Document 7v2VM45m9eq1rQDxKNbpw4aj

FILE NAME: Saranac 7th Symposium (SSY) DATE: 1952 DOC#: SSY027 DOCUMENT DESCRIPTION: Transcript of Presentation by Dr. Gregoire turn rwH Piax 525. WT PS. mOiSMt tb s MXt ipwdcer** a r te r ia l eerer# m - anch o f the ara, I i t weald be b ettor to d efer the d iecaeeioo on the to e paper* taxt i l v# can here the two paper# togeth er, #o 1*11 * aak Doctor G refoire to present hio paper on the pulmonary function studies in men exposed for ten or more years to the inhalation of asbestos fibers* | BY DOCTOR GRSGOIRBt ! (Doctor Gregoire read a prepared paper which was I to hare been filed with the Saranac Laboratory. Transcript I 0f his remarks is available In the event a formal paper was not file d )* | BY DOCTOR McCAHNt . There may be considerable discussion of these two papers, but I suggest that we take about a four or five minute recess for a stretch before we dlseuss them* (Recess from 12*30 to 1 2 *14-0 P* M*)* BY DOCTOR VOHVALDt My we all take our seats? I! BY DOCTOR McCJLiTKt W ill the meeting please come to order? Will you please come to order? W ill all those who have not gotten their banquet tickets please do so before twelve o'look* | before twelve. The two papers which I have just heard | by Doctor Wright and by Doctor Gregoire are now open for j discussion. ; b y DOCTOR HUGE-JONES* i i would like to make two comments really. The first is about Doctor Wright's paper with which I was ei- j tremoly interested, and he put forward a suggested definition, 52Z* shall we say, or a way of measuring a man's capacity fon* overall work. There was one question I would like to aek him about that, and that is this, that many people, I think Im wight in saying, Taylor and Briggs originally did that which they called the crest load, the maximum work that people can do in a staady state. Other people have done the maximum ability to work as measured by the oxygen eonsumption which Doctor Wright has used. Now, there is always one thing that worries ae slightly shout that, and that Is this, that although you and I , for instance, might have very different powers to do our maximum, does that necessarily limit us at tha ordinary work we're going to do in every day performance. In faot, the question is this, that does Doctor Wright have evidence to show that the performance at sub-maximal loada ie necessarily worse in people who show a falling off of their maximum ability? It doesn' t always seem to me to necessarily follow. For example, I might have a reduced maximum ven tilation or maximum ventilatory power of my lungs and, there fore, not t : able to run, shall we say, a half a mile as fast as I could before. On the other hand, I might be able to walk at a slow rate for a long time perfectly well if my j own thinking on that subject, and I would like his comments: on that. S2Sa The other thing I want, and I hop* people will axcuse mo because Im not a statistician, I*m a male physiol ogist, and I have a certain amount of fears, and worries about statistics, I think you know about the same kind of known estimations that are given that if all the blood oapillaries were put end to end, tney would stretch around frha world. Somebody once said if all the statist!elans wers put end to end, that would be a good thing. With those remarks, i f I may make two technical criticisms on the statistics, and I hope you'll forgive me. The first is on the use of thie correlation co-efficient. Doctor Wright was surprised at the extremely high co-*ffici?nt he got between the maximum breathing capacity combined with the ventilation equivalent for oxygen, and the msTimim power to work, I believe that ia an example of what technically called a spurious correlation. He has got the e a m thing coming into the top and bottom of the frac tion, namely, the ventilation in maximum breathing capacity in one case and in ventilation equivalent on the other, and I believe in his examples of comparing correlations, he should have bean using p a r tia l co rrelatio n s throughout that i f you are comparing the overall correlation, what you're observing is the amount one test relates to some j other test, and the degree of that ia a set thing if you're! lust comoaring one set of testa. I f you're comparing I 529. another test to the first thing, in this case oxygen capac ity for work, the reason why that correlates so highly may be due because it*s partially correlated with your orig inal teat and I don*t think you can put out or compare things on that basis tinless you take a count of the par tial correlations and particularly of the spurious corre lations which may arise from fractions# That is one technical point. There are two other* One is that it does seem to me that i f people, and I would like to ask Doctor Gregoire this question, when he says tha1 these tests are significantly different, what he precisely means# If he uses twice the standard error of the differ ence which I think he did, that assumes a normal distribu tio n curre and in a lot of these things which he was com paring, he is using a fraction tdiich I know and can demon strata is not normally distributed# I would like to ask him what he takes as a level o r statistical significance when the thing is on askewed I distribution, and then lastly, which I think is an important . point, and I put i t up in a ll humility because H a not sure ... m^t^i****** j the real answer to it , and that is this, that is a great i fashion in physiology to which many people have been addict-' j ed, and that is to express things in a percentage of the predicted normal. i ' Sow, it does seem to me that what Doctor Wright ! ; and Doctor Gregoire did in two of their slides was a much mors valuable way of doing things, and that is they showed the regression line with these tests scattering about it , and I think instead of saying that somebody at that point is a hundred percent of a predicted normal, you should say he lies within plus or minus a certain scatter of what would be expected at that age. In fact, you should sub tract the average fall with age and not express it as a percentage. To express i t as a percentage assumes, for one thing, a linear regression. It assumes the thing goes about the mean which i t doesn't in any case, and lastly, in the extremes, it is entirely incorrect and it*e a thing in physiology, I think we ought to fight very seriously* that i f ws are going to use statistics, I think we ought to eonmult expert statisticians on those things, and I do make those comments in all humil ity beeausa I do think a lot of the physiological conclusions oan be erroneous. I was extremely interested in Doctor Gregolro's conclusions, his last ones, about the d i f ferences between asbestosis and silicosis, and I have no doubt in my own Blind that all ho eaid was extremely correct statistically from that point of view, and I think i t was a fascinating and a very valuable and able study though I would like to ! ask him whether he did take cognizance of the various other | individual tests as far as their significance level was ! $31 concerned. BY DOCTOR MoCAffHt V s 'r e going to finish by your scheduled time, it w ill be necessary to limit this discussion and I ' l l aak Doctor Wright if he cares to answer Dootor Hugh-Jones* BY DOCTOR WRIGHT t Doctor Jones, I'm afraid you read more into my paper than I wanted to be in i t . You have gone beyond now and are applying the peak oxygon uptake to a man's ability to shovel coal, and I have refrained from doing that delib erately, because this is what we measured, and that's all I want to talk about, what enters into a man's ability to perform every day his most coinplaxjmotivatlon alone, how many children he srast fee* at home is extremely important, vhy people became fatigued on their Job is a most oaaplex question. Why doas the housewife who really, in many instances, has little physical labor to do, with our wash ing machines and so on, became dead tired at the end of the dayT I wouldn't for a moment say, and I refrain deliber ately from saying that peak oxygen uptake will tell you whether or not the man is able to carry out a full day's work, I can show you, I 'm sure you have many examples, o f men that stay on the p a y r o ll. They break Just as much tonnage underground as the next man who may have double his i!2. peak oxygen uptake* Vhat I do believe the peak oxygen uptake gives jox some information on is what his human engine is able to do in this preoise pieoe of work* Kow, there are two extremes that this soft of falls in the middle of. There is the sudden burst o f ener gy which a may be called upon to do in running from a burning building, whioh a severe eardiac might be able to do* That*a accomplished anaphobia. Then there is the other kind that you are referring to, the sub-maximal work that is carried out over a long period of time and that nay not bear a relationship to the peak oxygen uptake* kM a matter of fact, it was the failure of its ' bearing relationship that le d us to do this study origin ally, because we had observed Just in & practical way, that sn were - with a low rna-riwnrm breathing capacity who had arterial saturation, who had a high residual of air, were nevertheless able to do a full day underground, doing a job that was certainly a sub-maximal Job, so I agree with you fully* I'm glad you brought the point up that one can not transfer this sort of data in any exact manner to the ques tion of whether or not an individual is able to do a day's work at sub-maximal labor* I do believe, however, that it ie a tool that letn the clinician find out how well he is able to estimate the 533* depar ture from normal* How, our statistical problem would take a consid erable (mount of time* I recognize the things you are talking about and would like to have more opportunity to converse with you in that regard* We were worried about whether or not we had the same background, two aides of the correlation, a thing that I believes was a serious c r iti cism of Doctor Motley s data. It*a true that oxygen, oxygen uptake, is a faotor that appears, and ventilation appears, but they are dom under different circuitstanoes and I do not believe they ari the same* I t would be scenething like saying that a sum who has one dollar is a millionaire because he possesses a dollar* Oxygen uptake, during work, when i t 's related to ventilation equivalent, la simply the amount of oxygen bo Inf us^d in relation to the amount of air being breathed at the tine* It *t totally different from maximum breathing capac ity and it*a totally different from peak oxygen uptake and I think we're on fairly safe grounds from that point of view* You raise the question of asksved distribution. It *s true that one of these correlations definitely is a curvo-linear distribution and that *s the maximum breathing capacity against maximum oxygen uptake. The curve is in th 534* process of being fitted at the present time in an effort to see whether it would give us a better correlation than the formula we did use, which was a straight line formula, I would like to eay one thing that Doctor Gregoire perhaps wont be able to touch on, and that is when we say a thing is a certain percent of the predicted, we are taking into consideration the two standard deviations froa normal. These are most o f the time corrected curves for agr or some other factor and the standard deviation of the nor mal predicted value has been calculated as, for exanple, with wpTtwniM breathing capacity in which we say there is such a figure as one hundred percent or a normal figure, the scatter around that regression line gives you a etandart. deviation i f you wish to calculate it# The scatter, for example, around the maximum breathing capacity, is such that ties th e standard devia tion of the p r e d ic te d value requires you to c o n s id e r all p e o p le over B i x t y - s i x percent as being w it h in th e normal range. How, the matter of partial correlation is much to o involved for us to discuss here. We can do that afterwards,, BY DOCTOR yeCAKNi Do you wish to make further comment, Doctor Gregoiret EY DOCTOR GRSGOIREl I think he has cohered i t . j BY DOCTOR McCINH I I If not, I will proceed then to discuss the subject which was assigned to me, which concerned the cardio-cir cu- latory aspects of Pneumoconiosis* I migit say at the outset in answer to a remark of Doctor W eight's, that I do not thinlc the clinician should omit functional and physiological studies* The function of the clinician is to put the whole mess of things together* ! He's an integrator* He must take all aspects of the man concerned, into account, if i t 's going to make any sense* (Doctor McCann's paper, from this point, was prepared, and a copy has been filed with the Saranac Laboratory* BY DOCTOR McCAKSt In the printed record of these proceedings, I should like the names of Doctor Love joy, Hillfrank and othn: -m as co-authors of the paper which I have read* I'm afraid I haven't been too clear. I certainly have used up so much time, I ' l l certainly leave very little for discussion* Doctor Waring w ill open the discussion* BY DOCTOR WAR UNO t Doctor McCann and Members of the Symposium, Doctor 1 McCann has, as always, presented factual matter as well as i i philosophical comments w ith such a happy faci: Ity that I C envy him. I 'm reminded of the story which I hope our B r i t . : iI.: ish friends here w ill no W i n d incorrect, about Sir Joseph -h-- 11 CURRENT RESEARCHES IN ANESTHESIA & ANALGESIA Official Organ of the International Anesthesia Research Society Laukette M cM echan, A ss*t . E dtto*, Executive Seckitaky 318 H otel W estlake, R ocky Rtvtm, C leveland 16, O hio fir. Jb m i , V uim QoivaEvitgr o f Celasrado C e p irtsc a t o f KsdleLs* 4200 Ew t 9th 8t, Beavar 7 , C olo. nbnm rj 3* 29$) Door S r. lu la g s - Wt *jr* l*ppjr to fit* jros pennedob to tte tna 111nstratlon* f>0B Qr*. VM.tdMd sad Bnpor'a pttpar, saly anbar* 1 4 4, Am oil mnrtolurnnnt to soarcs f th orlcLnel pvbliottis*. I I TAKES FBCM PAGE 535. BT DOCTOR AKH6i Doctor MoCann and Mavhsrs of tbo (tyapoeiaa, Doctor MeCjm has, as d u g n , prseantad factoal natter as vail as philosophies! eosascsts with such a happy facility that Z wry hia. Z*a rescinded of ths story which I hops our British friends bars vill not find incorrect, abotrt 81r Joseph -- L----------------------------------------- 536, Lister, who was invited to attend a graduating exercise of one of the great universities in the British Dies, and he gave a magnificent address and at the end of his address, ^h,ri was some demand from the audience that the resident professor of medicine should get up and make a few remarks. Being a modest gentleman, he was reluctant to do it , but demand increased and finally he stood up and he said, Ladies and gentlemen, when the English nightingale sings, all other birds should be s t i l l " . How when this Rochester night ingale, who is both physician and physiologist, sings. I the Rocky Mountain magpie, perhaps, ought to shut j up* How, he has emphasized many Important things, and I can only touch on them In Just a few moments. He Indiets heavily emphysema and the physiological changes that accom pany emphysema and I agree with all that. He sings In praise of oarbon dioxide and I think very wisely, and also very cautiously so. He emphasises that In past times, i have emphasised too much heart Tallure and too little lung 1 failure, and one surely w ill have to agree with him on that,, i ! How, at the University of Colorado, we have had competent physiologists and bronchologista and sinco Doctor ! McCann was kind enough to send me a copy of his address to , ji try and digest at the higher and more rarified altitude of j the Rocky Mountain r egions, this denser atmosphere within j I * 537. ! and without, why I am grateful to him for letting me have that and I wanted to tell you perhaps something about the formal ph&rmical dynamics of carbondioxide as it has been studied by Doctor Whitehead and Doctor Draper, Doctor Goldenson and other men in the Departments of Physiology and pharmacology at the University of Colorado School of Medi cine. So, may I have that first slide, please? How, in 1908, Volhard talked about what he called 'oxygen pumpers' and the experiments which I w ill tell you about here will demonstrate something of this* How, I f you will look at the slide, you will see that we have the ambient atmosphere outside; we have an airway depicted and we have the r^splrstary alveolae, and moving from le ft to right, we have tho pulmonary circulatioE in the capillary bed* How, i f , as was done by my colleagues, if an an- 4Wli flrsL de-nitrogonated, that is if be is permitted to breathe one hundred per cent oxygen Tor forty-five min utes ur.til the nitrogen is pretty thoroughly vahhed out of his system, especially his repiratory airways and if then he is given pentothal of sodium Intravenously until his respiration ceases entirely and if he is now continued in a one hundred percent atmosphere or as the circulation proceeds through his capillary bed, oxygen is picked uo out! 5 3 Si of the alveolar spaces and carried away and carbon iloxlda comas into the alveolae* Hie respiration has ceased en tirely under the influence o f pentothal of sodium, but b e cause the uptake of oxygen volume exceeds the indigenous C(>2 in the alveolar apace, why a valent oi pressure is cre ated from the space to the alveolae and the oxygen which is alone in this animal's ambient atmostphere, the atmosphere then flows from his glottis down through his trachea and into his alveolae, is picked up and carried away, and the dog, without any artificial breathing whatsoever, and Doctor Whitehead calls this the fusion restoration rather than oxygen pumper as Vorhard described i t , the animal will live without any form of a rtificial respiration Just by virtue of this hemoglobin oxygen pump* The oxygen is taken away with sufficient rapidity in the alveolae to aet up a currant, to set up a radium of pressure from the atmosphere down into the lungs, and the animal will continue to survive for forty-five minutes* Now, he will die after that time i f the experiment is continued for the reason that the carhon dioxide elimin ation gradually blankets the alveolar capillary membrane ao that t>TM oxygen is no longer able to move into the - into ttye arterial and capillary into the blood* Now, the animal would die i f he was immediately taken out from this and put in a ir , because then there would 53#. l be a great inflow of nitrogen and the nitrogen would serve in the same blar.iceting way and he would die very quickly* How, i f , after say, say after twenty minutes the carbon dioxide has begun, has been steadily increasing, no longer is pentothal of sodium needed after twenty - between twenty and thirty minutes, because the carbon dioxide ac cumulation, as Doctor McCann referred to, is sufficient at this tine and has an oxidising influence upon respiration and for the last, say fifteen minutes or longer of the ex periment, the animal is not breathing, but ho does not re quire any longer pentothal of sodium to keep him in this state* Hext slide, please. How, this slide shows you here up above the blood pressure and the picket fenoe here Is the spirometer reading and the movements on the le ft hero show the respirations up and down and then the pentothal sodium is given In sufficient quantity to stop his breath ing entirely and that's where you see, over on the le ft , tho point where the up and down respiratory movements quit* i Each one of the large moving down of the lines | simply indicates the point at which the spirometer bell is | filled again* The moving down simply means the point where, i the spirometer bell is filled in with oxygenjover here are 1 the respiratory movements, and these figures here do not [ refer to minutes. These are the minutes down here, bu.. W imuii1 2 these refer to certain event* in what's happening here# How, you can see, although respiration has quit hero, oxygen is continued to be taken up by this oxygen hemoglobin from the b e ll. The bell is fille d again, oxygen continues to be taken up, the bell is f il l e d again, oxygen continues to be taken up, and so on# At this point up in here, you w ill notice that he had a little fall in blood pressure and then a little rise and then here, this is a run of X-ray cystolic contractions which Doctor Whitehead showed very nicely with - were due not to fall in blood pressure and not to fa ll in carbon dioxide, but to too much pentothal, and then you notice that they disappear and the blood pros sure falls slowly oxer here and after some sixty minutes over here, why with complete lack of circulation, there is complete stoppage of uptake of oxygen from the bell# Hext slide. How, he showed wary nicely in this slide here, time n minutes in here and oxygen saturation of the hemoglobin is here and here is the arterial satura tion and the veinous saturation, the control period. This IB during tHe period of abnema, of - during diffusion and this is after the period of abnema. You notice the period of arterial saturation maintains remarkably well for thirty minutes here as hypoxia develops. You notice -he , v e in o u s saturation d o e s th e same th in g and then v e ry rapidly at the torminatlon of the experiment which la simply ter minated by giving artificial respiration with oxygen. Hext slide. Now, this slide shows time In min utes down here,- control period here, the abnea appeared * here, the after abnea aperiod here, and the COg in control percent here. You w ill notice that the arterial PE during the accumulation of carbon dioxide, and arterial PH fa lls, the veinous PH falls and the arterial and veinous COg both rise quite remarkably. The PH falls down in the neighbor hood, in the average around to 6 .6 9 . The next slide, please. Now, here an interesting thing was done. This is similar to the other slide I shower you. There was a little rise in blood pressure here at the beginning of the experiment and a little f a l l . This is the respiratory movements here. This is where the abnea appear , or that period begins, but the oxygen uptake continues. The spirometer bell was fille d again and the oxygen uptake gains again. Now, at this point right here, the bell was held so that the bell could not fa ll and monomaters were placed j so as to record the negative pressure that would be created under these conditione, and you can see that this pressure fell quite remarkably here and amounted to about fourteen centimeters of water. In other words, the oxygen uptake by the alveolar capillary system, under these conditions. and you can se th a t t h is p re ssu r e f e l l q u ite rem arkably here and amounted to about fourteen centime tern of water. In other worda, the oxygen uptake by the alveolar capillary system, under these conditions, was sufficient to create a negative pressure In the - or in the airway amounting to umpteen centimeters of water. Hext slide. Now, they subjected same animals to carbon dioxide inhalation, and Doctor McCann referred to this work of Doctor Stott, and there is one in our clinic out there, that work of Doctor Stott, and that was he em phasised the importance that should be attributed or the significance attributed to the fact that the emphysematous patient has a remarkable tolerance to C02# He lives in an atmosphere of low oxygen and a high atmosphere of C0 Pow, i f you give this emphysematous patient car** bon dioxide to breathe, he establishes it remarkably well ^ ^ 1 1 a point where he oomea to a critical lev el. Perhaps Doctor Stott reported that when the C<>2 given to breathe wa^ around about 9.28 percent, the emphysematous patient was remarkably comfortable, but when he was given carbon diox ide to breathe as high as 11.28 percent, he was very ex tremely uncomfortable. How, on other thing in relation to that, and that was this, both in these animals and in the human beings who were subjected to ventilation with high percentages of curb m A li. dioxide, Doctor Whitehead found that a small dose ofpentothal, while the COg was being breathed at high ooncontratd oi, could show amazingly the discomfort of this high C02 Venti lation, A perfectly normal person breathes a high C02 con centration, why he becomes very quickly very uncomfortable and this discomfort is very easily controlled by the very small dose of pentothal sodium. Doctor Whitehead found, in addition, that during the high concentration of C0, there was more barbiturate apparently taken up in the central nervous system than when there was low C02 and that suggests the clinical danger per* haps of a patient who has been given, for surgical purposes, a barbiturate and then that patient comes back to the ward and beoomes anoxic because of an obstructed airway, and now, very quiokly, he has a combination of high C02 nd esthetic effect, and a high barbiturate can drive or can be driven into his centre! nervous system to add to his d i f f i culties Kow, ona other thing in relation to this, tha1 is this, that when a patient breathes oxygen, a higher per centage of oxygen, I should have mentioned this earlier in one of the slides, when this patient breathes a high per centage of oxygen and he gets an obstruction of the airway, why there is no nitrogen, there is only a very small amount of C02 there early, and he can get very quickly a couplete collapsible lung or a collapse of a lobe or a segment of his lung, simply because the residual oxygen is only there and that is very quickly absorbed under these conditions* Now, here you see the effect on a human being of breathing nearly ten percent CO2 * twenty percent, thirty and forty percent COg and the remarkab? * effect on the PH breathing these different percentages of Next slide. Now, experimental slide of treating psychotic patients with C02 and with this type of experiment* In other words, it was thought that maybe that inhalation oi higher C02 and the dropping down In PH might hare an impor tant Influence upon the underlying abnormalities within the central nervous system that made a patient schisophrenic or at least so abnormal that he couldn' t get along with the rest of us, and so they tried this on a number of patients and found that within a small number, that they were appar ently helped by breaking thia high percentage of CO2 with a change in their PH. j Now, they found also one other thing that was very interesting and that was that practically Inxaediately the abnea ensues, the kidneys stop aerating urine and when the J experiment was terminated and the respiration starts again,! the kidneys immediately start secreting urine again, and they determined t h a t t h i s was a reflex by denervating one kidney; vamii wmw* ___________________________ ______________________ 5US*- leaving the other kidney without any anesthetic around 4-t, and thaj found there that the normal kidnay not danarrated by local anesthetic continued or stopped secreting iranediately that the abnea was started. The other kidney that was denervated, why, continued to secrete urine, but at a lower rate than normal, and after the experiment was termin'1 sted, and a period of abnea was over here, why, the densrvated kidney rapidly returned to a higher rate of seeretlon of urine and the one that was not denervated, tdiy, resumed also its normal rate of secretion. How, I hare reported this bedause I thought that these slight have mono-dynamic influence or effects of csrbon dioxide might bear an important relation to what Doctor MoCann has been telling you, (Applause), BY DOCTOR VORWALD: May I be your patience just for a few moments* It is twelve o ` clock and there is only one announcement, if you remember, the photograph which was taken yesterday. There w ill be a young lady in the foyer of the building for most of you who wish to have one, I am sure she w ill satisfy your needs, and so with that, lot us be off to lu n d u | (Seseion adjourned at 12:00 noon) t !t' ' --o0o~ *