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6 for $5 and 12 buy admission essay for $10, and acircular sent to a physician contained this typewritten note. “fees -- while the physician fee is not regulated by this company, the physicians who use hemo-therapin get $5 00 and $10 00 for each treatment ”-- from the journal a m a , jan 5, 1918 venosal report of the council on pharmacy and chemistrythe following report on venosal has been adopted by the council, andits publication authorized w a puckner, secretary “venosal” is one of the products of the intravenous products company, denver, colo its composition has been variously, and obscurely, described. “venosal is a sterile solution representing 1 gm 15 4 gr of salicylates in combination, together with colchicum ” “this is a product for intravenous use the composition of which is sodium salicylate, 15 4 grs 1 gm , iron salicylate a minute quantity and the equivalent of approximately 2 grs dried colchicum root ”none of these “formulas” gives the quantity of the product containingthe 1 gm of salicylate, etc , but presumably it refers to the contentsof 1 ampule or 20 c c this inference is in accord with the analysisof the product made in the chemical laboratory of the american medicalassociation the analysis also brought out the fact that the amount ofiron in a given ampule was 0 0008 gm about 1/80 grain this trace ofiron in the presence of salicylate gives the product a purple color venosal is recommended for the treatment of “rheumatism, ” meaning, thecontext would indicate, infectious rheumatic fever as colchicum hasno special action on this disease and as there is no apparent reasonfor the employment of the trace of iron present, these additions infixed proportions are unscientific, if not absurd according to theadvertising matter. “venosal eliminates unpleasant digestive disturbances which frequently forbid the use of salicylates by mouth and, in addition, insures their full therapeutic value ”the statement is misleading, as the paper in which the oraladministration of the salicylates is contraindicated are not “frequent”but exceptional and there is no evidence to justify the implicationthat the “full therapeutic value” of salicylates cannot readily beattained by their oral use still more astonishing is the followingclaim. “venosal is a combination carrying the true salicylates sodii in doses much larger than given by mouth with this preparation given intravenously, there is no nausea or disagreeable digestive after-effects, tinnitus aurium, or the accumulating effects of the drug. Yet the specific action of the salicylates seems to be increased thesis-fold, according to reports received ”what are the facts?. by mouth sodium salicylate is given in doses offrom 3 to 15 gm in a day. Whereas venosal is advised as 1 gm , infrom one to three day intervals. As a matter of elementary arithmeticit is plain that these doses of venosal are smaller instead of being“much larger ” the absence of digestive ill effects, tinnitus, etc , is explained by the small dosage that the specific action of thesalicylates should be increased by intravenous administration issurprising when it is remembered that the drug is absorbed rapidlyand completely from the intestines. In fact, the quoted statement isincredible the company further alleges that, on the basis of “clinical reports”it has received, it does not “hesitate to recommend this product forroutine use in all streptococcic infections ” such a therapeuticsuggestion is, to put it conservatively, gross exaggeration the whole question of the justification of using salicylatesintravenously is open to grave doubt since it is possible to obtainthe salicylate effects promptly and certainly by oral administration, the inherent dangers of intravenous medication render its routineemployment unwarranted a further objection to venosal, especially atthis time when economy is a national policy, is the unnecessarily highexpense of venosal itself and of its administration the referee recommends that venosal be declared ineligible to new andnonofficial remedies because of conflicts with rule 1 indefinitechemical composition, rule 6 therapeutic exaggerations and rule10 unscientific composition -- from the journal a m a , jan 5, 1918 secretin-beveridge and the u s patent law report of the council on pharmacy and chemistrytwo years ago the council published reports on two proprietarypreparations said to contain secretin, namely, “secretogen, ” soldby the g w carnrick company the journal a m a , may 1, 1915, p 1518, and “duodenin, ” sold by armour and company the journala m a , aug 14, 1915, p 639 these reports explained that therewas no evidence to indicate that an insufficient amount of secretin wasthe cause of gastro-intestinal diseases, and further that there wasno evidence that secretin in any form was physiologically active whenadministered by the mouth subsequently, a j carlson and his co-workers, at the request ofthe council, studied the question of the stability of secretin anddemonstrated the journal a m a , jan 15, 1916, pp 178 and 208that commercial secretin preparations contained no secretin and, further, that secretin given both by the mouth and even in enormousdoses directly into the intestine is entirely inactive shortly after the publication of professor carlson work the attentionof the council was called to a u s patent issued, may 2, 1916, to james wallace beveridge, “means for and method of stabilizingsecretin ” in this patent beveridge claimed to have invented “theprocess of producing secretin in stable form as a commercial articlefor therapeutic use ” that is, a process for preparing preparationswhich would contain secretin when they reach the consumer and in a formresisting destruction in its passage through the stomach in view of the demonstrated instability of secretin, the councilasked professor carlson to investigate the validity of the claims ofthe beveridge patent the study on “the question of the stability ofsecretin, ” by a j carlson, a e kanter and i tumpowski, whichappears below, shows that the beveridge patent furnishes no process forthe manufacture of commercially stable secretin preparations, nor anymeans for preventing the destruction of secretin by the gastric juicewhen administered orally it further demonstrates that the preparationmade by beveridge was devoid of secretin the council adopted the report of carlson and his co-workers, anddeclared secretin-beveridge inadmissible to new and nonofficialremedies the council directed that the report of carlson and his collaboratorsbe sent to the commissioner of patents with a protest against thegranting of patents without competent and thorough investigation of theclaims advanced therein w a puckner, secretary the question of the stability of secretin a j carlson, a e kanter and i tumpowski from the hull physiological laboratory of the university of chicagoin a letters patent, filed may 6, 1914, the patent granted may 2, 1916, james w beveridge, m d , makes certain claims concerning the stabilityand physiologic activity of secretin prepared according to the methodpatented by him in brief, dr beveridge claims that secretin prepared by digestingintestinal mucosa with a weak acid at a temperature slightly belowboiling, and mixed with 0 2 per cent to 2 per cent blood serum, albumin or peptone 1 remains active for at least six months, 2stimulates the pancreas when given by mouth, and 3 “may be injectedintravenously in man, if desired ” the only thing in the letters patentin support of these claims is the statement. “i have found out byactual tests that the preparation maintains its stability for five orsix months ”here are the claims in detail. “for the source of secretin i preferably use that writing of the alimentary tract of any lower animal-- such as a hog or sheep-- including the gastric pylorus, the duodenum and the jejunum this writing is split open and washed with a normal saline solution to clean the mucosa or mucous membrane of any detritus which may be present the mucosa with the epithelial cells is then removed or separated from the muscular wall by scraping with a blunt knife or in any other suitable way the scrapings or cuttings, which contain the secretin, are then macerated or broken up ” “the macerated mass is placed in a suitable vessel and subjected to the action of an acid solution until digested the time for the digestion of the mass will, of course, depend upon the strength and temperature of the acid solution employed the stronger the solution and the higher the temperature, the shorter the time necessary for complete digestion this period may vary from several minutes to several hours in my experiments i found that the best results were obtained with hydrochloric acid solution of one-tenth to five-tenths of one per cent in strength, although as high as eight-tenths per cent might be used the mixture is brought to a temperature of approximately 210 f , and it may even for a few moments exceed that temperature, but it should be kept below the boiling point, for excessive heat injures or breaks down the secretin molecule and impairs or destroys its activity although i prefer to use hydrochloric acid, i would have it understood that other acids-- both organic or inorganic-- may be employed, provided that the percentage of acidity is regulated to prevent a chemical change in the secretin, and further provided, of course, that the acid has no injurious effect on the human system ” “after the mass has been digested in the heated solution, the decoction is decanted, and after being allowed to cool is passed through a suitable filter until the filtrate is clear i found that by filtering the decoction from four to six times through a carbon filter, i obtained a clear colorless filtrate this is a solution of secretin and the acid which was used, and the clearness of the solution shows that it is practically free from albumoses, gelatin and other impurities such as cell tissues, etc present in the raw material under treatment ” “to the solution of pure and active secretin prepared as above explained, there is added a suitable quantity of blood serum-- say from one-fifth to two per cent or any equivalent medium-- such as albumin solution or a peptone solution-- which will aid and sustain the activating power of secretin as provided by the blood that is to say, any medium having the same power, similar quality or chemical composition that the blood-stream possesses in combining with secretin to stimulate the pancreas the addition of such a medium to the active secretin solution increases the potency of the secretin and its degree of stability by preventing oxidation or deterioration thereof if this strengthening or fortifying medium, as it may be properly termed, is alkaline, it performs the additional function of lowering the acidity of the secretin filtrate it is preferable that the final product be just faintly acid if desired, the final product may be made into an elixir by the addition of aromatics ” “any desired strength of secretin solution may be obtained according to the quantity of acid solution in my experiments i used from ten to fourteen duodena to a pint of acid solution ” “the solution of secretin prepared as above described is characterized by its ability to resist oxidation or deterioration for a sufficient period of time to render the solution available as a commercial article, and is furthermore characterized by freedom from poisonous and irritable chemical substances, whereby the secretin is chemically adapted to the human system to stimulate the pancreas to increased secretion ” “as previously stated, the secretin prepared according to my method may be administered orally to produce the desired physiological action of course, if desired, the secretin might be injected intravenously, but this more or less dangerous procedure is not at all necessary, and i merely mention it here to point out that when i refer to the oral administration of my new secretin preparation, i do not mean to exclude its administration by injection ” “as to the commercial stability of the secretin prepared according to my method, i may say that i have found by actual tests that the preparation maintains its stability for as long a period as five or six months when i refer to my product as being “commercially stable, ” i mean that it resists oxidation or deterioration for a sufficient period to render the same available as a commercial article this period may vary from several weeks to several months, depending upon certain commercial factors well understood by the manufacturer so, roughly speaking, i should say that secretin is commercially stable when it retains its activity from one to six months i do not wish to be understood, however, as limiting myself to these exact figures ”that active secretin may be extracted from macerated intestinal mucosaby weak acids below the temperature of boiling is well known in fact, weak acids at body temperature in contact with the duodenal mucosa leadto the formation of secretin the claims that secretin given by mouthreaches the blood and acts on the pancreas has been made for otherpreparations of secretin it has also been shown that these claims areerroneous 122 thus it would appear that the only novel element indr beveridge patented secretin is the addition of serum, solubleproteins or peptones what reason is there for believing that thiswill render the secretin stable for months, and physiologically activewhen taken by mouth?. we do not believe dr beveridge ever injected hissecretin-- protein mixture-- intravenously in man or animals not underanesthesia, otherwise he would not have stated.

As an actual fact, one is entitled to say only that such tumors undergo central necrosis, in all probably owing to defective circulatory supply the process isexactly similar to the coagulation necrosis described in the case oftubercles by weigert if autolysis occurs, it is only secondary to thepreceding necrosis this explanation, however, is confronted by the fact that the internaltumors produced by keysser showed no tendency to effect a localizationof the dyes, and correspondingly no tendency to be affected by thetherapeutic agents one might be permitted to inquire whether theseinternal tumors had undergone any necrosis keysser unfortunately makesno mention of this matter it is certainly true that the infiltrativemode of growth of the internal tumors, which is entirely differentfrom that of the subcutaneous implantations, is associated with amuch better blood supply and a lessened tendency to undergo necrosis that such tumors can undergo necrosis, however, is evidenced bycertain illustrations given by carl lewin in his paper on internaltumors but such changes usually occur only in advanced stages tojudge from his plates, keysser worked with relatively small tumors, an assumption which is rendered even more likely by the fact that hisinjections were undertaken in a fairly early stage of their growth inthis connection i may quote certain experiments of my own on internaltumors 279 the implantations made in my experiments were produced byintravenous injections of a tumor suspension into the jugular vein ofrats such injections resulted almost invariably in the production ofa large number of tumors in the lungs, which, as is well shown in thefigures accompanying the original article, differed very markedly insize the smaller of these tumors are composed throughout of activelygrowing cells, while the large tumors present an area of centralnecrosis exactly as do the subcutaneous tumors if such an animal begiven an intravenous injection of a dye such as congo red, it will befound that the larger tumors present an area of central discolorationcorresponding to the area of previous necrosis, while the smallertumors, like normal tissues, are not colored thus, it is clear thatthe internal tumors implanted in animals are subject to the same lawsconcerning the distribution of dyes and, of course, other substances asare the subcutaneous tumors as i have stated previously, an exactlyanalogous observation has been made in a human breast tumor in theabsence of any contradictory evidence, therefore, i think that it isperfectly justifiable to assume that keysser failed to achieve a resultin the internal growths simply owing to the fact that those growthspresented practically no areas of necrosis at the time of his injection 279 j m research, 1913, p 497 another theoretical question which bears closely on the recenttherapeutic investigations in human beings concerns the rôle ofcolloids, as such, in the procedure it is quite clear from what hasalready been said that all experiments with animal tumors have beenlargely influenced by the belief that metals in the colloidal formexercise a peculiar and characteristic influence on the destructionof tumors even when the therapeutic agents have been introducedin crystalline form, as by neuberg and caspari, the authors findthemselves compelled to assume that the metals are reduced to colloidalform within the tumors for the latter assumption there is absolutelyno evidence. It is due simply to the influence of the colloidal theory if one critically examines the data on which this theory is based, oneis forced to the conclusion that it has practically no establishedclaim to validity if we grant that colloidal metals have been shown tostimulate autolysis in the test tube, the same fact must be admitted ofmetals in noncolloidal solution the experiments, however, are very farfrom establishing either of these facts satisfactorily but even werethis the case, it is an unjustifiable inference that living tumor cellswould be influenced in anything like the same manner as are the deadcells observed in test tube experiments as an actual fact, we knowfrom the work of evans and schulemann that only the “scavenger cells”of the body take up foreign colloids, and to this class the tumor cellsdo not belong moreover, the form in which metals are introducedinto the circulation is not necessarily or even probably the form inwhich they act on the tissues colloidal solutions of the metals arecertainly subject to precipitation and other changes on entering theblood this fact i have shown experimentally in a previous study oncolloidal copper 280 in the same way it is probable, as has beenpointed out by wells, that metals when introduced in crystalloid formmay rapidly be altered so that they are carried throughout the body incolloidal form all of these considerations indicate how unjustifiableis the assumption that colloidal metals exercise a peculiar action ongrowing tumors it is hardly surprising that their empiric use hasfailed to measure up to expectations based on so slim a foundation offact 280 weil, richard. The effects of colloidal copper with an analysisof the therapeutic criteria in human cancer, j a m a 61:1034 sept 27 1913 clinical observationclinicians have not been slow in following the lead suggested by thetherapeutic experiments in animals it is perfectly proper that thisshould be the case in dealing with a disease of the character ofcancer, in thesis instances entirely beyond our power to influence, noone can question the advisability of trying any and every agent whichholds out the slightest promise unfortunately, a closer analysis ofthe animal experiments fails to vindicate even that degree of faith when one considers the facts which have been analyzed in the precedingdiscussion, it would appear not only futile but actually dangerous toattempt to benefit cancer sufferers by means of any of the agencieswhich have been employed in animal experimentation nevertheless, thefact remains that a variety of preparations have been used in the humanclinic the various types of preparations may be satisfactorily groupedunder four classes, namely:1 the crystalline salts of selenium 2 selenium in colloidal solution 3 other metals in colloidal solution 4 compounds of metals with organic radicals these substances have been administered by injection or by the mouth in the case of injection, the injections have been made either into thesubcutaneous tissues, intramuscularly, or intravenously, or finally, directly into the tumors before passing to a further considerationof this subject in detail, it may be well to recall the fact that inthe experimental tumors of animals, no matter what preparation hasbeen used, it has been possible to accomplish therapeutic effects onlyby the use of relatively enormous doses of the medicament, of doses, in fact, which were scarcely lower than the lethal dose certainexperimenters have noted that smaller doses actually stimulated thegrowth of the tumors in the second place, it has almost invariablybeen found necessary to administer the treatment intravenously, inasmuch as the other modes of administration failed of therapeuticeffect it is quite apparent that a procedure in human beings in anydegree analogous to that pursued in animals is entirely impossible thedoses used, with one notable exception to be subsequently mentioned, have invariably been relatively small hence it is apparent at theoutset that at least one fundamental condition of success in thetreatment of animal tumors has been necessarily excluded in theclinical application the salt used by wassermann is not stated in his original publication wolff281 speaks of it as a sodium salt, whereas keysser says that itwas a combination with potassium cyanid in only one instance, as faras i am aware, has the sodium salt been used therapeutically in humanbeings delbet282 states that he employed this salt intravenouslyin one case, and that its use was shortly followed by death unquestionably the salts of selenium are very much too toxic to be usedin this way 281 wolff. Die lehre von der krebs krankheit 3:1913 282 delbet, p. Bull de l’assn franç pour l’étude du cancer5:121, 1912. Ibid 6:85, 1913 the majority of those who have worked with selenium have used it incolloidal form, either preparing it themselves or employing one of thepreparations put on the market by the pharmaceutic firms of the latterthe best known are the electro-selenium of clin, and the seleniol ofcouturieux of those who have made use of selenium in these formsmay be mentioned cade and girard, 283 bougeaut and galliot, 284blumenthal, 285 thiroloix and lancien, 286 delbet, laurent andbohec, 287 and most extensively of all, m touche 288 all of theseauthors have described paper of malignant new growths of the mostvaried character which were treated by these preparations 283 cade and girard. Bull soc méd d hôp de lyon 11:397, 1912 284 bougeaut and galliot. Clinique, paris 7:501, 1912 285 blumenthal, a.

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The juicesnuffed up the nose, purges the head, it is admirable for surfeits orheadache, or any other ill effects coming of drunkenness ground-ivyis that which usually is called alehoof, hot and dry, the juice helpsnoise in the ears, fistulas, gouts, stoppings of the liver, itstrengthens the reins and stops the menses, helps the yellow jaundice, and other diseases coming of stoppings of the liver, and is excellentfor wounded people herba camphorata stinking ground-pine, is of a drying quality, andtherefore stops defluxions either in the eyes or upon the lungs, thegout, cramps, palsies, aches. Strengthens the nerves herbu paralysis, primula veris primroses, or cowslips, which youwill the leaves help pains in the head and joints. See the flowerswhich are most in use herba paris herb true-love, or one-berry it is good for wounds, falls, bruises, aposthumes, inflammations, ulcers in the privities herb true-love, is very cold in temperature you may take half a dramof it at a time in powder herba roberti a kind of cranebill herba venti, anemone wind-flower the juice snuffed up in the nosepurgeth the head, it cleanses filthy ulcers, encreases milk in nurses, and outwardly by ointment helps leprosies herniaria the same with empetron helxine pellitory of the wall cold, moist, cleansing, helps thestone and gravel in the kidnies, difficulty of urine, sore throats, pains in the ears, the juice being dropped in them. Outwardly it helpsthe shingles and st anthony fire hyppoglossum horse-tongue, tongue-blade or double-tongue the rootshelp the stranguary, provoke urine, ease the hard labour of women, provoke the menses, the herb helps ruptures and the fits of the mother:it is hot in the second degree, dry in the first. Boil it in white wine hyppolapathum patience, or monk rhubarb. See the root hypposclinum alexanders, or alisanders. Provoke urine, expel theplacenta, help the stranguary, expel wind sage either taken inwardly or beaten and applied plaister-wise to thematrix, draws forth both menses and placenta horminum clary. Hot and dry in the third degree. Helps the weaknessin the back, stops the running of the reins, and the fluor albus, provokes the menses, and helps women that are barren through coldnessor moisture, or both.