the evolution of novel retroviruses with pathogenic properties.

Here is the crux of the matter:

The evidence that XMRV was generated as a consequence of studies aimed at elucidating the pathology of human disease is disturbing in that it highlights long feared dangers of use of xenograft tissues in clinical settings, including porcine valves [14,15]. Of even greater concern, the results support the idea that attempts to develop better therapeutic interventions might inadvertently promote the development of pathogenic viruses. However, the following observations refute this possibility: First, although xenotropic and polytropic MLVs have been described as far back as 1970 [16,17], as of yet there has been no validated evidence of human infection by this class of viruses. Second, despite intensive investigation of XMRV by many laboratories [1,18,19] there is no evidence that XMRV is capable of inducing transformation of cells [1,20], although there is recent evidence showing that XMRV infection of LNCaP cells resulted in modest increases in proliferation, and invasion of cells into Matrigel in vitro (Pandhare-Dash et al. [4,21]).

Are you reassured? Their first point is a basic logical fallacy. Absence of proof is not proof of absence. Nobody ever found it, so it isn’t there. Their second point says XMRV, the manmade gamma retrovirus about which we know the most, isn’t dangerous, maybe. What a relief. Yet even they are now admitting, XMRV is not the only one out there. They found a new one for this paper. So now there are at least two, and no longer such a remote possibility.

The studies described herein address these questions, and show that at least one other XMRV-like virus exists, and that the virus evolved the ability to infect human cells and to express gene products that impact tumor pathogenesis.

But no need to panic. The folks that brought you this mess, will figure it out one of these decades. Recombinant Origin of the Retrovirus XMRV, now a year old, where they argued that the chances were “vanishingly small” that XMRV wasn’t created in a lab in the mid 90′s, while studiously ignoring the fact that other similar events were in fact quite likely. So they are finally admitting that the chances aren’t so small, since there have been so many chances. Now there are two. Or is it three? This paper, identified a cell line in use at the NCI that produces another infectious XMLV: The Human Lung Adenocarcinoma Cell Line EKVX Produces an Infectious Xenotropic Murine Leukemia Virus.

Inductive logic is forbidden. No connecting the dots allowed. And who can blame them, when it has been recently demonstrated that dot connecting gets you burned at the stake in the scientific community. Have to start with what we know and carefully build step by step, hoping that the pyramid ends with something coherent. God forbid, we should decide that we have learned something new, something so big that a top down approach should be employed. It is so big in fact, it could explain why 133 million of our people and 55% of our children have chronic illnesses in the US, and why 20% of adults in the developed world have an autoimmune disease. ME/CFS is little. It is time for a revolution. It is an emergency. I wrote that same sentence in 2010 and nothing has changed.

How many young people have been felled by ME/CFS since then? I know about one teenager that was treated in 2010 with antiretroviral drugs and recovered. His mother posted on this blog anonymously at one point, but was presumably prevented from going public. Sick for 8 months, better in 6 weeks. Treated for 6 months and remained in remission off treatment, as far as I know. How did that case report not  make it into the literature? It is unconscionable. I am sick of hearing about how an N of 1 is irrelevant. An N of 1 is called a case report. If important enough, it leads to a pilot study and then a clinical trial.

This burden of chronic disease in children is our replacement for the 20% that used to die before the age of 5 of infectious diseases. So instead of dead children we have live disabled ones. What is going to happen to all these disabled children? Whether the cause turns out to be an activated HERV, or an exogenous simple animal retrovirus (alpha, beta or gamma), the use of antiretroviral drugs is a logical thing to try. It is unfortunate that the only drugs available to us were developed for a retrovirus that is phylogenetically dissimilar from the simple viruses in question here, but even so, AZT, Viread, and Isentress have had a positive effect on a number of patients with ME/CFS, incomplete and, after a while, not clearly worth it, but there is a noticeable positive response in a percentage of patients, which appears annecdotally to be greater than placebo. That should be a beacon in the fog, not a reason to make the drugs taboo. Dr. Snyderman’s cancer is stable on full HAART. Shame on both the scientific and medical communities for ignoring him.

What would happen if you gave antiretrovirals to children at the time of an autistic regression? I know your government wants you to believe that the astonishing increase in ASD, now acknowledged by CDC at about 2%, is because we got better at diagnosing it. While that is undoubtedly partially true, since it is now a common disease, it is insulting to our intelligence to reassure people on that basis. It is only 2%, so no worries; your individual chances of having an autisitic child are still low. But what are your chances if you have CFS or a first degree relative with CFS, or autism, GWI, Lyme Disease, PANDAS, RRMS? These diseases are running rampant. Certain families bear an incredible burden of illness, including early aggressive reproductive and hematologic cancers. It is frightening, even if you look at only one disease at a time, but as part of a preapocalyptic whole involving the health of the species? Terrifying. Virus, injury, genetics. Many perfect storms.

Whatever happened to vaccines being inappropriate for people with immunological abnormailities? Given that patients with various immunological problems now encompass a very significant proportion of the population, the entire vaccine program needs to be seriously reevaluated. Continuing to give ever increasing immunological challenges to a patient population with seriously declining immunological health, for diseases that are extremely unlikely to cause long term morbidity or mortality, is no longer clinically justifiable in my opinion. It is medically incorrect and unethical at this point to take the current vaccination schedules for civilians and the military at face value, especially in light of the implications from this paper, and the recent acknowledgement that GWI is not in fact limited to the veterans of Desert Storm, but still occurring.

The upcoming FDA meeting will no doubt give mention to many more dangerous treatment options than AIDS drugs. AIDS patients got the best. Lots of very clean drugs to work with that cost billions to develop. There are probably many drugs on the shelf that didn’t work well enough for HIV, but might have activity against the viruses we are dealing with. My guess is antiretrovirals will not even be on the table for discussion.

IT IS STILL HAPPENING. Every single day. New people getting sick that should be treatable. The scientific community should not be allowed to take their own sweet time about this. It is not acceptable in the midst of this pandemic for them to withhold anything clinically relevant, whilst expressly trying to prohibit the off-label use of legal, safe drugs that might help patients who are in dire straights, patients suffering beyond belief, for whom there is no meaningful treatment. But the culture is to “burn at the stake” any scientist that steps out of bounds, as we have already witnessed. Doctors too, for that matter.

Look at the tunnel vision in this paper. It is all about cancer and xenografts. No mention that gamma retroviruses cause neuroimmune diseases in vivo, as well as cancer. No mention that there are aspects of modern biotechnology that could be causing the same or worse problems than the ones described in this paper, notably hybridoma technology. And nothing about vaccines, the sacred cow, which contain foreign DNA and are parenterally introduced, given in ever increasing numbers and combinations to an ever more vulnerable population. Live attenuated vaccines are grown in cultures known to express animal retroviruses, e.g. chick embryo, mouse brain culture, monkey kidney cells. Here is a list of vaccine excipients and culture mediums used for production from Wikipedia. And that’s now. Can you imagine what the technology was like in the 50′s, 60′s and 70′s? Viruses successively passaged through mouse brains, passaged meaning brain sucked up with a big needle and injected into the next mouse, then eventually the resultant sludge was injected into or fed to people. Now we can tell what we are doing and we are still doing it. Chemical Induction of Endogenous Retrovirus Particles from the Vero Cell Line of African Green Monkeys.

The paper under discussion mentions the “plasticity” of these viruses. They recombine and rescue each other. But scientists aren’t allowed to connect the dots, even when obvious, as it should have been a couple of decades ago, since it was known by the 70′s that these viruses were there. Here, written by a couple of the scientists who have recently contributed to the distortion of the true significance of XMRV, telling us in 1995 what they feared, but did nothing about. I have posted it before and try not to repeat myself, but in light of this paper, it deserves to reappear.

CoffinStoye95

The assumption that these viruses could not harm humans was made on very shakey ground; everybody was having too much fun tinkering to be stopped by a few qualms. There were a few absence of proof experiments. What hubris! Now, this is the only explanation for ALL of the observed phenomena, encompassing the environmental and genetic aspects, the variations on a theme so clear to see in the various patient cohorts. The Lipkin paper came up with positive serology in 6% of the study population, patients and controls, to a very nasty defective murine retrovirus that produces Env. That particular mystery should be a high priority by now. Why is the 6% not being studied intensively? They found positive serology in human beings to pathogenic retroviral Env in Lombardi et al, they found it in Lo et al and they found it in the Lipkin study. The 6% may be, probably is, only one of many. But no need to panic.

On the personal side, as I reported last time, I went back on Viread. I again noticed an uptick in function and ability to withstand stress 6 or 7 weeks after starting it. My blood pressure is now well controlled on additional antihypertensive medicines, in fact better controlled than at any other time in my illness. I started Isentress a couple of days ago and plan to add Kaletra very soon. Ali remains remarkably stable on Viread and Isentress for 3 years now. Her life is very full. She is productive and happy. Her most limiting symptom remains MCS.

I just returned home after a trip to Tucson seeing patients. The first 5 patients I saw were 3 women almost exactly my age and 2 men, both 48 years old and sick for almost four decades. That strikes me as a bit much for coincidence. I have noticed for years, and especially since I’ve been writing this blog, that my December 1953 birth date seems to be at the peak of a bell curve for middle aged ME/CFS women, suggesting something went out horizontally. Was it when we were born? We received the oral polio vaccine, on a sugar cube, but we wouldn’t have all been the same age when we got it, since it wasn’t released until 1961. And we know that there were outbreaks before the polio vaccine. Papers have documented certain years with peak waves of onset. All of this fits with the idea that it has happened multiple times and each time, it looks a little different, e.g. average age of onset, gender susceptibility, most prominent symptoms, thus the misconception that it is a heterogeneous problem.

Just as there were many retroviral invasions in the distant past, in this paper we have emerging evidence that it has happened again, on a grand scale, over a very short period of time. There are most likely already some viruses that are endogenized in families, since it has gone unchecked for so long. The very high incidence of PCOS in young ME/CFS women may be consistent with a retrovirus invading the germline. When I first wrote about this possibility, I thought it was irreparable, a true doomsday scenario, but it is not. Evolution will deal with it, even while our fertility is dropping at an alarming rate. Deletions will occur, possibly in not very many generations. We will learn how to stay methylated to keep our viruses quiescent. We will eventually learn to manipulate epigentic factors in our favor. But like carbon emissions, we need to stop it now. A retrovirus or pieces of a retrovirus now and again, repeated exposures to endocrine disruptors, synthetic hormones and steroids, add a little Bt toxin, a “cover your ass” CT scan and a couple of radioactive tracers for worthless imaging, courtesy of your doctor, and voila! A recipe for the disaster that is occurring, while nobody panics.

Today’s song: You Haven’t Done Nothing by Stevie Wonder

MS Light?

What’s occurred in the last 30 years is criminal, Mikovits says today. “Mothers and fathers got sick, their children got sick.” But with heightened attention, she adds, patients are likely to get help soon. Even lacking a causal pathogen, biomarkers in this patient population can be studied for clues. “We can find therapies for the CFS patient population even before we determine the exact cause,” Mikovits says.
Chasing the Shadow Virus by Hillary Johnson Discover March 2013.

 

As I said last time, I started Viread again, because I became dangerously hypertensive, a few weeks after stopping it. I had a significant drop in my BP, almost to normal from days 6-12, then it went up again, not quite as high as before, but very high. After much fiddling, it is now controlled, but I had to add additional antihypertensive medication. Happily, after a month back on Viread, there is a downward trend again and I’m hoping I’ll be able to wean from the extra treatment soon. This is not the first time I’ve had this problem, but it was the worst episode yet, and was related in time to stopping Viread. I have been feeling significantly better for the last week, and am also back to baseline productivity. I flared for the first few weeks I went on Viread the first time also. I am going to Tucson to see patients in a couple of weeks and when I come home, am planning to restart Isentress and then Kaletra. I really didn’t want to go back on Viread, but it does seem that I’m getting a payoff again from it. I went off because I wasn’t doing well, and things got even worse, now better back on. I am just reporting, not explaining why or how. The disease is a relapsing remitting illness all on it’s own and changes may or may not have anything to do with the last thing you did.

My reading lately has been about retrotransposons and HERVs, especially MSRV, multiple sclerosis-associated retrovirus. Here is a cutting edge, must read paper, senior author Hervé Perron, whose name appears on most of the important papers on this topic: The DNA Copy Number of Human Endogenous Retrovirus-W (MSRV-Type) Is Increased in Multiple Sclerosis Patients and Is Influenced by Gender and Disease Severity.

MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease.

The envelope protein from multiple sclerosis (MS) associated retroviral element (MSRV), a member of the Human Endogenous Retroviral family ‘W’ (HERV-W), induces dysimmunity and inflammation.

Env antigen was detected in a serum of 73% of patients with MS with similar prevalence in all clinical forms, and not in chronic infection, systemic lupus, most other neurological diseases and healthy donors (p<0.01). Cases with chronic inflammatory demyelinating polyneuropathy (5/8) and rare HC (4/103) were positive. RNA expression in PBMC and DNA copy numbers were significantly elevated in patients with MS versus HC (p<0.001). In patients with MS, DNA copy numbers were significantly increased in chronic progressive MS (secondary progressive MS vs relapsing-remitting MS (RRMS) p<0.001; primary progressive MS vs RRMS -<0.02). Env protein was evidenced in macrophages within MS brain lesions with particular concentrations around vascular elements.

The above paper concludes that exogenous virus production is unlikely. Particles have been identified in MS patients going back to 1989: Leptomeningeal cell line from multiple sclerosis with reverse transcriptase activity and viral particles. 

In fact, a virus was identified in MS in 1975. Look at how far they got with the technology at hand at that time: Multiple sclerosis-associated agent: transmission to animals and some properties of the agent.

In confirmation and extension of observations by Carp and his associates, brain tissue and sera from patients with multiple sclerosis (MS) were found to harbor an agent which induces a transitory depression in polymorphonuclear leukocytes (PMN) in mice as well as in rats, hamsters, and guinea pigs. All of eight MD brains contained this agent at titers as high as 10(-9)/g of brain tissue. The agent was found in MS sera at titers up to 10(-3)/ml of serum, but its presence depended to some extent on the clinical status of the patients; it was observed more frequently in sera of patients with active disease (73%) thatn in sera of patients with quiescent disease (31%). Control brain tissues or sera failed to induce PMN depression. The apparently MS-associated agent (MSAA) passed through 50-nm but not 25-nm membrane filters (Millipore Corp.) and was largely sedimented at 105,000 X g but not at 50,000 X g for 1 h. It multiplied to high titers in the central nervous tissue of the inoculated animals and could be serially transmitted from animal to animal by passage of brain homeganates. Various observations and considerations appear to preclude that MS-associated agent represents an indigenous animal virus. Although its role in MS remains to be determined, it should be considered a candidate for the etiology of this disease.

Endogenous retroviral genes, Herpesviruses and gender in Multiple Sclerosis contains electron micrographs of MSRV particles.

Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human chromosome 7q: possible components of a ‘chain-reaction’ triggered by infectious agents in multiple sclerosis?

The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases associating neuroinflammation.

Endogenous retroviruses represent about 8% of the human genome and belong to the superfamily of transposable and retrotransposable genetic elements. Altogether, these mobile genetic elements and their numerous inactivated “junk” sequences represent nearly one half of the human DNA. Nonetheless, a significant part of this “non-conventional” genome has retained potential activity. Epigenetic control is notably involved in silencing most of these genetic elements but certain environmental factors such as viruses are known to dysregulate their expression in susceptible cells. More particularly, embryonal cells with limited gene methylation are most susceptible to uncontrolled activation of these mobile genetic elements by, e.g., viral infections. In particular, certain viruses transactivate promoters from endogenous retroviral family type W (HERV-W). HERV-W RNA was first isolated in circulating viral particles (Multiple Sclerosis-associated RetroViral element, MSRV) that have been associated with the evolution and prognosis of multiple sclerosis. HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-like receptor 4 on immune cells. This ENV protein has repeatedly been detected in MS brain lesions and may be involved in other diseases. Epigenetic factors controlling HERV-W ENV protein expression then reveal critical. This review addresses the gene-environment epigenetic interface of such HERV-W elements and its potential involvement in disease.

Here is a paper about something that could turn into useful therapy, overlooking the significant risks associated with the administration of monoclonal antibodies and the inherent risks involved in hybridoma technology, which involves fusing human cancer with animal B cells. GNbAC1, a humanized monoclonal antibody against the envelope protein of Multiple Sclerosis-associated endogenous retrovirus: a first-in-humans randomized clinical study.

Human endogenous retrovirus (HERV) genes represent about 8% of the human genome. A member of the HERV family W, the Multiple Sclerosis-Associated Retrovirus (MSRV) gene, encodes an envelope protein (Env), which can activate a proinflammatory and autoimmune cascade through its interaction with Toll-like receptor 4. Due to its proinflammatory property and an inhibitory effect on oligodendrocyte precursor cell differentiation, the MSRV-Env protein could play a crucial role in the pathogeny of multiple sclerosis. GNbAC1 is a humanized monoclonal antibody of the immunoglobulin G4 type, which is directed against MSRV-Env. After validation of the MSRV-Env as a therapeutic target in preclinical experimental models, a clinical development program was initiated.

In these healthy male subjects, the safety and pharmacokinetic profiles of GNbAC1 appeared favorable. These findings are expected to allow for the launch of a Phase II development program for this innovative therapeutic approach in patients with multiple sclerosis. ClinicalTrials.gov identifier: NCT01699555.

However, rather than injecting antibodies to gobble up the viral envelope, given the real and theoretical problems with monoclonal antibodies, it would be better to keep Env from being produced in the first place. Maybe a protease inhibitor is the missing link. AIDS drugs didn’t work well until they had PI’s. Dr. Snyderman’s data suggests this was the case for him. I am happy to report that he remains stable at 32 months. Does a response to a PI imply exogenous virus? How far does a HERV have to get in its reproductive cycle before a PI would do some good? SFFV is a defective virus with a pathogenic envelope. If MSRV produces variable particles, some of which appear complete on EM, is it ever infectious?

Reading about MS, thinking about my own clinical presentation and putting it together with everything we have learned since XMRV entered our lives, ME/CFS may exist on a spectrum with MS, in the same way that Aspergers Syndrome is part of the autistic spectrum. Certainly, we are a variation on a theme. I have called it MS light before and I think it is a good working hypothesis for now. Up To Date’s summary on MS is here. Note the many similarities, genetics, epidemiology (including cluster outbreaks), possible problems with the Hepatitis B vaccine. It seems to me our best hope post XMRV is to ride on the coattails of MS, even though it is pathetic that we need to, given that there are at least three times as many of us.

I’m getting lots of questions about what I think of the paper published by De Meirlier et al. Plasmacytoid dendritic cells in the duodenum of individuals diagnosed with myalgic encephalomyelitis are uniquely immunoreactive to antibodies to human endogenous retroviral proteins. I am not going to evoke all the reasons why I might have a problem with this paper, whatever it says. I have moved on. Much of it is documented elsewhere on this blog.

Taking the paper at face value, problems with it are the tiny sample size, from patients that I hope had very serious GI complaints, compared to the patient population as a whole, since, presumably, they warranted a duodenal biopsy. I would like to take this opportunity to emphasize that I am completely opposed to taking any risk of harming fragile patients with unnecessary procedures in order to study the disease. There is no reason to do duodenal biopsies on garden variety ME patients, so the patients in this study should have had significant inflammatory bowel disease, not just IBS. The procedure carries a significant risk. A duodenal punch biopsy can result in death. There is lots of tissue to study without resorting to that. Fresh tissue is harvested all the time for other reasons, there is lots of material to autopsy and lots of specimens in paraffin, which is what was used in this study. My small intestine in paraffin is stored down the street at the local hospital. And plasmacytoid dendritic cells can be harvested from peripheral blood.

The simplest explanation for the findings in this paper is that there was a range of proteins consistent with a generalized activation of HERVs. Many things can transactivate HERVs including recombination events and exposure to exogenous retroviruses. Perhaps they didn’t name the HERV because they were all transactivated? This is what you might expect in someone with inflammatory bowel disease. We have no idea whether these people had a neuroimmune disease or not. The fact that they had a range of symptoms that would qualify for a clasification of CFS is neither here nor there. Endogenous retrovirus-K promoter: a landing strip for inflammatory transcription factors?

There are quite a few papers worth reading in the references, but they missed one:  Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4(+) T cells.

I hope they are right. It would set us on a path to catch us up to MS, where we belong. However, the paper is so vague. Antibodies to proteins expressed by a generic HERV. This negative paper was also just published: Human Endogenous Retrovirus-K18 Superantigen Expression and Human Herpesvirus-6 and Human Herpesvirus-7 Viral Loads in Chronic Fatigue Patients. It is good news for us that this avenue of research is being pursued.

I expect the De Meirleir paper to get shot down or be ignored completely. The scientific world will probably only read it for laughs, considering the source. They didn’t find a “real” virus this time, so nobody needs to spend millions of dollars to prove it wrong. MSRV was ignored for decades, even though it is associated with a more sympathetic disease than ME/CFS. Progress with it has been glacial, revealing the non-urgent, almost lackadaisacal attitude of the biomedical world towards activated HERVs, even one that was shown to produce viral particles over 20 years ago. In any case, infectious or not, there is increasing agreement that HERV W is associated with MS and can transcribe an Env protein which is neuropathogenic.

And another related illness: HERVs expression in Autism Spectrum Disorders.

I am particularly happy to report that my friend Dr. Mikovits is doing well through it all. She has received many letters of support and asked me to let the community know that she is fine and excited about the future. She is consulting with respect to drugs and diagnostics. She continues to lecture. Currently, she is working on projects with Dr’s Ruscetti and Lipkin, and, in a translational capacity with several medical doctors, Eric Gordon, Chitra Bhakta, Derek Enlander, Paul Cheney, Michael Snyderman and myself.

This excerpt is from an email to me a couple of days ago when I asked her a few questions for this blog:

Planning for the April 25th FDA meeting…a two day meeting to get drug companies and clinical trials going..to avoid the failure of Hemispherx..we have a huge opportunity here..talk about that..tell the patient community I will go there and work to bring them the drugs that are out there as soon as possible..we as a community do not have to go back to basic research where we are decades away..we can translate what we know.. write about that …move forward..

My background is in antiviral drug mechanisms and epigenetic drug development..I am going back to my roots to focus on drug development in infectious/ inflammatory disease…I can now apply my expertise and extensive network to ME/CFS..

Dr. Lipkin said this about her in Nature, only a few months ago:

I feel very badly for Mikovits, [her co-author] Ruscetti and Harvey Alter [a hematologist at the NIH Clinical Center in Bethesda, Maryland, who led one of the CFS studies]. Mikovits in particular — she has lost everything. She can be wrong but she’s not a criminal. She has been honest in a respectful, forceful way and said that we have to conclude that we were wrong. You can imagine how difficult it must be, and I think she should be applauded. Lots of people wouldn’t have the balls to do that. She has come across as a scientist who really believes in the importance of truth.

Dr. Judy has come a long way since then, pulling herself up by her own bootstraps. I am in awe of her resilience. Handed lemons, she is making excellent lemonade. Stay tuned.

Today’s song: Titanium by David Guetta

Twists And Turns

The world will not be destroyed by those who do evil, but by those who watch them without doing anything. ~ Albert Einstein

When I started this blog, I promised to share my journey as it unfolded, before knowing the outcome. My goal was always to explore and learn, not convince anybody I’m right, since I clearly don’t know. So here’s what’s happened since I last wrote. A day after I wrote the last blog, I ran out of Cozaar (losartan), forgot I hadn’t put it in my pill case for the whole week and missed two doses. Before restarting it, I checked my blood pressure and it was 212/127. I’ve missed losartan other times in the last few years, but never with such a severe elevation and always responsive to restarting the med. But this time, my pressure stayed ridiculously high, even after adding a second drug, amlodipine, which I have used as a second drug before, but haven’t needed in several years. I have a long history of labile hypertension and a period of persistent severe hypertension was the problem that ended my Emergency Medicine career in 1996.

It happened about a year after my first symptom, following a period of unrelenting stress. The blood pressure elevation came with a feeling of doom. The numbers were often high, for most of a year, despite all the drugs my doctors threw at it. Initially my academically inclined physicians were excited by creepy medically unexplained symptoms in a colleague. They thought I had something cool, like a pheochromocytoma or carcinoid. They sent off all their esoteric tests and when it was all negative, or almost negative, they concluded that I either had a world class case of white coat hypertension or was crazy and not taking my meds. Indeed, the independent medical exam ordered by my disability carrier concluded I could return to the ER if I took my antidepressants like a good girl, despite my protestations that I wasn’t depressed and my blood pressure was very high at home too, with nary a white coat in sight, besides my own.

It is a long, sad story, filled with injustice and stupidity, mine and my doctors’. I’ve written some of it here before, but I’m mentioning it again now, because this current episode was so similar to what happened then. The hypertension occurred in the context of an abnormal stress response and autonomic dysfunction/instability. Because my dysautonomia occurs in the setting of hypertension, I don’t have POTS per se, but a variant. The autonomic nervous system wasn’t even part of the discussion back then, and here is why. The first paper in the medical literature on POTS, or orthostatic postural tachycardia syndrome, was published in 1993, only 2 years before my first symptoms and had no penetration as yet to an average work-a-day doc: Idiopathic postural orthostatic tachycardia syndrome: an attenuated form of acute pandysautonomia?

Even by 2002 when my husband developed severe dysautonomia, it was not part of the common medical lexicon, as it is beginning to be now, finally. Recognizing autonomic nervous system dysfunction as a core deficit in Gulf War Syndrome sufferers is a big step from our old concept of PTSD. So what do we think? Was it a new phenomenon? Or were all the doctors who came before me such poor physical diagnosticians that they missed it without the benefit of tilt tables?

As I have previously reported, I did not have viral onset CFS, but a very atypical onset and course, which was clinically more similar to Gulf War Illness than ME or CFIDS, as it was called then. If I’d been in the military at the time, instead of a civilian working in a trauma center, I might have landed in that bin. Now, 20 years later, it is finally starting to occur to the scientific and medical communities that the problem is in fact more extensive than the 250,000 soldiers who got sick at that one particular place and time: Report: New veterans showing Gulf War illness symptoms. Could this be a prelude to asking questions about the pathophysiological similarities observed in the various neuroimmune disease cohorts, diseases which were rare or unknown just a few decades ago? What risk factors are shared by vets with GWI-like illness, autistic children and patients with ME? Why is that question not being asked in the context of the public health emergency that it is?

So I’ve had problems with my BP all along, but nothing as severe or sustained since way back then, until now. I’m intolerant of most classes of antihypertensives, but have evolved an approach to BP spikes that works for me, basically temporizing until the episode resolves on its own, since experience has taught me that aggressive treatment will make me bottom out suddenly at some point. I’m better off accepting a mild elevation than pushing my luck, with such an unstable baseline. Hypotension is probably worse. Certainly, it feels worse. I did all the things this time that usually help, and everything else I could think of. I mentioned in the last blog that I had reduced my dose of Deplin as I was feeling sensitive to it while things were getting worse in December. I went back to my old dose of 7.5mg to see if that was the problem. Mood improved, but blood pressure didn’t. Went up to max dose on the newly added calcium channel blocker and took supplements and herbs which support vasodiliatation and relaxation. High dose Epsom salt baths. Biofeedback. Everything worked briefly, but still with regular readings above 200 systolic, plus the continuing waves of dread I was experiencing, so similar to the beginning of my illness. I was trying to figure out which 3rd drug to add soon if something didn’t give, knowing that all the choices were likely to be problematic.

Faced with only unpleasant choices, and since the problem was related, at least temporally, to discontinuing Viread, I decided to restart it. I was in no way excited or positive about it, but felt it was the least of the bad choices. Since stopping it, I had been feeling better in some important ways, with notably less nausea and possibly feeling a little stronger. So despite a strong preference for going ‘au naturelle’, and tired of being a guinea for drugs developed for patients with a different disease by drug companies with no interest in ours, and very tired of copays, I nevertheless found myself surprised to be back in a place where restarting antiretrovirals was looking like my best option. When Ali and I first started arv’s in early 2010, I believed we had a virus which had been confirmed at 3 labs, including the Cleveland Clinic and the NCI, plus published supportive in vitro testing. It made sense then, but now? I spend my energy working on natural solutions for patients. My own goal was to get off any drugs I possibly could. But the blood pressure wouldn’t give, trumping all my reasoning. I went back on…

On the 5th day back on Viread, with a resurgence of nausea worse than before I stopped, I was cursing drugs and drug companies, when my symptoms broke, like a fever. The high blood pressure let go, as did the other symptoms that came with it in a chicken or egg fashion, such as the fight or flight feeling from too much sympathetic tone. It isn’t just a number on a blood pressure monitor, but part of an entire symptom complex. Since things turned around 6 days ago, I’m doing better than before I stopped it in the first place. I have no logical explanation for that. BP is adequately controlled, at least pretty good for me. I am planning to restart Isentress in a week and I am considering lopinavir as a 3rd drug. See the last blog for Dr. Snyderman’s data demonstrating his response to lopinavir. Kaletra is currently part of a regimen undergoing a clinical trial for a beta retrovirus, similar to MMTV, in PBC (primary biliary cirrhosis), with evidence for growing, slowly, as is always the case when it comes to investigations of human retroviruses other than HIV.

Why might this recent experience of mine be interesting to other ME/CFS patients? Hypertension is not usually a finding in this patient group. However, vascular instability is. Increased sympathetic tone is. An abnormal stress response most definitely is. All of that apparently got worse and now better again, in an A – B – A fashion, taking, stopping and restarting Viread. And, distinct from my usual predicament, I could actually measure something. Numbers! BP now coming into line after 11 days back on, starting to decrease the second antihypertensive, didn’t have to start a 3rd class with intolerable side effects. I really wanted off, but I am not afraid of these drugs, so here I am again, and so far, so good.

After watching me twist in the wind for the last couple of months, Ali is planning to sit tight with respect to her antiretrovirals, enjoying her good fortune and relative stability. For those readers who are interested in her regimen for PCOS, she has decided to discontinue Actos for the long haul, even though it helps her in the here and now. She has started a slow wean, planning to increase metformin if necessary.

Having learned the hard lessons personally with respect to unvalidated tests from small labs with special interests, I came across this on Medscape and think it needs to be shared: Lyme Culture Test Causes Uproar. The link works if you have an account, but here is the first paragraph and exerpts of the article about a culture for Borrelia burgdorferi from a lab called Advanced Laboratory Services:

A new chapter in the Lyme disease controversy opened in September 2011 when Advanced Laboratory Services, Inc, announced the commercial availability of a new culture test for Borrelia burgdorferi. Some Lyme patient advocacy groups and physicians began encouraging patients to have the $595 test, but others are concerned about the early commercialization of the still-unvalidated test. This concern may result in changes to how the US Food and Drug Administration (FDA) regulates so-called “homebrew” or laboratory-developed tests (LDTs)…

Soon after Advanced Laboratory Services’ initial public announcements about the new culture test, emails and public statements attributed to Dr. Burrascano began appearing on Lyme-related Internet sites, including comments that the culture test was approximately 94% sensitive and 100% specific.

Dr. Burrascano told Medscape Medical News that the validity of the culture test was established using blood samples provided by physicians and that the identity of Borrelia was confirmed by its ability to grow in Borrelia-specific media, by its characteristic appearance on darkfield microscopy, by reacting to published Borrelia-specific polyclonal and monoclonal immunostains, by DNA polymerase chain reaction (PCR) at 2 different loci, and by direct DNA sequencing. These data are so far unpublished…

And here is the disclosure statement at the end of the article:

Dr. Burrascano has disclosed no financial interest in the laboratory, in the Borrelia culture, or in any intellectual property and receives no commissions from the tests. Dr. Burrascano is senior vice president of medical affairs and medical director for Advanced Research Corporation, a contract research organization with the same president and corporate address as Advanced Laboratory Services, Inc. Dr. Mead And Dr. Green have disclosed no relevant financial relationships.

Oy vey. Here we go again. Another unvalidated test to justify bad treatment. What’s wrong with the unvalidated tests they’ve been using all along? The ones that are almost never negative for various tick borne diseases? And this, hitting the presses coincident with the WPI promoting Dr. De Meirleir’s lecture, yet another doctor with a history of profiting from unvalidated lab tests. I think I’ll stop now, so my blood pressure stays down, and end on a positive note.

I just had the pleasure of reading Hillary Johnson’s very fine piece in the latest edition of Discover Magazine, available to non-subscribers soon in print at a newsstand near you. Her most excellent account of the XMRV saga, “Chasing The Shadow Virus” sheds journalistic light on the events that occurred and raises desperately needed awareness for our shadow illness. I was close to the events, have my own perspective and strong opinions about what happened and why; this article rings true to me, maybe because I have this same quote on my phone in a text message, “I still see the footprints of a retrovirus..” Yes, Pandora, the box is open forever. Denial is dark and powerful, but eventually, the truth will shine through.

We can discuss possible esoteric mechanisms from now until the cows come home as to why Viread stops an inflammatory process which causes my blood vessels to go into spasm: Brain Microglial Cytokines in Neurogenic Hypertension. But why not start with the most likely explanation? It is a drug which inhibits retroviral reverse transcription. Certainly it is a real possibility that it is doing what it was designed to do.

 

Big Yellow Taxi – Joni Mitchell

Our experience with antiretrovirals

Two months shy of three years, I discontinued antiretrovirals, began after receiving reports of positive XMRV cultures from VIP Dx in January 2010. Ali and I started AZT and Isentress in March 2010, added Viread in May 2010, discontinued AZT in Feb 2011. I discontinued Isentress in August 2011 and remained on Viread monotherapy until two weeks ago. Ali continues on Viread and Isentress. We also tried the protease inhibitor Lexiva, and I tried it a second time, but didn’t tolerate it.

We both improved for the first year, but it wasn’t a clean experiment, as I’ve said all along. We did other things concurrently. When we started, I thought we’d ride on the coattails of HIV and have viral load measures in a year or two. We sent lots of blood to the WPI and Dr. Mikovits was studying us, but the specific results were never shared with me and are now lost, with the rest of Dr. Mikovits’ data.

We stopped AZT after 11 months, with no way to monitor, to prevent long term toxicity. Neither of us noticed much of anything coming off of it. By the summer of 2011, I knew there would be no help with monitoring and came off Isentress in anticipation of our both stopping the drugs. I wanted to see what happened to me first, before Ali came off. I tried to stop Viread shortly after. Nothing noticeable happened when I stopped Isentress, but I felt worse after a few days of stopping Viread, better when I went back on. I did that two other times by the first part of 2012, with the same results.

Meanwhile, Ali continued to go uphill. Me not so much. In hindsight, I wish I had not stopped Isentress, since Ali continued to improve and I didn’t. I functioned fairly well, with lots of travel and stress, through my last trip to Hawaii in October, but then crashed pretty hard. By Christmas I was feeling very poorly. I always say, when things go south, stop the drugs, so I did. Since then, I am feeling a little better. I am having less nausea than I was having on Viread, but my nausea predated arv’s by several years and when I went on arv’s, I didn’t think it was worse. I am now on only Cozaar, baby aspirin and hormones. As I got sicker, I my tolerance for Deplin lessened, interestingly, and I am now taking an OTC dose of Folapro 800mcg once per day. I have increased nutriceutical and nutritional support, am doing biofeedback, and am about at my October baseline, I’d say.

Here’s an interesting paper about raltegravir, though reactivated Herpesviruses are not a part of our clinical picture: A Drug Against AIDS Could Be Effective Against The Herpesvirus and here’s the paper: Structure and inhibition of herpesvirus DNA packaging terminase nuclease domain. It isn’t new, but I hadn’t seen it before. Here’s a new one: Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase:

We demonstrated that XMRV RT mutants K103R and Q190M, which are equivalent to HIV-1 mutants that are resistant to tenofovir (K65R) and AZT (Q151M), are also resistant to the respective drugs, suggesting that XMRV can acquire resistance to these compounds through the decreased incorporation mechanism reported in HIV-1.

So there are still scientists working on this really creepy virus that was created in a lab and infects human cells, but fortunately, not particularly well, though the statement below is not very comforting. Severe Restriction of Xenotropic Murine Leukemia Virus-Related Virus Replication and Spread in Cultured Human Peripheral Blood Mononuclear Cells:

In summary, our results show that XMRV replication and spread is severely restricted in PBMCs, but these cells can serve as a reservoir for generation of infectious virus that can potentially spread to cells that express low levels of these restriction factors.

It’s good for us that they are still studying it, because, although we don’t have XMRV, we still may have something very much like it. I still find the extreme resistance to trying HIV drugs for something besides HIV to be completely bizarre. AIDS drugs have been noted to be useful on occasion for Sjogren’s, MS and HTLV, but then generally nobody follows up even so. Here is the latest reference on clinical trials for HTLV associated leukemia: Clinical Trials and Treatment of ATL. I aways find it disheartening to read about HTLV, because it has been neglected for so long, even though it was isolated by Bernard Poiesz, Francis Ruscetti and their co-workers in Gallo’s lab over 30 years ago.

Speaking of dishearteningly slow progress, look at this paper from 2005: Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses. From the abstract: “Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level.” And this one from 2010: The human endogenous retrovirus link between genes and environment in multiple sclerosis and in multifactorial diseases associating neuroinflammation. “In particular, certain viruses transactivate promoters from endogenous retroviral family type W (HERV-W). HERV-W RNA was first isolated in circulating viral particles (Multiple Sclerosis-associated RetroViral element, MSRV) that have been associated with the evolution and prognosis of multiple sclerosis. HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-like receptor 4 on immune cells. This ENV protein has repeatedly been detected in MS brain lesions and may be involved in other diseases.” But nobody wants to try antiretrovirals on these patients?

Why is it such a stretch that the concepts learned from the AIDS epidemic could have vast utility beyond the treatment of that one well funded infection. Where are the drug companies??? We don’t have specific drugs and we don’t have any way to monitor the effects of the drugs we do have. So we are effectively stopped from studying something promising. A good percentage of the people who tried antiretrovirals experienced mild to moderate improvement for a period of time. Very little harm happened, even though it was a completely random and uncontrolled experiment. The drugs are not scary compared to many drugs that are given to ME/CFS patients every day. I can tell you there is a lot more possibility of harm from the SSRI’s, pain and sleep meds which are routinely offered, with no chance of positively impacting the disease process.

So, we as a community paid VIP Dx a bunch of money to tell lots of us we had XMRV. They are lucky the damages were only financial and not large enough individually for anybody to spend the effort to recover. Several people have sent me this: Transcribed  and posted on MECFS forums from Mass CFIDS/ME & FM Association’s Fall 2012 Lecture: (YouTube video of lecture by Dr. Byron Hyde)

Byron Hyde: The other thing he [Lombardi] says is that he studied under Dr. Suhadolnik at Temple University. So I picked up the phone and I [Hyde] phoned Robert [Suhadolnik] – who is a wonderful wonderful researcher man – and I said: ‘Tell me about Lombardi – who studied Chronic fatigue Syndrome under you and did research with you’.

He [Suhadolnik] said: ‘He never did’.

I said: ‘Oh ? What do you mean he never did ?’

[Suhaldolnik:] ‘Well, he came here for a few days and I got rid of him because he was a nuisance and he didn’t knew what he was doing and that was it.’

…one minute later:

Byron Hyde: I figure they (WPI) made somewhere between two and three million dollars on that [XMRV-test]. People all over Europe, people all over Canada, the United States, were sending their blood in. The other thing which is interesting is the Whittemore-Peterson advertises as a charitable institute. It is not a charitable institute. It’s got a Cameo institute on the floor below which is for fee for service. And they are there to make money.

Here is the WPI version: Date: January 6, 2013 (link)

Vincent C. Lombardi, Ph.D., Director of Research (…) He later continued to work in CFS-related research in the laboratory of Dr. Robert Suhadolnik at Temple University, studying the interferon regulated RNase L antiviral pathway and its involvement in CFS. (…)

The bio then goes on to give Lombardi credit for Dr. Mikovits’ ideas. Of course they also give him credit for the collaboration with Silverman. You’d think he wouldn’t be so quick to take credit for that. So let’s see what is left. He got a PhD at University of Nevada, Reno in 2005 and then invested in Redlabs and went to work running tests on humans. What was his dissertation about? When did the training happen that qualified him to be culturing retroviruses from humans? What prior experience did he have running a clinical lab? It would appear that anything he learned after finishing school must have been from Dr. Mikovits. Actually he was already trying to take credit for her ideas when I was there. He took me to breakfast in December 2010 and told me that it was really his discovery. He was rewriting history already, a dishonest post-doc, trying to discredit his mentor to a new colleague.

Please read Larry’s comments after the last blog (link). We were robbed and the WPI is still sucking up all the money. I expected a federal investigation of the lab, holding them accountable for the money they made on the tests, but it hasn’t happened. There seems to be no critical thinking on the part of the government agencies in question. So they have the grants, which will run their multi-year courses, irrespective of whether the money is producing anything meaningful or not. Nevermind that it is a very significant chunk of all the government money available to study our disease and it might be much better used. Why not give that money to Dr. Ruscetti or Dr. Lipkin? Or give it back to Dr. Mikovits, so she can get on with her work, as should have happened in the first place.

Posted last night on Facebook by Joan McParland:

NEWRY & MOURNE ME/FMS SUPPORT GROUP STATEMENT

As most patients are aware, Dr. Judy Mikovits has been forced into bankruptcy due to recent unfortunate events. A number of members discussed this issue at our monthly meeting last night and have made a decision to send some financial help to Dr. Mikovits.

The main reason for this action by some members of the support group is to show our support and also in an attempt to return the unreported kind acts and dedication shown to us by Dr. Mikovits on her numerous visits to N. Ireland.

Many more patients, worldwide, who have contacted me recently have also witnessed and benefited from the caring nature of the human being behind the scientist.

As from today, Dr. Mikovits is now free to return to work, we wish her well and hopefully she will be able to continue her dedication to helping find the answers we all so desperately need and deserve.

The entire situation has already been well summed up by Ian Lipkin’s quote below..

“I feel very badly for Mikovits, [her co-author] Ruscetti and Harvey Alter [a hematologist at the NIH Clinical Center in Bethesda, Maryland, who led one of the CFS studies]. Mikovits in particular — she has lost everything. She can be wrong but she’s not a criminal. She has been honest in a respectful, forceful way and said that we have to conclude that we were wrong. You can imagine how difficult it must be, and I think she should be applauded. Lots of people wouldn’t have the balls to do that. She has come across as a scientist who really believes in the importance of truth.”

On a much happier note, Michael Snyderman is still stable on full HAART. Stable cancer for 31 months. No chemo brain. And still no interest from the scientific or medical communities??? It is a travesty.

Dr. Snyderman’s update…

My study so far shows:

1. The combination of AZT+raltegravir has activity but is not sufficient to maintain the response.

2. Tenofovir has activity but is not sufficient to maintain the response.

3. Lopinavir has activity which so far is longer than previous responses. More data is necessary to know how long this drug will work.

4. A trial with more cancer patients is indicated.  We need to know what are the predictors for response and what is the optimal drug combination.  What is learned from cancer patients would potentially be valuable to patients with CFS.

Click to enlarge

Click to enlarge

 

Tonight’s song: Slip Sliding Away by Simon and Garfunkel