Thursday, 1 June 2017

Unrelated Blogger Comments June

This month Summer arrives
If you have any comments unrelated to the threads this is the place for you.

59 comments:

  1. MouseDoctor is an attention seeker .

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    1. Maybe.......Maybe I know what's coming and am proud of the content;-)
      I had to do a last-minute change the post from that Scheduled.

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    2. He may be getting a lot of justly deserved attention shortly ;-)

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  2. Just get on with it man! If you have some news - share it! You always hint at some interesting stuff, but it never materialises. Remember the ridiculous knight rubbish from last year? Completely backfired and nothing came of it. Tell us how the spasticity trial is going. Tell us how the latest Charcot project is going. If you have something to say, say it. Stopping treating us like children. If I had to write your end of year school report it would read "David throws himself into all activities with great enthusiasm. However, as a young person he needs to show more maturity. He has worked hard on the blog, but needs to stop using it to post silly pictures or confuse the readers with silly riddles. His written work needs to be more concise and punchy. David would benefit from a new challenging environment as he has become too cosy at Barts. I will contact colleagues at Cambridge to see it there are any secondment opportunities. David needs to show more sympathy to those who hold other political views. He plays the downtrodden worker role, but his salary is well beyond want the Labour party consider to be "rich". Overall, not a great year for David."

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    1. Dear Mr Impatient

      I have changed the post and picture, so this will not make any sense to new readers, likewise the post Anon 2.19 above wont make any sense.

      Just get on with it...All embargoed.

      "Ridiculous knight rubbish from last year"..."nothing came of it". Tell that to the people who have being treated.

      Tell us how is the spasticity trial is going...it's going. There was a comment from Neuro last week about progress. If you want to know about the success, simply read Ipsen/Canbex website.

      How is the latest Charcot project is going....not my project ask the Gs

      Needs to show more maturity.....I won't respond to this :-)

      His written work needs to be more concise...apologies in advance

      Secondment in Cambridge.....Emm That's an idea, I wonder if they'll take me? I think I can offer them something that they don't do.

      Sympathy for other political views...I don't talk politics.

      Sympathy for alternative views....Why...that's what ProfB is there for.

      Not a great year.....We shall see:-)

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    2. LOL AnonymousThursday, June 01, 2017 7:53:00 am your comment sounds like the results of a personality test...

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    3. But actually I think it will be a good year for David, already happy with output so far....21 printed page paper (+ twelve page supplementary file) and its not a review will be out very soon, should of happened in June...don't ask why.

      So what does that say for the personality tests:-)...Jajce

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  3. Did i read "Salary well beyond rich"

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    1. The privilege of being able to do what we do, day in day out, for the benefit of pwMS makes us rich beyond measure, Luis ;-)

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    2. Lolllllllllllllllllll
      Nice way out...

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    3. Bob Weinberg very well know cancer research Like to say that nowdays there are more people living from cancer than dying from him

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    4. but we have to die from something - if i have to wait for old age to kill me, i shudder to think how long that could take :D

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  4. Sorry to distract from the chain above, resisted temptation to join in 'it will only encourage them to make more' (Mark Kermode, BBC film review 2017).

    Here's an old bit of review work 2012 by Michael Pender

    https://www.hindawi.com/journals/ad/2012/189096/

    Is it true in practice, pwMS have low CD8? If so, are we at particular risk of viral infections when on dmt? ie if CD8 already low and lowered even further by dmt? Starting to wonder if monitoring total lymphocyte count is really enough?

    Apologies, as usual, if this has been covered previously. Spend my life catching up ;-)

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    1. This one ius more recent
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5292561/
      From the same author
      Luis

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    2. Monitoring lymphocytes only and you can miss alot.

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    3. Thanks Luis. Way over my head (I rely on MD to talk us through this kind of thing) but get the general idea. Am fast becoming a Pender fan, love reading his papers almost as much as I love this blog :-)
      Interesting re ebv, Barts team have demonstrated that current dmt all work by depleting mem B cells meanwhile on the other side of the globe Pender has been working on boosting CD8 response. Same problem, two solutions. Add in Charcot and we have 3 solutions.
      Ironic the dogma MS is a T cell disease could be kinda right ;-) but further depleting CD8 sounds like the last thing we should do. I guess if do good enough job with depleting mem B it shouldn't matter...

      Apologies to everyone, I know I keep on about lymphocytes but with steadily worsening lymphopaenia (0.5 at last count, no dmt, v low CD8, all other subsets normal) and worsening MS :-( this really matters to me.

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  5. So its talked and talked about , treating MS aggressively as early in the disease as possible but Im yet to see any blogs on what medications are the most effective in doing this . I personal would like to know thoughts on whether Alemtuzumab and Ocrelizumab are both considered as effective and aggressive as each other ? Thanks

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    1. Okay , so now the FDA had approved Ocrevus , how does one decide ? Is it a bit of a gamble ? Toss of a coin? Your thoughts are appreciated MD !

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    2. MD, do you think Tysabri is just as effective as Lemtrada and Ocrevus?

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    3. Alemtuzumab is more effective than Ocrelizumab, and in my opinion (based on brain atrophy data) it is more effective than Natalizumab (Tysabri).

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  6. Here in Australia we had a segment on the news last night giving hope with the drug Minocycline !? Trial done in Canada ! Whats this about , thoughts please . Thanks

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    1. http://www.nejm.org/doi/full/10.1056/NEJMoa1608889?query=featured_home
      Minocycline was effective in preventing conversion to clinical MS after a CIS for 6 months but did not show efficacy after 2 years. Does this show that there are separate disease processes after the initial demyelinating event? Minocycline can ameliorate initial inflammation but after a period of 2 years the disease is refractory to the drug.

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    2. Anon 11.54
      Don't hold your breath.

      Steve S.
      My take is that it says that it's not a very good DMT. Post set for tomorrow. In glass half empty mode...sorry.

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    3. Thanks, I thought as much! It just frustrates me how they are giving false hope to many people!

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    4. Its called spin...You do a trial and look for the positives, everyone would do that, but I can appreciate that it is false hope. Sorry

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    5. P.S. I'll struck someone elses christams card list

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  7. https://www.ncbi.nlm.nih.gov/pubmed/22785389
    >These results indicate that alpha-lipoic acid improves memory and reverses indices of oxidative stress in extremely old SAMP8 mice, but decreases lifespan. These findings are similar to studies using other types of antioxidants.

    Why we can't have nice things, Prof Mouse?

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  8. What do you think of this. A verge of a Cure
    http://www.cambridge-news.co.uk/business/technology/meet-cambridge-scientist-verge-curing-13129687

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    1. I can't really comment on this, because of conflicts, but piss-poor media reporting yet again....a cure...come on. Where is the supporting evidence?

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  9. If we stimulate the Tregs cells would they be able to stimulate the stem cells or even the oligodendrocytes and assist in remyelination?

    This study pointed out that Treg cells activate skin stem cells for hair growth to occur. Previously, stem cells were believed to do this work alone.

    Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation.

    Ali N1, Zirak B2, Rodriguez RS2, Pauli ML2, Truong HA2, Lai K2, Ahn R2, Corbin K3, Lowe MM2, Scharschmidt TC2, Taravati K2, Tan MR2, Ricardo-Gonzalez RR2, Nosbaum A2, Bertolini M4, Liao W2, Nestle FO5, Paus R6, Cotsarelis G7, Abbas AK3, Rosenblum MD8.

    Abstract

    The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of Tregs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.


    https://www.ncbi.nlm.nih.gov/pubmed/28552347

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  10. This study appears to demonstrate the reactivation of EBV infection after withdrawal of Natalizumab.

    Massive intracerebral Epstein-Barr virus reactivation in lethal multiple sclerosis relapse after natalizumab withdrawal

    Barbara SerafiniEmail the author Barbara Serafini, Eleonora ScorsiEmail the author Eleonora Scorsi, Barbara RosicarelliEmail the author Barbara Rosicarelli, Valérie RigauEmail the author Valérie Rigau, Eric ThouvenotEmail the author Eric Thouvenot, Francesca Aloisi'Correspondence information about the author Francesca AloisiEmail the author Francesca Aloisi

    Abstract

    Rebound of disease activity in multiple sclerosis patients after natalizumab withdrawal is an potentially life-threatening event. To verify if highly destructive inflammation after natalizumab withdrawal is associated with Epstein-Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient who died during fulminating MS relapse Following natalizumab withdrawal. Numerous EBV infected B cells / plasma cells and CD8 + T cells infiltrated all white matter lesions; The highest frequency of EBV lytically infected cells and granzyme B + CD8 + T cells were observed in actively demyelinating lesions. These results may encourage switching to B-cell depleting therapy after natalizumab discontinuation.

    Http://www.jni-journal.com/article/S0165-5728(17)30055-3/abstract

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  11. Hello Barts team-I spelt brats first and almost left it like that:-)

    My question to you is that the treatments you have, even cladribine,seem to work at dampening down inflammation-what if you have PPMS and the inflammation is very low so its not worth getting cladribine? I can't think of another drug that would be recommended for this sorry lot of patients:_( Does that lack of inflammation mean that the damage is done and now your going to simply see the effects every passing day? As in not even the new boy in town-ocreliz whats it-is also not going to be of any help?
    Pretty bleak outlook right?
    Is it worth considering stem cells at this point providing you have the money or do you just give in gracefully to becoming a cripple who lives painfully and dies with some relief?
    Sorry to be so morbid but I'm not feeling happy this morning.

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    Replies
    1. Immune treatments can probably help people with PPMS, but they seemingly don't have a hope of curing the condition unlike in those with early RRMS.

      There are many compounds out there that have early data that suggests they're promising for PPMS (High dose biotin, anti-oxidants, estradiol, etc). Whether one takes them or not depends on their risk tolerance.

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  12. If an area that has recently lost feeling sustains an injury, could the nerves be confused and cause greater pain, disproportionate to the level of injury?

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  13. When is the next Research Day? Professor G told me in clinic that it was meant to be today.

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    1. Apologies, I may have told you the Research was today. However, UCL have postponed the day because it clashed with the Queen's birthday today. I not aware of a new date having been set by UCL at this point in time. We will notify you when it does.

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  14. Both legs aching when wearing skinny jeans and for several hours after taking them off. Could this be connected to MS or less likely? Cotton leggings are fine and there's no aching, its the tight jeans that stretch I've noticed a correlation with aching.

    Could this aching be the MS or meralgia paresthetica? A disorder that occurs when one of the nerves that runs in the outer part of a thigh gets compressed. thanks

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    1. Doesn't sound like meralgia paresthetica to me.

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  15. "Cotton leggings are fine and there's no aching, its the tight jeans that stretch I've noticed a correlation with aching."

    Pressure of clothing,shoes,socks,and blanket against skin can alter
    feelings of numbness and sensitivity that can be described at times like an ache.

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    1. Thanks for the reply. It feels like muscle ache rather than a change of skin sensation. I wonder if it could be compartment syndrome.

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  16. "..EBV has not been consistently found in MS lesions, as would be expected. EBV episome replication during B cell division is now known to be inefficient, resulting in some descendant B cells becoming EBV-free after a few dozen divisions.

    EBV-free memory B cells in the CNS may thus have descended from a memory B cell which matured while containing EBV episomes, enabling its B cell receptor to recognize “forbidden” MS-causing antigens in the CNS, even if EBV is absent from this site."

    http://www.sciencedirect.com/science/article/pii/S2211034817301189

    Is this saying memory B cells in CNS may not have any EBV and yet still be autoreactive ? Would seem problematic if one designed an
    immunotherapy to take out EBV in CNS...and there is not enough EBV
    for it to find.

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  17. You are talking about PIRTs for Alemtuzumab but would it be possible to imagine Tecfidera as a PIRTs. I know that pharma wouldn't like it, but do you think it could be imagined, one day?

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    1. Can I imagine it...Tec as a PIRT not really. Wheres the data. If you mean the persistent leucopenia or some orals I think this is cause for concern .

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  18. I was just reading the article here on toes. I have a couple of hammer toes and saw an orthopedic surgeon and he suggested surgery to correct them. They are painful yet my neurophysio advised against.
    I also have a very tight shortened achilles tendon and the surgeon suggested that a lengthening procedure on that would enable my foot to get to 90 degrees.
    Neuro physio suggests stretching which I have been doing but have had no improvement so I am tempted to go under the knife.

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  19. Hypertension and MS. Study Finds High Blood Pressure May Be Associated with MS Progression, this I find interesting.
    Disability Progression in Multiple Sclerosis Is Affected by the Emergence of Comorbid Arterial Hypertension.J Clin Neurol. 2016.

    Is blood pressure monitored with pwMS? Prof G could this be worthy of a survey?
    Mine isn't monitored at the hospital. I do have a home BP monitor.

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  20. Maybe I missed the discussion here - but what about the claim that
    "Dr Su Metcalfe is a woman who could be on the verge of curing multiple sclerosis"
    “I discovered a small binary switch, controlled by a LIF, which regulates inside the immune cell itself. LIF is able to control the cell to ensure it doesn’t attack your own body but then releases the attack when needed.

    “That LIF, in addition to regulating and protecting us against attack, also plays a major role in keeping the brain and spinal cord healthy. In fact it plays a major role in tissue repair generally, turning on stem cells that are naturally occurring in the body, making it a natural regenerative medicine, but also plays a big part in repairing the brain when it’s been damaged.

    “So I thought, this is fantastic. We can treat auto-immune disease, and we’ve got something to treat MS, which attacks both the brain and the spinal cord. So you have a double whammy that can stop and reverse the auto-immunity, and also repair the damage caused in the brain.”

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    1. This is totally irresponsible reporting by Cambridge and Su, it is so far from the clinic. This is essentially a sales pitch for investors.

      Happy to say this to her face and will do when I see her.

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  21. If new symptoms are a relapse, what determines the end of that relapse?

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  22. Regarding the statin trial. Statins can have common side effects of muscle pain and joint pain and occasionally muscle inflammation (swelling) and damage.
    What do you about this?, I know most medications can have side effects.

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  23. Could Parkinson's Disease have any immunomediated or even autoimmune implications, since the clusters of the alpha-synuclein protein are a major problem in PD?

    What would be very similar to MS, and that is why leflunomide can be reused in MS, because the immune system would also be involved in Parkinson's? Something like for example lymphocytes (T cells maybe) attacking alpha-synuclein, which would lead to the problem in the sudden decrease in dopamine production?

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    1. Looks like you're on to something Cinara. I've often wondered about this too. My father had 2 autoimmune diseases, Graves and Pernicious anaemia, he also developed Parkinson's maybe there's a correlation.
      This just out.
      https://www.nature.com/nature/journal/v546/n7660/full/nature22815.html

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    2. Med Hypotheses. 2005;64(3):458-63.
      Add Alzheimer's disease to the list of autoimmune diseases

      Saw this couple of weeks ago..bookmarked it
      https://www.ncbi.nlm.nih.gov/pubmed/15617848

      "Thus, it is possible that the mere presence of anti-neuronal autoantibodies in the serum, whose importance had been previously dismissed, may be without pathological consequence until there is a BBB dysfunction to allow the deleterious effects of these autoantibodies access on their targets. Hence, these observations suggest autoimmunity-induced cell death in AD."

      write up on the Nature study:
      https://www.sciencedaily.com/releases/2017/06/170621132904.htm

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    3. Once you have damage the cell contents are liberated and secondary autoantibodies could easily occur. T

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  24. That's serendipitous - I was just about to ask if anyone knows if there is a similar resource to this blog for Parkinson's Disease?

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  25. The 'leprosy hypothesis' has been mentioned on here before but without any further discussion. Does this research have any relevance to MS? Madigan, CA et al. A Macrophage Response To Mycobacterium leprae Phenolic Glycolipid Initiates Nerve Damage In Leprosy. Cell 24 Aug 2017; doi: 10.1016/j.cell.2017.07.030

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  26. MD,

    I tried starting a new hobby tonight, finally got Rocksmith 2014 for the xbox 360. This is a new brain health challenge for me. I got the software set up, then I had to pick my first song. I was scrolling through the list and found The Trooper and knew that I had to start there. I scored 0.8%, but you have to start somewhere! I think that I might pick something easier next time.

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    1. Brave man.... maybe try a bit of AC/DC...at least the rhythm section..
      The Trooper is an ace song by I can't play the gallop fast or long enough but MD2 can Rock just fine. Played it in the lab once when we had the gear in the seminar room....I cheated on the bass. Try "phantom of the opera" I can do the bass line just about, remember to say "Cha" before you rock out:-)

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