Saturday, December 27, 2014

Scientific misconduct?

The negative Canadian CCSVI diagnostic study, lead by University of British Columbia neurologist Dr. Anthony Traboulsee and published in The Lancet,  did not utilize the original scientific protocol of Dr. Paolo Zamboni.  
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)61747-X/abstract

This new study displayed even further arrogance and audacity, by deviating from all other published venous and arterial studies, utilizing a false criteria to assess jugular vein stenosis. 

Stenosis is routinely measured by comparing the narrowed segment to the adjacent normal section of vein or artery and expressing this as a percentage.  This is the accepted way to measure stenosis.  All international vascular researchers use this method.  It is published in vascular textbooks, which is where I found this diagram.  This is how Dr. Zamboni quantified stenotic jugular veins in CCSVI.


But the Canadian neurology study did not do this.  Instead, UBC researchers created a brand new measurement to quantify stenosis using the full length of the jugular vein.  This method has never before been utilized in published vascular studies. And when Dr. Zamboni pointed this problem out, the Lancet refused to publish his response.

The very first step in the scientific method is replication of results.   When a scientist comes forward with a new discovery, other scientists are asked to look at the evidence.  In order to do this, the original scientific protocol must be followed.

This means that scientists collaborate with each other.  They enter a dialogue with the discoverer of new information. They talk to each other, discuss diagnostic and treatment protocols.  They are open, they do not have agendas.  This step in the scientific method is recognized the world over.  It is part of the critical process used to further evidence-based research.

When this doesn't happen, the scientific method does not work.  Fraud and deception are the result.  This is called scientific misconduct.

"Deviations from the planned protocol can affect the validity or relevance of a study.
The most important component of critical appraisal is careful assessment of the study design; however, other steps, such as evaluation of the statistical methods used, interpretation of the findings and potential conflicts of interest are also essential." 
http://www.nature.com/nrgastro/journal/v6/n2/full/ncpgasthep1331.html


Not only did the Traboulsee et al CCSVI study not utilize the original protocol by Dr. Zamboni, the investigators refused to speak with the protocol designer.  They would not respond to his requests for input, and they did not respond to his comments on the erroneous study.  They went ahead with a poorly designed study, and published their results as the "final word" in CCSVI.  This is an egregious betrayal of the scientific method.

The medical journal, The Lancet, refused to publish the response of the original protocol designer. However,  Dr. Zamboni's response is now linked on pub med in the comments section.
http://www.ncbi.nlm.nih.gov/pubmed/24119384#cm24119384_8458

Here is the truth.  Dr. Zamboni responds to the errors of the Traboulsee et al study, "Prevelance of Extracranial Venous Narrowing" which is now published in a venous journal.  My comments will be in parentheses.
http://www.pagepressjournals.org/index.php/vl/article/view/vl.2014.4195

Last January The Lancet published the article by Traboulsee et alPrevalence of extracranial venous narrowing on catheter venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded, case control study

These Authors confirmed the presence of chronic cerebrospinal venous insufficiency with a high prevalence of about 70% in the Canadian population, but without significant differences between patients and healthy controls, yet. 

However, they used a criterion never published to assess stenosis, in alternative to the classic measurement of the diameter in the segment immediately preceding the narrowest point. 

Traboulsee et al. measure the stenosis along the entire length of the internal jugular vein, by comparing the maximum diameter with the narrowest point. It has been demonstrated, from normal anatomy findings, how the jugular bulb diameter normally exceeds 50% of the minimum diameter of the internal jugular vein, clearly showing the reason why Traboulsee et al. did not find significant differences between people with multiple sclerosis, their sibilings, and unrelated healthy controls. 

(In other words, using this new, not gold standard method, Traboulsee and team make it seem like most people have CCSVI.  If you compare the maximum diameter of the vein at the jugular bulb to the minimum location and call that result a "stenosis"-- well, heck!  Everyone has CCSVI!  But that's not science.  That's fraud.  It is scientific misconduct. Stenosis is classically measured in both veins and arteries by comparing the closed off area to the normal, open part right next to it.)

Furthermore, as the outcome measure of Traboulsee et al., wall stenosis is a neglected part of primary venous obstruction, because in the majority of cases obstruction is the consequence of intraluminal obstacles, as a considerable part of truncular venous malformations, and/or compression; rarely of external hypoplasia. 

(Dr. Zamboni has been saying this since 2009.  You need to look at obstacles inside the vein, as well as compression from the outside.  This study considered none of this.)

Finally, several recently published methods can be adopted for objective assessment of restricted jugular flow in course of chronic cerebrospinal venous insufficiency, by the means of non invasive magnetic resonance imaging, ultrasound and plethysmography. This may help us in improving the assessment of cerebral venous return in the near future.

(Why didn't the researchers work with Dr. Zamboni, a venous specialist?  NASA is using his technology, yet Traboulsee would not give him the courtesy of a phone call?  An e-mail?  Perhaps the honor of publishing his response?)


It is a dark time for science.  While neurological journals and researchers rule the MS dialogue, the science of the endothelium, venous function and cerebral blood flow are relegated to "death knells", "closed caskets" and "final words" in neurological publications.  Researchers refuse to speak to specialists in other fields.  Comments from the scientist who discovered CCSVI are not published.  False diagnostic criteria are created.  The death knell rings, not for CCSVI, but for the public's' trust.

And yes, there are serious conflicts of interest.  Here are Dr. Traboulsee's funding diclosures.
Anthony Traboulsee, MD, has received honoraria from EMD Serono, Teva Neurosciences, Bayer, Biogen Idec, Chugai Pharmaceuticals and Roche.  Traboulsee reported relationships with Bayer, Roche, Biogen Idec, Merck Serono, and Chugai. http://www.medpagetoday.com/Neurology/MultipleSclerosis/42151

Here are three new studies---published just this past month, two from Canada, ALL finding a connection to the vasculature and multiple sclerosis. This comes from cellular biologists, who are looking for real answers into disease etiology. And their research is being sponsored by universities and governmental agencies, not pharmaceutical companies.

Hoping for brighter days in the coming new year,
Joan










Monday, December 22, 2014

From cells to space stations--vascular research continues

While astronaut Samantha Cristoforetti works high above our planet on the International Space Station---studying venous return in microgravity and utilizing Dr. Paolo Zamboni's technologies----cellular biologists are looking at the MS brain. The macrocosm and the microcosm of MS vascular research is happening right now!

New technologies are allowing researchers to view the MS brain at a cellular level, before formation of lesions.  I wanted to share three of these new papers, all published in the last month.

Please note that the researchers are cellular biologists---they are looking at the MS brain on the most basic level, and they all see the vascular links to the disease.  They are not studying MS to find out how immune modulating drugs work, they are trying to solve the mystery of what causes MS.  And they are all seeing a connection to blood flow and the blood brain barrier.

When neurologists tell you CCSVI research is over, please point them to the continuing, confirming research which is further elucidating the vascular connection to MS. 

If NASA can work directly with Dr. Paolo Zamboni, why won't neurologists?
NASA wants to understand why 20% of their astronauts are coming back to earth with neurological and visual issues, and how it's related to blood flow.  So, they went to the expert.
http://www.nasa.gov/mission_pages/station/research/experiments/1278.html

Here are the brand new papers, all finding a link to MS and blood flow.

1.  The Role of Angiogenesis in the Pathology of MS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253611/

Cell biologists from the University of Irvine have noted how the loss of endothelial tight junctions in the blood brain barrier contributes to inflammation and angiogenesis (the growth of new blood vessels) in the MS brain,  and how this process is initiated by hypoxia.  This low oxygen state and resultant angiogenesis occurs prior to formation of demyelinating lesions.

This cellular research is further defining the hypothesis of cellular biologist Dr. Bernhard Juurlink, made in the 1990s.
http://ccsviinms.blogspot.com/2010/08/blood-flow-and-white-matter-lesions.html

It also fits in with my hypothesis of MS as a disease of hypoperfusion/reperfusion injury.
 http://ccsviinms.blogspot.com/2013/09/multiple-sclerosis-hypoperfusionreperfu.html


2. In vitro study of the direct effect of extracellular hemoglobin on myelin components.
http://www.ncbi.nlm.nih.gov/pubmed/25463632

The cellular biologists from the University of Guelph are looking at how blood particles damage myelin.  They are seeing microscopic deposits of hemoglobin in the MS brain, around the veins.  This blood contains iron, which when deposited into delicate brain tissue, begins a process of oxidative stress.
"This study provides new insight into the mechanism by which hemoglobin exerts its pathological oxidative activity towards myelin components. This work supports further research into the vascular pathology in MS, to gain insight into the origin and role of iron deposits in disease pathogenesis, or in stimulation of different comorbidities such as cardiovascular disease."
This work confirms the theory of Dr. Zamboni from 2006, called his "Big Idea" theory, which saw the similarities of venous disease to MS, by noting how blood particles caused damage to tissue via the iron found in our red blood cells.   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1633548/


3.  Focal disturbances in the blood brain barrier are associated with formation of neuroinflammatory lesions

Neurobiologists from the University of Montreal are seeing changes to the blood brain barrier which happen before immune cells enter the MS brain. There are changes to the tight junctions of endothelial cells. 
 Our findings suggest that BBB breach occurs before significant immune cell infiltration and demyelination.

I wanted to briefly highlight these new studies, and encourage all readers to pursue cardiovascular and endothelial health in 2015.  

The discoveries of endothelial dysfunction and the link to the breakdown of the blood brain barrier in MS are being made.  While we wait for the venoplasty and pharmaceutical solutions, there is much that can be accomplished with lifestyle changes.
http://ccsvi.org/index.php/helping-myself/endothelial-health

Happiest of holidays to all.  Here's to a healthy 2015.
Joan


Here is Samantha's view                                               Here is a microbiologist's view

Wednesday, December 10, 2014

You and Your Microbiome

During the past year, there has been a lot in the medical press on the "microbiome."   Researchers continue to explore the connection between the microbiome and neurodegenerative disease.  Articles on the microbiome and MS, Alzheimer's, and dementia as well as cardiovascular disease and stroke, are being published in medical journals and discussed in online communities.

You might say 2014 has been the Year of the Microbiome!

But what is it??  Microbiome literally means the "small living community" inside each of us.  It's the word doctors and researchers use to describe your own, unique ecosystem.  You see, we are not just "ourselves", we are also host to a universe of living organisms.  And most of these guests take up residence in our gut.

We have about two pounds of bacteria living inside us.  These bacteria are broken down into four families: the Actinobactera, Bacteroidetes, Firmicutes and Proteobacteria.  http://www.nature.com/nri/journal/v13/n11/fig_tab/nri3535_F2.html

When these families live in balance, the human body functions better.  When these families get knocked out of balance, diseases can be linked.  "Dysbiosis" is when inflammatory bacteria outnumber beneficial bacteria.  Whether the link to specific diseases is causal, or resultant, is yet to be established.  But there's more and more evidence connecting an imbalanced microbiome to inflammation and diseases of "autoimmunity."

Here are some more specifics on what researchers found, when looking at the fecal bacteria in people with MS, and comparing them to healthy controls.  This is Dr. Sushrit Jangi of Brigham and Women's Hospital discussing results of a recent study:

The preliminary data show that there are at least a couple of different genera of bacteria that are different in the gut of MS patients compared with healthy controls. We found that a bug called Methanobrevibacteriaceae *** is enriched in the gut of MS patients and seems to have immunoproliferative properties that drive inflammation. We also found that the population of Butyricimonas ### bacteria is low in MS patients compared with healthy controls. This is an interesting result because these bacteria produce butyrate, which is thought to be immunosuppressive, but we do need to repeat this study in a larger cohort.
So it seems that our work initially supports the idea that the gut in MS patients contains bugs that drive inflammation and are low in the types of bacteria that control inflammation. This is consistent with work in rheumatoid arthritis and inflammatory bowel disease.
This also mirrors the idea that MS is a disease of the western world. If you go to countries like India and parts of Asia, where diets are far more vegetarian, you don't really see MS. However, when these people come to the United States and adopt a more westernized diet, the incidence of the disease goes up. I think this is an exciting premise but it's still too early to say anything about the causality.
http://www.medscape.com/viewarticle/832385
***Methanobrevi bacteria are found to be enriched in those who are constipated.  
https://microbewiki.kenyon.edu/index.php/Methanobrevibacter_Smithii
### Batyricimonas is also low in RA and inflammatory bowel disease.
http://journals.lww.com/neurotodayonline/blog/breakingnews/pages/post.aspx?PostID=316

I included probiotics and eating more plants in the Endothelial Health Program, because I read a lot of research on the link between bacteria, inflammation and the endothelium.  And I wanted to help Jeff.  He was severely constipated when we started the program (sorry, hon!  Is that TMI?)  His serum numbers were off the charts for inflammation.  His meat and animal protein to plant food ratio was far too high in meats, too low in vegetables and fruits.  His just wasn't eating enough living, plant-based foods with phytonutrients and fiber.  I thought there might be a connection, and found it in the endothelium.  Here is a post from 2011, where I explain:
Probiotics, also know as helpful bacteria, are included in the Endothelial Health program, because they affect the lining of our blood vessels in a positive way, by reducing inflammation and regulating NO. A strong endothelium is less permeable, and will keep plasmic particles out of tissue--in the brain and the gut.  This can modify the reaction of immune cells, and reduce what is called the "autoimmune" reaction.  (Although I believe calling this reaction "autoimmune" is a misnomer.  The immune cells are simply doing their job, by responding to foreign particles which should not be in brain or intestinal wall tissue.)


What to do?  How can we create a more balanced, happier microbiome, and encourage growth of healthy bacteria?   There are a few things scientifically proven that we can do today, while the researchers continue to look for specific answers.

1. Work with your own healthcare provider, and find a probiotic solution that fits your lifestyle and needs.  Some people eat yogurt, others prefer fermented foods like sauerkraut, kimchi or kombucha, or some take a probiotic supplement.  Some folks (like me!) enjoy all three.  Jeff finds his supplement is enough.   Each individual needs to discover what works best for them.

2. Eat more plants, eat less meat and animal products.   And stay away from processed foods. The research shows that the more saturated and trans fats, the less balanced the microbiome.  The more fresh vegetable and fruits, the better the microbiome.

3. Watch your bowel movements!  Are you going at least once a day?  If not, you're not moving waste products through your body efficiently, and that build up of noxious or "bad" bacteria may be enhancing inflammation in your body.  If you are having a couple smooth, not runny, bowel movements a day, chances are, your microbiome is pretty happy.  (sorry, was that TMI again??)

4. Stay at a healthy weight.  Obesity is linked to an unbalanced microbiome.


Let's be good hosts to the universe within us all!
Joan