,issu$ ,april #d1 #aiab4 ,u4,s4 ,,dep>tm5t ,,( ,,agriculture1 ,,bureau ,,( ,,*emi/ry--,,bullet9 ,no4 #adh4 ,h4 ,w4 ,,wiley1 ,,*ief ,,( ,,bureau4 ,,! ,,toxicity ,,( ,,caffe93 ,,an ,,exp]im5tal ,,/udy ,,on ,,diff]5t ,,species ,,( ,,animals4 ,,by ,,william ,,salant1 ,*ief ,ph>macological ,laboratory1 ,division ( ,drugs1 ,,& ,j4 ,b4 ,,rieg]1 ,assi/ant ,*emi/4 ,illu/ration3 ,,unit$ ,,/ates ,,dep>tm5t ,,( ,,agriculture ,,seal ,,wa%+ton3 ,,gov]nm5t ,,pr9t+ ,,(fice4 #aiab4 ,,lett] ,,( ,,transmittal4 ,u4 ,s4 ,,dep>tm5t ,,( ,,agriculture1 ,,bureau ,,( ,,*emi/ry1 ,wa%+ton1 ,d4 ,c41 ,novemb] #ad1 #aiaa4 ,sir3 ,i h ! honor to submit = y\r approval a manuscript on ! toxicity ( caffe91 :i* is ! fir/ ( a s]ies ( reports to be made by ,dr4 ,salant on ! ph>macology ( ?is drug2 ! conclusions "h report$ are1 !re=e1 9 "s p>ticul>s to be reg>d$ z t5tative4 ,! data obta9$ are prim>ily ( use 9 ! execution ( ! food & drugs act1 b are capable ( mu* broad] application4 ,ackn[l$gm5t is made ( ! assi/ance r5d]$ by ,dr4 ,john ,r4 ,mohl]1 ,*ief ( ! ,pa?ological ,division1 ,bureau ( ,animal ,indu/ry1 & 8 assi/ants1 9 p]=m+ ! autopsies record$ 9 ?is report4 ,i recomm5d ! publication ( ! manuscript z ,bullet9 ,no4 #adh ( ! ,bureau ( ,*emi/ry4 ,respectfully1 ,h4 ,w4 ,,wiley1 ,*ief4 ,hon4 ,,james ,,wilson1 ,secret>y ( ,agriculture4 ,?is publication may be procur$ f ! ,sup]9t5d5t ( ,docum5ts1 ,gov]nm5t ,pr9t+ ,(fice ,wa%+ton1 ,d4 ,c41 at #ae c5ts p] copy ,,cont5ts4 ,page4 ,introduction #e ,hi/orical review ( ! lit]ature on ! toxicity ( caffe9 #i ,acute caffe9 intoxication #ah ,exp]im5ts on rabbits #ah ,subcutane\s injection #ah ,adm9i/ration by m\? #bf ,injection into ! p]itoneal cavity #bh ,intramuscul> injection #cc ,intrav5\s injection #cg ,summ>y #db ,exp]im5ts on gu9ea pigs #dc ,subcutane\s injection #dc ,injection into ! p]itoneal cavity #dg ,adm9i/ration by m\? #di ,summ>y #eb ,exp]im5ts on cats #ec ,subcutane\s injection #ec ,injection into ! p]itoneal cavity #ef ,adm9i/ration by m\? #eg ,summ>y #ei ,exp]im5ts on dogs #fj ,adm9i/ration by m\? #fj ,subcutane\s injection #fj ,exp]im5ts on puppies #fa ,summ>y #fb ,*ronic caffe9 intoxication #fc ,exp]im5ts on rabbits #fc ,exp]im5ts on dogs #ge ,discussion ( results #ia ,g5]al summ>y & conclusions #ie ,bibliography #ig ,,! ,,toxicity ,,( ,,caffe94 ,,introduction4 ,comp>ative physiology has e/abli%$ ! fundam5tal fact t "s prop]ties are common to all =ms ( liv+ matt]4 ,b ! same me?od ( inquiry has also l$ to ! recognition ( m>k$ diff]5ces 9 ! physiological processes ( v>i\s species ( animals4 ,among ! mo/ important inve/igations :i* contribut$ to ! k ( su* v>iation ( function are ! /udies 9 comp>ative metabolism4 ,x is n[ recogniz$ t metabolism is 9 "s respects q diff]5t 9 h]bivora & 9 c>nivora4 ,"s =ms ( oxidation are mu* great] 9 ! rabbit ?an 9 cats & dogs4 ,nucle9 metabolism pres5ts important diff]5ces 9 ! rabbit & 9 man1 :ile ! mode ( neutraliz+ acid 9 ! body may be cit$ z ano!r v>iation 9 ! metabolism ( ^! =ms4 ,p]haps ! mo/ /rik+ examples ( diff]5ces 9 ! metabolism ( diff]5t organisms is furni%$ by ! results ( /udies on ! fate ( c]ta9 poisons introduc$ into ! body4 ,! classical exp]im5ts ( ,bunge & ,s*mi$eb]g7#ae7;,a on ! syn!sis ( hippuric acid are ( int]e/ 9 ?is reg>d4 ,x w be recall$ t 9 ! dog ! syn!sis takes place 9 ! kidney2 ! rabbit is able to =m hippuric acid 9 ! liv] z well z 9 ! kidney1 :ile frogs c syn!size hippuric acid ev5 :5 bo? ( ^! organs h be5 remov$ or exclud$ f ! circulation4 ,obs]vations on ! fate ( "s ( ! alcohols ( ! fatty acid s]ies h likewise %[n t ^! sub/ances may be comb9$ ) glycuronic acid 9 "s animals b n 9 o!rs4 ,accord+ to ,?i]feld] & ,von ,m]+17#hd7 t]ti>y alcohols are comb9$ 9 ?is mann] 9 ! rabbit b n 9 ! dog4 ,accord+ to ,neubau]17#fd7 ! prim>y & second>y alcohols are s comb9$ 9 ! dog z well z 9 ! rabbit1 b to a great] degree 9 ! latt]4 ,a ,! small figures ref] to ! bibliography at ! end ( ?is bullet94 ,pohl7#gc7 f\nd t amyl alcohol is l>gely elim9at$ by ! lungs 9 ! cat & 9 ! dog4 ,! protocols ( 8 exp]im5ts %[ t #fe p] c5t ( ! alcohol giv5 ^! animals 0 ?us recov]$1 :ile he recov]$ only #bb p] c5t ( ?is sub/ance 9 ! expir$ air ( ! rabbit4 ,exam9ation ( ! ur9e %[$ ! pres5ce ( glycuronic acid4 ,h(mei/]'s7#cg7 "w ) tellurium 9 ! dog is ( int]e/ 9 ?is connection4 ,he made ! important discov]y t "s animals possess ! p[] ( me?ylation z well z ( deme?ylation4 ,abd]hald5 & ,brahm's7#a7 exp]im5ts ) pyrid9 %[ t ! same is true ( "y dogs :5 on a meat diet4 ,8 exp]im5ts on rabbits ) ?is sub/ance 7 negative4 ,! metabolism ( caffe9 & !obrom9 furni% ano!r illu/ration ( diff]5ces 9 ! physiological me*anism ( animals4 ,al?\gh ! sub/ances f\nd 9 ! ur9e ( man1 dog1 & rabbit aft] ! adm9i/ration ( caffe9 & !obrom9 7 ! same1 ! quantities v>i$ consid]ably4 ,accord+ to ,krg] & ,s*midt17#dg7 ov] #ad p] c5t ( ! !obrom9 introduc$ into ! rabbit is elim9at$ z #g-me?yl xan?9 9 ! ur9e4 ,! dog elim9ates only ab\t #j4fg p] c5t4 ,on ! o!r h&1 ! am\nt ( tri-me?yl xan?9 elim9at$ 0 only #c p] c5t 9 ! dog & n q #a p] c5t 9 ! rabbit4 ,x appe>s1 !re=e1 f /udies 9 comp>ative metabolism1 :e!r endog5\s or exog5\s1 t well-m>k$ physiologic & *emical diff]5ces exi/ 9 v>i\s species ( animals4 ,t ph>macological action may likewise v>y 9 diff]5t species ( animals is %[n by ! foll[+ inve/igations4 ,accord+ to ,gu9>d17#ca7 :o made an exhau/ive /udy ( morph91 ! reaction to ?is alkaloid v>ies 9 diff]5t =ms ( life1 bo? qualitatively & quantitatively4 ,he e/abli%$ its n>cotic effect 9 ! dog1 rabbit1 gu9ea pig1 :ite mice1 & rats1 :ile = ! cat1 horse1 ox1 %eep1 hog1 & goat x is1 on ! contr>y1 a /imulant4 ,moreov]1 !re is no evid5ce ( c]ebral effect4 ,! /imulat+ effect ( morph9 on ! n]v\s sy/em 9 "s animals 0 also obs]v$ by ,noe7#fe7 9 exp]im5ts ) ?is sub/ance on ! h$gehog4 ,gu9>d7#bi71 7#cj7 has also %[n t morph9 has no n>cotic effect 9 ! m>mot1 al?\gh ?is animal is v s5sitive to ! drug4 ,two milligrams p] kilo 7 f\nd to be a surely fatal dose = ?is animal4 ,8 exp]im5ts on ! comp>ative toxicity ( morph97#cj71 7#ca7 %[ a consid]able range ( v>iation 9 diff]5t species4 ,?us ! fatal dose = ! dog 0 f\nd to be #j4fe p] kilo1 :ile #g mg p] kilo is ! fatal dose = ! horse4 ,ab\t twice ! am\nt is fatal = ! ox & #j4b mg p] kilo kills ! pig4 ,exp]im5ts ) o!r drugs has %[n t a consid]able range ( v>iation 9 resi/ance exi/s 9 animals ( diff]5t species4 ,noe's7#fe7 /udies on ! comp>ative toxicity ( *loral br\ght out ! int]e/+ fact t ! rabbit is m resi/ant to x ?an ! h$gehog & ! latt] m resi/ant ?an ! gu9ea pig4 ,p]haps ! mo/ /rik+ example ( a diff]5ce 9 reaction ( ! same sub/ance 9 widely diff]5t species is t furni%$ by apocode91 qu991 & yohimb94 ,accord+ to ,gunn7#cb7 ^! sub/ances h be5 f\nd to cause vasodilation 9 w>m-blood$ animals1 b !y con/rict ! blood vessels ( ! frog4 ,exp]im5ts ) apomorph9 likewise %[ t ! reaction to ?is sub/ance v>ies 9 diff]5t species ( animals4 ,! resi/ance ( ! cat to ?is drug is1 accord+ to ,gu9>d7#ca71 t5 times great] ?an t ( ! dog1 & ! latt] is m s5sitive ?an ! rabbit to ! cry/all9e =m ( apomorph9 :5 giv5 intrav5\sly4 ,accord+ to ,kob]t7#de7 amygdal9 is )\t effect on dogs1 b x is poison\s to rabbits4 ,lapicque7#di7 f\nd t ! toxicity ( cur>a v>ies 9 diff]5t species ( frogs1 ! dose requir$ to produce p>alysis 9 ,rana escul5ta be+ ?ree times great] ?an 9 ,bufo vulg>is4 ,weir ,mit*ell7#ei7 po9t$ out long ago t turtles /& enorm\s doses ( cur>a4 ,s*mi$eb]g's exp]im5ts ) caffe9 on ,rana tempor>ia & ,rana escul5ta 7& m rec5tly ^? ( ,jacobi & ,gol[9ski7#db7 ) caffe91 !obrom91 & !ophyll97 are also ( int]e/ 9 ?is connection4 ,^! exp]im5t]s obs]v$ well-m>k$ diff]5ces ( reaction to me?yl-xan?9s 9 ^! closely alli$ =ms4 ,exp]im5ts ) qu99 h %[n t ! action ( ?is sub/ance diff]s 9 "s animals4 ,x causes a fall ( temp]ature imm$iately aft] its adm9i/ration 9 ! gu9ea pig1 b frequ5tly produces1 at fir/1 a rise ( temp]ature1 foll[$ by an unimportant fall1 9 rabbits1 dogs1 & man4 ,! num]\s inve/igations :i* h be5 c>ri$ out on ! effect ( atoxyl )9 rec5t ye>s h contribut$ mu* to ! comp>ative ph>macology ( ?is sub/ance4 ,al?\gh ! symptoms & organic *anges produc$ by ?is sub/ance 9 a v>iety ( animals pres5t no great diff]5ces1 ! resi/ance ( "s has be5 f\nd to v>y2 accord+ to ,k/]7#df7 x is m toxic = dogs ?an = rabbits4 ,a numb] ( o!r sub/ances h be5 f\nd by v>i\s exp]im5t]s to v>y 9 toxicity = diff]5t species ( animals4 ,can?>ad91 ph5ol1 atrop91 & /ry*n9 may be m5tion$ z illu/rations4 ,ph>macological /udies on l[] =ms ( life h also reveal$ m>k$ v>iations 9 ! effect ( "s poisons4 ,obs]vations made by ,danilewski7#ah7 ) hydro*9one indicate t solutions ( #a to #ajj or #bjj are toxic to ,cel5trates1 caus+ p>alysis 9 ^! organisms4 ,e*9od]ms are kill$ )9 "o or two h\rs 9 #a to #a1jjj or #b1jjj solution1 :ile 9 ,v]mes ev5 weak] solutions cause tetanus & f9ally p>alysis4 ,! exp]im5ts ( ,drzew9a7#ai7 ) potassium cyanid are also int]e/+ 9 ?is connection4 ,teleo/s plac$ 9 #ajj cc ( sea wat] conta9+ tw5tie?-normal potassium cyanid %[$ signs ( asphyxia & di$ 9 #aj to #bj m9utes4 ,act9ia plac$ 9 a solution ( sea wat] conta9+ five times z mu* potassium cyanid 7 active on ! ?irte5? day ( ! exp]im5t4 ,simil> results 7 obta9$ ) o!r m>9e organisms4 ,f ^! data x is evid5t t ! toxicity ( a sub/ance may v>y consid]ably 9 diff]5t =ms ( life4 ,x has be5 %[n also by "s inve/igations cit$ by ,salant7#gh7 t ! action ( drugs may be modifi$ by diff]5t conditions 9 ! environm5t z well z 9 ! subject ( ! exp]im5t4 ,! recognition ( ! importance ( ^! factors 9 det]m9+ ph>macological action has contribut$ mu* to ! elucidation ( ! me*anism by :i* drugs & o!r sub/ances produce physiological effects 9 ! body4 ,moreov]1 su* k has (t5 enhanc$ ! !rapeutic value ( ph>maco-dynamic ag5ts & has frequ5tly s]v$ to av]t effects ( an undesirable "* 9 man & dome/ic animals4 ,! results obta9$ 9 "o species ( animals "u a p>ticul> condition d n admit1 !re=e1 ( univ]sal application4 ,fur!rmore1 ! nature ( ! action ( a drug c only be p>tly le>n$ f ! manife/ation ( its acute effects4 ,equally important1 !re=e1 especially 9 /udies on toxicity1 are ! *anges produc$ 9 *ronic intoxication4 ,t ! acute effects ( a sub/ance c h>dly be consid]$ a correct e/imate ( its toxicity is %[n by ! evid5ce obta9$ 9 exp]im5ts on tol]ance & cumulative action ( drugs2 = ! toxicity ( a sub/ance may dim9i% :5 ! sub/ance is giv5 /eadily = a long "t if ! body acquires tol]ance = x4 ,ars5ic1 morph91 & cannabis indica may be cit$ z illu/rations ( drugs1 ! toxicity ( :i* decreases ) repeat$ doses1 :ile digitalis & lead %[ a t5d5cy to increas$ toxicity :5 simil>ly adm9i/]$4 ,moreov] ! acute & *ronic effects are sometimes qualitatively diff]5t4 ,accord+ to ,ig]%eim]7#da7 ! symptoms 9 acute atoxyl intoxication are nausea1 vomit+1 & di>rhea4 ,^! symptoms are abs5t 9 *ronic intoxication1 9 :i* trophic di/urbances ( ! sk9 & inflammation ( ! muc\s membranes 7 ! effects produc$4 ,t ! acute action ( atoxyl diff]s f ! *ronic effects 0 likewise %[n by exp]im5ts on animals4 ,! /udies ( von ,anrep7#e7 on *ronic atrop9 intoxication are ( int]e/ 9 ?is connection1 z he f\nd t aft] #aj to #ae injections ( atrop9 !re is no manife/ation ( symptoms su* z is obs]v$ 9 acute intoxication1 :ile ! effects on ! circulation are also less m>k$1 ! accel]ation ( ! pulse be+ less ?an aft] ! same dose 9 a normal subject n accu/om$ to its use4 ,:5 ! adm9i/ration ( atrop9 is cont9u$ = a long] "t its usual effects on ! pulse disappe> altoge!r2 !re is1 on ! contr>y a decreas$ frequ5cy ( ! pulse4 ,if atrop9 has be5 adm9i/]$ = f two to ?ree weeks1 respiration is likewise affect$4 ,,hi/orical ,,review ,,( ,,! ,,lit]ature ,,on ,,! ,,toxicity ,,( ,,caffe94 ,caffe9 0 discov]$ 9 #ahbj by ,runge17#gg7 ,pelleti]17#fj7 & ,robiquet7#ge7 & 0 fir/ analyz$ by ,dumas & ,pelleti]17#bj7 b its exact p]c5tage composition 0 det]m9$ by ,pfaff & ,liebig17#ga71 7#gb7 :ile to ,h]zog 7#ac71 7#ah7 belongs ! cr$it ( hav+ e/abli%$ t x is basic4 ,/reck]7#hb7 prep>$ caffe9 syn!tically by heat+ !obrom9 silv] & me?yl iodid 9 a clos$ tube = #bd h\rs4 ,soon aft] its discov]y 9 c(fee ,oudry7#fg7 report$ ! pres5ce ( a sub/ance 9 tea :i* he call$ !94 ,its id5tity ) caffe9 0 e/abli%$ #ae ye>s lat] by ,job/7#dc7 & also by ,muld]47#fb71 7#fc7 ,accord+ to ,brill17#ac7 ,muld] 7#ahch7 0 also ! fir/ to p]=m exp]im5ts ) caffe9 on animals4 ,aft] ! adm9i/ration ( "o-half gra9 to a pregnant rabbit he obs]v$ loss ( appetite & kyphosis4 ,! rabbit abort$ b recov]$ f ! effects ( caffe94 ,x has s9ce be5 made ! subject ( num]\s inve/igations :i* 7 c>ri$ out on a v>iety ( animals4 ,obs]vations ) caffe9 7 also made on ! human subject4 ,ab\t f\r ye>s aft] ,muld] publi%$ 8 results1 ,lehmann7#ea7 7#ahdb7 report$ exp]im5ts on a numb] ( p :o 7 giv5 caffe94 ,! adm9i/ration ( f #b to #aj gra9s ( ! alkaloid 0 foll[$ by heada*e1 palpitation ( ! he>t1 increas$ frequ5cy & irregul>ity ( ! pulse1 t9nitus aurium1 photopsia1 insomnia1 & ev5 delirium4 ,simil> exp]im5ts report$ by ,fr]i*s7#be7 7#ahdf7 indicate t 9 doses ( #be gra9s x may induce sev]e symptoms ab\t #ae m9utes aft] its adm9i/ration4 ,he also obs]v$ circulatory z well z n]v\s symptoms & vomit+4 ,accord+ to ,alb]s7#b7 7#aheb71 #d4e gra9s ( caffe9 citrate inject$ subcutane\sly into ! ?igh ( a rabbit 0 soon foll[$ by dim9i%$ motion & tremors ( ! op]at$ ?igh4 ,o!r symptoms report$ 7 spasms ( ! facial muscles1 increas$ respiratory movem5ts1 & m5tal confusion4 ,( int]e/ 9 ?is connection are ! exp]im5ts ( ,cogswell7#ag7 7#aheb7 on frogs4 ,he conclud$ t 9 po9t ( de/ructive action on ! tissues1 caffe9 is f> sup]ior to morph9 & may be comp>$ to /ry*n9 & coni91 its action on ! n]v\s sy/em he believ$ to be pr9cipally conf9$ to ! effect on ! bra9 & sp9al cord4 ,lehmann7#eb7 7#ahec7 obs]v$ increas$ frequ5cy ( he>t action aft] ! adm9i/ration ( #d gra9s1 :i* 7 giv5 ) a normal diet to an adult man4 ,:5 ! dose 0 d\bl$ ! frequ5cy ( ! pulse 0 /ill m increas$1 he>t action became /rong]1 & tremors & confusion ( ?\ght ) excitem5t ( ! imag9ation made _! appe>ance4 ,!re 0 also an increas$ desire to micturate4 ,/uhlmann & ,falck7#hc7 7#aheg7 7 ! fir/ to make a /udy ( ! toxicity ( caffe9 on animals ( diff]5t species4 ,! adm9i/ration ( #j4e gram ( caffe9 subcutane\sly or p] rectum 9 rabbits induc$ tremors1 tonic & clonic convulsions1 p>alysis1 & increas$ frequ5cy ( respiration at fir/ foll[$ by viol5t dyspnoea4 ,on autopsy he notic$ conge/ion ( ! organs & 9 two ( ! ?ree rabbits exp]im5t$ ^u puncti=m hemorrhages ( ! bra9 ) conge/ion ( ! m5+es 7 f\nd4 ,9 ! o!r rabbit anemia ( ! bra9 0 obs]v$4 ,exp]im5ts on cats 7 c>ri$ out by subcutane\s1 intrav5\s1 & rectal injections4 ,! symptoms obs]v$ aft] ! adm9i/ration ( #j4e to #j4g gram ( caffe9 7 ! same z 9 rabbits except t ! cats develop$ di>rhea :5 caffe9 0 giv5 & no anatomic lesions 7 f\nd on autopsy4 ,! effect ( caffe9 on dogs indicat$ t 9 subjects ( m$ium weight a dose ( #j4e gram giv5 by m\? might produce re/lessness & increas$ frequ5cy ( respiration1 :ile ! injection ( ! same am\nt intrav5\sly into su* animals may cause dea?4 ,l>ge1 full-gr[n dogs1 h[ev]1 surviv$ an intrav5\s injection ( #b grams ( caffe91 %[+ symptoms ( incoord9ation1 salivation1 & frequ5t defecation4 ,^! inve/igators also made obs]vations on caffe91 us+ pigeons & o!r birds2 #j4e to #j4a gram introduc$ into ! /oma* caus$ vomit+1 di>rhea1 tonic1 b m frequ5tly clonic1 convulsions1 incoord9ation1 tremors1 p>esis1 & p>alysis4 ,9 a few1 b n 9 all ( ! birds1 !re 0 at fir/ increas$ frequ5cy ( respiration foll[$ by dyspnoea & circulatory di/urbances4 ,^! am\nts ( caffe9 prov$ fatal 9 all ( ! exp]im5ts on birds4 ,inflammation ( ! inte/9al mucosa & conge/ion ( ! m5+es 7 ! only *anges f\nd on autopsy4 ,/uhlmann & ,falck also /udi$ ! effects ( caffe9 on fi%es & toads4 ,mits*]li*7#fj7 7#aheh7 f$ #j4d gram ( caffe9 ) bread to a rabbit & notic$ l[]$ temp]ature1 fatigue1 convulsions1 fir/ increas$ !n decreas$ frequ5cy ( respiration1 & on autopsy conge/ion ( all ! visc]a4 ,he also report$ obs]vations on two frogs1 "o ( :i* 0 giv5 "o-sixte5? ( a gra9 ( caffe9 9 a pill ) bread4 ,x 0 adm9i/]$ to ! o!r frog 9 aque\s solution1 b ! mode ( adm9i/ration 0 n publi%$4 ,! symptoms obs]v$ 7 9 ! ma9 ! same z 9 rabbits4 ,9 pigeons #j4abe gram introduc$ into ! /oma* caus$ sev]e vomit+1 muscul> incoord9ation1 tonic rigidity ( ! limbs1 & retraction ( ! head4 ,respiration 0 increas$ 9 frequ5cy4 ,dea? foll[$ )9 #c h\rs & #ae m9utes4 ,f a s]ies ( exp]im5ts on frogs :i* ,hoppe7#ch7 c>ri$ out 7#aheh7 by apply+ "o-f\r? ( a gra9 ( caffe9 to ! muscles ( ! back1 he conclud$ t caffe9 causes p>alysis ( ! n]ves1 sp9al cord1 & bra91 s5sation be+ p>alyz$ be=e movem5t4 ,! injuri\s action ( caffe9 proce$s1 accord+ to ,hoppe1 f ! sp9al cord4 ,?is 0 bas$ on exp]im5ts on two frogs1 ,rana escul5ta1 9 :i* ! "r leg 0 amputat$1 ! n]ve be+ left intact1 :ile ! n]ve ( ! o!r leg 0 ligat$4 ,at ! end ( #cj m9utes p>alysis 0 m m>k$ on ! "r ?an on ! left side4 ,9 ano!r frog ( ! same species he resect$ ! femoral n]ve on ! "r side2 ab\t #a h\rs aft] ! adm9i/ration ( caffe9 convulsions 7 obs]v$4 ,! left leg 0 rigid1 b ! "r 0 relax$4 ,voit7#he7 7#ahfj7 ligat$ ! vessels ( ! "r l[] extremity1 cut ! n]ves ( ! left leg1 & introduc$ a few drops ( caffe9 solution into ! /oma*4 ,%ortly aft]w>ds tetanus ( ! "r leg occurr$ on t\*+ ! back ( ! animal2 ! left leg 0 motionless4 ,lat] ! entire body exhibit$ tetanic convulsions4 ,f ?is & simil> exp]im5ts ,voit conclud$ t caffe9 acts fir/ & pr9cipally on ! c5tral n]v\s sy/em1 & t caffe9 is also poison\s to n]ve & muscle fib]s1 z !y die :5 a solution ( caffe9 is appli$ to !m4 ,! action ( caffe91 accord+ to ,voit1 is simil> 9 great "p to t ( /ry*n94 ,! effect on ! blood vessels is p>ticul>ly int]e/+1 z ,voit obs]v$ dilatation ( ! vessels1 due z he ?\ght to muscul> p>alysis1 & also transudation & conge/ion ( ! capill>ies4 ,kurzak7#dh7 7#ahfj7 made a /udy ( ! comp>ative toxicity ( caffe9 9 frogs & rabbits & came to ! conclusion t ! le?al dose = frogs is ab\t "o-sev5? ( t = rabbits4 ,caffe9 citrate 9 ! =m ( cry/als 0 adm9i/]$ 9 bo? cases by m\?4 ,! doses giv5 to frogs 7 #a to #a4e gra9s4 ,he obs]v$ convulsions & increas$ respiratory activity at fir/2 aft] "o h\r respiration dim9i%$ & volunt>y muscul> activity disappe>$4 ,ev5 on ! second day convulsions 7 sometimes notic$4 ,dea? occurr$ at ! end ( ! fir/ or second day4 ,exp]im5ts on only two rabbits 7 report$1 #j4h gram ( caffe9 citrate caus+ ! dea? ( "o at ! end ( #ac h\rs4 ,! symptoms notic$ 7 ! same practically z 9 frogs1 b x is int]e/+ to obs]ve t ec*ymosis ( ! muc\s membranes ( ! /oma* ne> ! c>dia 0 ! only lesion f\nd on autopsy4 ,sev]al exp]im5ts made on diff]5t days on ! o!r rabbit indicat$ t ! toxic dose exce$$ #j4e gram1 :ile small] doses caus$ b v mild symptoms4 ,accord+ to ,g5tilhomme7#bg7 7#ahfg71 aft] caffe9 ! reflexes are at fir/ dim9i%$ & !n disappe> altoge!r4 ,dea? is produc$ by /iffness & immobility ( all ! muscles1 p>ticul>ly ( ! muscles ( respiration1 ?us caus+ asphyxia4 ,he fur!rmore held t caffe9 has no effect on c>diac or smoo? muscle fib]1 its action be+ specific on volunt>y muscle fib]1 contractions ( :i* he obs]v$ "u ! microscope1 ?us diff]+ completely f /ry*n91 :i* is a n]ve poison4 ,^! obs]vations seem$ to be confirm$ by ,pratt7#gd7 7#ahfh71 :o report$ t ! isolat$ po/]ior extremities & muscle fib]s ( ! toad plac$ 9 a solution ( caffe9 7#a gra9 to a w9eglassful ( wat]7 = ?ree m9utes 7 contract$1 :ile controls plac$ 9 di/ill$ wat] 7 relax$4 ,?is exp]im5t is1 ( c\rse1 defective1 z normal salt solution %\ld h be5 us$ 9 bo? cases4 ,:5 ! muscul> fib]s previ\sly imm]s$ 9 caffe9 solution 7 plac$ "u ! microscope viol5t contractions 7 obs]v$4 ,! same au?or adm9i/]$ f #b to #ah gra9s at a dose to five heal?y "y m54 ,aft] ! adm9i/ration ( #ab gra9s he notic$ m5tal angui%1 tremors ( ! h&s & arms1 & insomnia4 ,doses "u #e gra9s _h no m>k$ effect except a dim9ution 9 ! frequ5cy ( ! pulse & wakefulness4 ,ab\t ! same "t ,amory7#d7 7#ahfh7 publi%$ ! results ( 8 /udies on ! toxicity ( caffe9 9 cats1 dogs1 rabbits1 & pigeons4 ,9 all cases v l>ge doses 7 introduc$ directly into ! /oma* by means ( a tempor>y ga/ric fi/ula4 ,t5 gra9s giv5 9 meat to a dog caus$ re/lessness1 b no o!r symptoms4 ,doses ( #cj gra9s & above 7 inv>iably fatal4 ,sev5ty-?ree gra9s giv5 to a cat caus$ dea? )9 #bj m9utes4 ,f obs]vations on frogs1 gu9ea pigs1 rabbits1 & on "o dog1 ,lev57#ec7 7#ahfh7 conclud$ t caffe9 :i* he gave 9 ! =m ( ! citrate 9 doses ( #aj mg to frogs1 f #aej to #bjj mg to gu9ea pigs1 & ?ree to f\r times ! latt] am\nt to rabbits1 /imulates ! c5tral n]v\s sy/em & ! volunt>y1 c>diac1 & smoo? muscles4 ,he f\nd t #j4i gram caffe9 0 fatal = a rabbit :5 inject$ subcutane\sly1 :ile #a gram ( ! citrate 0 n toxic = a dog ( m$ium size4 ,caffe9 appli$ directly to muscle fib] causes tetanus & de/roys muscul> contractility1 :ile a n]ve fib] simil>ly treat$ loses its irritability4 ,accord+ to ,johans57#dd7 7#ahfi71 caffe9 acts directly on ! muscul> fib]4 ,aft] ! subcutane\s injection ( #j4jb gram ( caffe9 into frogs1 he obs]v$ contraction ( ! muscles at ! site ( injection1 !n contraction ( ! ant]ior extremities1 & f9ally ! po/]ior extremities become rigid & ext5d$4 ,johans5 obs]v$ muscul> rigidity aft] caffe91 ev5 aft] cur>a 0 inject$1 or aft] ligat+ ! vessels1 or cutt+ ! n]ves :i* supply ! muscles4 ,he also obs]v$ t l>ge doses ( caffe9 dim9i% muscul> irritability4 ,:5 c>diac muscle 0 poison$ ) caffe91 microscopical exam9ation %[$ t ! /riations disappe>$4 ,johans5 also /ates t reflexes disappe> aft] caffe9 poison+4 ,he nev] obs]v$ tetanus 9 frogs1 b report$ tonic & clonic convulsions z a result ( caffe9 poison+ 9 mammals4 ,some:at diff]5t effects ( caffe9 9 frogs 7 obs]v$ by ,bu*heim & ,eis5m5g]7#ad7 7#ahgj74 ,aft] ! injection ( #b p] c5t ( ! citrate ! frogs soon become inactive4 ,he also obs]v$ muscul> twit*+ ( ! extremities1 :i* gradually increas$1 ) rigidity ( ! muscles & opi/hotonos1 :ile respiration became sl[ & sup]ficial1 f9ally /opp+ altoge!r4 ,aub]t7#f7 7#ahgb7 /udi$ ! toxicity ( caffe9 9 man & o!r animals4 ,aft] ! +e/ion ( #j4cf gram1 he obs]v$ dizz9ess1 b doses ( #j4ab & #j4bd gram 7 )\t any app>5t effect4 ,on ! o!r h&1 a dose ( #j4e gram ( caffe9 0 foll[$ by increas$ frequ5cy ( ! pulse1 :i* soon disappe>$4 ,aft] "o h\r he notic$ dizz9ess & trembl+ ( ! h&s1 :i* likewise pass$ away soon4 ,! injection ( #j4af gram ( a #b p] c5t solution ( caffe9 into ! jugul> ve9 ( a rabbit weigh+ #a1jij grams caus$ tetanus & dea? 9 two & "o-half m9utes1 & #j4ab gram inject$ into a rabbit weigh+ #ihj grams caus$ dea? 9 "o m9ute4 ,mu* l>g] doses c\ld be borne1 h[ev]1 :5 artificial respiration 0 resort$ to4 ,a dog :i* 0 giv5 #c grams ( caffe9 surviv$ :5 artificial respiration 0 p]=m$4 ,aub]t reports1 on ! o!r h&1 a simil> exp]im5t ) #j4be gram ( caffe9 :i* t]m9at$ fatally4 ,t caffe9 may give rise to diff]5t effects 9 v>i\s species ( animals 0 obs]v$ = ! fir/ "t by ,b5nett47#i7 ,he /udi$ its action on frogs1 mice1 rabbits1 & cats1 & attempt$ to det]m9e ! m9imum fatal dose 9 rabbits & cats4 ,he also report$ exp]im5ts ) !94 ,9 8 fir/ communication on ! subject he /ates t ! adm9i/ration ( !9 to rabbits fir/ increas$ & !n dim9i%$ ! frequ5cy ( respiration1 :ile ! pulse 0 decreas$ 9 frequ5cy4 ,caffe91 :i* he app>5tly ?\ght 0 diff]5t f !91 caus$ increas$ frequ5cy ( respiration1 :ile ! pulse 0 m>k$ly ret>d$ aft] a prelim9>y accel]ation4 ,he also notic$ conge/ion ( ! e>s1 muscul> incoord9ation1 tetanus1 p>alysis1 dim9i%$ reflexes1 & contraction ( ! pupils4 ,b5nett report$ ! m9imum fatal dose ( caffe9 = a rabbit weigh+ #c4be p\nds z be+ #e4be-e4e gra9s4 ,! symptoms 9 cats aft] ! adm9i/ration ( toxic doses ( !9 or ( caffe9 7 great excitem5t1 p>alysis alt]nat+ ) convulsions1 & pr(use salivation4 ,! m9imum fatal dose = a cat weigh+ #e p\nds 01 accord+ to ,b5nett1 #f gra9s ( caffe9 & #e4e gra9s ( !94 ,only "o exp]im5t on a m\se is report$2 ! adm9i/ration ( #j4a gra9 prov$ fatal4 ,! symptoms 7 ! same z ^? obs]v$ 9 cats & rabbits aft] ! adm9i/ration ( caffe94 ,! exp]im5ts on frogs indicate t ! symptoms 7 ab\t ! same z ^? previ\sly describ$ 9 ! case ( w>m-blood$ animals except t ! reflexes are almo/ completely lo/ aft] ! subcutane\s injection ( doses ( "o-sixte5? to "o-twelf? ( a gra94 ,! latt] dose 0 fatal = frogs4 ,x w\ld be ( int]e/ to "k ! comp>ative toxicity ( caffe9 to frogs & mammals1 b un=tunately ! weights 7 n report$4 ,s*mi$eb]g7#gi7 7#ahgd7 notic$ t ! adm9i/ration ( #bj mg ( caffe9 to frogs weigh+ ab\t #de grams 0 foll[$1 9 ,rana escul5ta1 9 ab\t #be m9utes1 by increas$ reflexes1 #g m9utes lat] by tetanus4 ,sev]al attacks occurr$1 b tonic spasms 7 nev] obs]v$4 ,on ! contr>y1 :5 ! same am\nt ( caffe9 0 giv5 to ,rana tempor>ia weigh+ #de grams he notic$ a m>k$ dim9ution ( ! reflexes & tonic rigidity ( ! muscles aft] #bc m9utes2 ! reflexes 7 greatly increas$1 h[ev]1 ab\t #bd h\rs lat]4 ,! frogs 7 "u obs]vation = ?ree days1 & al?\gh symptoms 7 /ill pres5t at ! end ( ?is "t 9 ! subjects ( bo? species tetanus 0 nev] obs]v$ 9 ,rana tempor>ia4 ,p]etti's7#gj7 7#ahge7 /udies on ! effects ( caffe9 7 conf9$ *iefly to obs]vations on dogs4 ,he also made obs]vations on a few rabbits & report$ an exp]im5t on "o cat to :i* he adm9i/]$1 by subcutane\s injection1 #j4ah gram ( caffe9 p] kilo & notic$ increas$ frequ5cy 9 la*rymation & cry+4 ,! cat 0 f\nd dead ! next day4 ,! subcutane\s injection ( a rabbit 9 :i* artificial respiration 0 in/itut$ ) #j4cf gram ( caffe9 p] kilo prov$ fatal soon aft] ! injection )\t any manife/ation ( symptoms4 ,small doses ( caffe91 #j4a gram1 giv5 to a rabbit weigh+ #c1fgj grams1 fail$ to produce any visible effects4 ,doses "u #j4a gram p] kilo likewise fail$ to induce any symptoms 9 dogs4 ,:5 #j4a gram ( caffe9 p] kilo 0 giv5 by m\? or subcutane\sly x 0 foll[$ by re/lessness1 salivation1 rigidity ( h9d legs1 & vomit+4 ,9 bo? in/ances ! dogs recov]$4 ,! symptoms 7 m sev]e :5 ! dose 0 increas$ to #j4ahe gram p] kilo1 b ev5 9 ?is case ! dog recov]$4 ,a dose ( #j4b gram p] kilo1 h[ev]1 prov$ fatal4 ,h5neguy7#cf7 7#ahge7 exp]im5t$ on ?ree frogs to :i* he gave #j4ja gram ( caffe9 citrate subcutane\sly4 ,he obs]v$ mild /imulation ( ! n]v\s sy/em & ( ! muscles1 z well z increas$ c>diac activity4 ,lat]1 volunt>y movem5t & respiration disappe>$ & s5sations dim9i%$1 b convulsions ( ! extremities appe>$4 ,c>diac activity 0 !n dim9i%$1 ! he>t be+ f9ally arre/$ 9 sy/ole4 ,s9ce ! motor n]ves reta9$ _! irritability ev5 aft] ! reflexes disappe>$1 he conclud$ t ! loss ( motion 0 due to ! action ( caffe9 on ! n]ve c5t]s4 ,b9z7#aa7 7#ahgh7 report$ exp]im5ts on dogs & also made "s obs]vations on man ) caffe94 ,! subcutane\s injections ( #j4b gram caffe9 may prove fatal to dogs1 al?\gh "s survive su* a dose4 ,! toxic dose 9 man v>ies f #j4e to #a4e grams4 ,di/urbance ( ! circulation1 su* z palpitation ( ! he>t & fullness ( pulse1 re/lessness1 & di>rhea 7 ! symptoms he obs]v$4 ,ext5sive inve/igations on ! action ( caffe9 7 c>ri$ out by ,leblond7#ej7 7#ahhc71 :o /udi$ its effect on ! circulation 9 man & l[] animals1 & its toxicity 9 ! l[] animals alone4 ,five to tw5ty c5tigrams ( caffe9 & #j4jf to #j4be gram ( salicylate ( soda 7 dissolv$ & inject$ into ! muscles ( ! ?igh ( "y gu9ea pigs weigh+ a little ov] #cjj grams4 ,9 ! ?ree exp]im5ts report$ ! dea? ( ! animals occurr$ aft] #bc m9utes1 #dj m9utes1 & #a h\r & #bj m9utes4 ,symptoms appe>$ 9 f #aj to #ae m9utes aft] ! injection ( caffe94 ,incoord9ation ( movem5ts1 convulsions1 bo? tonic & clonic1 opi/hotonos1 tremors1 increas$ frequ5cy ( respiration1 ataxia1 p>alysis 7 ! symptoms obs]v$4 ,x is wor?y ( note t ! appe>ance ( p>esis prec$$ ! convulsions4 ,dim9i%$ s5sation 0 report$ 9 "o pig1 b no s5sory di/urbances nor reflexes _h be5 obs]v$ 9 ! o!r4 ,two rabbits1 "o ( :i* receiv$ #j4e & ! o!r ab\t #j4c gram ( caffe9 p] kilo ) equal p>ts ( salicylate ( soda1 7 inject$ subcutane\sly into ! ?igh4 ,dim9i%$ s5sation1 p>esis ( ! po/]ior extremities1 hyp]excitability1 convulsions1 opi/hotonos1 dilation ( ! ve9s ( ! e> 7 obs]v$4 ,dea? foll[$ 9 #a h\r & #bc m9utes 9 "o rabbit & 9 #c h\rs & #g m9utes 9 ! o!r4 ,filehne7#bb7 7#ahhf7 exp]im5t$ ) caffe9 on ,rana escul5ta & ,rana tempor>ia4 ,! subcutane\s injection ( #g mg ( caffe9 into ,rana escul5ta caus$ tetanus1 :ile #ej mg giv5 by m\? caus$ tonic spasms4 ,he fur!r /at$ t ! diff]5ce betwe5 ,rana escul5ta & ,rana tempor>ia z reg>ds ! reaction to caffe9 0 "o ( degree only4 ,amat7#c7 7#ahhi7 report$ exp]im5ts on ?ree gu9ea pigs1 9 :i* #j4d to #j4e gram p] kilo inject$ subcutane\sly prov$ fatal )9 #ch & #dd m9utes4 ,"o gu9ea pig :i* receiv$ #j4a gram ( caffe9 p] kilo surviv$4 ,! symptoms obs]v$ 9 ! two fatal cases 7 g5]al muscul> rigidity & convulsions4 ,p>isot7#fh7 7#ahij7 made a /udy ( ! toxicity ( caffe9 on diff]5t species ( animals4 ,unlike mo/ ( 8 pr$ecessors1 h[ev]1 he report$1 at lea/ 9 "s cases1 ! weight ( ! animals on :i* he work$4 ,aft] ! subcutane\s & intramuscul> injections ( f #e to #bj mg ( caffe9 into ,rana tempor>ia weigh+ f #ad to #af grams1 he notic$ increas$ irritability at fir/2 lat]1 a loss ( reflexes1 inability to use ! muscles1 complete muscul> rigidity resembl+ rigor mortis1 & also cessation ( he>t action4 ,! effect ( caffe9 produc$ 9 ! gre5 frog 0 analog\s to t obs]v$ 9 /ry*n9 poison+4 ,p>isot f\nd1 h[ev]1 t muscul> rigidity develop$1 al?\gh v gradually1 also 9 ! gre5 frog1 b x set 9 mu* lat] ?an 9 frogs ( ! o!r species & )\t sup]s$+ ! clonic convulsions4 ,accord+ to ,p>isot1 ! muscul> rigidity aft] caffe9 p]si/s aft] ! de/ruction ( ! bra9 & sp9al cord1 ?us %[+ t x is n ( n]v\s orig94 ,he fur!r emphasiz$ ! diff]5ce 9 ! behavior ( ^! two species ( frogs t[>d caffe9 by /at+ t he nev] obs]v$ tetanic convulsions 9 ! r$ frog4 ,8 exp]im5ts also indicate t ! gre5 frog is m resi/ant to caffe9 ?an ,rana tempor>ia1 z ! same doses :i* are fatal = ! latt] 7 only toxic = ,rana escul5ta4 ,! numb] ( exp]im5ts1 h[ev]1 is too few to ju/ify a positive conclusion on ?is po9t4 ,p>isot also made "s exp]im5ts on turtles4 ,! results he obta9$ %[ t caffe9 is at lea/ z toxic = ^! animals z = ! frogs he exp]im5t$ ^u1 #j4cc gram p] kilo 7c>apace n includ$ 9 weight7 hav+ prov$ fatal )9 #bd h\rs4 ,two exp]im5ts on "o pigeon 7 also report$ by ! same obs]v]2 two doses ( #j4jf gram p] kilo giv5 at an int]val ( f\r h\rs caus$ m5tal depression & muscul> rigidity1 b ! pigeon surviv$4 ,exp]im5ts ) caffe9 on ! human subject made by ,p>isot %[$ t man is f> m susceptible to ?is sub/ance ?an ! o!r animals he inve/igat$4 ,aft] ! +e/ion ( #j4c gram ( caffe9 symptoms ( intoxication po9t+ to c]ebral di/urbance appe>$1 :i* became m m>k$ :5 ! size ( ! doses 0 increas$4 ,x w be notic$ t ! nature ( ! action ( caffe91 :e!r x is a n]ve or a muscle poison1 =m$ ! subject ( sev]al inve/igations4 ,b9z7#aa7 7#ahij7 br\ght =w>d additional evid5ce 9 support ( ! view t caffe9 acts prim>ily on ! ganglion cells1 & n on ! muscle directly4 ,?is he has %[n by inject+ #j4e gram into ea* ( two rabbits aft] cutt+ ! sciatic n]ve on "o side2 9 "o case he also resect$ ! obdurator & crural n]ves on ! same side4 ,clonic spasms develop$ 9 bo? subjects soon aft] caffe9 0 giv51 b 9 ea* rabbit ! side op]at$ ^u rema9$ p>alyz$4 ,baldi7#h7 7#ahia7 /udi$ ! action ( caffe9 on ,rana escul5ta4 ,aft] inject+ f #d to #bj mg tetanus1 su* z obs]v$ 9 /ry*n9 poison+1 0 notic$4 ,frhn]7#bf7 7#ahib7 made obs]vations on ! comp>ative toxicity ( caffe9 9 dome/icat$ animals4 ,aft] ! adm9i/ration ( #e grams ( caffe9 sodium salicylate by m\? to a dog weigh+ #aj kilos1 he notic$ salivation1 re/lessness1 vomit+1 & convulsions z 9 /ry*n9 poison+4 ,dea? occurr$ ?ree h\rs aft] ! drug 0 giv54 ,on autopsy he notic$ mild inflammation ( ! muc\s membranes ( ! /oma* & inte/9es & edema ( ! lungs2 ! he>t 0 9 dia/ole4 ,a dose ( #b grams ( caffe9 sodium salicylate giv5 to ! same animal subcutane\sly two days previ\sly provok$ only v slight symptoms4 ,! subcutane\s injection ( #aj grams ( ! same prep>ation into a pig weigh+ #cj kilos caus$ dea? 9 two & a half h\rs1 ) ! production ( symptoms ( di/urbance ( ! n]v\s sy/em & ( ga/ro9te/9al irritation4 ,! same dose p] kilo ( body weight giv5 to a goat likewise caus$ dea? 9 two & a half h\rs aft] its adm9i/ration4 ,exam9ation on autopsy reveal$ inflammation ( ! ga/ro9te/9al tract4 ,simil> lesions 7 f\nd 9 a horse kill$ by #ajj grams ( caffe91 9 :i* he also notic$ hemorrhage ( ! mucosa 9 ! fundus ( ! /oma*4 ,g\rewit*7#bh7 7#aijg7 conduct$ exp]im5ts ) caffe9 on rabbits1 pigeons1 & :ite rats4 ,x appe>s f 8 protocol t s+le doses ( ab\t #j4b to #j4be gram caffe9 p] kilo giv5 subcutane\sly prov$ to be fatal4 ,he /ates1 h[ev]1 t ! resi/ance to caffe9 0 m>k$ly dim9i%$1 :5 its adm9i/ration 0 repeat$ daily1 = mu* small] am\nts suffic$ to cause dea? 9 ^! animals4 ,a dose ( #abj mg ( caffe9 p] kilo prov$ fatal aft] ! ?ird injection4 ,:5 ! dose 0 increas$ to #agj mg p] kilo1 ! animal succumb$ to ! effects ( caffe9 aft] ! second injection4 ,8 exp]im5ts on ! o!r animals d n indicate ! degree ( resi/ance to caffe91 s9ce ! weights = "s 7 n giv5 :ile = ! o!rs no attempt 0 made to det]m9e ! m9imum toxic or fatal dose4 ,maurel7#ee7 7#aijg7 /udi$ ! influ5ce ( diff]5t me?ods ( adm9i/ration on ! toxicity ( caffe9 on frogs & rabbits4 ,he det]m9$ ! m9imum toxic & le?al doses ( caffe9 hydrobromid :i* he employ$ 9 #a to #b p] c5t solutions4 ,he conclud$ f 8 exp]im5ts t ! toxicity ( caffe9 :5 giv5 by m\? is twice z great = ! frog z = ! rabbit4 ,m rec5tly ,hale7#cc7 c>ri$ out a numb] ( exp]im5ts on gu9ea pigs 9 :i* he det]m9$ ! toxicity ( caffe9 giv5 9 ! =m ( ! citrate & made into a pill ) mucilage ( acacia & arr[-root />*4 ,aft] ! pill 0 dri$ x 0 f$ to ! animal1 due precaution be+ tak5 t none ( x 0 lo/ dur+ fe$+4 ,f exp]im5ts on gu9ea pigs :i* receiv$ doses ( #j4c to #j4f gram caffe9 citrate1 ! foll[+ data h be5 report$3 ,?ree decigrams p] kilo giv5 to "o pig 0 n fatal4 ,( ?ree pigs :i* receiv$ #j4d p] kilo1 "o di$ & two surviv$4 ,exactly ! same results 7 obta9$ 9 ?ree o!rs :i* receiv$ #j4e p] kilo4 ,two gu9ea pigs1 :i* receiv$ #j4ee & #j4f p] kilo ea*1 di$ aft] #ae & #g h\rs1 respectively1 :ile ano!r animal surviv$ a dose ( #j4de p] kilo4 ,?is review ( ! lit]ature on ! toxicity ( caffe91 al?\gh be>+ evid5ce ( consid]able inve/igation & ext5d+ ov] ?ree-qu>t]s ( a c5tury1 is l>gely qualitative 9 "*4 ,x appe>s f ! exp]im5ts t ! ma9 object ( ! inve/igations 0 to asc]ta9 ! nature ( ! action ( caffe91 :e!r x is a muscle or a n]ve poison4 ,! comp>ative toxicity 9 diff]5t species ( animals by ! accurate det]m9ation ( ! toxic & fatal doses receiv$ b little att5tion4 ,to fill ! gap 9 our k ( ! toxic effects ( caffe91 ! pres5t inve/igation 0 und]tak54 ,?is1 x w be se51 prov$ to be a mo/ labori\s task1 because 9 ! l>ge numb] ( exp]im5ts c>eful obs]vations %[$ t individuals ( ! same species v>i$ consid]ably 9 _! reaction to ! drug4 ,num]\s o!r factors1 z w be %[n1 7 also f\nd to play an important "p 9 ! det]m9ation ( ! toxicity ( caffe94 ,,acute ,,caffe9 ,,intoxication4 ,! object ( ^! exp]im5ts 0 to det]m9e ! resi/ance to caffe9 9 v>i\s species ( animals & by v>i\s me?ods ( adm9i/ration4 ,caffe9 0 !re=e giv5 by m\? & inject$ subcutane\sly into ! p]itoneal cavity1 into ! muscles1 & intrav5\sly4 ,z f> z c\ld be judg$ by appe>ance1 heal?y animals 7 select$ = ! subjects ( ! exp]im5ts1 b z x is impossible to diagnose ) any degree ( accuracy ! condition ( ! animal :ile x is alive1 po/ mortem exam9ations 7 resort$ to 9 _m cases 9 :i* ! issue ( ! exp]im5t 0 fatal4 ,s9ce ! age ( ! animal may modify toxicity full gr[n1 z well z "y1 animals 7 employ$ = ^! exp]im5ts2 diet1 race1 & season also play an important "p 9 det]m9+ ! toxicity ( a drug & ^! factors 7 also tak5 into acc\nt 9 ! pres5t inve/igation4 ,,exp]im5ts ,,on ,,rabbits4 ,animals ( diff]5t v>ieties 7 us$ & 7 giv5 caffe9 by all ( ! me?ods indicat$ 9 ! prec$+ p>agraph4 ,"s ( ! rabbits employ$ 9 ^! exp]im5ts receiv$ oats1 o!rs receiv$ a diet exclusively ( c>rots = sev]al days or weeks previ\s to ! adm9i/ration ( caffe94 ,! exp]im5ts 7 conduct$ at all seasons ( ! ye>4 ,,subcutane\s ,,injection4 ,f a /udy ( ! lit]ature on ! toxicity ( caffe9 x seem$ t ab\t #aej mg p] kilo is probably ! le?al dose = ! rabbit :5 ! drug is inject$ subcutane\sly4 ,prelim9>y obs]vations 7 !re=e c>ri$ out ) su* a dose1 b x 0 f\nd1 on ! contr>y1 t ?is am\nt p] kilo 0 h>dly suffici5t to induce symptoms 9 ! great majority ( cases4 ,,s]ies ,a4 ,doses ( #adg to #afg mg ( caffe9 p] kilo 7 employ$ 9 ^! exp]im5ts4 ,rabbit #ccb4 ,belgian h>e1 female4 ,weight1 #a1jgj grams4 ,diet1 oats4 ,m>* #be3 #h4e cc #b p] c5t caffe9 7#aeh mg p] kilo7 inject$ subcutane\sly at #b4ae p4 m42 #d p4 m41 reflexes increas$2 #e4de p4 m41 increases ( reflexes /ill m m>k$4 ,m>* #bf3 ,rabbit look$ normal2 no symptoms obs]v$4 ,rabbit #cca4 ,belgian h>e1 female4 ,weight1 #a1agj grams4 ,diet1 oats4 ,m>* #be3 #b4ae p4 m41 #i cc #b p] c5t caffe9 7#aec mg p] kilo7 inject$ subcutane\sly2 #d p4 m41 reflexes increas$2 #e4de p4 m41 condition ! same4 ,m>* #bf3 ,rabbit looks normal2 no symptoms obs]v$4 ,rabbit #cbh4 ,belgian h>e1 female4 ,weight1 #a1bjj grams4 ,diet1 oats4 ,m>* #be3 #i cc #b p] c5t caffe9 inject$ subcutane\sly 7#aej mg p] kilo72 #d p4 m41 reflexes increas$2 #e4de p4 m41 reflexes increas$ b n m>k$ly4 ,m>* #bf3 ,no symptoms2 rabbit looks normal4 ,rabbit #cbb4 ,:ite female4 ,weight1 #a1jfe grams4 ,diet1 oats4 ,m>* #ag3 #h cc #b p] c5t caffe9 7#aej mg p] kilo7 inject$ subcutane\sly at #aa4ee a4 m42 #ab4ee p4 m41 reflexes increas$1 b no tetanus nor any o!r symptoms4 ,m>* #ah3 ,rabbit runn+ ar\nd 9 cage2 condition app>5tly normal4 ,m>* #be3 ,condition ( rabbit good4 ,rabbit #bag4 ,:ite4 ,weight1 #a1cee grams4 ,diet1 oats4 ,octob] #bi3 #aj cc #b p] c5t caffe9 7#adg mg p] kilo7 inject$ subcutane\sly at #a4ea p4 m4 #e4ae p4 m41 rabbit alive2 surviv$4 ,rabbit #bai4 ,maltese4 ,weight1 #a1hbj grams4 ,diet1 oats4 ,octob] #bi3 #ad cc #b p] c5t caffe9 inject$ subcutane\sly at #a4dj p4 m4 7#aec mg p] kilo72 #e4ae1 rabbit alive2 surviv$4 ,rabbit #aid4 ,:ite female4 ,weight1 #a1dij grams4 ,diet1 oats4 ,octob] #ad3 #ac cc #b p] c5t caffe9 7#agd mg p] kilo7 inject$ subcutane\sly2 increas$ reflexes & tremors 7 obs]v$4 ,octob] #ae3 ,condition ( rabbit good2 no symptoms4 ,rabbit #aia4 ,br[n male4 ,weight1 #a1iae grams4 ,diet1 oats4 ,octob] #ad3 #af cc #b p] c5t caffe9 7#afg mg p] kilo7 inject$ subcutane\sly2 reflexes increas$ & tremors pres5t4 ,octob] #ae3 ,condition ( rabbit good4 ,a /udy ( ?is s]ies %[s t ab\t #aej mg ( caffe9 p] kilo caus$ increas$ reflexes )9 "o to two h\rs aft] injection4 ,:5 ! dose 0 increas$1 z 9 rabbits #aid & #aia1 ! symptoms 7 m pron\nc$2 #aej mg p] kilo may be reg>d$ z ! m9imum dose :i* produces symptoms ( n]v\s irritability :5 caffe9 is inject$ subcutane\sly4 ,exp]im5ts ) l>g] doses 7 !re=e c>ri$ out 9 ord] to det]m9e ! m9imum fatal dose4 ,,s]ies ,b4 ,approximately #j4b gram ( caffe9 p] kilo 0 employ$ 9 ^! exp]im5ts4 ,diet & race z possible factors :i* may influ5ce ! toxicity ( caffe9 7 made ! subject ( /udy 9 ^! exp]im5ts :i* 7 divid$ into two gr\ps z %[n 9 ! table1 page #be4 ,rabbit #ie4 ,gray & :ite male4 ,weight1 #a1dgh grams4 ,diet1 oats4 ,febru>y #bg3 #aa4cj a4 m41 #ae cc #b p] c5t caffe9 7#baj mg p] kilo7 inject$ subcutane\sly2 #b4bj p4 m41 no symptoms1 tremors obs]v$ :5 h&l$1 b n m>k$1 reflexes slightly increas$1 no muscul> rigidity nor any o!r symptoms2 #b4de p4 m41 rabbit sudd5ly became v re/less1 jump$ (f ! table1 & _h convulsions2 #c4de p4 m41 rabbit di$1 rigor mortis set 9 almo/ imm$iately aft] dea?4 ,rabbit #if4 ,gray & :ite male4 ,weight1 #a1ehe grams4 ,diet1 oats4 ,febru>y #bg3 #af cc #b p] c5t caffe9 7#bjj mg p] kilo7 inject$ subcutane\sly at #c4dj p4 m42 increas$ reflexes obs]v$ ab\t "o h\r aft] caffe9 0 inject$1 b no o!r symptoms4 ,febru>y #bh3 ,rabbit f\nd dead4 ,rabbit #aab4 ,black female4 ,weight1 #hge grams4 ,diet1 oats4 ,m>* #ah3 #i cc #b p] c5t caffe9 7#bje mg p] kilo7 inject$ subcutane\sly at #c p4 m42 #c4cj p4 m41 rabbit became re/less1 reflexes 7 increas$1 tremors 7 obs]v$1 b no o!r symptoms2 #d4ae p4 m41 rabbit _h tremors1 0 h&l$ b ?is fail$ to induce tetanus1 #aj m9utes lat] tetanus ( %ort duration ) recov]y occurr$4 ,m>* #ai3 #i a4 m41 f\nd dead4 ,rabbit #aai4 ,yell[ :ite female4 ,weight1 #a1jfj grams4 ,diet1 oats4 ,april #ag3 #aj cc #b p] c5t caffe9 7#ahh mg p] kilo7 inject$ subcutane\sly at #b4aj p4 m4 ,april #ah3 ,rabbit f\nd dead4 ,rabbit #aie4 ,:ite female4 ,weight1 #a1cjj grams4 ,diet1 c>rots1 s9ce ,octob] #g4 ,octob] #ad3 #ac cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ subcutane\sly at #aa4ae a4 m42 #b4be p4 m41 rabbit _h convulsions & di$4 ,note3 ,ulc]ation ( rectum 0 notic$4 ,rabbit #bjh4 ,gray4 ,weight1 #a1jfh grams4 ,diet1 c>rots1 ,octob] #g-ae1 inclusive4 ,octob] #ae3 #aj cc #b p] c5t caffe9 inject$ subcutane\sly at #aa a4 m42 #a p4 m41 increas$ reflexes & tremors obs]v$2 #c4de p4 m41 tremors 7 m>k$ :5 rabbit 0 h&l$4 ,octob] #af3 ,rabbit f\nd dead4 ,note3 ,look$ poorly n\ri%$4 ,rabbit #bdg4 ,belgian h>e1 female4 ,weight1 #a1bie grams4 ,diet1 oats la/ #aj days be=e exp]im5t4 ,novemb] #aj3 #aa a4 m41 ur9e obta9$ f ! bladd] 0 acid to litmus & did n conta9 sug> or album51 #ac cc #b p] c5t caffe9 0 inject$ subcutane\sly2 #a4cj p4 m41 #ae cc ur9e obta9$ 0 m>k$ly alkal9e to litmus & r$uc$ ,fehl+'s solution2 #b4cj p4 m41 r$uction ( ur9e consid]able1 m>k$ tremors obs]v$ b no tetanus4 ,novemb] #aa3 #aj4cj a4 m41 #ie cc ur9e collect$ gave mod]ate r$uction ( ,fehl+'s solution1 no symptoms1 condition ( rabbit seem$ to be good4 ,rabbit #bdh4 ,belgian h>e1 female4 ,weight1 #a1cje grams4 ,diet1 oats ! la/ #aj days be=e ! exp]im5t4 ,novemb] #aj3 #aa a4 m41 ur9e m>k$ly acid to litmus1 no album51 no sug>2 #ac cc #b p] c5t caffe9 inject$ subcutane\sly2 #a4cj p4 m41 ur9e 0 slightly alkal9e to litmus1 no r$uction ( ,fehl+'s solution2 #b p4 m41 reflexes increas$2 #b4cj p4 m41 #b cc ur9e obta9$ f bladd]1 sug> abundant2 #d4de p4 m41 reflexes increas$ z be=e1 b no tetanus4 ,novemb] #aa3 #aj4cj a4 m41 ur9e collect$ %[$ slight r$uction ( ,fehl+'s solution2 o!rwise condition ( rabbit 0 good2 rabbit did n %[ any effects ( caffe94 ,rabbit #ccg4 ,belgian h>e4 ,weight1 #a1jdj grams4 ,diet1 c>rots1 ,m>* #ca to ,april #f1 inclusive4 ,april #f3 #c p4 m41 #aa cc #b p] c5t caffe9 inject$ subcutane\sly 9 ! back 7#j4baa p] kilo72 #d4cj p4 m41 reflexes mu* exagg]at$4 ,april #g3 #h4ae a4 m42 condition good1 no symptoms4 ,rabbit #ccf4 ,belgian h>e4 ,weight1 #a1jdj grams4 ,diet1 c>rots1 ,m>* #ca to ,april #f1 inclusive4 ,april #f3 #c p4 m41 #aa cc #b p] c5t caffe9 inject$ subcutane\sly into tissues ( ! back4 ,april #g3 #h4ae a4 m41 no symptoms1 condition good4 ,al?\gh symptoms appe>$ 9 rabbits ( ,gr\p ,i 7see table1 page #be7 ab\t ! same "t aft] ! adm9i/ration ( caffe9 z 9 ! rabbits ( ! prec$+ s]ies all ( !m t]m9at$ fatally #b h\rs to #bd h\rs aft] its adm9i/ration4 ,two ( ^! rabbits 7,nos4 #aie & #bjh7 7 f$ c>rots = sev]al days be=e ! injection ( caffe91 ! o!rs 7 f$ oats4 ,s9ce symptoms & dea? appe>$ 9 ^! two rabbits ab\t ! same "t z 9 ! re/ ( ?is gr\p x may be conclud$ t caffe9 is n less toxic :5 c>rots are f$ ?an :5 oats =m ! exclusive diet4 ,b s9ce rabbit ,no4 #bjh 0 poorly n\ri%$ & ulc]ation ( ! rectum 0 obs]v$ 9 ,no4 #aie x is q possible t caffe9 might be less toxic 9 normal rabbits on ?is diet4 ,?is 0 te/$ 9 rabbits ,nos4 #ccf & #ccg1 bo? ( :i* seem$ to be free f abnormality & 7 well n\ri%$4 ,s9ce ^! rabbits surviv$ & manife/$ mild symptoms only ( intoxication x w\ld seem t a c>rot diet decreases ! toxicity ( caffe94 ,x 0 sugge/$1 h[ev]1 t ano!r factor might be ! cause ( ! great] resi/ance to caffe9 9 ^! two rabbits1 namely1 race4 ,?is 0 te/$ 9 rabbits #bdg & #bdh1 bo? ,belgian h>es4 ,s9ce ! toxicity ( caffe9 9 ^! two rabbits 0 ! same z 9 ,nos4 #ccf & #ccg1 diet z a factor 9 acute caffe9 intoxication may be disreg>d$4 ,! great] resi/ance to caffe9 ( ^! f\r rabbits is 9 all probability due1 !re=e1 to a diff]5ce ( race4 ,?is sugge/ion ga9$ additional support f ! exp]im5ts ( ! next s]ies4 ,,s]ies ,c4 ,! object ( ^! exp]im5ts 0 to det]m9e ! m9imum fatal dose = ! gray rabbit & to obta9 additional evid5ce z to ! toxicity ( caffe9 9 ! sev]al v>ieties ( rabbits4 ,eight exp]im5ts 7 p]=m$1 9 :i* f #bcf to #beb mg p] kilo 7 giv54 ,! :ite rabbits1 ?ree 9 numb]1 receiv$ #bej1 #bdb1 & #bch mg p] kilo4 ,all ! o!rs 7:i* 7 ,belgian h>es7 receiv$ f #bcf to #beb mg p] kilo4 ,two ( ! :ite rabbits 7 f$ c>rots = "o week prec$+ ! injection ( caffe94 ,! o!r 0 f$ oats4 ,?ree ( ! ,belgian h>es 7 on a diet ( oats1 two 7 f$ c>rots ! week be=e ! exp]im5t ) caffe94 ,rabbit #abb4 ,:ite1 female4 ,weight1 #b1jfj grams4 ,diet1 oats4 ,april #ad3 #be cc ( #b p] c5t caffe9 7#bej mg p] kilo7 9 aque\s solution inject$ subcutane\sly 9 ! back at #a4ce p4 m42 #d4cj p4 m41 tremors1 reflexes increas$1 condition o!rwise good4 ,april #af3 #i a4 m41 f\nd dead 9 cage4 ,autopsy3 ,liv] deeply conge/$2 kidneys conge/$ 9 cortex & m$ulla2 /oma* %[$ small hemorrhagic areas1 p]=at+ ulc]s 9 pyloric portion2 small inte/9e pete*iat$ on mucosa2 lungs & sple5 normal4 ,rabbit #bcd4 ,:ite1 female4 ,weight1 #a1fej grams4 ,diet1 ,novemb] #b-i1 c>rots4 ,novemb] #i3 #aj4de a4 m41 #bj cc #b p] c5t caffe9 7#bdb mg p] kilo7 adm9i/]$ subcutane\sly4 ,novemb] #aj3 #i p4 m41 f\nd dead4 ,rabbit #cce4 ,gray h>e1 female4 ,weight1 #a1agj grams4 ,diet1 ,m>* #ca to ,april #g1 c>rots4 ,april #g3 #i4cj a4 m41 #ad cc #b p] c5t caffe9 solution 7#bdj mg p] kilo7 inject$ subcutane\sly 9 ! back2 #aj4cj1 reflexes mu* increas$1 rabbit is extremely s5sitive4 ,april #h3 #i a4 m41 f\nd dead4 ,autopsy3 ,liv] 0 conge/$ & conta9$ sev]al coccidiosis nodules2 /oma* di/5d$ ) r dry food mass2 mucosa exhibit$ mild cat>rhal inflammation2 mucosa ( inte/9es also slightly inflam$4 ,rabbit #bdi4 ,belgian h>e1 female4 ,weight1 #a1ahe grams4 ,diet1 oats4 ,novemb] #aa3 ,ur9e1 #e cc1 f bladd] acid to litmus1 no sug>1 no album92 #aa4ej a4 m41 #ad cc #b p] c5t caffe9 7#bcf mg p] kilo7 adm9i/]$ subcutane\sly2 #c4de p4 m41 reflexes increas$1 hyp]/hesia m>k$1 b no tetanus1 ev5 :5 h&l$2 #cj cc ur9e collect$ at #d p4 m41 r$uction ( ,fehl+'s solution consid]able4 ,novemb] #ab3 #aj a4 m41 #h cc ur9e collect$1 r$uction heavy1 only a few cubic c5timet]s obta9$ f bladd]1 did n conta9 any sug>1 g5]al condition ( rabbit good1 no symptom ( caffe9 intoxication4 ,rabbit #cba4 ,yell[1 female4 ,weight1 #a1ace grams4 ,diet1 oats4 ,m>* #af1 #aiaj3 #aa4ej a4 m41 #ad cc #b p] c5t caffe9 7#bdf mg p] kilo7 inject$ subcutane\sly 9 ! back2 #b p4 m41 reflexes increas$1 is v s5sitive1 />t$ to run :5 put on floor1 no h&l+ except :at 0 requir$ = removal & return to cage1 feces s(t4 ,m>* #ag3 #i4cj a4 m41 condition good1 rabbit put on floor1 gait normal1 b does n c>e to walk4 ,m>* #ah3 #i a4 m41 walks ar\nd :5 put on floor1 appetite good1 condition seems to be normal4 ,m>* #be3 #aa a4 m41 rabbit /ill alive1 condition good4 ,rabbit #bej4 ,belgian h>e1 female4 ,weight1 #a1dce grams4 ,diet1 oats at lea/ two days be=e ! exp]im5t4 ,novemb] #aa3 #aa a4 m41 ur9e obta9$ f bladd] acid to litmus1 no album91 no sug>2 #aa4aj a4 m41 #ah cc1 #b p] c5t caffe9 7#beb mg p] kilo72 #c4de p4 m41 reflexes & hyp]/hesia1 no tetanus2 #d p4 m41 #fj cc ur9e1 m>k$ r$uction ( ,fehl+'s solution4 ,novemb] #ab3 #aj a4 m41 condition ( rabbit good1 no symptoms ( caffe9 intoxication1 #hj cc ur9e collect$1 sug> consid]able1 only a few cubic c5timet]s ( ur9e obta9$ f bladd]1 no r$uction ( ,fehl+'s solution4 ,rabbit #hcd4 ,belgian h>e1 female4 ,weight1 #a1bgj grams4 ,diet1 c>rots1 ,m>* #ca to ,april #g4 ,april #g3 #i4cj a4 m41 #ae cc #b p] c5t caffe9 7#bdj mg p] kilo7 inject$ subcutane\sly 9 ! back2 #aj4cj a4 m41 reflexes mu* increas$1 rabbit extremely s5sitive4 ,april #h3 #i a4 m41 condition good1 no symptoms4 ,rabbit #bcc4 ,:ite1 male4 ,weight1 #a1fge grams4 ,diet1 c>rots1 ,novemb] #b to #i4 ,novemb] #i3 #aj4ej a4 m41 #bj cc #b p] c5t caffe9 7#bch mg p] kilo7 inject$ subcutane\sly1 no symptoms obs]v$ until #e p4 m41 :5 increas$ reflexes & hyp]/hesia 7 notic$1 b no tetanus4 ,novemb] #aj3 #i a4 m41 p>alysis ( po/]ior extremities2 di$ at #a p4 m4 ,analysis ( ! results obta9$ 9 ! exp]im5ts ( ?is s]ies & inspection ( ,table ,i1 page #be1 %[ t all f\r ( ! rabbits :i* surviv$ doses ( #bcf to #beb mg ( caffe9 p] kilo 7 ,belgian h>es4 ,( ! f\r :i* di$ "o only 0 a ,belgian h>e4 ,! o!r ?ree 7 :ite rabbits4 ,two ( ^! 7 f$ oats2 ! o!r two receiv$ c>rots dur+ sev5 days prec$+ ! adm9i/ration ( caffe94 ,?is diet does n seem to be a factor1 !re=e1 9 ! toxicity ( caffe94 ,moreov]1 x may be obs]v$ t rabbit ,no4 #abb1 :i* 0 f$ oats1 di$ aft] receiv+ #bej mg p] kilo1 :ile rabbit ,no4 #bej receiv$ ! same diet & surviv$ ! same dose ( caffe9 p] kilo4 ,exp]im5ts #bcd & #ccd (f] ano!r illu/ration t ! toxicity ( caffe9 is n dep5d5t ^u diet1 s9ce bo? rabbits 7 f$ c>rots1 b ! same dose ( caffe9 caus$ only symptoms 9 "o :ile x prov$ fatal to ! o!r4 ,x is evid5t1 !re=e1 t ! diff]5ce 9 resi/ance to caffe9 %[n 9 ^! exp]im5ts is 9 all probability due to race1 ! ,belgian h>e be+ m resi/ant to caffe9 ?an rabbits ( o!r v>ieties4 ,rabbit ,no4 #cce seems to be an exception1 b ! po/-mortem exam9ation %[$ ! pres5ce ( coccidiosis ( ! liv]4 ,z w be %[n lat]1 :]ev] ?is condition prevail$ ev5 small] doses ( caffe9 prov$ fatal4 ,,s]ies ,d4 ,to obta9 additional evid5ce reg>d+ ! resi/ance ( ! v>i\s races ( rabbits to caffe9 & to asc]ta9 ! smalle/ dose :i* is surely fatal to ! gray rabbit or ,belgian h>e 0 ! object ( ?is s]ies ( exp]im5ts4 ,! diet 9 all cases consi/$ ( oats1 :i* 0 giv5 ad libitum except+ to rabbit ,no4 #bce1 :i* receiv$ c>rots = "o week previ\s to ! injection ( caffe94 ,! doses adm9i/]$ rang$ f #bfg to #cjj mg p] kilo & 7 adm9i/]$ to diff]5t v>ieties ( adult rabbits4 ,rabbit #bec4 ,br[n & black1 male4 ,weight1 #a1fjj grams4 ,diet1 oats1 ,novemb] #i to #ab4 ,novemb] #ab3 #aa4cj a4 m41 ur9e f bladd] acid1 no album51 no sug>2 #aa4ce a4 m41 #bb cc #b p] c5t caffe9 7#bge mg p] kilo7 inject$ subcutane\sly2 #aa4de a4 m41 rabbit jump$1 (f ! table1 _h convulsions1 retraction ( head & opi/hotonos1 g5]al tremors1 ant]ior extremities /ret*$ out1 po/]ior extremities almo/ normal1 frequ5t twit*+s2 di$ at #ab4ae p4 m4 ,rabbit #beb4 ,black1 female4 ,weight1 #a1cce grams4 ,diet1 oats1 ,novemb] #i to #ab4 ,novemb] #ab3 #aa4cj a4 m41 #ah cc #b p] c5t caffe9 7#bgj mg p] kilo7 inject$ subcutane\sly4 ,ur9e obta9$ f bladd] be=e injection1 acid1 no album51 no sug>1 color normal1 tremors & great excitem5t notic$ ab\t #ab noon2 #d4cj p4 m41 :5 h&l$1 %[$ unusual re/lessness & excitem5t foll[$ by convulsions ) opi/hotonos2 occasional twit*+1 condition bad4 ,di$ #d4ce p4 m4 ,rabbit #cbg4 ,:ite1 female4 ,weight1 #hbj grams4 ,diet1 oats1 ,m>* #h to #af4 ,m>* #af3 #aa4de a4 m41 #ab cc #b p] c5t caffe9 7#bib mg p] kilo7 inject$ subcutane\sly 9 ! back2 #b p4 m41 f\nd dead1 b 0 /ill w>m4 ,autopsy3 ,hemorrhagic area at po9t ( injection into sp9al muscles2 subcutane\s abdom9al region exhibit$ a l>ge area ( *eesy purul5t mat]ial2 liv] & sple5 7 engorg$2 bladd] fill$2 inte/9es normal4 ,rabbit #cdj4 ,:ite & br[n male4 ,weight1 #a1dfe grams4 ,diet1 oats4 ,m>* #cj3 #c4bj p4 m41 #bj cc ( #b p] c5t caffe9 7#bgc mg p] kilo7 inject$ subcutane\sly 9 back4 ,m>* #ca3 #i a4 m41 f\nd dead4 ,rabbit #cda4 ,:ite & br[n4 ,weight1 #a1dej grams4 ,diet1 oats4 ,m>* #cj3 #c4bj p4 m41 #bj cc #b p] c5t caffe9 7#bgj mg p] kilo7 inject$ subcutane\sly 9 back2 #d4dj p4 m41 f\nd 9 dy+ condition1 _h convulsions2 #d4de p4 m41 dead4 ,rabbit #cbf4 ,:ite1 male4 ,weight1 #a1fde grams4 ,diet1 oats1 ,m>* #h to #af4 ,m>* #af1 #aiaj3 #ab noon1 #bj cc #b p] c5t caffe9 7#bdc mg p] kilo7 inject$ subcutane\sly 9 ! back2 #b p4 m41 tremors m>k$1 hyp]s5sitive1 />t$ to run :5 put on floor2 rabbit 0 n h&l$ any m ?an 0 requir$ = 8 removal f & return to cage4 ,m>* #ag3 #i4cj a4 m41 tremors /ill pres5t & m>k$1 o!rwise g5]al condition good2 no o!r symptoms4 ,m>* #ah3 #i4cj a4 m41 no appetite1 tremors /ill pres5t1 g5]al condition poor2 di$ ab\t #b p4 m4 ,rabbit #bce4 ,belgian h>e1 male4 ,weight1 #a1hgj grams4 ,diet1 c>rots1 ,novemb] #b to #i4 ,novemb] #aj3 #aa4je a4 m41 #be cc #b p] c5t caffe9 7#bfg mg p] kilo7 inject$ subcutane\sly2 reflexes increas$ & tremors1 b no tetanus obs]v$2 f\nd dead next morn+4 ,rabbit #caf4 ,belgian h>e1 female4 ,weight1 #hfj grams4 ,diet1 oats1 ,m>* #h to #af4 ,m>* #af1 #aiaj3 #aa4dj a4 m41 #ab cc #b p] c5t caffe9 7#bfg mg p] kilo7 inject$ subcutane\sly 9 ! back2 #b4ae p4 m41 reflexes some:at increas$1 b n m>k$ly s2 walk$ :5 put on floor2 gait clumsy & sl[2 tremors ( head obs]v$2 #b4ce p4 m41 rabbit ly+ 9 8 cage1 po/]ior extremities ext5d$ & rigid1 ant]ior extremities flex$1 head retract$2 is /ill brea?+2 occasional spasms obs]v$4 ,rabbit di$ at #c p4 m4 ,autopsy3 ,no lesion at po9t ( injection 9 dorsal sp9al muscles2 liv] & sple5 engorg$2 inte/9es inject$2 o!r organs app>5tly normal4 ,rabbit #cie4 ,belgian h>e1 male4 ,weight1 #a1daj grams4 ,augu/ #ah3 #a p4 m41 #bj cc #b p] c5t caffe9 7#bhc mg p] kilo7 inject$ subcutane\sly 9 ! back2 #d p4 m41 reflexes m>k$ly increas$2 #e p4 m41 reflexes ab\t ! same1 b no tetanus4 ,augu/ #ai1 #i4ae a4 m43 ,reflexes increas$ m>k$ly4 ,augu/ #ba1 weight1 #a1bae grams4 ,giv5 #bge mg p] kilo ( caffe92 no symptoms obs]v$4 ,augu/ #bc1 f\nd dead4 ,autopsy3 ,liv] greatly engorg$2 /oma* fairly well di/5d$ & muc\s membrane 9 a slightly inflammatory condition2 cont5ts ( small inte/9e liquid 9 nature1 b walls ( same appe>$ normal2 o!r organs normal 9 appe>ance4 ,rabbit #cif4 ,belgian h>e1 female4 ,weight1 #a1dge grams4 ,diet1 oats4 ,augu/ #ah3 #a p4 m41 #bj cc #b p] c5t caffe9 7#bgb mg p] kilo7 inject$ subcutane\sly 9 ! back2 #d p4 m41 reflexes increas$ m>k$ly2 #e p4 m41 reflexes increas$ m>k$ly b no tetanus4 ,augu/ #ai3 #aj4cj a4 m41 reflexes /ill increas$ v m>k$ly2 rabbit jumps :5 t\*$4 ,augu/ #ba3 ,weight1 #a1bde grams4 ,inject$ subcutane\sly #bge mg ( caffe9 p] kilo2 reflexes increas$1 po/]ior extremities /iff ov] h\r lat]4 ,augu/ #bb3 #i a4 m41 f\nd dead4 ,autopsy3 ,?oracic organs normal 9 appe>ance2 /oma* di/5d$ & muc\s membrane affect$ ) a cat>rhal inflammation2 cont5ts ( /oma* 7 cov]$ ) a %9y mucus2 cont5ts ( small inte/9e liquid 9 nature & bile /a9$2 liv] %[$ a coccidial infe/ation2 kidneys & sple5 normal 9 appe>ance4 ,rabbit #cig4 ,belgian h>e1 male4 ,weight1 #a1cge grams4 ,diet1 oats4 ,augu/ #ai3 #aj4cj a4 m41 #bj cc #b p] c5t caffe9 7#bij mg p] kilo7 inject$ subcutane\sly 9 ! back4 ,augu/ #bb3 #i a4 m41 f\nd dead4 ,autopsy3 ,/oma* di/5d$ ) +e/a2 muc\s membrane exhibit$ a cat>rhal inflammation ) excessive secretions2 major portion ( inte/9es %[$ a condition simil> to t ( /oma*1 cont5ts consi/+ ma9ly ( a %9y mucus2 liv] enl>g$2 o!r organs app>5tly normal4 ,rabbit #cih1 ,belgian h>e1 female4 ,weight1 #a1egj grams4 ,diet1 oats4 ,augu/ #ai3 #aj4cj a4 m41 #bc cc #b p] c5t caffe9 7#bic mg p] kilo7 inject$ subcutane\sly 9 ! back2 #d p4 m41 f\nd dead4 ,autopsy3 ,?oracic organs seem+ly normal2 muc\s membrane ( /oma* exhibit$ a cat>rhal inflammation g5]ally2 l>ge inte/9es some:at impact$ b walls appe>$ normal2 o!r organs normal4 ,rabbit #cii1 ,belgian h>e1 male4 ,weight1 #a1gbe grams4 ,diet1 oats4 ,augu/ #ai3 #aj4cj a4 m41 #bf cc #b p] c5t caffe9 7#cjj mg p] kilo7 inject$ subcutane\sly 9 ! back2 f\nd dead at #d4cj p4 m4 ,autopsy3 ,lungs slightly conge/$2 liv] engorg$ & friable2 gall cy/ well fill$2 /oma* exhibit$ cat>rhal ga/ritis2 injection ( mes5t]ies & inte/9es2 kidney %[$ m>k$ cortical conge/ion4 ,! results ( ! exp]im5ts ( ?is s]ies likewise indicate t ! ,belgian h>e is m resi/ant to caffe9 ?an ! rabbits ( o!r v>ieties4 ,?us1 ( ! f\r gray rabbits 7,nos4 #bce1 #caf1 #cie1 & #cif71 :i* receiv$ #bfg to #bhc mg ( caffe9 p] kilo1 two di$ & two liv$1,b "o ( :i*1 #cif1 %[$ ! pres5ce ( coccidiosis ( ! liv]4 ,on ! o!r h& x w be obs]v$ t ! black & :ite rabbits :i* receiv$ f #bgj to #bge mg ( caffe9 p] kilo all di$ f ! effects ( ! drug2 "o )9 #a h\r & #be m9utes & ano!r )9 #ej h\rs aft] ! adm9i/ration ( ! caffe91 :ile ,no4 #cdj di$ 9 ! night4 ,fur!rmore x w be not$ t ( ! la/ ?ree rabbits ( ?is s]ies1 :i* 7 ,belgian h>es & receiv$ #bij1 #bic1 & #cjj mg ( caffe91 two di$ six h\rs aft] ! injection1 :ile ! o!r1 ,no4 #cig1 liv$ ?ree days4 ,! m9imum fatal dose ( caffe9 = ,belgian h>es is1 !re=e1 ab\t #bij to #cjj mg p] kilo :5 inject$ subcutane\sly1 :i* is ab\t #ej p] c5t great] ?an = rabbits ( o!r v>ieties4 ,b ,surviv$ fir/ dose4 ,,s]ies ,e4 ,x 0 %[n 9 s]ies ,a t #j4ae caffe9 p] kilo caus$ symptoms ( intoxication4 ,be=e conclud+1 h[ev]1 t ?is is ! smalle/ dose :i* causes symptoms ( poison+1 a numb] ( exp]im5ts 7 p]=m$ ) small] doses4 ,x 0 f\nd t 9 ! great majority ( cases #j4a caffe9 p] kilo may cause diuresis1 b no n]v\s or muscul> symptoms4 ,9 "s rabbits1 h[ev]1 ev5 su* a dose prov$ fatal4 ,po/-mortem exam9ations 9 ^! cases %[$ ! pres5ce ( coccidiosis ( ! liv]1 & x w be recall$ t simil> obs]vations 7 made be=e4 ,x is q possible1 !re=e1 t coccidiosis ( ! liv] is an important factor 9 decreas+ ! resi/ance to caffe94 ,exp]im5t #eea 7p4 #be7 %[s t o!r conditions may likewise increase ! toxicity ( caffe94 ,rabbit #cbe4 ,:ite1 female4 ,weight1 #a1jfe grams4 ,diet1 oats4 ,m>* #ag3 #aa a4 m41 #f cc #b p] c5t 7#aab mg p] kilo7 caffe9 inject$ subcutane\sly 9 ! back4 ,ab\t #e cc ( ur9e squeez$ out f bladd] be=e inject+ caffe94 ,m>* #ag3 #a p4 m41 h9d legs cross$ & /ret*$ out1 front legs also ext5d$2 rabbit ly+ /ret*$ out on h] belly4 ,m>* #ag3 #e4dj p4 m41 rabbit /ill alive1 condition some:at improv$4 ,m>* #ah3 #i a4 m41 f\nd dead1 /iff & cold4 ,autopsy3 ,hemorrhagic area at po9t ( inoculation2 subcutane\s region ( bo? ?ighs pres5t$ a hemorrhagic infiltration ( ! tissues2 liv] conta9$ lesions ( coccidiosis2 o!r organs app>5tly normal4 ,rabbit #ccj4 ,belgian h>e1 female4 ,weight1 #ice grams2 poorly n\ri%$4 ,m>* #ah3 #c4ce p4 m41 #e cc #b p] c5t caffe9 7#ajg mg p] kilo7 inject$ into subcutane\s tissues 9 ! back2 #e4cj p4 m41 no symptoms4 ,m>* #ai3 #i a4 m41 no symptoms4 ,m>* #be3 ,weight1 #hbe grams4 ,rabbit #cbi4 ,belgian h>e1 male4 ,weight1 #gge grams2 poorly n\ri%$4 ,receiv$ ,m>* #ah4 ,m>* #ah3 #c4cj p4 m41 #d cc #b p] c5t caffe9 7#ajc mg p] kilo7 inject$ into subcutane\s tissues 9 ! back2 #e4cj p4 m41 no symptoms4 ,m>* #ai3 #i a4 m41 no symptoms4 ,m>* #be3 ,rabbit alive 9 good condition2 weight1 #hbe grams4 ,rabbit #cbj4 ,black1 male4 ,weight1 #a1jdj grams4 ,diet1 oats4 ,m>* #ag3 #aa a4 m41 #f cc #b p] c5t caffe9 7#aae mg p] kilo7 inject$ subcutane\sly 9 ! back2 only a few drops ( ur9e obta9$ f bladd] be=e inject+ caffe92 #a p4 m41 rabbit v re/less2 ran away :5 plac$ on floor2 cri$ :5 t\*$ ) a piece ( pap]2 no tremors obs]v$1 b rabbit became exhau/$ & 0 unable to walk2 legs ext5d$ out2 aft] runn+ = ab\t a m9ute dyspnoea 0 v m>k$1 b rabbit soon rais$ himself on 8 legs2 #e4dj p4 m41 rabbit up on 8 legs4 ,m>* #ah3 #i a4 m41 f\nd dead1 b /ill w>m4 ,autopsy3 ,lungs /udd$ ) small grayi% :ite nodules1 adhesions to co/al pleura2 probably lesions ( coccidiosis2 liv] /udd$ ) coccidiosis nodules4 ,hemorrhages at po9t ( inoculation4 ,rabbit1 #eea4 ,gray1 female4 ,weight1 ,janu>y #bf1 #a1fej grams4 ,diet1 oats2 f$ #bj cc ( #be p] c5t alcohol daily f ,janu>y #bf-ca4 ,janu>y #ca3 ,weight1 #a1dej grams2 #aj4bj a4 m41 temp]ature #aja4f2 #aj4de1 a4 m41 temp]ature #aja4f2 receiv$ #g cc #b p] c5t caffe9 subcutane\sly into back2 #aa4ae a4 m41 convulsions ( %ort duration2 rais$ himself on po/]ior legs1 ant]ior legs wide ap>t2 #d4aj p4 m41 look$ normal1 n hyp]s5sitive2 #d4cj p4 m41 condition seem$ to be good4 ,febru>y #a3 #i a4 m41 f\nd dead1 0 alive at #e4cj p4 m4 ( previ\s day4 ,autopsy3 ,lesions f\nd involv$ ?oracic cavity ma9ly2 lungs 7 hepatiz$ & a fibro pla/ic exudate caus$ !m to adh]e to co/al pleura2 liv] engorg$ & appe>$ fatty2 no m>k$ lesions affect+ dige/ive tract1 a slight cat>rh ( /oma* be+ ! only noticeable feature2 kidneys & sple5 normal4 ,,table #a4--,subcutane\s injections ( caffe9--rabbits4 ,,s]ies ,a4 ---------------------------------------- ------------------------ ,caffe9 ,appe>ance ,duration ,no4 ,weight4 p] ( symptoms ( life4 ,diet4 ,rem>ks4 kilo 9-- ---------------------------------------- ------------------------ ,grams4 ,mg4 #ccb #a1jgj #aeh #a h\r ,surviv$ ,oats ,gray4 #de m9utes #cca #a1agj #aec d4 d4 d4 ,d4 #cbh #a1bjj #aej d4 d4 d4 ,d4 #cbb #a1jfe #aej #a h\r d4 d4 ,:ite4 #bag #a1cee #adg d4 d4 ,d4 #bai #a1hbj #aec d4 d4 ,maltese4 #aid #a1dij #agd d4 d4 ,:ite4 #aia #a1iae #afg d4 d4 ,light br[n4 ---------------------------------------- ------------------------- ,,s]ies ,b1 ,,gr\p ,i4 ---------------------------------------- -------------------------- #ie #a1dgh #baj #b h\rs #c h\rs ,oats ,:ite4 #ej m9utes #aj m9utes #if #a1ehe #bjj #a h\r ,ab\t #ah h\rs d4 ,gray :ite4 #aab #hge #bje #cj m9utes d4 d4 ,black4 #aai #a1jfj #ahh d4 d4 ,yell[ :ite4 #aie #a1cjj #bjj #c h\rs ,c>rots,:ite4 #aj m9utes #bjh #a1jfh #ahh #b h\rs ,ab\t #bd h\rs d4 ,gray4 ---------------------------------------- -------------------------- ,,s]ies ,b1 ,,gr\p ,,ii4 ---------------------------------------- ------------------------ #bdg #a1bie #bjj #b4e h\rs ,surviv$ ,oats ,gray4 #bdh #a1cje #bjj #c h\rs d4 d4 ,d4 #ccg #a1jdj #baa #a4e h\rs d4 ,c>rots ,d4 #ccf #a1jde #baa d4 d4 d4 ,d4 ---------------------------------------- ------------------------ ,,s]ies ,c4 ---------------------------------------- ------------------------- #abb #b1jfj #bej #b h\rs #a4e days ,oats ,:ite4 #ee m9utes #bcd #a1fej #bdb ,ab\t #bd h\rs,c>rots ,d4 #cce #a1agj #bdj #a h\r d4 d4 ,gray coccidiosis4 #bdi #a1ahe #bcf #d h\rs ,surviv$ ,oats ,gray4 #cba #a1ace #bdf #b h\rs d4 d4 ,yell[4 #aj m9utes #bej #a1dce #beb #d h\rs d4 d4 ,gray4 #ce m9utes #ccd #a1bgj #bdj #a h\r d4 ,c>rots ,d4 #bcc #a1fge #bch #f h\rs #bf h\rs d4 ,:ite4 #aj m9utes ---------------------------------------- ------------------------- ,,s]ies ,d4 ---------------------------------------- ------------------------ #bec #a1fjj #bge #aj m9utes #ce m9utes ,oats ,br[n & black4 #beb #a1cce #bgj #cj m9utes #d h\rs d4 ,black4 #ee m9utes #cbg #hbj #bib #b h\rs d4 ,:ite4 #ae m9utes #cdj #a1dfe #bgc ,ab\t #ah h\rs d4 ,:ite & br[n4 #cda #a1dej #bgj #a h\r d4 ,d4 #be m9utes #cbf #a1fde #bdc #b h\rs #ej h\rs d4 ,:ite4 #bce #a1hge #bfg #bj h\rs ,c>rots,gray4 #caf #hfj #bfg #b h\rs #c h\rs ,oats ,d4 #de m9utes #bj m9utes #cie #a1daj #bhc #c h\rs ,surviv$ ,d4 #cie #a1bae #bge d4 ,ab\t #b days ,oats ,d4 #cif #a1dge #bgb d4 ,surviv$ d4 ,d4 #cif #a1bde #bge #a h\r ,ab\t #ah h\rs d4 ,d4 #cig #a1cge #bij #c days d4 ,d4 #cih #a1egj #bic #e4e h\rs d4 ,d4 #cii #a1gbe #cjj #f h\rs d4 ,d4 ---------------------------------------- ------------------------ ,,s]ies ,e4 ---------------------------------------- ------------------------- #cbe #a1jfe #aab #b h\rs ,less ?an ,oats ,:ite female4 #bb h\rs #ccj #ice #ajg ,none ,surviv$ ,gray4 #cbi #gge #ajc d4 d4 ,gray male4 #cbj #a1jdj #aae #b h\rs #df h\rs ,oats ,black male4 #eea #a1dej #ajj #cj m9utes ,less ?an d4 ,gray female4 #bd h\rs ---------------------------------------- ------------------------- ,,adm9i/ration ,,by ,,m\?4 ,^! exp]im5ts 7 c>ri$ out on two v>ieties ( rabbits1 ! :ite & ! gray4 ,! diet consi/$ *iefly ( oats1 b 9 a few cases c>rots =m$ ! exclusive diet4 ,food & wat] 7 giv5 ad libitum4 ,a #b p] c5t solution ( caffe9 0 adm9i/]$ ?r\gh a /oma* tube4 ,s9ce ! resi/ance to mo/ drugs is commonly suppos$ to be great] :5 giv5 by m\? ?an :5 adm9i/]$ by any o!r pa?1 doses ( #age to #bjj mg p] kilo 7 f$ 9 a s]ies ( prelim9>y exp]im5ts1 all ( :i* 7 p]=m$ on gray rabbits weigh+ f #hfe to #a1ace grams1 & :i* 7 f$ c>rots = sev]al days previ\s to ! exp]im5t4 ,?ree ( ! rabbits surviv$1 two )\t %[+ any symptoms2 9 ! o!r case p>alysis ( ! po/]ior extremities 0 obs]v$ five h\rs aft] he receiv$ caffe9 & he 0 f\nd dead ! next morn+4 ,un=tunately no autopsy 0 p]=m$4 ,! l[ resi/ance to caffe9 ( ?is animal 0 probably due to "s abnormal condition :i* develop$ ab\t ! "t ( ! exp]im5t1 s9ce ?is rabbit receiv$ #cbe mg ( caffe9 p] kilo two weeks previ\sly & increas$ reflexes only 7 obs]v$ z a result ( ?is treatm5t4 ,h5ce #bjj mg ( caffe9 p] kilo c n be consid]$ ! toxic dose :5 f$ by m\?4 ,9 ! foll[+ exp]im5ts l>g] doses 7 !re=e giv54 ,,s]ies ,a4 ,rabbit #bdh4 ,belgian h>e4 ,weight1 #a1agj grams4 ,diet1 oats4 ,novemb] #ag3 #a4bj p4 m41 #ai4e cc #b p] c5t caffe9 7#ccj mg p] kilo7 adm9i/]$ by ! m\?2 #d4cj p4 m41 some:at hyp]s5sitive4 ,novemb] #ai3 ,no symptoms2 at #i a4 m41 ur9e collect$1 no r$uction ( ,fehl+'s solution2 rabbit surviv$4 ,rabbit #bda4 ,:ite male4 ,weight1 #a1chj grams4 ,diet1 oats4 ,novemb] #ag3 #a4ae p4 m41 #bj cc #b p] c5t caffe9 7#bij mg p] kilo7 adm9i/]$ by ! m\?2 #d4cj p4 m41 "s hyp]s5sitiv5ess1 b no o!r symptoms4 ,novemb] #ah3 #i a4 m41 ur9e collect$1 no r$uction ( ,fehl+'s solution2 no symptoms2 rabbit surviv$4 ,rabbit #bdi4 ,belgian h>e4 ,weight1 #hij grams4 ,diet1 oats4 ,novemb] #ag3 #a4cj p4 m41 #ad4e cc #b p] c5t caffe9 7#cbe mg p] kilo7 adm9i/]$2 #d4cj p4 m41 hyp]s5sitiv5ess2 no o!r symptoms4 ,novemb] #ah3 #aj a4 m41 no symptoms2 ur9e collect$1 no r$uction2 rabbit surviv$4 ,,s]ies ,b4 ,! object ( ^! exp]im5ts 0 to det]m9e ! m9imum fatal dose ( caffe9 9 ! two v>ieties ( rabbits1 ! :ite & ! gray4 ,all ( ! animals select$ 7 approximately ( ! same weight4 ,rabbit #bci4 ,belgian h>e1 male4 ,weight1 #ice grams4 ,diet1 oats4 ,novemb] #ai3 #d p4 m41 #ag cc #b p] c5t caffe9 7#cfc mg p] kilo7 adm9i/]$ by m\?1 foll[$ by #aj cc ( #j4i p] c5t salt solution4 ,novemb] #bj3 ,ur9e exam9$1 no sug> f\nd1 no symptom notic$ at any "t aft] injection4 ,rabbit #bed4 ,belgian h>e1 female4 ,weight1 #ige grams4 ,diet1 oats4 ,novemb] #ai3 #d4je p4 m41 #ah cc #b p] c5t caffe9 7#cfi mg p] kilo7 adm9i/]$ by m\?1 foll[$ by #aj cc ( #j4i p] c5t salt solution4 ,novemb] #bj3 #i a4 m41 rabbit f\nd dead4 ,rabbit #bfg4 ,:ite4 ,weight1 #a1jej grams4 ,diet1 oats4 ,novemb] #bc3 #ab4aj p4 m41 #ah cc #b p] c5t caffe9 7#cdb mg p] kilo7 giv5 by m\?1 foll[$ by #ah cc salt solution2 #a p4 m41 increas$ reflexes1 tremors m>k$ b no tetanus2 #a4je p4 m41 rabbit /ret*$ on abdom51 po/]ior extremities 9 ext5d$ position & p>alyz$1 soon aft] clonic spasms set 91 :i* recurr$ ab\t e m9ute2 #a4ad p4 m41 tetanus & dea?4 ,autopsy3 ,liv] %[$ fatty deg5]ation2 slight inflammation ( /oma* & inte/9es2 o!r organs normal4 ,rabbit #bfh4 ,:ite4 ,weight #a1ajj grams4 ,diet1 oats4 ,novemb] #bc3 #bj cc #b p] c5t caffe9 7#cfc mg p] kilo7 adm9i/]$ by m\?1 foll[$ by #bj cc salt solution2 #a4ae p4 m41 some:at hyp]s5sitive2 #d4cj p4 m41 tremors fairly m>k$1 no ur9e pass$1 ab\t #b cc ( bloody look+ ur9e obta9$ f bladd]1 :i* conta9$ album5 & a consid]able am\nt ( glycog52 rabbit di$4 ,rabbit #dai1 ,belgian h>e1 male4 ,weight1 #a1fjj grams4 ,diet1 oats4 ,septemb] #bf3 #aj a4 m41 #bh cc #b p] c5t caffe9 7#cej mg p] kilo7 giv5 by m\?2 reflexes increas$ at #d p4 m42 #f p4 m41 reflexes /ill increas$1 no o!r symptoms4 ,septemb] #bg3 #i a4 m41 f\nd dead4 ,autopsy3 ,lungs1 liv]1 & kidneys conge/$2 o!r organs normal4 ,rabbit #dbj4 ,belgian h>e1 male4 ,weight1 #a1bej grams4 ,diet1 oats4 ,septemb] #bf3 #aj a4 m41 #bb cc #b p] c5t caffe9 7#ceb mg p] kilo7 giv5 by m\?2 #aa4ce a4 m41 convulsions2 #ab noon1 f\nd dead4 ,autopsy3 ,liv] %[$ v ext5sive coccidiosis2 no o!r lesions4 ,rabbit #dba4 ,belgian h>e1 male4 ,weight1 #a1dhe grams4 ,diet1 oats4 ,septemb] #bf3 #aj a4 m41 #bf cc #b p] c5t caffe9 7#cea mg p] kilo7 adm9i/]$ by m\?2 #d p4 m41 reflexes increas$2 #f p4 m41 reflexes z be=e1 no tetanus obs]v$4 ,septemb] #bg3 #i a4 m41 rabbit f\nd dead4 ,autopsy3 ,conge/ion ( lungs & kidneys2 liv] conge/$ & slightly fatty4 ,rabbit #dbd4 ,:ite1 male4 ,weight1 #a1bie grams4 ,diet1 oats4 ,septemb] #bf3 #b p4 m41 #ai cc #b p] c5t caffe9 7#bic mg p] kilo7 adm9i/]$ by m\?2 #d p4 m41 reflexes increas$1 no o!r symptoms2 #f p4 m41 no *ange s9ce #d p4 m4 ,septemb] #bg3 #ab noon1 convulsions & dea?4 ,autopsy3 ,conge/ion ( ! lungs2 no o!r lesions4 ,rabbit #dbc4 ,:ite1 male4 ,weight1 #a1bje grams4 ,diet1 oats4 ,septemb] #bf3 #b p4 m41 #ah cc #b p] c5t caffe9 adm9i/]$ by m\?2 #d p4 m41 reflexes increas$1 no tetanus2 #f p4 m41 condition un*ang$ s9ce #d p4 m4 ,septemb] #bg3 #i a4 m41 f\nd dead4 ,autopsy3 ,lungs1 liv]1 & kidneys conge/$2 o!r organs normal4 ,rabbit #dbb4 ,:ite1 male4 ,weight1 #a1ddj grams4 ,diet1 oats4 ,septemb] #bf3 #b p4 m41 #ba cc #b p] c5t caffe9 7#bia mg p] kilo7 giv5 by m\?2 reflexes increas$ at #d p4 m4 ,septemb] #bg3 #c p4 m41 alive1 no symptoms2 #d p4 m41 convulsions ) recov]y1 ?is 0 soon foll[$ by a viol5t attack ( tetanus1 :i* la/$ ab\t "o m9ute & 0 succe$$ by p>alysis2 rabbit di$ at #d4cj4 ,autopsy3 ,liv] slightly conge/$2 a small portion ( ! inte/9e %[$ conge/ion & edema2 o!r organs normal4 ,a /udy ( ^! exp]im5ts %[s also consid]able v>iation 9 ! toxicity ( caffe9 :5 giv5 by m\?4 ,9 "s cases a dose ( #cjj mg p] kilo1 & ev5 less1 caus$ dea?1 z 9 rabbits #dbc & #dbd4 ,9 o!r rabbits1 h[ev]1 approximately ! same doses ( caffe9 produc$ increas$ reflexes only4 ,! same symptoms 7 produc$ 9 ,nos4 #bdh & #bdi aft] ! adm9i/ration ( #cbe-ccj mg ( caffe9 p] kilo1 :ile ano!r rabbit 7,no4 #bci7 surviv$ a dose ( #cfc mg p] kilo4 ,t ?is is exceptional1 h[ev]1 appe>s f ! result ( ! foll[+ exp]im5ts on rabbits ,nos4 #dai1 #dbj1 & #dba1 all ( :i* di$ aft] receiv+ #cej mg ( caffe9 p] kilo1 & rabbits #bfg & #bfh1 to :i* doses ( #cfc & #cdb mg1 respectively1 p] kilo prov$ fatal4 ,x w be obs]v$ fur!r t ! gray rabbits are m resi/ant to caffe9 ?an ! :ite animals1 z #cej mg p] kilo 0 ! smalle/ fatal dose = rabbits #dai1 #dbj1 & #dba1 all ( :i* 7 gray rabbits1 :ile a dose ( #bij mg p] kilo 0 fatal = "s ( ! :ite rabbits4 ,aga91 x w be notic$ t ( ! two gray rabbits1 ,nos4 #bed & #bci1 :i* receiv$ ! l>ge/ doses 9 ^! exp]im5ts1 namely1 #cfi & #cfc mg1 respectively1 "o surviv$4 ,! l>ge/ doses giv5 to ! :ite rabbits 7 #cfc & #cdb mg caffe9 p] kilo4 ,bo? ( ^! di$ f ! effects ( ! drug4 ,x may be conclud$1 !re=e1 t ! m9imum toxic dose = ! gray rabbit is ab\t #cbe mg ( caffe9 p] kilo1 & ! m9imum fatal dose is at lea/ #cej mg p] kilo4 ,x is to be rem>k$ 9 ?is connection t po/-mortem exam9ation %[$ ext5sive coccidiosis 9 rabbit #dbj & fatty liv] 9 ,no4 #dba1 :ile ! macroscopical exam9ation ( ! organs ( ,nos4 #dbd & #dbc fail$ to %[ ! pres5ce ( su* abnormalities4 ,s9ce1 z 0 obs]v$ 9 ! section on subcutane\s injection & else:]e 9 ?is inve/igation1 pa?ological *anges are apt to decrease ! resi/ance to caffe91 x is q possible t #cej mg p] kilo is n ! m9imum fatal dose = ! normal rabbit4 ,inde$1 ! exp]im5t on rabbit #bci l5ds support to ?is view1 ?us furni%+ additional evid5ce ( diff]5ce 9 ! resi/ance to caffe9 9 ! two v>ieties ( rabbits4 ,,table #b4--;,adm9i/ration ( caffe9 by m\?4 ,,s]ies ,a4 ---------------------------------------- ------------------------ ,rabbit ,caffe9 ,duration ,no4 ,weight4 p] ,symptoms ( life4 ,diet4 ,rem>ks4 kilo4 ---------------------------------------- ------------------------ ,grams4 ,mg4 #bdh #a1agj #ccj #c h\rs ,surviv$ ,oats ,gray4 #aj m9utes #bda #a1chj #bij #b h\rs d4 d4 ,:ite male4 #ae m9utes #bdi #hij #cbe #c h\rs d4 d4 ,gray male4 ---------------------------------------- ------------------------ ,,s]ies ,b4 ---------------------------------------- ------------------------ #bci #ice #cfc ,surviv$ ,oats ,gray male4 #bed #ige #cfi ,ab\t #b days d4 ,gray female4 #bfg #a1jej #cdb #ej m9utes #a h\r d4 ,:ite4 #d m9utes #bfh #a1ajj #cfc ,ab\t #c h\rs d4 ,d4 #dai #a1fjj #cej #f h\rs ,less ?an d4 ,gray male4 #bd h\rs #dbj #a1bej #ceb #a h\r #b h\rs d4 ,d4 #ce m9utes #dba #a1dhe #cea #f h\rs ,less ?an d4 ,d4 #bd h\rs #dbd #a1bie #bic #b h\rs #bb h\rs d4 ,:ite male4 #dbc #a1bje #cjj d4 ,less ?an d4 ,d4 #ai h\rs #dbb #a1ddj #bia d4 #b h\rs d4 ,d4 ---------------------------------------- ------------------------- ,,injection ,,into ,,! ,,p]itoneal ,,cavity4 ,9 a numb] ( exp]im5ts caffe9 0 introduc$ into ! p]itoneal cavity4 ,rabbits ( diff]5t v>ieties receiv+ a diet ( oats or c>rots 7 employ$ = ?is purpose2 food & wat] 7 giv5 ad libitum4 ,! m9imum doses requir$ to induce symptoms or cause dea? 9 ^! animals 7 det]m9$2 te/s ) caffe9 7 also made on "y rabbits 9 ord] to /udy ! influ5ce ( age on ! resi/ance to ?is sub/ance4 ,! results are %[n 9 ! foll[+ exp]im5ts3 ,,s]ies ,a4 ,9 ?is s]ies l>ge doses 7 adm9i/]$1 approximat+ #j4c gram p] kilo4 ,rabbit #ga4 ,gray female4 ,weight1 #a1fei grams4 ,janu>y #bj3 #b4bj p4 m41 #be cc aque\s solution #b p] c5t caffe9 7#cjj mg p] kilo7 7 inject$ into ! p]itoneal cavity2 #c4de p4 m41 :5 doors ( cage 7 op5$ rabbit _h spasm ( %ort duration4 ,janu>y #ba3 ,rabbit f\nd dead4 ,rabbit #gb4 ,gray & :ite4 ,weight1 #a1djb grams4 ,janu>y #ba3 #aa4ag a4 m41 #bj4b cc 7aque\s solution7 ( #b p] c5t caffe9 7#cjj mg p] kilo7 inject$ into p]itoneal cavity f burette2 #aa4be a4 m41 p>alysis2 #aa4cj a4 m41 rabbit _h convulsion :5 pick$ up f ! floor1 foll[$ by sev]al spasms lat]2 #aa4ce a4 m41 typical tetanus2 #ab4cj noon1 f\nd dead4 ,rabbit #fa4 ,black female4 ,weight1 #b1adc grams4 ,janu>y #ai3 #dj cc #b p] c5t caffe91 aque\s solution 7#cjj mg p] kilo71 inject$ into p]itoneal cavity f burette2 tetanus :5 ab\t #cj cc 7 inject$2 :5 remov$ f hold]1 repeat$ & viol5t convulsions1 t]m9at+ 9 dea?4 ,,s]ies ,b4 ,! object ( ^! exp]im5ts 0 to det]m9e ! m9imum le?al dose2 #j4b to #j4ae gram ( caffe9 p] kilo 0 inject$ into ! rabbits ( ?is s]ies4 ,rabbit #fi4 ,:ite female4 ,weight1 #a1gad grams4 ,janu>y #bj3 #aj4ae a4 m41 #f cc #b p] c5t caffe91 aque\s solution1 inject$ into p]itoneal cavity4 ,no symptoms1 "u obs]vation = #de m9utes1 rabbit defecat$ r copi\sly2 feces 7 s(t2 #aa a4 m41 #f cc #b p] c5t caffe91 aque\s solution1 inject$ into p]itoneal cavity1 no symptoms1 "u obs]vation = #dj m9utes2 #aa4dj1 #f cc #b p] c5t caffe9 inject$ into p]itoneal cavity2 #aa4de1 rabbit is re/less1 reflexes increas$4 ,rabbit #gj4 ,gray & :ite female4 ,weight1 #a1dhg grams4 ,janu>y #bj3 #a4cj p4 m41 #ae cc #b p] c5t aque\s solution ( caffe9 7#j4b gram p] kilo7 inject$ into ! p]itoneal cavity2 #b4bj p4 m41 no symptoms4 ,janu>y #cj3 ,ab\t #b p4 m4 rabbit di$4 ,febru>y #a3 ,autopsy3 ,cirrhosis ( ! liv]2 ent]itis ( small inte/9es2 /oma* & kidneys normal4 ,rabbit #ic4 ,maltese1 male4 ,weight1 #a1aig grams4 ,m>* #b3 #aa4cj a4 m41 #ab cc ( #b p] c5t caffe9 7#bjj mg p] kilo7 inject$ into p]itoneal cavity2 #aa4ce a4 m41 :ile be+ releas$ f hold]1 tetanus occurr$1 repeat$ attacks lat]1 clonic convulsions ) tonic rigidity ( po/]ior extremities dur+ ! attacks z well z dur+ int]vals1 ant]ior extremities 7 relax$ dur+ ! int]vals betwe5 ! attacks1 opi/hotonos ( c]vical region b kyphosis 9 lumb> region 7 obs]v$1 no salivation nor dilatation ( ! pupils2 #b p4 m41 rabbit di$4 ,rabbit #ib4 ,yell[ female4 ,weight1 #a1chh grams4 ,febru>y #be1 #d4ae p4 m41 #ad cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ into p]itoneal cavity2 #d4bj p4 m41 re/lessness & increas$ reflexes1 rabbit f\nd /ret*$ out 9 cage1 b rais$ himself on 8 legs aga92 #d4de1 g5]al tremor :5 t\*$4 ,febru>y #bf3 #i a4 m41 rabbit f\nd dead4 ,autopsy3 ,hemorrhage into abdom9al muscles at site ( injection2 hemorrhage also 9 walls ( /oma* opposite simil> spot 9 abdom9al wall4 ,rabbit #cji4 ,belgian h>e1 female4 ,weight1 #a1ejj grams4 ,diet1 oats4 ,m>* #b3 #b4je p4 m41 #b p] c5t caffe9 solution 7#j4b gram p] kilo7 inject$ into p]itoneal cavity2 #b4be p4 m41 f\nd dead1 no ur9e f\nd 9 bladd]4 ,rabbit #cjg4 ,belgian h>e1 female4 ,weight1 #a1cbj grams4 ,diet1 oats4 ,m>* #b3 #ab noon1 ur9e obta9$ f bladd]1 cle> amb] color$1 no album91 no r$uction2 #ab4jf p4 m41 #aj cc ( #b p] c5t caffe9 7#j4aea gram p] kilo7 inject$ into p]itoneal cavity2 #a4cj p4 m41 rabbit plac$ on floor1 runs ar\nd b ant]ior & po/]ior extremities soon ext5d$1 9 tonic condition2 #b4be p4 m41 reflexes increas$1 p>alysis ( extremities1 dyspnoea2 #d4ej p4 m41 ab\t #ajj cc ur9e collect$1 no album91 r$uction ( ,fehl+'s solution mod]ate4 ,m>* #c3 #i4cj a4 m41 po/]ior extremities ext5d$ & rigid1 ant]ior extremities p>alyz$1 respiration less frequ5t & deep] ?an normal4 ,rabbit di$ at #aa4ej a4 m42 ur9e collect$ s9ce #d4ej p4 m4 previ\s day gave v heavy r$uction ( ,fehl+'s solution4 ,autopsy3 ,animal 9 good condition2 9 ! left axill>y region 0 obs]v$ a hemorrhage into ! subcutane\s & muscul> tissue ( t region4 ,! v5tral portion ( ! l>ge colon1 9 contact ) ! v5tral abdom9al wall1 %[$ a hemorrhagic area ab\t "o-half in* 9 l5g?1 su* z might be produc$ by a puncture or bruise ( ! colon ?r\gh ! abdom9al wall4 ,a small portion ( ! small inte/9e adjac5t to ! colon 0 affect$ 9 a simil> mann]4 ,all int]nal organs 7 app>5tly normal4 ,rabbit #cjh4 ,belgian h>e1 female4 ,weight1 #a1cej grams4 ,diet1 oats4 ,m>* #b3 #aa4de a4 m41 ur9e obta9$ f bladd]1 no album51 no r$uction2 #aa4ej a4 m41 #aj cc #b p] c5t caffe9 7#j4ae gram p] kilo7 inject$ into p]itoneal cavity2 #a4cj p4 m41 n v active1 no abnormal symptoms o!rwise2 #c4cj p4 m41 rabbit look$ depress$1 made v little attempt to move ab\t1 rema9$ 9 "o position mo/ ( ! "t :5 plac$ on floor2 #d4cj p4 m41 #ahj cc ur9e collect$1 no album51 r$uction ( ,fehl+'s solution mod]ate4 ,m>* #c3 #i4cj a4 m41 rabbit looks normal1 is able to walk b is easily fatigu$ :5 made to walk ab\t or :5 plac$ on 8 side1 foll[$ by p>alysis ( ant]ior extremities1 po/]ior extremities app>5tly normal1 ab\t #ij cc ( ur9e collect$ at noon 0 free f album51 did n r$uce ,fehl+'s solution4 ,m>* #d3 #aa a4 m41 ly+ on 8 side 9 cage1 ant]ior extremities limp1 po/]ior extremities ext5d$ & rigid1 is 9 dy+ condition4 ,m>* #e3 #i a4 m41 f\nd dead4 ,autopsy3 ,liv] engorg$2 sple5 conge/$1 b n enl>g$2 kidneys1 "s conge/ion 9 cortex2 /oma* fill$1 mucosa ?ick5$ & easily pull$ (f2 pete*ial hemorrhages on s]osa ( colon4 ,,s]ies ,c4 ,! exp]im5ts ( ?is s]ies 7 made to det]m9e ! m9imum toxic dose4 ,rabbit #bie4 ,belgian h>e1 female4 ,weight1 #a1bje grams4 ,diet1 c>rots4 ,m>* #a3 #aj4dj a4 m41 #f cc #b p] c5t caffe9 7#j4a gram p] kilo7 inject$ into p]itoneal cavity2 ab\t #b cc ( ur9e obta9$ be=e inject+ caffe92 #b p4 m4 #ajj cc ur9e1 bloody 9 appe>ance1 collect$1 a mod]ate quantity ( album5 pres5t1 no r$uction2 #c4dj p4 m41 no symptoms4 ,m>* #d3 #b p4 m41 rabbit looks well4 ,rabbit #bic4 ,belgian h>e1 female4 ,weight1 #a1fje grams4 ,diet1 c>rots4 ,m>* #a3 ,ur9e f bladd] cle>1 alkal9e2 #aa4ee a4 m41 #h cc #b p] c5t caffe9 7#j4a gram p] kilo7 inject$ into p]itoneal cavity2 #c p4 m41 #ij cc ur9e normal 9 color collect$1 no album51 no r$uction2 #c4dj p4 m41 no symptoms4 ,m>* #d3 #a4ae p4 m41 rabbit looks normal4 ,rabbit #bib4 ,belgian h>e1 male4 ,weight1 #a1eie grams4 ,diet1 c>rots4 ,m>* #a3 #aj4aj a4 m41 #h cc #b p] c5t caffe9 7#j4a gram p] kilo7 solution inject$ into p]itoneal cavity2 #aj4dj a4 m41 rabbit ur9at$1 reflexes increas$1 b no o!r symptoms2 #aj4ej a4 m41 no ur9e obta9$ f bladd]2 #b p4 m41 #aje cc ( cle> pale ur9e collect$2 no album51 no r$uction2 #c4dj p4 m41 no symptoms4 ,m>* #d3 #b p4 m41 rabbit looks well1 ur9e collect$1 did n conta9 sug>4 ,rabbit #bih4 ,belgian h>e1 female4 ,weight1 #a1bje grams4 ,diet1 c>rots4 ,m>* #a3 #d4jf p4 m41 #g4e cc #b p] c5t caffe9 solution 7#j4abe gram p] kilo7 inject$ into p]itoneal cavity1 ur9e obta9$ f bladd] imm$iately aft] injection1 no album51 no r$uction2 #e4cj p4 m41 reflexes increas$1 rabbit 0 able to run ar\nd1 b became p>alyz$ soon2 #e4dj p4 m41 rabbit is aga9 able to run ar\nd4 ,m>* #c3 #aj a4 m41 ant]ior extremities p>alyz$1 is able to use po/]ior extremities4 ,m>* #d3 #a p4 m41 rabbit looks normal4 ,rabbit #bbc4 ,belgian h>e1 male4 ,weight1 #a1afe grams4 ,diet1 c>rots4 ,m>* #a3 #c4ej p4 m41 ur9e obta9$ f bladd] cle>1 amb] color$1 no album51 no sug>2 #c4eb p4 m41 #g4e cc #b p] c5t caffe9 7#abe mg p] kilo7 inject$ into p]itoneal cavity2 #e4dj p4 m41 rabbit makes little attempt to run :5 put on ! floor1 weakness ( extremities m>k$4 ,m>* #d3 #a4ae p4 m41 rabbit normal4 ,,s]ies ,d4 ,! object ( ! exp]im5ts ( ?is s]ies 0 to /udy ! effect ( age on ! resi/ance to caffe94 ,half-gr[n rabbits 71 !re=e1 us$ 9 ! foll[+ exp]im5ts4 ,rabbit #caj4 ,belgian h>e1 female4 ,weight1 #hhj grams4 ,diet1 oats4 ,m>* #b3 #c4be p4 m41 #i cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ into p]itoneal cavity4 ,m>* #c3 #i4cj a4 m41 no symptoms1 rabbit looks normal4 ,m>* #d3 #aa a4 m41 po/]ior extremities abduct$1 walk$ :5 plac$ on ! floor1 made no attempt to *ange attitude :5 plac$ on its side1 rema9$ "s "t 9 ?is position4 ,m>* #e3 #i a4 m41 f\nd dead4 ,autopsy3 ,liv] %[$ areas ( deg5]ation2 kidneys conge/ion & pete*ial hemorrhage on cortex2 small & l>ge inte/9es1 inflammation m>k$2 bladd] di/5d$4 ,rabbit #ge4 ,gray & :ite1 female4 ,weight1 #hdb grams4 ,janu>y #be3 #c p4 m41 #h4e cc #b p] c5t caffe9 solution 7#j4b gram p] kilo7 inject$ into p]itoneal cavity2 #c4ae p4 m41 ant]ior extremities weak & reflexes increas$4 ,janu>y #bg3 ,rabbit p>alyz$ b is able to turn ov] :5 plac$ on back4 ,rabbit #gd4 ,gray & :ite1 female4 ,weight1 #fib grams4 ,janu>y #be3 #c p4 m41 #g cc #b p] c5t caffe9 7#j4b gram p] kilo7 solution inject$ into p]itoneal cavity2 #c4ae p4 m41 reflexes increas$ & ant]ior extremities p>alyz$4 ,janu>y #bg3 ,rabbit recov]$ & is able to walk ab\t 9 ! room4 ,rabbit #cab1 maltese1 female4 ,weight1 #gdj grams4 ,diet1 oats4 ,m>* #c3 #aa4dg a4 m41 ur9e obta9$ f bladd]1 appe>ance normal1 no album51 no r$uction ( ,fehl+'s solution2 #aa4ej a4 m41 #g4e cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ into p]itoneal cavity2 #b4cj p4 m4 ant]ior extremities p>alyz$1 po/]ior extremities rigid & ext5d$2 #e p4 m4 7ab\t71 rabbit di$4 ,rabbit #caa4 ,belgian h>e1 female4 ,weight1 #fej grams4 ,diet1 oats4 ,m>* #c3 #aa4bf a4 m41 ur9e obta9$ f bladd] normal 9 appe>ance1 album5 consid]able1 r$uction ( ,fehl+'s solution none2 #aa4bg a4 m41 #f cc #b p] c5t caffe9 solution 7#j4b gram p] kilo7 inject$ into p]itoneal cavity2 #b4cj p4 m41 rabbit seem$ to be normal1 no symptoms _h develop$2 ur9e collect$ conta9$ a l>ge am\nt ( sug>1 r$uction 0 v heavy1 b no album5 0 f\nd4 ,m>* #d3 #aa a4 m41 condition good1 moves ab\t :5 put on floor2 gait1 normal4 ,rabbit #gh4 ,yell[ & :ite4 ,weight #fei grams4 ,janu>y #bf3 #a4cj p4 m41 #h4e cc #b p] c5t caffe9 7#bej mg p] kilo7 inject$ into p]itoneal cavity1 "u obs]vation ! re/ ( ! aft]noon1 no symptoms4 ,janu>y #bg3 #d p4 m41 no symptoms develop$4 ,rabbit #cag4 ,belgian h>e1 female4 ,weight #fce grams4 ,diet oats4 ,m>* #ae3 #aj4ce a4 m41 #h cc #b p] c5t caffe9 7#j4beb gram p] kilo7 inject$ into p]itoneal cavity2 #ab noon1 m>k$ abduction ( h9d legs1 0 unable to walk aft] a little ex]tion1 rabbit di$ betwe5 #ab4cj & #ab4ej p4 m4 ,autopsy4 ,"r lung hepatiz$ & %[$ adhesions to co/al & m$ia/9al pleura2 liv] /udd$ ) nodules ( coccidiosis2 sple5 conge/$2 /oma* fill$1 mucosa normal2 inte/9es inject$2 colon hemorrhagic on s]osa 9 v5tral region1 ne> po9t ( injection2 kidneys normal4 ,rabbit #cbc4 ,:ite1 female4 ,weight #hbj grams4 ,diet oats4 ,m>* #ae3 #aj4de a4 m41 #aj cc #b p] c5t caffe9 7#bej mg p] kilo7 inject$ into p]itoneal cavity2 #ab noon1 reflexes increas$1 h9d legs abduct$ b is able to walk1 symptoms are mild2 #a4dj p4 m41 tremors1 weakness1 & abduction ( head & legs mu* m m>k$ ?an at #ab noon4 ,m>* #af3 ,condition good4 ,m>* #ag3 ,condition good1 recov]y app>5tly complete4 ,s9ce ! exp]im5ts ( ,s]ies ,a1 :i* 7 int5d$ z prelim9>y te/s1 h %[n t #j4c gram ( caffe9 p] kilo :5 introduc$ into ! p]itoneal cavity is rapidly absorb$ & is fatal1 mu* small] doses 7 employ$ 9 subsequ5t trials ) ! drug4 ,?is is %[n 9 s]ies ,b1 :i* may be divid$ into two gr\ps4 ,gr\p ,i1 consi/+ ( rabbits #fi1 #gj1 #ib1 #ic1 & #cji1 :i* receiv$ #j4b gram ( caffe9 p] kilo1 & ,gr\p ,,ii1 ,nos4 #cjg & #cjh1 into :i* #j4ae gram ( caffe9 p] kilo 0 inject$4 ,?ree rabbits ( ,gr\p ,i 7,nos4 #ib1 #ic1 #cji7 di$ f ! effects ( caffe92 rabbit #cji tw5ty m9utes aft] injection1 & rabbits ,nos4 #ib & #ic1 tw5ty h\rs & two & "o-half h\rs1 respectively1 aft] ! adm9i/ration ( caffe94 ,9 bo? ( ^! rabbits symptoms appe>$ )9 five m9utes aft] ! injections 7 made4 ,rabbits #fi & #gj1 x w be notic$1 surviv$ ! same am\nt ( caffe9 9 proportion to body weight z 0 giv5 to ! o!r memb]s ( ?is gr\p4 ,increas$ p]i/alsis & ! di/ribution ( ! dose may acc\nt = ! great] resi/ance ( rabbit ,no4 #fi4 ,! case ( rabbit ,no4 #gj is evid5tly "o ( exceptional resi/ance to caffe91 s9ce bo? ! rabbits ( ,gr\p ,,ii di$ f ! effects ( a mu* small] dose1 namely1 #j4ae gram ( caffe9 p] kilo4 ,moreov]1 macroscopical exam9ation at ! autopsy ( ,nos4 #cjg & #cjh fail$ to %[ any lesions :i* might t5d to less5 ! resi/ance to caffe94 ,t a dose ( #j4ae gram p] kilo is !re=e 9 all probability ! m9imum fatal dose = ! rabbit :5 inject$ into ! p]itoneal cavity appe>s f ! results ( ! exp]im5ts 9 s]ies ,c1 9 :i* small] doses1 #j4abe gram ( caffe9 p] kilo caus$ mild symptoms only1 :ile #j4a gram p] kilo r>ely induc$ any symptoms4 ,x may be rem>k$ t ! rabbits ( s]ies ,c 7 f$ c>rots :ile rabbits ,nos4 #cjg & #cjh receiv$ oats4 ,_! resi/ance to caffe9 may be diff]5t1 b1 z 0 po9t$ out 9 ! e>li] "p ( ?is inve/igation1 diet does n seem to influ5ce ! toxicity ( ! s+le dose ( caffe94 ,doses ( #aej & ( #ajj to #abe mg p] kilo1 :5 inject$ into ! p]itoneal cavity1 may be consid]$1 respectively1 z ! m9imum fatal & m9imum toxic doses = ! gray rabbit4 ,analysis ( ! exp]im5ts 9 s]ies ,d %[s mu* great] resi/ance to caffe9 ?an 9 ! o!r rabbits :i* receiv$ x intrap]itoneally4 ,?us1 aft] ! adm9i/ration ( #j4b gram p] kilo to ea* ( five rabbits1 no effect 0 obs]v$ 9 two cases 7,nos4 #caj1 #caa71 :ile 9 two o!rs 7,nos4 #gd1 #ge7 symptoms develop$1 b !y surviv$4 ,only "o rabbit1 ,no4 #cab1 di$ f ! effects ( ?is dose2 ! autopsy %[$ ! pres5ce ( deg5]ation ( ! liv] & pete*ial hemorrhages on ! cortex ( ! kidneys 9 ! case ( ,no4 #caj1 :i* 0 probably ! cause ( dea? r ?an ! caffe94 ,two decigrams ( caffe9 c n be consid]$1 !re=e1 ! fatal dose = rabbits4 ,?is is fur!r corroborat$ by ! results obta9$ 9 exp]im5ts ) l>g] doses4 ,rabbit #gh1 :i* receiv$ #beg mg p] kilo1 fail$ to %[ any symptoms4 ,! same am\nt 9 proportion to body weight 9 ,no4 #cbc caus$ mild symptoms only1 :ile ! rapid dea? ( rabbit ,no4 #cag aft] ! same dose ( caffe9 may be expla9$ by ! lesion f\nd at autopsy1 ?us af=d+ additional evid5ce t disease may decrease ! resi/ance to caffe94 ,x w be obs]v$ t all ! memb]s ( ?is s]ies 7 "y rabbits &1 z w be %[n lat]1 "y animals ( o!r species are likewise m resi/ant to caffe9 ?an adult animals4 ,simil> results 7 obta9$ by von ,anrep1 :o obs]v$ t atrop9 is less toxic 9 "y ?an 9 full-gr[n animals4 ,obs]vations 7 also made on ! diuretic effect ( caffe9 :5 inject$ into ! p]itoneal cavity4 ,! results %[n 9 ! foll[+ table indicates ! /imulat+ effect on r5al secretion :e!r ! diet consi/$ ( oats or ( c>rots4 ,! ur9e ( "s rabbits conta9$ mod]ate am\nts ( sug> aft] f #j4b to #j4ae gram ( caffe9 p] kilo 0 giv52 album5 0 obs]v$ 9 "o case1 b 9 none ( ! o!rs4 ,9 rabbit ,no4 #caa album9 0 f\nd be=e ! injection ( caffe91 b none 9 ! ur9e :i* 0 collect$ ?ree h\rs aft] caffe9 0 inject$4 ,effect ( caffe9 on r5al secretion4 ---------------------------------------- ------------------ ,no4 ,weight4 ,caffe9 ,ur9e4 ,"t4 ,diet4 p] kilo4 ---------------------------------------- ------------------ ,grams4 ,gram4 cc4 #cjg #a1cbj #j4aej #ajj #d4e h\rs ,oats4 #cjh #a1cje 4#aej #ahj d4 ,d4 #bie #a1bje 4#ajj #ajj #b h\rs #bj m9utes ,c>rots4 #bic #a1fje 4#ajj #ij #c h\rs ,d4 #bib #a1eie 4#ajj #aje #d h\rs ,d4 ---------------------------------------- ------------------ ,,note4--,! am\nt ( ur9e secret$ 9 ?ree h\rs by control rabbits1 on a c>rot diet1 v>i$ betwe5 #ce & #ej cc1 ! av]age weight ( ! animals be+ a little above #a1fjj grams4 ,! secretion ( ur9e on an oat diet 0 mu* less = an equal p]iod ( "t4 ,,table #c4--;,intrap]itoneal injections4 ,,s]ies ,a4 ---------------------------------------- ------------------------- ,caffe9 ,"t ( ,duration ,no4 ,weight4 p] appe>ance ( life4 ,rem>ks4 kilo4 ( symptoms4 ---------------------------------------- ------------------------- ,grams4,gram4 #ga #a1fei #j4c #he m9utes #bd h\rs ,gray4 #fa #b1adc 4#c ,at ! end ( ,black4 injection #gb #a1djb 4#c #h m9utes #a4be h\r ,gray & :ite4 ---------------------------------------- ------------------------- ,,s]ies ,b1 ,,gr\p ,i4 ---------------------------------------- ------------------------- #gj #a1dhg #j4b #aj days ,gray & :ite4 #ic #a1dib 4#b #e m9utes #b4e h\rs ,maltese2 giv5 second dose aft] #c days1 di$ #b4e h\rs lat]4 #fi #a1dib 4#b ,ab\t ,surviv$ ,:ite4 #e m9utes #ib #a1chh 4#b #e m9utes #bd h\rs ,yell[4 #cji #a1ejj 4#b #bj m9utes ,belgian2 oats4 ---------------------------------------- ------------------------- ,,s]ies ,b1 ,,gr\p ,,ii4 ---------------------------------------- ------------------------- #cjh #a1cej #j4ae #c h\rs & ,ab\t #b4e days,belgian2 oats4 #dj m9utes #cjg #a1cbj 4#ae #a h\r #bd h\rs ,d4 #bd m9utes ---------------------------------------- ------------------------- ,,s]ies ,c4 ---------------------------------------- ------------------------- #bbc #a1afe #j4abeb h\rs ,surviv$ ,belgian2 c>rots4 #bic #a1fje 4#a d4 ,d4 #bie #a1bje 4#a d4 ,d4 #bib #a1eie 4#a d4 ,d4 #bih #a1bje 4#abea4e h\rs d4 ,d4 ---------------------------------------- ------------------------- ,,s]ies ,d4 ---------------------------------------- ------------------------- #caj #hhj #j4b #b days7#a7 ,ab\t ,belgian2 oats4 #b4e days7#a7 #caa #fej 4#b ,surviv$ ,d4 #cab #gdj 4#b #dj m9utes #d4e h\rs ,maltese2 oats4 #gh #fei 4#begae m9utes ,surviv$ ,yell[ & :ite2 oats4 #ge #hdb 4#b d4 d4 ,gray & :ite4 #gd #fib 4#b d4 d4 #cag #fce 4#beba h\r ,ab\t #b h\rs ,belgian2 oats4 #be m9utes #cbc #hbj 4#be #a h\r ,surviv$ ,:ite2 oats4 #ae m9utes ---------------------------------------- ------------------------- 7#a7 ,n due to caffe94 ,,intramuscul> ,,injection4 ,well-f$ rabbits1 :i* receiv$ a diet exclusively ( oats1 7 us$ = ^! exp]im5ts4 ,! injections 7 made into ! lumb> or into ! gluteal muscles4 ,,s]ies ,a4 ,9 ?is s]ies ! caffe9 0 inject$ into ! gluteal muscles4 ,rabbit #bhd4 ,br[n & :ite1 female4 ,weight1 #a1ajj grams4 ,decemb] #ad3 #b p4 m41 #aa cc #b p] c5t caffe9 inject$ into ! gluteal muscles 7#j4b gram p] kilo71 "u obs]vation until #e p4 m41 _h frequ5t convulsions2 at #e p4 m4 9 a comatose condition4 ,rabbit 0 f\nd dead ! next morn+4 ,rabbit #bhf1 :ite & black1 female4 ,weight1 #a1cae grams4 ,decemb] #ae3 #b4cj p4 m41 #ac cc #b p] c5t caffe9 inject$ into ! gluteal muscles 7#j4aigg gram p] kilo71 tremors & increas$ reflexes obs]v$ dur+ ! next two h\rs1 b no o!r symptoms4 ,decemb] #ag3 ,rabbit alive4 ,rabbit #bhe1 yell[ & :ite1 female4 ,weight1 #a1che grams4 ,decemb] #ad3 #aj4ae a4 m41 #ad cc #b p] c5t caffe9 inject$ into ! gluteal muscles 7#j4b gram p] kilo71 g5]al tremors1 b no convulsions obs]v$4 ,rabbit surviv$4 ,decemb] #ag3 ,rabbit /ill alive4 ,rabbit #bhg4 ,belgian h>e1 female4 ,weight1 #a1adj grams4 ,decemb] #ae3 #b4ae p4 m41 #aa cc ( #b p] c5t caffe9 inject$ into ! gluteal muscles2 #b4cj p4 m41 tonic contractions ( po/]ior limbs4 ,p>alysis & dea? at #b4dj p4 m4 ,,s]ies ,b4 ,9 s]ies ,b ! caffe9 0 inject$ into ! lumb> muscles4 ,rabbit #cjg4 ,belgian h>e1 female4 ,weight1 #a1age grams4 ,febru>y #af3 #aa4je a4 m41 #h cc #b p] c5t caffe9 inject$ 7#j4acf gram p] kilo7 into ! lumb> muscles2 "u obs]vation until #d p4 m41 no symptoms2 #d p4 m41 all[$ to walk on ! floor2 aft] walk+ a %ort di/ance loss ( coord9ation & p>alysis ( po/]ior extremities2 #e4bj p4 m41 f\nd dead4 ,rabbit #cjf4 ,belgian h>e1 female4 ,weight1 #a1hfj grams4 ,febru>y #af3 #aa a4 m41 #ab4e cc #b p] c5t caffe9 inject$ into ! lumb> muscles2 #ab noon1 no symptoms2 #b p4 m41 walk$ ab\t #aj feet1 exhau/ion & p>alysis2 #c p4 m4 f\nd dead4 ,rabbit #aha4 ,belgian h>e4 ,weight1 #a1bcj grams4 7,0 exp]im5t$ on "s "t previ\sly47 ,febru>y #af3 #aj4ee a4 m41 #h cc #b p] c5t caffe9 inject$ into ! lumb> muscles2 7#j4acj gram p] kilo72 #ab noon1 no symptoms2 #b p4 m41 no symptoms2 #c p4 m41 put on ! floor1 walk$ ab\t #aj feet & 0 exhau/$1 po/]ior extremities p>alyz$2 #d p4 m41 f\nd dead4 ,,s]ies ,c4 ,9 ! fall ( ! same ye> additional exp]im5ts 7 c>ri$ out ) doses rang+ f #ajj to #bjj milligrams ( caffe9 p] kilo1 :i* 7 inject$ into ! lumb> muscles4 ,! results are giv5 9 ! foll[+ abbreviat$ protocols3 ,rabbit #dbe4 ,belgian h>e4 ,weight #a1ebj grams4 ,septemb] #bg3 #aj4cj a4 m41 #g4e cc #b p] c5t caffe9 inject$ into ! lumb> muscles2 #b p4 m41 reflexes increas$4 ,septemb] #bh3 ,rabbit normal4 ,octob] #e3 ,weight1 #a1fbj grams2 #b4ej p4 m41 #aj cc #b p] c5t caffe9 inject$ into lumb> muscles2 #c4je p4 m41 reflexes increas$4 ,octob] #ac3 ,weight1 #a1ebj grams2 #aj4cj a4 m41 #aj cc #b p] c5t caffe9 7#aca mg p] kilo7 inject$2 #aa a4 m41 no symptoms2 #aa4cj a4 m41 reflexes mu* increas$4 ,octob] #ad3 ,alive1 no symptoms4 ,rabbit #dbf4 ,belgian h>e1 female4 ,weight1 #a1dbe grams4 ,septemb] #bg3 #g cc #b p] c5t caffe9 inject$ into ! lumb> muscles at #aj4cj a4 m42 #b p4 m41 reflexes increas$4 ,septemb] #bh3 ,rabbit normal4 ,octob] #e3 ,weight1 #a1dbe grams2 #b4ee p4 m41 #i cc #b p] c5t caffe9 inject$ into lumb> muscles2 #c4je p4 m41 reflexes increas$4 ,octob] #ac3 ,weight1 #a1dje grams2 #aj4cj a4 m41 #aj cc #b p] c5t caffe9 7#adb mg p] kilo7 inject$2 #aa a4 m41 no symptoms2 #aa4cj a4 m41 reflexes increas$4 ,octob] #ad3 ,rabbit alive1 no symptoms4 ,rabbit #dbg4 ,belgian h>e1 female4 ,weight1 #a1ghj grams4 ,septemb] #bg3 #i cc #b p] c5t caffe9 inject$ into ! lumb> muscles2 #b p4 m41 reflexes increas$4 ,septemb] #bh3 ,rabbit normal4 ,octob] #e3 ,weight1 #a1hej grams2 #c p4 m41 #aa4e cc #b p] c5t caffe9 inject$ into lumb> muscles2 #c4aj p4 m41 reflexes increas$4 ,octob] #ac3 ,weight1 #a1hcj grams2 #aj4dj a4 m41 #ad cc #b p] c5t caffe9 7#aec mg p] kilo7 inject$ into lumb> muscles2 #aa a4 m41 no symptoms2 #aa4cj a4 m41 reflexes increas$4 ,octob] #ad3 ,rabbit alive1 no symptoms4 ,rabbit #dec4 ,belgian h>e1 male4 ,weight1 #a1afj grams4 ,octob] #ab3 #c4de p4 m41 #aa4e cc #b p] c5t caffe9 9 aque\s solution inject$ into lumb> muscles2 #d4ae p4 m41 reflexes increas$2 #d4cj p4 m41 p>alyz$4 ,octob] #ac3 #i a4 m41 f\nd dead4 ,autopsy3 ,ga/ric mucosa hemorrhagic2 liv] d>k5$2 o!r organs normal4 ,rabbit #dee4 ,belgian h>e1 gray1 female4 ,weight1 #a1ahe grams4 ,octob] #ab3 #c4cj p4 m41 #aa4e cc #b p] c5t caffe9 inject$ into ! lumb> muscles2 #d p4 m41 reflexes increas$4 ,octob] #ac3 ,rabbit weigh$ #a1jgj grams1 no symptom ( caffe9 poison+1 reflexes normal2 #aj4cj a4 m41 #aj cc #b p] c5t caffe9 inject$ into ! lumb> muscles2 #aa4cj a4 m41 jump$ (f ! table1 _h attack ( convulsions & di$4 ,autopsy3 ,f9d+s same z 9 ,no4 #dec4 ,rabbit #dbh4 ,belgian h>e1 gray1 male4 ,weight1 #a1fej grams4 ,octob] #e3 #d p4 m41 #ad4h cc #b p] c5t caffe9 7#j4ah gram p] kilo7 inject$ into ! lumb> muscles4 ,octob] #f3 ,f\nd dead4 ,rabbit #dbi4 ,belgian h>e1 male4 ,weight1 #a1cdj grams4 ,octob] #e3 #d p4 m41 #ac4e cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ into lumb> muscles4 ,octob] #h3 ,rabbit f\nd dead4 ,,s]ies ,d4 ,fur!r exp]im5ts mak+ injections into bo? ! lumb> & ! gluteal muscles1 7 made 9 ?is s]ies4 ,rabbit #egg4 ,gray male4 ,weight1 #a1chj grams4 ,febru>y #ad3 #c p4 m4 #ad cc #b p] c5t caffe9 inject$ into ! gluteal muscles ( ! "r side2 #c4aj p4 m41 re/less1 jump$ (f ! table & walk$ ab\t1 reflexes increas$2 #c4de p4 m41 pass$ #cj cc cle>1 /raw-color$ ur9e2 #d4de p4 m41 all[$ to walk ab\t1 ran across ! room1 ab\t #bj feet1 look$ tir$1 /ret*$ himself out on ! floor1 !n rais$ himself & walk$ ab\t %[+ no di/urbance ( gait4 ,febru>y #ae3 #i a4 m41 f\nd dead4 ,rabbit #egh4 ,gray1 female4 ,weight1 #a1fgj grams4 ,febru>y #ad3 #c4je p4 m41 #ah cc #b p] c5t caffe9 solution inject$ into ! gluteal muscles ( ! "r side2 #c4ae reflexes increas$1 b n re/less2 #e p4 m41 all[$ to walk ab\t1 no symptoms obs]v$4 ,febru>y #ae3 ,f\nd dead4 ,rabbit #egi4 ,:ite & gray1 male4 ,weight1 #a1dij grams4 ,febru>y #ad3 #c4ae p4 m41 #ae cc #b p] c5t caffe9 solution inject$ into ! gluteal muscles ( ! "r side2 put 9 cage2 #c4cj p4 m41 reflexes increas$2 #e p4 m41 tak5 out ( cage & all[$ to walk across ! room1 no special symptoms notic$4 ,febru>y #bc3 ,/ill alive4 ,rabbit #ehj4 ,gray male4 ,weight1 #a1eaj grams4 ,febru>y #ad3 #c4ce p4 m41 #ae cc #b p] c5t caffe9 solution inject$ into lumb> muscles4 ,febru>y #bc3 ,/ill alive1 9 good condition4 ,rabbit #eha4 ,gray female4 ,weight1 #a1fhj grams4 ,febru>y #ad3 #c4de p4 m41 #ag cc #b p] c5t caffe9 solution inject$ into ! lumb> muscles ( ! "r side2 #d p4 m41 reflexes increas$2 #d4ae p4 m41 jump$ (f ! table & _h wild convulsions1 became v re/less1 walk$ ab\t ! laboratory2 #d4be p4 m41 _h convulsions occasionally2 #d4cj p4 m41 extremities ext5d$ & q rigid2 #d4ce p4 m41 convulsions & dea?4 ,rabbit #ehb4 ,gray male4 ,weight1 #a1hgj grams4 ,febru>y #ad3 #d4ae p4 m41 #ah cc #b p] c5t caffe9 solution inject$ into ! lumb> muscles ( "r side2 #e p4 m41 reflexes increas$2 walk$ ab\t 9 ! room1 !n re/$2 #e4ae p4 m41 _h %ort spasm :5 h&l$4 ,febru>y #bc3 ,alive2 good condition4 ,! data pres5t$ 9 ^! exp]im5ts %[ t ! toxicity ( caffe9 :5 inject$ into ! muscles ( ! lumb> regions is ! same z :5 inject$ into ! gluteal muscles4 ,! rabbits ( s]ies ,a receiv$ approximately #j4b gram caffe9 p] kilo & two di$ z a result ( ?is treatm5t4 ,! o!r two surviv$ b symptoms ( caffe9 intoxication 7 obs]v$4 ,9 s]ies ,b small] doses prov$ fatal1 f :i* x w\ld appe> t caffe9 is m toxic :5 inject$ into ! lumb> muscles4 ,fur!r obs]vations1 h[ev]1 fail$ to corroborate ! results obta9$ 9 ?is s]ies4 ,?us1 9 s]ies ,c1 #acj to #aej mg ( caffe9 p] kilo inject$ into ! lumb> muscles produc$ mild symptoms only4 ,exp]im5ts ) l>g] doses %[$ t #j4ahj gram caffe9 p] kilo may cause dea?4 ,x w be notic$1 on ! o!r h&1 t rabbit ,no4 #dee surviv$ a dose ( #j4b gram p] kilo4 ,new exp]im5ts 7 !re=e c>ri$ out 9 :i* ! same am\nts ( caffe9 9 proportion to ! weight ( ! animals 7 inject$ into ! lumb> muscles z into ! gluteal muscles4 ,z %[n 9 ! exp]im5ts ( s]ies ,d1 "o rabbit 7,no4 #eha7 di$ %ortly aft] caffe9 0 inject$ into ! lumb> muscles2 two recov]$4 ,two ( ! ?ree :i* receiv$ injections into ! gluteal muscles 7 f\nd dead ! next day2 "o recov]$4 ,po/-mortem exam9ation fail$ to indicate ! pres5ce ( any abnormalities4 ,! rate ( absorption ( caffe9 f ! gluteal & f ! lumb> muscles seems to be1 !re=e1 ! same1 or n to diff] v mu*4 ,! obs]vations ( ,au] & ,meltz]7#g7 are ( int]e/ 9 ?is connection4 ,accord+ to _! inve/igations adr5al9 is m rapidly absorb$ f ! lumb> ?an f ! gluteal muscles4 ,?is is 9 all probability due to ! great] delicacy ( ! te/ !y employ$ 7s9ce !y judg$ ! rate ( absorption by ! effect ( adr5al9 on blood pressure7 z well z to ! mu* great] activity ( ! sub/ance4 ,,table #d4--;,intramuscul> injections4 ,,s]ies ,a4 ---------------------------------------- ------------------------ ,caffe9 ,no4 ,weight4 p] ,symptoms ,duration ,site ( ,rem>ks4 kilo aft]-- ( life4 injection4 ---------------------------------------- ------------------------ ,grams4,gram4 #bhd #a1ajj #j4bjj #c h\rs ,less ?an ,gluteal ,:ite & #bj h\rs br[n female4 #bhf #a1cae 4#aigg #b h\rs ,surviv$ d4 ,:ite & black female4 #bhe #a1che 4#bjj ,pres5t d4 d4 ,yell[ & :ite female4 #bhg #a1adj 4#baj #ae m9utes#be m9utes d4 ,gray female4 ---------------------------------------- ------------------------ ,,s]ies ,b4 ---------------------------------------- ----------------------- #cjg #a1age #j4acf #e h\rs #f h\rs1 ,lumb> ,gray female4 #bj m9utes #cjf #a1hfj 4#acd #c h\rs #d h\rs d4 ,d4 #aha #a1bcj 4#acj #d h\rs #e h\rs d4 ,gray4 ---------------------------------------- ----------------------- ,,s]ies ,c4 ---------------------------------------- ----------------------- #dbe #a1ebj #j4aca #a h\r ,surviv$ ,lumb> ,gray4 #dbf #a1dje 4#adb #cj m9utes d4 d4 ,gray female4 #dbg #a1hcj 4#aec #ej m9utes d4 d4 ,d4 #dec #a1afj 4#bjj #cj m9utes,less ?an d4 ,gray male4 #bj h\rs #dee #a1ahe 4#bjj d4 ,surviv$ d4 ,gray female4 #dbh #a1fej 4#ahj ,less ?an d4 ,gray male4 #bj h\rs #dbi #a1cdj 4#bjj d4 d4 ,d4 ---------------------------------------- ----------------------- ,,s]ies ,d4 ---------------------------------------- ----------------------- #egg #a1chj #j4bjj #aj m9utes,less ?an ,gluteal ,gray male4 #ah h\rs #egh #a1fgj 4#baj d4 d4 d4 ,d4 #egi #a1dij 4#bjj #ae m9utes,surviv$ d4 ,:ite & gray male4 #ehj #a1eaj 4#bjj d4 ,lumb> ,gray male4 #eha #a1fhj 4#bjj #ae m9utes#ej m9utes d4 ,d4 #ehb #a1hgj 4#aib #de m9utes,surviv$ d4 ,d4 ---------------------------------------- ----------------------- ,exam9ation ( ,table #d %[s t #ad rabbits receiv$ f #ahj to #baj mg caffe9 p] kilo4 ,! appe>ance ( symptoms 9 ^! rabbits v>i$ consid]ably4 ,9 "s increas$ reflexes c\ld be notic$ 9 #aj to #ae m9utes aft] ! injection ( caffe92 9 o!rs x 0 delay$ #b or #c h\rs4 ,x might be add$ t ! onset ( symptoms occurr$ 9 _m cases v soon aft] ! adm9i/ration ( ! drug--on an av]age ab\t #aj to #cj m9utes aft] ! drug 0 inject$4 ,aft] small] doses 7 adm9i/]$ by injection into ! lumb> muscles ! appe>ance ( symptoms 0 delay$ sev]al h\rs 9 "s cases4 ,! duration ( life 9 ^! #ad rabbits v>i$ consid]ably4 ,eight ( !m di$ )9 #a to #bj h\rs2 six surviv$4 ,ab\t #j4b gram caffe9 p] kilo may be reg>d$ z ! m9imum fatal dose1 :ile ! m9imum toxic dose is some:]e betwe5 #acj & #aej mg p] kilo4 ,,intrav5\s ,,injection4 ,^! exp]im5ts 7 c>ri$ out on well-f$1 full-gr[n gray rabbits4 ,! diet = sev]al days prec$+ ! exp]im5ts consi/$ ( oats or c>rots1 :i* 7 giv5 ad libitum4 ,! injections 7 made into ! e> ve9s f a burette or by means ( a syr+e1 ! temp]ature ( ! caffe9 solution be+ ab\t #dj ,c4 ,att5tion 0 also direct$ to ! effect ( ! rate ( injection & ( ! conc5tration on ! toxicity4 ,! m9imum toxic z well z le?al doses 7 det]m9$ z %[n 9 ! foll[+ exp]im5ts4 ,,s]ies ,a4 ,9 ^! exp]im5ts ! rate ( injection 0 ab\t #a cc ( #b p] c5t caffe9 solution p] m9ute4 ,rabbit #aid4 ,:ite1 female4 ,weight1 #a1caj grams4 ,octob] #ai3 ,inject$ #g4e cc #b p] c5t solution caffe9 7#aae mg p] kilo7 into ! e> ve94 ,rabbit %[$ /iffness2 p>alysis ( extremities appe>$ soon aft]4,c ,rabbit surviv$4 ,c ,"t ( injection inadv]t5tly omitt$1 b 0 probably n sl[] ?an 9 ! o!r cases ( ?is s]ies4 ,rabbit #eef4 ,gray1 female4 ,weight1 #a1fce grams4 ,janu>y #ca3 #b p4 m41 #aa cc #b p] c5t caffe9 7#acd mg p] kilo7 inject$ into e> ve91 9 ab\t #aa m9utes2 #b4aj p4 m41 convulsions1 rabbit rema9$ ly+ on its side2 dur+ ! re/ ( ! h\r x _h convulsions occasionally2 #c4bj p4 m41 convulsions & di$4 ,rabbit did n ur9ate aft] ! injection ( caffe94 ,rabbit #eeg4 ,gray1 female4 ,weight1 #a1ehj grams4 ,janu>y #ca3 #b4cj to #b4cg p4 m41 #g cc #b p] c5t caffe9 inject$ f ! burette at ! rate ( #a cc p] m9ute2 #b4cg p4 m41 fl[ ( liquid ceas$1 ve9s 7 engorg$ & bl$ freely1 injection 0 cont9u$ by means ( a syr+e2 #b cc #b p] c5t caffe9 inject$ 9 two m9utes2 injections discont9u$ z convulsions appe>$2 #b4ej p4 m41 rabbit rais$ itself b fell ov]2 #c4aj p4 m41 rabbit assum$ normal attitude1 walk$ ab\t ! floor )\t manife/+ any signs ( ! effects ( caffe92 #d4cj p4 m41 walk$ ab\t1 gait normal1 condition seem$ to be good4 ,febru>y #a3 #b p4 m41 condition good1 appetite good1 total am\nt ( caffe9 inject$1 #i cc #b p] c5t solution1 or #aad mg p] kilo4 ,rabbit #eeh4 ,gray1 female4 ,weight1 #a1eij grams4 ,janu>y #ca3 #c p4 m41 giv5 #h cc #b p] c5t caffe9 9 eight m9utes2 #c4aj p4 m41 viol5t convulsions2 #c4bj p4 m41 rabbit 0 /ret*$ out on 8 abdom51 extremities ext5d$1 ur9at$2 #d4cj p4 m41 look$ normal2 0 able to walk ab\t4 ,febru>y #a3 #b p4 m41 condition good1 appetite good4 ,rabbit #bib4 ,belgian h>e1 male4 ,weight1 #a1ggj grams4 ,febru>y #ah3 #d4bf to #d4ci p4 m41 #ab4e cc w>m caffe9 solution 7#j4ada gram p] kilo7 inject$ into e> ve91 convulsion foll[$ :5 ?is quantity 0 inject$1 tonic rigidity ( limbs foll[$ soon aft]2 #d4eb p4 m41 condition un*ang$1 rabbit on floor1 limbs /ret*$ out1 & ly+ on abdom54 ,rabbit #bid4 ,belgian h>e1 female4 ,weight1 #a1cej grams4 ,c>rot diet = ab\t #aj days be=e ! exp]im5t4 ,febru>y #ai3 #ab4bj p4 m41 #e cc #b p] c5t caffe9 7#gd mg p] kilo7 inject$ into e> ve9 9 five m9utes1 edema ( ! e>1 o!r e> us$1 #c4e cc inject$ 9 #aj m9utes1 repeat$ convulsions2 #a4be p4 m41 rabbit /ill alive1 frequ5t attacks ( convulsions2 #b4cj p4 m41 f\nd dead4 ,total am\nt inject$ 9 #ae m9utes1 #h4e cc1 or #j4abf gram p] kilo4 ,x w be obs]v$ 9 ! prec$+ exp]im5ts t symptoms ( sev]e intoxication 7 pres5t 9 all ( ! six rabbits1 b only two ( ^! 7,nos4 #bid & #eef7 di$ f ! effects ( caffe94 ,( ^? :i* surviv$1 ?ree receiv$ doses ( #ajj to #aad mg caffe9 p] kilo1 & ano!r 7,no4 #bib7 receiv$ #ada mg ( caffe9 p] kilo4 ,! dea? ( rabbits ,nos4 #bid & #eef may be reg>d$ !re=e z a case ( exceptionally l[ resi/ance to caffe94 ,,s]ies ,b4 ,doses ( #afj to #bjj mg caffe9 p] kilo 7 employ$ 9 ^! exp]im5ts4 ,! rate ( injection 0 #a cc p] m9ute1 ) ! exception ( ,exp]im5t #bed1 9 :i* #aj4h cc #b p] c5t caffe9 7 introduc$ 9 #ag m9utes & #be seconds4 ,rabbit #efb4 ,gray female4 ,weight1 #a1fej grams4 ,diet1 oats4 ,febru>y #a3 ,injection began at #c p4 m41 inject$ #aj cc 9 #ab m9utes2 #c4ja p4 m4 to #c4ji p4 m41 #c cc inject$1 convulsions2 #c4ji p4 m4 to #c4ad p4 m41 #c cc inject$1 foll[$ by viol5t convulsions1 m>k$ opi/hotonos2 #d4cj p4 m41 rabbit di$2 total quantity inject$1 #af cc4 ,rabbit #efa4 ,gray female4 ,weight1 #a1dej grams4 ,diet1 oats4 ,febru>y #a3 ,injection began at #aa4dj a4 m42 #aa4dh1 rabbit /ruggl$1 #g cc #b p] c5t caffe9 inject$2 #aa4ej1 convulsions1 #aj cc #b p] c5t caffe9 total am\nt inject$2 #aa4ee a4 m41 injections /opp$2 injections resum$ #aa4eh1 viol5t convulsions1 injections discont9u$1 total quantity receiv$1 #ad4e cc #b p] c5t caffe9 solution2 #a4cj p4 m41 f\nd dead1 did n ur9ate1 #be cc ur9e f\nd 9 ! bladd]4 ,rabbit #efj4 ,gray male4 ,weight1 #a1fbj grams4 ,diet1 oats4 ,febru>y #a3 ,injection began #aa a4 m42 #aa4aj a4 m41 #g cc #b p] c5t caffe9 inject$1 rabbit /ruggl$2 #a cc 0 inject$ dur+ ! next ?ree m9utes1 rabbit /ruggl$ b !re 7 no convulsions1 injection /opp$2 resum$ at #aa4ae a4 m4 & cont9u$ #aj m9utes1 #h cc #b p] c5t caffe9 introduc$ dur+ ?is "t2 total am\nt caffe9 inject$1 #af cc2 reflexes m>k$ly increas$2 #ab noon1 tetanic convulsions (f & on until #b p4 m41 !n rema9$ /ret*$ out on abdom51 extremities ext5d$4 ,febru>y #b3 #i a4 m41 f\nd dead4 ,rabbit #eei4 ,gray female4 ,weight1 #a1hge grams4 ,diet1 oats4 ,janu>y #ca3 #d p4 m41 convulsions aft] injection ( #i cc #b p] c5t caffe9 9 #ad m9utes2 #d4jh p4 m41 convulsions aft] injection ( #g cc caffe9 9 #h m9utes2 #d4aj to #d4ab p4 m41 inject$ #b cc m1 rabbit ly+ /ret*$ out on abdom51 extremities ext5d$2 total am\nt ( caffe9 inject$1 #ah cc 7#aij mg p] kilo74 ,febru>y #a3 #b p4 m41 condition good1 walk$ ab\t1 appetite good1 pass$ #aee cc d>k1 r$di%-br[n ur9e s9ce #e4cj p4 m4 previ\s day4 ,rabbit #bgi4 ,gray & :ite female4 ,weight1 #a1cbj grams4 ,febru>y #bd3 #aj4ji a4 m41 #f cc #b p] c5t caffe9 pass$ rapidly into jugul> ve92 #aj4ae a4 m41 involunt>y twit*+ ( muscles ( legs1 b no o!r symptoms2 #aj4bc to #aj4bf1 #c cc ( #b p] c5t caffe9 inject$2 #aj4bg to #aj4bh1 #b cc #b p] c5t caffe9 inject$1 convulsions2 #aj4bi1 convulsions /opp$2 #aj4cb1 convulsions2 #aa a4 m41 rabbit ly+ on its side1 ant]ior extremities p>alyz$1 po/]ior extremities contract$1 no clonic convulsions1 brea!d deep] & m sl[ly ?an normal2 #aa4aj a4 m41 rabbit di$1 _h no convulsions imm$iately be=e dea?2 am\nt ( caffe9 inject$1 #aa cc #b p] c5t solution1 or #j4aff gram p] kilo4 ,rabbit #bed4 ,belgian h>e1 female4 ,weight1 #a1bhe grams4 ,diet1 oats4 ,novemb] #ab3 #a4cj-a_/c to #a4dg p4 m41 receiv$ #aj4h cc #b p] c5t caffe9 f burette into e> ve91 aft] injection ( #f4b cc dyspnoea1 #f4g cc /ruggl+1 convulsions2 at #a4ej p4 m41 releas$ f hold]1 p>alysis especially m>k$ 9 ! ant]ior extremities2 #a4ej p4 m41 recov]$1 surviv$2 total am\nt inject$1 #aj4h cc #b p] c5t caffe9 9 #ag m9utes & #be seconds1 or #j4af gram caffe9 p] kilo4 ,rabbit #bee4 ,belgian h>e1 male4 ,weight1 #a1aje grams4 ,diet1 oats4 ,novemb] #ab3 #b4ca to #b4ce p4 m41 receiv$ #c4g cc2 f #b4cg-a_/f to #b4df-a_/f p4 m41 #e cc inject$2 aft] injection ( #f4a cc convulsions foll[$ by dyspnoea1 !n cont9u\s /ruggl+2 :5 #h4c cc 7 inject$ rabbit _h ano!r convulsion2 #b4dg p4 m41 tonic contraction ( ant]ior extremities2 am\nt inject$1 #h4g cc 7#aeh mg p] kilo7 9 #ae m9utes & #ce seconds4 ,rabbit #efg4 ,gray female4 ,diet1 oats4 ,febru>y #f3 ,injection began at #d4aa p4 m42 #d4ah1 convulsions aft] injection ( #e cc #b p] c5t caffe92 #d4ba1 convulsion aft] total injection ( #h cc2 #d4bd p4 m41 injection resum$ & #b cc m introduc$2 #d4bh p4 m41 convulsions1 inject$ #b cc m2 total caffe9 inject$1 #ab cc1 or #afb mg p] kilo2 #d4dj p4 m41 rabbit p>alyz$ 9 po/]ior extremities2 #e p4 m41 f\nd dead4 ,9 ! eight exp]im5ts compris+ s]ies ,b rabbits ,nos4 #efg1 #bed1 #bgi1 & #bee1 :i* may be designat$ z ,gr\p ,,ii1 receiv$ doses ( #afb1 #afj1 #aff1 & #aeh mg1 respectively4 ,nos4 #efb1 #efa1 #efj1 & #eei1 :i* may be designat$ z ,gr\p ,i1 receiv$ ab\t #bjj mg caffe9 p] kilo4 ,9 ,gr\p ,,ii1 :i* receiv$ ! small] doses1 "o 7,no4 #bed7 surviv$4 ,?is may be reg>d$ z exceptional1 s9ce1 z 0 %[n 9 ! exp]im5ts ( ! prec$+ s]ies1 ev5 small] doses may be fatal4 ,ab\t #afj mg p] kilo is1 !re=e1 ! smalle/ surely fatal dose4 ,?is might be reg>d$ z a contradiction ( ! results obta9$ = rabbit ,no4 #eei1 b x w be notic$ t 9 ?is case diuresis 0 v m>k$4 ,! results ( exp]im5ts ,nos4 #bid & #bee are ( int]e/ 9 ?is connection1 s9ce !y indicate t a mod]ate diff]5ce 9 ! rate ( injection is )\t any effect on ! toxicity ( caffe94 ,! great] resi/ance to caffe9 ( rabbit ,no4 #eei is 9 all probability due1 !re=e1 to increas$ diuresis4 ,,s]ies ,c4 ,9 ^! exp]im5ts ! m9imum toxic dose 0 det]m9$4 ,! conditions 7 ! same z 9 ! exp]im5ts ( ! o!r s]ies4 ,rabbit #bic4 ,belgian h>e1 female4 ,weight1 #a1faj grams4 ,diet1 oats4 ,febru>y #ah3 #c4dj to #c4dc p4 m41 #d cc #b p] c5t w>m caffe9 solution inject$ into e> ve91 convulsions :5 #c cc 7 inject$1 repeat$ attacks2 #d p4 m41 rais$ itself on legs1 b fell ov] imm$iately & lay /ret*$ on abdom54 ,febru>y #ai3 #i a4 m41 rabbit look$ normal1 app>5tly recov]$4 ,rabbit #bbg4 ,:ite male4 ,weight1 #b1cbj grams4 ,octob] #bf3 #c4bi to #c4cg p4 m41 inject$ into e> f burette #f4g cc #b p] c5t caffe91 no symptoms2 exp]im5t discont9u$2 surviv$4 ,rabbit #efc4 ,gray female4 ,weight1 #a1fej grams4 ,diet1 oats4 ,febru>y #f3 ,injection began at #a4jb p4 m41 inject$ #c4e cc #b p] c5t caffe9 7#db mg p] kilo7 9 f\r m9utes1 #j4f cc m )9 ! next two & "o-half m9utes1 total am\nt inject$ #d4a cc2 #a4aj p4 m41 hyp]s5sitive1 "s di/urbance ( muscul> coord9ation2 re/lessness2 #a4ce4 p4 m41 reflexes decreas$1 ur9at$ & walk$ ab\t1 gait normal4 ,"u obs]vation = sev]al days2 no symptoms not$4 ,rabbit #efd4 ,gray female4 ,weight1 #a1eae grams4 ,febru>y #f3 ,injection began at #a4bf p4 m41 #c4e cc #b p] c5t caffe9 7#df mg p] kilo7 inject$ at ! rate ( #a cc p] m9ute2 #a4cj p4 m41 reflexes increas$2 #a4cd p4 m41 m>k$ p>esis ( ! extremities1 rabbit /ret*$ out on abdom51 legs abduct$ & p>tly ext5d$1 able to hop ab\t b gait di/urb$1 no unt[>d symptoms notic$1 "u obs]vation = sev]al days aft] exp]im5t4 ,rabbit #efe4 ,gray female4 ,weight1 #a1ede grams4 ,diet1 oats4 ,febru>y #f3 ,/>t$ to inject at #c4dj p4 m41 receiv$ #b4e cc #b p] c5t caffe9 intrav5\sly 9 two m9utes or #cb mg p] kilo1 "u obs]vation all aft]noon1 no symptoms4 ,rabbit #eff4 ,gray female4 ,weight1 #a1ijj grams4 ,diet oats4 ,febru>y #f3 ,injection began at #c4je p4 m41 receiv$ #c cc #b p] c5t caffe9 intrav5\sly 9 ?ree m9utes or #ca mg p] kilo1 no symptoms obs]v$4 ,^! exp]im5ts %[ t a dose ( ab\t #ej mg p] kilo :5 inject$ intrav5\sly produces mild symptoms1 su* z increas$ reflexes4 ,9 ! f\r exp]im5ts ) ?is am\nt ( caffe9 ^! effects 7 obs]v$ 9 ea* case4 ,9 ! exp]im5ts 9 :i* small] quantities1 #cj mg p] kilo1 7 giv5 intrav5\sly !re 0 no manife/ation ( symptoms4 ,a dose n ov] #ej mg p] kilo may1 !re=e1 be reg>d$ z ! m9imum toxic dose :5 inject$ intrav5\sly "u ! conditions /at$4 ,,s]ies ,d4 ,a #j4e p] c5t caffe9 solution 0 us$ 9 ^! exp]im5ts 9 ord] to te/ ! effect ( conc5tration on its toxicity2 ! rate ( injection 0 #a cc p] m9ute4 ,rabbit #efi4 ,gray male4 ,weight1 #a1dge grams4 ,diet1 oats4 ,febru>y #f3 #aa4ej a4 m4 to #ab4ja p4 m41 inject$ #aj cc #j4e p] c5t caffe92 #ab4jc to #ab4ab p4 m41 inject$ #aj cc ( #j4e p] c5t caffe92 #ab4ac to #ab4bf p4 m41 inject$ #aj cc ( #j4e p] c5t caffe91 total am\nt inject$1 #cj cc2 #ab4bj1 pass$ #ce cc ( ur9e2 #ab4cj1 increas$ reflexes1 b no convulsions2 #d p4 m41 reflexes increas$4 ,febru>y #aa3 ,alive1 condition good4 ,rabbit #egd4 ,gray female4 ,weight1 #a1eee grams4 ,diet1 oats4 ,febru>y #h3 #aj4be to #aj4cc a4 m41 inject$ #d cc ( #j4e p] c5t caffe9 9 salt solution1 injection discont9u$ = five m9utes2 #aj4ch to #aa4aj1 inject$ #cj cc1 total am\nt ( caffe9 solution receiv$1 #cd cc2 #aa4ee a4 m41 v s5sitive2 reflexes m>k$ly increas$4 ,febru>y #i3 ,alive1 condition good4 ,rabbit #ega4 ,gray female4 ,weight1 #a1ecj grams4 ,diet1 oats4 ,febru>y #g3 ,injection #c4ah to #c4ej p4 m41 receiv$ #cj cc 9 #cb m9utes1 n hyp]s5sitive2 #c4ee1 re/lessness & weakness ( extremities2 #d4aj p4 m41 control ( ant]ior extremities impair$1 di/9ctly p>etic b tri$ to walk ab\t1 di$ ! same aft]noon4 ,rabbit #efh4 ,gray male4 ,weight1 #a1fje grams4 ,diet1 oats4 ,febru>y #g3 ,injection #aj4ec to #aa4ja a4 m41 inject$ #aj cc #j4e p] c5t caffe92 #aa4jc1 injection resum$ aft] two m9utes int]val2 #aa4ad1 receiv$ #aj cc #j4e p] c5t caffe9 intrav5\sly 9 #aa m9utes2 #aa4af1 injection resum$2 #aa4ce1 receiv$ #ab cc #j4e p] c5t caffe91 total am\nt ( caffe9 solution receiv$1 #cb cc2 #ab4cj p4 m41 ur9at$ #ad cc ( bloody ur9e2 #ab4ee p4 m41 convulsions & dea? a few m9utes lat]4 ,autopsy %[$ conge/ion ( visc]a1 b no o!r lesions4 ,rabbit #egj4 ,gray female4 ,weight1 #a1bbe grams4 ,diet1 oats4 ,febru>y #g3 #b4jf to #b4ce p4 m41 inject$ #bd4e cc #j4e p] c5t caffe91 reflexes increas$ b no convulsions1 p>esis especially m>k$ 9 ! ant]ior extremities2 #c p4 m41 pass$ ur9e :i* 0 normal 9 appe>ance1 reflexes n increas$ b rabbit 0 weak4 ,febru>y #i3 ,f\nd dead4 ,autopsy3 ,liv]1 sple51 & kidneys conge/$2 l>ge inte/9es hemorrhagic2 om5tum conge/$ & %[$ ! pres5ce ( small case\s nodules2 liv] %[$ adhesion to diaphragm2 visc]a pres5t$ ! appe>ance ( intraabdom9al infection4 ,( ! five rabbits ( ?is s]ies ?ree di$ z a result ( ! adm9i/ration ( caffe94 ,! o!r two :i* surviv$ %[$ mild symptoms only1 su* z increas$ reflexes1 b no evid5ce ( sev]e poison+ su* z 0 obs]v$ aft] ! injection ( ! same doses ( caffe9 9 s]ies ,a :5 a #b p] c5t solution ( caffe9 0 inject$4 ,convulsions 7 notic$ 9 "o case only 7,no4 #efh72 p>esis 9 two cases 7,nos4 #egj & #ega74 ,! n]v\s symptoms ev5 9 ?is gr\p1 !re=e1 7 mu* mild] ?an 9 s]ies ,a4 ,! p]c5tage ( dea?1 h[ev]1 0 great] ?an 9 s]ies ,a1 9 :i* ! conc5tration ( caffe9 0 f\r times z great4 ,x is q probable t ! /ra9 on ! he>t due to ! sudd5 increase 9 volume ( ! blood & its dilution might be an important factor 9 increas+ ! toxicity ( caffe94 ,x is conceivable t doses j suffici5tly l>ge to depress ! normal he>t may cause p>alysis ( an already ov]/ra9$ organ4 ,,s]ies ,e4 ,9 ! two exp]im5ts ( ?is s]ies ! rate ( injection z a possible factor influ5c+ ! toxicity ( caffe9 0 te/$4 ,a #b p] c5t caffe9 solution 0 inject$ at ! rate ( #a cc 9 two & "o-half to ?ree m9utes4 ,rabbit #egb4 ,gray male4 ,weight1 #a1ggj grams4 ,diet1 oats4 ,febru>y #h3 ,injection began at #c p4 m41 discont9u$ at #c4cg p4 m41 & resum$ at #c4ch p4 m42 rabbit 0 re/less2 injection f9i%$ at #c4eb p4 m4 ,total quantity receiv$1 #ag4d cc #b p] c5t caffe9 intrav5\sly 9 #eb m9utes2 /ruggl$ int]mitt5tly dur+ ! injection2 ant]ior legs p>alyz$4 ,febru>y #i3 ,f\nd dead4 ,rabbit #egc4 ,gray male4 ,weight1 #a1haj grams4 ,diet1 oats4 ,febru>y #h3 ,/>t$ to inject at #a4ce & discont9u$ at #b4bg p4 m42 receiv$ #ah cc #b p] c5t caffe9 intrav5\sly 9 #eb m9utes2 reflexes m>k$ly increas$ soon aft]2 #b4de1 pass$ bloody ur9e2 #d4cj p4 m4 reflexes increas$2 no o!r symptoms4 ,febru>y #i3 #i a4 m41 f\nd dead4 ,x w be obs]v$ t "s ret>dation ( ! onset ( symptoms 0 caus$ by sl[] injection1 b ! f9al result 0 ! same z :5 ! injections 7 made m rapidly4 ,x is q probable1 !re=e1 t a mu* sl[] rate ( injection may less5 consid]ably ! toxicity ( caffe94 ,f ! results ( ! exp]im5ts by intrav5\s injection summ>iz$ 9 ! table1 x appe>s t ! m9imum toxic dose = rabbits ( a #b p] c5t caffe9 solution1 inject$ at ! rate ( #a cc p] m9ute1 is ab\t #ej mg p] kilo4 ,twice ! dose induces sev]e symptoms & may be fatal2 #afj mg p] kilo are surely fatal4 ,if ! rate ( injection is dim9i%$1 ! toxicity ( caffe9 is less5$1 b ?is effect is n m>k$ unless ! injections are v sl[4 ,dilution ( ! caffe9 solution suppresses to "s ext5t ! n]v\s symptoms1 b ! toxicity1 on ! contr>y1 seems to be increas$4 ,,table #e4--;,intrav5\s injections4 ,,s]ies ,a4 ---------------------------------------- ----------------------- ,caffe9 ,duration ,no4,weight4 p] ,symptoms4 ( life4 ,diet4 ,rem>ks4 kilo4 ---------------------------------------- ----------------------- ,grams4 ,mg4 #aid #a1caj #aad ,pres5t ,surviv$ ,oats ,:ite female4 #eef #a1fce #acd #aj m9utes #bj m9utes d4 ,gray female4 #eeg #a1ehj #aad ,pres5t ,surviv$ d4 ,d4 #eeh #a1eij #ajj d4 d4 d4 ,d4 #bib #a1ggj #ada d4 d4 d4 ,d4 #aid #a1cej #abf d4 #aj m9utes ,c>rots ,d4 ---------------------------------------- ----------------------- ,,s]ies ,b1 ,,gr\p ,i4 ---------------------------------------- ----------------------- #efb #a1fej #bjj #a h\rs ,oats ,gray female4 #efa #a1dej #bjj d4 d4 ,d4 #efj #a1fbj #bjj ,pres5t ,less ?an d4 ,d4 #bd h\rs #eei #a1hge #aij d4 ,surviv$ d4 ,d4 ---------------------------------------- ----------------------- ,,s]ies ,b1 ,,gr\p ,,ii4 ---------------------------------------- ----------------------- #bgi #a1cbj #aff #a h\r ,gray & :ite female4 #bed #a1bhe #afj ,surviv$ ,oats ,gray female4 #efg #afb ,ab\t #de ,d4 m9utes #bee #aeh ,di$ ---------------------------------------- ----------------------- ,,s]ies ,c4 ---------------------------------------- ----------------------- #bic #a1faj #ejj ,pres5t ,surviv$ ,oats ,gray female4 #bbg #b1cbj #egj ,none d4 ,:ite male4 #efc #a1fej #ejj ,pres5t d4 d4 ,gray female4 #efd #a1eae #dfj d4 d4 ,d4 #efe #a1ede #cbj ,none d4 d4 ,d4 #eff #a1ijj #caj d4 d4 d4 ,d4 ---------------------------------------- ----------------------- ,,s]ies ,d4 ---------------------------------------- ----------------------- #efi #a1dge #ajj ,pres5t ,surviv$ ,oats ,gray male4 #egd #a1eee #aab d4 d4 d4 ,gray female4 #ega #a1ecj #ajj d4 ,ab\t d4 ,d4 #b h\rs #efh #a1fje #ajj #bj m9utes d4 ,gray male4 #egj #a1bbe #ajj ,less ?an d4 ,d4 #bj h\rs ---------------------------------------- ----------------------- ,,s]ies ,e4 ---------------------------------------- ----------------------- #egb #a1ggj #bjj ,pres5t ,ab\t ,oats #bd h\rs #egc #a1haj #bjj d4 d4 ---------------------------------------- ----------------------- ,,summ>y4 ,! results ( ! exp]im5ts on rabbits %[ consid]able v>iation 9 ! toxicity ( ! s+le dose4 ,individuals diff]$ s widely 9 _! resi/ance to ?is drug t ! same exp]im5ts _h to be repeat$ _m times ) ea* me?od ( adm9i/ration be=e satisfactory conclusions c\ld be drawn4 ,?is is /rik+ly illu/rat$ 9 ! exp]im5ts by intrav5\s injection 9 :i* a dose ( ne>ly #j4b gram p] kilo 0 n fatal4 ,simil> in/ances ( exceptional resi/ance or ( s5sitiv5ess to caffe9 7 obs]v$ :5 x 0 giv5 9 o!r ways4 ,a comp>ison ( ! toxicity ( caffe9 adm9i/]$ by diff]5t me?ods 9 ?is inve/igation %[s well-m>k$ diff]5ces 9 its activity1 al?\gh !y are n q s /rik+ z simil> exp]im5ts ) o!r alkaloids report$ by sev]al obs]v]s4 ,! toxicity ( caffe9 9 ^! exp]im5ts on ! rabbit indicates t x is greate/ :5 giv5 by ve9 & lea/ :5 giv5 by m\?4 ,! ratio ( ! m9imum toxic doses by ^! two me?ods ( introduction ( caffe9 0 ab\t #g4a2 ! relation ( ! m9imum fatal dose 0 ab\t #c4a4 ,! toxicity :5 giv5 subcutane\sly is ab\t #ae to #bj p] c5t great] ?an :5 giv5 by m\?4 ,! diff]5ce betwe5 ! intramuscul> & subcutane\s injection is ev5 m m>k$4 ,! toxicity ( caffe9 :5 inject$ into ! muscles is ab\t midway betwe5 t adm9i/]$ by ! subcutane\s & intrap]itoneal r\tes1 & is ab\t half t inject$ intrav5\sly4 ,meltz] & ,au]17#eh7 :o exp]im5t$ ) a numb] ( drugs f\nd t ! intramuscul> me?od ( adm9i/ration is z effective z ! intrav5\s1 fluoresc9 =m+ ! only exception accord+ to _! obs]vations4 ,9 ! exp]im5ts ( ,sollman & ,br[n7#ha7 ) ergot1 ! effect 0 q diff]5t f ^? obta9$ by ,meltz] & ,au]7#eh7 ) ! drugs !y us$4 ,x is q possible t ! result obta9$ ) ergot is m]ely illu/rative ( a diff]5ce 9 ! behavior ( v>i\s sub/ances 9 ?is reg>d4 ,?is appe>s probable on acc\nt ( ! diff]5ce 9 ! rate ( absorption = v>i\s sub/ances4 ,?us1 accord+ to ,a*>d1 ,gaill>d1 & ,ribot 7,compt4 r5d4 ,soc4 biol41 #aijg1 #fb3 #ij71 absorption f ! p]itoneal cavity v>ies ) ! conc5tration ( ! solution & ! size ( ! molecule4 ,! small] ! molecule & ! great] ! conc5tration ! m rapid ! absorption4 ,t ! rate ( absorption f ! intramuscul> tissues is unequal & v>ies = diff]5t sub/ances appe>s f ! exp]im5ts ( ,meltz] & ,au]47#eh7 ,! diff]5ce 0 v /rik+ betwe5 intramuscul> & subcutane\s adm9i/ration ( cur>a or adr5al92 ! results 7 some:at diff]5t ) morph9 & ) fluoresc94 ,z %[n 9 _! protocols1 ! onset ( ! symptoms aft] ! intramuscul> injection ( morph9 0 soon] ?an aft] subcutane\s injection1 b 9 "t ! diff]5ce dim9i%es & disappe>s altoge!r4 ,! absorption ( fluoresc9 is mu* fa/] :5 ! intramuscul> pa? is us$ ?an :5 giv5 subcutane\sly1 b ! writ]s /ate t ! rate falls f> beh9d t ( ! intrav5\s adm9i/ration4 ,! diff]5ce 9 toxicity we obs]v$ betwe5 fe$+ by m\? & subcutane\s injection1 al?\gh di/9ct1 0 n v great4 ,x 0 mu* less ?an ,maurel7#ee7 obta9$ ) ! hydrobromid ( caffe9 9 ! rabbit4 ,:e!r ?is diff]5ce betwe5 8 results & ours is due to ! use ( ! pure alkaloid 9 our exp]im5ts & ! hydrobromid employ$ by ,maurel c n be /at$ at pres5t ) any degree ( accuracy4 ,x is hop$ t ! "w 9 progress 9 ! laboratory w ?r[ "s light on ! subject 9 ! ne> future4 ,b ,maurel's7#ef7 exp]im5ts %[ t v>i\s sub/ances behave diff]5tly 9 ?is reg>d4 ,?us ! toxicity ( /ry*n91 he /ates1 is ?ree times z great :5 giv5 subcutane\sly z :5 giv5 by m\? & six times t ( ! m9imum fatal dose by ve94 ,x may be rem>k$1 h[ev]1 t exam9ation ( 8 data %[s t 8 doses are mu* too l>ge = ! rabbit4 ,9 exp]im5ts ) o!r drugs little or no diff]5ce betwe5 ! two modes ( adm9i/ration 0 notic$4 ,?us1 digital9 0 b slightly m active :5 giv5 subcutane\sly ?an by m\?1 :ile ! toxicity ( emet9 hydro*lorid 0 j ! same1 :i*ev] "o ( ^! me?ods ( introduc+ ! sub/ance 0 us$4 ,diff]5ces 9 ! toxicity ( sub/ances h also be5 obs]v$ betwe5 subcutane\s & intrav5\s modes ( adm9i/ration1 b "h1 too1 ! diff]5ces = v>i\s sub/ances 7 unequal4 ,,exp]im5ts ,,on ,,gu9ea ,,pigs4 ,! toxicity ( caffe9 0 /udi$ 9 a l>ge numb] ( individuals4 ,! exp]im5ts 7 conduct$ on full-gr[n animals & 7 c>ri$ out at diff]5t seasons ( ! ye> 9 a v>iety ( ways4 ,special att5tion 0 giv5 to diet z a possible factor influ5c+ resi/ance to caffe91 & ! effect ( diff]5t modes ( adm9i/ration on toxicity4 ,"s animals 7 !re=e f$ oats1 "s c>rots1 o!rs receiv$ bo? hay & oats4 ,caffe9 0 introduc$ subcutane\sly1 intrap]itoneally1 & by m\?4 ,,subcutane\s ,,injection4 ,,s]ies ,a4 ,prelim9>y exp]im5ts c>ri$ out on ?ree gu9ea pigs1 :i* receiv$ #cfj1 #cjj1 & #bij mg ( caffe9 p] kilo subcutane\sly h %[n t su* doses 7 rapidly fatal4 ,two ( ! animals 7 seiz$ ) convulsions half an h\r aft] ! introduction ( caffe9 & di$ dur+ ! attack4 ,! o!r _h tetanus two m9utes aft] ! injection ( caffe94 ,repeat$ attacks foll[$1 :i* t]m9at$ 9 ! dea? ( ! animal two & a half h\rs lat]4 ,! fatal & toxic doses mu/ !re=e be consid]ably "u #j4c gram ( caffe9 p] kilo :5 introduc$ by ?is pa? & small] doses 7 !re=e inject$4 ,! results are %[n 9 ! exp]im5ts ( ! next s]ies4 ,,s]ies ,b4 ,exp]im5ts ) #b decigrams p] kilo con/itut$ ?is s]ies4 ,gu9ea pig #bj4 ,female4 ,weight1 #dig grams4 ,diet1 oats4 ,april #b3 #e cc #b p] c5t caffe9 inject$ subcutane\sly at #aa4cj a4 m42 #a4ej p4 m41 spasm ( %ort duration4 ,di$ at #c p4 m41 ?ree & "o-half h\rs aft] injection4 ,gu9ea pig #ch4 ,br[n male4 ,weight1 #egj grams4 ,diet1 c>rots & oats week previ\s to injection4 ,febru>y #aa3 #c4ej p4 m41 #f cc #b p] c5t caffe9 inject$ subcutane\sly 9 back 7#baj mg p] kilo72 #d4ae1 reflexes increas$1 _h convulsion ( %ort duration :5 di/urb$2 #d4de p4 m41 on h&l+1 repeat$ convulsion & p>alysis2 #e p4 m41 gu9ea pig ly+ on 8 side1 respiration difficult & labor$4 ,febru>y #aa3 #e4je p4 m41 gu9ea pig f\nd dead1 #b h\rs & #ae m9utes aft] injection4 ,gu9ea pig #cg4 ,male4 ,weight1 #hbj grams4 ,diet1 c>rots & oats dur+ week prec$+ ! injection ( caffe94 ,febru>y #aa3 #c4ce p4 m41 #h4e cc #b p] c5t caffe9 inject$ subcutane\sly 9 ! back2 #e p4 m41 pig v s5sitive1 ant]ior extremities p>alyz$ :5 h&l$1 frequ5t spasms ( po/]ior extremities1 no symptoms notic$ be=e #e p4 m41 al?\gh wat*$ all ! "t2 #e4je p4 m41 gu9ea pig on 8 legs & look$ normal4 ,no attack on h&l+4 ,febru>y #ab3 #i a4 m41 f\nd dead2 di$ )9 #ah h\rs4 ,gu9ea pig #ac4 ,female4 ,weight1 #fah grams4 ,diet1 oats4 ,m>* #bi3 #b4de1 #f cc #b p] c5t caffe9 inject$ subcutane\sly 7#j4aid grams p] kilo74 ,m>* #cj3 ,di$ at #d p4 m41 #be h\rs aft] injection4 ,gu9ea pig #cf4 ,male4 ,weight1 #hej grams4 ,f$ oats & c>rots = "o week previ\s to injection4 ,febru>y #aa3 #c4cj p4 m41 #h4e cc #b p] c5t caffe9 inject$ subcutane\sly into back2 #e p4 m41 some:at m s5sitive ?an normal1 no o!r symptoms1 no effect on h&l+2 #e4je p4 m41 no symptoms4 ,febru>y #ab3 #i a4 m41 f\nd dead1 ab\t #ah h\rs aft] injection4 ,! results ( ^! exp]im5ts1 z obs]v$ 9 five gu9ea pigs1 indicate t two decigrams ( caffe9 p] kilo ( animal produce symptoms )9 a half to ab\t two & a qu>t] h\rs aft] injection4 ,dea? foll[$ 9 two gu9ea pigs #gj m9utes to #a h\r aft] ! fir/ manife/ations ( symptoms4 ,two o!rs di$ dur+ ! night1 :ile "o liv$ #be h\rs aft] ! injection ( caffe94 ,ev5 #b decigrams caffe9 p] kilo weight might !re=e be fatal to ! gu9ea pig4 ,exp]im5ts c>ri$ out lat] h %[n1 h[ev]1 t ! resi/ance to caffe9 is appreciably great] 9 "s gu9ea pigs4 ,?is is indicat$ by ! foll[+ exp]im5ts1 9 :i* doses ( #j4b to #j4bd gram caffe9 p] kilo 7 adm9i/]$ by ! same pa?4 ,,s]ies ,c4 ,gu9ea pig #ff4 ,yell[ & d>k br[n male4 ,weight1 #eaj grams4 ,diet1 oats4 ,octob] #d3 #e cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ subcutane\sly 9 ! back at #c p4 m42 #e p4 m41 no symptoms4 ,octob] #e3 #i a4 m41 alive2 condition good4 ,octob] #i3 ,f\nd dead4 ,autopsy3 ,conge/ion ( liv]1 kidney1 & small inte/9e4 ,gu9ea pig #fe4 ,:ite & black male4 ,weight1 #eaj grams4 ,diet1 oats4 ,octob] #d3 #e cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ subcutane\sly 9 ! back at #c p4 m42 #e p4 m41 no symptoms4 ,octob] #e3 #i a4 m41 condition good4 ,gu9ea pig #fj4 ,:ite & gray female4 ,weight1 #cbj grams4 ,diet1 oats4 ,octob] #c3 #b4be p4 m41 #c4e cc #b p] c5t caffe9 7#j4bai gram p] kilo7 inject$ subcutane\sly 9 ! back2 #c4dj p4 m41 convulsion ) recov]y2 #c4ej p4 m41 frequ5t spasms ) p>alysis1 especially ( ant]ior extremities2 #e4cj p4 m41 tetanus :5 remov$ f cage & put on floor4 ,octob] #d3 #h4ej a4 m41 f\nd dead4 ,autopsy3 ,conge/ion ( small inte/9es1 lungs1 liv]4 ,gu9ea pig #eg4 ,:ite & gray female4 ,weight1 #cej grams4 ,diet1 oats4 ,octob] #c3 #b4ae p4 m41 #c4e cc #b p] c5t caffe9 inject$ subcutane\sly 9 ! back 7#j4b gram p] kilo72 #c4dj p4 m41 convulsions ) recov]y2 #e4cj p4 m41 no m>k$ symptoms4 ,octob] #d3 #h4ej a4 m41 alive1 active4 ,octob] #f3 ,f\nd dead at #i a4 m4 ,autopsy3 ,conge/ion ( lungs & liv]2 kidneys pete*iat$2 sev]e ga/ro-ent]itis4 ,gu9ea pig #fh4 ,yell[ male4 ,weight1 #ghe grams4 ,diet1 oats4 ,octob] #f3 #aa4ce a4 m41 #g4h cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ subcutane\sly2 #ab noon1 reflexes increas$ m>k$ly2 #d4bj p4 m41 reflexes ! same z at #ab noon4 ,octob] #g3 #i a4 m41 dead4 ,autopsy3 ,lungs conge/$2 liv] conge/$ & fatty2 sple5 conge/$1 kidney %[$ hemorrhagic spots2 ga/ric mucosa necrotic2 small portion ( small inte/9e inflam$4 ,gu9ea pig #fi4 ,:ite male4 ,weight1 #ehe grams4 ,diet1 oats4 ,octob] #f3 #aa4dj a4 m41 #e4h cc #b p] c5t caffe9 inject$ subcutane\sly2 #ab noon1 reflexes increas$1 b n z mu* z 9 ,no4 #fh2 #d4bj p4 m41 gu9ea pig hyp]s5sitive1 reflexes increas$ m ?an at #ab noon4 ,octob] #g3 #i a4 m41 alive4 ,octob] #ae3 #i a4 m41 f\nd dead4 ,gu9ea pig #fa4 ,br[n & black female4 ,weight1 #ccj grams4 ,diet1 oats4 ,octob] #c3 #d p4 m41 #d cc #b p] c5t caffe9 7#bdj mg p] kilo7 inject$ subcutane\sly2 #e4cj p4 m41 reflexes increas$2 runs1 b drags po/]ior extremities4 ,octob] #d3 #h4ej a4 m41 f\nd dead4 ,gu9ea pig #fb4 ,:ite1 yell[1 & black female4 ,weight1 #cce grams4 ,diet1 oats4 ,octob] #c3 #d4je p4 m41 #d cc #b p] c5t caffe9 7#bch mg p] kilo7 inject$ subcutane\sly 9 ! back2 #e p4 m41 convulsions2 #e4bj p4 m41 convulsions1 alt]nat+ ) p>alysis ( ant]ior & po/]ior extremities4 ,octob] #d3 #h4ej a4 m41 f\nd dead4 ,gu9ea pig #gj4 ,:ite & br[n male4 ,weight1 #ede grams4 ,diet1 oats4 ,octob] #g3 #c p4 m41 #f4e cc #b p] c5t caffe9 7#bch mg p] kilo7 aque\s solution inject$ subcutane\sly2 #c4ej p4 m41 reflexes increas$4 ,octob] #i3 #i a4 m41 f\nd dead4 ,gu9ea pig #ga4 ,br[n & :ite male4 ,weight1 #edj grams4 ,diet1 oats4 ,octob] #g3 #c p4 m41 #f4e cc #b p] c5t caffe9 solution 7#j4bd gram p] kilo7 inject$ subcutane\sly2 #c4de p4 m41 reflexes increas$1 tetanus4 ,octob] #i3 #i a4 m41 f\nd dead4 ,gu9ea pig #gb4 ,br[n & :ite male4 ,weight1 #efj grams4 ,diet1 oats4 ,octob] #g3 #c p4 m41 #f4e cc #b p] c5t caffe9 7#j4bcb gram p] kilo7 aque\s solution adm9i/]$ by subcutane\s injection2 #c4ce p4 m41 reflexes increas$4 ,octob] #aj3 f\nd dead4 ,autopsy3 ,nos4 #gj1 #ga1 #gb %[$ conge/ion ( organs4 ,! reaction to caffe9 9 ! exp]im5ts ( ?is s]ies 7,c7 %[$ consid]able v>iation4 ,! appe>ance ( symptoms1 z well z ! f9al outcome ( ! exp]im5ts1 diff]$ m>k$ly 9 a numb] ( cases1 not)/&+ ! fact t ! conditions 7 ! same2 ?us ! adm9i/ration ( #j4b gram p] kilo to gu9ea pigs1 all ( :i* receiv$ ! same diet1 induc$ no symptoms 9 two ( ! animals 7,nos4 #ff & #fe71 :ile m>k$ symptoms 7 obs]v$ 9 ! o!r f\r2 9 two ( ^! ! symptoms appe>$ 9 "o h\r & a qu>t] aft] injection1 & 9 two o!rs 7,nos4 #fh & #fi71 mild symptoms only appe>$ 9 #bj or #be m9utes4 ,! la/ two 7 "u obs]vation = #d h\rs long]1 b !re 0 no visible *ange 9 _! condition4 ,! duration ( life 9 all ( ^! gu9ea pigs1 z indicat$ 9 ! table1 likewise v>i$4 ,two 7,nos4 #fj & #fh7 di$ dur+ ! night aft] !y receiv$ caffe91 "o surviv$ 7,no4 #fe71 & ?ree o!rs 7,nos4 #eg1 #ff1 & #fi7 liv$ #b1 #e1 & #i days1 respectively4 ,exp]im5ts ) l>g] doses likewise %[$ diff]5ces 9 ! behavior ( ^! animals t[>d caffe91 b !y 7 n q s m>k$4 ,z %[n 9 ! table1 symptoms appe>$ 9 f #ce m9utes to #a4e h\rs aft] injection4 ,! duration ( life 0 less ?an #a day 9 two pigs1 ab\t twice z long 9 two o!rs1 & 9 "o case betwe5 #b & #c days4 ,a comp>ison made ) results obta9$ 9 ! prec$+ s]ies %[s a /rik+ diff]5ce 9 ! resi/ance to caffe94 ,z #b decigrams p] kilo prov$ m rapidly fatal to ! gu9ea pig ?an ! l>g] doses employ$ 9 ! lat] exp]im5ts1 ?is diff]5ce 9 ! resi/ance to caffe9 may be due to sev]al factors4 ,z po9t$ out 9 ! exp]im5ts on rabbits1 age might be an important factor influ5c+ ! toxicity ( caffe94 ,un=tunately1 no accurate data 7 available on ! age ( ! gu9ea pigs1 b !y 7 all app>5tly full gr[n1 al?\gh !y diff]$ 9 weight consid]ably4 ,! diff]5ce 9 _! ages 0 9 all probability n v great4 ,moreov]1 x w be obs]v$ t ! resi/ance 9 s]ies ,b & ,c diff]$ 9 animals ( approximately ! same weight4 ,?is is evid5t on comp>+ exp]im5ts ,nos4 #bj1 #ch1 & #ac ( s]ies ,b ) ,nos4 #fe1 #ff1 & #fi ( ! next s]ies4 ,aga91 fur!r inspection & analysis ( ^! tables %[ no diff]5ce 9 ! toxicity1 al?\gh !re may be consid]able diff]5ce 9 ! weight1 f :i* x may be conclud$ t ! animals 7 ( ab\t ! same age or t ?is plays no "p 9 ! resi/ance to caffe9 9 ! gu9ea pig4 ,diet is ano!r factor :i* %\ld be tak5 into consid]ation 9 ?is connection4 ,! rec5t "w ( ,hunt7#ci7 indicates t ?is may influ5ce ! resi/ance ( animals to "s poisons4 ,our exp]im5ts1 h[ev]1 fail to %[ any diff]5ce 9 ! toxicity ( ! caffe9 9 gu9ea pigs1 :e!r f$ oats1 c>rots1 or bo?1 = diff]5t results 7 obta9$ on ! same diet1 & !re seem$ to be little or no diff]5ce 9 ! toxicity ( caffe9 :5 ! diet 0 diff]5t4 ,o!r explanations sugge/ !mselves to acc\nt = ! results obta9$4 ,seasonal *anges h be5 assign$ by a numb] ( inve/igators z a cause ( v>iation 9 ! resi/ance to drugs4 ,accord+ to ,focke17#bd7 frogs are m susceptible to digitalis 9 ! spr+ ?an 9 ! summ]1 :ile ,mos*k[its*7#fa7 & ,edmunds7#ba7 report$ ! v opposite results4 ,s*mi$eb]g's7#hj7 obs]vations on /rophant9 9 frogs 7 9 h>mony ) ^? ( ,edmunds7#ba7 & ,mos*k[its*47#fa7 ,simil> results 7 report$ ) gu9ea pigs4 ,h>r+ton's7#cd7 exp]im5ts indicate t /imulation ( ! vagus is less effective f ,octob] to ,janu>y ?an f ,febru>y to ,april1 :5 !y are also mu* m susceptible to op]ative proc$ure4 ,hunt f\nd t ! resi/ance ( gu9ea pigs to aceto nitril is ab\t twice z great 9 ! summ] mon?s z x is 9 ,janu>y & ,febru>y4 ,race might also be ?\ght ( z an important factor 9 ?is connection4 ,s9ce ! gu9ea pigs us$ at diff]5t seasons ( ! ye> 7 ( sev]al v>ieties1 !re is no reason to suppose1 h[ev]1 t ! v>ieties exp]im5t$ ^u 9 ! summ] 7 m resi/ant ?an ^? us$ 9 ! w9t] & spr+4 ,x is highly probable1 !re=e1 t ! great] resi/ance to caffe9 ( ! gu9ea pigs ( s]ies ,c ?an ^? ( s]ies ,b 0 due to seasonal v>iation4 ,doses ( #j4bj to #j4bd gram caffe9 p] kilo weight1 !re=e1 may be reg>d$ z ! m9imum fatal dose = ! gu9ea pig1 dep5d+ ^u ! season4 ,s9ce #j4b gram p] kilo prov$ to be rapidly fatal 9 s]ies ,b1 ?is quantity 0 p]haps n ! m9imum fatal dose = ! gu9ea pig at ! season dur+ :i* ! exp]im5ts 7 made4 ,additional te/s ) small] doses 7 !re=e c>ri$ out dur+ ,febru>y & ,m>*4 ,! results are %[n 9 s]ies ,d4 ,,s]ies ,d4 ,gu9ea pig #di4 ,male4 ,weight1 #eaj grams4 ,diet1 oats = #a mon? previ\s to exp]im5t4 ,m>* #ag3 #c p4 m41 #d cc #b p] c5t caffe9 7#j4af gram p] kilo7 7 inject$ subcutane\sly2 #d4dj p4 m41 reflexes increas$2 #e4dj p4 m41 no symptoms4 ,m>* #ah3 #i a4 m41 f\nd dead1 di$ 9 less ?an #ah h\rs4 ,autopsy3 ,hemorrhage into abdom9al cavity2 liv] & sple5 unduly conge/$2 inte/9es inject$2 hemorrhagic area at po9t ( injection4 ,gu9ea pig #dj4 ,male4 ,weight1 #fcj grams4 ,diet1 oats & c>rots "o week previ\s to injection4 ,febru>y #ab3 #aa a4 m41 #e cc #b p] c5t caffe9 7#j4aeh gram p] kilo7 inject$ subcutane\sly into back4 ,febru>y #ac3 #a p4 m41 /ill alive4 ,febru>y #ad3 #i a4 m41 f\nd dead4 ,gu9ea pig #de4 ,female4 ,weight1 #dce grams4 ,diet1 oats = ab\t "o mon? previ\s to injection4 ,m>* #ag3 #c p4 m41 #c4e cc ( #b p] c5t caffe9 inject$ subcutane\sly 9 ! back 7#j4afj gram p] kilo72 #d4ce p4 m41 no symptoms2 #e4dj p4 m41 no symptoms4 ,gu9ea pig #ci4 ,male4 ,weight1 #hbj grams4 ,diet1 oats & c>rots4 ,febru>y #ab3 #aa a4 m41 #f cc 7#j4ae gram p] kilo7 #b p] c5t caffe9 inject$ subcutane\sly 9 back4 ,febru>y #ad3 #i a4 m41 alive2 seem$ to be 9 good condition2 f\nd dead at #a p4 m4 ,gu9ea pig #da4 ,weight1 #ffj grams4 ,diet1 oats & c>rots "o week previ\s to injection4 ,febru>y #ab3 #aa a4 m41 #e cc 7#j4ae gram p] kilo7 #b p] c5t caffe9 inject$ subcutane\sly4 ,febru>y #ad3 #b p4 m41 pig alive2 app>5tly normal4 ,febru>y #ah3 ,gu9ea pig /ill alive & app>5tly 9 good condition4 ,gu9ea pig #df4 ,female4 ,weight1 #dgj grams4 ,diet1 oats ab\t "o mon? previ\s to exp]im5t4 ,m>* #ag3 #c4ae p4 m41 #d cc 7#j4agj gram p] kilo7 #b p] c5t caffe9 inject$ into back subcutane\sly2 #d4ce p4 m41 reflexes increas$1 tremors on h&l+ m>k$2 #e4dj p4 m41 no *ange1 symptoms ab\t z be=e4 ,m>* #ah3 #b4cj p4 m41 no symptoms4 ,! exp]im5ts ( ?is s]ies 7,d7 likewise %[$ a consid]able diff]5ce 9 ! resi/ance ( ! individual gu9ea pigs4 ,nos4 #da1 #de1 & #df surviv$2 ! re/ ( ! pigs di$ )9 #ah h\rs to #b days aft] ! adm9i/ration ( caffe94 ,s9ce an autopsy 0 held on "o only1 x is impossible to assign a cause = ! v>iation 9 ! toxicity ( caffe9 9 ^! gu9ea gigs1 z ! diet & ! o!r conditions "u :i* ! exp]im5ts 7 conduct$ 7 ! same4 ,x 0 f\nd 9 ! exp]im5ts on cats & rabbits t ! pres5ce ( morbid processes t5ds to increase ! toxicity ( caffe94 ,! obs]vations ( ,ophls7#ff7 are ( int]e/ 9 ?is connection4 ,he f\nd spontane\s lesions ( ! kidney & liv] 9 a l>ge proportion ( gu9ea pigs exam9$4 ,! great] susceptibility to caffe9 ( gu9ea pigs ,nos4 #ci1 #dj1 #di1 is probably due !re=e to "s pa?ological *ange :i* increas$ its toxicity4 ,ab\t #j4b to #j4bd gram p] kilo may !re=e be reg>d$ z ! m9imum le?al dose = ! normal gu9ea pig :5 caffe9 is introduc$ subcutane\sly1 ! m9imum toxic dose be+ ab\t #aej-afj mg p] kilo4 ,exp]im5ts 7 also conduct$ to det]m9e ! l>ge/ dose :i* does n produce any visible effects4 ,9 a numb] ( te/s ) f #ajj to #abj mg caffe9 p] kilo 7s]ies ,e1 see ,table #f1 p4 #ea7 no manife/ation ( n]v\s or muscul> di/urbance nor any dep>ture f ! normal 9 respiratory activity 0 obs]v$4 ,su* quantities may be reg>d$ z ! l>ge/ doses :i* are surely safe = ^! animals4 ,x is q possible1 !re=e1 t ! great] v>iation 9 ! toxicity ( caffe9 obs]v$ 9 ^! exp]im5ts is due to morbid conditions4 ,moreov]1 !re is "s evid5ce t caffe9 increases ! toxicity ( c]ta9 poisons1 z %[n by ,hale7#cc7 = acetanilid4 ,is x n possible t caffe9 may simil>ly be affect$ by poisons circulat+ )9 ! body8 ,inde$ ! rec5t "w ( ,loeb7#bc7 makes ?is supposition highly probable4 ,?is inve/igator f\nd t caffe9 & adr5al9 inject$ toge!r produce myoc>ditis 9 ! rabbit4 ,x is conceivable t ! comb9$ action ( caffe9 & "s preexi/+ poison may cause *anges :i* t]m9ate 9 ! dea? ( ! animal4 ,! delay$ dea? ( gu9ea pigs aft] ! adm9i/ration ( caffe9 obs]v$ 9 ?is & o!r s]ies may probably be acc\nt$ = 9 ?is way4 ,exp]im5t #eg l5ds "s support to ?is view4 ,! condition ( ! kidneys & ! pres5ce ( a sev]e ga/ro-ent]itis are suffici5t to acc\nt = ! dea? ( ?is case4 ,aga9 ! frequ5t association ( ga/ro-ent]itis & conge/ion ( ! organs 9 caffe9 intoxication f\nd 9 diff]5t animals makes x highly probable t ^! lesions 7 caus$ by caffe94 ,,injection ,,into ,,! ,,p]itoneal ,,cavity4 ,! exp]im5ts 7 c>ri$ out ) diff]5t doses4 ,all ! gu9ea pigs 9 ?is s]ies 7 kept on a uni=m diet1 consi/+ ( oats4 ,mo/ ( !m 7 ( av]age size & !re 7 no wide v>iations 9 _! weights4 ,! exp]im5ts ( s]ies ,a ) ! smalle/ doses 7 conduct$ 9 ,m>* & ,april2 all ! o!r exp]im5ts x w be notic$ 7 made 9 ,octob]4 ,,s]ies ,a4 ,gu9ea pig #da4 ,weight1 #gjj grams4 ,diet1 oats4 ,april #a3 #c4cj p4 m41 #d4e cc #b p] c5t caffe9 7#acj mg p] kilo7 inject$ into p]itoneal cavity4 #e4ce p4 m41 symptoms pres5t b no tetanus4 ,april #b3 ,f\nd dead ab\t #b p4 m41 duration ( life ab\t #bb h\rs4 ,autopsy3 ,subcutane\s hemorrhage at ! po9t ( inoculation2 s]i\s exudate on visc]al & p>ietal p]itoneum ) m>k$ inflammation ( p]itoneum2 portions ( inte/9es %[$ slight ent]itis4 ,gu9ea pig #di4 ,male4 ,weight1 #cgj grams4 ,diet1 oats4 ,april #a3 #c4ae p4 m41 #b4e cc #b p] c5t caffe9 7#ace mg p] kilo7 inject$ into ! p]itoneal cavity2 #e4cj p4 m41 symptoms pres5t2 reflexes increas$1 b no tetanus4 ,gu9ea pig surviv$4 ,gu9ea pig #dg4 ,female4 ,weight1 #eej grams4 ,diet1 oats s9ce ab\t ,febru>y #d4 ,m>* #ag3 #c4cj p4 m41 #c4e cc #b p] c5t caffe9 7#abg mg p] kilo7 inject$ into p]itoneal cavity2 #d4ce p4 m41 increas$ irritability pres5t1 b n m>k$2 #e4dj p4 m41 symptoms ab\t ! same z be=e4 ,m>* #ah3 #b4cj p4 m41 condition good2 no symptoms4 ,surviv$4 ,gu9ea pig #ej4 ,female4 ,weight1 #bij grams4 ,diet1 oats4 ,april #a3 #c4cj p4 m41 #b cc #b p] c5t caffe9 7#ach mg p] kilo7 inject$ into p]itoneal cavity2 #e4ce p4 m41 symptoms pres5t2 reflexes mu* increas$1 b no tetanus4 ,surviv$4 ,,s]ies ,b4 ,gu9ea pig #ea4 ,yell[ female4 ,weight1 #dae grams4 ,octob] #a3 #i4ej a4 m41 #c cc 7#add mg p] kilo7 #b p] c5t caffe9 inject$ into p]itoneal cavity2 #d4cj p4 m41 no symptoms1 al?\gh "u obs]vation all day4 ,octob] #c3 #b p4 m41 alive4 ,gu9ea pig #eb4 ,:ite male4 ,weight1 #dej grams4 ,octob] #a3 #i4de a4 m41 #c4e cc1 #b p] c5t caffe9 7#aee mg p] kilo71 inject$ into p]itoneal cavity2 #d4cj p4 m41 no symptoms develop$ s9ce injection4 ,octob] #c3 #b p4 m41 alive4 ,gu9ea pig #eh4 ,br[n & :ite male4 ,weight1 #dij grams4 ,octob] #a3 #i4de a4 m41 #d cc1 #b p] c5t caffe9 7#afc mg p] kilo71 inject$ into p]itoneal cavity2 #d4cj p4 m41 no symptoms develop$ s9ce injection4 ,octob] #c3 #b p4 m41 alive4 ,octob] #h3 ,f\nd dead4 ,autopsy3 ,conge/ion ( lungs1 sple51 liv]1 kidneys1 & small inte/9es4 ,,s]ies ,c4 ,gu9ea pig #ei4 ,gray & :ite4 ,weight1 #cge grams4 ,diet1 oats4 ,octob] #c3 #b p4 m41 #c4ge cc 7#j4b gram p] kilo7 inject$ into p]itoneal cavity2 #b4ae p4 m41 reflexes increas$ b n m>k$ly2 #d p4 m41 reflexes /ill m increas$2 no o!r symptoms2 #e4cj p4 m41 no symptoms4 ,octob] #d3 #h4ej a4 m41 gu9ea pig alive & active4 ,gu9ea pig #eh4 ,br[n & :ite4 ,weight1 #chj grams4 ,diet1 oats4 ,octob] #c3 #b p4 m41 #c4h cc caffe9 7#j4b gram p] kilo71 #b p] c5t solution1 inject$ into p]itoneal cavity2 #b4aj p4 m41 h9d legs ext5d$1 !n tetanus2 attack la/$ a few seconds1 aft] :i* pig rais$ himself on 8 legs1 b reflexes rema9$ mu* exagg]at$2 #d p4 m4 to #e4cj p4 m41 no symptoms ( caffe9 intoxication4 ,octob] #d3 #h4ej a4 m41 gu9ea pig alive & active4 ,gu9ea pig #ef4 ,gray & :ite male4 ,weight1 #ddj grams4 ,diet1 oats4 ,octob] #a3 #aa4cj a4 m41 receiv$ #d4f cc ( #b p] c5t caffe9 solution 7#j4b gram p] kilo7 into abdom9al cavity2 #aa4de a4 m41 /iffness & rigidity ( po/]ior extremities1 reflexes increas$2 #ab4cj p4 m41 h9d legs p>alyz$1 reflexes increas$2 #d4ce p4 m41 no symptoms1 gu9ea pig 9 good condition4 ,octob] #c3 ,/ill alive 9 good condition4 ,octob] #ad3 ,di$4 ,autopsy3 ,ant]ior lobe ( "r lung hepatiz$4 ,small portion ( small inte/9e edemat\s4 ,o!r organs normal4 ,gu9ea pig #ee4 ,:ite & yell[ male4 ,weight1 #fij grams4 ,diet1 oats4 ,octob] #a3 #aa4cj a4 m41 receiv$ #f4e cc ( #b p] c5t solution caffe9 7#ahh mg p] kilo7 into p]itoneal cavity2 #aa4dj a4 m41 /iffness 9 all extremities1 reflexes m>k$ly increas$2 #ab4cj p4 m41 reflexes increas$1 ant]ior & po/]ior extremities p>alyz$2 #c p4 m41 f\nd dead4 ,,s]ies ,d4 ,gu9ea pig #fg4 ,gray & yell[ male4 ,weight1 #ccj grams4 ,diet1 oats4 ,octob] #e3 #aa4be a4 m41 #d cc ( #b p] c5t caffe9 inject$ into p]itoneal cavity 7#bdj mg p] kilo72 #aa4cj a4 m41 tetanus--surviv$1 convulsions (f & on4 ,dea? at #b4ee p4 m4 ,autopsy3 ,sev]e ga/ro5t]itis2 kidney pete*iat$2 conge/ion ( lungs & liv]4 ,gu9ea pig #fc4 ,gray & :ite male4 ,weight1 #cdj grams4 ,diet1 oats4 ,octob] #e3 #aa4bj a4 m41 #d cc ( #b p] c5t caffe9 7#bce mg p] kilo7 inject$ into p]itoneal cavity4 ,octob] #ad3 ,alive & 9 good condition4 ,gu9ea pig #fd4 ,br[n & black female4 ,weight1 #cje grams4 ,octob] #e3 #aa4ce a4 m41 #c4h cc #b p] c5t solution caffe9 7#bej mg p] kilo7 inject$ into p]itoneal cavity2 #aa4dj a4 m41 tetanus--surviv$1 convulsions (f & on1 di$ at #d4ae p4 m4 ,autopsy3 ,f9d+s exactly ! same z 9 ,no4 #fg4 ,exam9ation ( ! results ( ! exp]im5ts by intrap]itoneal injections %[$ t #j4b gram caffe9 p] kilo 0 toxic 9 two gu9ea pigs 7,nos4 #ei & #eh74 ,sev]e symptoms 7 obs]v$ )9 #ae m9utes 9 ,no4 #ef & )9 "o h\r 9 ,no4 #ee aft] ! adm9i/ration ( approximately ! same dose ( caffe94 ,"o ( ^! di$ )9 ?ree & "o-half h\rs2 ! o!r1 ,no4 #ef1 made a good recov]y f ! acute effects4 ,?is am\nt ( caffe9 may be reg>d$1 !re=e1 z ! m9imum toxic dose = ! gu9ea pig :5 inject$ into ! p]itoneal cavity4 ,?is is corroborat$ by ! exp]im5ts ( s]ies ,b 9 :i* small] doses fail$ to %[ any muscul>1 n]v\s1 or respiratory symptoms1 nor 7 !re any aft] effects notic$1 z all ( !m surviv$ & 7 kept "u obs]vation = "s "t4 ,! gu9ea pigs ( s]ies ,a1 h[ev]1 seem to contradict ^! results4 ,x w be rem>k$ t appreciably small] doses induc$ symptoms 9 all ( !m1 & "o case t]m9at$ fatally4 ,! seasonal v>iation1 z already po9t$ out1 is 9 all probability likewise responsible = ! diff]5ce 9 ! resi/ance betwe5 ! gu9ea pigs ( s]ies ,a & ,b4 ,te/s 7 made also to det]m9e ! m9imum fatal dose4 ,= ?is purpose ! exp]im5ts ( s]ies ,d 7 p]=m$4 ,! resi/ance ( ,no4 #fc 9 ?is s]ies is q /rik+4 ,we are unable to expla9 su* a discrepancy 9 ! results obta9$ "u practically uni=m conditions4 ,! m9imum fatal dose ( caffe91 :5 inject$ into ! p]itoneal cavity1 is !re=e ab\t #bdj to #bej milligrams p] kilo4 ,^! am\nts1 x w be obs]v$1 7 rapidly fatal1 9 /rik+ contra/ to ! results obta9$ :5 su* doses 7 inject$ subcutane\sly4 ,?is is probably due to a bett] absorption f ! p]itoneal cavity ?an f ! subcutane\s tissues4 ,,adm9i/ration ,,by ,,m\?4 ,all ! gu9ea pigs 9 ^! exp]im5ts 7 kept on a diet ( hay & oats & 7 ( l>ge size4 ,! te/s 7 made ) diff]5t doses ( caffe9 9 ord] to det]m9e ! limits ( toxicity :5 ! drug 0 adm9i/]$ by m\?4 ,gu9ea pig #abi4 ,:ite & black male4 ,weight1 #hee grams4 ,diet1 oats & hay4 ,june #f3 #b4bj p4 m41 #ab cc ( #b p] c5t caffe9 7#j4bh gram p] kilo7 by m\?2 #c p4 m41 reflexes increas$2 #e p4 m41 reflexes /ill m increas$2 no o!r symptoms4 ,june #g3 #i a4 m41 f\nd dead2 gu9ea pig pass$ #ge cc ur9e1 :i* 0 almo/ colorless4 ,autopsy3 ,he>t & blood vessels inject$2 lungs conge/$2 small inte/9es conge/$2 o!r organs app>5tly normal4 ,gu9ea pig #acj4 ,black & br[n male4 ,weight1 #hjj grams4 ,diet1 oats & hay4 ,june #f3 #b4cj p4 m41 #ab cc ( #b p] c5t caffe9 7#j4c gram p] kilo7 adm9i/]$ by m\?2 #c p4 m41 reflexes increas$2 #e p4 m41 increase ( reflexes great] ?an at #c p4 m4 ,june #g3 #i a4 m41 f\nd dead2 only a few cubic c5timet]s ( ur9e pass$ s9ce #d p4 m4 ,autopsy3 ,he>t & blood vessels inject$2 lungs conge/$2 small inte/9es conge/$ slightly4 ,gu9ea pig #aha4 ,:ite & yell[ male4 ,weight1 #hfj grams4 ,diet1 oats & hay4 ,june #f3 #b4dj p4 m41 #ab cc #b p] c5t caffe9 adm9i/]$ by m\?2 #c p4 m41 reflexes increas$2 #e p4 m41 reflexes /ill m m>k$4 ,june #g3 #i a4 m41 f\nd dead1 pig pass$ ab\t #e cc ur9e s9ce #d p4 m4 ( previ\s day4 ,autopsy3 ,same z 9 ,no4 #acj4 ,gu9ea pig #acf4 ,:ite & black male4 ,weight1 #a1jjj grams4 ,diet1 oats & hay4 ,june #i3 #d p4 m41 #g4e cc #b p] c5t caffe9 solution inject$ subcutane\sly into ! back2 #d4ej p4 m41 reflexes increas$4 ,june #aj3 #i4cj a4 m41 m s5sitive ?an normal gu9ea pigs1 b reflexes n q s m>k$ z at #e p4 m4 previ\s day1 ab\t #ae cc ur9e pass$ s9ce caffe9 0 inject$1 r$uction ( ,fehl+'s solution consid]able1 no album94 ,june #ac3 ,alive & 9 good condition4 ,appetite good4 7,,note4--,p>allel te/ ) ur9e f two gu9ea pigs :i* did n receive caffe9 fail$ to %[ r$uction ( ,fehl+'s solution47 ,gu9ea pig #acg4 ,:ite & br[n male4 ,weight1 #ibe grams4 ,diet1 oats & hay4 ,june #i3 #d p4 m41 #g cc #b p] c5t solution caffe9 inject$ subcutane\sly2 #d4ej p4 m41 reflexes increas$4 ,june #aj3 ,reflexes less m>k$ ?an at #e p4 m4 previ\s day1 b is m s5sitive ?an normal gu9ea pig1 ab\t #aj cc ur9e pass$ s9ce injection ( caffe91 mod]ate am\nt ( r$uction ( ,fehl+'s solution4 ,june #ac3 ,gu9ea pig alive1 appetite good1 condition good4 ,june #af3 #i a4 m41 f\nd dead4 ,gu9ea pig #ace4 ,:ite & black male4 ,weight1 #iee grams4 ,diet1 hay & oats4 ,june #i3 #c p4 m41 #g4e cc #b p] c5t caffe9 solution giv5 by m\? ?r\gh /oma* tube2 #d4ej p4 m41 reflexes increas$4 ,june #aj3 ,reflexes less ?an on previ\s day & less m>k$ ?an 9 ,no4 #acf1 a few cubic c5timet]s dirty br[n ur9e collect$ b c\ld n be te/$ = r$uction4 ,june #ac3 ,condition good1 appetite good4 ,june #af3 #i a4 m41 f\nd dead4 ,gu9ea pig #acd4 ,:ite & br[n male4 ,weight1 #gdj grams4 ,diet1 hay & oats4 ,june #i3 #b4ee p4 m41 #f cc w>m #b p] c5t caffe9 solution giv5 by m\? ?r\gh /oma* tube2 #d4ej p4 m41 reflexes increas$4 ,june #aj3 #i4cj a4 m41 reflexes mu* less ?an day be=e1 increase slight1 a few cubic c5timet]s ( ur9e pass$ s9ce injection ( caffe91 look$ br[n & dirty1 c\ld n be te/$ = r$uc+ sub/ances4 ,june #ac3 ,gu9ea pig alive1 appetite good1 condition good4 ,june #ad3 #i a4 m41 f\nd dead4 ,gu9ea pig #abh4 ,:ite & black male4 ,weight1 #a1jge grams4 ,diet1 hay & oats4 ,june #g3 #aj a4 m41 #aa cc #b p] c5t caffe9 by m\? ?r\gh /oma* tube2 #aa4aj a4 m41 no symptoms1 no ur9e pass$2 #a p4 m41 increas$ reflexes1 ab\t #ae cc 7e/imat$7 ur9e pass$2 #d p4 m41 reflexes increas$1 /ill m ur9e pass$ 7ab\t #bj cc72 #d4ej p4 m41 tetanus1 frequ5t attacks1 !n p>alysis & dea? at #d4eh p4 m4 ,autopsy3 ,lungs conge/$2 blood vessels ( he>t inject$2 inte/9es slightly conge/$2 fatty liv]4 ,gu9ea pig #abf4 ,:ite & gray male4 ,weight1 #ihj grams4 ,diet1 oats & hay4 ,june #g3 #i4dj a4 m41 #i4h cc #b p] c5t caffe9 giv5 by m\? ?r\gh /oma* tube2 #aj a4 m41 no symptoms2 #aa4aj a4 m41 no ur9e pass$1 reflexes increas$2 #a p4 m41 m s5sitive ?an be=e2 #d p4 m41 increase ( reflexes m m>k$1 no ur9e pass$2 #d4de p4 m41 ab\t #ae cc ur9e collect$2 #e p4 m41 no *ange4 ,june #h3 #i a4 m41 reflexes ab\t ! same z #e p4 m4 previ\s day1 no ur9e pass$ s9ce #d4de p4 m4 previ\s day1 consid]able r$uction ( ,fehl+'s solution1 mu* m ?an ur9e ( gu9ea pig ,no4 #abg2 #aa4je a4 m41 convulsions2 #ab noon1 /ill alive & /ret*$ out on abdom52 di$ at #a p4 m4 ,autopsy3 ,lungs badly conge/$2 he>t & blood vessels inject$2 blood vessels ( kidney & ( small inte/9es inject$2 liv] engorg$ ) blood2 a few necrotic spots 9 /oma*4 ,gu9ea pig #abg4 ,:ite1 black1 & br[n male4 ,weight1 #gfj grams4 ,diet1 oats & hay4 ,june #g3 #i4ej a4 m41 #g4f cc #b p] c5t caffe9 by m\? ?r\gh /oma* tube2 #aj a4 m41 no symptoms2 #aa4aj a4 m41 reflexes increas$1 no ur9e pass$2 #a p4 m41 v s5sitive2 #d p4 m41 s5sitiv5ess increas$1 ab\t #bj cc ur9e pass$2 #e p4 m41 no *ange4 ,june #h3 #i a4 m41 reflexes ab\t ! same z #e p4 m4 previ\s day2 #i4cj a4 m41 gu9ea pig pass$ #cj cc ur9e s9ce he receiv$ caffe91 ur9e %[$ a mod]ate am\nt ( r$uction2 #ab noon1 convulsions2 di$ at #b4cj p4 m4 ,autopsy3 ,lungs conge/$2 blood vessels ( he>t & ( inte/9es inject$2 num]\s necrotic spots 9 /oma*2 o!r organs app>5tly normal4 ,exam9ation ( ! protocols %[s t ! absorption ( caffe9 f ! ga/ro-inte/9al canal 0 q rapid1 symptoms hav+ be5 obs]v$ z e>ly z #bj m9utes aft] its introduction4 ,! duration ( life1 x w be rem>k$1 v>i$ ) ! size ( ! dose4 ,:5 approximately #c decigrams p] kilo 7 f$1 all ! animals di$ 9 ! night4 ,!y liv$1 !re=e1 less ?an #ah h\rs4 ,two decigrams p] kilo 7 likewise fatal1 b ! duration ( life 0 long]4 ,to decide :e!r or n ?is is ! smalle/ fatal dose1 small] am\nts 7 f$4 ,x seem$ at fir/ t ab\t #aej mg p] kilo 0 ! smalle/ toxic dose1 & ab\t #bjj mg p] kilo ! m9imum fatal dose4 ,macroscopic exam9ation ( ! organs1 h[ev]1 ?rew "s d\bt on ?is supposition1 = well-m>k$ lesions 7 notic$ 9 all ( ! gu9ea pigs :i* receiv$ #j4b gram p] kilo4 ,x is q possible1 !re=e1 t ! m9imum fatal dose may be some:at high]1 z we h reason to believe t1 at lea/ 9 "s pa?ologic conditions1 ! susceptibility to caffe9 is increas$4 ,! pres5ce ( fatty *anges 9 ! liv] ( ,no4 #abh & ! rapid dea? 9 ?is case l5ds especial support to ?is view4 ,h5ce1 ! m9imum fatal dose is probably great] ?an #j4b gram p] kilo = ! normal gu9ea pig4 ,! doses employ$ = ! te/s on gu9ea pigs ,nos4 #abi1 #acj1 & #aca may be consid]$ !re=e ! m9imum fatal dose = ^! animals4 ,x w be also rem>k$ t macroscopical exam9ation ( ! organs ( ^! animals fail$ to reveal ! pres5ce ( sev]e lesions4 ,t ! m9imum toxic dose is probably mu* small] ?an #j4bh gram p] kilo is indicat$ by ! exp]im5ts on gu9ea pigs ,nos4 #ace & #acd1 9 :i* #j4ae gram caffe9 p] kilo induc$ mild symptoms 9 f two to ?ree h\rs4 ,bo? ( ^!1 h[ev]1 & also ,no4 #acg di$ f\r to six days aft] ! drug 0 f$4 ,z already po9t$ out1 caffe9 may be a factor 9 ! delay$ dea? ( gu9ea pigs :i* receiv$ mod]ate doses ( x4 ,t ?is supposition may also be true = gu9ea pigs ,nos4 #acd1 #ace1 & #acg is inde$ made probable by ! obs]vation t aft] mod]ate am\nts ( caffe9 symptoms may p]si/ 9 ! gu9ea pig = ab\t #bd h\rs1 & also by ! fact t ! secretion ( ur9e 9 ^! animals 0 v scanty1 z %[n 9 ! prec$+ record ( ! exp]im5ts2 ?is means sl[ elim9ation ( caffe9 & its products ( decomposition4 ,x is conceivable t ! pres5ce ( toxic am\nts ( caffe9 9 ! body = a consid]able l5g? ( "t w\ld induce *anges t ultimately lead to ! dea? ( ! animal or t morbid processes are set up by ! comb9$ action ( caffe9 & "s preexi/+ poison4 ,s9ce "s gu9ea pigs1 h[ev]1 surviv$ ! doses indicat$1 x is m probable t su* *anges w\ld be br\ght ab\t by caffe9 9 ! pres5ce ( a preexi/+ poison4 ,! dea? ( ^! pigs1 & also ( ,no4 #acg sev]al days lat]1 is difficult to acc\nt = on any o!r !ory ?an ! "o sugge/$4 ,7 x n = ! fact t controls1 t is1 animals ( ! same lot :i* _h n receiv$ caffe9 surviv$ all ( ! exp]im5tal animals1 *ang$ conditions ( environm5t or accid5t might be consid]$ ! cause ( dea? 9 ! gu9ea pigs ( ! la/ s]ies4 ,,table #f4--,subcutane\s injection ( gu9ea pigs4 ,,s]ies ,a4 ---------------------------------------- ----------------------- ,numb] ,caffe9,appe>ance ,duration ( pig,weight4 p] ( ( ,diet4 ,mon?4,rem>ks4 kilo4 symptoms4 life ---------------------------------------- ----------------------- ,grams4,gram4 #ah #ejj #j4cjj #b m9utes #b h\rs ,c>rots ,m>* ,female4 #dj m9utes #ae #edh 4#bij #cj m9utes ,oats d4 ,d4 #ad #ddb #cfj #ae m9utes d4 d4 d4 ,d4 ---------------------------------------- ----------------------- ,,s]ies ,b4 ---------------------------------------- ----------------------- #bj #dig #j4bjj #b h\rs #c h\rs ,oats ,april ,female4 #bj m9utes#cj m9utes #ch #egj 4#baj #be m9utes#b h\rs ,c>rots,febru ,male4 #ae m9utes -ary #cg #hbj 4#bjj #a h\r ,less ?an ,c>rots d4 ,d4 #be m9utes #ah h\rs & oats #ac #fah 4#aid #be h\rs ,oats ,m>* ,female4 #cf #hej 4#bjj #a h\r #ah h\rs ,c>rots ,febru ,male4 #cj m9utes & oats -ary ---------------------------------------- ----------------------- ,,s]ies ,c4 ---------------------------------------- ----------------------- #ff #eaj #j4bjj ,none #e days ,oats ,octob],male4 #fe #eaj 4#bjj d4 ,surviv$ d4 d4 ,d4 #fj #cbj 4#bai #a h\r ,)9 d4 d4 ,female4 #ae m9utes #ah h\rs #eg #cej 4#bjj d4 ,ab\t d4 d4 ,d4 #b-ab days #fh #ghe 4#bjj #be m9utes,less ?an d4 d4 ,male4 #bb h\rs #fi #ehe 4#bjj #bj m9utes#i days d4 d4 ,d4 #fa #ccj 4#bdj #a h\r ,less ?an d4 d4 ,female4 #cj m9utes #bd h\rs #fb #cce 4#bch #a h\r d4 d4 d4 ,d4 #gj #ede 4#bch #ej m9utes,ab\t #b d4 d4 ,male4 days #ga #edj 4#bdj #de m9utes d4 d4 d4 ,d4 #gb #efj 4#bcb #ce m9utes,ab\t #c d4 d4 ,d4 days ---------------------------------------- ----------------------- ,,s]ies ,d4 ---------------------------------------- ----------------------- #di #eaj #j4afj #a h\r ,less ?an ,oats ,m>* ,male4 #dj m9utes #ah h\rs #dj #fcj 4#aeh ,less ?an ,oats &,febru ,d4 #b days c>rots4 -ary #de #dce 4#afj ,none ,surviv$ ,oats ,m>* ,female4 #ci #hbj 4#aej #b days ,oats &,febru>y,male4 c>rots4 #da #ffj 4#aej ,surviv$ d4 d4 #df #dgj 4#agj #a h\r d4 ,oats 787,m>* ,female4 #bj m9utes ---------------------------------------- ----------------------- ,,s]ies ,e4 ---------------------------------------- ----------------------- #ai #eef #j4ajj ,surviv$ ,oats ,april #db #dij 4#abj ,none d4 d4 ,febru>y #dc #dcj 4#aaf d4 d4 d4 d4 #dd #ece 4#aab d4 d4 d4 d4 #ig #ccj 4#ajj d4 d4 d4 ,novemb] #ih #ebj 4#ajj d4 ,ab\t #c days,c>rots d4 ---------------------------------------- ----------------------- ,,table #g4--;,injection into p]itoneal cavity2 gu9ea pigs4 ,,s]ies ,a4 ---------------------------------------- ----------------------- ,numb] ,caffe9,appe>ance ,duration ( pig,weight4 p] ( ( ,diet4 ,mon?4,rem>ks4 kilo4 symptoms4 life ---------------------------------------- ----------------------- ,grams4,gram4 #da #gjj #j4acj #b h\rs #bb h\rs ,oats ,april ,male4 #di #cgj 4#ace #b h\rs ,surviv$ d4 d4 ,d4 #ae m9utes #dg #eej 4#abg #a h\r d4 d4 ,m>* ,female4 #ej #bij 4#ach #b h\rs d4 d4 ,april ,d4 ---------------------------------------- ----------------------- ,,s]ies ,b4 ---------------------------------------- ---------------------- #ea #dae #j4add ,none ,surviv$ ,oats ,octob],female4 #eb #dej 4#aee d4 d4 d4 d4 ,male4 #ec #dij 4#afc d4 d4 d4 d4 ,d4 ---------------------------------------- ---------------------- ,,s]ies ,c4 ---------------------------------------- ----------------------- #ei #cge #j4bjj #ae m9utes,surviv$ ,oats ,octob],gray & :ite4 #eh #chj 4#bjj #aj m9utes d4 d4 d4 #ef #ddj 4#bjj #ae m9utes#ad days d4 d4 ,male4 #ee #fij 4#ahh #a h\r #c h\rs d4 d4 ,d4 #cj m9utes ---------------------------------------- ----------------------- ,,s]ies ,d4 ---------------------------------------- ----------------------- #fg #ccj #j4bdj #e m9utes #cj m9utes,oats ,octob],male4 #fc #cdj 4#bce ,surviv$ d4 d4 ,d4 #fd #cje 4#bej #be m9utes#d h\rs d4 d4 ,female4 #dj m9utes ---------------------------------------- ----------------------- ,,table #h4--;,caffe9 by m\?2 gu9ea pigs4 ,,s]ies ,j4 ---------------------------------------- ----------------------- ,numb] ,caffe9,appe>ance ,duration ( pig,weight4 p] ( ( ,diet4 ,mon?4,rem>ks4 kilo4 symptoms4 life ---------------------------------------- ----------------------- ,grams4,gram4 #abi #hee #j4bhj #dj m9utes,less ?an ,hay &,june ,male4 #h h\rs oats #acj #hjj 4#cjj #cj m9utes,less ?an d4 d4 ,d4 #ah h\rs #aca #hfj 4#bhj #bj m9utes d4 d4 d4 ,d4 #ace #iee 4#aej #a h\r #ej #f days d4 d4 ,d4 m9utes #acd #gdj 4#afj #c h\rs #d days d4 d4 ,d4 7#a7acg #ibe 4#aej #ej m9utes#f days d4 d4 ,d4 7#a7acf #a1jjj 4#aej d4 ,surviv$ d4 d4 ,d4 #abf #ihj 4#bjj #bj m9utes#bg h\rs d4 d4 ,d4 #abg #gfj 4#bjj #a h\r #bh h\rs d4 d4 ,d4 #abh #a1jge 4#bjj #c h\rs #g h\rs d4 d4 ,d4 ---------------------------------------- ----------------------- 7#a7 ,subcutane\s injection = comp>ison4 ,,summ>y4 ,a survey ( ! results obta9$ 9 exp]im5ts on gu9ea pigs %[s t ! mode ( introduction ( caffe9 ex]ts b little influ5ce on its toxicity4 ,on c>eful analysis x w be obs]v$ t ! rate ( absorption aft] ! adm9i/ration ( caffe9 by m\?1 subcutane\sly1 or intrap]itoneally is ab\t ! same = ! "t ( appe>ance ( symptoms4 ,! p]si/5ce ( ! symptoms ( caffe9 intoxication obs]v$ 9 ^! exp]im5ts = #bd h\rs aft] adm9i/ration po9ts to sl[ elim9ation1 :i* may be expect$1 ow+ to ! fact t ! gu9ea pigs pass$ b little ur9e & caffe9 is n diuretic = ^! animals4 ,! prolong$ pres5ce ( caffe9 9 ! body probably ex]ts a h>mful influ5ce or aft] effect1 :i* may acc\nt = ! delay$ dea? ( "s animals _m days aft] a s+le dose ( caffe9 0 giv54 ,among ! factors :i* und\bt$ly influ5ce toxicity1 season %\ld be consid]$1 :ile ! pres5ce ( a diseas$ condition und\bt$ly t5ds to decrease ! resi/ance ( ! gu9ea pig to caffe94 ,diet 0 )\t any influ5ce on ! toxicity ( ! s+le dose ( caffe94 ,,exp]im5ts ,,on ,,cats4 ,^! exp]im5ts 7 p]=m$ on well-f$ animals :i* 7 kept "u obs]vation = sev]al days be=e ! te/s ) caffe9 7 made4 ,! diet consi/$ ( meat exclusively4 ,9 "s cases ! ur9e 0 exam9$ = album9 & sug> be=e caffe9 0 giv54 ,no te/s ) caffe9 7 made if l>ge am\nts ( album9 7 f\nd4 ,x may be rem>k$ t sug> 0 nev] f\nd 9 cats be=e ! adm9i/ration ( caffe91 b t consid]able am\nts ( x 7 f\nd 9 "s cases aft] x 0 giv54 ,/udies by v>i\s modes ( adm9i/ration 7 made1 by subcutane\s injection1 intrap]itoneally1 or by m\?4 ,att5tion 0 also direct$ to ! resi/ance to caffe9 9 "y cats1 sev]al exp]im5ts on kitt5s be+ made ) ?is object 9 view4 ,,subcutane\s ,,injection4 ,ro/ /at$ t caffe9 is elim9at$ 9 ! ur9e un*ang$ aft] its introduction into ! body & t ! am\nts f\nd v>i$ ) diff]5t species ( animals4 ,9 ! rabbit ! am\nt elim9at$ 0 ab\t #ba p] c5t2 9 ! dog ab\t #h p] c5t2 & 9 ! cat some:at less ?an #b4e p] c5t4 ,x w\ld appe>1 !re=e1 t ! cat decomposes caffe9 m readily ?an ! rabbit or dog2 its resi/ance consequ5tly ought to be great] ?an t ( ! o!r animals4 ,mod]ately l>ge doses 7 accord+ly employ$ 9 ! prelim9>y exp]im5ts 7s]ies ,a71 b ! results obta9$1 z %[n 9 ! protocols1 indicat$ t caffe9 is fully z toxic = ! cat z = ! rabbit or dog4 ,! doses 7 !n decreas$ & exp]im5ts 7 p]=m$ 9 ord] to asc]ta9 ! smalle/ toxic z well z ! smalle/ fatal dose4 ,,s]ies ,a4 ,?ree decigrams ( caffe9 p] kilo 7 adm9i/]$ 9 ^! exp]im5ts4 ,! results are %[n 9 ! foll[+ protocols3 ,cat #d4 ,black & :ite4 ,weight1 #a1ddj grams4 ,may #bf3 #aj4je a4 m41 #bb cc #b p] c5t caffe9 7#j4c gram p] kilo7 inject$ subcutane\sly2 #aa4aj a4 m41 copi\s salivation1 cat irritable1 muscul> /iffness pres5t1 b no tetanus2 #aa4de a4 m41 cat re/less1 convulsions1 attacks ( %ort duration1 no p>alysis obs]v$ aft] ! convulsions1 pupils dilat$2 #d4de p4 m41 cat quiet1 slight p>alysis pres5t4 ,may #bg3 ,cat exhau/$4 ,may #bh3 ,f\nd dead4 ,cat #e4 ,black & :ite male4 ,weight1 #a1cif grams4 ,june #c3 #aj a4 m4 #ba cc ( #b p] c5t caffe9 7#j4c gram p] kilo7 inject$ subcutane\sly2 #ab noon1 f\nd dead4 ,al?\gh !re 0 consid]able diff]5ce 9 ! duration ( life foll[+ ! injection ( ! same dose ( caffe9 p] kilo1 ! f9al outcome 0 ! same1 z bo? cats di$ f ! effects ( ! drug4 ,"o di$ )9 #b h\rs & ! o!r liv$ m ?an #cj h\rs aft] its adm9i/ration4 ,?ree decigrams ( caffe9 p] kilo is1 !re=e1 surely fatal to ^! animals4 ,te/s made ) small] doses are %[n 9 ! foll[+ exp]im5ts3 ,,s]ies ,b4 ,9 ^! exp]im5ts ! doses employ$ rang$ betwe5 #j4bj & #j4be gram caffe9 p] kilo4 ,cat #c4 ,black & :ite female4 ,weight1 #b1hed grams4 ,well f$4 ,june #d3 #aj4cj a4 m41 #ce cc #b p] c5t caffe9 7#j4be gram p] kilo7 inject$ subcutane\sly2 #aa a4 m41 f\nd dead4 ,cat #f4 ,black & :ite4 ,weight1 #a1fde grams4 ,june #c3 #bj cc #b p] c5t caffe9 7#j4bdc gram p] kilo7 inject$ subcutane\sly at #c p4 m41 cat grew v irritable 9 a few m9utes2 ab\t #d4 p4 m4 reflexes decid$ly increas$2 #e p4 m41 cat p>alyz$4 ,june #d3 ,cat f\nd dead4 ,cat #h4 ,weight1 #a1gce grams4 ,octob] #g3 #d p4 m41 #bb cc #b p] c5t caffe9 7#j4be gram p] kilo7 inject$ subcutane\sly 9 ! back2 #d4cj p4 m41 cat irritable1 salivation pr(use1 convulsions2 di$ at #e4cj p4 m42 no ur9e pass$ aft] caffe9 0 giv54 ,cat #i4 ,weight1 #a1ifj grams4 ,octob] #g3 #c4de p4 m41 #be cc #b p] c5t caffe9 7#j4be gram p] kilo7 inject$ subcutane\sly 9 ! back2 #d4de p4 m41 cat v irritable1 repeat$ attacks ( convulsions1 salivation copi\s2 di$ at #e4cj p4 m42 cat did n ur9ate aft] injection ( caffe94 ,cat #ab4 ,/rip$ kitt54 ,weight1 #a1ahe grams4 ,octob] #i3 ,ur9e exam9$1 no album91 no sug>2 #a4de p4 m41 #ab cc #b p] c5t caffe9 adm9i/]$2 #e p4 m41 cat alive1 no symptoms except salivation & g5]al irritability4 ,octob] #aj3 #aj4cj a4 m41 f\nd dead4 ,ab\t #ae cc ur9e collect$1 b no exam9ation made4 ,cat #ad4 ,black4 ,weight1 #a1hee grams4 ,octob] #h3 #a4dj p4 m41 #ah4e cc #b p] c5t caffe9 7#j4b gram p] kilo72 #c p4 m41 cat became re/less ab\t #aj m9utes aft] caffe9 0 inject$2 cri$ p]si/5tly & mov$ ab\t 9 cage1 no convulsions1 cat ur9at$ ab\t #ae cc1 cat defecat$4 ,octob] #i3 #i a4 m41 cat f\nd dead 9 cage4 ,ur9e gave v heavy r$uction ( ,fehl+'s solution 7mu* m ?an 0 obta9$ f ur9e ( rabbits72 #bj cc ur9e analyz$ conta9$ #d4fe p] c5t sug>4 ,autopsy3 ,lungs deeply conge/$2 liv] m>k$ fatty infiltration & deg5]ation2 sple5 normal2 kidneys pale & anemic2 inte/9es normal2 /oma* normal4 ,cat #ae4 ,/rip$4 ,weight1 #b1ade grams4 ,octob] #h3 #b p4 m41 #bb cc 7#j4b gram p] kilo7 #b p] c5t caffe9 inject$ subcutane\sly2 #b4cj p4 m41 cat irritable1 re/less1 try+ to get out ( cage1 cry+ p]si/5tly2 #b4dj1 convulsions la/+ ab\t two m9utes1 !n cat rais$ itself & made attempts to get out ( cage1 no salivation1 cat ur9at$ ab\t #aj cc & defecat$4 ,octob] #i3 #i a4 m41 cat f\nd dead 9 cage1 ab\t #aj cc ( ur9e conta9$ enorm\s quantities ( sug>4 ,autopsy3 ,lungs sev]ely conge/$2 liv] %[$ m>k$ fatty deg5]ation2 sple5 normal2 kidneys slightly pale & anemic2 inte/9es mildly conge/$2 /oma* normal4 ,cat #ai4 ,:ite4 ,weight1 #a1ajj grams4 ,octob] #bj3 #ac cc ( #b p] c5t caffe9 7#j4bcf gram p] kilo74 ,ab\t #ae m9utes lat] cat became irritable1 reflexes increas$1 p]si/5t cry+1 /iffness ( extremities1 di>rhea pres5t2 #d4cj p4 m41 /iffness ( muscles1 coord9ation mu* di/urb$1 walk$ ) great difficulty2 #d4cj p4 m41 no new symptoms1 p]si/5t cry+ cont9u$4 ,octob] #ba3 ,f\nd dead4 ,cat #bj4 ,:ite kitt54 ,weight1 #gij grams4 ,octob] #bj3 #aa4ce a4 m41 #aj cc #b p] c5t caffe9 7#j4be gram p] kilo7 giv5 subcutane\sly2 #ab noon1 convulsions foll[$ by p>alysis2 #a4cj p4 m41 /ill brea?+1 app>5tly 9 comatose condition1 lay on its side1 dyspnoea1 pr(use salivation2 #d p4 m41 convulsions & dea?4 ,! results ( ! exp]im5ts ( s]ies ,b %[ t a dose ( ev5 #j4b caffe9 p] kilo is v toxic = ! cat4 ,symptoms appe>$ 9 "o animal #dj m9utes aft] ! injection ( caffe94 ,"s ( !m 7 f\nd dead #ah h\rs aft] injection1 :i* means t ! duration ( life 0 probably a great deal less s9ce !re 0 evid5ce t !y _h be5 dead = "s "t4 ,dea? occurr$ q soon aft] l>g] doses 7 inject$4 ,cat ,no4 #c di$ #cj m9utes aft] x receiv$ caffe94 ,! am\nts employ$ 9 ^! exp]im5ts c n be consid]$ !re=e z ! m9imum fatal doses4 ,small] doses 7 !n tri$1 z %[n 9 ! exp]im5ts ( ! next s]ies4 ,,s]ies ,c4 ,exp]im5ts 7 p]=m$ on five cats :i* receiv$ f #adj to #aee mg p] kilo1 z foll[s3 ,cat #bd4 ,/rip$4 ,weight1 #a1cjj grams4 ,octob] #be3 #aj a4 m41 #ej cc ur9e1 album9 mod]ate am\nt--no sug>2 #aj cc caffe9 inject$ subcutane\sly at #ab noon2 #ab4cj1 irritable1 cri$ p]si/5tly1 no appetite2 #d p4 m41 no convulsions1 b p]si/5t cry+4 ,octob] #bg3 ,cat 0 /ill alive4 ,cat #ag4 ,weight1 #b1fbj grams4 ,octob] #ab3 #i4cj a4 m41 #fe cc ur9e collect$2 m ?an a trace ( album9 pres5t1 no r$uction ( ,fehl+'s solution2 #c p4 m41 #bj cc #b p] c5t caffe9 7#aej mg p] kilo7 inject$ subcutane\sly2 #c4ae p4 m41 irritable & re/less4 ,octob] #ac3 #i a4 m41 ab\t #ae cc ur9e collect$1 r$uction ( ,fehl+'s solution m>k$2 osazone te/ also positive4 ,cat #bc4 ,black & :ite4 ,weight1 #a1fde grams4 ,octob] #be3 #aj a4 m41 #adj cc ur9e collect$ 7s9ce ,octob] #bc71 small am\nt ( album9 pres5t1 no sug>4 ,octob] #bg3 #i a4 m41 no album92 no sug> 9 ur9e2 #aa4ej a4 m41 #ab4e cc caffe9 inject$ subcutane\sly 7#j4ae gram p] kilo72 #a p4 m41 convulsions & dea?4 ,cat #g4 ,/rip$ kitt54 ,weight1 #a1bhe grams4 ,octob] #aa3 ,ur9e collect$1 no album91 no sug>2 #i4ej a4 m41 #aj cc #b p] c5t caffe9 inject$ subcutane\sly 9 ! back2 #aj4aj1 viol5t convulsions la/+ ab\t #cj seconds2 #aj4bj1 convulsions ( %ort] duration2 #aj4cj convulsions2 #aj4ce1 convulsions la/+ a few seconds2 ur9e pass$ ab\t #aj4bj1 conta9$ a mod]ate am\nt ( album91 b !re 0 no r$uction ( ,fehl+'s solution2 #aj4de1 pr(use salivation & p>alysis2 di$ ab\t #aj4ej4 ,cat #ci4 ,yell[4 ,weight1 #b1bhe grams4 ,april #ac3 #b4dj p4 m41 #af cc #b p] c5t caffe9 7#j4ad gram p] kilo7 inject$ subcutane\sly 9 ! back2 #c4de p4 m41 cat di$4 ,( ! five exp]im5ts ( ?is s]ies ?ree di$ aft] doses ( #adj1 #aej1 & #aee mg p] kilo4 ,! o!r two %[$ symptoms ( toxicity1 b surviv$ a dose ( #aej mg p] kilo :i* indicat$ t ! m9imum fatal dose 0 probably rea*$4 ,to te/ ?is supposition small] doses 7 adm9i/]$1 z %[n 9 ! foll[+ exp]im5ts4 ,,s]ies ,d4 ,t5 cats 7 us$ = ?is s]ies ( exp]im5ts1 & ! doses adm9i/]$ v>i$ betwe5 #ajc & #aci mg p] kilo4 ,! results %[n 9 ! app5d$ table 7p4#eh7 indicate t ab\t #abj to #adj mg ( caffe9 p] kilo may induce mild symptoms 9 "s cases4 ,! conclusion may be safely drawn !re=e t #aej mg p] kilo is approximately ! m9imum fatal dose = ! cat :5 ! drug is giv5 subcutane\sly4 ,t small] doses are1 h[ev]1 by no means to be reg>d$ z always safe is %[n 9 ! foll[+ exp]im5ts4 ,,s]ies ,e4 ,cat #dc4 ,weight1 #c1bbe grams4,d ,d ,cat probably old2 _h be5 9 ! laboratory = sev]al weeks be=e ! exp]im5t4 ,ga9$ 9 weight #age grams4 ,septemb] #ad3 #aj4bj a4 m41 #bj cc #b p] c5t caffe9 7#j4abd gram p] kilo7 inject$ into ! back2 #aa a4 m41 tetanus & dea?4 ,autopsy3 ,lungs conge/$2 liv] conge/$ & %[$ hemorrhagic spots 9 capsules & fatty deg5]ation2 kidneys slightly conge/$2 o!r organs normal4 ,cat #dh4 ,black female4 ,weight1 #c1jej grams4 ,septemb] #ad3 #ah cc #b p] c5t caffe9 7#j4aah gram p] kilo7 inject$ subcutane\sly 9 ! back2 #aj4cj a4 m41 viol5t convulsions & dea?4 ,autopsy3 ,lungs conge/$ 9 spots %[+ num]\s pete*ia2 liv] conge/$2 sple5 conge/$2 o!r organs normal4 ,! dim9i%$ resi/ance to caffe9 ( cats ,nos4 #dc & #dh might be due to ! pa?ologic *anges f\nd on autopsy1 = evid5ce is n want+ t ! toxicity ( drugs might be greatly alt]$ "u pa?ological conditions4 ,hunt7#dj7 has %[n t resi/ance to acetonitril is consid]ably dim9i%$ 9 *ronic alcoholism4 ,?is seems to be true also ( o!r drugs "u abnormal conditions4 ,small] doses ( atrop97#gh7 are requir$ 9 lead poison+ ?an "u normal conditions to produce ! same results4 ,! foll[+ exp]im5t is ( int]e/ 9 ?is connection1 = 9 ?is case a mu* small] dose ?an 0 giv5 9 exp]im5ts ,nos4 #dc & #dh produc$ ! typical symptoms ( caffe9 poison+ & prov$ to be fatal4 ,cat #dg1 black & :ite male4 ,weight1 #d1bbj grams4 ,septemb] #ae3 ,receiv$ subcutane\sly #ah cc #b p] c5t caffe9 7#j4jhd gram p] kilo72 no symptoms obs]v$ = ab\t six h\rs4 ,septemb] #af3 ,no symptoms4 ,septemb] #ag3 ,weight1 #d1bej grams2 inject$ #ah cc #b p] c5t caffe9 7#j4jhd gram p] kilo72 tetanus & dea? aft] two h\rs4 ,autopsy3 ,sev]e hemorrhagic pneumonia2 kidneys pale1 o!r organs normal4 ,s9ce two controls surviv$ ! same dose 9 proportion to ! body weight ( ! animal )\t %[+ any symptoms1 ! assumption is ju/ifi$ t ! l[] resi/ance to caffe9 0 due to ! pres5ce ( pneumonia1 ?us af=d+ additional support to ! view t ! toxicity ( caffe9 may be increas$ 9 disease4 ,,injection ,,into ,,! ,,p]itoneal ,,cavity4 ,^! exp]im5ts 7 c>ri$ out on full-gr[n & on "y subjects4 ,z 9 previ\s exp]im5ts1 doses ( diff]5t sizes 7 employ$4 ,a dose ( #j4b gram p] kilo 0 tri$ fir/ & !n r$uc$ gradually to #j4a gram p] kilo4 ,cat #aj4 ,female4 ,weight1 #b1igj grams4 ,octob] #i1 #aiji3 #a4cj p4 m41 #cj cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ into ! p]itoneal cavity2 ur9e exam9$ = album9 & sug>1 negative2 cat f\nd dead at #b4cj p4 m4 ,no ur9e 9 ! bladd]4 ,cat #af4 ,black female4 ,weight1 #b1dbj grams4 ,octob] #i1 #aiaj3 ,ur9e exam9$ = album9 & sug>1 negative2 #b4cj p4 m41 #bb cc #b p] c5t caffe9 7#j4ahc gram p] kilo7 inject$ into ! p]itoneal cavity2 f\nd dead at #c p4 m4 ,cat #ii4 ,well-f$ gray female4 ,weight1 #c kilos4 ,june #bb1 #aiaa3 #c4dj p4 m41 #ae cc #b p] c5t caffe9 inject$ into p]itoneal cavity2 salivation & m>k$ irritability )9 "o h\r aft] injection4 ,june #bd3 ,alive1 appetite good4 ,cat #ih4 ,well-f$ black male4 ,weight1 #d1ajj grams4 ,june #bb3 #c4de p4 m41 #bj4e cc #b p] c5t caffe9 7#j4a gram p] kilo7 inject$ into p]itoneal cavity2 v irritable a few m9utes aft] injection1 no o!r symptoms4 ,june #bd3 ,no symptoms1 appetite good4 ,cat #ic4 ,black & :ite4 ,weight1 #a1dej grams4 ,june #bb3 #c p4 m41 #cj cc #b p] c5t caffe9 7#j4acg gram p] kilo7 inject$ into p]itoneal cavity2 salivation1 no o!r symptoms2 "u obs]vation until #f p4 m4 ,june #bc3 #i a4 m41 no ur9e1 cat %[$ no symptoms4 ,june #bd3 #i a4 m41 no symptoms1 took n\ri%m5t z usual4 ,cat #hg4 ,well-f$ :ite female4 ,weight1 #b1fae grams4 ,june #bc3 #b4de p4 m41 #ai cc #b p] c5t caffe9 7#j4ade gram p] kilo7 inject$ into p]itoneal cavity2 became irritable & re/less4 ,june #bd3 #i a4 m41 no symptoms1 took n\ri%m5t z usual4 ,cat #ig4 ,gray4 ,age1 #c mon?s4 ,weight1 #ejj grams4 ,diet1 meat4 ,june #bd3 #b4be p4 m41 #e cc #b p] c5t caffe9 7#j4b gram p] kilo7 inject$ into p]itoneal cavity2 #d p4 m41 no symptoms4 ,june #bi3 ,di$4 ,cat #if4 ,gray & :ite4 ,age1 #c mon?s4 ,weight1 #ege grams4 ,diet1 meat4 ,june #bd3 #b4bj p4 m41 #d cc #b p] c5t caffe9 7#j4aci gram p] kilo7 inject$ into p]itoneal cavity2 #c4ee p4 m41 no symptoms4 ,june #cj3 ,di$4 ,cat #ie4 ,black4 ,age1 ab\t #c mon?s4 ,weight1 #hfj grams4 ,diet1 meat4 ,june #bd3 #aj4ae a4 m41 #h4f cc #b p] c5t caffe9 inject$ into p]itoneal cavity1 salivation imm$iately aft] injection2 #aj4be1 convulsions & p>alysis2 di$ #aj4de a4 m4 ,autopsy3 ,macroscopical exam9ation ( ! organs1 negative4 ,cat #id4 ,black & :ite4 ,weight1 #gij grams4 ,age1 ab\t #c mon?s4 ,diet1 meat4 ,june #bd3 #aj a4 m41 #h cc #b p] c5t caffe9 inject$ into p]itoneal cavity2 #d p4 m4 "u cont9ual obs]vation s9ce injection1 cat v irritable1 respiration m rapid ?an normal1 di>rhea pres5t4 ,exam9ation ( ! above protocols %[ t a dose ( #b decigrams p] kilo 0 fatal )9 "o h\r to "o cat & t a some:at small] dose kill$ ano!r individual 9 #cj m9utes4 ,am\nts "u #j4ae gram p] kilo 7 j suffici5t to induce mild symptoms1 su* z increas$ irritability & salivation1 :i* disappe>$ )9 a few h\rs4 ,9 no case 7 ! effects noticeable on ! foll[+ day4 ,! exp]im5ts on "y kitt5s are especially int]e/+1 z !y prov$1 contr>y to expectation1 to be di/9ctly m resi/ant ?an full gr[n individuals4 ,! dea? ( ,nos4 #ig & #if )9 five & six days1 respectively1 c n be ascrib$ to caffe91 s9ce "s ( ! controls also di$4 ,moreov]1 x w be rem>k$ 9 ?is connection t no symptoms appe>$ 9 ?ree ( ! f\r "y kitt5s aft] ! adm9i/ration ( a dose :i* 0 rapidly fatal to adult cats4 ,! rapid dea? ( ,no4 #ie aft] ! same dose =ms an exception :i* c n be acc\nt$ =1 z macroscopical exam9ation at autopsy prov$ negative4 ,,adm9i/ration ,,by ,,m\?4 ,two decigrams p] kilo 7 giv5 at fir/1 b x 0 f\nd t ?is am\nt 0 surely fatal4 ,! dose 0 !re=e r$uc$ to #j4abe gram p] kilo4 ,9 all ( ^! exp]im5ts caffe9 0 giv5 by means ( a s(t rubb] ca!t] slipp$ ov] ! /em ( a funnel :i* s]v$ z a /oma* tube4 ,a #b p] c5t aque\s solution 0 us$ ?r\gh\t ^! te/s except 9 "o case 9 :i* caffe9 0 giv5 mix$ ) ! food4 ,cat #ib4 ,black & :ite female4 ,weight1 #a1gej grams4 ,june #aj3 #ab4je p4 m41 #ad cc #b p] c5t caffe9 7#j4af gram p] kilo7 giv5 by m\?2 cat 0 quiet :5 ti$ on hold]1 /ruggl$ only a little :5 tube 0 put into /oma*2 #ab4cj p4 m41 cat vomit$1 no o!r symptoms4 ,june #ac3 ,condition good1 appetite good4 ,cat #hg4 ,:ite female4 ,weight1 #b1fbj grams4 ,diet1 meat4 ,june #e3 #b4ae p4 m41 #bj cc #b p] c5t caffe9 7#j4ae gram p] kilo7 solution adm9i/]$ by m\? ?r\gh /oma* tube2 #b4cj p4 m41 cat irritable1 b no o!r symptoms2 #e p4 m41 condition ab\t ! same1 except t x 0 m irritable & %[$ "s /iffness ( ! extremities4 ,june #ac3 ,alive & 9 good condition1 appetite good1 n irritable4 ,cat #ia4 ,:ite female4 ,weight1 #c1jej grams4 ,june #aj3 #ab noon1 #bc cc 7#j4ae gram p] kilo7 ( #b p] c5t caffe9 adm9i/]$ by m\?1 cat /ruggl$ viol5tly2 #a4cj1 salivation2 #a4dj p4 m41 convulsions2 di$ at #b p4 m4 ,autopsy3 ,conge/ion ( lungs1 liv]1 & sple52 he>t vessels inject$2 o!r organs normal4 ,cat #hh4 ,black & :ite female4 ,weight1 #c1bfj grams4 ,diet1 meat4 ,june #e3 #b4bj p4 m41 #be cc ( #b p] c5t caffe9 7#j4ae gram p] kilo7 giv5 by m\?2 #b4de p4 m41 cat irritable1 no o!r symptoms 7cat did n vomit aft] ! adm9i/ration ( caffe972 #d p4 m41 cat f\nd dead4 ,autopsy3 ,liv] v mu* conge/$2 he>t contract$2 body 0 /ill w>m at ! "t ( autopsy4 ,cat #ij4 ,:ite & yell[ female4 ,weight1 #b1fhe grams4 ,diet1 meat4 ,june #e3 #c4ae p4 m41 #bg cc ( #b p] c5t caffe9 7#j4b gram p] kilo7 giv5 by m\? ?r\gh /oma* tube1 ab\t half an h\r lat] cat became irritable & began to salivate2 at #d4cj p4 m4 salivation became m m>k$1 dyspnoea 0 well develop$1 & ! cat 0 q re/less & _h tremors2 #e p4 m41 %ort spasms ( po/]ior extremities1 b lay quietly 9 ! cage mo/ ( ! "t2 #e4bj p4 m41 convulsions ( %ort duration & dea?1 muscul> relaxation foll[$ imm$iately aft] convulsions1 no vomit+1 di>rhea obs]v$ aft] adm9i/ration ( caffe91 & cat pass$ ab\t #aj cc ( ur9e4 ,june #f3 #i a4 m41 f\nd dead4 ,cat #hi4 ,:ite & black female4 ,weight1 #b1hfj grams4 ,diet1 meat4 ,june #e3 #c4ae p4 m41 #bh4f cc 7#j4b gram p] kilo7 ( #b p] c5t caffe9 giv5 by m\? ?r\gh /oma* tube1 no vomit+ obs]v$1 nor any o!r symptoms2 #c4cj1 f\nd dead4 ,autopsy3 ,organs normal2 liv] conge/$4 ,cat #hb4 ,gray female4 ,m>* #c1 weight #b1dej grams2 ,june #f1 weight #b1gej grams4 ,diet1 #aej grams ( meat daily4 ,june #g3 ,giv5 #j4dabe gram ( caffe9 9 #aej grams ( meat1 did n eat4 ,june #h3 ,giv5 #j4dabe gram ( caffe9 9 #aej grams ( meat1 refus$ to eat4 ,june #i3 ,giv5 #aej grams ( meat )\t caffe91 ate all ( x4 ,june #aj3 ,no food giv54 ,june #aa3 ,no food giv54 ,june #ab3 ,giv5 #j4dabe gram caffe9 9 #aej grams ( meat 7#aej mg p] kilo71 ate all ( x4 ,june #ac3 ,f\nd dead4 ,autopsy3 ,lungs conge/$1 liv] conge/$2 o!r organs app>5tly normal4 ,cat #ajj4 ,gray female4 ,weight1 #b1gdj grams4 ,diet1 meat4 ,july #ag3 #c p4 m41 #ag cc ( #b p] c5t caffe9 7#abd mg p] kilo7 giv5 by m\? ?r\gh /oma* tube at #c4bj p4 m42 #e p4 m41 v irritable1 b no o!r symptoms4 ,july #ah3 ,"u obs]vation all day1 no symptoms4 ,cat #ic4 ,black & :ite female4 ,weight1 #a1fdj grams4 ,july #ag3 #c4cj p4 m41 #aj cc 7#j4abe gram p] kilo7 ( #b p] c5t caffe9 giv5 by m\? ?r\gh /oma* tube4 ,july #ah3 ,"u obs]vation all day1 no symptoms4 ,f ! results ( ! exp]im5ts ( ?is s]ies x appe>s t #j4ae gram caffe9 p] kilo may be fatal )9 a few h\rs aft] its adm9i/ration1 ev5 if ! drug is mix$ ) a mod]ate am\nt ( meat4 ,exp]im5ts #hg & #ib %[1 h[ev]1 t ?is am\nt may be borne by "s individuals )\t any s]i\s consequ5ces1 z ! cats 7 "u obs]vation = "s "t aft] !y receiv$ caffe91 & no unt[>d symptoms 7 notic$ 9 ei!r ( !m dur+ ?is "t4 ,x may be rem>k$ t cat ,no4 #ib vomit$ %ortly aft] x receiv$ caffe94 ,x is practically c]ta91 !re=e1 t ?is am\nt ( caffe9 9 proportion to ! weight ( ! animal w 9 ! great majority ( cases prove fatal1 & p]haps 9 a small] p]c5tage ( individuals x is surely toxic if x does n escape absorption4 ,small] doses may cause irritability 9 "s individuals1 b symptoms ref]able to n]v\s symptoms ( muscles 7 abs5t1 z 9 exp]im5ts ,nos4 #ic & #ajj4 ,! m9imum fatal dose ( caffe9 = ! cat :5 giv5 by m\? is1 !re=e1 #j4ae gram p] kilo4 ,,table #i4--,subcutane\s injection2 cats4 ,,s]ies ,a4 ---------------------------------------- -------------------------- ,numb]4 ,weight4 ,caffe9 ,symptoms4 ,duration ( life4 p] kilo4 ---------------------------------------- -------------------------- ,grams4 ,gram4 #d #a1ddj #j4cj #fe m9utes ,ov] #bi h\rs4 #e #a1cif 4#cj ,ab\t #b h\rs4 ---------------------------------------- -------------------------- ,,s]ies ,b4 ---------------------------------------- -------------------------- #c #b1hed #j4be #cj m9utes4 #f #a1fde 4#bdc ,few m9utes #a h\r #cj m9utes4 #h #a1gce 4#be #cj m9utes4 #a h\r4 #i #a1ifj 4#be #a h\r #a h\r #de m9utes4 #ab #a1ahe 4#bj #c h\rs ,less ?an #ah h\rs4 #ad #a1hee 4#bj #a h\r #bj m9utes ,d4 #ae #b1ade 4#bj #dj m9utes4 ,d4 #ai #a1ajj 4#bcf #ae m9utes ,d4 #bj #gij 4#be #d h\rs #cj m9utes4 ---------------------------------------- --------------------------- ,,s]ies ,c4 ---------------------------------------- -------------------------- #bd #a1cjj #j4aec #a h\r ,surviv$4 #ag #b1fbj 4#ae #ae m9utes ,d4 #bc #a1fde 4#ae #a h\r #aj m9utes4 #g #a1bhe 4#aee #bj m9utes #a h\r4 #i #b1bhe 4#ad #fe m9utes4 ---------------------------------------- -------------------------- ,,s]ies ,d4 ---------------------------------------- -------------------------- ,numb]4,weight4 ,caffe9 ,symptoms4 ,duration ( life4 p] kilo4 ---------------------------------------- -------------------------- ,grams4 ,gram4 #ac #gcj #j4aci ,re/lessness #ba #a1afe 4#ach ,none #be #ife 4#ajc d4 #bf #a1fje 4#abe d4 #bg #a1fbe 4#abe d4 #bh #b1cce 4#abh d4 ,receiv$ #b doses3 surviv$4 #dj #b1gaj 4#abi d4 ,d4 #da #a1ghe 4#abc d4 ,d4 #db #b1cae 4#aab d4 ,d4 #ch #b1cbe 4#abj ,mild ,di$ aft] second dose4 ---------------------------------------- -------------------------- ,,s]ies ,e47#a7 ---------------------------------------- -------------------------- #dc #c1bbe #j4abd #dj m9utes4 #dh #c1jej 4#aah ,di$ soon aft]4 #dg #d1bbj 4#jhd ,surviv$4 7#b7dg #d1bej 4#jhd #b h\rs4 ---------------------------------------- -------------------------- 7#a7 ,pa?ological conditions4 7#b7 ,two days aft] fir/ injection4 ,,table #aj4--;,injections into p]itoneal cavity2 cats4 ---------------------------------------- -------------------------- ,numb]4,weight4 ,caffe9 ,symptoms4 ,duration ( life4 p] kilo4 ---------------------------------------- -------------------------- ,grams4 ,gram4 #ii #c1jjj #j4ajj ,mild ,surviv$4 #ih #d1ajj 4#ajj d47#a7 ,d4 #ic #a1dej 4#acg ,v mild ,d4 #hg #b1fae 4#ade d4 ,d4 #ig #eje 4#bjj ,none #e days4 #if #ege 4#aci d4 #f days4 #ie #hfj 4#bjj #ae m9utes #cj m9utes4 #id #gij 4#bjj ,di>rhea ,surviv$4 #aj #b1igj 4#bjj #a h\r4 #af #b1dbj 4#ahc #cj m9utes4 ---------------------------------------- -------------------------- 7#a7 ,9 few m9utes4 ,,table #aa4--;,adm9i/ration ( caffe9 by m\?2 cats4 ---------------------------------------- -------------------------- ,numb]4,weight4 ,caffe9 ,symptoms4 ,duration ( life4 p] kilo4 ---------------------------------------- -------------------------- ,grams4 ,gram4 #ia #c1jej #j4ae #a h\r #dj m9utes #b h\rs4 #hh #c1bfj 4#ae #a h\r #dj m9utes4 #ib #a1gej 4#af #be m9utes ,surviv$4 #hg #b1fbj 4#ae #c h\rs ,d4 #ij #b1fhe 4#bj #a h\r #ae m9utes ,less ?an #ah h\rs4 #hi #b1hfj 4#bj #ge m9utes4 #hb #b1dej 4#ae ,less ?an #bd h\rs4 #ajj #b1gdj 4#abd #a h\r #dj m9utes ,surviv$4 #ic #a1fdj 4#abe ,d4 ---------------------------------------- -------------------------- ,,summ>y4 ,! toxicity ( caffe9 9 cats is %[n to be ! same :5 giv5 by m\? z :5 inject$ subcutane\sly1 ! m9imum fatal doses 9 bo? cases be+ #j4ae gram p] kilo4 ,:5 introduc$ by ! intrap]itoneal r\te1 caffe9 is1 on ! contr>y1 di/9ctly less toxic4 ,aft] ! adm9i/ration ( #j4acg & #j4ade gram caffe9 p] kilo 7,nos4 #ic & #hg7 salivation 9 "o cat 7,no4 #ic7 & irritability & muscul> /iffness 9 ! o!r 7 ! only effects notic$4 ,^! symptoms 7 no long] obs]v$ ! next day & ! cats appe>$ to be p]fectly normal4 ,exp]im5ts ) l>g] doses indicate t ! m9imum fatal dose by ?is me?od ( adm9i/ration is ab\t #j4b gram p] kilo4 ,,exp]im5ts ,,on ,,dogs4 ,! exp]im5ts 7 c>ri$ out on well-f$ adult dogs & on puppies1 kept "u obs]vation = "s "t be=e ! drug 0 adm9i/]$4 ,only ^? manife/+ no signs ( abnormality 7 us$ = ^! te/s4 ,caffe9 0 giv5 by m\? mix$ ) #aj to #bj grams ( meat1 or subcutane\sly 9 #b p] c5t aque\s solution4 ,! "y animals receiv$ caffe9 dissolv$ 9 milk4 ,! det]m9ation ( ! m9imum toxic or fatal doses :5 ! drug 0 f$ pres5t$ consid]able difficulty1 z 9 _m in/ances ! +e/ion ( ! drug 0 closely foll[$ by vomit+4 ,,adm9i/ration ,,by ,,m\?4 ,,s]ies ,a4 ,! effective dose 9 ^! exp]im5ts %[$ consid]able v>iation4 ,"o dog 7,no4 #ch7 di$ aft] a dose ( #j4ab gram caffe9 p] kilo1 :ile "s subjects surviv$ doses ( #j4b & #j4bc gram p] kilo4 ,9 ! #ab exp]im5ts giv5 9 ,table #ab1 page #fb1 x w be notic$ t f #j4ab to #j4aeb gram p] kilo prov$ fatal to ?ree dogs1 :ile ?ree o!rs surviv$ ! same am\nts 9 proportion to ! body weight4 ,! results 7 ! same ) l>g] doses4 ,x may be obs]v$ 9 ?is connection t 9 ! case ( ! five dogs 9 :i* vomit+ 0 notic$ "s "t dur+ ! #bd h\rs foll[+ ! adm9i/ration ( caffe91 f\r surviv$1 ,no4 #ch be+ ! exception4 ,! great] toxicity ( caffe9 9 ?is case is 9 all probability due to "s morbid process1 ! pres5ce ( :i* 0 indicat$ by ! high temp]ature ( ?is subject4 ,t vomit+ may av]t a fatal issue aft] l>g] doses ( caffe9 is made fur!r probable by exp]im5t on dog ,no4 #dh1 = :i*1 9 ! abs5ce ( vomit+1 a dose ( #j4b gram ( caffe9 p] kilo prov$ fatal4 ,on ?is supposition ! discrepancy 9 ! results obta9$ 9 ?is s]ies may be readily expla9$4 ,! smalle/ doses :i* prov$ fatal 9 ^! exp]im5ts 7 #j4ade & #j4aeb gram p] kilo4 ,no4 #ch1 :i* di$ f a dose ( #j4ab gram p] kilo1 may be consid]$ z an exception1 z ?is subject 0 n normal4 ,exp]im5ts ) caffe9 on dogs 7 made at v>i\s o!r times 9 ?is laboratory b fail$ to %[ t small] doses ( caffe91 ev5 :5 vomit+ did n occur aft] its adm9i/ration1 7 fatal1 al?\gh toxic effects 7 obs]v$4 ,! conclusion is !re=e ju/ifi$ t ! m9imum fatal dose ( caffe9 = ! normal dog is ab\t #j4ae gram p] kilo :5 giv5 by m\?4 ,,subcutane\s ,,injection4 ,,s]ies ,b4 ,to det]m9e ! toxicity ( caffe9 m accurately1 especially = comp>ison ) animals ( o!r species1 ! subcutane\s me?od ( adm9i/ration 0 also us$4 ,! injections 7 made ) a syr+e ( #bj cc capacity1 ! cont5ts ( :i* 7 introduc$ into contigu\s areas4 ,! results ( exp]im5ts on six dogs indicate t approximately #aej to #afj mg p] kilo is ! m9imum fatal dose1 s9ce su* doses prov$ fatal to two out ( ! ?ree animals receiv+ ?is am\nt1 :ile ?ree o!rs :i* receiv$ doses ( f #adc to #afj mg p] kilo surviv$4 ,,exp]im5ts ,,on ,,puppies4 ,,s]ies ,c4 ,9 ^! exp]im5ts ! resi/ance ( "y gr[+ puppies to caffe9 0 /udi$4 ,caffe9 0 giv5 by m\? to all ! subjects except "o1 to :i* x 0 adm9i/]$ subcutane\sly4 ,! protocols1 only a few ( :i* are giv51 & ! tabulat$ data ( ! exp]im5ts 7p4 #fb7 %[ t ! age ( ! animal has a decid$ influ5ce on ! toxicity ( caffe94 ,dog #aa4 ,weight1 #a1bfj grams4 ,augu/ #b3 ,at #aj a4 m4 giv5 #ab4e cc ( #b p] c5t ( caffe9 ?r\gh /oma* tube2 #b p4 m41 _h convulsions1 di>rhea1 salivation1 & /iffness ( limbs4 ,augu/ #c3 ,f\nd dead #i a4 m4 ,autopsy3 ,?oracic visc]a app>5tly normal2 /oma* imm5sely di/5d$ & fill$ ) a :ite1 *eesy mass & "s fluid2 r\nd worms pl5tiful 9 /oma* & small inte/9e2 mucosa ( entire inte/9e conge/$2 cont5ts ( l[] inte/9e conge/$2 liv] pale2 sple5 flabby2 kidney conge/$4 ,dog #aj4 ,weight1 #a1fej grams4 ,july #bf3 #i4cj a4 m41 #bi cc ( #b p] c5t caffe9 add$ to #fj cc ( milk (f]$1 b refus$1 & 0 !re=e f$ by m\? ?r\gh /oma* tube2 #aj4be a4 m41 no symptoms2 #aa4cj a4 m41 re/lessness1 extremities /iff1 po/4 extremities spread ap>t1 dog %[s well-m>k$ symptoms ( caffe9 poison+2 #ab4aj p4 m41 symptoms m sev]e1 extremities ext5d$ & spread out1 is ly+ flat on belly s t nose t\*es floor ( ! cage2 #ab4dj p4 m41 f\nd dead2 0 alive at #ab4aj p4 m4 ,autopsy3 ,lungs %[$ hemorrhagic foci 9 all lobes2 he>t app>5tly normal2 liv] fatty2 /oma* & inte/9es fill$ ) r\nd worms2 sple5 & kidney app>5tly normal4 ,dog #i4 ,weight1 #c1jjj grams4 ,july #be3 #cej mg caffe9 p] kilo2 #e p4 m41 ly+ d[n mo/ ( ! "t1 occasionally walks ab\t 9 /all2 re/lessness pres5t1 b n m>k$2 #e4cj p4 m41 vomit :i* look$ fro?y & mucilag9\s notic$ on ! floor ( ! /all2 no meat p>ticles notic$ 9 vomit1 ?\gh se>*$ =2 :9es occasionally4 ,july #bf3 #i a4 m41 looks well2 no signs ( ! effect ( caffe9 giv5 ! day previ\s4 ,dog #h4 ,yell[ female4 ,weight1 #c1ajj grams4 ,july #bb3 #aj4ej a4 m41 receiv$ #a4a grams ( caffe9 9 #aj grams ( meat 7#ced mg caffe9 p] kilo72 #c p4 m41 vomit$ mucus2 gait clumsy2 refus$ to eat2 cont9ually dr9k+ wat]2 v re/less2 #d p4 m41 convulsions set 9 at #c4ee p4 m42 tonic rigidity ( ! po/]ior extremities2 pr(use salivation2 convulsions 7 bo? tonic & clonic 9 "*1 & resembl$ ^? se5 9 rabbits 9 caffe9 intoxication2 a /rik+ feature 0 ! duration ( ! spasm1 :i* began at #c4ee p4 m4 & kept up = m ?an two h\rs4 ,july #bc3 ,f\nd dead at #i a4 m4 ,! data record$ 9 ! table & 9 ! protocols ( ! exp]im5ts ( s]ies ,c %[ t f\r out ( ! sev5 animals exp]im5t$ ^u di$ 9 less ?an #bd h\rs aft] caffe9 0 f$2 ?ree ( ^! receiv$ #cjj to #ced mg caffe9 p] kilo1 & "o receiv$ #bjj mg caffe9 p] kilo4 ,no4 #h vomit$ f\r h\rs aft] caffe9 0 giv54 ,no vomit+ 0 obs]v$ 9 ! o!r ?ree dogs4 ,f #j4cjj to #j4cej gram ( caffe9 p] kilo may be reg>d$1 !re=e1 z surely fatal to "y gr[+ puppies4 ,t ?is is 9 all probability ! m9imum le?al dose appe>s f ! foll[+ exp]im5ts3 ,no4 #i1 :i* receiv$ #cej mg p] kilo1 vomit$ "o h\r aft] & surviv$1 :i* indicates t "s ( x 0 probably n absorb$4 ,! am\nt :i* ent]$ ! circulation 0 !re=e less ?an #cej mg p] kilo4 ,s9ce ,no4 #ae1 :i* receiv$ #bej mg caffe9 subcutane\sly1 likewise surviv$1 ! probabilities are t #cjj to #cej mg p] kilo 7 ! m9imum fatal doses = ^! animals4 ,moreov]1 ,no4 #ab1 :i* receiv$ #bjj mg caffe9 p] kilo1 surviv$1 no vomit+ hav+ be5 obs]v$4 ,! case ( ,no4 #aa1 9 :i* ! same am\nt ( caffe9 9 proportion to body weight prov$ fatal1 may be expla9$ p]haps by ! f9d+s ( ! autopsy4 ,! results obta9$ 9 ^! exp]im5ts ju/ify ! conclusion t "y gr[+ dogs c /& l>g] doses ( caffe9 ?an full-gr[n & old] dogs4 ,att5tion may also be call$ "h to ! diff]5ce 9 ! symptoms produc$ by caffe9 9 v "y & 9 adult dogs4 ,x 0 (t5 notic$ 9 ^! exp]im5ts t ! symptoms 9 old] subjects :5 giv5 toxic doses ( caffe9 set 9 r abruptly & end$ 9 in/antane\s dea?4 ,we fail$ to obs]ve ?is ph5om5on aft] ! adm9i/ration ( l>ge am\nts ( caffe9 to v "y dogs1 9 :i* tonic & clonic convulsions alt]nat+ ) p>esis 7 obs]v$4 ,^! symptoms set 9 r gradually & la/$ sev]al h\rs 7see exp]im5t ,no4 #h71 resembl+ ! rabbit 9 ?is reg>d4 ,,summ>y4 ,! toxicity ( caffe9 = adult dogs is ab\t ! same1 :e!r giv5 by m\? or inject$ subcutane\sly4 ,! resi/ance ( puppies to caffe9 is mu* great] ?an t ( adults4 ,,table #ab4--;,adm9i/ration by m\?2 dogs4 7,s]ies ,a47 ---------------------------------------- -------------------------- ,caffe9 ,no4 ,weight4 p] ,results4 ,rem>ks4 kilo4 ---------------------------------------- -------------------------- ,kilos4,gram4 #dg #ac4fj #j4add ,surviv$ ,vomit+ obs]v$4 #ee #ab4ge 4#bjj d4 ,/iffness ( muscles2 no o!r symptoms4 #ef #g4ie 4#bjj ,f\nd dead next day #eb #ac4fj 4#adg ,surviv$ #eg #f4ej 4#bcj d4 ,vomit$ aft] #a h\r2 convulsions aft] #a h\r & #de m9utes4 #ci #bc4aj 4#abj d4 ,increas$ frequ5cy ( respiration1 ?ir/1 loss ( appetite1 vomit$ re/ ( day :5 he drank wat]1 salivation1 re/lessness1 pass$ feces frequ5tly4 #dh #aa4ej 4#agd d4 ,vomit+ obs]v$4 #dh #ab4jj 4#bjj ,f\nd dead ,no vomit+ obs]v$4 ,second dose next day 0 giv5 #h days aft] fir/4 #ed #ac4dj 4#bjj ,surviv$ ,vomit+ obs]v$4 #di #ac4ae 4#aeb ,f\nd dead next day #ch #ad4ej 4#abj d4 ,symptoms aft] #a h\rs3 ,dog _h a temp]ature ( #ajd ,f4 be=e caffe9 0 giv52 vomit$ #c h\rs aft] caffe9 0 f$4 #ah #aj4hj 4#ade d4 ---------------------------------------- -------------------------- ,,table #ac4--,subcutane\s injection2 dogs4 7,s]ies ,b47 ---------------------------------------- -------------------------- ,caffe9 ,no4 ,weight4 p] ,results4 ,rem>ks4 kilo4 ---------------------------------------- -------------------------- ,kilos4,gram4 #fb #i4cj #j4afa ,surviv$ ,re/lessness & vomit+ "o-half h\r aft] injection4 #fa;,a #ad4jj 4#afj ,f\nd dead next day #fc #ab4jj 4#aej ,surviv$ ,re/lessness #a h\r aft] injection4 #fd #ad4jj 4#aej d4 ,re/lessness & ?ir/ #de m9utes aft] injection4 #ei #g4bj 4#afj ,di$ #a h\r,m>k$ re/lessness1 b no & #bj convulsion4 m9utes aft] injection46 #fa #ad4fj 4#adc ,surviv$ ,symptoms obs]v$ 9 #a h\rs4 ---------------------------------------- -------------------------- ,,table #ad4--;,adm9i/ration by m\? to puppies4 7,s]ies ,c47 ---------------------------------------- -------------------------- ,caffe9 ,no4 ,weight4 p] ,results4 ,rem>ks4 kilo4 ---------------------------------------- -------------------------- ,kilos4,gram4 #h #c4aj #j4ced ,f\nd dead ,vomit$ 9 #d h\rs aft] fe$+2 next day re/lessness1 loss ( appetite1 ?ir/1 incoord9ation ( muscles1 convulsions4 #i #c4ae 4#cej ,surviv$ ,muscul> incoord9ation & /iffness1 re/lessness1 vomit$ #a h\r aft] caffe9 0 giv54 #aj #a4fj 4#cej ,di$ 9 ,convulsion2 no vomit+4 #c h\rs #aa #a4bf 4#bjj ,f\nd dead ,salivation2 convulsions4 next day #ab #a4bh 4#bjj ,surviv$ ,no symptoms4 #ae #a4bj 4#bej d4 ,subcutane\s injection4 #af #c4ej 4#cjj ,di$ 9 ,convulsions #de m9utes aft] caffe9 #a h\r 0 f$4 ---------------------------------------- -------------------------- ,,*ronic ,,caffe9 ,,intoxication4 ,! object ( ?is /udy 0 to asc]ta9 ! effect ( repeat$ dosage :5 caffe9 0 giv5 daily or at long] int]vals4 ,! exp]im5ts 7 tri$ on rabbits & on dogs4 ,z 9 ! exp]im5ts on acute intoxication1 ! animals 7 "u obs]vation = "s "t 9 ! laboratory be=e ! adm9i/ration ( caffe9 0 begun 9 ord] to asc]ta9 ! pres5ce or abs5ce ( abnormality4 ,! relation ( diet to toxicity receiv$ "s att5tion1 b ! "q 0 n /udi$ exhau/ively 9 ! pres5t inve/igation4 ,,exp]im5ts ,,on ,,rabbits4 ,full-gr[n adult z well z "y rabbits 7 employ$4 ,! diet consi/$ ei!r ( c>rots or ( oats2 wat] 0 giv5 ad libitum4 ,! rabbits 7 kept 9 metal cages 9 a well-light$ & well-v5tilat$ room4 ,unnecess>y h&l+ or any o!r proc$ure t5d+ to fatigue or to cause discom=t to ! animals 0 v c>efully avoid$1 s9ce we _h f\nd t su* treatm5t 0 likely to decrease ! resi/ance ( ! rabbit to caffe94 ,! caffe9 0 adm9i/]$ by fe$+ by m\? & ?r\gh a /oma* tube1 or by ! subcutane\s me?od4 ,9 a good _m cases x 0 giv5 daily1 9 "s at long] int]vals4 ,,s]ies ,a4 ,! exp]im5ts ( ?is s]ies =m$ a prelim9>y /udy = ! purpose ( te/+ ! effect ( mod]ate doses4 ,"o decigram ( caffe9 p] kilo 0 giv5 daily = sev]al days2 :5 adm9i/]$ at long] int]vals ! dose 0 increas$ to #aej to #bjj mg p] kilo4 ,x 0 f\nd t ! small] doses did n produce any symptoms2 ev5 ! weights ( ! animals 7 n influ5c$4 ,doses ( m$ium size giv5 on two successive days 7 likewise )\t any noticeable effect 7,nos4 #ahb1 #ahc1 #abc1 #aja74 ,:5 a ?ird dose ( ?is size 0 giv5 )9 #dh or #bd h\rs x prov$ fatal 7,nos4 #abc1 #ahb1 & #ahc74 ,exceptionally1 h[ev]1 mod]ately l>ge doses 7= rabbits7 may be giv5 = ?ree consecutive days )\t fatal issue1 z 9 rabbit ,no4 #aja4 ,:5 giv5 at int]vals ( two to ?ree days1 l>g] doses1 z may be se5 f ! protocols1 c be adm9i/]$ )\t caus+ acute dea? 7,nos4 #agc1 #aha1 #bja74 ,! results ( ! te/s ( ?is s]ies po9t to ! abs5ce ( any accumulation & to ! possible elim9ation ( mod]ate doses ( caffe9 & its products ( decomposition )9 #bd h\rs or !reab\ts4 ,:5 ! doses are l>g] ! "t ( its elim9ation is app>5tly long]1 z %[n by ! fact t repetitions ( ! dose ! next day may be fatal1 b :5 a long] int]val is all[$ x may be giv5 )\t caus+ dea?4 ,x w be obs]v$ t only "o rabbit ( ?is s]ies surviv$1 b x 0 extremely emaciat$4 ,?is condition has be5 obs]v$ 9 a numb] ( cases aft] caffe9 _h be5 giv5 = sev]al days4 ,ev5 :5 ! drug 0 )drawn ! animals cont9u$ to lose weight4 ,?is may be expla9$ by ! condition ( ! ga/ro-inte/9al canal z f\nd at autopsy4 ,! pres5ce ( inflammation ( ! muc\s membrane ( ! /oma* & inte/9es1 ) ulc]ation ( ! muc\s membrane ( ! pylorus 9 "o ( ! rabbits 7,no4 #agc7 ( ! s]ies1 9 all probability caus$ dim9ution or loss ( appetite1 :i* ( itself w\ld t5d to cause loss ( fle% & /r5g? & f9ally dea?4 ,protocols ( ! exp]im5ts foll[4 ,rabbit #agc4 ,c>rots 7 f$ f ,octob] #a to #ah & oats = ! rema9d] ( ! exp]im5t4 --------------------------- ,date4 ,weight4 ,caffe9 p] kilo4 --------------------------- ,grams4 ,gram4 ,oct4 #i #a1ihj #j4ada ,oct4 #aa #a1ije 4#aij ,oct4 #ac #a1icj 4#bjg ,oct4 #af #b1jje #j4bbj ,oct4 #ah #a1hde ,oct4 #bj #a1gdj 4#bcj -------------------------- ,octob] #ba3 ,p>alysis ( po/]ior extremities4 ,octob] #bb3 #i a4 m41 f\nd dead4 ,! ur9e 0 exam9$ be=e & aft] ! adm9i/ration ( caffe94 ,no symptoms 7 obs]v$ aft] ! adm9i/ration ( caffe9 7#e doses 9 #aa days71 nor 0 album5 or sug> f\nd 9 ! ur9e aft] any ( ! exp]im5ts on ?is rabbit4 ,autopsy3 ,pyloric mucosa exhibit$ sev]al ulc]s2 small inte/9es %[$ slight inflammation2 liv] deeply conge/$2 kidneys %[$ m>k$ inflammation ( cortex2 o!r organs practically normal4 ,rabbit #aha4 ,diet1 c>rots ,septemb] #bi-,octob] #ag1 !n oats4 ---------------------------- ,date4 ,weight4 ,caffe9 p] kilo4 ---------------------------- ,grams4 ,gram4 ,oct4 #d #a1dbe #j4aje ,oct4 #e #a1dej 4#ajj ,oct4 #f #a1bgj 4#ajj ,oct4 #g #a1baj 4#ajj ,oct4 #h #a1cge 4#acj ,oct4 #i #a1cje 4#aec ,oct4 #aa #a1cgj #j4age ,oct4 #ac #a1che 4#ahj ,oct4 #af #a1cde 4#bjj ,oct4 #ag #a1jcj ,oct4 #ah #a1bcj ,oct4 #bj #a1bae ---------------------------- ,rabbit 0 m>k$ly emaciat$ & weak4 ,no album5 or sug> f\nd 9 ! ur9e z a result ( caffe9 fe$+4 ,rabbit #ahb4 ,diet ( c>rots f ,septemb] #bi4 ,receiv$ caffe9 subcutane\sly z foll[s3 ----------------------------- ,date4 ,weight4 ,caffe9 p] kilo4 ----------------------------- ,grams4 ,gram4 ,oct4 #d #a1gfe #j4ajj ,oct4 #e #a1hhj 4#ajj ,oct4 #f #a1gej 4#ajj ,oct4 #g #a1gaj 4#ajj ,oct4 #h #a1fhe 4#ace ,oct4 #i 4#aej ,oct4 #aa #a1fje 4#agd ---------------------------- ,octob] #ab3 #aa a4 m41 #bc h\rs aft] caffe9 0 giv51 convulsions ) recov]y2 rabbit di$ at #a4cj p4 m4 ,no sug> 0 f\nd 9 ! ur9e at any "t aft] ! adm9i/ration ( caffe94 ,album5 0 pres5t only 9 "o specim54 ,rabbit #ahc4 ,diet ( c>rots f ,septemb] #bi4 ,receiv$ caffe9 subcutane\sly z foll[s3 ---------------------------- ,date4 ,weight4 ,caffe9 p] kilo4 ---------------------------- ,grams4 ,gram4 ,oct4 #d #a1che #j4ajj ,oct4 #e #a1dfj 4#ajj ,oct4 #f #a1che 4#ajj ,oct4 #g #a1bdj 4#abb ,oct4 #h #a1caj #j4aec ,oct4 #i #a1cij 4#adb ,oct4 #aa #a1cij 4#ahg --------------------------- ,octob] #ab3 #i a4 m41 f\nd dead4 ,no album5 0 f\nd 9 ! ur9e4 ,only "o sample conta9$ sug>4 ,rabbit #abc4 ,:ite1 female4 ,diet1 oats4 ,receiv$ caffe9 subcutane\sly z foll[s3 --------------------------- ,date4 ,weight4 ,caffe9 p] kilo4 --------------------------- ,grams4 ,grams4 ,apr4 #ad #b1cej #db ,apr4 #af #b1bej #ij ,apr4 #ag #b1cbe #hf ,apr4 #bj #b1abf #ada ,apr4 #ba #a1ife #aeb ,apr4 #bb #a1hgf #afj --------------------------- ,rabbit di$ #cj m9utes aft] la/ injection ( caffe94 ,autopsy3 ,/oma* exhibit$ m>k$ inflammation ( mucosa4 ,slight ent]itis4 ,liv] & kidneys 7 deeply conge/$ & d>k color$4 ,rabbit ,no4 #aja1 :ite male4 ,diet1 oats4 ,receiv$ caffe9 subcutane\sly z foll[s3 --------------------------- ,date4 ,weight4 ,caffe9 p] kilo4 --------------------------- ,grams4 ,grams4 ,m>4 #ah #b1jbe #j4ajj ,m>4 #ai #a1igj 4#ajj ,m>4 #bj #b1jji 4#ajj ,m>4 #bb #a1hee 4#ajj ,m>4 #bc #a1gch 4#aad ,m>4 #bd #a1hae 4#aff ,m>4 #be #a1hcj 4#ahe ,m>4 #bf #a1gaj 4#agf ,m>4 #bi #a1gcd 4#bai ,apr4 #a #a1fjf 4#bbd --------------------------- ,april #e3 ,f\nd dead4 ,autopsy3 ,m>k$ inflammation ( ga/ric mucosa4 ,consid]able ent]itis affect+ ! :ole ext5t ( ! inte/9es2 liv] conge/$ & friable2 kidneys deeply conge/$ 9 cortical & m$ull>y portions2 sple5 conge/$1 b ( normal size2 lungs & he>t normal4 ,f\r days1 #j4a p] kilo2 #aj doses 9 #ad days4 ,rabbit #bja4 ,diet ( c>rots begun ,octob] #a2 ,octob] #ai1 oats4 ,subcutane\s injections z foll[s3 --------------------------- ,date4 ,weight4 ,caffe9 p] kilo4 --------------------------- ,grams4 ,grams4 ,oct4 #i #a1jjj #j4aej ,oct4 #aa #a1jae 4#ahj ,oct4 #ac #a1jfe 4#ahg ,oct4 #af #a1jfe 4#bbe ,oct4 #ah #hej ,oct4 #bj #hij 4#aaa --------------------------- ,"u obs]vation six h\rs ,octob] #bj2 no symptoms4 ,octob] #bc3 ,di$2 0 mu* emaciat$ b did n %[ any symptoms2 emaciation set 9 :5 caffe9 0 )drawn2 ur9e nev] conta9$ sug> or album52 symptoms obs]v$ aft] second dose only4 ,,s]ies ,b4 ,! "q :e!r caffe9 is cumulative 9 ! rabbit1 sugge/$ 9 ! prec$+ exp]im5ts1 0 ! subject ( fur!r inve/igation 9 ,s]ies ,b4 ,caffe9 0 giv5 by m\? or subcutane\sly4 ,c>rots =m$ ! exclusive diet1 a measur$ am\nt be+ giv54 ,! rabbits 7 kept "u obs]vation = two weeks1 except ,nos4 #cgj & #cgc1 records ( :i* 7 made only = f\r days be=e ! adm9i/ration ( caffe9 0 begun4 ,caffe9 0 giv5 by m\? 9 exp]im5ts ( ,gr\ps ,i & ,,iii4 ,rabbits #bib1 #bic1 & #bie receiv$ daily #bj cc wat] by m\? = f\r days previ\s to ! adm9i/ration ( caffe91 :ile 9 ! rabbits ( ,gr\p ,,ii ! caffe9 treatm5t 0 prec$$ by ! injection ( #j4h p] c5t salt solution subcutane\sly4 ,! object 9 bo? cases 0 to asc]ta9 :e!r or n ! me?od ( ! adm9i/ration ( caffe9 has any influ5ce on ! animal1 b obs]vation made f day to day fail$ to %[ any effect ( su* treatm5t4 ,ab\t #a decigram ( caffe9 p] kilo 0 adm9i/]$ daily1 ) occasional int]missions4 ,lat] 9 ! c\rse ( ! exp]im5t ! doses 7 increas$1 #j4ae gram p] kilo be+ ! maximum dose giv54 ,rabbit #bic di$ aft] ! ?ird dose ) symptoms ( typical caffe9 poison+4 ,! adm9i/ration ( ! same dose ( caffe9 0 cont9u$ #aj days long] 9 ,nos4 #bib & #bie4 ,x 0 omitt$ on ! sev5?1 f\rte5?1 & fifte5? days ( ! exp]im5t4 ,on ! eighte5? day ( ! exp]im5t ! dose 0 increas$ to #aej mg p] kilo & 0 repeat$ #b days lat]4 ,no4 #bie 0 f\nd dead ! next day4 ,no4 #bib surviv$4 ,rabbits #cac & #cae may be consid]$ toge!r1 z !y 7 treat$ alike 9 e respect4 ,! initial dose ( #ajj mg caffe9 p] kilo 0 f9ally increas$ to #abb mg4 ,aft] ! twelf? dose ! emaciation 0 well m>k$ & ! rabbits 7 v weak4 ,no4 #cac 0 f\nd dead #b days1 & ,no4 #cae #c days1 aft] ! la/ dose ( caffe9 0 giv54 ,x %\ld be rem>k$ 9 ?is connection t symptoms ( caffe9 poison+ 7 nev] obs]v$ 9 ^! rabbits4 ,dea? 0 n due1 !re=e1 prim>ily to caffe91 b ! rapid loss ( fle% & /r5g? obs]v$ dur+ ! la/ few days sugge/s t x 0 due to malnutrition app>5tly br\ght ab\t by caffe94 ,! results obta9$ by subcutane\s injection ( caffe9 are giv5 9 ! table z ,gr\p ,,ii4 ,! initial dose ( #ajj mg p] kilo 0 inject$ daily4 ,no4 #bih di$ aft] ! second dose4 ,nos4 #bbc & #bif receiv$ ?is am\nt daily = #f days4 ,an int]mission ( #b days foll[$1 at ! end ( :i* ! same dose 0 giv5 aga94 ,! next day x 0 increas$ to #aej mg p] kilo1 b no effect 0 obs]v$2 #dh h\rs lat] ?is dose 0 repeat$4 ,no4 #bbc 0 f\nd dead1 b its mate surviv$4 ,symptoms ( acute caffe9 intoxication 7 n obs]v$ 9 any ( ^! rabbits4 ,x w\ld seem1 !re=e1 t caffe9 is n cumulative4 ,?is supposition1 h[ev]1 appe>s some:at contradictory 9 view ( ! fact t out ( ! eight rabbits ( ?is s]ies six di$1 nor c\ld any cause ( dea? be ascrib$ o!r ?an caffe94 ,also ! fir/ results ( ,exp]im5ts #bic1 #cgj1 & #cgc might be consid]$ z indicat+ t cumulation1 ?\gh to a mod]ate ext5t1 does take place1 s9ce 9 ^! cases reflexes develop$ aft] ! drug 0 giv5 = "s "t4 ,b ?is view is contradict$ by ! results ( ,exp]im5t #cga1 9 :i* #aej mg p] kilo giv5 #e days aft] ! daily dosage ( caffe9 0 susp5d$ likewise caus$ increas$ reflexes4 ,cumulation1 !re=e1 does n acc\nt = ! effects not$ 9 ! o!r rabbit4 ,x w be obs]v$ t rabbit ,no4 #cgj1 z well z ,nos4 #cga & #cgc1 _h di>rhea = sev]al days4 ,x is q possible t ! weak5$ condition r5d]$ ! rabbits m s5sitive to ! action ( ! drug4 ,?is is made highly probable by ! obs]vations record$ 9 ! exp]im5ts on acute intoxication ) caffe9 9 :i* dea? occurr$ aft] small doses4 ,9 su* cases "s pa?ological condition 0 (t5 disclos$ by ! autopsy4 ,! results ( ?is s]ies corroborate1 !re=e1 ^? ( ,s]ies ,a1 & indicate aga9 ! abs5ce ( cumulative action4 ,! results obta9$ are 9 all probability due to malnutrition & o!r conditions br\ght ab\t by conge/ion ( ! visc]a & consequ5t injury to ! ga/ro-inte/9al canal4 ,,table #af4--;,*ronic caffe9 intoxication ( rabbits2 ,s]ies ,b on cumulation4 ---------------------------------------- --------------------------- ,gr\p ,i4 ,gr\p ,,ii4 ,gr\p ,,iii4 ,data4 ---------------------------------------- -------- ,no4 ,no4 ,no4 ,no4 ,no4 ,no4 ,no4 ,no4 #bib4 #bic4 #bie4 #bif4 #bbc4 #bih4 #cae4 #cac4 ---------------------------------------- ---------------------- ,diet 7grams c>rots 9 #b days7 #a1jjj #a1jjj #ige #icj #ije #hhj #cee #cjj ,caffe9 adm9i/]$ 7cc7 & weight 7grams73 ,m>4 #e #a1daj #a1dgj #a1jde #a1jdj #a1jgj #iee #ggj #ggj ,m>4 #g #a1dae #a1cfj #a1adj #a1jij #a1jie #a1jjj #gae #fij ,m>4 #i #a1cej #a1bgj #a1jgj #a1jjj #a1jee #a1jje #fee #ffe ,m>4 #aa #a1eje #a1dfe #a1aij #a1bcj #a1bhe #a1bej #gee #gfj ,m>4 #af #a1ehj #a1dfj #a1bcj #a1afe #a1agj #a1ade #gcj #gde ,m>4 #ag #a1eae #a1dae #a1jhj #a1jdj #a1aae #a1aje #gbj #fhe ,m>4 #ai #a1efe #a1egj #a1bhj #a1aie #a1bce #a1bbj #gaj #gce ,m>4 #ba #g #g #f #d #d #a1ehe #a1ecj #a1bfe #a1aej #a1bae #a1bfj #gee #gjj ,m>4 #bb #g #g #f 7#a7 7#a7 7#a7 #d #d #a1ddj #a1cae #a1age #a1ajj #a1jde #a1aej #fge #fce ,m>4 #bc #g #g #f 7#a7 7#a7 7#a7 #d #d #a1cce #a1adj #a1aaj #a1ade #a1aij #a1bcj #gae #gjj ,m>4 #bd #g #f 7#a7 7#a7 7#a7 #d #d #a1caj 7#b7 #a1jij #a1aae #a1agj #a1bej #fhj #fej ,m>4 #be #g #f 7#a7 7#a7 7#a7 #d #d #a1cge #a1jce #a1abe #a1bae #a1bae #fie #fhe ,m>4 #bf #g #f #d #a1bee #a1jie #a1aje #a1aee #a1aej #fge #fie ,m>4 #bg ,m>4 #bh #g #f #e4e #f #f #d #d #a1cee #a1aae #a1abj #a1afj #a1aee #eie #fhe ,m>4 #bi #g #f #f #f #e #d #d #a1che #a1aej #a1aee #a1afe #iee #fie #fge ,m>4 #cj #g #f #f #f #d #d #a1ccj #a1jge #a1jce #a1jie ,dead4 #fcj #faj ,m>4 #ca #g #f #f #f #d #d #a1cbe #a1agj #a1aaj #a1adj #fij #fje ,apr4 #a #g #f #f #f #d #d #a1cce #a1jej #a1jej #a1abj #fbe #fbj ,apr4 #b #g #f #f #f #d #d #a1cij #a1abe #a1jij #a1aee #fie #fbe ,apr4 #c #bjj ,apr4 #d #a1cjj #a1jje #a1aje #a1jhj #ehe #ehj ,apr4 #e #g #f #f #f #d #d #a1che #a1jij #a1acj #a1jij #fee #fcj ,apr4 #f #i #g4e #g4e #h #a1bfj #a1jaj #a1jej #a1aaj #efj #ecj ,apr4 #g 7#c7 ,apr4 #h #i #g4e #g4e #h #a1bfj #a1jjj #a4jij #a4ife ,dead4 ,apr4 #i ,surviv$4 ,dead4,surv4 ,dead4 ,dead4 ---------------------------------------- ----------------------- 7#a7 ,on ^! days #e cc ( salt solution 0 adm9i/]$ subcutane\sly4 7#b7 ,dead ,m>4 #bc4 7#c7 ,f\nd dead #i a4 m4 ,,table #ag4--;,*ronic intoxication ( rabbits1 s]ies ,b1 ,gr\p ,,iv1 on cumulation4 ,,rabbit1 #cgj4 ---------------------------------------- ------------------------ ,caffe9 ,date4 ,weight4 ,c>rots4 ,wat]4 ,ur9e4 by ,symptoms4 /oma*4 ---------------------------------------- ------------------------ ,mg p] ,grams4 ,grams4 cc4 kilo4 ,aug4 #g #b1aee #dej #ej #bhj ,aug4 #h #b1jcj #dej #be #ahe ,aug4 #i #b1aje #bij #j #bge ,aug4 #aj #b1jie #dej #cj #cce ,aug4 #aa #b1aje #dej #fe #cfj #ej ,aug4 #ab #b1abe #dej #fe #bbj #ej ,aug4 #ac #b1abj #cej #be #bfe #ej ,aug4 #ad #b1agj #dej #ce #bge #ge ,aug4 #ae #b1age #cej 787 #bjj #ge ,aug4 #af #b1agj #cfj #fe #bej #ge ,aug4 #ag #b1age #caj #ce #agj #ajj ,aug4 #ah #b1jie #ahj #dj #bhe #ajj ,sev]e di>rhea4 ,aug4 #ai #b1abj #djj 787 #bhe #abe ,d4 ,aug4 #bj #b1abj #djj 787 #caj #abe ,bett]4 ,aug4 #ba #b1abj #djj #gj #bej #abe ,d4 ,aug4 #bb #b1jdj #djj #de #bfe #aej ,di>rhea bad4 ,aug4 #bc #b1jcj #cgj #ce #bbj #aej ,di>rhea bett]4 ,aug4 #bd #a1iej #bae #dj #abj #aej ,d4 ,aug4 #be #a1hhe #aie #ce #fj #bjj ,reflexes4 ,aug4 #bf ,f\nd dead at #i4 ---------------------------------------- ------------------------ ,,rabbit1 #cgc4 ---------------------------------------- ------------------------ ,aug4 #g #b1bdj #dej #ej #bcj ,aug4 #h #b1aej #aej #cj #cjj ,aug4 #i #b1abj #bje #j #aej ,aug4 #aj #b1aej #dej #ae #bde ,aug4 #aa #b1aie #dej #e #bhe #ej ,aug4 #ab #b1afj #dej #fe #cbe #ej ,aug4 #ac #b1abj #cjj #de #aij #ej ,aug4 #ad #b1aie #dej #dj #bfe #ge ,aug4 #ae #b1bae #cej #ce #bjj #ge ,aug4 #af #b1bje #caj #de #bbe #ge ,aug4 #ag #b1bdj #djj #dj #bfe #ajj ,aug4 #ah #b1bee #cej #cj #cbj #ajj ,aug4 #ai #b1aae #ahe 787 #agj #abe ,sev]e di>rhea4 ,aug4 #bj #b1aae #bhj #ce #aie #abe ,di>rhea4 bett] ,aug4 #ba #b1jej #age #ge #aae #abe ,slight di>rhea4 ,aug4 #bb #b1jfj #ahj #ge #acj #aej ,aug4 #bc #b1jje #bjj #ge #abe #aej ,reflexes4 ,aug4 #bd #a1iij #bjj #ge #aej #aej ,slight di>rhea4 ,aug4 #be #a1iej #bee #ee #acb #age ,sev]e di>rhea4 ,aug4 #bf #a1hgj #bje #hj #adj ,none ,d4 ,aug4 #bg #a1hcj #bjj #ej #adj d4 ,d4 ,aug4 #bh #a1iej #djj #be #bfe d4 ,slight di>rhea4 ,aug4 #bi #a1hbe #djj #j #cae d4 ,v weak & 9 poor condition ,aug4 #cj #a1hej #aj #adj d4 ,aug4 #ca #a1hce ---------------------------------------- ------------------------ ,,rabbit1 #cga4 ---------------------------------------- ------------------------ ,aug4 #g #b1bdj #dej #ej #cjj ,aug4 #h #b1bfj #dej #ej #bbe ,aug4 #i #b1caj #dcj 787 #cjj ,aug4 #aj #b1bie #dej #ej #cje ,aug4 #aa #b1cbj #dej #ej #cce #ej ,aug4 #ab #b1bhj #dej #gj #djj #ej ,aug4 #ac #b1cjj #cej #gj #bee #ej ,aug4 #ad #b1bfe #dbe #ee #aed #ge ,aug4 #ae #b1bfj #bej #dj #abe #ge ,aug4 #af #b1bie #aee #gj ,lo/ #ge ,aug4 #ag #b1ahj #aje #gj #abj #ajj ,sev]e di>rhea4 ,aug4 #ah #b1aej #abe #gj #ajj #ajj ,di>rhea bett]4 ,aug4 #ai #b1jge #baj 787 #aib #ajj ,di>rhea sev]e4 ,aug4 #bj #b1jge #bhj #gj #ahj #ajj ,d4 ,aug4 #ba #b1afe #bfj #ej #bbe ,none ,di>rhea bett]4 ,aug4 #bb #b1aje #djj #ej #bge d4 ,aug4 #bc #b1jhj #cjj #j #ade d4 ,di>rhea sev]e4 ,aug4 #bd #b1aje #bej #ae #bde d4 ,d4 ,aug4 #be #b1jee #cbj #aj #agf #aej ,reflexes4 ,aug4 #bf #b1jdj #aij #ge #bej #aej ,di$ at #a p4 m41 )\t hav+ %[$ any symptoms o!r ?an reflexes4 ---------------------------------------- ------------------------ ,,s]ies ,c4 ,! subjects us$ 9 ^! exp]im5ts 7 rabbits ( m$ium size & 7 app>5tly "y or at any rate 7 n v old4 ,! s]ies 0 plann$ = ! /udy ( ! possible effect ( diet on ! toxicity ( caffe9 :5 giv5 = "s "t1 & !re=e oats 7 sub/itut$ = c>rots1 :i* _h be5 f$ 9 ! previ\s "w1 z already /at$4 ,caffe9 0 giv5 by m\? 9 ! usual way1 9 #a p] c5t solution1 #ajj mg4 p] kilo daily4 ,f\rte5 rabbits 7 us$ = ^! te/s4 ,_! weights 7 record$ daily & obs]vations made at frequ5t int]vals dur+ ! day4 ,! only *ange notic$ 9 all ( ! exp]im5ts ( ?is s]ies 0 progressive loss ( weight :i* set 9 f #c to #h days aft] ! adm9i/ration ( ! drug 0 begun4 ,! duration ( life v>i$ consid]ably4 ,no4 #chb di$ aft] ! fir/ dose4 ,no4 #chi liv$ #b days1 ,no4 #chf1 #c days1 & ,no4 #che1 #e days2 ,no4 #cij liv$ #g days & ,no4 #djd liv$ #bj days aft] ! adm9i/ration ( caffe9 0 begun4 ,! duration ( life 9 all ! o!rs 0 f #aa to #af days4 ,! f9d+s at autopsy are int]e/+ & sugge/ive z reg>ds ! possible explanation ( ! effects ( repeat$ dosage ( caffe94 ,9 eight ( ! rabbits !re 0 involvem5t ( ! muc\s membrane ( ! /oma* or inte/9es or ( bo?4 ,s9ce ! same condition ( ! ga/ro-inte/9al canal 0 obs]v$ 9 previ\s exp]im5ts ) caffe9 :5 inject$ subcutane\sly1 ! m]e pass+ ( ! tube into ! /oma* is obvi\sly n ! cause ( ?is condition4 ,! fatal outcome due is !re=e1 z 0 sugge/$ above1 to inanition br\ght ab\t by ! condition ( ! ga/ro-inte/9al canal4 ,moreov] p>allel exp]im5ts c>ri$ out on rabbits 9 ! same way ) alcohol surviv$ ?is treatm5t mu* long]4 ,obvi\sly !n ! pass+ ( ! s(t rubb] ca!t] is n ! cause ( ?is condition ( ! ga/ro-inte/9al canal nor ! diet4 ,rabbits 7 f$ oats exclusively = sev]al mon?s 9 ?is laboratory & ?riv$4 ,! pres5ce ( pneumonia 9 ! o!r rabbits ( ?is s]ies may be reg>d$ z accid5tal1 z x is inconceivable t "o or two doses ( caffe91 z 0 ! case 9 ,nos4 #chb & #chi1 c\ld pr$ispose ! lungs to infection4 ,! results ( ^! exp]im5ts !re=e are 9 h>mony ) ^? ( ! prec$+ two s]ies1 indicat+ t caffe9 does n accumulate 9 ! body1 & t ! toxicity ( caffe91 :e!r ( ! s+le dose or ( repeat$ doses is ! same1 on a diet ( c>rots or ( oats4 ,^! results also %[ t caffe9 is mu* m toxic ) repeat$ dosage4 ,z /at$ 9 ! hi/orical "p ( ?is bullet9 ! same view 0 held by ,g\rewit*47#bh7 ,rabbit #chf4 ,belgian female4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams1 ?r\gh /oma* tube4 -------------------------- ,date4 ,weight4,treatm5t4 -------------------------- ,grams4 cc4 ,aug4 #ag #a1cjj #ac4j ,aug4 #ah #a1bae #ab4j ,aug4 #ai 787 787 -------------------------- ,augu/ #bj3 ,f\nd dead #i a4 m4 ,autopsy3 ,lungs slightly conge/$2 liv] engorg$ & friable2 gall cy/ well fill$4 ,rabbit #chi4 ,black male4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams1 ?r\gh /oma* tube4 -------------------------- ,date4 ,weight4,treatm5t4 -------------------------- ,grams4 cc4 ,aug4 #ag #a1jgj #aj4j ,aug4 #ah #a1jbe #aj4j -------------------------- ,augu/ #ai3 ,f\nd dead #i a4 m4 ,autopsy3 ,lungs sev]ely conge/$ & p>tially hepatiz$2 liv] 0 engorg$2 o!r organs appe>$ normal4 ,rabbit #chb4 ,belgian female4 ,on ,augu/ #ag weigh$ #a1jce grams2 receiv$ #a cc ( #a p] c5t caffe9 = ea* #ajj grams2 #aj cc ( #a p] c5t caffe9 giv5 9 all4 ,augu/ #ah3 ,f\nd dead #i a4 m4 ,autopsy3 ,lungs conge/$ & hepatiz$2 liv] engorg$2 /oma* %[$ num]\s pete*ial hemorrhages on mucosa2 kidneys slightly conge/$2 inte/9es appe>$ normal4 ,rabbit #che4 ,belgian female4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams1 ?r\gh /oma* tube4 -------------------------- ,date4 ,weight4,treatm5t4 -------------------------- ,grams4 cc4 ,aug4 #ag #ghj #h4j ,aug4 #ah #gfj #g4e ,aug4 #ai #gee #g4e ,aug4 #bj #gae #g4j ,aug4 #ba #gjj #g4j -------------------------- ,augu/ #bb3 ,f\nd dead #i a4 m4 ,autopsy3 ,lungs exhibit$ pneumonic lesions1 ) inflammation ( adjac5t pleura2 a fibro-pla/ic exudate pres5t ar\nd lung2 liv] %[$ a coccidial infe/ation2 /oma* di/5d$ ) +e/a2 muc\s membrane *>act]iz$ by a cat>rhal inflammation2 cont5ts ( small inte/9e liquid 9 nature & bile /a9$2 l>ge inte/9e some:at impact$2 liv] & kidneys seem+ly normal4 ,rabbit #djd4 ,:ite male4 ,giv5 #a cc #a p] c5t caffe9 = ea* #ajj grams4 --------------------------------- ,date4 ,weight4 ,treatm5t4 --------------------------------- ,grams4 cc4 ,aug4 #bj #a1dfe #ad4e ,aug4 #ba #a1dge #ad4e ,aug4 #bb7a7 ,aug4 #bc #a1dge #ad4e ,aug4 #bd #a1djj #ad4j ,aug4 #be7b7 #a1dje #ad4j ,aug4 #bf #a1dae #ad4j ,aug4 #bg #a1djj #ad4j ,aug4 #bh7a7 ,aug4 #bi #a1caj #ac4j ,aug4 #cj #a1cbj #ac4j ,aug4 #ca #a1ccj #ac4e ,sept4 #a #a1cce #ac4e ,sept4 #b #a1cae #ac4j ,sept4 #c #a1cej #ac4e ,sept4 #d #a1cce #ac4e ,sept4 #e #a1cej #ac4e ,sept4 #f #a1chj #ad4j ,sept4 #g #a1cge #ad4j ,sept4 #h #a1cbe #ac4j --------------------------------- 7#a7 ,n f$4 7#b7 ,reflexes4 ,septemb] #i3 ,f\nd dead #i a4 m4 ,autopsy3 ,bo? lungs %[$ ext5sive pneumonia1 ) adhesions to pleura2 pleuritis & p]ic>ditis v m>k$2 l>ge am\nt ( fibr\s exudate 9 pleural cavity2 pyloric end ( /oma* slightly conge/$2 liv] conge/$2 o!r organs normal4 ,rabbit #cic4 ,belgian4 ,giv5 #a cc ( #a p] c5t caffe9 to ea* #ajj grams1 ?r\gh /oma* tube4 --------------------------------- ,date4 ,weight4 ,treatm5t4 --------------------------------- ,grams4 cc4 ,aug4 #ag #iej #i4e ,aug4 #ah #iaj #i4j ,aug4 #ai #hie #i4j ,aug4 #bj #iaj #i4j ,aug4 #ba #ije #i4j ,aug4 #bb7a7 ,aug4 #bc #hbe #h4j ,aug4 #bd #hgj #h4e ,aug4 #be #hce #h4e ,aug4 #bf #ghj #h4j ,aug4 #bg #gfe #g4e ,aug4 #bh7a7 ,aug4 #bi #gaj ,aug4 #cj7b7 ,aug4 #ca7a7 --------------------------------- 7#a7 ,n f$4 7#b7 ,condition v poor2 n f$4 ,septemb] #a3 ,f\nd dead4 ,autopsy3 ,lungs conge/$ & adh]+ to ! pleura2 ext5sive inflammation ( pleura2 liv] slightly enl>g$ & conge/$2 mucosa ( /oma* & small inte/9es slightly conge/$2 o!r organs normal4 ,rabbit #cij4 ,belgian1 male4 ,giv5 #a cc ( #a p] c5t caffe9 to ea* #ajj grams ?r\gh /oma* tube4 --------------------------------- ,date4 ,weight4 ,treatm5t4 --------------------------------- ,grams4 cc4 ,aug4 #ag #a1dij #ae4j ,aug4 #ah #a1cgj #ad4j ,aug4 #ai #a1cfe #ac4e ,aug4 #bj #a1cdj #ac4e ,aug4 #ba #a1bfe #ab4e ,aug4 #bb7a7 ,aug4 #bc #a1abj #aa4j --------------------------------- 7#a7 ,n f$4 ,augu/ #bd3 ,f\nd dead #i a4 m4 ,autopsy3 ,he>t & lungs appe>$ normal2 abdom9al visc]a %[$ no app>5t pa?ologic *ange o!r ?an coccidial infection ( ! liv] & fullness ( ! blood vessels4 ,rabbit #cib4 ,maltese1 female4 ,giv5 #a cc ( #a p] c5t caffe9 to ea* #ajj grams ?r\gh /oma* tube4 -------------------------------- ,date4 ,weight4 ,treatm5t4 -------------------------------- ,grams4 cc4 ,aug4 #ag #a1bfe #ab4e ,aug4 #ah #a1bge #ab4e ,aug4 #ai #a1bdj #ab4e ,aug4 #bj #a1bbj #ab4j ,aug4 #ba #a1bde #ab4e ,aug4 #bb7a7 ,aug4 #bc #a1ahj #ab4j ,aug4 #bd #a1aij #ab4j ,aug4 #be #a1aee #aa4e ,aug4 #bf #a1adj #aa4e ,aug4 #bg #a1adj #aa4e ,aug4 #bh7a7 ,aug4 #bi #a1aae #aa4j ,aug4 #cj #a1jhj #aa4j ,aug4 #ca #a1jbj #aj4j ,sept4 #a #iie #aj4j ,sept4 #b #icj #i4j -------------------------------- 7#a7 ,n f$4 ,di$ at #c p4 m4 ,septemb] #b4 ,autopsy3 ,! /oma* & small inte/9es %[$ num]\s small hemorrhagic spots2 a ?ick coat+ ( mucus surr\nd$ ! cont5ts ( ! /oma*2 ! o!r organs 7 app>5tly normal4 ,rabbit #djc4 ,black4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams4 -------------------------------- ,date4 ,weight4 ,treatm5t4 -------------------------------- ,grams4 cc4 ,aug4 #bj #a1fdj #af4e ,aug4 #ba #a1fdj #af4e ,aug4 #bb7a7 ,aug4 #bc #a1dij #ae4j ,aug4 #bd #a1eae #ae4j ,aug4 #be #a1dge #ae4j ,aug4 #bf #a1cij #ad4j ,aug4 #bg #a1ccj #ac4e ,aug4 #bh7a7 ,aug4 #bi #a1acj #aa4e ,aug4 #cj #a1jee #aj4e -------------------------------- 7#a7 ,n f$4 ,augu/ #ca3 ,f\nd dead at #c p4 m4 ,autopsy3 ,ext5sive ga/ro5t]itis2 liv] enl>g$ & conge/$2 sple5 slightly conge/$2 p]itoneum ?ick5$ & conge/$2 o!r organs normal4 ,rabbit #hhd4 ,black1 female4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams ?r\gh /oma* tube4 -------------------------------- ,date4 ,weight4 ,treatm5t4 -------------------------------- ,grams4 cc4 ,aug4 #af #a1aie #ab4j ,aug4 #ag #a1bje #ab4j ,aug4 #ah #a1adj #aa4e ,aug4 #ai #a1ahj #ab4j ,aug4 #bj #a1ade #aa4e ,aug4 #ba #a1ade #aa4e ,aug4 #bb7a7 ,aug4 #bc #a1jje #aj4j ,aug4 #bd #a1jce #aj4e ,aug4 #be #iij #aj4j ,aug4 #bf #ifj #i4e ,aug4 #bg #iee #i4e ,aug4 #bh7a7 ,aug4 #bi #hgj #i4j ,aug4 #cj7b7 #hej #h4e ,aug4 #ca #haj #h4j ,sept4 #a #gdj #g4e -------------------------------- 7#a7 ,n f$4 7#b7 ,poor condition1 mucus f rectum4 ,septemb] #b3 ,f\nd dead at #i a4 m4 ,autopsy3 ,! mucosa ( /oma* %[$ num]\s hemorrhagic spots2 ! fir/ portion ( ! small inte/9es 0 slightly conge/$2 ! o!r organs 7 app>5tly normal 9 appe>ance4 ,rabbit #chc4 ,belgian1 female4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams ?r\gh /oma* tube4 -------------------------------- ,date4 ,weight4 ,treatm5t4 -------------------------------- ,grams4 cc4 ,aug4 #af #iie #aj4j ,aug4 #ag #a1jje #aj4j ,aug4 #ah #iij #aj4j ,aug4 #ai #hie #i4j ,aug4 #bj #ide #i4e ,aug4 #ba #ife #i4e ,aug4 #bb7a7 ,aug4 #bc #hge #i4j ,aug4 #bd #hee #h4e ,aug4 #be #hej #h4e ,aug4 #bf #ghe #h4j ,aug4 #bg #gaj #g4j -------------------------------- 7#a7 ,n f$4 ,augu/ #bh3 ,f\nd dead at #i a4 m4 ,autopsy3 ,lungs1 he>t1 & sple5 app>5tly normal2 liv] infect$ ) coccidia2 /oma* app>5tly normal2 walls ( small inte/9es inject$2 colon m>k$ conge/ion & hemorrhagic2 kidneys hemorrhagic4 ,rabbit #chg4 ,belgian male4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams ?r\gh /oma* tube4 -------------------------------- ,date4 ,weight4 ,treatm5t4 -------------------------------- ,grams4 cc4 ,aug4 #ag #a1bfj #ab4e ,aug4 #ah #a1cdj #ac4j ,aug4 #ai #a1cce #ac4j ,aug4 #bj #a1cjj #ac4j ,aug4 #ba #a1cbe #ac4j ,aug4 #bb7a7 ,aug4 #bc #a1bje #ab4j ,aug4 #bd #a1bjj #ab4j ,aug4 #be #a1bhe #ab4e ,aug4 #bf #a1ahe #ab4j ,aug4 #bg #a1bee #ab4e ,aug4 #bh7a7 ,aug4 #bi #a1aae #aa4j ,aug4 #cj #a1ace #aa4e ,aug4 #ca #a1age #ab4j ,sept4 #a #a1jej #aj4e ,sept4 #b #ijj #i4j -------------------------------- 7#a7 ,n f$4 ,septemb] #c1 f\nd dead4 ,autopsy3 ,/oma* & small inte/9es %[$ num]\s hemorrhagic spots2 ?ick coat+ ( mucus surr\nd$ ! cont5ts ( ! /oma*2 bladd] 0 greatly di/5d$ ) ur9e2 ! o!r organs 7 app>5tly normal4 ,rabbit #chh4 ,belgian male4 ,giv5 #a cc ( #a p] c5t caffe9 = ea* #ajj grams1 ?r\gh /oma* tube4 -------------------------------- ,date4 ,weight4 ,treatm5t4 -------------------------------- ,grams4 cc4 ,aug4 #ag #a1jhj #aj4j ,aug4 #ah #a1aae #aa4j ,aug4 #ai #a1aej #aa4e ,aug4 #bj #a1acj #aa4e ,aug4 #ba #a1abj #aa4j ,aug4 #bb7a7 ,aug4 #bc #a1jbj #aj4j ,aug4 #bd #ihe #aj4j ,aug4 #be #ifj #i4e ,aug4 #bf #ijj #i4j ,aug4 #bg #hge #i4j ,aug4 #bh7a7 -------------------------------- 7#a7 ,n f$4 ,augu/ #bi1 f\nd dead #i a4 m4 ,autopsy3 ,he>t & lungs normal2 liv] & kidneys engorg$2 /oma* normal2 inte/9es %[$ a cat>rhal inflammation1 ?\gh n sev]e2 sple5 normal2 walls ( colon some:at inject$4 ,rabbit #cia4 ,belgian4 ,giv5 #a cc ( #a p] c5t caffe9 to ea* #ajj grams ?r\gh /oma* tube4 ------------------------------ ,date4 ,weight4,treatm5t4 ------------------------------ ,grams4 cc4 ,aug4 #ag #idj #i4e ,aug4 #ah #iej #i4e ,aug4 #ai #iee #i4e ,aug4 #bj #ice #i4e ,aug4 #ba #ide #i4e ,aug4 #bb7a7 ,aug4 #bc #hce #h4e ,aug4 #bd #hje #h4j ,aug4 #be #hjj #h4j ,aug4 #bf #gfe #g4e ,aug4 #bg7b7 #fij #g4j ,aug4 #bh7a7 ,aug4 #bi #efe #e4e ------------------------------ 7#a7 ,n f$4 7#b7 ,poor condition4 ,augu/ #cj1 f\nd dead #i a4 m4 ,autopsy3 ,he>t inject$2 lungs normal2 liv] affect$ slightly ) coccidiidea2 /oma* normal 9 appe>ance2 small inte/9es normal1 b colon consid]ably inflam$2 kidneys slightly engorg$2 o!r organs normal4 ,rabbit #djb4 ,black female4 ,giv5 #a cc ( #a p] c5t caffe9 to ea* #ajj grams4 ------------------------------ ,date4 ,weight4,treatm5t4 ------------------------------ ,grams4 cc4 ,aug4 #bj #b1jcj #bj4j ,aug4 #ba #a1iej #ai4e ,aug4 #bb7a7 ,aug4 #bc #a1iee #ai4e ,aug4 #bd #a1ije #ai4j ,aug4 #be #a1hij #ai4j ,aug4 #bf #a1ghj #ah4j ,aug4 #bg #a1gfe #ag4e ,aug4 #bh7a7 ,aug4 #bi #a1fcj #af4e ,aug4 #cj #a1edj #ae4e ,aug4 #ca #a1eaj #ae4j ,sept4 #a #a1dbe #ad4j ------------------------------ 7#a7 ,n f$4 ,septemb] #b1 f\nd dead #i a4 m4 ,autopsy3 ,! lungs 7 badly conge/$1 ! po/]ior lobe ( ! "r lung %[+ hepatization2 ! liv] 0 consid]ably enl>g$ & conge/$2 ! muc\s membrane ( ! /oma* & small inte/9es 0 conge/$ & %[$ num]\s hemorrhagic spots2 ! kidneys %[$ slight conge/ion2 all o!r organs normal4 ,,s]ies ,d4 ,! evid5ce br\ght =? 9 ! prec$+ pages reg>d+ cumulation ( caffe9 naturally sugge/s ! "q :e!r or n ! body acquires a tol]ance = x4 ,?is "q has already be5 answ]$ 9 ! affirmative by ,g\rewit*17#bh7 b ow+ to ! me?od he us$ = ! id5tification ( caffe9 & ! few exp]im5ts made 8 results are n conclusive4 ,! exp]im5ts ( s]ies ,a1 ,b1 & ,c might be reg>d$ z indicat+ t tol]ance = caffe9 is n acquir$ by ! rabbit4 ,x 0 notic$1 h[ev]1 t ! rabbit app>5tly does tol]ate increas+ly l>g] doses "u c]ta9 conditions1 z ! foll[+ exp]im5ts %[3 ,rabbit #bbc4 ,belgian h>e1 male4 ,octob] #bb3 ,weight1 #a1ebj grams2 #ae cc #b p] c5t caffe9 inject$ subcutane\sly at #b p4 m4 ,novemb] #a3 #aj4cj a4 m41 weight1 #a1eaj grams2 #ag cc #b p] c5t caffe9 inject$ subcutane\sly 7#bbe mg p] kilo71 reflexes obs]v$1 b no tetanus4 ,novemb] #d3 #aj4cj a4 m41 weight #a1ece grams2 #ai cc #b p] c5t caffe9 inject$ subcutane\sly at #b4dj p4 m42 #d4dj p4 m41 no symptoms4 ,novemb] #h3 ,weight1 #a1dbe grams2 #bj cc #b p] c5t caffe9 7#bhe mg p] kilo7 inject$ at #aa4de p4 m42 #e p4 m41 no symptoms4 ,novemb] #ag3 ,weight1 #a1cbe grams2 #bb cc #b p] c5t caffe9 inject$ at #b4ee p4 m4 7#cbi mg p] kilo71 no symptoms4 ,novemb] #ah3 ,rabbit 9 good condition4 ,rabbit #bbd4 ,belgian h>e1 female4 ,diet1 c>rots4 ,octob] #ah3 ,weight1 #a1ice grams2 #aa4bj a4 m41 #ae cc #b p] c5t caffe9 7#aee mg p] kilo7 inject$4 ,novemb] #a3 ,weight1 #a1ghj grams2 #bj cc #b p] c5t caffe9 7#bbd mg p] kilo7 inject$ subcutane\sly1 reflexes increas$1 muscle tremors pres5t1 b no o!r symptoms4 ,novemb] #d3 ,weight1 #a1gaj grams2 #ba4e cc #b p] c5t caffe9 7#beb mg p] kilo7 inject$4 ,novemb] #h3 ,weight1 #a1dce grams2 #bb4e cc #b p] c5t caffe9 or #cad mg p] kilo inject$ at #aa4dj p4 m42 #e a4 m41 no symptoms4 ,novemb] #ag3 ,weight1 #a1cdj grams2 #bd cc #b p] c5t caffe9 7#ceh mg p] kilo7 inject$ subcutane\sly4 ,novemb] #ah3 #i a4 m41 rabbit di$4 ,rabbit #bbf4 ,gray male4 ,diet1 c>rots4 ,octob] #bh3 ,weight1 #a1jde grams2 #aj cc #b p] c5t caffe9 inject$ subcutane\sly at #a4ej p4 m42 #d4cj p4 m41 tremors obs]v$1 b no o!r symptoms4 ,octob] #bi3 ,rabbit 9 good condition4 ,novemb] #a3 ,weight1 #iej grams2 #aj4ee a4 m41 #aa cc #b p] c5t caffe9 inject$ subcutane\sly 7#bca mg p] kilo74 ,novemb] #d3 ,weight1 #icj grams2 #b4ej p4 m41 #ab cc #b p] c5t caffe9 inject$ subcutane\sly 7#beh mg caffe9 p] kilo74 ,novemb] #f3 ,weight1 #ide grams2 #aa4de a4 m41 #ae cc #b p] c5t caffe9 7#cac mg p] kilo7 inject$ subcutane\sly4 ,novemb] #ag3 ,rabbit /ill alive2 weight1 #hij grams4 ,! results ( ^! exp]im5ts indicate t :5 suffici5t "t is all[$ betwe5 two successive injections1 susceptibility to caffe9 is n increas$4 ,! rabbit1 on ! contr>y1 seems to acquire a tol]ance = ! drug1 = ! f\r? dose 0 #ae p] c5t l>g] ?an ! m9imum fatal dose ( caffe94 ,?is is 9 all probability due to ! bett] elim9ation ( caffe9 & its products ( decomposition & to recov]y f ! delet]i\s effects ( ea* dose1 made possible by long int]vals betwe5 injections4 ,! results ( ^! exp]im5ts may be briefly summ$ up by /at+ t subm9imum doses ( caffe9 giv5 to ! rabbit daily or at int]vals 7n too long7 d n produce any symptoms su* z 7 obs]v$ 9 acute caffe9 intoxication1 namely1 increas$ reflexes & convulsions1 or increas$ rate ( respiration1 ?us %[+ t x is n cumulative4 ,b evid5ce ( und\bt$ summation ( effect 0 adduc$ to %[ t if ! adm9i/ration ( subm9imum doses ( caffe9 be cont9u$ daily = a p]iod ( #aa to #ah days ! result is fatal4 ,tol]ance1 h[ev]1 may be acquir$1 al?\gh to a limit$ ext5t only1 provid$ suffici5tly long int]vals betwe5 injections are all[$ to give "t = repair ( ! injury done by ! drug & to develop a me*anism = its bett] decomposition & elim9ation4 ,fur!rmore1 ! evid5ce j giv5 indicates t ! elim9ation ( subm9imum doses ( caffe9 & its products ( decomposition is probably accompli%$ )9 #bd h\rs or !reab\ts4 ,t ! elim9ation ( l>g] doses is n accompli%$ 9 ?is int]val is made probable by ! foll[+ exp]im5t3 ,gray rabbit #dee4 ,female4 ,diet1 oats4 ,octob] #ab3 ,weight1 #a1ahe grams2 #c4cj p4 m41 #aa4e cc #b ( p] c5t caffe9 inject$ into ! lumb> muscles2 #c p4 m41 reflexes increas$4 ,octob] #ac3 #aj a4 m41 rabbit weigh$ #a1jgj grams2 no symptoms ( caffe9 poison+1 reflexes normal2 #aj4cj a4 m41 #aj cc #b p] c5t caffe9 inject$ into ! lumb> muscles2 #aa4cj a4 m41 rabbit jump$ (f ! table1 _h convulsions1 & di$4 ,,exp]im5ts ,,on ,,dogs4 ,hav+ ga9$ "s in=mation respect+ ! effects ( repeat$ doses ( caffe9 on rabbits1 x 0 ( int]e/ to f9d out h[ c>nivora react$ to ! drug :5 simil>ly adm9i/]$4 ,a numb] ( dogs 7 us$ = ! purpose4 ,consid]able v>iation 9 ! mode ( exp]im5tation1 z w appe> lat]1 0 all[$4 ,s9ce ! condition ( ! animal1 its age1 environm5t1 or diet might be factors influ5c+ toxicity1 te/s 7 made on full-gr[n & on "y gr[+ dogs ^: food 0 v>i$4 ,! subjects ( ! exp]im5t 7 kept "u obs]vation = a few days to sev]al weeks be=e ! adm9i/ration ( caffe9 0 begun1 9 ord] to det]m9e :e!r or n any morbid condition exi/$1 z well z to asc]ta9 :e!r ! new environm5t _h any effect on ^! animals4 ,caffe9 0 giv5 *iefly by m\?1 b ! subcutane\s me?od 0 also employ$ dur+ a portion ( ! exp]im5tal p]iod 9 "s dogs4 ,! initial dose1 :i* v>i$ = diff]5t individuals1 0 ma9ta9$ = a v>iable l5g? ( "t4 ,x 0 !n progressively increas$1 9 mo/ cases until ! dea? ( ! animal4 ,) l>g] doses ! int]vals betwe5 successive injections 7 also increas$4 ,,s]ies ,a4 ,six dogs 7 us$ 9 ?is s]ies4 ,caffe9 0 adm9i/]$ by m\? = p]iods ( six days to five weeks4 ,x 0 giv5 daily or at int]vals ( two1 & sometimes ( ?ree1 days4 ,9 a few in/ances ! drug 0 )held = f\r or ev5 = sev5 days1 & its adm9i/ration 0 resum$ at ! end ( ?is "t4 ,! initial dose 9 ^! exp]im5ts v>i$ approximately betwe5 #dj & #adj mg p] kilo4 ,! doses 7 !n increas$ gradually1 & ?us ! maximum resi/ance ( ! subject to caffe9 0 te/$4 ,! diet consi/$ ei!r exclusively ( meat or l>gely ( c>bohydrates ) a m9imum am\nt ( meat to give flavor to ! food4 ,dog #aa4 ,female4 ,diet consi/$ ( rice1 #bej grams2 cane sug>1 #bej grams2 meat1 #ej grams2 crack] meal1 ab\t #ajj grams4 ,caffe9 0 giv5 by m\? daily or at int]vals ( "o day1 :5 ! dose did n exce$ #a4e grams4 ,be=e ! dose 0 increas$ to #b grams1 or approximately #j4bac gram caffe9 p] kilo1 an int]val ( two days 0 all[$4 ,symptoms 7 notic$ ! next day4 ,an int]val ( two days 0 !re=e all[$ aga9 at ! end ( :i* ! same dose 0 repeat$4 ,x w be rem>k$ t !re 7 no symptoms ?is "t1 & ! g5]al condition ( ! dog seem$ to be good4 ,two grams ( caffe9 71 !re=e1 giv5 daily dur+ ! next two days )\t any unt[>d effects2 ! dose 0 !n increas$ to #b4e grams4 ,ev5 aft] ?is enorm\s quantity no symptoms 7 obs]v$ except slight tremors4 ,:5 ?is dose 0 repeat$ #bf h\rs lat]1 x prov$ fatal4 ,no album9 or sug> 0 f\nd 9 ! ur9e1 al?\gh ! dog 0 f$ on a v lib]al c>bohydrate diet4 ,! foll[+ is a complete record ( ! exp]im5t4 ,april #bj3 ,ur9e acid1 no album91 no sug>4 ,april #ba3 ,ur9e free f sug>4 ,april #bb3 ,ur9e free f sug>4 #a gram caffe9 giv5 9 ! aft]noon4 ,april #bc3 #i a4 m41 dog 0 v ?ir/y1 drank a l>ge quantity ( wat]1 ur9e did n r$uce ,fehl+'s solution4 ,april #bd3 #b4cj p4 m41 #a gram caffe91 no sug> 9 ur9e4 ,april #be3 #a gram caffe9 adm9i/]$4 ,april #bf3 ,weight1 #aj4f kilos1 ur9e collect$ 9 ! morn+1 no sug>2 #d4aj p4 m41 #a4e grams caffe94 ,april #bg3 #a4e grams caffe92 #a4cj p4 m41 diet z be=e1 no sug> 9 ur9e4 ,april #bh3 ,weight1 #aj4b kilos1 no caffe91 no sug> 9 ur9e4 ,april #cj3 ,weight1 #aj4d kilos1 no sug> 9 ur9e2 #d4bj p4 m41 #b grams caffe94 ,may #a3 ,ur9e exam9$1 sug> abs5t1 weight #aj kilos1 vomit$1 sick1 tremors obs]v$1 drank #ejj cc wat] at "o "t1 appetite poor4 ,may #b3 ,no caffe91 drank #aej cc wat]4 ,may #c3 ,ur9e1 no sug>1 mod]ate quantity ( album5 pres5t2 #ab noon1 #b grams caffe9 giv5 by m\?1 weight #aj4c kilos2 #b p4 m41 ur9e1 sug> negative1 condition ( dog good1 no symptoms ( caffe9 intoxication4 ,may #d3 #aj a4 m41 ab\t #aj cc ?ick1 d>k-color$ mucilag9\s ur9e f\nd 9 collect+ bottle2 album9 a little m ?an a trace1 decid$ly less ?an on ,may #c1 no sug>1 condition ( dog pretty good except = slight muscul> tremors2 #d p4 m41 #b grams caffe9 by m\? 7z usual74 ,may #e3 ,ur9e n exam9$1 no symptoms2 #d p4 m41 #b grams caffe94 ,may #f3 ,ur9e n exam9$2 #b4cj p4 m41 #b4e grams caffe9 giv5 by m\?2 #d p4 m41 slight tremor1 no o!r symptoms4 ,may #g3 ,no exam9ation ( ur9e1 no symptoms obs]v$2 #d p4 m41 #b4e grams caffe94 ,may #h3 #i a4 m41 f\nd dead1 ur9e collect$ s9ce la/ dose ( caffe9 0 giv5 did n conta9 any sug> or album91 ! am\nt ( caffe9 f$ to ?is dog 0 #ah grams 9 #ah days4 ,autopsy3 ,po/-mortem exam9ation %[$ m>k$ ent]itis ) hemorrhagic spots on ! mucosa2 liv] & kidneys conge/$ & d>k color$2 lungs conge/$2 ?yroid gl& 0 greatly enl>g$ & conge/$4 ,dog #bh4 ,april #cj3 ,weight1 #f4h kilos2 ! diet consi/$ ( #bej grams rice1 #bej grams sug>1 #ajj grams crack] meal1 & #ajj grams ( meat4 ,on ,may #c 8 weight 0 #g kilos4 ,he receiv$ #a gram ( caffe9 by m\? at #ab noon4 ,at #b p4 m4 he vomit$ & tremors 7 obs]v$4 ,! next day1 ,may #d1 tremors 7 /ill pres5t ?\gh less pron\nc$4 ,exam9ation ( ! ur9e = sug> & album9 0 negative2 on ,may #d1 #a gram caffe9 0 giv5 aga9 & repeat$ on ,may #e4 ,on ?is date 8 g5]al condition 0 n good--dog _h no appetite & refus$ to take caffe94 ,z ! dog lo/ #aj p] c5t ( 8 weight he 0 put on a meat diet exclusively & ! dose ( caffe9 0 r$uc$ to #j4e gram4 ,he became sick aft] ! second dose1 & ! adm9i/ration ( caffe9 0 !re=e discont9u$4 ,x 0 resum$ aft] five days & ! caffe9 0 adm9i/]$ 9 increas+ am\nts1 i4 e41 on ,may #ah1 #j4e gram2 ,may #ai1 #j4e2 ,may #bj1 #a2 ,may #ba1 #a gram 9 two doses ( #j4e ea*1 giv5 at int]vals ( "o h\r2 ,may #bb1 #a gram4 ,dog became irritable1 b no o!r symptoms 7 obs]v$4 ,! adm9i/ration ( caffe9 0 omitt$ ! next day4 ,on ! foll[+ day :5 ! same dose ( caffe9 0 giv5 !re 0 aga9 m>k$ irritability & tremors4 ,! exp]im5t 0 !re=e discont9u$4 ,dog #bb4 ,male bulldog4 ,june #bd3 ,dog weigh$ #ac4g kilos4 ,diet consi/$ ( meat exclusively2 #a gram caffe9 0 giv5 by m\?2 di>rhea develop$2 no caffe9 0 giv5 = ?ree days4 ,june #bh3 ,dog weigh$ #ac4f kilos1 #a4e grams caffe9 giv5 at #aj a4 m4 ,june #cj3 #a4ge grams caffe9 adm9i/]$4 ,july #b3 ,dog weigh$ #ac4e kilos2 #b grams caffe9 or #j4ae gram p] kilo1 caus$ well-m>k$ ?ir/1 b did n produce any o!r symptoms4 ,dog #bj4 ,female4 ,may #ab3 ,weight1 #g4g kilos4 ,f$ lib]al c>bohydrate diet1 consi/+ ( rice1 #ajj grams2 sug> #ajj grams2 meat & crack] meal1 a suffici5t quantity to flavor ! food4 ,may #ad3 ,weight1 #g4g kilos4 ,exam9ation ( ur9e = album9 & sug> gave negative results4 ,ur9e 0 acid to litmus4 ,may #ag3 ,weight1 #g4d kilos4 ,?ree h\rs aft] x 0 f$ ! dog receiv$ #j4e gram caffe9 by m\?4 ,! te/ ( ! ur9e ! next day = sug> 0 negative1 b a trace ( album9 0 pres5t4 ,x w be notic$ t ! doses 7 increas$ gradually & t symptoms 7 obs]v$ only aft] ! f\r? dose ( #j4a gram p] kilo4 ,lat] meat 0 sub/itut$ = ! c>bohydrate diet & ! adm9i/ration ( caffe9 0 /opp$ = f\r days4 ,at ! end ( ?is p]iod #ajj mg caffe9 p] kilo 0 f$ daily = five days1 & ! dose 0 !n v gradually increas$4 ,di>rhea occurr$ twice1 b no o!r symptoms1 ! second attack hav+ la/$ a few days4 ,! foll[+ is a complete record ( ! exp]im5t3 ,may #ai3 #j4e gram caffe9 #aa4de a4 m4 ,may #bj3 #j4ge gram caffe9 #ab4de a4 m4 ,may #ba3 #j4ge gram caffe9 #ab noon2 no sug>1 no album9 9 ur9e4 ,may #bb3 #j4ge gram caffe92 ur9e1 same condition f\nd2 no symptoms4 ,may #bc3 ,weight1 #g4e kilos2 no caffe94 ,may #bd3 #j4ge gram caffe92 tremors v m>k$4 ,may #be3 ,no caffe94 ,may #bf3 #j4ge gram caffe94 ,may #bg3 #j4ge gram caffe94 ,may #bh3 #j4ge gram caffe94 ,may #bi3 #a gram caffe9 9 two doses ( #j4ge & #j4be gram4 ,may #cj3 ,no caffe94 ,may #ca3 ,no caffe92 meat diet exclusively4 ,june #a3 ,no caffe92 meat diet exclusively4 ,june #b3 ,no caffe92 no sug>1 no album9 9 ur9e4 ,june #c3 ,weight1 #g4f kilos2 #j4ge gram caffe92 no sug> 9 ur9e4 ,june #d3 ,weight1 #g4c kilos2 #j4ge gram caffe92 no sug> 9 ur9e4 ,june #e3 ,weight1 #g4e kilos2 #j4h gram caffe92 drank #ejj cc wat]2 ate #bjj grams meat4 ,june #f3 ,weight1 #g4d kilos2 #j4h gram caffe92 #ejj cc ur9e2 drank #ejj cc wat]2 ate #bjj grams meat2 no symptoms4 ,june #g3 ,weight1 #g4g kilos2 #j4h gram caffe9 #aj a4 m42 #djj cc ur9e1 #ejj cc wat]1 #bjj grams meat4 ,june #h3 ,weight1 #g4e kilos2 #j4i gram caffe91 #dej cc ur9e1 #a p4 m42 #bjj grams meat1 #ejj cc wat]4 ,june #i3 ,weight1 #g4f kilos2 #j4i gram caffe91 #a p4 m42 #ejj cc wat]1 #bjj grams meat & bone du/2 di>rhea & re/lessness all aft]noon4 ,june #aj3 ,weight1 #g4f kilos2 #a gram caffe91 #ejj cc wat]1 #bjj grams meat1 #dhj cc ur9e4 ,june #aa3 ,weight1 #h kilos2 #a gram caffe91 #dgj cc ur9e1 #ejj cc wat]1 #bjj grams meat4 ,june #ab3 ,weight1 #g4h kilos2 #a gram caffe91 #gaj cc ur9e1 #ejj cc wat]1 #bjj grams meat4 ,june #ac3 #dej cc ur9e1 #ejj cc wat]1 #cjj grams meat4 ,june #ad3 ,weight1 #g4i kilos2 #a4b grams caffe91 #ejj cc wat]1 #cjj grams meat1 #dij cc ur9e4 ,june #ae3 ,weight #g4h kilos1 #ejj cc wat]1 #cjj grams meat1 #eej cc ur9e4 ,june #af3 ,weight #h4j kilos1 #a4b gram caffe91 #ejj cc wat]1 #cjj grams meat1 bone du/ add$ to *eck di>rhea4 ,june #ag3 #ejj cc wat]1 #cjj grams meat1 #dej cc ur9e1 di>rhea cont9ues1 bone du/ add$4 ,june #ah4 ,weight #g4h kilos1 #a4c gram caffe91 #cjj grams meat1 #ejj cc wat]1 #cjj cc ur9e4 ,june #ai3 ,dog v ?ir/y1 drank #a lit] ( wat] & ate #cej grams ( meat2 #ifj cc ur9e pass$ dur+ ! pa/ #bd h\r4 ,june #ba3 ,weight #g4e kilos1 #a4e grams caffe9 giv5 at #aj a4 m4 ,at #b p4 m4 convulsions & dea?4 ,?is dog receiv$ a total ( #ba4ae grams caffe9 9 #be doses dur+ a p]iod ( #ce days1 :i* am\nts to an av]age ( #he mg p] kilo daily4 ,dog #ai4 ,female fox t]ri]4 ,may #ac3 ,weight #f4d kilos4 ,diet consi/$ ( rice1 #ajj grams2 sug>1 #ajj grams2 & a suffici5t quantity ( meat & crack] meal to give flavor to ! food4 ,exam9ation ( ! ur9e %[$ a trace ( album9 b no sug>4 ,! ur9e 0 acid to litmus4 ,two days lat] ! ur9e 0 alkal9e to litmus4 ,!re 0 /ill a small am\nt ( album9 b no sug>4 ,may #ag3 #j4e gram caffe9 0 giv5 by m\?4 ,exam9ation ( ! ur9e collect$ ! next day /ill %[$ ! pres5ce ( album9 & ! abs5ce ( r$uc+ sub/ances4 ,! dog _h tremors4 ,caffe9 01 !re=e1 n adm9i/]$4 ,may #ai3 #j4e gram caffe9 0 giv5 by m\?4 ,may #bj3 #j4ge gram caffe9 0 f$ at #ab4de p4 m4 ,! dog vomit$ dur+ ! night & tremors 7 obs]v$ ! next morn+4 ,! ur9e collect$ 0 exam9$ = album9 & sug>1 b nei!r 0 f\nd4 ,may #ba3 #ab noon1 #j4ge gram caffe9 0 f$4 ,! dog weigh$ #f kilos1 :i* !re=e repres5t$ a loss ( #j4d kilo4 ,grew abnormally ?ir/y & lo/ appetite1 b no o!r symptoms ( caffe9 poison+ 7 obs]v$4 ,may #bb3 ,! dog 0 aga9 giv5 #j4ge gram caffe9 at #ab noon4 ,! exam9ation ( ! ur9e = album9 & sug> gave negative results4 ,! dog di$ at #d4ae p4 m4 ,! fatal dose = ?is dog 0 !re=e #j4abe gram caffe9 p] kilo1 & ! total am\nt ( caffe9 +e/$ 9 six days am\nt$ to #c4be grams1 or #j4ed gram p] day1 :i* makes #ij mg p] kilo4 ,dog #ba4 ,:ite female bull4 ,?is dog 0 kept on a diet exclusively ( meat1 & 0 giv5 wat] ab libitum4 ,f #j4e to #j4f gram ( caffe9 0 adm9i/]$ daily = sev5 days2 ! doses 7 !n increas$ & 7 giv5 at long] int]vals4 ,no symptoms ( ! effects ( caffe9 7 obs]v$ until a dose ( #a4e gram 0 f$1 :5 di>rhea 0 notic$ on ! next day4 ,9 ! foll[+ record ! details ( ! exp]im5t are giv53 ----------------------------- ,date4 ,weight4 ,caffe94 ----------------------------- ,kilos4 ,grams4 ,june #g #ab4e #j4e ,june #h #ab4e 4#e ,june #i #ab4e 4#e ,june #aj #ab4c 4#f ,june #aa #ab4c 4#f ,june #ab #ab4c 4#f ,june #ac #ab4c 4#f ,june #ad #ab4c 4#h ,june #af #ab4g #j4h ,june #ah #ab4i #a4j ,june #ba #ac4d #a4b ,june #bd #ac4c #a4e ,june #be 7#a7 4#j ,june #bg #ac4e #a4e ,june #cj #ac4e #a4ge ----------------------------- 7#a7 ,di>rhea4 ,july #b3 #aa4cj a4 m41 #b4j gram caffe9 f$ by m\?2 #a4cj p4 m41 tetanus1 dog di$4 ,! total am\nt ( caffe9 f$ to dog ,no4 #ba out ( ! #be days ( ! exp]im5t 0 #ad4de grams1 or an av]age ( #egh mg p] day1 :i* am\nts to ab\t #db to #dc mg p] kilo ( body weight4 ,not)/&+ ! div]sity 9 ! me?od ( exp]im5tation1 !re 0 a /rik+ uni=mity 9 "s ( ! results obta9$4 ,all ! exp]im5ts ( ! s]ies %[$ abs5ce ( cumulative action ( caffe94 ,! exp]im5tal evid5ce pres5t$ indicates t mod]ately l>ge doses may be giv5 at int]vals ( ab\t #bd h\rs )\t induc+ any symptoms ( n]v\s or any o!r di/urbance4 ,?is is illu/rat$ 9 ! te/s on dog #aa1 :i* 7 prelim9>y 9 "*4 ,9 ?is subject #ajj to #aej mg ( caffe9 p] kilo 7 +e/$ daily = sev]al days )\t %[+ any *anges4 ,lat] 9 ! c\rse ( ! exp]im5t1 aft] l>g] doses 7 giv51 mild symptoms only1 su* z tremors1 7 obs]v$4 ,additional evid5ce ( ! abs5ce ( cumulative action ( caffe9 0 furni%$ by ! results ( ! foll[+ exp]im5ts3 ,dog #bc receiv$ #adb mg ( caffe9 p] kilo on ?ree successive days4 ,8 g5]al condition indicat$ t ^! am\nts ( caffe9 7 toxic1 b he surviv$4 ,9 ano!r s]ies ( te/s1 made aft] he 0 all[$ to re/ a few days1 he aga9 fail$ to %[ any cumulation ( ! drug1 z he surviv$ ?is "t a s]ies ( te/s ( long] duration ?an ! fir/4 ,a mu* bett] illu/ration ( ! abs5ce ( cumulative action ( ! drug is furni%$ by ! exp]im5ts on dog ,no4 #bj4 ,9 ?is case #ajj to #abe mg ( caffe9 p] kilo1 giv5 on #aj consecutive days1 did n cause any m>k$ effects4 ,di>rhea & re/lessness 7 ! only symptoms obs]v$4 ,^! exp]im5ts !re=e %[ t ! elim9ation & decomposition ( caffe9 are app>5tly effect$ by ! body )9 tw5ty-f\r h\rs or !reab\ts4 ,exp]im5ts on dog #ai1 h[ev]1 =m an exception--! ?ird dose ( #abe mg caffe9 p] kilo hav+ prov$ fatal4 ,! v l[ prote9 cont5t ( ! diet ( ?is dog sugge/s itself z a possible cause ( ! l[] resi/ance to caffe9 ( ?is subject4 ,b x may be obs]v$ t ! same diet 0 furni%$ to dog #bj1 :i* /ood su* am\nts ( caffe9 mu* long]4 ,! pres5ce ( a trace ( album9 9 ! ur9e ( dog #ai is likewise inadmissible z a cause ( ! diff]5ce 9 ! toxicity ( caffe9 9 ?is dog1 = ! ur9e ( dog #bj likewise conta9$ a trace ( album94 ,! alkal9e reaction ( ! ur9e1 toge!r ) ! fact t ! fir/ dose ( only #fj mg ( caffe9 p] kilo induc$ symptoms ( toxicity1 sugge/s ! pres5ce ( an abnormal condition :i* 9 all probability 0 ! cause ( ! dea? ( ?is subject "u ! conditions indicat$4 ,9 a l>ge numb] ( exp]im5ts on caffe9 p]=m$ 9 ?is laboratory x has be5 obs]v$ t symptoms due to caffe9 (t5 disappe>$ :5 ! adm9i/ration ( ! same dose ( ! drug 0 cont9u$4 ,?us dog #ai vomit$ :5 ! am\nt ( caffe9 0 increas$ to #abe mg p] kilo4 ,:5 ?is am\nt 0 repeat$ ! next day !re 0 no vomit+4 ,simil> obs]vations 7 made on dogs #aa & #bc1 also on o!r dogs4 ,no4 #bb develop$ di>rhea at fir/2 :5 ! adm9i/ration ( caffe9 0 resum$ sev]al days lat]1 h[ev]1 !re 0 no di>rhea4 ,9 o!r exp]im5ts p]=m$ 9 ?is laboratory1 symptoms ( n]v\s irritability induc$ by caffe9 disappe>$ on cont9u$ treatm5t4 ,x 0 int]e/+1 !re=e1 to inquire :e!r resi/ance to caffe9 w\ld be increas$ by ! cont9u$ adm9i/ration ( progressively l>g] am\nts ( ! drug4 ,:5 doses ( #aej & ov] 7 f$1 ! int]vals all[$ 7 usually long] ?an #bd h\rs4 ,two & sometimes ?ree days 7 p]mitt$ to elapse betwe5 two successive doses4 ,?is 0 done 9 ord] to all[ "t = recov]y f possible *anges induc$ by l>g] doses ( caffe91 & ?us prev5t ! summation ( effect4 ,9 ! exp]im5ts consid]$1 !re=e1 ,nos4 #aa1 #bc1 #bj1 & #ai1 ! toxicity ( caffe9 does n seem to be great] ?an 9 ! exp]im5ts on acute caffe9 intoxication 9 ! dog4 ,x 0 ?\ght1 h[ev]1 t ! l>ge initial doses or ! quick *ange to l>ge doses :5 ! am\nts us$ 9 ! beg9n+ 7 small1 might h some?+ to d ) failure to induce a m>k$ degree ( tol]ance4 ,! exp]im5t on dog #ba 0 !re=e c>ri$ out by giv+ f #dj to #fj mg p] kilo = eight days1 & !n increas+ ! dose1 b tol]ance c\ld n be induc$1 z is %[n 9 ! protocol to ! exp]im5t4 ,,s]ies ,b4 ,accord+ to ! /udies ( ,*itt5d517#af7 l[ prote9 diet improves ! g5]al metabolism ( ! body1 fatigue is dim9i%$1 & bodily vigor1 !re=e1 correspond+ly increas$4 ,! expectation is1 !re=e1 ju/ifi$ t ! def5se ( ! organism aga9/ delet]i\s sub/ances introduc$ into ! body is mu* improv$ by su* a diet1 ?us increas+ its resi/ance to poisons4 ,hunt's exp]im5t on ?is subject1 also quot$ by ,*itt5d51 l5ds support to ?is view4 ,he f\nd t mice f$ on c>bohydrates *iefly1 or on foods conta9+ only a small am\nt ( prote91 7 m resi/ant to acetonitril4 ,x 0 int]e/+1 !re=e1 to inquire :e!r ! toxicity ( caffe9 diff]s "u simil> conditions ( diet4 ,a fix$ diet ( ! same calorific value 0 provid$ = all dogs ( ?is s]ies1 b ! prote9 cont5t = ?ree ( ! animals 0 approximately "o-?ird ( ! am\nt usually f$ to dogs4 ,caffe9 0 at fir/ adm9i/]$ subcutane\sly1 b all ! dogs on a l[ prote9 diet develop$ abscesses at ! site ( injection1 :ile none ( ^? on high prote9 diet %[$ a local reaction4 ,fe$+ by m\? 0 !n begun & cont9u$ ?r\gh\t ! exp]im5t 9 ea* case4 ,! initial dose 0 #ej mg p] kilo1 :i* 0 giv5 daily = sev5 to n9e days4 ,x 0 !n increas$ progressively by #be mg p] kilo2 #ge mg p] kilo 7 adm9i/]$ = "o to two days1 #ajj mg = two to ?ree days1 #abe mg = "o to two days1 #aej mg = "o to two days1 & a s+le dose ( #age mg4 ,x w be rem>k$ t sometimes an int]val ( "o day _h to be all[$ dur+ :i* no caffe9 0 f$4 ,dog #cj4 ,black & tan h\nd1 male4 ,! dog 0 "u obs]vation = ab\t eight weeks be=e ! exp]im5t 0 begun & _h receiv$ a high prote9 diet4 ,he 0 !n giv5 #ej mg caffe9 = n9e consecutive days4 ,on ! t5? day ! dose 0 increas$ to #ge mg p] kilo4 ,z no symptoms develop$1 ?is dose 0 increas$ to #ajj mg p] kilo1 & 0 f$ "o day ap>t4 ,x 0 !n rais$ to #abe mg p] kilo4 ,= ! fir/ "t s9ce ! drug 0 f$1 symptoms appe>$2 !y 7 notic$ a few h\rs aft] fe$+ & p]si/$ dur+ ! next day4 ,al?\gh ! appetite 0 good1 no caffe9 0 giv5 on ?is day4 ,on ! foll[+ day ?is dose 0 repeat$4 ,z ! symptoms 7 n s]i\s1 #aej mg p] kilo 7 giv5 daily = ! next ?ree days1 until #age mg p] kilo 0 rea*$4 ,?is dose prov$ fatal )9 six h\rs4 ,record ( exp]im5t foll[s3 ,octob] #i3 ,weight1 #i kilos1 on full nitrog5 diet1 receiv$ daily #j4gbd gram nitrog5 p] kilo or #hg calories p] kilo1 receiv$ #ah grams meat p] kilo1 #d grams l>d p] kilo1 #c grams c>bohydrates p] kilo1 bone du/1 ad libitum4 ,novemb] #c3 ,weight1 #i4aj kilos4 ,novemb] #aj3 ,weight1 #i kilos4 ,novemb] #bj3 ,weight1 #i4ee kilos4 ,novemb] #bi3 ,weight1 #h4gj kilos4 ,decemb] #f1 #g1 #h1 & #i3 ,receiv$ subcutane\sly #bb cc #b p] c5t caffe94 ,condition good1 site ( injection normal4 ,decemb] #aj1 #aa1 #ab1 #ac1 & #ad3 ,receiv$ #j4dcge gram caffe9 by m\? equal to #j4jej gram p] kilo1 no symptoms1 appetite & g5]al condition good4 ,decemb] #ae3 #aa4cj a4 m41 receiv$ #j4fefc gram caffe9 by m\?1 or #j4ge gram p] kilo1 no symptoms1 appetite good1 condition excell5t4 ,decemb] #af3 #aa a4 m41 receiv$ #j4hgj gram caffe9 by m\?1 or #j4a gram p] kilo1 weight #h4gj kilos1 no symptoms4 ,decemb] #ag3 ,no caffe9 giv54 ,decemb] #ah3 ,receiv$ #j4hgj gram caffe91 or #j4a gram p] kilo1 no symptoms4 ,decemb] #bj3 #b4de p4 m41 receiv$ #a4jhge grams caffe91 or #j4abe p] kilo2 #d p4 m41 ate food readily1 seem$ v uncom=table & sick4 ,decemb] #ba3 #i a4 m41 /iffness 9 muscles1 b no o!r symptoms1 appetite good1 no caffe9 giv54 ,decemb] #bb3 #aa a4 m41 receiv$ #a4jhge grams caffe91 or #j4abe gram p] kilo2 #c p4 m41 depress$ 9 spirits & sick1 b no o!r symptoms obs]v$4 ,decemb] #bc3 #aa4cj a4 m41 receiv$ #a4cje grams caffe91 or #j4aej gram caffe9 p] kilo2 #a4cj p4 m41 app>5tly q sick1 b no o!r symptoms1 _h good appetite4 ,decemb] #bd3 #aj a4 m41 receiv$ #j4age gram caffe9 p] kilo2 #d p4 m41 :5 ab\t to be f$ fell ov] & di$2 no autopsy4 ,! total am\nt ( caffe9 giv5 dog #cj 0 #aa4cdeh grams1 adm9i/]$ = a p]iod ( eighte5 days4 ,! av]age daily am\nt p] kilo 0 !re=e #gb mg4 ,! feces became (f5sive :5 ! am\nts ( caffe9 7 increas$ to #ge mg p] kilo4 ,x w be obs]v$ t 9 ?is dog ! appetite 0 uni=mly good until ! day ( 8 dea?4 ,:e!r or n ?is is ! cause ( 8 resi/ance to caffe9 w be discuss$ lat]4 ,dog #cb4 ,:ite1 male1 "y4 ,al?\gh he 0 gr[+ rapidly ?is dog's weight 0 con/ant1 b he look$ anemic4 ,he receiv$ a high prote9 diet until ,decemb] #c1 :5 ! rations 7 increas$ by "o-?ird4 ,?is dog 0 "u obs]vation f ,octob] #bf to ,decemb] #f :5 ! adm9i/ration ( caffe9 0 begun4 ,he !n receiv$ #ej mg caffe9 p] kilo daily = n9e days consecutively )\t %[+ any effects1 :5 ! dose 0 increas$ to #ge mg p] kilo1 !n to #ajj mg p] kilo4 ,?is dose 0 fur!r increas$ to #aej mg p] kilo )\t caus+ symptoms1 :i* 0 repeat$ ! next day4 ,no symptoms hav+ be5 obs]v$ aft] su* am\nts ( caffe91 #age mg p] kilo 7 f$4 ,?is dose1 h[ev]1 prov$ fatal )9 two h\rs4 ,record ( exp]im5t foll[s3 ,octob] #bf3 ,weight1 #f4ij kilos4 ,novemb] #c3 ,weight1 #f4ij kilos4 ,novemb] #aj3 ,weight1 #f4ij kilos4 ,novemb] #bj3 ,weight1 #f4ij kilos4 ,novemb] #bi3 ,weight1 #f4ee kilos4 ,decemb] #c3 ,put into cage1 diet increas$ "o-?ird4 ,decemb] #f1 #g1 #h1 #i3 ,weight #f4cj kilos2 #ab4cj p4 m41 receiv$ #af cc #b p] c5t caffe9 by subcutane\s injection 9 back1 no symptoms ( any k9d notic$1 site ( injection normal4 ,decemb] #aj1 #ad3 #j4je gram caffe9 p] kilo4 ,decemb] #ae3 ,receiv$ #j4dgbe gram caffe9 by m\?1 no symptoms4 ,decemb] #af3 ,receiv$ #j4fee gram caffe91 #j4ajj gram p] kilo4 ,decemb] #ag3 ,no caffe9 giv54 ,decemb] #ah3 ,receiv$ #j4fee gram caffe9 daily1 #j4ajj gram p] kilo1 no symptoms4 ,decemb] #bj3 ,receiv$ #j4hahh gram caffe91 #j4abe gram p] kilo1 no symptoms1 appetite good4 ,decemb] #ba3 ,receiv$ #j4ihbe gram caffe91 #j4aej gram p] kilo1 some:at uncom=table1 no o!r symptoms4 ,decemb] #bb3 ,receiv$ #j4ihbe gram caffe91 #j4aej gram p] kilo1 no symptoms except "s uneas9ess4 ,decemb] #bc3 #i a4 m41 no symptoms1 appetite good2 #aa4cj a4 m41 receiv$ #a4adf grams caffe91 #j4agei gram p] kilo2 #a4cj p4 m41 di$ :ile mak+ an ef=t to get out ( cage1 tonic contraction ( limbs obs]v$ be=e dea?4 ,! am\nt ( caffe9 receiv$ dur+ ! entire exp]im5tal p]iod 0 #i4bbbc grams1 or an av]age p] day approximately ( #hj mg p] kilo1 & !re=e #aj p] c5t m ?an dog ,no4 #cj receiv$4 ,x w be obs]v$ t ! appetite 9 dog ,no4 #cb 0 likewise uni=mly good1 & t he receiv$ a v high prote9 diet :i* 0 also ( a v high calorific value4 ,autopsy 7dog #cb74--,/oma* pres5t$ a sev]e inflammation ( ! mucosa1 especially 9 ! fundus & pyloric portions4 ,! ga/ritis 0 m m>k$ 9 pyloric portion1 & ! inflammatory condition ext5d$ along ! :ole c\rse ( small inte/9es1 :i* pres5t$ num]\s hemorrhagic areas1 & a ?ick cat>rhal exudate on ! mucosa4 ,! l>ge inte/9e conta9$ q a l>ge numb] ( p>asites1 probably r\nd worms4 ,! liv] 0 enl>g$ & ! gall cy/ well fill$4 ,! sple5 0 also consid]ably engorg$1 kidneys appe>$ normal1 o!r organs all appe>$ normal4 ,dog #ca4 ,black spaniel1 male4 ,?is dog _h be5 "u obs]vation "o mon? previ\s to ! exp]im5ts ) caffe94 ,! usual initial dose 0 !n adm9i/]$ = n9e days4 ,!re 7 no signs ( local irritation :5 ! drug 0 giv5 subcutane\sly1 b symptoms ( toxicity 7 pres5t4 ,^! disappe>$1 h[ev]1 :5 ! drug 0 adm9i/]$ by m\?4 ,! dose 0 !re=e increas$ to #ge mg p] kilo4 ,?is1 z w be se51 prov$ fatal )9 six h\rs4 ,high nitrog5 diet1 same z ,no4 #cj4 ,novemb] #c3 ,weight #aj4bej kilos4 ,novemb] #aj3 ,weight1 #aj4be kilos4 ,novemb] #bj3 ,weight1 #aj4cj kilos4 ,decemb] #a3 ,put 9 cage4 ,decemb] #f1 #g1 #h1 #i3 ,weight1 #aj4bj kilos2 receiv$ #bf cc #b p] c5t caffe9 subcutane\sly1 site ( injection normal4 ,decemb] #f3 ,v re/less & excit$1 :9$ :5 h&l$ z ?\gh muscles 7 sore1 appe>$ to be sick4 ,decemb] #aj-ad3 ,condition good1 receiv$ #j4ea gram caffe9 by m\? daily1 no notewor?y symptoms1 appetite cont9ues good1 some:at re/less at int]vals4 ,decemb] #ae3 #aa4cj a4 m41 receiv$ #j4gfe gram caffe9 p] m\? 7#j4jge gram p] kilo72 #b p4 m41 depress$ 9 _s1 seem$ sick & uncom=table2 #d4ae p4 m41 :5 ab\t to fe$1 animal jump$ up1 !n fell back dead4 ,autopsy 7dog #ca73 ,lungs conge/$2 he>t fill$ ) blood & conta9$ small am\nt ( blood-/a9$ fluid 9 p]ic>dial sac4 ,liv] deeply conge/$1 s(t & friable2 gall bladd] di/5d$ ) bile2 kidneys %[$ inflammation ( cortex2 sple5 pale1 normal 9 size & consi/5cy2 /oma* practically empty1 ! mucosa ( ! pyloric portion exhibit$ sev]e ga/ritis1 ) ?ick cat>rhal exudate4 ,?is cat>rhal inflammation ext5d$ ?r\gh ! duod5um2 rema9+ portion ( small inte/9e %[$ mild inflammation2 l>ge inte/9e appe>$ practically normal4 ,! total am\nt ( caffe9 receiv$ by dog #ca dur+ #aj days 0 #e4cie mg1 or a daily av]age ( #ec4i mg p] kilo4 ,?is unusually l[ resi/ance to caffe9 7:i* 0 practically ! only case 9 all ! exp]im5ts on dogs pres5t$ 9 ?is rese>*7 sugge/s ! pres5ce ( "s abnormal condition4 ,! bloody exudate 9 ! p]ic>dial cavity indicat+ p]ic>ditis1 :i* is likely to induce second>y *anges ( c>diac muscle1 may be consid]$ z a possible cause ( ! increas$ toxicity ( caffe9 9 ?is case4 ,dog #bi4 ,male fox t]ri]1 black4 ,?is dog 0 kept on a l[ nitrog5 diet = ne>ly five weeks be=e ! fe$+ ( caffe9 0 begun4 ,! adm9i/ration ( #ej mg ( caffe9 p] kilo 0 !n c>ri$ on = eight days )\t %[+ any symptoms ( toxicity4 ,! usual increase ( dose 0 !n giv5--#ge mg p] kilo--:i* 0 foll[$ by a manife/ation ( symptoms4 ,fur!r increase1 h[ev]1 to #ajj mg p] kilo _h no visible effect4 ,nev]!less x 0 consid]$ advisable to susp5d ! fe$+ ( caffe9 = "o day4 ,! same am\nts 7 !n repeat$ on two consecutive days4 ,no symptoms hav+ be5 obs]v$1 #abe mg p] kilo 7 giv54 ,z symptoms ( toxicity & especially loss ( appetite 7 obs]v$1 ! dog 0 n giv5 any caffe9 ! next day4 ,s9ce 8 appetite _h n[ improv$1 ! exp]im5t ) l>g] doses 0 resum$4 ,dea? foll[$ aft] ! second dose ( #aej mg p] kilo4 ,protocol foll[s3 ,weight1 #i4ij kilos4 ,"o-?ird nitrog5 diet4 ,receives #j4bfi gram nitrog5 p] kilo 7#hh4bfi calories p] kilo74 ,novemb] #c3 ,weight1 #i4he kilos4 ,novemb] #aj3 ,weight1 #i4ee kilos4 ,novemb] #ab3 ,weight1 #i4dj kilos4 ,novemb] #bi3 ,weight1 #i4he kilos4 ,decemb] #f3 ,weight1 #i4ij kilos2 #aa4ce a4 m41 receiv$ #be cc #b p] c5t caffe9 solution by subcutane\s injection 9 back2 #d p4 m41 no symptoms1 appetite good4 ,decemb] #g-i3 ,receiv$ #be cc caffe9 #b p] c5t solution--subcutane\s injection1 no symptoms1 area ( injection inflam$ & swoll54 ,decemb] #aj1 #ac3 ,site ( injection %[$ increas$ inflammation1 receiv$ #j4die gram caffe9 7#ej mg p] kilo7 9 #cj grams meat daily )\t %[+ any symptoms4 ,decemb] #ad3 #ab noon1 receiv$ #j4gdbe gram caffe9 by m\? 7#j4jge p] kilo72 #b4cj p4 m41 re/less & uneasy4 ,decemb] #ae3 #aa4cj a4 m41 receiv$ #j4gdbe gram caffe9 by m\?2 #b p4 m41 depress$ 9 spirits1 al?\gh cont9ues to h good appetite4 ,decemb] #af3 ,weight1 #i4ej kilos2 #c4ae p4 m41 receiv$ #j4ieji gram caffe9 by m\?2 #d4ej p4 m41 no symptoms4 ,decemb] #ag3 ,animal re/$4 ,decemb] #ah3 ,receiv$ #j4iej gram caffe9 by m\?1 no symptoms4 ,decemb] #ai3 ,receiv$ #j4ieji gram caffe9 by m\?1 no symptoms4 ,decemb] #bj3 #b4de p4 m41 receiv$ #a4ahge grams caffe9 7#j4abe gram p] kilo72 #d p4 m41 re/less & q sick2 ate only a little food4 ,decemb] #ba3 #i a4 m41 /ill uncom=table1 all[$ to re/1 no caffe9 giv51 gradually recov]$ appetite4 ,decemb] #bb3 #aa a4 m41 receiv$ #a4hge grams caffe92 #c p4 m41 seem$ sick1 b %[$ no o!r symptoms1 appetite fair4 ,decemb] #bc3 #i a4 m41 %[$ no symptoms f ! day be=e1 ate food gradually1 seem$ sick2 #aa4cj a4 m41 receiv$ #a4dbe grams caffe9 7#j4aej gram p] kilo72 #a4cj p4 m41 look$ & behav$ z if v sick1 no o!r symptoms2 #c4de p4 m41 9 attempt+ to get out ( box fell ov] on back1 _h convulsions1 :9$1 dyspnoea1 di$ )9 #cj seconds4 ,autopsy3 ,/oma* exhibit$ mild inflammation2 small inte/9e inflam$ & hemorrhagic areas on mucosa2 liv] engorg$ & friable2 sple5 normal2 kidneys slightly conge/$2 o!r organs appe>$ normal4 ,! total am\nt ( caffe9 f$ to ,dog #bi 0 #ab4ace grams1 :i* 0 giv5 9 #ah days4 ,! av]age daily am\nt p] kilo 0 !re=e #fg4fh mg4 ,dog #bh4 ,male fox t]ri]4 ,l[ nitrog5 diet 0 begun ab\t f\r weeks be=e ! fe$+ ( caffe92 #ej mg ( caffe9 0 !n f$ = sev5 consecutive days4 ,p>tial loss ( appetite 0 obs]v$ aft] ! fir/ dose4 ,z ! exp]im5t progress$ ! desire = food /eadily dim9i%$1 & ! feces became fetid4 ,symptoms ( intoxication manife/$ !mselves e>ly 9 ! exp]im5t1 & vomit+ occurr$ aft] ! f\r? dose4 ,! dog 0 !n put on a diet exclusively ( meat4 ,aft] an int]mission ( #aj days #aji mg caffe9 p] kilo 7 giv54 ,s9ce !re 7 no symptoms1 ! foll[+ day ! am\nt 0 increas$ to #abe mg p] kilo4 ,?is dose prov$ fatal )9 #af to #bj h\rs4 ,?is dog 0 /\t & /rong1 weight #ab4be kilos1 receiv$ daily #j4bfi gram nitrog5 p] kilo 7#hh4bfi calories p] kilo74 ,novemb] #c3 ,weight1 #aa4ge kilos4 ,novemb] #aj3 ,weight1 #aa4ie kilos4 ,novemb] #bj3 ,weight1 #aa4bj kilos4 ,all ?r\gh ?is p]iod _h be5 kept 9 a cold1 poorly v5tilat$ room1 put 9 a w>m room1 ) b$d+ & good v5tilation4 ,novemb] #bi3 ,weight1 #aa4ie kilos4 ,decemb] #a3 ,put 9 a cage2 weight1 #aa4ie kilos4 ,decemb] #f3 ,weight1 #aa4ie kilos2 #aa4de a4 m41 receiv$ #j4jej gram caffe9 p] kilo2 !n receiv$ #cj cc #b p] c5t caffe9 7#j4f gram7 9 practically "o subcutane\s injection2 #d4cj p4 m41 ate only "p ( food4 ,decemb] #g3 #aj4be a4 m41 receiv$ #cj cc #b p] c5t caffe9 by subcutane\s injection 7#j4f gram1 or #ej mg1 p] kilo72 #a4de p4 m41 seem$ s5sitive to t\*1 no desire = food1 depress$ 9 _s4 ,decemb] #h3 #aa4dj a4 m41 receiv$ #cj cc #b p] c5t caffe9 by subcutane\s injection 7#ej mg p] kilo72 #a p4 m41 depress$ 9 _s1 h9d legs seem$ some:at /iff1 no desire = regul> food1 site ( injection inflam$4 ,decemb] #i3 #aj4ej a4 m41 receiv$ #cj cc #b p] c5t caffe9 by subcutane\s injection 7#ej mg p] kilo72 #b4cj p4 m41 _h vomit$1 no desire = regul> food4 ,decemb] #aj3 ,inflammation ( site ( injection1 & swell+ v pron\nc$2 #b p4 m41 receiv$ #j4eige gram caffe91 or #ej mg p] kilo1 ) #cj grams ( meat1 refus$ regul> food4 ,decemb] #aa1 #ab3 ,receiv$ #j4eige gram caffe9 by m\?1 no symptoms except refusal ( regul> food1 feces fetid4 ,decemb] #ac-bb3 ,put on meat diet exclusively1 high temp]ature1 no caffe91 weight #aj kilos1 appetite good1 feces fetid4 ,decemb] #bb3 #ab a4 m41 weight #aa kilos1 receiv$ #a4b grams caffe9 by m\? 7#j4aji gram p] kilo72 #d p4 m41 no symptoms4 ,decemb] #bc3 #aa4cj a4 m41 receiv$ #a4cge grams caffe9 7#j4abe gram p] kilo7 _h vomit$ food ( ! day be=e1 b c\ld notice no caffe9 or capsules 9 vomit2 #d4cj p4 m41 no symptoms1 seem$ 9 good spirits1 appetite good1 _h no meat to fe$ )1 s 0 giv5 l[ nitrog5 fe$1 ( :i* he ate ab\t "o-f\r?4 ,decemb] #bd3 #i a4 m41 f\nd dead1 /iff1 & cold4 ,! mo/ /rik+ effect ( caffe9 9 ?is dog is ! increas$ inte/9al putrefaction4 ,! feces 7 /ill fetid #aj days aft] ! adm9i/ration ( caffe9 0 /opp$4 ,autopsy1 dog #bh3 ,/oma* p>tially fill$ ) an undige/$ food mass2 mucosa %[$ sev]e inflammation2 small inte/9es pres5t$ a hemorrhagic ent]itis along :ole ext5t2 l>ge inte/9e also exhibit$ mild inflammation2 liv] 0 engorg$2 sple5 appe>$ normal2 kidneys slightly conge/$ 9 cortical portion2 o!r organs appe>$ normal4 ,dog #bd4 ,:ite & tan male3 ,0 put on l[ prote9 diet six weeks be=e exp]im5ts ) caffe9 7 begun4 ,! initial dose ( #ej mg p] kilo 0 !n adm9i/]$ on eight consecutive days4 ,! only symptoms obs]v$ dur+ ?is p]iod ( caffe9 adm9i/ration 7 ^? ( inte/9al putrefaction4 ,fetid feces 7 notic$ already aft] ! fir/ dose ( caffe9 0 inject$4 ,:5 ! second dose ( #ge mg ( caffe9 0 repeat$1 mild symptoms appe>$1 b none h be5 obs]v$ ev5 ) increas$ am\nts ( caffe94 ,"o-?ird nitrog5 diet4 ,receiv$ daily #j4bfi gram nitrog5 p] kilo 7#hh4bfi calories p] kilo74 ,octob] #bf3 ,weight #aa4ae kilos4 ,food consi/$ ( #e grams crack] meal p] kilo2 meat1 #c grams p] kilo2 l>d1 #b grams p] kilo2 tapioca1 #aj4fi grams p] kilo4 ,kept 9 a cold1 damp room ) poor v5tilation until ,novemb] #bj4 ,novemb] #c3 ,weight1 #aa kilos4 ,novemb] #aj3 ,weight1 #aj4ge kilos4 ,novemb] #bj3 ,weight1 #aj4ee kilos2 *ang$ to a w>m room1 ) b$d+ & good v5tilation4 ,novemb] #bi3 ,weight1 #aj4he kilos4 ,decemb] #a3 ,put into a cage4 ,decemb] #f3 ,weight1 #aj4ij kilos2 #aa4be a4 m41 receiv$ #bh cc #b p] c5t caffe9 subcutane\sly 9 side1 bel[ ! %\ld]s1 area wa%$ ) alcohol & e!r1 approximately #ej mg p] kilo adm9i/]$1 no symptoms4 ,decemb] #g3 #aj4ae a4 m41 receiv$ #bh cc #b p] c5t caffe9 inject$ subcutane\sly2 feces s(t & v fetid2 #a p4 m41 depress$ 9 _s1 eyes dull4 ,decemb] #i3 #aj4de a4 m41 receiv$ #be cc #b p] c5t caffe9 solution subcutane\sly1 feces /ill fetid1 site ( injection inflam$ & swoll51 no o!r symptoms4 ,decemb] #aj3 ,inflammation ( area ( injection m pron\nc$2 #b p4 m41 giv5 #j4eddi gram caffe9 & #cj grams ( meat2 #d p4 m41 f$1 no symptoms1 feces fetid4 ,decemb] #aa3 #ab a4 m41 giv5 #j4edei gram caffe9 & #cj grams ( meat1 no symptoms1 feces fetid4 ,decemb] #ab1 #ac3 ,giv5 #j4edei gram caffe9 daily1 )\t notic+ any symptoms4 ,decemb] #ad3 #ab a4 m41 receiv$ #j4hag gram caffe9 7#ge mg p] kilo72 #b4cj p4 m41 re/less & uncom=table1 no o!r symptoms4 ,decemb] #ae3 #aa4cj a4 m41 receiv$ #j4hage gram caffe9 by m\?2 #b p4 m41 depress$ 9 _s1 act$ z ?\gh sick1 no o!r symptoms4 ,decemb] #af3 ,weight1 #aa kilos2 #aa a4 m41 receiv$ #j4ajj gram caffe9 p] kilo 7#a4ajj grams7 by m\?1 no symptoms4 ,decemb] #ag3 ,re/$4 ,decemb] #ah3 #b4cj p4 m41 receiv$ #a4ajj grams caffe9 by m\?2 #d p4 m41 no symptoms4 ,decemb] #ai3 #ab noon1 receiv$ #a4ajj grams caffe9 by m\?2 #d4ae p4 m41 no symptoms4 ,decemb] #bj3 #b4de p4 m41 giv5 #a4cge grams caffe9 7#j4abe gram p] kilo72 #c4de p4 m41 vomit$--"o ( ! capsules be+ f\nd intact1 ! o!r brok5 op52 #d p4 m41 giv5 regul> diet1 conta9+ #a4cgeg grams caffe9 9 capsules1 ate mo/ ( ?is dur+ ! night1 :9$ at int]vals1 coord9ation di/urb$1 appe>$ v sick1 b exhibit$ no o!r symptoms4 ,decemb] #ba3 #i a4 m41 f\nd dead1 /iff1 & cold4 ,! total am\nt ( caffe9 receiv$ by dog #bd 0 betwe5 #aj4aji & #aa4dhd grams4 ,z "o ( ! capsules vomit$ 0 intact & ! o!r brok5 op51 ! am\nt 0 probably ab\t #aj4ge grams4 ,! fatal dose 9 ?is case 0 und\bt$ly less ?an #ahe mg p] kilo--some:]e betwe5 #abe & #ahe mg4 ,autopsy %[$ he>t 9 dia/ole2 po/]ior lobe ( "r lung deeply conge/$2 liv] engorg$2 gall cy/ fill$2 sple5 appe>$ normal2 /oma* well fill$ ) semifluid mass2 pyloric portion ( /oma* exhibit$ a sev]e inflammation ( mucosa2 mucosa ( duod5um greatly inflam$ & %[$ hemorrhagic areas & cat>rhal exudate2 rema9d] ( small inte/9e also exhibit$ mild inflammation2 kidneys deeply engorg$1 mes5t]y inject$4 ,a comp>ison ( ! fatal doses ( caffe9 9 ! exp]im5ts on high & l[ prote9 diet does n %[ mu* diff]5ce 9 ! resi/ance to caffe91 s9ce #age mg p] kilo prov$ fatal to ,nos4 #cj & #cb1 :ile ,no4 #bi di$ aft] receiv+ #aej mg p] kilo1 & ,no4 #bd receiv$ #abe to #ahe mg p] kilo4 ,moreov]1 ,no4 #bh1 :i* 0 *ang$ f l[ to high prote9 diet1 succumb$ :5 giv5 #abe mg p] kilo4 ,obs]vations made dur+ ! exp]im5tal p]iod indicate1 h[ev]1 great] toxicity ( caffe9 9 ! subjects on l[ prote9 diet4 ,dog #cj %[$ ! effects ( ! drug :5 ! dose 0 increas$ to #abe mg ( caffe9 p] kilo1 :ile 9 ,no4 #cb1 #aej mg p] kilo 7 receiv$ )\t any manife/ation ( symptoms4 ,dog #ca1 :i* 0 likewise on a high prote9 diet1 is evid5tly an exception1 & its l[ resi/ance to caffe9 may be acc\nt$ = by ! condition f\nd at autopsy4 ,9 o!r dogs on l[ prote9 diet symptoms ( intoxication appe>$ e>ly 9 ! exp]im5t4 ,9 ,nos4 #bi & #bd x 0 obs]v$ z soon z ! am\nt ( caffe9 0 increas$ to #ge mg p] kilo4 ,9 dog #bh ! fir/ dose ( caffe9 #ej mg p] kilo 0 toxic4 ,! symptoms ( ga/ro-inte/9al di/urbance 7 especially m>k$ aft] caffe9 on l[ prote9 diet4 ,?is may seem to contradict ! results ( exp]im5ts on dogs #aa & #bj1 9 :i* l>g] doses ( caffe9 fail$ to induce symptoms ( intoxication4 ,b x %\ld be obs]v$ t ! diet1 :i* consi/$ almo/ exclusively ( c>bohydrates1 0 giv5 only dur+ ! adm9i/ration ( caffe91 :ile 9 ! exp]im5ts ( s]ies ,b ! subjects receiv$ a l[ prote9 diet = sev]al weeks be=e ! adm9i/ration ( caffe9 0 begun1 & x 0 cont9u$ ?r\gh ! entire caffe9 p]iod4 ,x w be rem>k$ t ! abs5ce ( cumulative action 9 ! exp]im5ts ( ! prec$+ s]ies 0 also obs]v$ 9 dogs on high z well z on l[ prote9 diet4 ,! appe>ance ( symptoms aft] small] doses ( caffe9 9 ! latt] exp]im5ts might sugge/ cumulative action1 b s9ce ^! symptoms disappe>$ on cont9u$ adm9i/ration ( ! sub/ance cumulation is cle>ly n indicat$4 ,! ga/ro9te/9al lesions obs]v$ on po/-mortem exam9ation 71 x w be recall$1 also f\nd 9 rabbits simil>ly treat$4 ,! explanation sugge/$ probably applies also 9 ! case ( dogs4 ,,s]ies ,c4 ,z already po9t$ out 9 ! exp]im5ts on acute toxicity ( caffe91 "y gr[+ dogs are probably m resi/ant to caffe9 ?an adults4 ,t ?is may also hold true 9 *ronic caffe9 intoxication seem$ indicat$ by ! foll[+ exp]im5ts4 ,dog #cc4 ,black female puppy4 ,weight1 #d kilos4 ,_h be5 cont9u\sly on a meat diet4 ,decemb] #bb3 #b4cj p4 m41 receiv$ #j4fi gram ( caffe9 7#j4agb gram p] kilo72 #c4ae p4 m41 no symptoms except t feces 7 fetid4 ,decemb] #bc3 #aa4cj a4 m41 receiv$ #j4gi gram ( caffe9 7#j4aig gram p] kilo72 #a4cj p4 m41 no symptoms4 ,decemb] #bd3 #aa a4 m41 receiv$ #j4hg gram ( caffe9 7#j4bjji gram p] kilo72 #d p4 m41 no symptoms4 ,x w be obs]v$ t ! only effect produc$ 9 dog #cc by fe$+ caffe9 0 increas$ inte/9al putrefaction1 al?\gh #b4cg grams ( caffe9 7 giv5 9 ?ree days4 ,additional data on ! effects ( ! age ( animals on ! resi/ance to caffe9 seem$ desirable4 ,! foll[+ exp]im5ts 7 !re=e c>ri$ out4 ,six puppies ( ! same litt] 7 wean$ :5 #g to #h weeks old & put on a milk diet4 ,?ree ( !m receiv$ ?is diet ?r\gh\t ! exp]im5tal p]iod4 ,meat 0 sub/itut$ 9 ! o!r ?ree a few days be=e ! adm9i/ration ( caffe9 0 begun1 & 0 cont9u$ until ! end ( ! exp]im5t4 ,caffe9 0 giv5 by m\?2 ! initial dose1 :i* 0 adm9i/]$ = sev]al days & !n gradually increas$1 be+ #afj to #bjj mg = ea* dog1 except "o1 :i* receiv$ only #ajj mg p] kilo = sev]al days & !n an increas$ am\nt4 ,an int]mission ( a few days 7dur+ :i* no caffe9 0 giv57 0 all[$4 ,?is 0 done on acc\nt ( "s /udies c>ri$ on at ! same "t on ! effect ( caffe9 on c]ta9 con/itu5ts ( ! ur9e4 ,,pup ,,no4 #a4 ---------------------------------------- ------------------------- ,treatm5t ,date4 ,weight4 ,food 7#b p] c5t ,symptoms4 7milk74 caffe974 ---------------------------------------- ------------------------- ,grams4 cc4 cc4 ,apr4 #ba #a1dej #cjj #aj4j ,no symptoms4 ,apr4 #bb #a1ebj #cjj #aj4j ,d4 ,apr4 #bc #a1dej #bej #aj4j ,d4 ,apr4 #bd #a1cge #bej #aj4j ,d4 ,apr4 #be #a1dbj #bej #aj4j ,d4 ,apr4 #bf #a1cij #bej ,none4 ,apr4 #bg #a1djj #bej ,none4 ,apr4 #bh #a1dje #bej ,none4 ,apr4 #bi #a1dbj #bej ,none4 ,pass$ worms4 ,apr4 #cj #a1dcj #bej ,none4 ,d4 ,may #a #a1dej #bej #aj4j ,no symptoms4 ,may #b #a1eae #bej #ae4j ,d4 ,may #c #a1dge #bej #ae4j ,d4 ,may #d #a1die #bej #ae4j ,d4 ,may #e #a1eae #bej #bb4j ,seems dull & :9es4 ,may #f #a1ece #bej #bj4j ,:9es4 ,may #g #a1ebe #bej #bj4j ,no symptoms4 ,may #h #a1ecj #bej #bj4j ,d4 ,may #i #a1ejj #bej #bc4j ,di>rhea2 pass$ worms2 tremor & rigidity ( legs2 :9es4 ,may #aj #a1dij #bej ,none4 ,completely recov]$ f ! effects ( #i?4 ,may #aa #a1ece #bej #be4j ,c n balance itself2 cont9ually vomit+4 ,may #ab #a1dfj #cjj ,none4 ,recov]$ f effects4 ,may #ac #a1dge #cej ,none4 ,9 good condition4 ,may #ad #a1ede #bej ,none4 ,may #ae #a1eej #bej ,none4 ,may #af #a1eee #bej ,none4 ,may #ag #a1efj #bej #be4j ,salivat$ 9 cage2 /iffness ( muscles4 ,may #ah #a1dej #bej ,none4 ,weak & /iff2 di>rhea4 ,may #ai #a1ejj #bej ,none4 ,no symptoms4 ,may #bj #a1efe #bej ,none4 ,may #ba #a1ede #bej ,none4 ,may #bb 7#a7 #bej ,none4 ,may #bc #a1eie #bej #bg4j ,tremors2 gait clumsy2 9- coord9ation ( movem5ts4 ,may #bd #a1die #bej #bg4j ,di>rhea2 vomit$2 weak & /iff2 f\nd dead #i a4 m4 #be?4 ---------------------------------------- ------------------------- 7#a7 ,sunday4 ,autopsy3 ,m>k$ pulmon>y conge/ion2 liv] v pale2 he>t wall inject$2 slight inflammation ( /oma* & inte/9es4 ,,pup ,,no4 #b4 ---------------------------------------- -------------------- ,food ,treatm5t ,date4 ,weight4 7milk74 7#b p] c5t ,symptoms4 caffe974 ---------------------------------------- -------------------- ,grams4 cc4 cc4 ,apr4 #ba #a1cej #cjj #e4j ,no symptoms4 ,apr4 #bb #a1bdj #cjj #e4j ,d4 ,apr4 #bc #a1bej #bjj #g4e ,d4 ,apr4 #bd #a1bje #bjj #g4j ,d4 ,apr4 #be #a1bbj #bjj #g4j ,d4 ,apr4 #bf #a1baj #bjj ,none4 ,apr4 #bg #a1baj #bjj ,none4 ,apr4 #bh #a1bje #bjj ,none4 ,apr4 #bi #a1bjj #bjj ,none4 ,pass$ worms4 ,apr4 #cj #a1baj #bjj ,none4 ,may #a #a1bbj #bjj #aj4j ,no symptoms4 ,may #b #a1bbj #bjj #aj4j ,d4 ,may #c #a1bce #bjj #aj4j ,d4 ,may #d #a1bce #bjj #aj4j ,d4 ,may #e #a1bce #bjj #ag4j ,:9es4 ,may #f #a1bej #bjj #ag4j ,d4 ,may #g #a1bce #bjj #ae4j ,di>rhea & worms4 ,may #h #a1bej #bjj #ae4j ,di>rhea4 ,may #i #a1afe #bjj #ah4j ,little or no symptoms4 ,may #aj #a1bce #bjj ,none4 ,no symptoms4 ,may #aa #a1cjj #bjj #bj4j ,salivat$ 9 cage2 refus$ to eat2 draws up h9d legs4 ,may #ab #a1bjj #bjj ,none4 ,recov]$4 ,may #ac #a1bae #bjj ,none4 ,9 good condition4 ,may #ad #a1bhj #bjj ,none4 ,may #ae #a1cjj #bjj ,none4 ,may #af #a1caj #bjj ,none4 ,may #ag #a1caj #bjj #bj4j ,salivat$ 9 cage2 /iff2 all symptoms4 ,may #ah #a1bej #bjj ,none4 ,weak & /iff4 ,may #ai #a1bde #bjj ,none4 ,no symptoms4 ,may #bj #a1caj #bjj ,none4 ,may #ba #a1cbe #bjj ,none4 ,may #bb #a1cbe #bjj ,none4 ,may #bc #a1cbe #bjj #bb4j ,some:at /iff4 ,may #bd #a1cae #bjj #bb4j ,re/less2 scrat*es eyes2 sick4 ---------------------------------------- -------------------- ,,pup ,,no4 #c4 ---------------------------------------- ----------------------- ,apr4 #ba #a1bae #cjj ,none4 ,apr4 #bb #a1bbj #cjj ,none4 ,apr4 #bc #a1bbj #bjj ,none4 ,apr4 #bd #a1bjj #bjj ,none4 ,apr4 #be #a1bje #bjj ,none4 ,apr4 #bf #a1aie #bjj ,none4 ,apr4 #bg #a1bjj #bjj 7#a7 ,apr4 #bh #a1bae #bjj ,none4 ,apr4 #bi #a1bbj #bjj ,none4 ,apr4 #cj #a1bjj #bjj ,none4 ,may #a #a1bbe #bjj #aj4j ,no symptoms4 ,may #b #a1bcj #bjj #aj4j ,d4 ,may #c #a1bce #bjj #aj4j ,c\ghs & :9es4 ,may #d #a1bde #bjj #aj4j ,pass$ worms4 ,may #e #a1bgj #bjj #ag4j ,eyes appe> dim & is cont9ually scrat*+ !m4 ,may #f #a1bfj #bjj #ag4j ,appe>s re/less & draws up h9d legs :5 walk+4 ,may #g #a1bdj #bjj #ae4j ,eyes dim2 pass$ worms2 di>rhea4 ,may #h #a1bfe #bjj #ae4j ,c\gh+ cont9ually2 v re/less4 ,may #i #a1bdj #bjj #ah4j #ab noon2 salivat$ 9 cage2 pass$ worms2 di>rhea2 foam+ at m\?2 c n balance himself2 rigidity & tremor ( h9d legs4 #b4ae1 f\nd dead4 ---------------------------------------- ----------------------- 7#a7 ,ur9e squeez$ f bladd]4 ,autopsy3 ,sev]e pulmon>y conge/ion2 cat>rhal ga/ritis2 mild ent]itis ) small hemorrhagic areas on mucosa4 ,,pup ,,no4 #d4 ---------------------------------------- -------------------------- ,treatm5t ,date4 ,weight4 ,food4 7#b p] c5t ,symptoms4 caffe974 ---------------------------------------- -------------------------- ,grams4 ,milk cc4 7cc74 ,apr4 #bh #a1fgj #cjj ,apr4 #bi #a1fgj #cjj ,apr4 #cj #a1fgj #cjj ,may #a #a1fij #cjj ,may #b #a1fij #cjj ,may #c #cjj ,may #d #a1gbj #cjj ,may #e #a1gce #cjj ,meat 7grams74 ,may #f #a1gfj #fj ,may #g #a1gde #hj ,may #h #a1gaj #ahj ,may #i #a1gej #ahj ,may #aj #a1gej #ahj ,may #aa #a1gee #ahj #aj4j ,no symptoms4 ,may #ab #a1gcj #ahj ,none4 ,may #ac #a1ghe #ahj ,none4 ,may #ad #a1hce #aae #aj4j ,d4 ,may #ae #a1hbj #aae #aj4j ,d4 ,may #af #a1hce #aae #aj4j ,pass$ worms4 ,may #ag #a1hfj #aae #aj4j ,feces s(t & black4 ,may #ah #a1hee #aae #ae4j ,/iff2 loss ( appetite4 ,may #ai #a1ggj #aae #ae4j ,loss ( appetite4 ,may #bj #a1gee #aae #ae4j ,d4 ,may #ba #a1ghj #aae #ag4j ,re/less4 ,may #bb #aae #ag4j ,feces s(t & black4 ,may #bc #a1ghe #aae #ag4j ,loss ( appetite4 ,may #bd #a1gie #aae ,loss ( appetite2 ?rew up worms4 ,may #be #a1fcj #aae #bj4j ,loss ( appetite2 worms2 c\gh2 di>rhea4 ,may #bf #a1fjj #aae #bc4j ,weak2 no appetite2 di>rhea2 c\gh4 ,may #bg ,f\nd dead1 #i a4 m4 ---------------------------------------- -------------------------- ,autopsy4--,lung uni=mly conge/$2 liv] deeply conge/$2 he>t muscle pale ) hemorrhagic areas2 kidneys pale ) hemorrhagic spots on surface & 9 cortex2 slight cat>rhal inflammation ( /oma* & ! small inte/9es4 ,,pup ,,no4 #e4 ---------------------------------------- -------------------------- ,treatm5t ,date4 ,weight4 ,food4 7#b p] c5t ,symptoms4 caffe974 ---------------------------------------- -------------------------- ,grams4 ,milk cc4 7cc74 ,apr4 #bh #a1gde #cjj ,apr4 #bi #a1gde #cjj ,apr4 #cj #a1gej #cjj ,may #a #a1gfe #cjj ,may #b #a1gfe #cjj ,may #c #cjj ,may #d #a1dij #cjj ,may #e #a1hje #cjj ,meat 7grams74 ,may #f #a1hae #fj ,may #g #a1hbe #hj ,may #h #a1ggj #ahj ,may #i #a1gie #ahj ,may #aj #a1hje #ahj ,may #aa #a1hjj #ahj #aj4j ,no symptoms4 ,may #ab #a1gbj #ahj ,none4 ,may #ac #a1hae #ahj ,none4 ,may #ad #a1hde #aae #aj4j ,d4 ,may #ae #a1hcj #aae #aj4j ,d4 ,may #af #a1hae #aae #aj4j ,loss ( weight2 no o!r symptoms4 ,may #ag #a1hcj #aae #ae4j ,no symptoms4 ,may #ah #a1hce #aae #ae4j ,/iffness4 ,may #ai #a1hbe #aae #ae4j ,no symptoms4 ,may #bj #a1hej #aae #ae4j ,a little /iff4 ,may #ba #a1hce #aae #ag4j ,no symptoms4 ,may #bb #aae #ag4j ,may #bc #a1hbj #aae #ag4j ,d4 ,may #bd #a1hce #aae #bj4j ,d4 ,may #be #a1hdj #aae #bj4j ,feces s(t & black4 ,may #bf #a1hbj #aae #bc4j ,may #bg #a1hdj #aae #be4j ,a little /iff4 ,may #bh #a1hcj #aae #be4j ,may #bi #aae ,none4 ,may #cj #aae ,none4 ,may #ca #a1ggj #aae ,none4 ,june #a #a1gfe #aae #be4j ,di>rhea2 /iff 9 h9d legs4 ,june #b #a1gej #aae #bg4e ,di>rhea & worms4 ,june #c #a1fce #bg4e ,p>alyz$2 vomit$2 di$ at #c p4 m4 ---------------------------------------- -------------------------- ,,pup ,,no4 #f4 ---------------------------------------- -------------------------- ,treatm5t ,date4 ,weight4 ,food4 7#b p] c5t ,symptoms4 caffe974 ---------------------------------------- -------------------------- ,grams4 ,milk cc4 7cc74 ,apr4 #bh #cjj ,apr4 #bi #a1bhj #cjj ,apr4 #cj #a1bij #cjj ,may #a #a1cae #cjj ,may #b #a1ccj #cjj ,may #c #cjj ,may #d #a1cfj #cjj ,may #e #a1cfe #cjj ,meat 7grams74 ,may #f #a1cie #fj ,may #g #a1cfe #hj ,may #h #a1cdj #ahj ,may #i #a1chj #ahj ,may #aj #a1djj #ahj ,may #aa #a1dbe #ahj #ad4e ,no symptoms4 ,may #ab #a1dgj #ahj ,none4 ,may #ac #a1dhe #ahj ,none4 ,may #ad #a1eaj #aae #ad4e ,d4 ,may #ae #a1ejj #aae #ad4e ,d4 ,may #af #a1dhe #aae #ad4e ,pass$ worms4 ,may #ag #a1dhj #aae #ad4e ,may #ah #a1dhe #aae #ai4e ,feces s(t & black2 almo/ di>rhea4 ,may #ai #a1die #aae #ai4e ,may #bj #a1ejj #aae #ai4e ,scrat*es h] eyes & *ases h] tail4 ,may #ba #a1ejj #aae #ag4j ,may #bb #aae #ag4j ,may #bc #a1dgj #aae #ag4j ,may #bd #a1dfe #aae #bj4j ,may #be #a1dej #aae #bj4j ,feces s(t & black4 ,may #bf #a1dej #aae #bc4j ,di>rhea & worms4 ,may #bg #a1cee #aae #bc4j ,refus$ to eat all food4 ,may #bh #a1bgj #aae #bc4j ,?rew up worms1 /iff1 & has sk9 ov] bo? eyes4 ,may #bi ,f\nd dead4 ---------------------------------------- -------------------------- ,highe/ am\nt ( caffe9 giv51 #cfb mg p] kilo4 ,no autopsy4 ,exam9ation ( ! results obta9$ 9 ! exp]im5ts ( s]ies ,c %[s t "y & gr[+ dogs tol]ate l>ge am\nts ( caffe94 ,9 f\r subjects ( ?is s]ies1 ,nos4 #a1 #b1 #c1 & #f1 no effect 0 obs]v$ :5 mod]ately l>ge am\nts 7#afj to #bjj mg p] kilo ( caffe97 7 f$4 ,symptoms 7 notic$ only :5 ^! am\nts ( caffe9 7 increas$ f #ej to #fj p] c5t4 ,! o!r two dogs1 ,nos4 #d & #e1 ( ?is s]ies 7 less resi/ant1 h[ev]1 to caffe91 z #j4af gram ( ! drug p] kilo induc$ well-m>k$ symptoms4 ,s9ce ^! 7 f$ meat1 :ile ,nos4 #a1 #b1 & #c receiv$ milk1 ! diff]5ce 9 toxicity may be due to ! diet employ$1 b ,no4 #f1 :i* likewise receiv$ a meat diet1 fail$ to %[ ! effects ( caffe9 :5 #bjj mg p] kilo 7 f$4 ,on ! o!r h&1 x %\ld be notic$ t ,no4 #a di$ aft] receiv+ #cfj mg p] kilo1 ,no4 #b surviv$ a dose ( #ccd mg1 :ile ,no4 #c di$ aft] a dose ( #cbb mg p] kilo ( caffe94 ,! fatal doses = ,nos4 #d1 #e1 & #f 7 #bhg1 #cce1 & #cjj mg p] kilo1 respectively4 ,al?\gh ! diff]5ces are too small to ju/ify any def9ite conclusion reg>d+ ! effect ( a milk diet or ( a meat diet on ! toxicity ( caffe91 ! results nev]!less sugge/ a reasonable possibility t caffe9 is m toxic to "y dogs :5 on an exclusively meat diet ?an :5 f$ milk4 ,x is p]fectly evid5t1 h[ev]1 t ! resi/ance to caffe9 9 ei!r case is v great1 almo/ twice t ( adult subjects4 ,z %[n 9 s]ies ,a & ,b1 #abe to #age mg p] kilo prov$ fatal to all b two animals 9 ^! exp]im5ts1 :ile symptoms ( toxicity appe>$ aft] mu* small] doses4 ,9 o!r respects ! behavior ( "y dogs t[>d caffe9 0 ! same z t ( ! adult4 ,9 nei!r case 0 cumulation nor tol]ance obs]v$ "u ! conditions ( ^! exp]im5ts4 ,! f9d+s at autopsy 7 likewise simil>1 z ga/ro-ent]itis 0 ! *ief lesion obs]v$ on macroscopic exam9ation4 ,x might be m5tion$1 h[ev]1 9 ?is connection1 t ! symptoms ( caffe9 intoxication 9 "y dogs (t5 pres5t$ m>k$ diff]5ces f ^? obs]v$ 9 ^? ( m advanc$ age4 ,! resemblance ( ! effects ( caffe9 9 "y puppies & 9 rabbits 0 v /rik+4 ,9 bo?1 ! tonic ) clonic convulsions 7 obs]v$ aft] a suffici5t quantity ( caffe9 0 adm9i/]$4 ,9 ! dogs :i* 7 fully gr[n a l>ge dose ( caffe9 0 usually foll[$ by tonic convulsions & almo/ in/antane\s dea?4 ,mod]ately l>ge am\nts ( caffe9 f$ daily to puppies = sev]al days--9 "s cases z long z #aj days--induc$ mild symptoms only4 ,no cumulative effect 0 obs]v$ 9 any ( ! exp]im5ts ( s]ies ,c4 ,!re seems to be tol]ance ( c]ta9 functions t[>d caffe91 b no g5]al tol]ance ( ! body c\ld be obta9$ 9 ^! exp]im5ts4 ,caffe9 is app>5tly less toxic = adult dogs on high ?an on l[ prote9 diet4 ,9 "y & gr[+ dogs caffe9 is some:at less toxic :5 milk1 r ?an meat1 =ms ! exclusive diet4 ,"s pa?ological conditions app>5tly increase ! toxicity ( caffe9 also 9 dogs4 ,! symptoms ( caffe9 intoxication obs]v$ 9 "y dogs are 9 "s respects diff]5t f ^? 9 full gr[n & old] animals1 & resemble ^? notic$ 9 rabbits4 ,,discussion ,,( ,,results4 ,x 0 po9t$ out at "s l5g? 9 ! introduction t ! toxicity ( "s drugs may n be ! same = all =ms ( life4 ,?is obs]vation 0 also made by "s inve/igators :o exp]im5t$ ) caffe9 on diff]5t species ( animals4 ,?us ,maurel7#ee7 /at$ t caffe9 is twice z toxic = ! frog z = ! rabbit :5 adm9i/]$ by m\?4 ,frhn]'s7#bf7 exp]im5ts1 on ! o!r h&1 made on dome/ic animals1 fail$ to %[ great diff]5ces 9 ! toxicity ( caffe94 ,accord+ to ?is obs]v]1 horses seem to be m susceptible ?an cattle1 goats1 & sw9e1 ! m9imum toxic dose be+ ! same = all ( ^!1 :ile ! resi/ance ( ! dog to caffe9 is ab\t midway betwe5 t ( ! horse & ! o!r animals m5tion$4 ,x may be rem>k$1 h[ev]1 t ,frhn] made only #ac exp]im5ts4 ,t ^! data are inadequate = ! =mation ( any conclusions z to ! toxicity ( caffe9 is evid5t s9ce ! mo/ /rik+ effect ( caffe9 obs]v$ 9 ! "w h]e9 report$ 0 ! comp>atively wide range ( v>iation 9 ! resi/ance ( individuals ( ! same species to ?is drug4 ,?is 0 f\nd to be ! case ev5 :5 ! conditions ( exp]im5tation 7 approximately uni=m1 & 0 obs]v$ :atev] ! mode ( adm9i/ration ( ! drug employ$4 ,! toxicity = diff]5t individuals also v>i$ 9 acute z well z 9 *ronic intoxication4 ,x is = ?is reason t ! numb] ( te/s employ$ 7 (t5 q l>ge1 = no conclusions ( any value c\ld be drawn )\t av]ag+ ! results ( a suffici5tly l>ge numb] ( exp]im5ts4 ,fur!rmore1 x is to be borne 9 m9d t ! action ( a drug may diff] accord+ to ! mode ( its introduction into ! body & t diff]5t species ( animals may v>y 9 ?is reg>d4 ,?is is especially true ( "s sub/ances :5 giv5 by m\?1 ! range 9 toxicity = c]ta9 species ( animals be+ mu* great] :5 ?us adm9i/]$ ?an :5 inject$ subcutane\sly or intrav5\sly4 ,maurel's7#ef7 inve/igations are ( int]e/ 9 ?is connection1 z 8 "w embraces a sy/ematic /udy ( ! toxicity ( a l>ge numb] ( sub/ances 9 ! rabbit1 pigeon1 & frog :5 giv5 by m\?1 subcutane\sly1 intrav5\sly1 or :5 inject$ into ! muscles4 ,accord+ to ?is inve/igator ! range ( v>iation ( ! toxicity ( a sub/ance is wide/ :5 giv5 by m\?4 ,potassium sulphocyanid1 = example1 is ab\t #b4e times z toxic = ! frog z = ! rabbit :5 giv5 by m\?4 ,qu99 hydrobromid is ?ree times z toxic = ! frog z = ! pigeon1 :ile = ! rabbit x is twice z toxic z = ! pigeon4 ,:5 giv5 by hypod]mic injection ! toxic dose p] kilo weight is practically ! same = all ?ree species4 ,! diff]5ce ( resi/ance accord+ to ! mode ( adm9i/ration is ev5 m m>k$ = sp>te9 sulphate4 ,:5 giv5 by m\? ! toxicity = ! rabbit is six times z great z = ! frog1 b :5 inject$ subcutane\sly ! toxic dose is ab\t ! same = ! rabbit & = ! frog4 ,! relation ( ! mode ( adm9i/ration to toxicity is fur!r %[n 9 ! foll[+ sub/ances3 ,= ! rabbit ! m9imum fatal dose p] kilo ( qu99 hydrobromid is #a4e grams adm9i/]$ by m\?1 #j4e gram :5 inject$ subcutane\sly1 & #j4jg gram by ! intrav5\s pa?1 :ile /ry*n9 sulphate is twice z toxic adm9i/]$ intrav5\sly z subcutane\sly1 & six times z toxic z :5 adm9i/]$ by m\?4 ,! mode ( introduction1 h[ev]1 does n always affect ! toxicity ( a sub/ance4 ,?is is made evid5t by ! action ( /ry*n9 on frogs 9 :i*1 accord+ to ,maurel7#ef71 ! toxic dose is ! same :e!r giv5 by m\? or inject$ into ! subcutane\s tissues4 ,?is appe>s to hold true also = o!r animals z demon/rat$ by ! exp]im5ts ( ,hat*]7#ce7 on ! cat1 9 :i* he obs]v$ t /ry*n9 is z readily absorb$ f a full /oma* z f ! subcutane\s tissues4 ,^! f9d+s are extremely int]e/+1 especially 9 view ( ,maurel's7#eg7 "w on ! subject1 accord+ to :i* he f9ds t a sub/ance is mu* less toxic :5 giv5 by m\? ?an :5 adm9i/]$ by hypod]mic injection or intrav5\sly4 ,t ?is g5]alization does n admit1 h[ev]1 ( univ]sal application is made evid5t by ! "w ( v>i\s exp]im5t]s4 ,claude ,b]n>d7#aj7 obs]v$ t cur>a is z poison\s = ! pigeon :5 giv5 by m\? z :5 inject$ subcutane\sly1 :ile ,zalesky7#hf7 f\nd t sam&>9 is m toxic = frogs :5 introduc$ into ! /oma* ?an by injection into ! lymph sacs4 ,our exp]im5ts ) caffe9 likewise %[ t ,maurel's g5]alization does n always hold good1 s9ce x 0 f\nd 9 exp]im5ts ) gray rabbits t ! m9imum fatal dose is b mod]ately great] by m\? ?an by ! subcutane\s pa?4 ,equally int]e/+ is ! obs]vation ( ! writ]1 t 9 ! gu9ea pig ! diff]5ce 9 ! toxicity betwe5 ! subcutane\s & intrap]itoneal injections is v slight1 :ile 9 ! cat ! toxicity ( caffe9 is ! same :e!r giv5 by m\? or inject$ into ! subcutane\s tissues1 & is m>k$ly less :5 inject$ into ! p]itoneal cavity4 ,! exp]im5ts on dogs %[ consid]able v>iation ( effective dose :5 giv5 by m\?1 b ! int]e/+ obs]vation 0 made t ! toxic dose by m\? may be small] 9 "s cases ?an ! av]age dose by subcutane\s injection4 ,if ! resi/ance to caffe9 by subcutane\s injection ( ! diff]5t species ( animals exp]im5t$ ^u 9 ! pres5t rese>* be comp>$1 x w be notic$ t ! gray rabbit or ,belgian h>e1 :i* is m resi/ant ?an ! o!r v>ieties employ$1 /&s m caffe9 9 proportion to ! weight ( ! body ?an ! o!r animals4 ,al?\gh ! m9imum fatal dose 0 f\nd to be some:at l>g] = ! gu9ea pig ?an = ! gray rabbit :5 caffe9 0 inject$ intrap]itoneally1 x 0 on ! contr>y small] by o!r pa?s ( introduction1 & approximat$ q closely ! m9imum fatal dose = rabbits ( ! o!r v>ieties4 ,cats z well z dogs 7 f\nd to be di/9ctly less resi/ant to caffe9 ?an ! h]bivora4 ,!re are a numb] ( factors f> m important ?an zoological diff]5ces :i* influ5ce ! toxicity ( caffe94 ,"s ( ^! are age1 season1 & pa?ologic conditions4 ,z ^! factors h already be5 dwelt ^u 9 _! appropriate places1 fur!r discussion might seem unnecess>y1 b ow+ to _! importance 9 det]m9+ ! action ( a drug1 emphasis is desirable4 ,especially is ?is ! case ) pa?ological conditions 9 relation to toxicity4 ,:ile no positive pro( ( dim9i%$ resi/ance to caffe9 9 pa?ological conditions 0 obta9$ by subject+ ! sugge/ion to exp]im5tal te/1 x 0 obs]v$ 9 ^! exp]im5ts on rabbits t dea? occurr$ 9 "s individuals aft] small doses :i* are usually n ev5 toxic4 ,! f9d+s at autopsy indicate ! pres5ce ( pa?ological conditions4 ,! same 0 obs]v$ 9 "s exp]im5ts on cats & dogs4 ,x is extremely probable1 !re=e1 t disease modifies ! reaction ( ! organism to caffe9 z well z to o!r drugs47#gh7 ,t ! resi/ance to drugs may v>y accord+ to ! age ( ! subject has be5 ma9ta9$ by a numb] ( ph>macologi/s4 ,accord+ to ,gu9>d17#cj7 "y dogs1 rabbits1 & gu9ea pigs are v susceptible to morph91 resembl+ *ildr5 9 ?is reg>d4,e ,! m9imum fatal dose = ^! animals is ab\t "o-?ird less ?an = ! adult4 ,?is is n true1 h[ev]1 = ! "y ( o!r species4 ,cats "u #ae days ( age tol]ate twice ! toxic dose ( morph9 = ! adult cat4 ,"y beeves & goats are likewise m resi/ant to ?is alkaloid ?an adults4 ,on ! o!r h&1 accord+ to ,livon17#ed7 "y gu9ea pigs are m s5sitive to alkaloids ?an adults4 ,! toxicity ( caffe91 z %[n 9 ! pres5t inve/igation1 0 f\nd to be less 9 ! "y ?an 9 ! adult4 ,9 dogs ! "y subjects are 9 "s in/ances almo/ twice z resi/ant z adults4 ,! diff]5ce 0 f\nd to be less 9 cats & rabbits ?an 9 dogs1 b x 0 q m>k$4 ,e ,a case ( accid5tal poison+ report$ rec5tly by ,wi*ura 7,mni*4 ,md4 ,wo*41 #aiaa1 ,no4 #cj1 p4 #afah7 ?r[s "s d\bt on ! accept$ view t ! susceptibility ( "y *ildr5 to morph9 is great] ?an t ( adults4 ,wi*ura also f\nd t ! !rapeutic doses ( code9 prep>ations ord9>ily recomm5d$ = *ildr5 9 pleuritic c\gh are n effective 9 ?is condition4 ,! effect ( season on ! toxicity ( drugs has be5 discuss$ 9 ! section on ! exp]im5ts on gu9ea pigs1 :i* 7 m resi/ant to caffe9 9 ! fall ?an 9 ,febru>y & ,m>*4 ,! effect ( season seems to v>y ) ! animal1 b x may also diff] ) ! sub/ance employ$4 ,9 ,noe's7#fe7 /udies on ?is subject can?>id9 0 f\nd to be m toxic = ! h$gehog 9 ,novemb] ?an 9 ,july4 ,! effect ( season 0 diff]5t = morph91 z x 0 obs]v$ t ! resi/ance ( ! h$gehog 0 great] at ! end ( ! summ] ?an e>li] 9 ! season4 ,! relation ( diet to toxicity ( drugs has be5 /udi$ by ,hunt47#ci7 ,8 exp]im5ts indicate t ?is is an important factor 9 ! resi/ance to acetonitril4 ,! /udies "h report$ on ! effect ( diet on toxicity ( caffe9 9 rabbits 7 conf9$ to exp]im5ts ) oats & c>rots & d n %[ any modification ( ! resi/ance to caffe94 ,! "q ( diet 9 *ronic intoxication 9 dogs1 h[ev]1 sugge/s t 9 ^! animals diet may affect ! toxicity ( caffe91 al?\gh ! data on ?is subject are f> f satisfactory4 ,!re is nev]!less suffici5t evid5ce to sugge/ t a high prote9 diet = ! adult dog t5ds to great] resi/ance ( ! animal to caffe9 & simil>ly ! gr[+ dog tol]ates l>g] quantities ( caffe9 on a milk diet ?an on a diet ( meat4 ,?is br+s u to a consid]ation ( ! behavior ( caffe9 9 *ronic intoxication4 ,al?\gh 9 bo? rabbits & dogs abs5ce ( cumulation 0 evid5t1 9 o!r respects decid$ diff]5ces 9 ! resi/ance to caffe9 7 obs]v$4 ,:ile ! rabbit tol]ates m ?an twice ! s+le dose ( caffe9 p] kilo = ! dog1 ! result is q diff]5t 9 repeat$ dosage ( ! drug1 ! rabbit succumb+ to cont9u$ adm9i/ration ( mu* small] doses ( ! drug ?an ! dog4 ,?is is probably due to lesions ( ! ga/ro-inte/9al canal caus$ by caffe9 :i* occasions loss ( appetite mu* m readily 9 ! rabbit ?an 9 ! dog4 ,! abundant en]gy res]ve 9 ! dog makes x possible = ?is animal to /& inanition mu* long] ?an ! rabbit & o!r h]bivora4 ,! diff]5ce 9 ! behavior ( ! rabbit & dog t[>d caffe9 is int]e/+ z %[+ complete rev]sal ( resi/ance 9 acute & *ronic intoxication4 ,f ! /atem5t 9 ! introduction x is evid5t t ! size ( ! s+le toxic or le?al dose ( a sub/ance is 9 no wise an index ( ! active degree ( its toxicity4 ,! exp]im5ts ) caffe9 "h report$ furni% additional evid5ce t ?is is true1 at lea/ = ! rabbit4 ,,g5]al ,,summ>y ,,& ,,conclusions4 ,! toxicity ( caffe9 9 ! rabbit v>ies ) ! mode ( its adm9i/ration1 be+ lea/ :5 giv5 by m\? & greate/ by intrav5\s adm9i/ration4 ,! toxicity is f #ae to #bj p] c5t great] by subcutane\s injections ?an by m\?1 b is ab\t half ( t :5 inject$ into ! p]itoneal cavity4 ,no diff]5ce 0 obs]v$ 9 ! toxicity ( caffe9 :e!r adm9i/]$ into gluteal or into ! lumb> muscles4 ,:5 introduc$ by ?is r\te ! toxicity 0 f\nd to be less by "o-?ird ?an :5 x is inject$ into ! p]itoneal cavity1 b is ab\t #cj p] c5t m toxic ?an ! subcutane\s injections4 ,:ite or black rabbits 7 f\nd to be less resi/ant to caffe9 ?an gray rabbits4 ,! resi/ance ( ! gu9ea pig to caffe91 z ( ! rabbit1 is greate/ :5 giv5 by m\?4 ,! m9imum fatal dose is less by intrap]itoneal injections1 b great] ?an by subcutane\s injections1 ?us diff]+ f ! rabbit 9 ?is reg>d4 ,! adult cat is less resi/ant ?an ! gu9ea pig or rabbit to caffe94 ,! m9imum le?al dose by m\? is ! same z by subcutane\s1 & is less ?an by intrap]itoneal1 injection4 ,! m9imum fatal dose = dogs 0 f\nd to be ! same by m\? z by subcutane\s injection & is almo/ ! same z = ! cat4 ,! toxicity ( caffe9 v>ies 9 ! gu9ea pig accord+ to season ( ! ye>4 ,age is likewise a factor 9 ! toxicity ( caffe91 "y animals be+ m resi/ant ?an ! full-gr[n & old] animals2 ?is 0 %[n 9 exp]im5ts on rabbits1 cats1 & dogs4 ,! symptoms ( caffe9 poison+ also 7 diff]5t 9 puppies & 9 full-gr[n dogs4 ,diff]5t diets1 su* z c>rots & oats1 did n influ5ce ! resi/ance ( rabbits & gu9ea pigs to caffe94 ,l[ prote9 diet t5ds to decrease resi/ance to caffe9 9 dogs4 ,"y gr[+ dogs are less resi/ant to caffe9 on a meat ?an on a milk diet4 ,caffe9 is n cumulative 9 ! rabbit or dog1 ev5 if adm9i/]$ = a consid]able l5g? ( "t4 ,"s degree ( tol]ance may be induc$ 9 ! rabbit "u c]ta9 conditions1 b n 9 dogs "u ! conditions ( ! exp]im5ts made 9 ?is inve/igation4 ,! possibility1 h[ev]1 t dogs may acquire tol]ance = caffe9 is n exclud$4 ,al?\gh ! rabbit tol]ates a mu* l>g] s+le dose ( caffe9 ?an ! dog1 x 0 f\nd1 9 exp]im5ts on *ronic intoxication t ! rabbit is less resi/ant to caffe9 ?an ! dog4 ,! toxicity ( caffe9 is probably increas$ "u pa?ological conditions1 s9ce comp>atively small] doses 7 fatal to rabbits1 cats1 & dogs1 :5 m>k$ lesions n due to caffe9 7 f\nd at autopsy4 ,glycosuria 0 obs]v$ 9 rabbits1 gu9ea pigs1 & cats :5 caffe9 0 giv5 9 suffici5t am\nts4 ,,table #ah4--;,acute caffe9 intoxication3 ,table %[+ av]age m9imum toxic & m9imum fatal doses = adult animals4 ,table head+s3 ,,sc3 ,subcutane\sly4 ,,bm3 ,by m\?4 ,,ip3 ,intrap]itoneally4 ,,im3 ,intramuscul>4 ,,iv3 ,intrav5\s4 ---------------------------------------- ---------------------------- ,effect ,dose p] kilo 7grams7 ,animal4 ( ---------------------------------------- ----- dose4 ,,sc ,,bm ,,ip ,,im ,,iv ---------------------------------------- ------------------------ ,rabbit1 gray ,toxic #j4ae #j4cbe #j4ajj #j4ac #j4je -#j4abe -#j4ae ,fatal 4#cj 4#cej 4#aej 4#bj #j4aj -4#af ,rabbit1 :ite,toxic or black ,fatal 4#bj 4#bij ,gu9ea pig ,toxic#j4ae- 4#af 4#aej 4#bjj ,fatal 4#bj- 4#bdj4bhj- 4#cjj 4#bdj- 4#bej ,cat ,toxic 4#ab- 4#ad 4#abe 4#abe- 4#aej ,fatal 4#ae 4#aej 4#ahj- 4#bjj ,dog ,toxic 4#ajj- 4#abj ,fatal 4#ae- 4#af 4#adj- 4#aej ---------------------------------------- ------------------------ ,,note4--,! doses giv5 9 ?is table are approximate4 ,,caffe9 ,,bibliography4 #a4 ,,abd]hald5 & ,,brahm4 ,zts4 ,physiol4 ,*em41 #aiji1 #fb3 #acc4 #b4 ,,alb]s4 ,deut4 ,kl941 #aheb1 #e3 #egg4 #c4 ,,amat4 ,diss4 ,p>is1 #ahhi4 #d4 ,,amory4 ,bo/on ,m$4 ,surg4 ,j41 #ahfh1 #a3 #bfa4 #e4 ,,von ,,anrep4 ,ar*4 ,ges4 ,phys41 #ahhj1 #ba3 #ahe4 #f4 ,,aub]t4 ,pflg]'s ,ar*41 #ahgb1 #e3 #ehi4 #g4 ,,au] & ,,meltz]4 ,j4 ,ph>m4 ,exp]4 ,!r41 #aiaa1 #b3 #djb4 #h4 ,,baldi4 ,t]apia ,mod]na1 #ahia1 #e3 #fag4 #i4 ,,b5nett4 ,brit4 ,m$4 ,j41 #ahgd1 #b3 #fgd4 #aj4 ,,b]n>d1 ,,claude4 ,leons sur les sub/ances toxiques1 ,p>is1 #aheg1 p4 #bib4 #aa4 ,,b9z4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #ahgh1 #i3 #ca4 #ab4 ---- ,ibid41 #ahia1 #bh3 #aig4 #ac4 ,,brill4 ,diss4 ,m>burg1 #ahfa4 #ad4 ,,bu*heim & ,,eis5m5g]4 ,beitr4 ,anat4 ,physiol41 #ahgj1 #e3 #aae4 #ae4 ,,bunge & ,,s*mi$eb]g4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #ahgf1 #f3 #bcc4 #af4 ,,*itt5d54 ,! ,nutrition ( ,man1 #aijg4 #ag4 ,,cogswell4 ,lancet 7,london71 #aheb1 #b3 #dhh4 #ah4 ,,danilewski4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #ahid1 #ce3 #aje4 #ai4 ,,drzew9a4 ,compt4 r5d4 ,soc4 biol41 #aiaa1 #gj3 #ggb4 #bj4 ,,dumas & ,,pelleti]4 ,ann4 *im4 phys41 #ahbc1 #bd3 #ahb4 #ba4 ,,edmunds4 ,j4 ,am]4 ,m$4 ,assoc41 #aijg1 #dh3 #agdd4 #bb4 ,,filehne4 ,ar*4 ,phys41 #ahhf1 p4 #gb4 #bc4 ,,fleis*] & ,,loeb4 ,ar*ives ( ,int]nal ,m$ic9e1 #aiji1 #c3 #gh4 #bd4 ,,focke4 ,ar*4 ,ph>m41 #aijc1 #bda3 #fgh4 #be4 ,,fr]i*s4 ,h&wrt]bu* ,phys41 #ahdf1 #c3 #gba4 #bf4 ,,fr,,hn]4 ,monats4 prakt4 ,ti]h41 #ahib1 #c3 #ebi4 #bg4 ,,g5tilhomme4 ,bull4 ,soc4 ,m$4 ,reims1 #ahfg1 #e3 #ic4 #bh4 ,,g\rewit*4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #aijg1 #eg3 #cad4 #bi4 ,,gu9>d4 ,compt4 r5d4 ,soc4 biol41 #aijj1 #b 7#b;d s]473 #gbg4 #cj4 ----4 ,compt4 r5d41 #ahic1 #aac3 #ebj4 #ca4 ----4 ,la ,morph9e et l'apomorph9e1 ,p>is1 #aijc4 #cb4 ,,gunn4 ,ar*4 ,int4 ,ph>m4 ,!r41 #aiji1 #ai3 #cai4 #cc4 ,,hale4 ,u4 ,s4 ,public ,heal? & ,m>9e-,hospital ,s]vice4 ,hyg4 ,lab4 ,bul4 #ec1 p4 #dc4 #cd4 ,,h>r+ton4 ,am]4 ,j4 ,phys41 #ahih1 #a3 #che4 #ce4 ,,hat*]4 ,j4 ,am]4 ,m$4 ,assoc41 #aiaj1 #fj3 #gdf4 #cf4 ,,h5neguy4 ,diss4 ,montpelli]1 #ahge4 #cg4 ,,h(mei/]4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #ahid1 #cc3 #aih4 #ch4 ,,hoppe4 *o ,md4 ,neu*tel1 #aheh4 #ci4 ,,hunt4 ,u4 ,s4 ,public ,heal? & ,m>9e-,hospital ,s]vice4 ,hyg4 ,lab4 ,bul4 #fi1 p4 #ea4 #dj4 ----4 ,ibid41 ,bul4 #cc4 #da4 ,,ig]%eim] & ,,/ami4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #aiji1 #fa3 #ah4 #db4 ,,jacobi & ,,gol[9ski4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 ,supplem5t ,bd4 #aijh1 p4 #bhf4 #dc4 ,,job/4 ,ann4 ,ph>m41 #ahch1 #be3 #fc4 #dd4 ,,johans54 ,diss4 ,dorpat1 #ahfi4 #de4 ,,kob]t4 ,lehrbu* d] ,intoxication51 #aijb1 #a3 #bd4 #df4 ,k,,/]4 ,ar*4 ,gesamt4 ,phys41 #aiaj1 #acf3 #ag4 #dg4 ,,kr,,g] & ,,s*midt4 ,b]4 d4 *em4 ,ges41 #ahii1 #cb3 #bfgg4 #dh4 ,,kurzak4 ,zts4 ,a]zte zu ,wi51 #ahfj1 n4 f41 #c3 #fbe4 #di4 ,,lapicque4 ,compt4 r5d4 ,soc4 biol41 #aiaj1 #fh3 #ajjg4 #ej4 ,,leblond4 ,diss4 ,p>is1 #ahhc4 #ea4 ,,lehmann1 ,c4 ,g4 ,lehrbu* fr physiolis*e ,*emie1 #ahdb1 #a3 #ccf4 #eb4 ,,lehmann1 ,j4 ,ann4 *im4 ph>m41 #ahec1 #hg3 #bje4 #ec4 ,,lev54 ,ar*4 ,phys41 #ahfh1 #a3 #ahj4 #ed4 ,,livon4 ,compt4 r5d4 ,soc4 biol41 #ahig1 #d3 #igi4 #ee4 ,,maurel4 ,compt4 r5d4 ,soc4 biol41 #aijg1 #fb3 #hig4 #ef4 -----4 ,ibid41 #aiji1 #ff3 #ghb4 #eg4 -----4 ,ibid41 #aiaj1 #fi3 #e4 #eh4 ,,meltz] & ,,au]4 ,j4 ,exp]4 ,m$41 #aije1 #g3 #ei4 #ei4 ,,mit*ell4 ,j4 ,phys41 #ahfb1 #e3 #aji4 #fj4 ,,mits*]li*4 ,diss4 ,b]l91 #ahei4 #fa4 ,,mos*k[its*4 ,ar*4 ,ph>m41 #aijc1 #bda3 #ceh4 #fb4 ,,muld]4 ,j4 prakt4 ,*em41 #ahch1 #ae3 #bhj4 #fc4 ----4 ,pogg5dorff's ,ann4 ,physik ,*em41 #ahch1 #dc3 #ahj4 #fd4 ,,neubau]4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #aija1 #df3 #acc4 #fe4 ,,noe4 ,ar*4 ,int4 ,ph>m4 ,!r41 #aijd1 #ab3 #afj4 #ff4 ,,oph,,ls4 ,proc4 ,soc4 exp]4 biol4 m$41 #aiaa1 #h3 #ge4 #fg4 ,,oudry4 ,n\velle ,biblio!k ,mdicale1 #ahbg2 ,geig]'s ,magaz9 ,ph>m41 #ahbg1 #ai3 #di4 #fh4 ,,p>isot4 ,diss4 ,p>is1 #ahij4 #fi4 ,,pelleti]4 ,j4 ,ph>m41 #ahbf1 #ab3 #bbi2 also quot$ by ,brill1 #c4 #gj4 ,,p]etti4 ,diss4 ,bonn1 #ahge4 #ga4 ,,pfaff4 ,s*weigg]-,seidel1 #ahca1 #a3 #hg4 #gb4 ,,pfaff & ,,liebig4 ,ann4 ,ph>m41 #ahcb1 #a3 #ag4 #gc4 ,,pohl4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 ,suppl4 ,bd41 #aijh1 p4 #dbg4 #gd4 ,,pratt4 ,bo/on ,m$4 ,surg4 ,j41 #ahfh1 #b3 #hb4 #ge4 ,,robiquet4 ,dict4 ,te*41 ,p>is1 #ahbc1 #d3 #ei4 #gf4 ,,ro/4 ,diss4 ,heidelb]g1 #ahie4 #gg4 ,,runge4 ,neu/e phyto-*em4 ,entdeckung51 ,breslau1 #ahbj4 #gh4 ,,salant4 ,u4 ,s4 ,dept4 ,agr41 ,bureau ( ,*emi/ry ,cir4 #ha4 #gi4 ,,s*mi$eb]g & ,,bunge4 ,ar*4 ,exp]4 ,pa?4 ,ph>m41 #ahgd1 #b3 #fb4 #hj4 -----4 ,ibid41 #aiaj1 #fb3 #bif4 #ha4 ,,sollman & ,,br[n4 ,j4 ,am]4 ,m$4 ,assoc41 #aije1 #de3 #bbi4 #hb4 ,,/reck]4 ,ann4 ,*em4 ,ph>m41 #ahfa1 #aah3 #aea #hc4 ,,/uhlmann & ,,falck4 ,ar*4 pa?4 ,anat4 ,phys41 #aheg1 #aa3 #cbd4 #hd4 ,,?i]feld] & ,,von ,,m]+4 ,zts4 physiol4 ,*em41 #ahhe1 #i3 #eaa4 #he4 ,,voit4 ,unt]su*4 b] d5 ,e9fluss des ,ko*salzes1 des ,kaffes ,mn*51 #ahfj4 #hf4 ,,zalesky4 ,hoppe-,seyl] ,m$4 ,*em4 ,unt]su*41 ,b]l91 #ahff1 #he-aaf4 99 99 99 99 99 ,transcrib]'s ,notes ,obvi\s typographical errors h be5 correct$1 b v>iations 9 spell+1 punctuation & hyph5ation h be5 reta9$4 ,rabbit #cif4 ,! date ,augu/ #ae has be5 correct$ to ,augu/ #ai4 ,! data = ,rabbit #abc is pres5t$ z pr9t$ 9 ! orig9al1 al?\gh x is likely t ! ,caffe9 p] kilo4 values %\ld be prec$$ by a decimal po9t 7or t ! head+ %\ld be ,mg474 ,/&>d footnotes are id5ti$ alphabetically ?us ,a4 ,notes to ! tables are plac$ directly "u ! tables & id5tifi$ num]ically ?us 7#a74 ,num]ic ref]5ces )9 ! text ref] to ! bibliography4 ,! head+s ( ,table #ah h be5 abbreviat$ = cl>ity on small scre5s4 ,italics are %[n ?us italic & bold ?us bold4