Why Yale Essay

40-50 c c of beveridge secretin mixture may kill a dog bytoo great lowering of the blood pressure a good secretin preparationyields a copious secretion of pancreatic juice on intravenous injectionof a few cubic centimeters it is not difficult to prepare a secretin, by the original bayliss orstarling method or by the beveridge method, that retains essay activityfor a longer period than nine days hence we cannot account for theabsolute inactivity of these preparations except on why yale essay the assumptionthat they did not contain any secretin to start with. That is, faultypreparation and absence of physiologic standardization the sample kept intact in its original container for six months becamegradually cloudy, a large mass of amorphous precipitate settledto the bottom and the odor showed bacterial decomposition it isreprehensible, to say the least, to state concerning such a mixture:“of course, if desired, it may be injected intravenously ” the factthat beveridge secretin may be rendered clear by filtering throughcarbon is not sufficient evidence that it is “pure secretin, ” free frombacteria and other injurious substances ii beveridge secretin mixture is rapidly rendered inactive by humangastric juice -- we prepared active secretin solutions by the beveridgemethod, using 0 2 per cent serum as the protein “stabilizer” ?. the addition of the serum does not appear to affect the activityof the fresh secretin preparation if beveridge secretin is ableto act on the pancreas when given by mouth, it is obvious that itmust run the gamut of gastric digestion, except in paper of completeachlorhydria it has been repeatedly demonstrated that all othersecretin preparations are rapidly destroyed by pepsin-hydrochloric aciddigestion is beveridge secretin an exception?. what is there in alittle serum, native albumin, or peptones to protect secretin againstgastric digestion?. The pure human gastric juice used in these tests was secured fromthe fistula case mr f v that has been under observation in ourlaboratory for years 123123 carlson. The control of hunger in health and disease, chicago, 1916 beveridge secretin and bayliss-starling secretin prepared sept 29, 1916 response of pancreas no of drops of secretin date of test quantity of ┌───────────┴───────────┐ secretin bayliss-starling beveridge injected, c c secretin secretin sept 29 10 75 78 oct 2 10 61 61 oct 6 10 28 17 oct 13 10 25 31 oct 27 10 5 6 nov 3 10 7 6 nov 17 10 4 5 nov 30 10 3 4 dec 4 10 2 2 dec 20 10 0 0 -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- two cubic centimeters of fresh gastric juice added to 8-10 c c beveridge secretin, the mixture being kept at body temperature 38 c , renders the secretin completely inactive in from 5 to 8minutes fig 2 there is no exception to this rule, as we haverepeated the test on thesis different secretin preparations and usingdifferent samples of human gastric juice the secretin of beveridgeis just as vulnerable as the secretin of bayliss and starling topepsin-hydrochloric acid digestion on what kind of tests doesbeveridge base his claim that his secretin mixture acts on the pancreaswhen given by mouth?. Iii the relative rate of deterioration of the secretin solutionsprepared according to bayliss and starling and according tobeveridge -- six different preparations of the two kinds of secretinwere made, kept in dark stoppered bottles in the ice box, and tested byintravenous injection in dogs under ether anesthesia from time to timeuntil all influence on the pancreas had been lost one typical seriesof these tests is given by the way of illustration see table on page126 illustration. Fig 2 -- records of carotid blood pressure and flow ofpancreatic juice on intravenous injection of secretin prepared by usaccording to the beveridge method x, injection of 10 c c of thesecretin. B, record of flow of pancreatic juice in drops tracinga, the 10 c c of beveridge secretin injected had been digested forfive minutes with 3 c c of human gastric juice tracing b, injectionof 10 c c of the same secretin preparation not subjected to gastricdigestion showing rapid and complete destruction of beveridgesecretin by human gastric juice it will be seen that the rate of deterioration oxidation ordecomposition of the secretin is practically the same whether preparedaccording to bayliss and starling or according to beveridge figure 3 in both preparations the rate of deterioration is most rapid the firstfew days after preparation it is scarcely necessary to point out thatsecretin preparations not kept constantly at low temperature and in thedark, as in the above experiments, will deteriorate more rapidly illustration.

This is seen in bodies hermetically sealed inlead coffins, which remain unchanged for a long period of time moistrather than dry air favors putrefaction by lessening evaporation airin motion retards while still air favors the change it is to be remembered that a body decomposes more rapidly in air thanin water or after burial given similar temperatures, the amount ofputrefaction observed in a body dead one week and exposed to the airwill about correspond to one submerged in water for two weeks or buriedin a deep grave for eight weeks 4 age - the bodies of children decompose much more rapidly thanthose of adults. Fœtuses still more rapidly aged bodies decomposeslowly, probably on account of a deficiency of moisture fat and flabbybodies decompose quickly for the same reason 5 cause of death - in paper of sudden death, as from accident orviolence, the body decomposes more rapidly than when death resultsfrom disease putrefaction sets in early in death from the infectiousfevers, such as typhus, pyæmia, and typhoid fever, also in death fromsuffocation by smoke or coal gas, by strangulation or after narcoticpoisoning those writings of a body which are the seat of bruises, wounds, or fractures, decompose rapidly. This is especially seen inwritings after a surgical operation 6 manner of burial - when a body is buried in low ground in a damp, swampy, clay soil, decomposition advances rapidly, as also when thegrave is shallow so the body can be exposed to constant variations oftemperature a porous soil impregnated with animal and vegetable matterfavors putrefaction, as also burying a body without clothes or coffin;this is especially seen where infants have been thrown into the groundand loosely covered with earth circumstances retarding putrefaction 1 the temperature - below 32° f and above 212° f putrefaction isentirely arrested the rapidity of the change considerably lessens asthe temperature advances above 100° f a remarkable instance of thepreservative power of cold is given by adolph erman, who states thatthe body of prince menschikoff, a favorite of peter the great, exhumedafter ninety-two years’ burial in frozen soil, had undergone hardly anychange buried in hot sand as is seen in the desert, a body putrefiesvery slowly and generally becomes mummified 2 moisture - absence of moisture retards decomposition in the dryair of the desert bodies have been preserved for a long period of time 3 air - if access of air to a body be prevented in any way by itsinclosure in a coffin, by closely fitting clothes, or by completeimmersion in water, putrefaction is retarded 4 age - adults and old people decompose more slowly than children males are said to change less rapidly than females, lean people thanfleshy ones 5 cause of death - putrefaction is delayed after death from chronicdiseases unless they are associated with dropsy poisoning by alcohol, chloroform, strychnine, and arsenic retard putrefaction in the lattercase the putrefactive changes seem to stop after they have oncecommenced, and often a result very similar to mummification is seen death from the mineral acids, especially sulphuric, appears to delayputrefaction 6 manner of burial - putrefaction is retarded by burial a shorttime after death. By interment on high ground, in dry, sandy, orgravelly soil. By having the grave deep, over six feet in depth ifpossible by the body being well wrapped and secured in a tight coffin, a lead one being the best in this respect lime or charcoal appliedfreely about a body will retard decomposition, as will also injectionof the body through the arteries with such substances as arsenic, chloride of zinc, or antimony the ultimate effect of putrefactionis to reduce all bodies to inorganic compounds, chiefly water, ammonia, and carbon dioxide three conditions are necessary for itsestablishment, 1 a given temperature, 2 moisture, 3 free accessof air the order in which the various organs and tissues undergodecomposition, as given by casper, who has investigated the subjectcarefully, is as follows. Trachea and larynx, brain of infants, stomachand intestines, spleen, omentum and mesentery, liver, brain of adults, heart and lungs, kidney, bladder and œsophagus, pancreas, largevessels, and last of all the uterus as the result of putrefaction, fluids, generally blood-stained, collectin the serous cavities of the body, and should not be confoundedwith serous effusions occurring during life so also the softeningof the organs and tissue resulting from decomposition should becarefully distinguished from those resulting from inflammation thesecadaveric softenings are most frequently found in the brain, spleen, and gastro-intestinal mucous membrane inflammatory softenings aredifferentiated by being rarely general but almost always limited, bythe substance of the inflamed writing being infiltrated with serum orpus and showing traces of vascular injection in doubtful paper thepathologist should have recourse to the microscope as the result of putrefaction, various changes take place in the mucousmembrane of the stomach and intestines which simulate the effectsof poisons the color of the stomach varies from red, which becomesbrighter on exposure to the air, to a brown, slate, or livid purple wecan only presume that these color-changes are the result of irritantpoisons when they are found in non-dependent writings and writings not incontact with organs engorged with blood, when they are seen soon afterdeath, and when the membrane is covered with coagulated blood, mucus, or flakes of membrane effects on putrefaction of submersion in water there are certain modifications of the putrefactive changes when bodieshave been submerged in water in the first place, the changes are muchless rapid. They often do not show themselves until about the twelfthday, and then as discolorations appearing generally first about theears and temples, then on the face, from which they spread to the neck, shoulders, chest, abdomen, and finally to the legs this is almost theinverse order of the putrefactive changes in bodies exposed to the air as a result of the formation of gases, the body in a short time becomesbuoyant. After floating on the surface of the water for a time, thegases escape and the body sinks, rising a second time when fresh gashas formed the rapidity of decomposition in water varies, being most rapid whenthe temperature is from 64° to 68° f stagnant as well as shallow waterfavors putrefaction if a body becomes coated with mud the change isdelayed submersion in a cesspool also retards it, and the conditionsare such as to favor the formation of adipocere after a body has been removed from the water an exposure of a very fewhours to the air causes rapid decomposition, so that in twenty-fourhours more marked changes may occur than would have resulted from afortnight longer submersion the face soon becomes bloated and black, so that identification is well-nigh impossible it is quite importantin medico-legal paper to estimate the time which has elapsed sincedeath in bodies found submersed in water the following are the variouschanges ordinarily seen at different periods of time, as estimated bydevergie, who has especially investigated the subject:first four or five days - little change. Rigor mortis may persist, writingicularly if the water is cold fourth or fifth day - skin of the ball of the thumb and littlefinger, also the lateral surface of the fingers, begins to whiten thiswhitening gradually extends to the palms of the hands and soles of thefeet the skin of the face will appear softened and of a more fadedwhite than the rest of the body fifteenth day - face slightly swollen and red.

But it is all too apt to creepin why yale essay unawares, unless one takes great precautions indeed clinical evidence needs especially to be on its guard against thispitfall, for the conditions of disease never remain constant. Nor is itpossible to foresee with certainty the direction which they are goingto take it is just this point which makes the clinical evidence somuch more difficult to interpret than laboratory evidence, in whichthe conditions can be more or less exactly controlled, and any changesforeseen it is on this account, also, that clinical experiments mustbe surrounded with extra painstaking precautions in brief, while the “proof” of a remedy is on the patient, that is notthe whole story, but merely an introduction the real problem is toestablish the causative connection between the remedy and the events the imperfect realization of this has blocked therapeutic advance, hasdisgusted critical men to the point of therapeutic nihilism, and hasfertilized the ground for the commercial exploitation of drugs that areof doubtful value or worse this has been impressed on me writingicularly by my service on the councilon pharmacy and chemistry in the course of its work of passing on theclaims advanced for commercial remedies, this council is forced toinquire critically into the basis of the claims of manufacturers it is interesting to note the qualitative differences in the evidencefor the various kinds of claims. The chemical data are usuallypresented in such a form that it is possible to tell at a glancewhether or not they are based on demonstrated facts, which couldusually be verified or refuted without special difficulty thedeductions are usually such as can be legitimately drawn from the data, or else they are obviously absurd all this agrees with the relativelyexact status of chemical science in passing to data and deductions from animal experiments, a distinctchange is noticeable. Not only are the data less reliable, and lessworthy of confidence, but they are more often stated in a lessstraightforward manner the presentation of the data often showsevidence of manipulation of the results, so as to make them mostfavorable to a preconceived conclusion that would recommend the drug this is not always intentional, but is writingly due to the less exactnature of animal experimentation, which leaves a wider play to thearbitrary interpretation of the reporter a certain amount of thisis unavoidable no serious objection can be raised, provided theexperimenter presents all the essential data, and discusses fairly allof the interpretations that would apply to them on the whole, it is usually possible to form a fairly definite estimateof the value of experimental data when one comes to the clinical evidence, an entirely differentatmosphere obtains when the council demands evidence of the usefulnessof a remedy, the manufacturers generally respond with every sign ofenthusiasm they may have ready a series of articles already published, or they instruct their agents to bring in letters from physicians thelast method seems to meet the most cordial response, judging from thedeluge of letters and opinions that floods the council the quality of the published papers is a fair reflection of thedeficiencies of what is still the common type of clinical evidence a little thought suffices to show that the greater writing cannotbe taken as serious evidence at all essay of the data are merelyimpressions-- usually the latest impressions of an impressionableenthusiast-- the type of man who does not consider it necessary topresent evidence for his own opinions. The type of man who does noteven realize that scientific conclusions must be based on objectivephenomena essay of the papers masquerade as “clinical reports, ” essaytimes with asplendid disregard for all details that could enable one to judge oftheir value and bearing, essaytimes with the most tedious presentationof all sorts of routine observations that have no relation to theproblem the majority of reports obtained by the agents belong to these classes, notwithstanding the fact that they are often written for the specialuse of the council, and therefore with the realization that theyare likely to be subjected to a thorough examination, and thereforepresumably representing the best type of work of which the reporter iscapable so, at least, one would suppose it is also possible, however, that essay of these reports are writtenmerely out of thoughtlessness, or perhaps often to get rid of animportunate agent this is illustrated by the following correspondence, taken literally from the files of the council a letter from a prominent physician “a, ” endorsing a certainpreparation “d, ” having been submitted to the council, the secretarywas directed to write to dr a as follows:dear dr a:-- the b company of c has requested the council on pharmacyand chemistry to admit its preparation d to new and nonofficialremedies as writing evidence for the value of the preparation, thecompany submitted a letter from you which contains the following. So far as my experience has thus far gone, they are certainly superior to a number of other iodine compounds now on the market, and i should judge that they ought to take a superior place in therapy involving the use of iodine the referee of the council in charge of d writes that he was interestedby your letter and asks that i inquire. As compared with sodium orpotassium iodid, what would you say are the differences between, and real advantages of, d and the alkaline iodids?. did you make anycomparative experiments and keep a record of them?. if so, the refereewould like to receive an account of your trials in what directioncould d be expected to occupy a superior place in iodin therapy?. i hope that you can give the information asked by the referee and thus aid the council in arriving at a correct estimate regarding the value of d the following reply was received from the physician in response to theforegoing. Dear professor puckner:-- in reply to yours of january 19, i did not proceed far enough in the investigation of d to draw conclusions of any writingicular value for the purpose of the council on pharmacy and chemistry. And i so stated in my letter to the proprietors of that remedy answers to the questions you put in your letter require an amount of investigation of the remedy far beyond anything i undertook as a matter of fact, i returned about five sixths of the capsules sent me, because of lack of time and opportunity to carry out the extensive clinical experiments that i plainly saw would be required to give an opinion at all worth while i believe you had better not consider me in the matter at all the report was furnished by a physician for whom i have a high personalregard i introduce it here, not so much in a spirit of criticism, but as a justification of the opinion that i have formed of clinicalevidence obtained by manufacturers through their clinical adjutors when commercial firms claim to base their conclusions on clinicalreports, the profession has a right to expect that these reportsshould be submitted to competent and independent review when suchreports are kept secret, it is impossible for any one to decide whatproportion of them are trustworthy, and what proportion thoughtless, incompetent or accommodating however, if this were done it is quitepossible that such firms would find much more difficulty in obtainingthe reports those who collaborate should realize frankly that underpresent conditions they are collaborating, not so much in determiningthe scientific value, but rather in establishing the commercial valueof the article often the best type of clinical reports-- those in which theobservations are directed to the significant events and not to mereside lines, and in which the significant events are correctly andadequately reported-- generally lack one important essential, namely, anadequate control of the natural course of the disease since this cannot be controlled directly, it must be compensatedindirectly for this purpose, there are available two methods:the first is the statistical method, in which alternate patientsreceive or do not receive the treatment this method can usuallyonly be of value when a very large series of patients is available even then, its value is limited or doubtful, because it cannot takesufficient account of the individuality of paper the second method consists in the attempt to distinguish unknownpreparations by their effects-- the method that might be called the“comparative method” or the “blind test ”in this, the patient, or a series of patients, is given the preparationwhich is to be tested, and another preparation which is inactive, and the observer aims to distinguish the two preparations by theireffects on the patient surely if the drug has any actions at all itwill be possible to select correctly in a decided majority of theadministrations the same principle can be applied in distinguishing the superiorityof one preparation over another in this case, the two preparationswould be given alternately to different patients, and the observerwould try to distinguish them by their effects here again, if onedrug is really superior or otherwise different from another, to apractically important extent, the observer will surely be able to makethe distinction this method is really the only one that avoids the pitfalls of clinicalobservation.

Opinion, that it was the former 34 van haumeder. Wien med woch , 1882, xxxii , pp 531-533 - suicide by hanging or homicide there were thesis wounds inthe head. These occurred during the delirium of typhus 35 maschka. “sammlung gericht gutacht , ” etc prag, leipzig, 1873, p 137 - boy, age 9. Found dead in sitting position injuries on neckand elsewhere question, had he hung himself or been choked?. were theinjuries inflicted before or after death?. opinion, suicide 36 ibid , p 144 - boy, age 13 found hanging in sitting position question whether murder, suicide, or accident opinion, suicide 37 ibid , p 149 - woman, age 60. Found hanging, sitting position suicide or homicide opinion, suicide 38 ibid , p 156 - woman, age 30. Found hanging opinion, suicide 39 ibid , p 165 - man, age 63 suicide by hanging, or homicide bystrangling?.

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Thelower were impressions of fingers close together, nearly uninterrupted, and which had bruised, flattened, and tanned the skin, which here wasdry, hard, and horny this lesion was above the intraclavicular notchand extended toward the sides of the neck with regularity of curve andneatness of imprint, evidently made with the right hand above thefirst furrow under the skin was a kind of track, less extended, moreregular, a bruising of the same nature as the preceding, but continued, due to the pressure of the index finger and thumb of left hand alittle below the jaw was a livid place on the skin, which was otherwiseunaffected by the ligature there was nothing to indicate a circularaction of the ligature froth in larynx and bronchi lungs apparentlynormal food had passed from stomach into œsophagus and air-passages 66 ibid , p 122 - woman found hanging in her room, and wasresuscitated she stated that the man who lived with her had triedto strangle her and then hung her tardieu saw her in hospital respiration short and embarrassed. Pains in neck and jaw found narrow, circular, sinuous, horizontal, uninterrupted line around the neck belowthyroid cartilage. Line everywhere equal, deep, and three to four mm wide. The skin excoriated and covered with thick crust below this wereseveral superficial excoriations there were thesis contusions on otherwritings of the body tardieu concluded that the mark on the neck wasfrom attempt to strangle.