NIH intramural research program update

[Bob]

@Yogi, I don't know if this helps your project, but FYI, Dr Nath had this to say about Neil Young (who is on the list of investigators): “So, I put together a panel of really outstanding immunologists to guide me, although I do consider myself a neuro-immunologist, there are people… every immunologist is not the same. People who specialize in B cells and T cells and NK cells, and so on and so forth. So what I did is call on Dr Neil Young who is an expert immunologist at NIH and Ronald Germain who is a National Academy of Science member so we sat and discussed various kinds of things."

 

[Cheshire]

Wendy A. Henderson
http://irp.nih.gov/pi/wendy-henderson

Researching IBS (biology and behaviour)

The primary goal of Dr. Henderson’s research is to discover the mechanisms involved in symptom distress related to digestive disorders, specifically the biobehavioral relationships between inflammation and patient symptoms. Through her research, she has demonstrated that chronic GI symptoms have an underlying subclinical inflammatory mechanism. Now identified as another layer of gene control that affects signatures and digestive or gastrointestinal (GI) symptoms, microRNAs are undergoing intensive study. Such approaches are expected to differentiate chronic GI symptoms from healthy phenotypes with combined novel biomarker profiles, which may aid in the discovery of novel miRNA targets for treatment of patients with these symptoms.

Publications

Del Valle-Pinero AY, Sherwin LB, Anderson EM, Caudle RM, and Henderson WA. Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis. World J Gastro. In press.

Reddy SY, Rasmussen NA, Fourie NH, Berger RS, Martino AC, Gill J, Longchamps R, Wang XM, Heitkemper MM, Henderson WA. Sleep quality, BDNF genotype and gene expression in individuals with chronic abdominal pain. BMC Medical Genomics 2014 Oct 31; 7(1):61. [Epub ahead of print]

Fourie N, Peace RM, Abey SA, Sherwin LB, Rahim-Williams B, Smyser PA, Wiley J, Henderson WA. Elevated miR-150 and miR-342-3p in Patients with Irritable Bowel Syndrome, Exp Mol Pathol. 2014 April 21; 96(3): 422-25, PMID: 24768587.

Del Valle-Pinero AY, van Deventer HE, Fourie N, Martino AC, Remaley AT, Patel NS, Henderson WA. Gastrointestinal permeability in patients with irritable bowel syndrome assessed using a four probe permeability solution. Clinica Chimica Acta, published online: 14-JAN-2013 DOI: 10.1016/j.cca.2012.12.032. http://www.sciencedirect.com/science/article/pii/S000989811300017X

Henderson WA, Shankar R, Taylor TJ, Del Valle-Pinero A, Kleiner DE, Kim KH & Youssef NN. Inverse relationship of interleukin-6 and mast cells in children with inflammatory and non-inflammatory abdominal pain phenotypes. Manuscript World Journal of Gastrointestinal Pathophysiology, 15-DEC-2012 DOI: 10.4291/wjgp.v3.i6.102 . PMC3602438. http://www.wjgnet.com/2150-5330/full/v3/i6/102.htm

An upregulation of the gene coding the pro-inflammatory cytokine IL-1α suggests that the mechanism behind stress-related changes in GI symptoms is pro-inflammatory in nature. The results of this study contribute to the knowledge of the mechanism behind stress-related CAP symptoms and gender differences associated with these disorders.


Peace RM, Majors BL, Patel NS, Wang D, Del Valle-Pinero AY, Martino AC, Henderson WA. Stress and Gene Expression of Individuals with Chronic Abdominal Pain. Biological Research in Nursing, 2012; 14 (4) 405-411. DOI: 10.1177/1099800412458350 http://brn.sagepub.com/content/14/4/405.long

Del Valle-Pinero AY, Martino AC, Taylor TJ, Majors BL, Patel NS, Heitkemper MM, Henderson WA. Pro-Inflammatory Chemokine C-C Motif Ligand 16 (CCL-16) Dysregulation in Irritable Bowel Syndrome (IBS): A Pilot Study. Neurogastroenterology and Motility. 2011; 23(12) 1092-7. http://onlinelibrary.wiley.com/doi/...ionid=969A8EA39FDD23EBDFDDA9F67F316300.f03t01

Taylor TJ, Youssef NN, Shankar R, Kleiner DE, & Henderson WA. The Association of Mast Cells and Serotonin in Children with Chronic Abdominal Pain of Unknown Origin. Biomed Central Gastroenterology, Research Notes 2010; Oct 21; 3(1):265. http://www.biomedcentral.com/1756-0500/3/265

 

[Yogi]

Acevedo is in physical med and rehabilitation and a senior staff physiatrist in Rehabilitation Medicine? No CFS research before.

http://www.niaid.nih.gov/labsandres...ction/Pages/cohen.aspx#niaid_inlineNav_Anchor

Jeffrey Cohen is Chief of laboratory infectious diseases and Chief of Medical Virology. Nothing of concern.

http://www.niaid.nih.gov/labsandres...ction/Pages/cohen.aspx#niaid_inlineNav_Anchor

However Brian Walitt is BIG problem. It was him who probably decided on study of post lyme and FMD in this study. He believes they are all the same.

Describe your research interests and how you chose this area of research.

My research interest is perceptual illness. In these disorders, a person experiences a range of different bodily sensations, such as pain and fatigue, without any clear external cause. In some, these sensations can be bothersome while in others they can be disabling. The perceptual illnesses that interest me change their names with every generation, with current disorders being called fibromyalgia, chronic fatigue syndrome, and post-Lyme syndrome.

- See more at: http://georgetownhowardctsa.org/researchers/researcher-stories/brian-t--walitt-#sthash.d9W85cUJ.dpuf

My view: There are alot of positives with this NIH study and it sounds good overall with Avi Nath in charge and Ian Lipkin involved. However this Brian Walitt (Lead clinical investigator) is a big and serious concern and we need to be aware of this and perhaps channel this back via the patient committee that is being set up.

 

[ScottTriGuy]

I dare say that as long as Walitt (and his ilk) is in such a powerful position in the study, much of the patient population will be (rightfully) suspicious until the data is published.

That is a lot of years to have a strained relationship with the patient community.

 

[MeSci]

Such an odd mix. I agree that there's a seriousness of purpose there, but also a deep weirdness with the FMD control group. I hope Dr Nath will respond more fully about that control group in days to come, and I'm pleased that there will be a Patients Advisory Group. I'm hopeful that that control group will come out in the wash and that by working with the NIH, we can make this a study that everyone can get behind without reservation.

I'm way behind on this thread, but need clarification re FMD - this is Fibromuscular Dysplasia according to a quick search. Or are we talking about something else?

 

[duncan]

Joseph Snow may be a psych, but I think he is an independent who subcontracts to the NIH. Not sure. I do not know what his relationship to Walitt would be.

If he is the person I think he is, then I know he has done work for the NIH Lyme Team, and imo, that is not good.

 

[Yogi]

Fred Gill is a junior in this so should not be a big concern as Brian Walitt

However from CFS central for those who did not read it all:

"The bad news: Gill was even worse than I expected, touting graded exercise therapy as the best treatment for CFS. That wasn’t terribly surprising, as Gill worked with Stephen Straus and treated Straus's patients. Gill remarked that when he was in private practice, he asked his patients to exercise, and they improved. He noted that many patient advocates feel that exercise exacerbates their symptoms, but he believes exercise is the right treatment for CFS.

Gill gave kudos to the just-released PACE study. "For those of us who've been preaching this [graded exercise therapy],” he said, “it's nice to show this study." Gill was particularly pleased that the same fatigue questionnaires used by the CDC were also used in the PACE study.

Gill’s a big fan of the Centers for Disease Control’s Empirical case definition, AKA the Reeves definition. He loves the—gasp—"excellent" questionnaires that the Reeves definition used, as well as the CDC's 2006 gene study.

The clinician's approach, he said, should mirror the CDC's toolkit recommendations. Gill’s big on reassuring the patient, avoiding unnecessary tests, avoiding debate over whether it’s psychological, and above all, getting patients to remain active and exercise no matter what."

"Gill, who looks to be well into his 60s, went through a series of ancient slides from the 1980s. Oh joy—he started by pointing out that CFS was first recognized as neurasthenia by Beard in 1869, and it went downhill from there. He went through the different names for CFS and selected case definitions (ignoring the Canadian).

Just in case anyone in the audience still thought there might be a real disease buried under the CFS construct, Gill ran through all the studies done by Straus that rebutted any positive treatment trials. Resurrecting his BFF Straus once again, he gave a big thumb’s up to studies done on stress and CFS. As to "pacing,” Gill oddly claimed that “he didn't fully understand pacing.”

"Gill concluded his presentation by recommending the CDC's CFS website as well as that of the CFIDS Association of America (CAA). Gill said that he has a high regard for the CAA because he agrees with their views. So now it’s abundantly clear the kind of scientists whose thinking dovetails with the CAA’s. "

"In the Q & A session that followed the talks, Gill was hopelessly out of touch, invoking the Simon Wessely school of misinformation about CFS, circa 1988, by insisting that the disease is "not common" in children.

During the Q & A, I said that the Canadian Consensus Criteria (CCC) should be used to select patient cohorts and that audience members should read it as well as Dr. Lenny Jason's "Development of a Revised Canadian Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Case Definition.”
In the Q & A session that followed the talks, Gill was hopelessly out of touch, invoking the Simon Wessely school of misinformation about CFS, circa 1988, by insisting that the disease is "not common" in children.


"
Questions and answers
In the Q & A session that followed the talks, Gill was hopelessly out of touch, invoking the Simon Wessely school of misinformation about CFS, circa 1988, by insisting that the disease is "not common" in children.

During the Q & A, I said that the Canadian Consensus Criteria (CCC) should be used to select patient cohorts and that audience members should read it as well as Dr. Lenny Jason's "Development of a Revised Canadian Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Case Definition.”

I was cut off as I was making a statement rather than asking a question. So I don't know if what I said will make it to the edited videotape.

I did ask Gill a detailed question (mainly for the audience's benefit) about the Pacific Fatigue Lab's findings with repeat exercise testing, as well as the Lights’ exercise studies in CFS patients. Both groups of researchers found objective, measurable and significantly abnormal biomarkers that distinguished the sick from the healthy controls after exercise. Their findings allowed me to bring up post-exertional malaise as the hallmark of CCC-defined patients.

Gill replied that he disagreed with those studies but didn’t explain why.

In the Q & A, I told Gill that I was on the drug Midodrine for neurally mediated hypotension, and that was the only reason I was functional enough to attend the lecture.

Gill’s response was that studies have shown that there’s no orthostatic intolerance in CFS. Earth to Gill: Have you not read any of the formidable research by cardiologist Hugh Caulkins’ and pediatrician Peter Rowe’s group at Johns Hopkins?

Harvey Alter spoke again, pointing out that CFS has a viral-like “picture.”

Gill asked Alter, “Is CFS a real disease—and if so, what’s its etiology?”

Alter replied cryptically, as if he were the wisest of fortune cookies: “The answer depends on the effort to find the cause.”

 

[Cheshire]

I'm way behind on this thread, but need clarification re FMD - this is Fibromuscular Dysplasia according to a quick search. Or are we talking about something else?

Functional movement disorder, previously part of the conversion disorder spectrum.

 

[Sasha]

I'm way behind on this thread, but need clarification re FMD - this is Fibromuscular Dysplasia according to a quick search. Or are we talking about something else?

No, it's "functional movement disorder", which the NIH consider to be a psychological disorder presenting as a neurological one - hence everyone's concern that this is another bunch of patients with a poorly understood organic illness who are being inappropriately dismissed as psych patients and who would therefore be catastrophic for us as a control group if we look similar to them.

 

[Sidereal]

Gill’s response was that studies have shown that there’s no orthostatic intolerance in CFS.

My pulse pressure of 20 and heart rate of 120 when upright disagree.

 

[MeSci]

Yogi said: ↑

Gill’s response was that studies have shown that there’s no orthostatic intolerance in CFS.

My pulse pressure of 20 and heart rate of 120 when upright disagree.

Maybe he hasn't read this study.

 

[MeSci]

Functional movement disorder, previously part of the conversion disorder spectrum.

 

[Snow Leopard]

Harvey Alter spoke again, pointing out that CFS has a viral-like “picture.”

Gill asked Alter, “Is CFS a real disease—and if so, what’s its etiology?”

Alter replied cryptically, as if he were the wisest of fortune cookies: “The answer depends on the effort to find the cause.”

Wow, Alter with a great answer to a (pointless) question...

 

[Snow Leopard]

By the way, it is important to put the different roles in perspective.
Brian Walitt is the clinical investigator - he is not in charge of doing the experiments, but rather in charge of patient recruitment/screening and so forth. https://en.wikipedia.org/wiki/Clinical_investigator

He's probably the guy who thought the Reeves criteria was a good idea.

While his involvement is not very pleasing to us, provided the study protocol is sound, there is not that much he can do to bias the results.

 

[Valentijn]

While his involvement is not very pleasing to us, provided the study protocol is sound, there is not that much he can do to bias the results.

Aside from select the patients who best fit his view of a psychosomatic disorder? I'd think that could cause a lot of damage.

 

[Sasha]

provided the study protocol is sound, there is not that much he can do to bias the results.

With an FMD control, the study protocol is far from sound, IMO.

 

[Sasha]

Can you explain specifically how he could bias the study in that way?

The study has an FMD control group - considered by the NIH to be a psychosomatic disorder.

 

[BurnA]

The study has an FMD control group - considered by the NIH to be a psychosomatic disorder.

Why is this a concern. As long as the ME/CFS patients are nominated by recognised Dr.s and fulfill the criteria then we should be ok ?

 

[duncan]

@BurnA, I do not think this is how the real world operates. History tells us it is certainly not how the ME/CFS research world operates.

It is also not the way other illnesses operate. I doubt you would see many disputed disease controls in studies for TB or forms of cancer.

There are many red flags associated with the study as it stands.

 

[Comet]

This study fills me with both hope and terror. It seems as though there is to be a huge amount of testing - possibly more than ever before - and that is absolutely fantastic ... But how in the world did they come up with the FMD and post Lyme controls?

It's like the study itself is bipolar. On one end of the spectrum - huge amounts of testing (woohoo!). On the other - comparisons to perceived psychosomatic disorders (seriously?!). Also there Lipkin, but then there is Walitt. The study seems to be encompassing both the sublime and the ridiculous.

Still, I choose to remain positive about it, and look forward to getting results. Though I can also understand why some are nervous. Too bad there is no waffle icon!