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Immune Response to DCI

Discussion in 'Ask Dr. Decompression' started by Elizabeth Weintraub, Mar 26, 2001.

  1. In my recent readings of both the "The Last Dive" by Bernie Chowdhury and the March 2001 "Undercurrent" there were references in both to DCI triggering an immune response to bubbling. Mr. Chowdhury referred to research done by a Dr. Bill Hamilton and in the latest Undercurrent the authors made reference to a speech given by a Dr. Bill Bateman on the same subject. The brief references described the triggering of nitrogen-specific and helium-specific antigens, the activation of complement, and the effect on platelets. Are there any specific journal articles or other sites you could direct me to for further information? I'm fascinated by the whole idea.
     
  2. Dr Deco

    Dr Deco Medical Moderator Staff Member

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    Dear Group:

    We have lost the original postings on this topic and time does not permit a rewrite. I can duplicate a small part. (Unfortunately, I saved only a small part of the responses.)

    The two models for DCS today are the Biochemical and the Biophysical Models (as I term them). The Biochemical Model purports to show that DCS pain is the result of biochemical changes in the body that are triggered by a gas bubble. After the triggering, the role of the bubble is inconsequential. What this model does not explain is how pressure can reverse the pain response – even only a little pressure. Since molecules are not influenced by small changes in pressure, I do not see how this cam be the correct pathophysiology. Naturally, after a few hours have passed, many biochemical changes can occur in tissues and, indeed, the DCS becomes refractory to pressure increases.

    The Biophysical model states that
    • micronuclei are present in tissue and are generated by hydrodynamic cavitation;
    • Bubbles are spread in a certain size-number distribution (there are many small ones, some medium sized, and a few large ones (radius = 0.1 to 3 microns);
    • Only bubbles above a certain radius (Laplace cut off) can grow during supersaturations (this is because of surface tension);
      {*} Increase in volume of gas phase leads to nerve pain and capillary occlusion (i.e., a compartment syndrome)
    There does not exist any specificity of the immune system for dissolved gas. Whatever reactions occur, these are directed at the gas phase. Some have even claimed specificity. I once heard a presentation by Dr. Ward at an Undersea and Hyperbaric Medical Society meeting in which he found a difference in complement activation between bubbles of helium versus bubbles on nitrogen. I asked him then if that implied that had indeed found a chemical test, at room temperature, for an inert gas. He indicated that he thought so - - - I expressed doubt.

    Dr. Turner correctly indicated earlier [posting was lost], the amount of research that has gone into DCS over the past several decades is minuscule in terms of dollar amount when compared to other fields. This was not always so, and in the 1970’s, many diving companies had industrial laboratories. I started at the Ocean Systems, Inc., laboratory in 1969. In 1982, the Office of Naval Research ended its program of hyperbaric research and that was the death knell of the field in the United States. There is little research (none actually) by commercial manufacturers of recreational scuba equipment in decompression with the exception of the DSAT Recreational Dive Planner. As is true with most things, it is the dollar value. Medical research will be near the top (along with military) and recreational will be at the bottom. This is not an indictment, simply an observation. When deep-water oil recovery by divers was important, more money went into this field.

    The material from NASA research that is passed to the recreational community exists only because I chose to do it. There does not exist a NASA program to do this (although NASA is happy to disseminate information in outreach situations).

    Research funding is possibly available through NASA and the new program for the Office Of naval research. The ONR had a very vigorous program in barophysiology until 1982. It was one of the best research agencies with which I ever had contact. (If only NASA was ¼ as good!). :confused:
    ______________
    Dr. Deco
     
  3. scubadoc

    scubadoc Medical Moderator

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    Research Opportunity with the US Navy

    The Office of Naval Research wishes to make you aware of our recent broad agency announcement (BAA) on diving-related issues, see item "I" in the announcement. The hyperlink to the BAA is provided below.
    http://www.onr.navy.mil/02/baa/baa01010.htm

    We are looking for the highest quality of research on issues relating to diving medicine. This does not preclude researchers from outside the U.S..

    CDR Stephen T. Ahlers, MSC, USN
    Program Officer
    Undersea Medicine & Combat Casualty Care
    Advanced Development Programs
    Medical Science and Technology Division (Code 341)
    Office of Naval Research
    800 N. Quincy
    Arlington, VA 22217-5660
    Voice: (703) 696-0367/ DSN: 426-0367
    Fax: (703) 696-1212/8384 / DSN: 426-1212/8384
    E-mail: ahlerss@onr.navy.mil
    WebSite: http://www.onr.navy.mil/sci_tech/personnel
     
  4. turnerjd

    turnerjd Divemaster

    # of Dives: I'm a Fish!
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    For those of you that don't know (I can't remember if I ever said) I reached the dizzy heights (or doubious station) in life as a vaccine / immunology bod via a degree in chemistry, and then a PhD in Pharmacy (vaccine delivery mechanisms) so........

    As a chemist -- This test for a noble gas is bollocks!
    Simple chemistry should immediately tell us that helium, which has a full, complete, and nice and happy set of molecular orbitals has never been made to react with ANYTHING at any temperature anywhere near RT.

    Similarly, N2, which although is not a noble gas, is a very nice and inert gas. There are very few (if any) reactions of gaseous nitrogen. Without a textbook here to look things up in, I don't know of any, and I suspect that gaseous N2 is about as inert as helium.

    If he has a simple chemical test for these two, then it isn't just time for a paper or two in nature, this is nobel prize type work (certainly one in chemistry, and probably a second for physics) as it is overturning the vast majority of theoretical chemistry research for the last 100 years or so (plus invalidating the whole of quantum mechanics, all chemical bonding theory etc.....)

    As an immunologist............ someone posted a link to an article about DCS and the immune system, (I printed it and didn't keep the link). My opinion was that this article was pretty much wishfull thinking with minimum scientific evidence to support it.

    The article described most of the key areas of the immune system, and tried to apply them to DCS. Unfortunately, the authors also failed to put everything into perspective as to where everything fitted into the grand scale of things. certain mechanisms they quoted, for example protein denaturation, don't just occur in DCS, but occur all the time, and there are specific (and highly successfull) mechanisms for dealing with them.

    They also considered the raising of antibodies to N2, and other disolved (and bubbles of) gasses (the humoral response). Unfortunately (as Dr Deco points out) disolved gasses can't induce an immune response. They fail to mention in the article processes such as antigen presentation which are necessary to induce a humoral response. Basically antigen presentation only works for proteins, although there are other (not humoral, but innate) mechanisms that can induce an immune response. But, if you think that even at ambient pressure we are saturated with dissolved N2 (don't forget saturation level is dependent upon the partial pressure of the gas we breath). As this is the case, if it was possible to raise antibodies to N2 we would have been doing so ever since birth, and would have some pretty nasty reactions every time we breath. Something that is evolutionarily negative!

    What I concluded from the article was that bubbles caused minor MECHANICAL damage, and the body mounted a NORMAL immune response to minor damage - in essense the same reaction as to a minor insult such as a cut.

    I wasn't impressed by the article, neither am I impressed by the idea that someone can readily distinguish between bubbles of different inert gasses, unless they have spent a lot of money attaching their experiment to something like a MALDI-TOF-MS. In the past identifying inert gasses has been the work of nobel prizes, and it is still not the easiest of things to do.

    .02 as always

    Jon T
     
  5. Dr Deco

    Dr Deco Medical Moderator Staff Member

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    Dear Readers:

    Curiously, we are seeing in the "Immune Response Theory" a real example of science in the “front line trenches.” The “classical” world of barophysiology is more prone to “biochemical novelty” than “biophysical novelty.” While more than thirty years has passed since the introduction of this idea(s), nothing of substance, either in diagnosis, prevention, or treatment, nothing of substance has come of it.

    In the area of the “biophysical model,” we have ideas of nuclei reduction (in seated and inactive individuals - - such as astronauts in zero gravity) and thus DCS reduction. We also have ideas of elimination of musculoskeletal straining maneuvers after diving (as mentioned many times in this FORUM) to mitigate bubble formation and DCS. This is modeled in part on NASA studies in altitude chambers.

    It would be unfair to say that this "bubble model" has been neglected by the scientific community, because it has not gone unnoted. There are references to nuclei reduction in legs in DAN literature because divers are in water (though not necessarily in these words). Nonetheless, we do see considerable effort devoted to less than productive avenues with the "blood-bubble" interaction concepts. (I review proposals from time to time and know that there is currently considerable rubbish in the scientific world of barophysiology.) Considerable material is in the Bennett and Elliott books devoted to the pathophysiology of DCS based on "blood-bubble interactions." Much if this is, in my opinion, a pious fantasy. (This is pretty stong stuff for mild-manner Dr. Deco. Perhaps I am having a bad day.)

    Once again, blood-bubble interactions for short tern DCS is a second order effect. However, for problems of several hours duration, these effects begin to play a role. Thus the admonition, seek held early with DCS to avoid turning a reversible problem into a refractory one.
    _________________
    Dr. Deco
     
  6. danreind

    danreind Guest

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    Hi Dr. Deco

    >>. I once heard a presentation by Dr. Ward at an Undersea and Hyperbaric Medical Society meeting in which he found a difference in complement activation between bubbles of helium versus bubbles on nitrogen.<<

    I was just curious how he arrived at that conclusion. Clearly the nature of the gas phase itself is irrelevant. But I could conceive of different patterns of bubble formation for nitrogen vs. helium affecting the overall systemic response. Nitrogen might make lots of bubbles in the fatty tissues, while helium might favor the aqueous with an immune response specific to these tissues? I don't know, but unless he controlled for these effects I could see how he could be misled. Even injected bubbles would behave differently (due to counterdiffusive bubble growth effects etc).

    I think a big part of the fixation on biochemical effects is the great need for an assay of DCI stress. It would be wonderful if animals came with little markers which showed how bent they were with a simple blood test. Too bad they don't.

    Cheers,

    Dan Reinders
     
  7. Dr Deco

    Dr Deco Medical Moderator Staff Member

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    Dan:

    Your question is a good one. Surprisingly, the complement inactivation test was an in vitro one. Gas, nitrogen or helium, was bubbled through serum. Possibly, there was a difference in the setup of the equipment such that the driving pressure of the gas was different. This could result in a different number of bubbles being formed, or perhaps pressure differences resulted in a different in radius and therefore surface area. What ever it was, it certainly could not be a chemical difference. Yet, that was claimed.

    Certainly, in the area of bubbles and DCS, biochemical markers have been one of the “holy grails” for at least three of decades. At NASA, I have sought with my colleagues (mostly it was their work) to develop a bubble-monitoring test. I term this “the chemical Doppler.” Such has not yet been found, although I believe that some form of blood-bubble interaction in the initial stages of depressurization should be present.

    Mike Powell
     
  8. BillP

    BillP Senior Member

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    Thanks to turnerjd, Dr. Deco, and scubadoc for trying to recreate their responses in this excellent discussion. The Immersed article that rcohn linked prior to the board crash can be found at http://www.immersed.com/Articles/hit.pdf .

    When the Immersed article compares the immune system sending out "soldier" antibodies against bacteria to the immune response in DCS, it does seem to be implying that the immune response in DCS also involves an antibody reaction to the bubble "invaders". On the sixth page of the article, an illustration demonstrates an antibody response and the caption suggests the possibility of a vaccination for DCS, again seeming to imply that DCS involves an antibody- bubble/antigen reaction.

    I believe that the "soldier/ invader" comparison was just an inaccurate (and somewhat unfortunate and misleading) simile, and the caption to the humoral response illustration was put in by an editor rather than the author of the article, but I've asked Dr. Bill Hamilton to comment. Hopefully he'll contact me, or better yet join us here.

    Bill
     

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