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Our Presentation at the FDA CDER is now online
 Moderated by: Prof Trevor Marshall Page:  First Page Previous Page  1  2  3  4  Next Page Last Page  
 

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Frans
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 Posted: Sat Mar 18th, 2006 12:17

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Especially this exerpt from the hippocratic oath is something he should read up on:

I will not be ashamed to say "I know not," nor will I fail to call in my colleagues when the skills of another are needed for a patient's recovery.

from here: http://tinyurl.com/ogre7

This seems lost in his recollection.

Sincerely, Frans



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wrotek
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 Posted: Sat Mar 18th, 2006 14:49

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Just for translation pursposes, person announcing Dr Marshall is Commander Perez ?



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Prof Trevor Marshall
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 Posted: Sat Mar 18th, 2006 14:51

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My mistake, he was actually "Captain Perez"
Always better to bump somebody up in rank when in any doubt at all:)
All those gold bars on the sleeves, and medals on the chest, looked quite impressive, close-up:)

wrotek
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 Posted: Sat Mar 18th, 2006 15:00

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So That is why he smiled :) Yes very impressive distinctions, i watched and wondered what is different with this picture, is it military starts to be intrested in MP ?

When i received a magazine with MP article in it, it was adressed to me as a professor :)

Last edited on Sat Mar 18th, 2006 15:03 by wrotek



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Prof Trevor Marshall
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 Posted: Sat Mar 18th, 2006 15:10

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The US Public Health Service has a uniformed division, the Commissioned Corps. It has the promotional structure of the Navy, and many of the most dedicated staff members at NIH and FDA are lifetime members of the Commissioned Corps.
http://www.usphs.gov/

Lantern
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 Posted: Sat Mar 18th, 2006 16:56

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OK, I think I've found the reason why I can't seem to download the torrent file (from the ĀµTorrent FAQ);

ĀµTorrent's DHT implementation is the same as Mainline and BitComet's, but unfortunately this is incompatible with Azureus's implementation.

I think the file is relying on DHT as the tracker itself doesn't seem to be working for me. I think Azureus is less compatible overall with other bittorrent clients, so it might mean I'll have to get Azureus to get the FDA file. The other peer I can see might have to do the same also.



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John McDonald
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 Posted: Sat Mar 18th, 2006 18:02

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HEY FOLKS, those of you with full copies of the DVD - please leave your Bittorrent on as SEEDS.Yes that's true. I leave mine on as a seed and Frans also does. There are a few client who seem to have problems with our tracker i guess. So when you want to be sure it works... use Azureus. And when it does not work with Azureus it's probably your firewall what is causing the problems.I downloaded Azureus and managed over 3 days to load the full ISO file at an impossibly slow bit rate, but despite poking about my router and firewall I couldn't get Azureus to work bidirectionally.  Maybe you have to have a public IP address, or at least exposure to the outside internet which I cannot get without paying extra.  I am behind at least one other router that doesn't belong to me.  So I am one of those scoflaws who downloaded the full DVD but cannot seed or supply it to anyone else.

A very short while ago I attempted to burn the ISO onto my wife's DVD burner only to discover that her Win2k and DVD burning sofware only supports data DVDs.  Arghh!  I guess I can burn it at work next week.

I tell young engineers that "High Technology" means that it barely works and sometimes doesn't but we have to ship it anyway.

john



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Prof Trevor Marshall
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 Posted: Sat Mar 18th, 2006 18:43

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Hey John - you live just 20 minutes away - you could have driven over and picked up a DVD, case and all:)

Shadowzone:
Azureus is pretty CPU-intensive, but its security is unmatched (with the SafePeer plugin), and it is free, open source. So all the geeks use it:):) I can see an Aussie site trying to connect - but never seem to get through the handshake:X
Your client might also be confused by the fact that I use port 51001 (rather than the default 6881) so as to confuse my ISP as to the reason I am using so much outgoing bandwidth (9 gigabytes so far):)

John McDonald
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 Posted: Sat Mar 18th, 2006 23:42

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Heck, I could have walked over and back in the time it took to download. I have a fast connection, so my super slow download speeds were all about my mis-mastery of Azureus.

Have some of my bandwidth.  I have put another copy of the 50M version for downloading via right click here: http://tinyurl.com/n8bvf 

(Right click to save target.  Normal left click will not be as satisfying)

john 

 



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shamutooth
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 Posted: Sun Mar 19th, 2006 07:37

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I finally was able to watch Trevor's latest presentation, and IMO it was fantastic. When did MP thinking give up the idea that Vitamin D was an inert precursor to 1,25D, and that it had immunosupressive actions on its own? Also, Trevor's computer human model has to have vast implications in the future development of designer medications. I can't believe the large drug companies aren't beating on your door to hire you :) Sam



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Prof Trevor Marshall
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 Posted: Sun Mar 19th, 2006 08:16

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Sam,
The realization that all the Vitamin D metabolites were steroids came about when I started to model the molecules while preparing our recent paper.

Being a good scientist:) I was also drawn to model corticosteroids, the androgen hormones, and a number of other drugs which I thought might affect the immune system.

At this point I realized that the conversion of 7-dehydrocholesterol to 1,25-D is the primary pathway for activation of the VDR in man, and that ingested vitamin-D has no beneficial part to play in the immune system.

Vitamin D supplementation, which includes a sun-loving life style, is something which has come along quite recently (the last 50 years) and understanding the innate immune response at the molecular level made it clear that not only is Vitamin D not a vitamin, but it is actually immunosuppressive (generally harmful) in the doses currently being ingested by the population.

I did compute up the affinity of all the Vitamin D metabolites into the VDR, and also examined their mechanisms of action in the VDR. Only 1,25-D activates the VDR, both 25-D and Vitamin D inactivate it. Since these are present in such large quntities in the bloodstream these days (one thousand times the bloodstream concentration of 1,25-D) there was clearly the potential for interference in innate immunity. At about that time everything started to make sense...

I haven't published this through the peer-review journals, I doubt that the world is ready for this news quite yet.

..Trevor..

Prof Trevor Marshall
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 Posted: Sun Mar 19th, 2006 08:36

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Further to the previous message, I also found that 1,25-D had a ten times higher affinity for the Alpha1 and Beta1 Thyroid receptors than it did even for the VDR, and also a very high affinity for the Glucocorticoid receptor (approx same affinity as VDR). Clearly these are not the actions of a vitamin, but of a steroid, in this case, a powerful immune suppressant.

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 Posted: Sun Mar 19th, 2006 08:51

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Trevor, The androgen steroids acting on the immune system correlates with my experience also. In my early 20's I used testosterone and some of the anabolic steroids like Deca-Duarabolin and Winstrol for body-building, and had a dramatic reduction in TH1 symptoms, which were probably acting as Prednisone. My next question is, can you use your model to find out why an asthma medication called Clenbuterol can have the same effects as the androgens (dramatic lean muscle building and fat burning capabilities,fast recovery time, but W/O the androgenic effects in females such as hirsutism, reduction in TH1 symptoms) and then design a medication W/O the side effects of Clen (fast heart rate, intense muscle cramping).This could be the ultimate diet pill. We could go into business together and make millions LOL :) Sam



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wrotek
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 Posted: Mon Mar 20th, 2006 07:00

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At the end of presentation Dr Marshall is comparing vitamin D to prednisolone. I would like to know which metabolite of vitamin D is presented on the left side of the photo because it is not 1,25-D yes ?

Last edited on Mon Mar 20th, 2006 07:23 by wrotek



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Prof Trevor Marshall
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 Posted: Mon Mar 20th, 2006 07:13

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I am comparing Vitamin-D3 to Prednisolone. The metabolism goes thus:-

7-dehydrocholesterol >> Vitamin-D3 >> 25hydroxyvitamin-D >> 1,25dihydroxyvitamin-D

At each 'hydroxy' stage an oxygen (and hydrogen) are added. You need the hydroxy at the 1-alpha position (designated as O1 in Figure 5 of our recent paper) in order to activate the VDR. Only 1,25-D has that. You also need the hydroxy group at the C25 position (in Figure 5 you can see that hydrogen-bonding to HIS305 and HIS397).
All the D-metabolites are seco-steroids, as I demonstrate on the video.

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 Posted: Tue Mar 21st, 2006 14:21

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Have viewed and orderd copies of this excellent presentation. Slide PDFs will be printed for benefit of those who will be given copies. (FDA isn't the only one that loves charts.) Excellent strategy, and nice touch to throw in corticosteroids and model relationships to D, as well as picking out a couple of other random advertised drugs and modelling those. Nice keyword choice with title.

Hopefully, there can now be no question to the authenticity or value of main topic models described for clinicians to use as they carefully consider errant consensus and researchers to focus new efforts.

Will look at some of the abstracts of other ARB papers in the "one a day" publication by multiple folks. Someone has got to be finding supporting evidence, and likely those and new researchers will not quickly discount the perspectives outlined in this report to the FDA.

And most of all, thank you.

Last edited on Tue Mar 21st, 2006 14:23 by jrfoutin



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Frans
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 Posted: Tue Mar 21st, 2006 23:46

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Janet,

The one a day publication at pubmed is not about ARBs, but about VDR IMO. Just type in VDR in Pubmed and dr Marshall's paper will be at the third page. At least, it was a couple of days ago :cool:

Sincerely, Frans



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Frans
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 Posted: Wed Mar 22nd, 2006 02:41

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dr Marshall, did you ever read my suggestion Posted on: Sat Mar 18th, 2006 22:10 at page 2 of this thread? Is there anything we can do as a cohort?

Sincerely, Frans



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jdc
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 Posted: Wed Mar 22nd, 2006 09:28

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I'm afraid I'm a little confused about how to view the presentation and I wonder if I might not be the only one. I only have a slow 56 k modem, no dsl. I downloaded the first file that Trevor mentioned and it seemed to stall on my version of Real Video 9 (I think it was Real Video--it was certainly a Realnetworks product that was viewable). It seemed to be trying to stream the presentation but was interrupted and then the sound never came on.

OK, so then I tried to download Azureus and got very frustrated trying to make sense of it. Who ever designed the user interfaces for these products? For me it was totally confounding. I tried to find out ways to "enter in" magnet files, and then torrent files (or whatever they are). I even spoke to a software engineer with a Harvard Engineering degree. He confessed that he had no idea what a torrent file was and had never heard of Azureus.

Then it dawned on me that maybe I should use FTP to receive one of the files that Trevor mentions, but to tell you the truth, I just ran out of gas and interest in trying to work my way through all the techno computer speak which doesn't interest me in the least and I find trouble concentrating on in my current state.

Maybe someone who really loves all of this computer-dewiring-disentanglement can offer a few simple ideas. I don't need the "Idiots Guide" just a few pointers. Or maybe a 56k connection just won't cut it. Thanks.

Maybe I was on the right track thinking that FTP was the way to import and download one of the files...



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Prof Trevor Marshall
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 Posted: Wed Mar 22nd, 2006 09:42

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Jim,
The DVD of the presentation can be requested from
http://autoimmunityresearch.org/fdacder.htm

It comes in a presentation box and is suitable for loaning to friends and physicians:)


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