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THE EFFECT OF THE DIGESTIVE SECRETIONS ON THE ACTIVITY OF DIGITALIS AND ALLIED DRUGS

THE EFFECT OF THE DIGESTIVE SECRETIONS ON THE ACTIVITY OF DIGITALIS AND ALLIED DRUGS THE alkali of Solutions decreased the activity EFFECT OF THE SECRE- (O.S per cent.) DIGESTIVE the infusion. TIONS ON THEACTIVITY OF to be The of was not found activity strophanthin ALLIED DIGITALIS AND acid changed by digestion. pepsin DRUGS in As tllis hitler view I to lalcher," working opposed to that both acid with came the conclusion WORTH strophanthin, HALE hours U. S. P. H. and M.-H. Service and alkaline for two Assistant Pharmacologist, pancreatic digestion peptic D. C. WASHINGTON, caused diminuí ion in the of the some strophini- to.xicity is known, tbin. two In the of the well the in are com- considering opposed finding general glucosids As it is noted and to be that Chemical substances are strophan- however, paratively easily investigators, unstable thin is and it is that into a an indefinite term some substance. A broken and other quite possible sugar down of worked the observers with different factorsare the two in strophanthins-, up operative splitting number one of which was more attacked the glucosidal but chief them, in easily by digestive molecule, among especially the the are certain presence of beat, enzymes, agents. alkalies, As a more it was fact of and acids. considerably importance, the mineral In found Hatcher and that dose of the.toxic of the facts not at all find it is by Bailey* to view surprising six the for tbe stomach was five or cats that certain of have been by Btrophanthin digitalis reported glucosids times that and after a be to intravenous a by lengthy or lesser either injection, greater down degree, by to broken that series conclusion of came to the gastric or or experiments they pancreatic secretion, enzymes of by the the or the lessened the when the of added drug given these to make activity by alkalies to enzymes the acids stomach small on the desl rue- themactive. to a Three only degree researches be noted as depended may speci- live the and that the chief action ol' this fically showing secretions, deterioration. digestive its In factor in on a Deucher in cases heart depended delayed observed clincally of decreasing toxicity dropsical and disease absorption. conditions that verum digitalin the such as these with with was almostinvariablymuch when bindings digitalin verum, more given potent and with raises the infusion, As this slrophanthhi, very impor- the mouth. by subcutaneously than when given tant oí oí these bodies. With a proper dosage than when other question is common greater so no can difference was much as be drug therapy he came to (he conclusion powerful digitalis, regarded the (l; ^/"h'linisteretl unless the of the ,lln us sale exact drug employed • "'¡»s either in the strength •'" Un,.!, pi'ohahlv changed „,. is and if on in the stomach tile known, deterioration goes intestinal tract into inert .'.""'""ukU ]'" partially and intestines before these facts should be absorption action acid ""neb of thé of the hydrochloric I ,„. i;\""' known. 'J the in I'ermeiils found the stomach and "''"'¡ne, this end of To a number further along experiments Ibis line were deemed worlh while, not as COll- to only ibis was !'""M prove whether <„.'ll<"'t hypothesis of Ihe hut also to lest Ih'inatorv above recorded, findings oui series carried a of '" experi- 'iTU l »hi 1)''1!('1."'1'' ' the rate of deterioration use of an exact by making assay definite amounts of venini were digitalin l('''i(,e|(.(|. Wjl method for the of of the sub- "l" determining degree change .' 't'l'¡1'11 Fur honrs exceptions, twenty-four actioi in them the action stances after to subjecting For artificial Becretions. the question, digestive » k^of b„k lime of the l'or a more nearly digestive cl) agents analogous the if "''Tii'inly changes, any, determining a| »ere to the conditions found in These wiav vivo. ' accordingly >'""'s with »ere injected equiv- 'li'"' '""'.un"".''''''• tested i" determine the of deterioration when degree ^e artificial to digitaliní subjected u';,'s|'"l) and "•" and an the action of with to acid, subjected hydrochloric of the of ,' ,j1(', undigested time control, appear- without the of and of alkali with "'' "' addition pan- of pepsin, the hearts .-, as being ' Stoppage exposed a,,' <'1"1 cat and in instances of a el in, certain emulsin, glucOSldal- to I'enctinn. Kroin these he t| I,'""' experiments found in hitler almond other and ferment that the was splitting ,,., ¡inclusion digitalin partiallv (1.!'Ken "' SCI'lls. '"«'''i action of the compounds by |l|."1" chiefly bv,!,, (he Por the of before "lioric purpose assaying ,iei,|. cent., preparation 0.2 the per although ,|(i";"ii,.(.'0|. one-hour and after the method was digestion frog-heart ,0 to seemed accelerate the In-"/! breaking sim„l"','s"1 ""' I. mi , - . ,'Yrmil- ' ,- , , , in used. in consists the least V1'"' This, brief, determining solid The i.""1 »as pancreatic ion'-employed • of the which amount will t0 drug just permanent produce he inactive. «¿»«C'Sa? " Rana the ' of the ventricle of the at Erog systole pipiens tlie the that mat Hie the suggested i1' ^iicosi, "'.'' suggested possibility possibility n., lin i siiiic0sj(| end is of one hour. The in solution into drug injected "li"'1'1 '"' broken the -''""I' di.Sitalia «ave action ithue ¡interior and is ° the a of 22 C. temperature ""'v to Lymph-sac, but he seems digestive agents, iii'id heart maintained the the being throughout experiment, with vertun. 1!)"' digitalin v'-l" l'.,'b'.'. X|'l'l''"K'nis al the end of one hour. exposed Deucher's work in- ''n by nrat'"t-r the ^«8uPPhmiented "I' acid and alkalies, acid, "n!v| pepsin, !„.,,'"' DIG1T0X1N 'iil'iisj^ "' ! and the '''(•in digitalis, on ,, pure principles for He found that in A control was lirst established dis- strol)hanthin. the digitoxin °f by hi ii'-iil"'"'" t ' The after a amount in cent, alcohol. hydrochloric weighed 30 il,,,-1"!'! hours, solving per acia twenty-four the method described above was solutions reduced the of value .,, assay briefly "--¡'.ii activity by Hi-,, l,H'|,Sln "' found to he of He conclu,led. 0.008 "•'- l"'ll,'l,,"'''i|i- ing. gram frog weight. however, per ''"is,!,"' per To iest the effect of the secretion on '.''''''- acid at the the alone gastric digitoxin. ,|(1. body temperature u¡,l amount in a to n,,!,.,! the was a was and that weighed cylinder \J"M HI,,,., "'.""'dtion pepsin placed subjected ion the ¡id of an artificial 0.25 on gastric juice containing the Section Pharmacology Read in and Therapeutics of the acid and scale cent, 0.] cent, per pepsin. per hydrochloric at the Sixty-Second Annual Session, Medical Association. American The undissolved was in an incubator digitoxin placed June, at Angeles,1911. held Los Deutsch. Archiv. f. 3. Hatcher: Am. Jour, xxiii, Deucher: klin. Med., 1896, lvii, 1;1896-7, Physiol., 1908, 303. and II. 4. Hatcher, R. A., C. : Tincture of lviii, Bailey, Strophanthus and The Journal A. M. Jan. p. 5. 2. L\l=o"\wy: Wien. klin.Wchnschr., 1906, xix, 1157. Strophanthin, A., 2, 1909, Downloaded From: http://jama.jamanetwork.com/ by a University of Leeds User on 05/17/2015 tllC i» >,1 at for three and then taken 38 bonis, was with and are ¡,, all up represent j toxin,'digitalin, digitalein. alcohol form be to solution. This would "' enough just tliese also tincture, complete experiments eX-^iU-;e solution 0.011 A results be in the and lo assayed mg. per gram frog weight. give analogous second amount treated after weighed similarly assayed duplicates. . bel'1'11' ,u three hours in the The 0.010 lirsf be a incubator, tincture lo assayed nig. lier gram frog gave vi,,r y:i later hours this solution ,,i of 0.010 e.c. of «'('^''. weight. Eighteen digitoxin digestion per frog gram |H.|,|,"'¡'' *1 which was al room 0.013 of the alcohol. cent, nyu kept assayed mg. 0.25 temperature evaporation per ^ep| '"" and weight. acid o.l were added per grain frog cent, , per ;i-.'v pepsin of was then to for three time weighed amount 38° hours. At the end of that digitoxin subjected the action of acid lince 0.25 cent, for Value was found lo he per hydrochloric 0.01 I e.c. |ï"~ Qf bonis at 38°. AI ihe end Ibis il A second of time 0.(11 I assayed incline (I.DOS e.c. assayed .-''"," ¡H11' I»'1'. (l, the end at oí hours An mg. per gram ; was subjectea frog weight eighteen weight. ^ evaporated portion it :i's a! I This decrease ficial at ipom OjOl for three hours temperature assayed gastric digestion rag. ei^1 ¡-.„ in that of the an 8tflD acid vail.' 0.012 All«1'' '** approximately parallelling gave assay e.c. activity, "fue would indicate thai the acid alone was een al the assay hours room pepsin digestion, temperature the active in down ihe mole- 0.016 c.c. agent breaking digitoxin .-.!«» and acw« thai the This the cule, was inactive. tincture was also to ,,.„[. pepsin subjected Pancreatic secretion ihe 0.1 artificial made with containing pancreatin per pancreatic juice up „.i-iui1"'' eXP in sodium alkali two cent, dissolved II.lo carbonate was and 0.1 cent, in. In . cent, {h]Vc per per pancrcat 1"' allowed here lo act at 38° on of i was about weighed amounts 85 cent, deterioration digitoxin per 0\ hours for of three hours, and also hours at Whether is invariable periods al :1s0. this eighteen "iili|(„,-i'l- t&e room Ai ihe end of hours ihe but in view of the none QÍ three fact that «1»" assay Stated, temperature. °jt 0.008 showed in it may be per gram frog weight gave mg. duplicate experi- deterioration, questioned- (ilzViin" ihn- the that, no .from in the crude tincture,^ ments, showing up pancreatic brings point decomposition When natural the to for to leal' become digestion digestion. subjected digitalis may eighteen l'~!"'''¡'¡^..yi'e'"'* the hours, an there was some the with alkali and llius deterioration, however, assay present, explain value in invests results. This will be being 0.01.g. further point ninlTAl.lX -'<' FRENCH s'l'ltnl'll IN INTII ¡^ French The of in Ihe dose of digitalin. consisting mainly verum, digitalin discrepancy sll'Ol.hi'"'1^'],,!«"1 was Ihe control by 0.012 stomach and m"-- tested, great ad undigested assaying mg. iuiraveiiou>«ii t intravenously ,-, that-J^ o-iiiin"7'. ^„.„-".'"j of A in was view „f the the weighed amount sub- deterioration with per gram frog weight. digitsm>partjflci» UllU til Ihe to action of an artificial l'or a an OH jecie.l of the juice gastric investigation changes going' qJJ of three K- hours, lt then 11.111:1 throw , ihight some further period assayed mg. per digestion A fier hours room at grain weight. eighteen temperature question. va'1"' Ihe showed further 0.OÍ6 control of assay deterioration, The ga?e ,. mg. per assay strophanthin lo 0.00055 of gram frog necessary syslolie . Weight being produce mg. per gram frog weight. :1riil!''i;.. of Ihe hearl. alone acid was A of lio«1 stoppage amount '"!" Hydrochloric weighed ¡x strophanthin ,n' in ion effective détériorai assayed 0.00065 mg.: gastric approximately equally causing digestion >'"'"(1 /„'¡d ihe i.hi.I acid and as the'assay showed later marked deteriora«« seCo» pepsin. Xo under deterioration was ment of ihe obtained I real value 0.0015 temperature, being .nl£',-on a-":l'\'|U of French with an amounts artificial after three dig»'- weighed digitalin weighed hours' sample ,,|v"^ secret ion. o.oon; and the al end of Iwciii.v-f»'1.1' pancreatic „ig., '"¡j()|| &<>«% DMIIT.VI.KIS" Pancreatic "ig** 0.0010 temperature, mg. &ubjéc^ much less action on was the dose effective 0.02-4 being strophanthin. Digitalein assayed, BaI?jL.rg "ßSa*jjll to three alkaline for of pancreatic ¡nice ^gg mg. per gram frog weight. as the fl,, 0.0006 hours later In a ¡iiuouhi. 0.25 cent, acid mg.: twenty-four weighed ¡j d¡geg per hydrochloric t(.. 0.0006 A second and under pancres 0.1 were added. After at 38" for mg. sample ^fí pepsin digestion Ihree hours three hours showed for showed .leterioration, temp the a tlie am,.¡nil n«-*, assay deterioration, at hours after and then of the to heart twenty-four necessary produce thirty-six systolic stoppage ature. . "<'"* 0.032 being 0.26 cent., fte mg. Hydrochloric acid, with- ,i' per had eifert. Emulsin a '" -' out the caused détériorai ion thai Ihe end so al of very slight pepsin 'eduCfj(foO'¡ to aller in three hours the incubator, three hours was r at :i,S°. 0.0:10 to the nig. bring required gram j ventricle svslolc. ^ weight. t'"'. into frog ¡n „,,1 ' permanent «nl.-j. ,lestl'OUJ" _f!_1.r,..i,.¡.c.i.i. ..!,.„ 1,„ ii,. ,„|11' That also Under be artificial or no little, strophanthin might pancreatic destroy«'^ digestion very „ji^ too' is a but conclusion, was A value of was expi'i'ii"1'"'1" )lfjti<>" observed. 0.026 possible deterioration, mg. „ipos" decomj eats' and that no livers showed t hid to in a frogs' obtained, owing large incomplete absorption lace hours hours after aller two two at al number of Ibis is be 38°. noi°" n"'(l<l result lo place 38", nie assays t¡ {¡) " «^ De questioned. il . this series of From 'f was tested to determine the effect of emul- Digitalein experiments cause8. aj«<i W.Y invarlB acid Ihe the secretion the id' of ferment bitter almond gastric Bin, ¿¡gjtal-8-,-! glucosid-splitting o e> .,„ in the action of tlie e seuls. after diminution t The value hours 38° glucosids three at assay gave however, It is believed, ihe not in 0.028 as ainoiini to of strophanthus. l,n"v|,;ii mg. systole required produce of decompos» H*n'lt' I the determination of the i thus a ,g degree (lt ventricle, showing slight decomposition. rat the be tne can made, for in all probability ^ J^--,,. OK TIMIIIÎI-: DKIITAI.IS owing more under aclual conditions, eateí r rapid found the ihe chief ifv above that of the and the tjofl« -„. stomach comparatively llaiing by assays detw "I found in lion rale were less active after of the The glucosids diges- glucosids. digitalis gl8l vftrjo^ I"1' tion with an artificial were he about the same ever, lo appears _ |J(uir-- gastric juice, experiments tl»'« in carried oui with the As the about to cent, tincture. co-ids, 25 35 per glucosids digi- Downloaded From: http://jama.jamanetwork.com/ by a University of Leeds User on 05/17/2015 j i ! ¡\ i á i% i%> j--ii / JJ /y-> L \ / /' -.I I 1 wi .i /iï'i.i i j j j i ix \y j. » t J it Ij I —— fact '''lu- "", ¡hese described 'as be talen sistent use of into notice in remedies, generally therapeutics. l'iivo'"'1'1,1 bul under- tlccom- which in some direct, the aelion of the however, of alteratives; imperfectly P°8ition /'1'.la(',(l'', J)10('l'('ls of the ""(1 of i hese stood influence the nutrition must be manner, it myo- i glucosids considered, of them ")¡if untoward cardium. I have new to all certain of effects of no p0s's.ll)l11 the agents suggest; •''-'' dis m the "(,('u'iilion are to bill in be due lo them. At rate familiar bo every practitioner, majority may any f.,,. ls are mentioned in Vei-t Possible it seem advisable lo of hooks so would they cursorily comparison sii',1 pre- '', on that this with the discussions and it is digitalis, strophanihiis iniRlit prolonged omP°sition, suggested be i and ""' that often their value is underestimated, ''-V Official ''''M'iii'in.í-Í galenical prep- squills very '"'"'"Us to l"1"' fair is and cases in an in, trial them and given consequently many a*i .eutral, practice, by prescribing ? aloi "'''' heen their and that would have benefited ,il"t irri- '''.-íi'i'''8- .the early per- Ignoring spécifie by action^ " "' unchecked these tract sisten! administration are allowed to bodies on the intestinal also, go along w•,,|j,j °eei» until the a chronic to whom advisable that the should be becomes patient sufferer, '"¡v,,,,,, drug given ,'li,n death comes as a merciful relief. at ;l1 when ihe -er gastric meals, acidity the j», ""I ''IXi|iniiu When are in with a weak ami such a we contact myo- might eail procedure possibh brought the is to the frere irritation if a of lluid cardium first endeavor depict case, clearly quantity taken V iue large a| ""' is assoeiated with a same lo decide whether the condition time. in endocarditis and valvular lesion, as combined myo- to a in or if it is valvular lesion, as carditis, secondary failed whether it to ourselves is IN satisfy SOME FACTORS THE TREATMENT OF compensation; lack dis- due of as in aortic and to nutrition, coronary MYOCARDIAL LESIONS toxins such us we ease or is the result of and anemia, WATT M.D. KERR, find in uterine fibroids, habitual WILLIAM syphilis, of influenza, Clinical Professor of California Medicine, University not or disordered metabolism. Is it pos- constipation FRANCISCO SAN all sible while is realized much the it how fully that, of at conclusion as The arriving of on cardiac for their positive the body efficiency difficulty organs depend to the exact of tissue in the the changes existing in mind functional it is not so borne nature constantly activity, cardiac of undoubted evi- patients of presenting disturbance in the have a muscle that may any body of part dances heart makes it discuss the disease to I this prudent deleterious influence .the heart? mention on title rather than one a clinical of under because much of the recent literature on disease the following cases dis- for few, if can anatomy, any, that individ- based the impression on morbid circulatory system conveys tinguish the of chronic and signs between of is liable to lead to the myocarditis ual oi diseases the heart study of those or can say the molecular when other as in of same results the degeneration, study specialization or disturbance consequent on febrile ther intoxication and this it narrows the horizon; while clinical organs; and infiltration of congestion with small-cell a the much the man who be with to ends not (langer may fraught It true that the draws is the ¡1 is abso- is of sense, myocarditis begins. physician special treating only organs his in each case, picture of the changes but is inadmissible to the internist who with own mental dealing lutely he will in describing it in words that will difficulty another viscera which are so on one have mutually dependent stand the criticism of his audience. the of their functions. for normal of performance The our knowledge regarding diseases of the heart, Dr. James MacKenzie and other increase teachings that be made One of the first criticisms might to regard- members of the English school have done much and to have orginial impetus such remedies as given the use of constitutional the iodids additional ing disorders is fact in the treatment of the thai myocardial in research their continued administration is not very frequently of to the In eases medicine, but, up pres- for a sufficient of time to results. obtain tli'i." length bntti""'. ,rancl- 8iiv advance does to be not to his appeal' accompanied the does not hesitate tí of c'or keep syphilis physician in methods of treatment. niiiv progress these remedies for it iu, be, taking weeks, or, may ^ponding patient "" erroneous but it on impression part, but in the treatment my without u"'il,ra| months, any interruption; as ir ""' to were exclusive give he after tendency of inefficiency very slops Ration ' tg myocardial frequently which influence the mechanism of l,''"u'('i,'s weeks because has Ihe two he not obtained heart / ten or days '" discuss '"'.-¡'L'.'t or to treat- that so follow Ihe u^ superlii-ally same brilliant results often of ¡'"hi Him'„,' ' ""''viule in '""s'le or arrest thecardiae changes same of he seems to for the argue time; ¡ts,!|'i- digitalis length ^''v"s .' theni- too often do eases Only present a in restores in that because often W| digitalis '' compensation '''I I" treatment seems have censed after to disease within two the .sll'-.-(.SS|. case of valvular weeks, therefore, been '"' Un8Uccessfu] effort has made to '';| service, must if are to be of in bean iodids. going any l! they •"''' means of some raem- of "!,(.' compensation by the of time restore to full muscular |]'1(i same length activity ."''nils and in group, many and although libers which have been in which the toxic ,'| ¡'s|i,iie..s poisoned ""' "'' ""' to '"''"I l'('s"1' N- l)ll,¡('"' eeasing is he seems to that he is still on; , liiiii's'ei process going forget ''"' "dvit-c he feels well '"""'ib so soon as to ¡iisl hut some ait not with a cardiac that stimulant, ' dealing (" • ,H|'d his vocation, nevertheless (his be has , y daily form malnutrition elimination to of or imperfect """i modified if from the commence grea% the not? be corrected before Ihe recover so as to muscle can fully '" W('1'1' made that after his to understand 'l'l'l,'ireid ,' it is this correction that to and the respond stimulation, '' would '"' por him <0 neeessary iodids PNowcertain ? accomplish. "' 'i'1' '"' continue sonic "' " to i"" iik'.,|M particular The ease was one that me very- impressed following llCation if retain his restored '"'• li. he wished to henchís thai sometimes arise from much with the may iodids the use of : m,í!;v °>3ect i '" prolonged "'u factors in Ihe treat- "some Considering ,,|-;||v nl A. \V. nie in Itllll. l-'or CASE 1.—Mr. consulted August, lesions" is to the benefits emphasize uî^very '„n';!,, theSixty-Second Annual Session, from on ¡nul some weeks lie had Buffered exertion at American Association, dyspnea Medical a without an attack of cardiac in the Section on Pharmacology and Therapeutics of the asthma, Read hardly night passed heid at LosAngeles,June,1911. in ho tlmt lie dreaded to bed and going always slept latterly led ¡m was had ¡i armchair, lie of build, good life, spare Downloaded From: http://jama.jamanetwork.com/ by a University of Leeds User on 05/17/2015 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the American Medical Association Unpaywall

THE EFFECT OF THE DIGESTIVE SECRETIONS ON THE ACTIVITY OF DIGITALIS AND ALLIED DRUGS

Journal of the American Medical AssociationNov 4, 1911

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10.1001/jama.1911.04260110015006
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Abstract

THE alkali of Solutions decreased the activity EFFECT OF THE SECRE- (O.S per cent.) DIGESTIVE the infusion. TIONS ON THEACTIVITY OF to be The of was not found activity strophanthin ALLIED DIGITALIS AND acid changed by digestion. pepsin DRUGS in As tllis hitler view I to lalcher," working opposed to that both acid with came the conclusion WORTH strophanthin, HALE hours U. S. P. H. and M.-H. Service and alkaline for two Assistant Pharmacologist, pancreatic digestion peptic D. C. WASHINGTON, caused diminuí ion in the of the some strophini- to.xicity is known, tbin. two In the of the well the in are com- considering opposed finding general glucosids As it is noted and to be that Chemical substances are strophan- however, paratively easily investigators, unstable thin is and it is that into a an indefinite term some substance. A broken and other quite possible sugar down of worked the observers with different factorsare the two in strophanthins-, up operative splitting number one of which was more attacked the glucosidal but chief them, in easily by digestive molecule, among especially the the are certain presence of beat, enzymes, agents. alkalies, As a more it was fact of and acids. considerably importance, the mineral In found Hatcher and that dose of the.toxic of the facts not at all find it is by Bailey* to view surprising six the for tbe stomach was five or cats that certain of have been by Btrophanthin digitalis reported glucosids times that and after a be to intravenous a by lengthy or lesser either injection, greater down degree, by to broken that series conclusion of came to the gastric or or experiments they pancreatic secretion, enzymes of by the the or the lessened the when the of added drug given these to make activity by alkalies to enzymes the acids stomach small on the desl rue- themactive. to a Three only degree researches be noted as depended may speci- live the and that the chief action ol' this fically showing secretions, deterioration. digestive its In factor in on a Deucher in cases heart depended delayed observed clincally of decreasing toxicity dropsical and disease absorption. conditions that verum digitalin the such as these with with was almostinvariablymuch when bindings digitalin verum, more given potent and with raises the infusion, As this slrophanthhi, very impor- the mouth. by subcutaneously than when given tant oí oí these bodies. With a proper dosage than when other question is common greater so no can difference was much as be drug therapy he came to (he conclusion powerful digitalis, regarded the (l; ^/"h'linisteretl unless the of the ,lln us sale exact drug employed • "'¡»s either in the strength •'" Un,.!, pi'ohahlv changed „,. is and if on in the stomach tile known, deterioration goes intestinal tract into inert .'.""'""ukU ]'" partially and intestines before these facts should be absorption action acid ""neb of thé of the hydrochloric I ,„. i;\""' known. 'J the in I'ermeiils found the stomach and "''"'¡ne, this end of To a number further along experiments Ibis line were deemed worlh while, not as COll- to only ibis was !'""M prove whether <„.'ll<"'t hypothesis of Ihe hut also to lest Ih'inatorv above recorded, findings oui series carried a of '" experi- 'iTU l »hi 1)''1!('1."'1'' ' the rate of deterioration use of an exact by making assay definite amounts of venini were digitalin l('''i(,e|(.(|. Wjl method for the of of the sub- "l" determining degree change .' 't'l'¡1'11 Fur honrs exceptions, twenty-four actioi in them the action stances after to subjecting For artificial Becretions. the question, digestive » k^of b„k lime of the l'or a more nearly digestive cl) agents analogous the if "''Tii'inly changes, any, determining a| »ere to the conditions found in These wiav vivo. ' accordingly >'""'s with »ere injected equiv- 'li'"' '""'.un"".''''''• tested i" determine the of deterioration when degree ^e artificial to digitaliní subjected u';,'s|'"l) and "•" and an the action of with to acid, subjected hydrochloric of the of ,' ,j1(', undigested time control, appear- without the of and of alkali with "'' "' addition pan- of pepsin, the hearts .-, as being ' Stoppage exposed a,,' <'1"1 cat and in instances of a el in, certain emulsin, glucOSldal- to I'enctinn. Kroin these he t| I,'""' experiments found in hitler almond other and ferment that the was splitting ,,., ¡inclusion digitalin partiallv (1.!'Ken "' SCI'lls. '"«'''i action of the compounds by |l|."1" chiefly bv,!,, (he Por the of before "lioric purpose assaying ,iei,|. cent., preparation 0.2 the per although ,|(i";"ii,.(.'0|. one-hour and after the method was digestion frog-heart ,0 to seemed accelerate the In-"/! breaking sim„l"','s"1 ""' I. mi , - . ,'Yrmil- ' ,- , , , in used. in consists the least V1'"' This, brief, determining solid The i.""1 »as pancreatic ion'-employed • of the which amount will t0 drug just permanent produce he inactive. «¿»«C'Sa? " Rana the ' of the ventricle of the at Erog systole pipiens tlie the that mat Hie the suggested i1' ^iicosi, "'.'' suggested possibility possibility n., lin i siiiic0sj(| end is of one hour. The in solution into drug injected "li"'1'1 '"' broken the -''""I' di.Sitalia «ave action ithue ¡interior and is ° the a of 22 C. temperature ""'v to Lymph-sac, but he seems digestive agents, iii'id heart maintained the the being throughout experiment, with vertun. 1!)"' digitalin v'-l" l'.,'b'.'. X|'l'l''"K'nis al the end of one hour. exposed Deucher's work in- ''n by nrat'"t-r the ^«8uPPhmiented "I' acid and alkalies, acid, "n!v| pepsin, !„.,,'"' DIG1T0X1N 'iil'iisj^ "' ! and the '''(•in digitalis, on ,, pure principles for He found that in A control was lirst established dis- strol)hanthin. the digitoxin °f by hi ii'-iil"'"'" t ' The after a amount in cent, alcohol. hydrochloric weighed 30 il,,,-1"!'! hours, solving per acia twenty-four the method described above was solutions reduced the of value .,, assay briefly "--¡'.ii activity by Hi-,, l,H'|,Sln "' found to he of He conclu,led. 0.008 "•'- l"'ll,'l,,"'''i|i- ing. gram frog weight. however, per ''"is,!,"' per To iest the effect of the secretion on '.''''''- acid at the the alone gastric digitoxin. ,|(1. body temperature u¡,l amount in a to n,,!,.,! the was a was and that weighed cylinder \J"M HI,,,., "'.""'dtion pepsin placed subjected ion the ¡id of an artificial 0.25 on gastric juice containing the Section Pharmacology Read in and Therapeutics of the acid and scale cent, 0.] cent, per pepsin. per hydrochloric at the Sixty-Second Annual Session, Medical Association. American The undissolved was in an incubator digitoxin placed June, at Angeles,1911. held Los Deutsch. Archiv. f. 3. Hatcher: Am. Jour, xxiii, Deucher: klin. Med., 1896, lvii, 1;1896-7, Physiol., 1908, 303. and II. 4. Hatcher, R. A., C. : Tincture of lviii, Bailey, Strophanthus and The Journal A. M. Jan. p. 5. 2. L\l=o"\wy: Wien. klin.Wchnschr., 1906, xix, 1157. Strophanthin, A., 2, 1909, Downloaded From: http://jama.jamanetwork.com/ by a University of Leeds User on 05/17/2015 tllC i» >,1 at for three and then taken 38 bonis, was with and are ¡,, all up represent j toxin,'digitalin, digitalein. alcohol form be to solution. This would "' enough just tliese also tincture, complete experiments eX-^iU-;e solution 0.011 A results be in the and lo assayed mg. per gram frog weight. give analogous second amount treated after weighed similarly assayed duplicates. . bel'1'11' ,u three hours in the The 0.010 lirsf be a incubator, tincture lo assayed nig. lier gram frog gave vi,,r y:i later hours this solution ,,i of 0.010 e.c. of «'('^''. weight. Eighteen digitoxin digestion per frog gram |H.|,|,"'¡'' *1 which was al room 0.013 of the alcohol. cent, nyu kept assayed mg. 0.25 temperature evaporation per ^ep| '"" and weight. acid o.l were added per grain frog cent, , per ;i-.'v pepsin of was then to for three time weighed amount 38° hours. At the end of that digitoxin subjected the action of acid lince 0.25 cent, for Value was found lo he per hydrochloric 0.01 I e.c. |ï"~ Qf bonis at 38°. AI ihe end Ibis il A second of time 0.(11 I assayed incline (I.DOS e.c. assayed .-''"," ¡H11' I»'1'. (l, the end at oí hours An mg. per gram ; was subjectea frog weight eighteen weight. ^ evaporated portion it :i's a! I This decrease ficial at ipom OjOl for three hours temperature assayed gastric digestion rag. ei^1 ¡-.„ in that of the an 8tflD acid vail.' 0.012 All«1'' '** approximately parallelling gave assay e.c. activity, "fue would indicate thai the acid alone was een al the assay hours room pepsin digestion, temperature the active in down ihe mole- 0.016 c.c. agent breaking digitoxin .-.!«» and acw« thai the This the cule, was inactive. tincture was also to ,,.„[. pepsin subjected Pancreatic secretion ihe 0.1 artificial made with containing pancreatin per pancreatic juice up „.i-iui1"'' eXP in sodium alkali two cent, dissolved II.lo carbonate was and 0.1 cent, in. In . cent, {h]Vc per per pancrcat 1"' allowed here lo act at 38° on of i was about weighed amounts 85 cent, deterioration digitoxin per 0\ hours for of three hours, and also hours at Whether is invariable periods al :1s0. this eighteen "iili|(„,-i'l- t&e room Ai ihe end of hours ihe but in view of the none QÍ three fact that «1»" assay Stated, temperature. °jt 0.008 showed in it may be per gram frog weight gave mg. duplicate experi- deterioration, questioned- (ilzViin" ihn- the that, no .from in the crude tincture,^ ments, showing up pancreatic brings point decomposition When natural the to for to leal' become digestion digestion. subjected digitalis may eighteen l'~!"'''¡'¡^..yi'e'"'* the hours, an there was some the with alkali and llius deterioration, however, assay present, explain value in invests results. This will be being 0.01.g. further point ninlTAl.lX -'<' FRENCH s'l'ltnl'll IN INTII ¡^ French The of in Ihe dose of digitalin. consisting mainly verum, digitalin discrepancy sll'Ol.hi'"'1^'],,!«"1 was Ihe control by 0.012 stomach and m"-- tested, great ad undigested assaying mg. iuiraveiiou>«ii t intravenously ,-, that-J^ o-iiiin"7'. ^„.„-".'"j of A in was view „f the the weighed amount sub- deterioration with per gram frog weight. digitsm>partjflci» UllU til Ihe to action of an artificial l'or a an OH jecie.l of the juice gastric investigation changes going' qJJ of three K- hours, lt then 11.111:1 throw , ihight some further period assayed mg. per digestion A fier hours room at grain weight. eighteen temperature question. va'1"' Ihe showed further 0.OÍ6 control of assay deterioration, The ga?e ,. mg. per assay strophanthin lo 0.00055 of gram frog necessary syslolie . Weight being produce mg. per gram frog weight. :1riil!''i;.. of Ihe hearl. alone acid was A of lio«1 stoppage amount '"!" Hydrochloric weighed ¡x strophanthin ,n' in ion effective détériorai assayed 0.00065 mg.: gastric approximately equally causing digestion >'"'"(1 /„'¡d ihe i.hi.I acid and as the'assay showed later marked deteriora«« seCo» pepsin. Xo under deterioration was ment of ihe obtained I real value 0.0015 temperature, being .nl£',-on a-":l'\'|U of French with an amounts artificial after three dig»'- weighed digitalin weighed hours' sample ,,|v"^ secret ion. o.oon; and the al end of Iwciii.v-f»'1.1' pancreatic „ig., '"¡j()|| &<>«% DMIIT.VI.KIS" Pancreatic "ig** 0.0010 temperature, mg. &ubjéc^ much less action on was the dose effective 0.02-4 being strophanthin. Digitalein assayed, BaI?jL.rg "ßSa*jjll to three alkaline for of pancreatic ¡nice ^gg mg. per gram frog weight. as the fl,, 0.0006 hours later In a ¡iiuouhi. 0.25 cent, acid mg.: twenty-four weighed ¡j d¡geg per hydrochloric t(.. 0.0006 A second and under pancres 0.1 were added. After at 38" for mg. sample ^fí pepsin digestion Ihree hours three hours showed for showed .leterioration, temp the a tlie am,.¡nil n«-*, assay deterioration, at hours after and then of the to heart twenty-four necessary produce thirty-six systolic stoppage ature. . "<'"* 0.032 being 0.26 cent., fte mg. Hydrochloric acid, with- ,i' per had eifert. Emulsin a '" -' out the caused détériorai ion thai Ihe end so al of very slight pepsin 'eduCfj(foO'¡ to aller in three hours the incubator, three hours was r at :i,S°. 0.0:10 to the nig. bring required gram j ventricle svslolc. ^ weight. t'"'. into frog ¡n „,,1 ' permanent «nl.-j. ,lestl'OUJ" _f!_1.r,..i,.¡.c.i.i. ..!,.„ 1,„ ii,. ,„|11' That also Under be artificial or no little, strophanthin might pancreatic destroy«'^ digestion very „ji^ too' is a but conclusion, was A value of was expi'i'ii"1'"'1" )lfjti<>" observed. 0.026 possible deterioration, mg. „ipos" decomj eats' and that no livers showed t hid to in a frogs' obtained, owing large incomplete absorption lace hours hours after aller two two at al number of Ibis is be 38°. noi°" n"'(l<l result lo place 38", nie assays t¡ {¡) " «^ De questioned. il . this series of From 'f was tested to determine the effect of emul- Digitalein experiments cause8. aj«<i W.Y invarlB acid Ihe the secretion the id' of ferment bitter almond gastric Bin, ¿¡gjtal-8-,-! glucosid-splitting o e> .,„ in the action of tlie e seuls. after diminution t The value hours 38° glucosids three at assay gave however, It is believed, ihe not in 0.028 as ainoiini to of strophanthus. l,n"v|,;ii mg. systole required produce of decompos» H*n'lt' I the determination of the i thus a ,g degree (lt ventricle, showing slight decomposition. rat the be tne can made, for in all probability ^ J^--,,. OK TIMIIIÎI-: DKIITAI.IS owing more under aclual conditions, eateí r rapid found the ihe chief ifv above that of the and the tjofl« -„. stomach comparatively llaiing by assays detw "I found in lion rale were less active after of the The glucosids diges- glucosids. digitalis gl8l vftrjo^ I"1' tion with an artificial were he about the same ever, lo appears _ |J(uir-- gastric juice, experiments tl»'« in carried oui with the As the about to cent, tincture. co-ids, 25 35 per glucosids digi- Downloaded From: http://jama.jamanetwork.com/ by a University of Leeds User on 05/17/2015 j i ! ¡\ i á i% i%> j--ii / JJ /y-> L \ / /' -.I I 1 wi .i /iï'i.i i j j j i ix \y j. » t J it Ij I —— fact '''lu- "", ¡hese described 'as be talen sistent use of into notice in remedies, generally therapeutics. l'iivo'"'1'1,1 bul under- tlccom- which in some direct, the aelion of the however, of alteratives; imperfectly P°8ition /'1'.la(',(l'', J)10('l'('ls of the ""(1 of i hese stood influence the nutrition must be manner, it myo- i glucosids considered, of them ")¡if untoward cardium. I have new to all certain of effects of no p0s's.ll)l11 the agents suggest; •''-'' dis m the "(,('u'iilion are to bill in be due lo them. At rate familiar bo every practitioner, majority may any f.,,. ls are mentioned in Vei-t Possible it seem advisable lo of hooks so would they cursorily comparison sii',1 pre- '', on that this with the discussions and it is digitalis, strophanihiis iniRlit prolonged omP°sition, suggested be i and ""' that often their value is underestimated, ''-V Official ''''M'iii'in.í-Í galenical prep- squills very '"'"'"Us to l"1"' fair is and cases in an in, trial them and given consequently many a*i .eutral, practice, by prescribing ? aloi "'''' heen their and that would have benefited ,il"t irri- '''.-íi'i'''8- .the early per- Ignoring spécifie by action^ " "' unchecked these tract sisten! administration are allowed to bodies on the intestinal also, go along w•,,|j,j °eei» until the a chronic to whom advisable that the should be becomes patient sufferer, '"¡v,,,,,, drug given ,'li,n death comes as a merciful relief. at ;l1 when ihe -er gastric meals, acidity the j», ""I ''IXi|iniiu When are in with a weak ami such a we contact myo- might eail procedure possibh brought the is to the frere irritation if a of lluid cardium first endeavor depict case, clearly quantity taken V iue large a| ""' is assoeiated with a same lo decide whether the condition time. in endocarditis and valvular lesion, as combined myo- to a in or if it is valvular lesion, as carditis, secondary failed whether it to ourselves is IN satisfy SOME FACTORS THE TREATMENT OF compensation; lack dis- due of as in aortic and to nutrition, coronary MYOCARDIAL LESIONS toxins such us we ease or is the result of and anemia, WATT M.D. KERR, find in uterine fibroids, habitual WILLIAM syphilis, of influenza, Clinical Professor of California Medicine, University not or disordered metabolism. Is it pos- constipation FRANCISCO SAN all sible while is realized much the it how fully that, of at conclusion as The arriving of on cardiac for their positive the body efficiency difficulty organs depend to the exact of tissue in the the changes existing in mind functional it is not so borne nature constantly activity, cardiac of undoubted evi- patients of presenting disturbance in the have a muscle that may any body of part dances heart makes it discuss the disease to I this prudent deleterious influence .the heart? mention on title rather than one a clinical of under because much of the recent literature on disease the following cases dis- for few, if can anatomy, any, that individ- based the impression on morbid circulatory system conveys tinguish the of chronic and signs between of is liable to lead to the myocarditis ual oi diseases the heart study of those or can say the molecular when other as in of same results the degeneration, study specialization or disturbance consequent on febrile ther intoxication and this it narrows the horizon; while clinical organs; and infiltration of congestion with small-cell a the much the man who be with to ends not (langer may fraught It true that the draws is the ¡1 is abso- is of sense, myocarditis begins. physician special treating only organs his in each case, picture of the changes but is inadmissible to the internist who with own mental dealing lutely he will in describing it in words that will difficulty another viscera which are so on one have mutually dependent stand the criticism of his audience. the of their functions. for normal of performance The our knowledge regarding diseases of the heart, Dr. James MacKenzie and other increase teachings that be made One of the first criticisms might to regard- members of the English school have done much and to have orginial impetus such remedies as given the use of constitutional the iodids additional ing disorders is fact in the treatment of the thai myocardial in research their continued administration is not very frequently of to the In eases medicine, but, up pres- for a sufficient of time to results. obtain tli'i." length bntti""'. ,rancl- 8iiv advance does to be not to his appeal' accompanied the does not hesitate tí of c'or keep syphilis physician in methods of treatment. niiiv progress these remedies for it iu, be, taking weeks, or, may ^ponding patient "" erroneous but it on impression part, but in the treatment my without u"'il,ra| months, any interruption; as ir ""' to were exclusive give he after tendency of inefficiency very slops Ration ' tg myocardial frequently which influence the mechanism of l,''"u'('i,'s weeks because has Ihe two he not obtained heart / ten or days '" discuss '"'.-¡'L'.'t or to treat- that so follow Ihe u^ superlii-ally same brilliant results often of ¡'"hi Him'„,' ' ""''viule in '""s'le or arrest thecardiae changes same of he seems to for the argue time; ¡ts,!|'i- digitalis length ^''v"s .' theni- too often do eases Only present a in restores in that because often W| digitalis '' compensation '''I I" treatment seems have censed after to disease within two the .sll'-.-(.SS|. case of valvular weeks, therefore, been '"' Un8Uccessfu] effort has made to '';| service, must if are to be of in bean iodids. going any l! they •"''' means of some raem- of "!,(.' compensation by the of time restore to full muscular |]'1(i same length activity ."''nils and in group, many and although libers which have been in which the toxic ,'| ¡'s|i,iie..s poisoned ""' "'' ""' to '"''"I l'('s"1' N- l)ll,¡('"' eeasing is he seems to that he is still on; , liiiii's'ei process going forget ''"' "dvit-c he feels well '"""'ib so soon as to ¡iisl hut some ait not with a cardiac that stimulant, ' dealing (" • ,H|'d his vocation, nevertheless (his be has , y daily form malnutrition elimination to of or imperfect """i modified if from the commence grea% the not? be corrected before Ihe recover so as to muscle can fully '" W('1'1' made that after his to understand 'l'l'l,'ireid ,' it is this correction that to and the respond stimulation, '' would '"' por him <0 neeessary iodids PNowcertain ? accomplish. "' 'i'1' '"' continue sonic "' " to i"" iik'.,|M particular The ease was one that me very- impressed following llCation if retain his restored '"'• li. he wished to henchís thai sometimes arise from much with the may iodids the use of : m,í!;v °>3ect i '" prolonged "'u factors in Ihe treat- "some Considering ,,|-;||v nl A. \V. nie in Itllll. l-'or CASE 1.—Mr. consulted August, lesions" is to the benefits emphasize uî^very '„n';!,, theSixty-Second Annual Session, from on ¡nul some weeks lie had Buffered exertion at American Association, dyspnea Medical a without an attack of cardiac in the Section on Pharmacology and Therapeutics of the asthma, Read hardly night passed heid at LosAngeles,June,1911. in ho tlmt lie dreaded to bed and going always slept latterly led ¡m was had ¡i armchair, lie of build, good life, spare Downloaded From: http://jama.jamanetwork.com/ by a University of Leeds User on 05/17/2015

Journal

Journal of the American Medical AssociationUnpaywall

Published: Nov 4, 1911

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