Thread: Stephen Davies Update

  1. #1331
    Quote Originally Posted by Charles Hansen View Post
    Grammy,

    You write as though Dr. Davies has thrown in the towel and is no longer performing any research. Why?

    Thanks,
    Charlie
    No, I apologize Charlie. I did not mean that at all. I have no idea what research project he may or may not be working on. The last I knew he was working on 12 day unilateral injury models. His research thus far has all been in 12 day or less and I simply don't follow the acute labs too closely.

    I follow research on chronic SCI lab projects and try to keep pace with the experiments and progress working in that particular arena. I can't say the acute work in Davies lab is even on my radar right now.

  2. #1332
    Quote Originally Posted by Charles Hansen View Post
    Is there somebody else out there who is doing better work than Dr. Davies?
    Yes there is

  3. #1333
    Quote Originally Posted by GRAMMY View Post
    No, I apologize Charlie. I did not mean that at all. I have no idea what research project he may or may not be working on. The last I knew he was working on 12 day unilateral injury models. His research thus far has all been in 12 day or less and I simply don't follow the acute labs too closely.

    I follow research on chronic SCI lab projects and try to keep pace with the experiments and progress working in that particular arena. I can't say the acute work in Davies lab is even on my radar right now.
    Grammy,

    I have to say that you certainly have me confused. In so many areas you have a great deal of knowledge to share, but other areas I am baffled by some of the things you say.

    Lab rats have a typical lifespan of 24 months. If I recall correctly, they reach maturity at 3 months (12 weeks). The most stringent chronic test you could possibly give a lab rat would be to take a 3 month old (mature rat), train it for gridwalk tests, injure it and wait 9 more months (36 weeks) before treating it. That would roughly the equivalent of injuring an 18 year old human and then waiting over 30 years before treatment.

    One couldn't wait much longer to apply treatment as the rats would be dying off from natural causes before the experiments were concluded. So when Dr. Davies most recent decorin experiments waited 12 days post-injury before treatment, that is at least the equivalent of waiting over 12 months to treat a human.

    Twelve days does not qualify as acute studies in humans, and it is FAR from acute studies in rats. So if I were you, I would definitely keep Dr. Davies on your radar, at the very least.

    Thanks,
    Charlie
    Last edited by Charles Hansen; 01-22-2013 at 02:49 AM.

  4. #1334
    Quote Originally Posted by Christopher Paddon View Post
    Yes there is
    Hello Christopher,

    No need to be snarky. Just let us know who is doing better work, what they are doing, and what they have accomplished.

    Thanks,
    Charlie

    PS -- Nice guitar in your avatar. Looks like an ES355 to me. Too nice to be an old one (unless you're a millionaire), so I'd guess a re-issue. Can you still play? I can't. At about T6 I have no trunk control and when I try to play I just fall over. I have to support myself with one arm, which makes it difficult to play.

  5. #1335
    Yeah I was being 'snarky' - too many scientists to mention really - Oswald Steward, Jerry Silver, Geoffrey Raisman - there are loads more.

    That's not my 355 but I do have a 1961 355, a 1962 335 and a 1960 345 which I have collected over the years (plus a couple of custom shop ones). I'm certainly not a millionaire but I am an enthusiast and a really good musician, if I do say so myself. I am a complete T7 but I have no problem playing the guitar which I have done all of my 30 years in a chair. I am in a gigging blues and rock band.

    It's odd how such similar injuries affect people differently. I saw it all the time back in the spinal unit 30 years ago - we were all expected to do archery, wheelchair basketball and wheelchair races. Apart from the fact that I had no interest in disabled sport it seemed incredibly unfair as each disability was so different from another.

    I'm not sure why you can't play the guitar - I have no trunk muscle control.

  6. #1336
    Quote Originally Posted by Charles Hansen View Post
    Grammy, I have to say that you certainly have me confused. In so many areas you have a great deal of knowledge to share, but other areas I am baffled by some of the things you say. Twelve days does not qualify as acute studies in humans, and it is FAR from acute studies in rats.
    You have an interesting time theory Charlie, but going off scientifc data from a research abstract here Dr. Davies disagrees with your theory. Davies says that peak levels of 245/130 kD neurocan, NG2, and 250/200 kD tenascin-C were reached at 8 days, with (maximum levels of phosphacan and 140/80 kD brevican attained later, at 1 month post injury).

    According to his study, a 12 day injury wouldn't be so relevant if maximum phosphacan and brevican haven't even been reached yet. By reading this abstract, I'd say this particular lab would start chronic studies at a very minimum of 1 month to 6 months post injury by their own results rather than the 12 days you suggest.

    J Neurosci Res. 2003 Feb 1;71(3):427-44. Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue.
    Tang X, Davies JE, Davies SJ. Source
    Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
    Abstract
    Previous studies have correlated the failure of axon regeneration after spinal cord injury with axons contacting scar tissue rich in chondroitin sulfate proteoglycans (CSPGs; Davies et al., 1999). In the present study, we have conducted immunohistochemical and quantitative Western blot analysis of five axon-growth-inhibitory CSPGs and tenascin-C within stab injuries of adult rat spinal cord at time points ranging from 24 hr to 6 months post injury. Quantitative Western blot analysis showed robust increases in neurocan, tenascin-C, and NG2 levels by 24 hr, suggesting that these molecules play a role in preventing axon regeneration across acutely forming scar tissue. Peak levels of 245/130 kD neurocan, NG2, and 250/200 kD tenascin-C were reached at 8 days, with maximum levels of phosphacan and 140/80 kD brevican attained later, at 1 month post injury. Versican V2 protein levels, however, displayed an opposite trend, dropping below unlesioned spinal cord values at all time points studied. Confocal microscopy at 8 days post injury revealed heightened immunoreactivity for phosphacan, NG2, and tenascin-C, particularly within fibronectin(+) scar tissue at lesion centers. In contrast, neurocan was displayed within lesion margins on the processes of stellate NG2(+) cells and, to a much lesser extent, by astrocytes. At 6 months post injury, 130 kD neurocan, brevican, and NG2 levels within chronic scar tissue remained significantly above control. Our results show novel expression patterns and cell associations of inhibitory CSPGs and tenascin-C that have important implications for axon regeneration across acute and chronic spinal cord scar tissue.

    Here's the 2006, 8 day post injury "acute" paper.
    http://www.ncbi.nlm.nih.gov/pubmed/16629625

    I don't believe Dr. Davies would say that adding 4 days over this past decade to his acute injury model would now be considered chronic research in rats. I believe the experts would concur.

    As far as injury in humans, for instance, the Proneuron trial which had a center in Colorado accepted patients up to 14 days post and qualified them acutes. http://www.clinicaltrials.gov/ct2/sh...oneuron&rank=1

    Perhaps this could help: http://thejns.org/doi/full/10.3171/2010.3.SPINE09190
    Last edited by GRAMMY; 01-25-2013 at 03:31 PM.

  7. #1337
    Quote Originally Posted by Charles Hansen View Post
    Hello Christopher,

    No need to be snarky. Just let us know who is doing better work, what they are doing, and what they have accomplished.

    Thanks,
    Charlie

    PS -- Nice guitar in your avatar. Looks like an ES355 to me. Too nice to be an old one (unless you're a millionaire), so I'd guess a re-issue. Can you still play? I can't. At about T6 I have no trunk control and when I try to play I just fall over. I have to support myself with one arm, which makes it difficult to play.
    No offence Charles, but you freely admit to not keeping up with the field yet you devoutly support Davies and his work. He may or may not be onto something - but you cant support someone who is not providing a return on investment ie papers, data and collaboration. Hence why he spends more time outside of his lab looking for funding in places like China, Australia and Europe.

  8. #1338
    Quote Originally Posted by Christopher Paddon View Post
    Yeah I was being 'snarky' - too many scientists to mention really - Oswald Steward, Jerry Silver, Geoffrey Raisman - there are loads more.

    That's not my 355 but I do have a 1961 355, a 1962 335 and a 1960 345 which I have collected over the years (plus a couple of custom shop ones). I'm certainly not a millionaire but I am an enthusiast and a really good musician, if I do say so myself. I am a complete T7 but I have no problem playing the guitar which I have done all of my 30 years in a chair. I am in a gigging blues and rock band.

    It's odd how such similar injuries affect people differently. I saw it all the time back in the spinal unit 30 years ago - we were all expected to do archery, wheelchair basketball and wheelchair races. Apart from the fact that I had no interest in disabled sport it seemed incredibly unfair as each disability was so different from another.

    I'm not sure why you can't play the guitar - I have no trunk muscle control.
    Quite a nice collection! I had a '61 (I think that's what it was) ES-345 for a while. It's not really my kind of guitar -- I ended up with one as repayment for a trade that had gone bad. At the time I had a '57 Les Paul Custom with 3 humbuckers and a friend arranged a trade for a '58 LP Gold-Top. Turned out to be a rip-off and I ended up with nothing. My friend felt bad so he gave me the '345, but I never warmed up to it. I was just a solid-body kind of guy. I ended up selling it in the early '80s for $900 to pay rent when I broke my leg and couldn't work. Then things really got out of control. There was a time when Sumburst Les Pauls were worth $50.000 but the Black Beauty was barely worth $10,000. By the time Sunbursts reached $250,000, if I still had the Black Beauty, it would have been worth $75,000. But prices have fallen off since that peak. Heck, my first good guitar in '72 was a '64 Strat. I bought it for $250 and sold it for the same price two years later. I was flabbergasted to find out that at one point it had reached about $25,000. Crazy market. I haven't kept up with it, but would guess that each of your guitars must be worth at least $25,000 these day, maybe even double that.

    How do you stay sitting up while holding the guitar? Does your chair have a reclining back? Mine is pretty upright and I have to brace myself with a hand or elbow to keep from pitching forward. My chair has armrests and I can't get the guitar close enough to play. The most I've been able to do is hunch over the guitar and lean on it for support, but after five minutes I have a huge dent in my leg from my upper body weight pushing on the sharp edge of an acoustic. The only time I even try is just to show my kids how to do something. They are 100x more talented than I ever was, so they pick it up in two minutes and a week later are playing it better than I did after ten years of fairly serious playing. Makes me smile!

    These days, with the insurance companies calling the shots, you get sent home as soon as you can transfer by yourself. That's about it. I wouldn't do much anyway for two reasons -- I can still work on the computer to pay the bills (which have a way of piling up), and my neuropathic pain is too distracting to have much fun doing things like trying to play the guitar.

    How about giving me one good link to something that each of the three researchers you noted have done?

    Thanks,
    Charlie

  9. #1339
    Quote Originally Posted by GRAMMY View Post
    You have an interesting time theory Charlie, but going off scientifc data from a research abstract here Dr. Davies disagrees with your theory.

    >Snip<

    By reading this abstract, I'd say this particular lab would start chronic studies at a very minimum of 1 month to 6 months post injury by their own results rather than the 12 days you suggest.

    >Snip<

    Here's the 2006, 8 day post injury "acute" paper.
    http://www.ncbi.nlm.nih.gov/pubmed/16629625

    I don't believe Dr. Davies would say that adding 4 days over this past decade to his acute injury model would now be considered chronic research in rats. I believe the experts would concur.

    As far as injury in humans, for instance, the Proneuron trial which had a center in Colorado accepted patients up to 14 days post and qualified them acutes. http://www.clinicaltrials.gov/ct2/sh...oneuron&rank=1
    Grammy,

    I don't want to get into an argument over semantics (ie, the definitions of "acute: and "chronic"). Yet I think you are painting a very one-sided picture.

    Davies work with rats published since moving to Colorado involved treating the lesions during the same operation as the one where the injury was inflicted. If this doesn't qualify as "acute", I don't know what does.

    The Davies paper from 2006 that you linked said "Infusion of hr-decorin over the first 8 days post-SCI" provided significant improvements. Without reading the full paper, this sounds to me that he began infusion of decorin immediately following the injury and continuing for 8 days. Again, this sounds to me like there is no question that it is acute treatment.

    In his most recent oral presentation (abstract posted by Dr. Young in Post 1285), Dr. Davies began treatment with decorin 12 days post-injury. In the abstract, Dr. Davies referred to this as sub-acute. Clearly it is a significant change in protocol compared with his previously released studies. He once told me that a true chronic trial would begin with treatment 9 months post-injury, which is even longer than your estimate of 1 to 6 months.

    As far as studies with humans are concerned, I have read in several places that injuries within 12 to 24 hours are considered "acute". If there is a trial that is accepting patients up to 14 days and considering them "acute" (rather than "sub-acute"), I would assume that it has to do with the realities of finding patients for their trials.

    I know of no human studies where the patients were injured specifically for the purpose of studying recovery. Instead, the patients come from injured persons. If I recall correctly the leading cause of SCI is from motor vehicle accidents, distantly followed by diving accidents and then even further down gunshot wounds and then other sports-related accidents. Clearly the priority in these cases is to first, save the life of the victims, second to stabilize the other associated wounds.

    When I was injured I was bed-bound for 120 days just waiting for the broken bones to heal (most had healed at 90 days, but they missed some for another month, which required ten more days to recover from an infection before they could even perform the surgery then required). I am fairly confident that if they stuck hard and fast to the traditional definition of acute being within 24 hours that they would be lucky to find one or two patients a year that had no other injuries besides the SCI that they could begin studies within the first 24 hours.

    It only makes sense that they would have to relax their definition of "acute". At 14 days out, I think that calling these patients even "sub-acute" is probably stretching things a bit. But again, I don't want to argue about definitions and semantics.

    I simply want to point out that Dr. Davies was criticized for not using contusion injuries and only doing acute studies. But when he did a study with contusion injuries and waited 12 day longer before applying treatment that his previous studies (not 4 days longer), all he seems to get is still more criticism.

    Then he receives even more criticism for not posting here. And people wonder why? I don't.

  10. #1340
    Quote Originally Posted by Fly_Pelican_Fly View Post
    No offence Charles, but you freely admit to not keeping up with the field yet you devoutly support Davies and his work. He may or may not be onto something - but you cant support someone who is not providing a return on investment ie papers, data and collaboration. Hence why he spends more time outside of his lab looking for funding in places like China, Australia and Europe.
    Yes, I freely admit not keeping up with the latest research by anyone, including Dr. Davies. I have asked several times for links to any research that shows more promise than the papers presented by Dr. Davies but not one poster has give a link.

    I agree that he may or may not be on to something. Personally I believe he is, but I have been wrong before about many things, and will no doubt continue to do so for the rest of my life. Fortunately, the success (or failure) of Dr. Davies has nothing to do with my beliefs.

    Each of us is free to support anyone they choose to, for any reasons they choose, or even to support no one at all. While all of us wish that all of the researchers would be more prolific, I don't think that Dr. Davies is sitting around on his hands hoping that something falls into his lap. I believe that he is working as hard as possible to solve the problems associated with SCI recovery. I believe that his ideas will require funding to complete, and that money from another country that may be easier to get (for whatever reason) is just as good for research as money that is difficult to procure in the US. (However, I am surprised that you seem to know so much about how he divides his fund-raising activities.)

    Best,
    Charlie

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