Dr Myhill at the International ME Conference

I found Dr Myhill's conference report very helpful in translating science down to my level. I can't agree with her that it is less important to find causes of ME than treatments for it (treatment being her own field) - I am just very glad that there are people focusing on both. We are very very lucky that people like Dr Myhill are working on treatments. However, I have not given up hope of a cure, so I place a lot of importance on research into causes too.

Here's the report:

May 26th 2010 - Invest in ME International - 5th Conference
A summary of the day and implications for treatment

Speakers: Professor Leonard Jason, Professor Norah Chapman, Dr John Chia, Dr Paul Cheney, Dr Jonathan Kerr, Dr Nancy Klimas, Professor Brigitte Huber and Doctor Judy Mikovits
The role of viruses in CFS/ME
The emphasis of this conference was very much on viral causes of chronic fatigue syndrome / ME and the immune responses that go with that. Much discussion went into the classification of types of ME by various sub-groups particularly by Professor Jason and Dr Kerr, but my view is that at present this has little implication for treatment. Norah Chapman concentrated on cocksackie B infections, Dr John Chia on enteroviral infections, Brigitte Huber on retrovirus HERV K-18 (which we all have in our genome) and Judy Mikovits on the new XMRV virus. All these viruses are implicated in cases of CFS/ME but what makes the difference between a short illness and recovery and illness and prolonged CFS is the response of the immune system to those viral insults. Studies show the virus continues to be present albeit at very low levels and because the virus is at such low levels this explains why many tests do not pick it up - it is simply below the level of the radar.

However this low level viral persistence may result in chronic inflammation in susceptible individuals wherever that virus happens to be and this would explain many of the symptoms of CFS/ME. So for example Dr John Chia found that in 165 patients with CFS 82% had high levels of entrovirus in the gastric antrum of the stomach. Norah Chapman found low level infection by defective cocksackie B viruses in non-dividing cells in particular muscle cells (including the heart muscle) and by implication brain cells (because these enteroviruses persist in non-dividing cells). Brigitte Huber showed that HERV K-18 MRNA levels are higher in CFS patients. Judy Mikovits of course has demonstrated the presence of XMRV infection in 67% of patients diagnosed with ME/CFS compared to 3% of normal controls.

What this tells us is that patients with CFS/ME are not good at dealing with viral infections, they do not eradicate them efficiently and this viral DNA gets in the way of cell metabolism causing a low grade chronic inflammation which means cells malfunction.

The most important point about all this wonderful work is that it clearly establishes CFS/ME as a physical disorder with physical lesions and physical treatments.
The clinical picture
John Chia made the point that enteroviruses are the commonest cause of 'flu-like symptoms. Enteroviruses may be picked up as a result of travel, water sports, gut infections or from local epidemics. He specifically mentioned vaccinations and allergies as risk factors. The way to diagnose an enteroviral infection is first of all to have an high index of suspicion! 'Flu-like symptoms that persist for more than two weeks are highly suspect, but blood testing for antibodies can be misleading. There are often few physical signs, perhaps some ulcers on the tongue, possibly lymphadenopathy and tenderness of the abdomen particularly in the epigastrium, left iliac fossa and right iliac fossa. Sometimes there is sinusitis, colonic inertia and pelvic pain.

How well one deals with the virus depends on whether the immune system is in a state of Th1 or Th2 activation. If one is in a state of Th2 activation one will struggle to get rid of the infection and this state is characterised by allergy, female sex hormones (pregnancy, Pill, between menarche and menopause - ergo women are much more susceptible than men), excessive exercise, vaccinations or another recently acquired infection.

So for example Professor Huber pointed out that we all have HERV K-18 (indeed 8% of the human genome is made up of retrovirus) but the expression of this is induced by Epstein Barr and herpes virus, this activates virus in a way to produce a super-antigen which results in massive T-cell activation, i.e. inflammation. Epstein Barr virus is particularly good at doing this.

An awful lot of the discussion of the day revolved round immune responses to virus. My interest of course is in getting patients well and I have to say I dozed off during some of these discussions - partly because I'd had a 4am start and partly because I don't see the relevance of esoteric immune discussions when it comes the business of getting patients well! I see the immune system as the army of the body and all the various players have army equivalents. So natural killer cells are our soldiers with machine guns, B-lymphocytes and T-lymphocytes are the messengers rushing around telling everybody what to do as well as lobbing cytokines and antibodies - our bombs and grenades. In chronic fatigue syndrome much of this activity is self destructive - it's as if the army can't stop fighting foreigners and has embarked on a civil war.

What is clear is that the total load of virus during the early phases is critical. Indeed this is well established in HIV infections. The above issues do of course have implications for treatment and this is how I see it all fits together.
During the acute stage
Treatment of the initial viral infection
Keeping viral numbers down helps a lot. Viruses are killed by fever, one should rest up in bed to allow the immune system to be active, take high dose vitamin C which effectively kills everything in the gut - indeed in high doses this will cause diarrhoea and strip out virus yeasts and bacteria generally in the gut. An acid stomach will be protected against enteroviral infection because acid will kill virus. Do not take symptom suppression medication which reduces fever and pain because these are useful symptoms which kill virus - see Viral infections - avoid them and treat them aggressively.
Interventions to reduce inflammation
Inflammation is highly desirable in the early stages of viral infection but after two weeks probably counter-productive. Nutritional interventions to reduce inflammation will be very helpful. The problem with Western lifestyles is that with their high levels of sugar and refined carbohydrate, lack of sleep, lack of sunshine, chemical, physical and mental stress etc. they tend to be pro-inflammatory. This predisposes us to states associated with chronic inflammation - see Inflammation. All this will tend to be made worse by having poor antioxidant status - this is a disease-amplifying process - poor antioxidants means more free radicals means more inflammation. See http://drmyhill.co.uk/wiki/Antioxidants

During the chronic stage
http://drmyhill.co.uk/wiki/Summary_of_my_approach_for_CFS_/_ME_sufferers.
Oxymatrine
John Chia looked for Chinese herbs which had anti-viral activity - the idea here is to try to get rid of those last few viral particles that were causing so much havoc in terms of chronic inflammation. He came up with oxymatrine which he has now trialled in 500 ME/CFS patients and seen beneficial effects in 52%. In the short term this can increase symptoms, but in the medium term beneficial effects were seen in 52%. In a few of the responders and non-responders in which he measured cytokines gene expression there was an increase in the IL12/IL10 ratio in 7/7 and no increase in any of the 10 non-responders. Again those that responded showed low levels of enteroviral protein in stomach biopsies. This suggests that oxymatrine is useful in half of patients with chronic and low grade viral infections. Dr Chia has made up his own product Equilibrant which contains the active principle oxymatrine and recommends starting at one daily, gradually increasing to 3 twice daily according to clinical response. Expect to get worse initially, hence the need to start with low doses and build up slowly. My guess is Equilibrant will be more effective if the basic work up to treating CFS is followed (as in summary approach above!).
Paul Cheney and heart problems in CFS
I have already written extensively about Paul Cheney's work in chronic fatigue syndrome and how he demonstrates it is a symptom of low cardiac output - see http://drmyhill.co.uk/wiki/Dr_Cheney_on_heart_function and Patent foramen ovale as a cause of fatigue.

Essentially people with CFS have diastolic dysfunction. Let me explain. One would think that the hardest job of the heart was the business of pumping blood round the body as it contracts. Interestingly this is not the bit that goes wrong in chronic fatigue syndrome. What goes wrong is the ability of the heart to fill with blood during the relaxation phase. This doesn't happen properly and it is called diastolic dysfunction. Essentially the heart muscle is stiff and doesn't relax so the heart doesn't fill with blood properly and therefore there is less available to pump around the body. So this begs the question why is the heart muscle stiff?

In order to contract, muscle needs calcium. In order to relax it needs magnesium and we know magnesium deficiency is pretty much pandemic in CFS. Magnesium is also necessary in oxidative phosphorylation in order to make ATP, furthermore it is also necessary for ATP to release its energy and be converted to ADP. So magnesium is centrally important in energy production and muscle function in the heart.

I see the heart as working like a coiled spring but in a rather counter-intuitive way. During relaxation energy is required to pump calcium out of cells and drag magnesium into cells. This is a little bit like charging up a battery with electricity. When the heart contracts this is triggered by a bolt of lightening as calcium suddenly influxes back into cells and magnesium out - indeed this bolt of lightening is the energy by which this process happens. So relaxation is coiling of the spring and contraction is its release - as I say rather counter-intuitive!

Mitochondria are centrally important in this diastolic dysfunction. I have to say that if I were Paul Cheney and delivering his lecture I would find it impossible to give the lecture without discussing mitochondrial function. Afterwards when I spoke with him he agreed that mitochondria are likely to be centrally important in diastolic dysfunction.

This low output cardiac state explains a great many of the symptoms of chronic fatigue syndrome from low blood pressure, postural orthostatic tachycardia syndrome to low energy levels, lack of stamina and foggy brain.

There are further complications to this low cardiac output state - if the ventricle of the heart doesn't fill properly the heart responds by trying to squeeze more blood out of it to maintain blood pressure. This intense constriction can collapse the left atrium in a process called cavitation. When this happens blood is sucked from the right side of the heart and can blow open patent foramen ovale. When this occurs of course blood is shunted from the right side to the left side, doesn't pass through the lungs and oxygen levels can drop precipitously. So a patent foramen ovale again is a symptom-magnifying process that occurs downstream of poor mitochondrial function - again see Patent foramen ovale as a cause of fatigue.

So heart pathology is centrally important in chronic fatigue syndrome and the treatment of course is to address mitochondrial dysfunction.
Conclusions
A very worthwhile day! Professor Malcolm Hooper chaired the whole day and ran an excellent question and answer session at the end of the day. He brought the discussion back to reality by asking pertinent questions of the Panel of speakers about implications for treatment and this gave me a chance to explain the importance of mitochondria and how they explain many of the facets of CFS/ME. Let's face it - every living cell needs to be powered by energy! This explains the great many symptoms we see in CFS. I will give you some examples:

Foggy brain - the brain weighs 2% of body weight but consumes 20% of the total amount of energy of the body! No wonder cognitive function in CFS is slow. See http://drmyhill.co.uk/wiki/Brain_fog_-_poor_memory,_difficulty_thinking_clearly_etc

Light intolerance - the retina is part of the brain and this consumes more energy than any other part! No wonder there is light intolerance - there just is not the energy needed to process!

Heat intolerance - the skin is the largest organ of the body - to lose heat we need to pump blood round the skin - CFS patients just do not have the cardiac reserve to do this - they cannot tolerate hot days. See
http://drmyhill.co.uk/wiki/CFS_-_The_Central_Cause:_Mitochondrial_Failure#Low_cardiac_output_explains_the_symptoms_of_CFS

Understand what is going wrong and you have the key to treatment! This Invest in Me day helped us all to understand better the underlying processes that result in CFS/ME.

You're not paranoid if they are out to GET you: Part 1

Invest in ME have updated their page on the Magical Medicine report and Malcolm Hooper's attempts to get anyone to actually engage in debate.

In an earlier entry, I reported back on the pathetic response he got from NICE, who saw fit to return the report unread with a refusal to discuss the matter at all. Now, I don't expect NICE to be fluffy bunnies - they are all about saving money and openly so. But they do call themselves the National Institute for Clinical Excellence. So when people point out that they are not abiding by their own guidelines, when people feel some of their guidelines are so far from correct that they take them to court, when someone sends them a report of over 400 pages detailing the misrepresentation of ME and the mass of evidence for it not being a somatoform condition...well, one does rather feel they might come up with a more dignified and intelligent response than sticking their fingers in their institutional ears and going 'la la la...can't hear you...'

Professor Hooper never gives up on us, though, and continues to try to get someone in any kind of position of power to listen to his painstakingly-researched concerns.

His most recent missive winged its way to the MRC on 30th March and I reprint it below. He has now lodged a formal complaint about the PACE trial with the relevant Minister (though one wonders if he might not have done better to just send it to the Shadow version at this stage!).

The MRC are, of course, the lovely people with the Super Secret Files (I kid you not, mostly because you couldn't make this stuff up) on ME. The file in question, is held in the National Archives at Kew (formerly called the Public Record Office - I preferred the old name, by the way, which implied the information was held there for us, the public! ) - its 'closed' period has been recently extended from ending in 2023 to ending in 2071. By which time, as Margaret Williams points out, most current ME sufferers and campaigners will be 'conveniently dead'.

You can read here an account of Nicola Reiss's experience when she tried to see these files or be given a sensible reason why she should not be allowed so to do...another account I have read tells of how the enquirer was put through to an employee at Kew whose dedicated task is to take calls enquiring about 'those documents' - who read them a script on protecting privacy of individuals and answered no direct questions.

Now, my last job before ME kicked me in the head was in a local archive office. So I get the closure of hospital records etc. But we are talking here about people who amongst other things gave evidence to an inquiry. An inquiry meant to deal with a public concern. Their privacy can be protected perfectly adequately by the astonishingly complex means of getting a marker pen and blacking the names out. Do correct me if I'm wrong? So you have to be a very laid-back kind of ME girl to not wonder at this point - what is it they don't want us to know? As an historian, as a human being with an alleged IQ somewhere above pond slime, seemingly gratuitous suppression of information makes me automatically suspicious. My gut tells me this is not quite on the level, somehow, some way. I promise myself an attempt to view these documents, so I can report back for myself on what happens...

But for now, here's Professor Hooper. Please wish him luck, everyone.

LETTER to Dr Morven Roberts, Clinical Trials Manager, UK MEDICAL RESEARCH COUNCIL from Professor Malcolm Hooper

From Malcolm Hooper Ph.D.,B.Pharm.,C.Chem.,MRIC Emeritus Professor of Medicinal Chemistry School of Sciences Fleming Building Wharncliffe Street University of Sunderland SUNDERLAND SR2 3SD 30th March 2010 Chief Scientific Adviser to the Gulf Veterans' Association President: the National Gulf War Veterans and Families Association, NGVFA, (2002) Dear Dr Roberts, re: MRC PACE Trial You will doubtless be aware from Lord Drayson (the Minister with responsibility for the MRC) that on 11th February 2010 I lodged a formal complaint with him about the PACE Trial (reference 2010/0013270POLD). There were three reasons for going directly to him instead of to you in the first instance, as would have been customary: 1. In response to a formal complaint made in November 2004 by an alpha-rated former MRC grant-holder, and despite the involvement of the then Science Minister, Lord Sainsbury of Turville (reference SAMP001/040728) and Dr Rudi Vis MP, the MRC External Communications Manager, Elizabeth Mitchell, had already made plain that the MRC is not interested in considering complaints about the PACE Trial. 2. By lodging a complaint with the MRC Clinical Trials Manager, we are mindful of the fact that the person intimately involved with the PACE Trial, Professor Simon Wessely, is in charge of the PACE Clinical Trial Unit. 3. Given that the MRC is co-funding the PACE Trial, inviting the MRC to consider this substantial complaint would seem to be inviting the MRC to be both judge and jury in its own court – hardly consistent with the most elementary standards of independence and justice. However, following the advice of Lord Drayson, a copy of "Magical Medicine: how to make a disease disappear" is enclosed, which sets out our concerns in detail. Many members of the international research community are monitoring the PACE Trial particularly in the light of – - The total failure to engage with the vast body of significant biomedical evidence about the nature of ME/CFS contained in more that 4,000 published, peer-reviewed research papers. - The misleading and contradictory content of the Trial manuals demonstrating the apparent coercion, and exploitation of patients. - The seriously flawed and inadequate science that under pins the Trial. We have taken much time and great care in compiling the evidence presented in ‘Magical Medicine’ and I look forward to receiving your reasoned response to our legitimate concerns expressed therein. I would, therefore, appreciate an informed and considered reply and not the standard and dismissive MRC proforma letter that has been sent to many people who have already written expressing their concerns about the inadequacy of the PACE Trial. Yours sincerely Malcolm Hooper Enc. “Magical Medicine: how to make a disease disappear.” Dr Morven Roberts Clinical Trials Manager MRC 20 Park Crescent London W1B 1AL