Tuesday, 31 July 2012

Unrelated Blogger comments 2

Unrelated Blogger Comments July-2

Unrelated BLOGGER Comments

Sometimes you want to say something that is unrelated to the threads. This is a spot for you
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"If you are a MSer at the Royal London Hospital please sign-up for our cognition study!"


Anonymous said...
I see you are recruiting for ppms. I turned 50 in June would I still be able to apply?
MouseDoctor said...
As long as you fit the criteria required for trial entry there should be no issues. I am sure G can tell you more.
Vasilis Vasilopoulos said...
Why did you tag the article "Veins in MS" as CCSVI? It is a histological study for people with MS. Should we only be intersted in what happens in our CNS only?
MouseDoctor said...
Why was the study on veins done, because of context of CCSVI simple as that.

At some stage we will streamline the tags because we have been told their are too many.


Should we be only interested in what happens in CNS.

Stupid comment off course not

You should be interested in other things like music literature and sport;-)
Vasilis Vasilopoulos said...
" Why was the study on veins done, because of context of CCSVI simple as that."

Despite that, it says something about MS that you didn't know before, doesn't it? Are you willing to B-rate it just because it's not about the immune system?
MouseDoctor said...
I did not know we were A-rating or B-rating articles, so do not know what you are talking about....As is often the case.

Maybe I should have tagged it- yellow-green birefringence or collagen, vein but these were not in the list
Gavin Giovannoni said...
Re: "I see you are recruiting for ppms. I turned 50 in June would I still be able to apply?"

Potentially; the ocrelizumab study has extended the age cut-off to 55 years. I must warn you that the inclusion and exclusion criteria are very strict and most PPMSers fail pre-screening or screening.
Anonymous said...
What is the use of having such strict exclusion criteria? If most PPMSers fail to qualify for the trial, it means the trial population isn't representative. Finally the same PPMSers will need treatment.

25 comments:

  1. I just got my yearly MRI report back (no new activity!) and looked up hyperintensity on wikipedia.

    http://en.wikipedia.org/wiki/Hyperintensity

    At the end of the introduction is this sentence:

    "Postmortem studies combined with MRI suggest that hyperintensities are dilated perivascular spaces, or demyelination caused by reduced local blood flow."

    with this footnote:

    "Thomas, A.J., Perry, R., Barber, R., Kalaria, R.N., O’Brien, J.T. (2002). "Pathologies and pathological mechanisms for white matter hyperintensities in depression," Ann N Y Acad Sci., 977:333–339."


    I'll form my question in multiple choice format. Which of the following is true:

    1. This is false, blood flow is not related to hyperintensities.

    2. This is true, but has nothing to do with MS.

    3. This is true, and is related to MS but does not support for the CCSVI theories due to the details.

    4. OMG! This proves CCSVI! Drop everything!

    5. Other (please explain)

    ReplyDelete
  2. This:

    http://www.phdcomics.com/comics/archive.php?comicid=1174

    ReplyDelete
  3. 5. You should not rely on Wikipedia for serious information.

    ReplyDelete
  4. I'd like to come back to something that has been interesting me: modafinil.

    I know that it is used to combat MS fatigue, and as Prof G has pointed out, it works in about 30% of cases.

    But is there another role for modafinil? As a neuroprotective drug?

    The reason I ask is that

    Here
    http://linkinghub.elsevier.com/retrieve/pii/S2211034812000429?via=sd&cc=y
    It states: "In relapsing-remitting (RR) patients treated with modafinil there was no significant EDSS change over the follow-up period. In RR patients not treated with modafinil, the mean EDSS increased significantly (0.94; p=0.0001) over the follow-up period".

    Modafininil has been implicated in helping reduce disability in other neurological ailments: http://jcn.sagepub.com/content/21/4/294.short (Modafinil, a central nervous system stimulant, appears to improve tone and ambulation in spastic diplegic cerebral palsy.)

    It has also been extensively looked at for its neuroprotective qualities:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654794/
    This article concludes: In summary, the bulk of research into modafinil’s wake-promoting mechanism has focused mostly on possible extracellular activities of modafinil. We propose that more work be done on examining potential intracellular mechanisms of modafinil and finding a point of convergence of modafinil’s stimulant and neuroprotective effects. It is likely that modafinil both enhances cellular metabolism and reduces free-radicals in neurons (Pierard et al 1995; Xiao et al 2004). Reduction in brain oxidation or an increase in cortical creatine could promote vigilance (Ikeda et al 2005; McMorris et al 2006), and each effect can increase neurotransmitter release by reducing inhibitory KATP-channel activity. Thus, through any disruption in the positive feedback loop of increased free-radical production and reduced ATP production modafinil could potentially exert its neuroprotective and wake-promoting effects.

    So the question is this: is there any interest in doing a trial of modafinil in the UK? It is off label (I think) so who would fund it? It strikes me as being a real possible neuroprotective drug... and yet isn't being used as such, at least in the UK.

    Thoughts?

    ReplyDelete
  5. Re: "But is there another role for modafinil? As a neuroprotective drug?"

    Possibly, but who is going to pay for the study now that the drug is off patent. I for one would want to see how effective it is in our animal model before trying to get funds to test in progressive MS, possibly with our CSF NF assay. The animal experiments alone with cost £70,000. If you can crowd source the money I am sure MD and MD2 will do the studies.

    ReplyDelete
  6. " I for one would want to see how effective it is in our animal model before trying to get funds to test in progressive MS, possibly with our CSF NF assay"

    Why don't you try the same approach with the EBV conjecture prior to launching the Charcot project?

    ReplyDelete
  7. "Why don't (didn't?) you try the same approach with the EBV conjecture prior to launching the Charcot project?"

    Please give us a rough idea of the design you envision for your experimental plan?

    ReplyDelete
  8. It was a wonderful show and Danny Boyle is a genius! Doesn't matter that I've never heard of Gregory's Girl etc.
    Enjoy the holiday

    ReplyDelete
  9. "Please give us a rough idea of the design you envision for your experimental plan? "

    Don't you have a mouse model of EBV infection? I mean, you don't know what MS is, but you have a mouse model for it and use it to test drugs. I guess EBV must be easier to model since you know all about it. Test the Charcot drugs on it before testing them on MSers.

    ReplyDelete
  10. Your CCSVI updates missed some articles that at least prove the existence of CCSVI. For example:

    http://www.techvir.com/article/S1089-2516%2812%2900025-X/fulltext
    Intravascular Ultrasound in the Diagnosis and Treatment of Chronic Cerebrospinal Venous Insufficiency

    Patients should read this to be fully informed about what might be their case also.

    ReplyDelete
  11. Re: "Don't you have a mouse model of EBV infection? I mean, you don't know what MS is, but you have a mouse model for it and use it to test drugs. I guess EBV must be easier to model since you know all about it. Test the Charcot drugs on it before testing them on MSers."

    Unfortunately, EBV only infects humans hence the lack of an animal model. Fortunately, all the drugs we are testing have all been into humans before. Rituximab, Ocrelizumab, etc. So MSers don't have to worry about the therapies we are proposing, they have a well-defined safety profile. This is the main reason we are taking them into MS.

    ReplyDelete
  12. "Missed an article"

    http://www.techvir.com/article/S1089-2516%2812%2900025-X/fulltext

    This appears to be a review article which I do not normally cover. This suggests this is just a reguritation of others work so couch potato science. This is just an opinion

    ReplyDelete
  13. As Prof G meant to say EBV does not infect meeces so this experiement is pointless and is not going to happen. EBV is largely a human virus, if not maybe animals would get MS..they don't.

    Before you waste your time hunting the literature I know that you can infect marmosets with EBV where it has been used for tumourogenesis. I used to work in a lab where this was done..but have no intention of going down this route as it would not give the answer.

    Maybe do your homework before asking questions?

    ReplyDelete
  14. "This suggests this is just a reguritation of others work so couch potato science."

    You are absolutely wrong. You disorientate your readers with statements like this. At least, read it before telling your opinion.

    It is the personal experience of an Interventional Radiologist that describes in detail and with the support of images from intravascular ultrasound (IVUS) the places and the nature of venous abnormalities found in patients with CCSVI.

    ReplyDelete
  15. "Unfortunately, EBV only infects humans hence the lack of an animal model"

    As far as anybody knows MS affects only humans, yet EAE is widely used as an MS model. Don't you find this paradoxical?

    "they have a well-defined safety profile."

    In plain language this does not mean they are safe, but that you know exactly what side effects they have.

    Who decides that the EBV conjecture is strong enough to allow exposure of MSers to these side effects? What if you are just hunting a ghost? Will the participants be left with permanent disabilities due to these drugs?

    ReplyDelete
  16. Re: "Who decides that the EBV conjecture is strong enough to allow exposure of MSers to these side effects? What if you are just hunting a ghost? Will the participants be left with permanent disabilities due to these drugs?"

    A peer-review panel and an ethics committee. Once the study is started individual MSers give informed consent based on the information sheet and questions. At the end of the day MSers decide whether or not they want to take part or not.

    The drugs we are planning to test are not associated with any life threatening side effects and don't cause permanent disabilities.

    ReplyDelete
  17. Not sure if you saw this Prof G, Mouse Doc:

    http://www.cosmosmagazine.com/news/5847/venom-sea-anemone-could-treat-ms

    It seems that ShK targets the potassium ion channel Kv1.3, which is found in a specific set of white blood cells responsible for recognising body invaders – bacteria and viruses – that the immune system has already fought off in the past.

    This made me think of an EBV connection? What do you think?

    Does this strike a chord?

    ReplyDelete
  18. Interestingly, others are onto the Kv1.3 blocking angle.

    http://www.airmid.com/kv-potassium-channel.html

    And blocking the channel has been shown to have possible therapeutic value on psoriasis: http://www.nature.com/jid/journal/v131/n1/full/jid2010245a.html
    (I note this because BG12 - fumaric acid ester - is used for the treatment of psoriasis and has some real potential in MS treatment).

    What's the connection - if any - between EBV and KV1.3? Can blocking KV1.3 downregulate EBV-B cells?

    ReplyDelete
  19. Just curious if anyone knows if magnesium tablets can somehow neuralize potassium - is there a connection? Thanks.

    ReplyDelete
  20. "It is the personal experience of an Interventional Radiologist that describes in detail and with the support of images from intravascular ultrasound (IVUS) the places and the nature of venous abnormalities found in patients with CCSVI."

    It is written by someone with a personal interest in making money out of CCSVI so it can hardly be regarded as unbiased.

    ReplyDelete
  21. I'm in my third trimester of pregnancy and due to recommence Tysabri once I've given birth in October. Whilst I've continued to take 5000ui vitamin d3 during pregnancy, what amount should a newborn have ( ie is that in formula adequate or should babies also be supplemented)?

    Thanks, PM

    ReplyDelete
  22. Re 'Your CCSVI updates missed some articles'
    VV it's not their job to keep us updated on everything CCSVI (or even on everything MS)
    Blog owners decide what is interesting & important enough for their blog

    ReplyDelete
  23. Re: "I'm in my third trimester of pregnancy and due to recommence Tysabri once I've given birth in October. Whilst I've continued to take 5000ui vitamin d3 during pregnancy, what amount should a newborn have ( ie is that in formula adequate or should babies also be supplemented)?"

    Depending where you live in the world supplementation of newborns happens anyway, i.e. the health visitors come to your home to give vD drops. If not Brenda Banwell has recommended a dose of 600U per day in children under the age of 2.

    ReplyDelete
  24. Re: "Just curious if anyone knows if magnesium tablets can somehow neuralize potassium - is there a connection?"

    Not in the body; homeostasis keeps the levels of potassium and magnesium stable.

    No connection!

    ReplyDelete
  25. "Blog owners decide what is interesting & important enough for their blog".

    VV Maybe its on your BLOG what's the website?

    ReplyDelete

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