5feui fork Bms QJoUege of JKgnculture At OforttcU IniuErsttH Stljata, a. % Utbtracii Cornell University Library "Sllfinillflllllllill^i?'''' """^ '" ""^ laboratory 3 1924 003 361 288' Cornell University Library The original of tiiis book is in tine Cornell University Library. There are no known copyright restrictions in the United States on the use of the text. http://www.archive.org/details/cu31924003361288 Ooznnltmi'ntii of PIERRE A. FISH ABSTRACTS OF WORK DONE IN THE LABORATORY OF VETERINARY PHYSIOLOGY AND . . . .PHARMACOLOGY .... UNDEF* THE DIRECTION OF P. A. FISH NO. 1 NEW YORK STATE VETERINARY COLLEGE CORNELL UNIVERSITY ITHACA, N.Y. 1904 o o c o U Z TABI.E OF CONTENTS PAGES Prefatory Note i Department Courses 1-3 Echinacea in Veterinary Practice — P. A. Fish i-ii The Digestive Action of Bile in some Domestic Animals — O. P. Johnston 1-17 Calcium Sulphide in' the Treatment of Poll-Evil and Fistu- lous Withers — B. R. Wilbur 1-6 The Effects of Certain Drugs upon Blood Pressure and Car- diac Inhibition in the Horse — P. A. Fish 1-16 PREFATORY NOTE. As indicated by the title of this pamphlet, it is proposed to publish abstracts of the longer scientific articles written in this de- partment. Short articles will be published entire. In certain cases reprints of articles published in other journals are included ; but other papers will appear here for the first time. Such a collection, annually in a single pamphlet, it is believed will present certain advantages from the standpoint of the depart- ment, in that some record of all the work will be available in a compact and convenient form. It is also planned to publish short articles on methods, tests and technique, bearing upon physiologic and pharmacologic work. Such articles have a value of their own ; but at the present time, unfortunately, in this country there is a dearth or complete absence of journals where such work may be presented. Finally the department desires to keep in touch with its alumni and others interested in its work, and to this end invites suggestions. May I, 1904. , P. A. F. DEPARTMENT COURSES PHYSIOLOGY P. A. Fish, Professor H. J. Milks, Assistant W. B. Mack, Assistant It is the aim of this department to select from a wide field of im- portant topics, those which will be of greater use to the student, in comprehending the vital processes of the animal body. Without a complete understanding of the normal functions, it is obviously useless to attempt progress in the proper conception of diseased conditions. The proper correlation of work in the laboratory, recitation and lecture room, it is believed will afford to the student a more compre- hensive grasp and understanding of the perspective and symmetry of a subject than can otherwise be obtained. The lectures are illustrated with lantern slides, charts, histological preparations, dissections and practical demonstrations relative to the subject under discussion.' The department has a good library of modern elementary and advanced text books on physiology and students are urged to make the fullest use of it in connection with the lecture and laboratory courses. The laboratory is located on the second floor of the Veterinary College. It is well lighted and ventilated and equipped with new apparatus. The equipment includes kymographs, induction coils, sphygmographs, cardiographs, circulation schemas, tambours, cen- trifuges, microscopes, and other apparatus for complete and satisfactory work. Every encouragement is offered, to those properly fitted, to pur- sue their work beyond that given in the regular course. Courses 20. Physiologry Recitations. — Two hours weekly. First Term. Two sections. Section I, M., 9, T., 10. Section II, T., 11, W., 10. Drs. Fish, Milks and Mack. 20. a. Physiology Recitations. — One hour weekly. Second term. Two sections. S. 10, 11. Drs. Fish, Muks and Mack. 21. Physiology Lectures. — Three hours weekly. Second term. T., Th., F., 10. Dr. Fish. 22. Pliysiolog'ical Laboratory. — A portion of the course is devoted to chemical physiology- Artificial dixestive juices are tested upon the various kinds of foodstuffs by the stu- dents and careful notes kept of the various changes. Milk, Bile and Blood are also studied includinj; a spectroscopic ex- amination of the latter. \ large proportion of the work is devoted to a study of the phenomena as.sociated with the circulatory, respiratory, muscular and nervous systems. Students are to obtain and preserve graphic records of these phenomena, whenever possible. Certain experiments requir- ing special apparatus and care are performed by the instruct- ors, as demonstrations, students assisting when possible. Five hours each week, .second term. Section I, T. n-i, W. 2-5. Section II, Th,, 11 -i, b'. 8-10, 71-12. Dr.s. Fish, Milks anrl Mack. 23. Course in Urine Analysis. — I^aboratory work tlevoted to the comparative .study of urine. Examinations are maile of human urine and that of the domestic animals, especially the horse. In addition to the chemical examination some time will be devoted to a microscopic study of urinarj' deposits. So far as possible each student is expected to prepare and preserve a series of "typical slides." Five hours weekly, first term. W. , lo-j, S. , 11 -I, September-December. Drs. Fish, Milks and .Mack. 24. Research and Thesis. — 7 U' hours per week throughout the year. This course includes advanced work, independent of the thesis and reports of progress are given at the department seminary every fortnight. Drs. F'isH, Milks and Mack. PHARMACOLOGY P. \. Fish, Professor H. J. Milks, Assistant W. B. Mack, Assistant The term is employed in its comprehensive meaning to include not only the materials of medicine, but their preparation, use and physiological action, .-allowing for certain exceptional differences, there is, in general, a resemblance in the action of drugs in the lower animals and in human beings. The clinics furnish abundant material for the use of medicines and the study of their actions. The physiological changes in certain tissues resulting from the toxic doses of many drugs is as yet unknown, and opportunities for research are abundant in this field. 25. Pharmacology.~A study of the actions and uses of the various drugs and their preparation. A varied collection of the crude drugs and their official preparations is available and exam- ined at the lectures. The course is conducted in the form of lectures with short weekly examinations. First term. Th. , F. , lo. Dr. Fish. 26. Materia Medica and Pharmacy Laboratory. — The work in this course consists of the study of a selected group of inor- ganic drugs ; the study of certain crude organic drugs and their official preparations; in making pharmaceutical prepara- tions, such as syrups, emulsions, spirits, liniments, tinctures, fluid extracts, extracts, ointments, pills and others. Some exercises will also be devoted to the study of the direct physiological action of a few selected drugs upon some of the lower animals. In their study the students are required to write concise notes of the physiological action of the drugs examined and to make tests of their incompatibility. In addition to this each student will have practical experience in writing and compounding prescriptions. The importance of a discrim- inating and accurate system for dispensing medicines is thor- oughly emphasized. Five hours each week. First term. vSect. I, W., 2-5, Th., ii-i. Sect. II, M., lo-i, Tu., lo-i. Drs. Fish, Mii" marked changes in the respiration, pulse nor temperature. The lowest number of respira- tions recorded were 8, the highest i8 ; the lowest pulse record was 38, the highest 56 ; the lowest temperature was gfi.4.'''', and the highest 101.8^"'. These variations were due not merel>- to the dosage, but in part at least to a variation in the condition of the animal as a result of the disease. It was observed that no digestive disturbances appeared as a result of the large doses, which seems to be contrary to the experience in human medicine. Cases two, three and four were of a similar character, except that they received a uniform dosage of fifteen grains of calcium sul- phide three times a day. Case three was a cow and was discharged after twenty-three days, but later on was returned for further treat- ment. Cases two and four were horses and were under observation for thirty-seven and thirty-three days respectively. Potassium iodide was also given internally. In both of these cases it was found that the pus had burrowed a second time after the treatment had begun. Ca.ses five to eleven inclusive were not diseased but were used solely for experimental dosage. Three of the horses received one drachm doses of the sulphide three times daily. In one of them the temperature and pulse increased slightly above normal ; in the other two the temperature and pulse were slightly decreased. In another horse receiving one drachm once a day there was a slight rise in temperature and pulse ; but in another horse receiving a half-drachm dose once daily there was a slight decrease. The two remaining horses in this series received five and fifteen grain doses respectively of the sulphide once daily. The temperature, pulse and respiration remaining within normal limits. Although an in- crease and decrease is referred to above, the variations from normal were verj' slight. Case twelve was a sorrel mare weighing about looo pounds. This case was purely experimental, the aim being to produce the disea.se and begin treatment early in the course. vSome pus was col- lected from a patient suffering from poll-evil. Bouillon cultures were made from the pus and 3.5 c.c. of a one-day old culture were inoculated over the region of the poll of the mare, but a little to one side of the median line. Due antiseptic precautions were taken in collecting the pus and making the inoculation. The day after the inoculation a large tender swelling appeared at the point of inocu- lation. The mare's appetite declined and the swelling increa.sed in size. The neck became somewhat stiffened and there was evidence of increasing tenderness over the poll. Six days after the inocula- tion five grain doses of the calcium sulphide were given twice daily. The swelling remained at about the same size but there was evi- dence of less soreness and the patient ate freely. After five days the dose was raised to ten grains twice dailj' and three days later fifteen grain doses were given. There was less stiffness of the neck and no increase in the size of the swelling, although it was still quite sore. Sixteen days after the inoculation, a thin watery fluid was discharged from the swelling and a day later a thick creamy pus appeared. On examination it was found that nearly the entire surface of the swelling was necrotic and the hair upon this surface was loose and easily removed. The mare was confined in the stocks and the abcess freely opened, discharging a half pint of pus. On probing, a fistula was revealed running down the side of the neck, for a distance of five or six inches. The silver probe used in exploring the abscess became considerably blackened, indicating the presence of sulphuretted hydrogen from the calcium sulphide which had been administered. As much pus and necrotic tissue as possible were removed in- volving a total area of six or eight square inches. A ring of hair, one or two inches in width, was removed around this area, the hair coming out quite easily. After securing efficient drainage the wound was carefully disinfected and dressed with a pack soaked in a solution of lysol. Subsequent dressings consisted of injections and washings with a solution of echafolta. Internal treatment with calcium sulphide was kept up and in two weeks recovery was complete. During treatment the lowest pulse was 40 and the high- est 60. The lowest temperature was 99^ and the highest 103°. Case thirteen was a control of the previous case. This subject was inocculated with the same amount of bouillon culture as case twelve. The swelling appeared the next day and the general symp- toms coincided clo.sely with those of the previous case. After two weeks the subject was killed and about half a pint of partly in- spissated pus was obtained from the abscess. In neither of these two cases was the ligamentum nuchte involved. Case thirteen re- ceived no treatment whatever. At the time of killing there was no indication of pointing in the abscess and the pus was less fluid than in number twelve. The inference is that the calcium sulphide, in the previous case,, hastened the ripening of the abscess (which was discharging after sixteen days) and stimulated the healing process. Cases fourteen, fifteen, sixteen and seventeen were regular patients at the clinic and received ten grain doses of calcium sulphide twice daily, except number irfteen, which received a twenty grain dose once a day. This patient also received potas- sium iodide internally. Two of these cases had received previous treatment outside of the clinic, without success, but yielded readily to the combined local and internal treatment. Case seventeen was under observation one week, but was sent home before complete recovery with directions to the owner as to proper treatment. This was not carried out and the patient was returned later in poor con- dition and with new pockets of pus forming. The calcium sulphide had been administered but the local treatment had been neglected. This case is cited to emphasize the desirability of maintaining good local treatment. The evidence is that the quickest results may be obtained by the proper combination of the two. As a summary of the observations taken during this work it would appear: i. Doses of calcium sulphide larger than ten or fifteen grains twice daily tend to increase the discharge and per- haps hinder the healing process. 2. Large doses disturb the tem- perature and pulse. 3, Large doses, even as high as two ounces daily, do not appear to cause derangement of the digestive system in the horse. 4. Calcium sulphide locally applied increases the discharge. 5. The best effects are obtained when calcium sulphide is used without the administration of other drugs. 6. The admin- istration of small doses of the sulphide (10 grains) appears to les- sen the discharge and prevent the burrowing of the pus, 7. Good local treatment is essential, by freely opening the fistulse and keep- ing the wound thoroughh^ disinfected. 8. A convenient method to administer the drug is in gelatin capsules of the proper size. These protect the drug from the air and will be readily taken by the horse when given with moistened feed. g. It is best not to administer the drug until the fever caused by the operation has subsided. 10. The patients do not appear to lose condition during the treatment, but tend to increase in ffesh. 11. Without a good quality of the drug, no good results can be obtained. Calcium sulphide rapidly loses its properties when exposed to the air. Acknowledgments for advice and suggestions are due to Drs. Fish, Law, Williams and Hopkins. THE EFFECT OF CERTAIN DRUGS UPON BLOOD PRESSURE AND CARDIAC INHIBITION IN THE HORSE. PIIOKRK A. FISH, ITHACA, N, Y. The more a man knows of his tools, the better qualified is he for his work. This truism ajjplies with peculiar force to all who ])rescribe medicines. Drugs are the tools with which the ])hysician works to assist nature in overcoming abnormal conditions in the organism. Massed personal experience and clinical evidence or therajjeutics stand high in determining the value of the use of ])articular drugs for certain pathologic con- ditions. Pharmacology endeavors to supply detailed facts C(;ncerning the ]j]iysiologic action of drugs, and aims to sup- ])lement clinical observations with reliable data. In the following exijeriments the usual apparatus for blood ])ressure demonstrations was em]doyed. In all cases the caro- tid artery was connected with a mercury manometer, the flfjater of which wrote its record u])0n a cylinder revolving at a unif(jrm speed. Data have been obtained from sixteen horses, two cows, one calf, one cat and. a number of dogs; the special purpose being to note the effects (jf drugs upon the rate and force of the heart and its susceptibility to inhibitory stimuli trans- mitted through the vagus nerve. In nearly all cases the drugs were administered intravenously, the jugular vein being util- ized in the larger and the femoral vein in the smaller animals. Chlor(jf(jrm anaesthesia was employed for the horses, cows and calf; m(jr])hine or cliloretone with ether or chloroform for the dogs and cats. In general an increase in the amount of blood pressure is due to an increased force or activity of the heart-beat, or an increased resistance or constriction oi the jjeripheral blood vessels: the o])i)o.site conditions with regard to the heart and peripheral vessels cause a diminislied ])ressure. Effect of Drugs Upon iiiooa rrcssiirc. Inhibition means a diminution in the frequency of the heart-beat, or complete standstill — the heart remaning in di- astole — according to the strength of the stimulus sent into the lieart through the inhibitor}- fibers of the \agus nerve. Con- tinued stimulation, however, does not produce continued in- liibition, for after a variable limit the heart escapes from the control of the vagus and resumes its beating in spite of the stimulus. The \-agus nerves also vary in their power of con- trolling the action of the heart ; for in some cases while stim- FIG. 1.— TR.\CIXGS OF BLOOD PRESSURE AND RESPIRATION, DOG. Effect of Vagus Stimulation. The upper tracing is of the blood pressure; the drop in the tracing occurred when the vagus nerve was stimulated. The lower tracing is of the respiration. Stimulation of the vagus had the effect of increasing the respirations. Reduced three-eighths. ulation of the nerve on one side will inhibit the heart the same stimulus applied to the opposite vagus may actually cause acceleration. In other instances either vagus controls the heart with equal facility. The tracings represent cardiac auto- graphs, in which the heart writes its own record, strongly or weakly as the case may be. Fig, I shows complete cardiac inhibition and consequent fall in blood pressure fiom moderate electric stimulation of the vagus nerve. The response was not immediate, there beino- at Ficrre A. Fish. least one beat before inhibition ensued. Wlien the stimulus was removed there was again an appreciable delay before the beating was resumed. Ultimately there was a somewhat increased rate with higher blood pressure as if to make up for the time lost during inhibition. The upstrokes in the blood pressure curves represent the systole; the downstrokes the diastole of the heart. Upon respiration there was at first inhibition, followed almost immediately by increased depth and frequency and some irregularity in breathing. Upon the removal of the stimulus, the depth and frequency was still maintained slightly above the normal. PIG. -BLOOD PRESSURE TRACING. HORSE NO. Strongest Stimulus. The broad line below the tracing indicates the period of vagus excitation. The lower line marks seconds. Reduced one-halt. The tracing in Fig. 2 shows a fatal termination. Through an inadvertency the short circuiting key of the apparatus was not opened until the strongest stimulus was reached. The usual practice in the experiments was to first apply a weak stimulus and graduall}^ lead up to the strongest. This has been done a number of times, and in such cases there has been no fatal result. As an explanation, it may be suggested that the weaker stimuli ''educate" the heart to resist the vagus ef- fect, so that it acquires to some extent an immunity against strong stimuli. Such an hypothesis, however, requires further confirmation. Effect of Drugs Upon Blood Frcssurc. It sliould be noted in this case that the heart showetl con- siderable resistance to the excitation, giving three normal beats and then continuing to beat with diminished force and frequency while the blood pressure fell gradually. The stim- ulus was applied for seventy seconds. When this was re- moved the blood pressure continued to fall slightly. After about seventy seconds more the heart gave one abortive beat, when death ensued. The cylinder was allowed to revolve its whole circumference (about eighteen inches), and the floater showed a continued but almost imperceptible decrease in blood pressure. FIG. :!. -INTERMITTENT PULSE. HORSE NO. 8. Blood Pressure Tracing. Natural size. An abnormal condition not infrequently encountered is an intermittent and irregular pulse. The tracing shows the missing beats at more or less regular intervals and that there is usuallv an abortive attempt to beat, which, however, is too slight for the finger to detect. In this experiment a single electrode was placed upon each vagus, and the stimulus sent through both nerves simultaneoush- Blood pressure is considerably lowered, with diminished frc- Pierre A. Fish. quenc}' but increased amplitude in the heart beat. The result ifi much the same as when a pair of electrodes is placed upon the single nerve. -^^^U^'LAJ FIG. 4. -BLOOD PRESSURE TRACING. CALF NO. 1. Moderate Stimulus to Vagus Nerve. Natural size. 1 II 1 " w ■1 IIH^^^^IhjI^^^ ' FIG. 5.— BLOOD PRESSURE TRACING. COW NO. 1. Moderate Stimulation of Vagus Nerve. Reduced one-halt. This COW was tuberculous. The heart was slow to react to the stimulus, giving eight beats before the blood pressure Effect of Drugs Upon Blood Pressure. fell. The decrease in fre(juency is very great, but the enor- mous increase in the amplitude of the heart beat during the period of stimulation is remarkable. Shortly after the re- moval of the stimulus the blood pressure rose, but soon re- turned to normal. FIG. i;.— BLOOD PRESST'RE TRACING. COW NO. 1. Effect of Eserine Ujion the Heart. Reduced one-eighlh. Three grains of eserine sulphate were injected into the right jugular vein at the point on the tracing indicated by the vertical line. The efifect was to soon slow the action of the heart, but to increase the force of its beat. In general the FIG. -.-BLOOD PRESSURE TRACING. HORSE NO. Ifi. Effect of Nitroglycerine Upon Blood Pres.sure. Reduced three-.sixteenths. force of the beat is measured by the vertical distance of each individual curve and the frequency by the horizontal distance between each curve. Eserine exerts a direct stimulating ac- tion upon the cardiac muscle independently of the vagus nerve. Pierre A. Fish. One grain of nitroglycerine was injected into the left jugu- lar vein at the point indicated on the tracing. The blood pres- sure fell gradually with decreased frequency but increased am- FIG. -BLOOD PRESSURE TRACING. HORSE NO. Itl. Strong Stimulus Applied to the Left Vagus after the Injection of Nitro- glycerine. The distance between the two sets of vertical lines shows the period of vagus stimulation. plitude of the heart beat ; this effect being brought about by the paralyzing action of the drug upon the vaso-motor inech- anism. The peripheral as well as the central mechanism being affected. FIG. 9.— BLOOD PRESSURE TRACING. HORSE NO. 16. Strong Stimulus to the Right Vagus after Nitroglycerine. The two sets of vertical lines indicate the period of vagus stimulation. Reduced one-six- teenth. After the effect of the nitroglycerine was apparent a strong stimulus was applied to the vagus nerve of the left side for Effect of Drugs Uf^oii Blood Pressure. y! twenty-eight sceonds. The principal action is the slowing ef- fect upon the rate, which was maintained for a short time after the stimulus was removed. There is a slight fall in blood pressure, the amplitude of the beat being practically the same throughout. Nitroglycerine tends to paralyze the vagus cen- ter as well as the vaso-motor, and a mild stimulus produces practically no marked effect upon the heart beat. In this experiment the same strength of stimulus was sent into the right \-agns as had just previously been sent into the left, and illustrates the difference in susceptibility of the vagus ner\es in their control of the heart. Although there is a fall in blood pressure, there is not complete inliibiti(jn, as the FIG. ](l.^BLOOD PRESSURE TRACIXG. HORSE NO. 1(1. Nitroglycerine Experiment; Stimulation of Both Vagi. The distance between the first and last vertical lines represents the long period of stimu- lation (right vagus). Between the second and third verticals, the perind of short stimulation (left vagus). Reduced one-fourth. tracing shows a number of aborti\'e beats. The stimulus was applied for forty-three seconds, during which the heart es- caped from the control of the vagus, and beat with increased force and frecjuency and with higher blood pressure for thir- teen seconds before the removal of the stimulus. A strong stimulus extending through a period of seventy- eight seconds was sent into the right vagus. During the first twent_\--six seconds there was practically no effect upon the heart rhytlim except a slight slowing in the rate. (Compare with Fig. 9.) After twenty-six seconds, while the right vagus was still being stimulated, a current of the same strength was turned into the left vagus for twentv-seven seconds. After Pierre A. Fish. some dela}- there was a slight fall in blood pressure, with marked slowing of the heart. After the removal of the stim- ulus from the left vagus there was an increase in the blood pressure and increased force to the beat, in spite of the fact that the right vagus was still receiving its stimulus. The re- mo\"al of all stimulation produced no apparent change in the heart beat nor in the blood pressure. The experiment was concluded by cuttmg both vagus nerves, without producing any material change in the character of the tracing. FIG. 11.— BLOOD PRESSURE TRACING. HORSE NO r,. Normal Pressure Tracing at the Left; Effect of Barium Chloride Sliown at the Right. The vertical line above the tracing indicates the point at which the barium chloride was injected. Natural size. Ten grains of barium chloride were injected into the jug- ular vein, causing a ^•er}- decided increase in the force of the contraction, at the same time slowing the rate of the heart. The rise in blood pressure is also striking. The strongest stimulus was applied for one hundred and fi\-e seconds. The response was almost immediate, as shown by the sudden fall in blood pressure. The beating of the heart was checked only temporarily: the beats, though somewhat irregular and of less amplitude, were nearly as \'igorous as normal, and the blood pressure rose materially in spite of the Effect of Drugs Upon Blood Frcssiire. strong and long stimulation. Upon the removal of the stim- ulus there was immediate recovery, as shown by the increased frequency, and some rise in blood pressure, although the lat- ter remained lower than the normal. Barium chloride evi- dently interferes with the vagus control of the heart. FIG. 12.— BI^OOD PRESSURE TRACING. HORSE NO. 0. Strongest Stimulus to Vagus after Barium Chloride. Tlie vertical line.s above the tracing indicate the period of vagus stimulation. Reduced one- sixteenth. /::• The strongest stimulus was applied to both \-agus nerves for thirty-one seconds. The slow response is remarkable. There is considerable fall in blood pressure and the slowing and irregularity of the heart is marked with greath' increased amplitude in the beat, but there is not complete inhibition. The recovery from stimulation is even slower than was the response. The blood pressure rose above normal for a short time, and the frequency of the heart beat did not quite return to the original. In this experiment the barium was in- jected subcutaneously. Pierre A. Fish. As in the preceding experiment the strongest stimulus was emplo\-ed, but for a longer period (one hundred and twenty- seven seconds). There is also noted the same delay in re- sponse and recovery from the stimulation. At first there is a little irregular fall in blood pressure ; but this is soon main- tained at the normal, while the force of the contraction is greatly increased, but somewhat slowed. In this experiment both vagi had been cut and the stimuli were applied to the FIG. 13.— BLOOD PRESSURE TRACING. HORSE NO. 7. Stimulation of Both Vagi after Barium Chloride. The vertical lines below the tracing show the period ot vagus stimulation. Natural size. peripheral portions of the cut nerves ; the cardio-inhibitory center was therefore separated irom direct connection with the heart and its influence was removed. A comparison of Figs. 13 and 14 is most interesting. In the former the vagi were intact, and the center formed a portion of the circuit ; in the latter case the center was excluded, all other conditions, however, being the same. The more pronounced effect in the first case su.ggests that normally or under the influence of the Effect of Drugs Upon tuood l^rcssiirc. drug tlic center responds to the electric excitation, and sends inliibitor}- stimuli to the heart in addition to those directly transiiiitte(l In- tlic electrodes: for in the second case, wliere al! tlU. 14.— BT.OOD PRESSURE TRACIXG. HORSE NO. 7. Stimuhition of the Peripheral Portions of the Cut Vagi after Barium Chloride. Period i.tf ^■agus stimulation is shown by the \'ertical lines abo\'e and iDelow the tracing. Reduced three-eighths. of the conditions were the same except the inclusion of the center, the inhibitory effects were very much less pronounced. FIG. 1."..— BLOOD PRESSURE TRACING. DOG. Normal Condition at the Left and Effects of Barium Chloride at the Right. Natural size. The question as to the acquisition of immunit_y by the heart from previous stimulation, if this be a fact, may also have an application here. ticrrc A. Fish. In this dog one-fourth of a grain of barium chloride was A ; r athninistered in the femoral vein. The increase in the blood '~^' FIG. IC.^BLOOD PRESSURE TRACING. DOG. Vagu.s Stimulation after Barium Chloride. The vertical lines above the tracing show the period of stimulation. Natural size. pressure, more forcible contraction and slowing of the beat is well demonstrated. FIG. 17.— BLOOD PRESSURE TRACING. DOG. Vagus Stimulation Between Vertical I^ines after Atropine Following Barium Chloride. Natural size. As in the case of the horse, some resistance is shown to- ward the vagus control of the heart. With a moderate stimu- Effect of Drugs Upon unnm i ic^mif. ■!■/ his the aniplitiule of the beat is not much decreased, although there is a fall in blood pressure and some slowing. The administration of atropine (same dose as barium chlo- ride) shows an increased acti\-itv of the heart on account of the paralysis of the vagus endings. There is also an increased blood pressure, due to the greater output of blood from the lieart as well as to stimulation of the vaso-motor center in the oblongata. Excitation of the vagus after atropine does not produce inhibition. In this case it caused the opposite result, producing a rise in blood pressure without any very appre- ciable effect upon the amplittide or frequency of the beat. FIG. IS.— BLOOD PRESSURE TRACING. CAT. Tracing of Normal Pressure at the Left, and after the Administration of Barium Chloride at the Right. Reduced one-half. This cat received a very large dose of barium chloride in the femoral vein (i.y centigrams per kilogram of body weight, or a total dose of about 5-6 grain). As shown b}^ the tracing, the first effect of the drug was to produce vaso-constriction. The blood pressure increased in amount to seventy-six per cent above normal. In time the pressure fell a little, but was maintained at a point much higher than normal, with slowing and increased force in the contraction. In general the tracings show an important effect of barium chloride upon the heart and circulation. The resemblance to digitalis in these respects is very marked, and is extended also to its diuretic effect. In an experiment upon a clog it r icrrc ^1 Fish. was observed that the flow of urine through the ureters and collected in a graduate exceeded the normal volume consider- ably in a given time. The diuretic effect of barium chloride as well as of digitalis is undoubtedly due to the action of the ■drugs upon the blood pressure in the kidneys. Loeb has shown that the barium ion exercises a stimulating eft'ect upon protoplasm, especially all forms of muscle tissue. The results of the foregoing experiment^ would indicate that the barium, by stimulating the cardiac muscle directly, enables it to resist, within certain limits, the vagus control. The increase in blood pressure is effected by the vaso-con- stricting action of the salt, possibly by its direct action upon the muscular tissue of the vessels. The increased force of the heart beat should also be considered a factor. The slowing of the heart would indicate that barium chloride also has a stimulating eft'ect upon the vagus mechanism. Dr. Schedel of Nauheim, Germany (Dent. Med. Woch. xxix No. 13), experimenting upon himself, observed the eff'ect of barium chloride upon the heart and circulation. After ob- taining his normal pulse and blood pressure by the use of a sphygmograph and tonometer, he found that, taking one-third of a grain of the salt twice daily, two hours after the principal meals, the effects were produced two hours later. These ef- fects were a fall in the pulse rate, an increase of 10 mm. in the blood pressure, and greater amplitude of the pulse curve. There was still some eft'ect of the drug three days after it was discontinued. In another experiment, where three-fourths of a grain was taken twice daily, the results were the same, except that the blood pressure increased 30 mm. in amount. Clinically the drug was used upon nineteen patients, some suffering from organic heart disease and others with lowered blood pressure resulting from such diseases as pulmonary tu- berculosis, leukemia or chlorosis. Doses of one-third grain or one-half grain, twice daily, caused considerable improvement, the pulse becoming regular, full and slower, the grave symp- toms disappearing with the rise in blood pressure and free diuresis. The increased blood pressure did not last longer than three days, but the general improvement and the strengthened pulse persisted for eight days. Effect of Drugs Upon _.„. Dr. Schedel concludes that the indications for barium chlo- ride are the same as those for digitalis, and that small doses do not disturb the digestive functions. It would appear from the data already given that the veter- inarian will probably find in barium chloride, with proper dosage, a valuable drug in animal therapeutics, aside from its use in producing purgation, where doses bordering upon tox- icity are required. ABSTRACTS OF ^ WORK DONE IN THE LABORATORY OF VETERINARY PHYSIOLOGY AND . . PHARMACOLOGY . . . . UNDER THE DIRECTION OF P. A. FISH NO. 2 NEW YORK STATE VETERINARY COLLEGE CORNELL UNIVERSITY ITHACA, N. Y. 1905 ' TABLE OF CONTENTS PAGES The Effect of Molasses Feeding on Horses at Rest P. A. Fish and A. M. Seaman i The Source of Mucin in the Urine of the Horse--//^ /. Milks 20 The Eflect of Certain Drugs upon Metabolism as Determined by Urinary Examination /. A. Madden 32 THE EFFECT OF MOLASSES FEEDING ON HORSES AT REST. p. A. FISH AND A. M. SEAMAN. ITHACA, N. Y. (Read at the meeting of the N. Y. Stite Veterinary Society, Brooklyn, Sept. 14, 1904. ) The use of molasses as a food for stock was suggested by Hermstadt as early as 181 1. In Europe it has been used as a stock food for a number of years. In some countries it has been subject to taxation and its cost, therefore, has been an important factor in determining its general use. In Austro-Hungary during 1900- igoi, six per cent., and in Germany 27.6 per cent, of the total pro- duct of molasses was used for feeding purposes. It has been fed largely to cattle with the idea of improving the quality of the beef and in some cases of increasing the milk production. It was found that when molasses was used, the hay and grain might be dimin- ished and that it rendered food of poorer quality more palatable. It was fed in quantities ranging from 5 to 12}^, pounds per day. Some experiments in molasses feeding were carried on by Dr. Griffin in Porto Rico from 1898 to 1901. Thirty-five pounds of grass and 13 to 15 pounds of molasses were used as a daily ration. When beginning the new ration there was an average loss of 27 pounds in weight. This loss, however was soon made up and the animals gained over the original weight. He found that the horses did more work and presented a better appearance as a result of the molasses feed and the cost of their maintenance was reduced from 27 cents to 15 cents per day. Dr. Liautard of Paris reports, concerning molasses peat, that there is no danger nor inconvenience in its use ; that the general condition, muscular power, energy to work and the health of the animals remained perfect the coat presenting a better and more glossy appearance ; that when subject to colic and indigestion, the attacks are less severe, less frequent and sometimes disappear. In 1902 Berns experimented with molasses upon two unthrifty horses weighing 900 and 940 pounds respectively, feeding one quart of molasses diluted with three quarts of water three times a day with some grain and hay. There was no constipation nor indigestion. In six weeks horse No. i had gained 175 lbs. and No. 2, 146 lbs. A number of truck horses were also experimented with. All improved in condition ; the general health was excellent, acute indigestion and spasmodic colic were rare although they had been frequent before the experiment. The Colonial Sugar Co., of Fiji, Australia, also report experi- ments with molasses. They fed at one time as much as 30 pounds per day, but believing this too high they reduced the amount to 15 pounds per day as a steady diet, given along with 3 pounds of bran and 4 pounds of corn with as many green cane tops as the animal could eat. Some constipation was noticed and the bran was given to correct it. They concluded that an albuminoid ratio as low (wide) as i:ii.S is suitable for heavy continuous work. (1.13 lbs. digestible albuminoid, 13.30 lbs. of carbohydrates including 0.24 lb. fat equals 1:11.8). Such a ration they believe to be suitable in a tropical climate. No undue fattening, softness or injury to wind was observed. Grandeau's experiments showed sugar to possess a coefficient of digestibility amounting to 100, i.e., all the sugar was digested, none being found in the droppings. The thirst was not increased, in fact, it was a fraction less than when sugar was not used. Other experimenters also report quite uniformly favorable results. As a summar3' of the testimony in numerous reports the follow- ing conclusions seem warranted : Good molasses is a highly nutritive food easily digested, and assimilated, and in some cases at least corrects faulty digestion. One quart of molasses at 3 cents will take the place of three to four quarts of good oats at 4)4 to 6 cents. The sudden change from dry oats to molasses mixed with other foodstuffs is safe and causes no marked disturbance of the digestive organs. Molasses fed horses will do as much or more work and remain as a rule in much better general condition. The cost of feeding, depending upon locality, maj' be reduced from 25 per cent to 33 per cent. In some localities there is no re- duction. In general, molasses ma}' be considered as a product containing sugar that cannot be crystalized by any known method. Its com- position is to a certain extent variable and the following would per- haps represent an average analysis : Water 20 per cent. Dry substances containing : Nitrogeueous substances 10 per cent. Sugar 50 per cent. Non-nitrogenous 10 per cent. Salts ID per cent. Molasses contains from i per cent to 1.5 per cent of nitrogen, sometimes more. It is reported that sugar molasses possesses greater activitj' than sugar alone. Its nourishing value is high and it is easily assimilated. Being soluble it requires but little diges- tive action and in this way there is some saving of the vital energy of the organism. Molasses or sugar is readily diffusible, the os- motic processes are rapid and the passage through the intestinal tube into the circulation is not prolonged. Because the osmotic action is rapid, it is doubtful if there is complete oxidation of the sugar. Assuming that the blood is not able to supply sufficient oxygen for complete transformation, there probabl}' results a stored up energy for subsequent tissue and fat formation. Kellner found molasses to be four times as valuable for flesh production as ripe wheat straw. Meat from molasses-fed cattle has been pronounced of first class quality. As compared with sugar, starch must undergo considerable modification and various changes before it can undergo assimilation. Up to the present there has been no record of toxic effects from molasses feeding. Occasionally diarrhoea has been reported, pre- sumably due to the salts in the molasses ; on the other hand some have reported constipation, which has usually been corrected by the addition of a Httle bran to the feed. Some untoward effects and inconveniences incident to the use of molasses have been reported. It has been believed by some that molasses tends to cause miscarriage in pregnant cows and that in young animals it appears to have a tendency to cause softening of the bones, unless calcium phosphate be added to the diet. As examples of inconveniences may be mentioned the smearing of the manger and parts of the stall, the body of the animal, cloth- ing, stable implements, and serving to attract the flies in warm sea- sons. In summer there is some danger of fermentation and the bursting of the barrel. As a result of fermentation there is a loss of sugar practically rendering the molasses unfit for use. With a good grade of molasses, the keeping qualities are good and there is not much danger of fermentation. It should contain not over 20 to 22 per cent of water. If there is 25 per cent of water there is dan- ger of change. EXPERIBIENTS. Experiments in molasses feeding were conducted upon three horses at the New York State Veterinary College. No. i was un- der observation from December 21, 1903, to April 2, 1904. No. 2, from January 18 to February 4, 1904. No. 3, from February 5 to April 18, 1904. These animals were brought to the college to be disposed of. They were all well along in years and were not there- fore in the best of condition. They were under observation for a week before the experi- ments began in order to determine as well as possible their normal conditions. After the experiments were concluded, the observations were still continued, upon two of them for a week or more longer. A total of eighty examinations of the urine were made and the body weight was taken at regular intervals throughout the whole period of observation. No I was a mare badly affected with the heaves, but otherwise was apparently in very good condition. Her age was estimated at 12 years. Her weight, the evening the experiment was begun, was 892 pounds. She was kept in her stall throughout the experiment and received no exercise further than a walk to the scales three times a week, a distance of about one-eighth of a mile. Beginning December 21, her urine was examined daily up to December 25. The average of these determinations is shown in the following table : Specific Gravity 1.041 Solids 95-53 per 1000 Chlorides 13-449 " Sulphates 2.25 " Phosphates 0.8375 " Urea 35.25 Albumen absent Sugar absent The formula recommended by Dr. Berns was used in a modified form, corn meal being omitted and some oats substituted. Because the mare was doing no work she was put on half rations. For the month previous to the experiments she had been getting about 1.5 pints of oats ; 2.5 quarts bran and 6 lbs. of wet hay twice daily. On the evening of December 24, she was put on the following ration : Molasses i pint Water 3 pints Cut hay 2.5 lbs. Oats I lb. Coarse bran 2 qts. The hay, oats, and bran were mixed and the diluted molasses slowly added and mixed thoroughly. This was refused at first, but the feed was all gone the next morning. After three or four days she ate the mixture readily. She was fed morning and night. On December 28, her weight was 878 lbs., showing a loss of 14 lbs. since the 24th. As she ate her bedding and seemed hun- gry, it was thought best in connection with her loss of weight, to increase the ration to the following amount : Molasses i qt. Water 3 qts. I.03I 73-395 per looo 8.0S9 " 1.5 " 1.08 K 20. absent absent Cut hay 5 l^^s- Oats I pt. Bran 2 qts. The average of two urinar}' examinations taken since the 24th, and the period of increased ration gave the following results : Specific gravity Solids Chlorides Sulphates Phosphates Urea Albumen Sugar Comparing the two tables there is found to be a loss in all of the solids except the phosphates, which are increased. In spite of the increased ration the weight of the animal con- tinned to decrease and she did not regain her weight of December 28 until January 12. She had been weighed seven times in the in- terval and the average of these weights was found to be 865.39 ^bs. Seven urinary determinations were also made during this period. The average of these is as follows : Specific gravity Solids Chlorides Sulphates Phosphates Urea Albumen Sugar On December 30 a trace of sugar was noticed in the urine. This increased somewhat in amount later and averaged about 0.33 per cent to 0.42 per cent. A comparison with the other urinary table shows that during this period of decreased weight there was an increased amount of solid constituents in the urine, except urea, which had fallen to nearly one-third of the amount found in the 1.042 ■4 98. S5 per 1000 15. So " 1.85 " 2. " 13-14 absent present normal urine. The sulphates are also somewhat lower than found in the normal but higher than in table No. 2. During the next period from Januar\' 12 to January 25 the ani- mal was weighed 7 times and the average of these weights amounted to 872.9 lbs., a gain over the preceding period but still about 20 lbs. less than the normal weight. Six urinary examinations were made during this period with the following average ; Specific gravity 1.0391 Solids 91. 25S per 1000 Chlorides ii-57i " Sulphates 2.0S " Phosphates 1.98 " Urea 13. oS " Albumen present Sugar present With a slight increase in weight there is a corresponding decrease in the urinary solids except in the case of the sulphates. On Jan. 18 the presence of albumin was noted. It was also present on Jan. 20 and Jan. 22 but had disappeared by Jan. 25. On Jan. 25 there was added to the ration 4 oz. of dried blood from which the serum had been previously removed. The addition of the blood did not lessen the animal's eagerness for food. No further change was made in the diet until Feb. 8. During this period the animal was weighed five times and the average weight was S83.6 lbs., a gain of 10.5 lbs. over the preceding period. Five urinary examinations were also made with the following average : Specific gravity Solids Chlorides Sulphates Phosphates Urea Albumen Sugar Owing to an error the chlorides were not correctly reported and they are therefore ommitted. In spite of the increased albumen in 1.0402 93.655 per 1000 o.S " 1.27 " 14.2 " absent present lO the diet there was no appearance of it in the urine although the sugar persisted. On Feb. 8 the diet was again changed by reducing the amount of molasses to I pt. for each ration until Feb. 15. The horse was weighed four times during this period and the average weight obtained was 885.7 lbs. showing a gradual gain. Four urinary examinations were also made with the following average : Specific gravity 1.043 Solids 105.19 per 1000 Chlorides Suphates trace Phosphates 1.13 " Urea 23. " Albumen absent Sugar present The gain in urea is noticable. In the urine of Feb. 15 it was found that the sugar had disappeared, probably on account of the lessened amount of molasses in the ration. From Feb. 15 to Feb. 22 no molasses was fed. The ration consisted of : Bran 3 qts. Oats I pt. Long hay 6 lbs. This was fed morning and night. The horse was weighed three times in this period and gave the average weight of 889.1 lbs. Three urinary examinations were made with the following average : Specific gravity 1-038 Solids 85.54 per 1000 Chlorides 4.967 " Sulphates trace Phosphates 0.60 Urea 32.9 " Albumen absent Sugar trace The gain in urea and decrease in phosphates is very noticable. Although the animal received no molasses a trace of sugar appeared during the middle of this period and persisted. II On Feb. 22 she was given a pint of molasses diluted with- water, sprinkled over her haj'. On Feb. 25 her weight was 896 lbs., a gain of 6.9 lbs. over the previous period or a gain of 4 lbs. over her original weight at the beginning of the experiment Dec. 24. Urinary examinations were made Feb. 25 and Feb. 27 witk the following average : Specific gravity . 1.040 Solids 93- 20 per 1000 Chlorides 4.362 " Sulphates trace " Phosphates 0.75 Albumen absent Sugar present On Feb. 27 the experiment was discontinued, but the animal was kept under observation until April 2. During this period she was weighed 12 times and an average weight of 86 1.8 lbs. obtained. Eleven urinary examinations were made and these averaged as follows : Specific gravity 1.0426 Solids 99-34 per 1000 Chlorides 3 99S " Sulphates trace Phosphates 1.25 " Urea 32.9 " Traces of sugar appeared Mar. i and Mar. 5. Traces of albumen also appeared Mar. 12 and Mar. 17. No positive tests for these substances were obtained at any other time during this period. The condition of the animal through the molasses period was excellent ; her coat presented a fine appearance and her general health was good. There was no evidence of either constipation or diarrhoea, and no noticeable effect seemed to be produced upon the heaves. At times she was quite frisky and playful. When she was put on her former ration without molasses, a marked falling off took place as shown by the average loss of 34.2 lbs. in weight and lessened vigor generally. A summary of the urinary examinations is shown in the appended table ; 12 Horse No. i. tf. V .;;- ^ ^ o a. O (U ^ Dec. 21-25. 892 1. 041 95.53 13.45 2.25 0.S4 35.25 Dec. 25-28- 878 1. 031 73.39 8. 09 1.5 1.08 20. Dec. 28-Jan. 12. 865 1.042 98. 85 15.80 1. 85 2. 13.14 present Jan. 12-25. S73 1.039 91-29 ii-57 2.08 1.9S 13.08 present " Jan. 25-Feb. 8. 8S3.6 1.040 93.66 0,8 1.27 14.2 Feb. 8-15. 885.7 I-043 105.2 trace 1.13 23. " Feb. 15-22. 8S9.1 1.038 85.54 4.97 " 0.6039.3 trace Feb. 22-27. 896 1.040 93.20 4.362 " 0.75 35.5 present Feb. 27-Apr. 2. 86[.8 1.0426 99.34 3.998 " 1.25 32.9 The urinar}' figures in this table represents parts per 1000. No. 2 was a mare well along in 5'ears and in good condition. Her weight, averaged from four weighings before the experiment, was 912 lbs. Her ration had been four quarts of bran and 5 or 6 lbs. of long ha}' morning and night. Daily tests were made of her urine from Jan. 18 to Jan. 25 inclusive, and the normal average was as follows : Specific gravity 1.0342 Solids 79. SS per 1000 Chlorides 7.722 " Sulphates i. " Phosphates 1.63 " Urea 34.2 " Albumen absent Sugar " On the evening of Jan. 25 the molasses ration was begun (morning and night) as follows : Molasses i qt. Water 3 qts. Bran 3 qts. Cut hay 5 lbs. Like No. i she refused her feed at first, but had cleaned her box by the next morning. The next day there was a suspicious 13 trace of sugar in the urine which became more pronounced the day following and persisted until the end of the experiment, Feb. 4. The average weight of the animal from Jan. 26 to Feb. 4 was 947 lbs., a gain of 35 lbs. over her normal weight. At no time during the molasses feeding did her weight fall to normal. During this period 7 urine examinations were made and the following averages obtained. Specific gravity 10334 Solids 77. S8 per icoo Chlorides Sulphates 0.7 " Phosphates 1.47 " Urea 13.5 Albumen absent Sugar present The great decrease in urea during the molasses ration is very striking. On her way back from the scales, February 4, the mare fell on the ice and required assistance to rise. When returned to her stall she showed labored breathing and again lay down. She could not be induced to rise and as she seemed to be in a serious condition, she was killed and a post mortem held the next morning. The point of the ilium was found to be fractured ; there was also some hemorrhage in the sub-lumbar region. Some frothy blood was noted near the duodenum. The diaphragm was ruptured and the intestines protruded into the thoracic cavity. Whether this re- sulted from the fall or not we do not care to say. Ruptured dia- phragms are encountered occasionally in the dissection room, pro- bably as a result of bloating. In this case there was an interval of about fifteen hours between the death and the post-mortem, and the cool February weather was not especially conducive to fermentation processes. In the dissection it was noticed that the tissues seemed to have a greasy "feel" suggesting the presence of fluid fat. A series of five blood examinations was made before the mo- lasses was fed and a similar number made while it was being fed. The average of each series is as follows : Red cells Leucocytes 7,125,480 5.265 5,768,228 5,434 14 Before molasses During molasses The balance of the red cells is in favor of the normal period while for the leucocytes a small balance is shown in favor of the molasses. The result is interesting but more experin.ents are ne- cessary before arriving at definite conclusions as to the effect of the molasses upon the blood. No. 3. This subject was a mare well along in years, afflicted with sweeny but otherwise in quite fair condition. From February 5 to February 13 her ration consisted of three quarts of oats and five lbs. of hay morning and night. Her average weight during this period was 704.5 lbs. Through an unfortunate misunderstanding the records of the normal urine were not kept completely and cannot therefore be used for reference, except that it was determined that no albumin or sugar were present. A prepared food was used in this experiment, consisting of blood, molasses and chopped cereal. The proportions of the ingre- dients not being given. The use of this food was begun on the evening of February 13 by withdrawing some of the oats and substituting the same amount of the new food, until on the 17th she was getting the proportion recommended by the manufacturers, namely : 1.5 quarts of oats 2.5 quarts of the prepared food with hay as usual. This proportion was continued until February 25. During this period her average weight increased to 727.1 lbs. Three urinary examinations were also made during this period with the following average : Specific gravity Solids Chlorides Sulphates Phosphates Urea Albumen Sugar 1.0366 85-43 per 1000 2.19 - 16.6 " absent presen t Feb. 25 15 On the evening of February 25 she was fed 5 quarts of the pre- pared food and the oats were altogether withdrawn. Hay as usual. This was continued until March 12. During this period her aver- age weight increased to 765.4 lbs. Seven urinary examinations were made and gave the following average : Specific gravity 1.0442 Solids 103.18 per 1000 Chlorides 4.664 " Sulphates trace Phosphates 2.45 " Urea 25.1 " Albumen present Mar. 10 and 12 Sugar present The gain in solids, especially urea, is noticeable. From the evening of March 12 to March 29 the ration was changed to 2 quarts of the prepared food with three quarts of bran. Hay as usual. The average weight for this period increased to 792.8 lbs. Six urinary examinations for this period averaged ; Specific gravity 1.0401 Solids 93-58 per 1000 Chlorides 8.36 Sulphates trace Phosphates 1.51 " Urea 20.3 Albumen at intervals Sugar at intervals decreasing There was a little sugar present at the beginning of this period but it quickly disappeared. Albumen was found March 17, 24 and 26. During the next period from March 29 to April 15 it was de- cided to give an increased amount of the molasses constituent ; the amount of bran was reduced a little with a corresponding increase in the prepared food ; to this was added i pint of molasses morning and night. The animal was weighed twice during this period and the average was 788 lbs. Four examinations of urine were made and gave the following average : i6 Specific gravity I-0477 Solids III. 26 per 1000 Chlorides 4.544 Sulphates trace Phosphates 2.78 " Urea 14.25 Albumen present, not constant Sugar present, not constant From the evening of April 15 to April 18 inclusive, the mare was fed 5 quarts of prepared food and 2 quarts of molasses twice daih-, with hay in usual amount but of a poorer quality. On the iS when she was killed her weight was S51 lbs., showing a gain of 146.5 lbs. over her normal average weight. The urine was exam- ined April 16 and showed the following results : Specific gravity . 1.043 Solids III. 19 per 1000 Chlorides 9.451 Sulphates * trace Phosphates 1.4 " Urea 9. " Albumen absent Sugar pronounced The decrease in urea is pronounced and this may be correlated with the increased carbo-hydrate diet. The following table is a summary of the urinary examinations. Horse No. 3. 4) JO ^ ."3 o X: M Q ?WcflU-J3?Hp< CO (Feb. 5-13 Normal) 704.5 Feb. 13-25 727.1 1.036 S5.43 2.19 16.6 Feb. 25 Feb. 25-Mar. 12. 765.4 1.04S 103. iS 4.664 trace 2.45 25.1 Mar. 10 present Mar. 12-29 792. S 1.040 93. 58 S.36 " 1. 51 20.3 at in- at in- tervals tervals Mar. 29-Ap. 15. 7S8. 1.0477 III. 26 4.544 " 2. 78 14.25 present present Apr. 15-18 851. 1.043 101.19 9-451 " 1.40 9. absent present 17 In this table the urinary figures refer to parts per thousand. Like No. 2 there was an increase in the body weight after the molasses food was used. The animal was in good spirits through- out and her coat was smooth and glossy. When the animal was dissected the same greasy condition was noted as in No. 2. After the death of the animal sections of the liver and kidney were studied histologically. The following report was kindly furnished by Dr. S. H. Burnett of the Pathologic Department. Liver. — The liver shows marked parenchymatous degeneration throughout the entire lobules. The cells are swollen so that the capillaries are very narrow. The cells are coarsely granular and the nuclei pale. The central vein and the peripheral vessels are congested. There are a few leucocytes in the connective tissue surrounding the peripheral blood vessels. The conditions indicate acute parenchymatous hepatitis. Kidney. — The glomeruli and vessels near them are congested ; the epithelial cells of the convoluted tubules are swollen and coarsely granular ; the cells of the straight collecting tubules have lost their granules and are clear, their nuclei seem shrunken. In the medulla the epithelial cells of the smaller collecting tubules are swollen and coarsely granular while in the larger tubules the epithelial cells are clear ; the nuclei seem to be shrunken. The interstitial tissue in the medulla is thickened by a fibrinous exudate more markedly near the pelvis, while the tubules near the pelvis have mostly lost their epithelium. There is marked conges- tion especially in the middle portion of the medulla. The indi- cations point toward acute mixed neprhitis. GENERAL CONCLUSIONS. The various reports upon molasses feeding that we have en- countered have been uniformly of a favorable nature, but seem to have been based upon external observations as to the general health and condition of the animals. The fact that sugar appeared in the urine of all three of our ex- perimental subjects, soon after the molasses was given, is interest- i8 ing and perhaps significant. The later appearance of albumen in- termittently, in two of the cases, is also noteworthy. The presence of either of these substances is usually regarded as an abnormal condition and yet, during their appearance the general health of these animals seemed good, and they exhibited more vigor than be- fore. Albumen and sugar serve as foods for the tissues, their un- due loss through the kidneys would mean a drain upon the system, a distinctly pathologic condition. Their elimination intermittently or in small amounts may represent a physiologic condition, merely the removel of an excess of the given substance in the system. With regard to the constituents of the urine, the most striking effect of molasses feeding was upon the urea. This constituent in- variably fell considerablj' below normal when molasses was used. Perhaps, in a general waj', this may be due to the fact that the molasses contained less material from which urea might be formed. In a carbohydrate diet the nutritive ratio is wide. (Beet molasses, however, has a ratio of i :6.5). When an increased body weight occurs, this may be due to the conversion of the albuminoid mate- rial in the ration into tissue forming substances and thus account for the diminished urea. In subject No. i, however, there was at first diminished urea and decreased weight. As this subject was afflicted with a pathologic condition (heaves), it is not unlikely that the body metabolism was influenced and some irregular results produced in connection with the molasses feed. The pathologic conditions noted in No. 3 would likewise have an important influ- ence upon the elimination of urea ; the diseased epithelial cells be- ing no longer able to do their work properly, it might be expected that the urea would be stored up in the system. The phosphates fluctuated considerably ; the sulphates, al- though fluctuating somewhat, had a marked tendency to diminish as the experiment progressed. The chlorides were unreliable on account of some errors in the early part of the experiments ; the later data showed that they had a tendency to diminish. All of our experiments agree in the fact that abnormal consti- tuents (sugar and some albumen) were found in the urine, soon af- 19 ter the molasses ration was begun. In the only case examined his- tologically, marked pathological conditions were present in the liver and kidney. It would be difScult, without further observa- tions, to prove that these conditions were caused directly by the molasses ; but the fact that all of the urines contained abnormal products seems to be significant in this connection. We do not go so far as to state that the results above men- tioned are present or are to be expected in all cases, where molasses is used as food. The title of our paper limits it distinctly to horses at rest and even here the results may not be uniform. Age is quite likely to be a factor. All of our subjects were quite well advanced in years and the tissues, more or less worn out with the wear and tear of advancing age, were doubtless either more susceptible or less responsive to any unusual demands made upon them. In horses doing work it is quite reasonable to suppose that the effects we have described may not appear to any noticeable effect if at all. In general, a rich carbohydrate diet is productive of much energy. If this energy is used up in the accomplishment of work it is an economic arrangement so far as the body tissues are con- cerned. If on the other hand this energy is stored up in the system without adequate outlet the effect upon the tissues must be pro- nounced and the results that we have encountered might be ex- pected. Molasses is a concentrated food and an undue proportion in the system, under any condition, may be productive of more harm than good. Its value as a food is generally accepted, but, it seems to us there should be certain reservations as to the amount and time of feeding, dependent upon the age and amount of work done by the animal. A careful study of the nutritive ratio in all rations into which molasses enters as a constituent is important. T?IE SOURCE OF MUCIN IN THE URINE OF THE HORSE. H. J. MILKS. In a study of the urine of the horse, one of the most noticeable characteristics is the consistency. It is the rule, rather than the exception, to find it stringy and viscid. Indeed, it is only occa- sionally clear and of a watery consistency. It was due to this vis- cidness and the fact that there is some controversy concerning the origin of the mucin that I investigated the source of its secretion. The work has been carried on with two views in mind : First, to clear up, if possible, the origin of the mucin ; and secondly, to work out its characteristics and to find a reliable test for mucin. Naturally, it has fallen under two heads : histological and physio- logical. The histological will be taken up first. Several authorities were studied with a view of ascertaining the structure of the intra-and extra-renal passages. A summary of these will show that there is quite a diversity of opinion in regard to their structure, the general opinion, however, seems to be that there are no glands present, or, if present, are in very small numbers. Picrsol — Text Book of Histology. — The greater part of the renal sinus is occupied by the dilated ureter, the mucosa of which is covered with the stratified squamous epithelium, which comprises few layers of cells. The epithelium is termed transitional because of the rapid change from columnar, in the deep layer to squamous in the superficial strata. The tunica propriaor stroma of the mu- cosa contains a few racemose glands. Bohm-Davidoff — Huber. — The renal pelvis, ureter, and uri- nary bladder are lined with the stratified transitional epithelium. A few mucous glands are met with in the upper portion of the ureter and pelvis. None are found in the bladder. Stohr, Schafer, and Strieker do not mention the presence of glands, while Szymonowicz and MacCullum say that glands are wanting in the pelvis and ureter mucosa. 21 It must be remembered that the above authorities refer particu- larly to human histology. In none did I find a description of the urinary apparatus of the horse. The following books refer more to the latter. Malkmiis — Clinical Diagnostics. — The mucin in the urine comes from the bladder. Chaiivcau — Anatomy of the Domestic Auimals. — Although, this work treats of the microscopical as well as the gross anotomy, nothing is said concerning the presence of glands in the urinary passages. Ellenberger und Giinther — Histologie der Haussaugetiere — The pelvis of the kidney is lined with the transitional epithelium. The mucosa, in the horse, is partly gland containing. Also in the dog, glands are sometimes found. It will be observed from the preceeding, that the structure of the intra-and extra-renal passages is not well agreed upon. Some experiments upon a living horse, a few years ago, by Drs. Fish and Fisher, in which, by ligating the ureters, they demonstrated that the bladder was not the sole source of supply. They found that the urine between the ligature and kidney was of a much more viscid nature than that in the bladder ; they even compared it to egg albumen in its consistency. The material used in the histological work was taken from horses recently killed. In one instance a kidney was removed from a horse under anaesthesia. Technic. The kidneys were studied, both as to their gross and micro- scopical anotomy. For the former, both the fresh and hardened specimens were examined. For the latter, they were fixed by both the mercuric chloride and formalin methods. Only paraffin was used for embedding purposes. On account of the large size of the kidney, serial sections were not used. Blocks were cut from various sections of the gland, labeled, and a drawing made showing their exact location. Various stains were used : hematoxylin and eosin, 22 hematoxylin and orange G, eosin, methylene blue and eosin (Manns) and muchaematin. Gross Anatomy. By making a cross section of the kidney, the cortex, medulla, and pelvis will be readily distinguished, as outlined in Fig. i. In this drawing it was not the purpose to show the different parts in detail simply to indicate them. An examination of the pelvis shows it to be rather extensive, and its mucosa roughened and thrown into folds. Fig. I. Cross section of kidney of a horse. C. Cortex. M. Medulla. P. Pelvis. H. H. Horns of pelvis. U. Ureter. Upon closer examination, leading in either direction from the main pelvis, are the horns of the pelvis H. H. Fig. i. These are, as a rule smaller than is indicated upon the diagram. Their mu- cosa is smooth. If the examination is made with a hand lens, it will be seen that the pelvis contains the openings of the uriniferous tubules. This is also true of the horns of the pelvis. These tubules- open into the pelvis in different directions, as is indicated by the arrows, a. a. Fig. i. 23 Sections were made from different areas of the pelvis, horns of the pelvis, and other portions of the gland, i.e., cortex and medulla. Sections taken from the main pehis (region A, Fig. i), and stained with hematoxylin thirty minutes, and eosin ten seconds, showed the lining epithelium of the transitional variety, consisting of few layers of cells. Beneath this and imbedded in a connective tissue stroma were numerous glandular structures, composed of simple columnar epithelium, the cells being rather long, well defined, and having their nuclei, oblong in shape, lying near their bases. Within the cells of the glands were numerous granules, more abundant in that part of the cell nearest the lumen of the gland. They had, in some cases, evidently passed without the cell. The glands were found to belong to the compound tubular variety, and, as before stated, were made up of the simple columnar epithelium. Fig. II is a drawing made from one of these glands. Fig. 11. Isolated gland from pelvis of kidney of horse. (Drawing made with Camera Lucida, ) 1 and 3 are secreting cells from pelvis. 2 Transitional epithelium of urinary passage. ■ 24 Besides the general glandular outline, it will be seen that the change from the columnar cells of the gland to the transitional lining the pelvis is gradual. As the columnar cells 1. approach the surface tliey become shortened and are underlaid by a layer or two of the transitional varietj- ; 2, 2, represents the transitional epithe- lium underlying the shorter but thicker secreting cells 3, 3. Cells represented by i and 3 are secreting cells ; those by 2 are non secreting. The glands were further studied with regard to their reaction to certain stains. Mann's methylene blue and eosin was first used. This is supposed to stain mucous secretions and connective tissue a deep blue. In the section from the kidne}' it stained only the connective tissue ; tlie secretion from the cells did not stain at all. However, it revealed, very nicely, the fibers of connective tissue in which the glands were embedded. A stain described as muchaematin by Robert R. Bensley of Chicago in his publication "The structure of the Glands of Brunner" was then used. It is prepared and used as follows : Aluminium Chloride 0,5 gm. Pure Haematin i.o gm. 70 per cent Alcohol 100. cc. Triturate the aluminium chloride and haematin in a mortar, gradually' adding the alcohol, and filter. The solution is then allowed to stand for a week, during which time it deepens in color and its mucin staining power is increased. Slides are treated with benzol, then absolute alcohol, flooded with the stain, and watched under the microscope until the cell contents became deeply stained ; wash quickly with 95 per cent alcohol, dehydrate, clear, and mount in balsam. The preparation has no effect upon the protoplasm of the cells. While it stains a deep blue the secretions from the following sources ; mucous cells from the sub-maxillary, sublingual, palatine, tracheal, oesophageal glands, gastric epithelial cells, cells of the cardiac end of the stomach, cells of the pyloric glands, the chief 25 neck cells of the fundus glands of the stomach, t(oblet cells and cells of Brunner ; except the dark tubules of the rabbits glands. It does not stain the demilune cells of the salivary glands, cells of the parotid, serous cells of the submaxillar}- or sublingual, serous portions of the palatine or tracheal glands, nor the ferment forming cells of the pancreas and fundus glands of the stomach. Fig. III. Pelvis of kidney of horse. xSS. Section stained with Muchaematin. The black areas represent the stained mucin. Sections removed from region A (Fig. i) were stained with muchaematin, and gave the following reaction : the protoplasm did not react at all ; the secretion, however, was stained a deep blue. This was found in more abundance near the lumen of the gland and was of a granular appearance. Under the }i objective, the secre- tion stands out as a feather}- mass (see Fig. III). In this figure an idea of the intensity of the stain and its selective action, will be ob- tained. A section to which mucous was adherent was stained in a similar manner and it was found that the staining properties of the secretion within the cell were identical with those of the secretion without the cell. 26 To substantiate the proof that the substance in the cells was mucin, the experiment was made of dissolving it out by means of an alkaline tiuid. As potassium carbonate is the salt to which the alkalinity of the urine of the horse is due, it was used as the solv- ent, employing the following method : A number of sections were fastened to slides, carried through benzine, alcohol, and water, then placed in a jar containing a 5"o' solution of potassium carbon- ate, and put in an incubator at 37° C. At intervals sections were removed, washed in water, and then in a o.i''() solution of acetic acid, again washed in water, transferred to alcohol, stained with muchaematin , cleared and mounted in balsam. In sections sub- jected to the solvent action of the fluid for (12) to eighteen (18) hours the mucin had almost entirely disappeared. Fig. IV. Section of ureter f^f hor.'Je showing glands. Drawing made by Camera Lucida, 27 Further examination proved that mucous follicles were con- stantly present in the main pelvis (P, Fig. I.) but that in the horns of the pelvis (H H Fig. I), they were not found. Neither was I able to obtain any reaction to the muchaematin from any other area ot the kidney except the main pelvis. Ureters. Glands identical with those of the pelvis were found in large numbers in the upper portions of the ureters, extending, probably, not more than five ( -,') or six (6) inches from the kidney toward the bladder. These glands gave the same reaction to the muchae- matin as did those of the pelvis. Fig. IV, is a drawing made from a section of one of these glands. Bladder. Xo mucous follicles were found in the bladder, although many sections from different areas were studied. Physiology. Although much work has been done upon the subject of mucin in the urine of human beings, very little study has been made of its presence in the urine of the horse, and yet, in the latter secretion, it undoubtedly exists in much greater proportions. Xormal horse urine is viscid and stringy and may be drawn into threads. It is rarely of a watery consistency. That its viscid- ness is not due to contamination from the genital passages is proven not only by the fact that urine drawn directly from the bladder has the same syrupy appearance, but also by the experi- ments of Drs. Fish and Fisher, in which thej- ligated a ureter of a horse under anaesthesia, and although no qualitative tests were made, concluded it to be thicker than that in the bladder, even comparing it to egg albumen in consistency. This experiment has been repeated by me, and the urine anal5'zed so far as the amount would permit. In each case a sample was taken from the bladder 28 and used as a control. I found the urine from the ligated ureter to be so thick that it was necessary to use considerable pressure to expel it from the ureters and pelvis of the kidney. In some cases it could not be expelled at all, and, upon opening the pelvis, was found so thick that it could be lifted out with the hands. The following analysis will give a fair idea of the composition of the two urines. Horse No. i. M.4.I.E. Ureter Lig.^ted Two Hours. Urine from bladder. Uriue from kidney above the ligated portion. Consistency, slightly viscid. Thick like egg albumen. Specific Gravity. 1040. 1040 Albumen. None present. A trace only. 3cc. urine + 4 cc. acetic. acid + centrifuge for 3 i cc. of precipitate Mucin. min. = Trace of ppt. Mucin. No. 2. M.^LE. Ureter Lig-^ted Two Hours. Consistency. Slightly viscid. Thick, Syrupy. Specific Gravity. 1040. 1045. Albumen. Not present. Trace only. 3 cc. urine + 4cc. alcohol + centrifuge for three min. ^ i cc. of precipitate. Mucin. ys cc. Precipitate. Mucin. No other tests were emploj'ed on account of the small amounts of urine obtained from the ligatured ureter. According to a classification by Hammersten but attributed to Hoppe-Seyler and Drechsel, mucins are proteid bodies, classified as compound proteids, under the subhead of glycoproteids. Mucins are colloid substances whose solutions are thready and which, when treated with acetic acid, give a precipitate, insoluble in an excess of the acid, and, upon boiling with dilute mineral acids, yields a substance capable of reducing copper ox^'hydrate. All mucins contain carbon, nitrogen, hydrogen, sulphur, and oxygen. Compared with albuminous bodies they contain less ni- trogen and, as a rule, less carbon. As immediate decomposition 29 products, they yield an albuminous substance on the one hand and a carbohydrate, or allied body, upon the other. All give a reduc- ible substance, if boiled with dilute mineral acids. True mucins are secreted bj' the larger mucous glands. By the action of superheated steam, mucin gives off a carbo-hydrate. This is not always true, as the submaxillary mucin gives off a sub- stance containing nitrogen. On boiling with dilute mineral acids, acid albumen (syntonin) and bodies similar to albumoses and pep- tones are given off. Also a carbo-hydrate that has not been closely studied. With stronger acids, they produce among other sub- stances, leucin, tyrosin, levulic acid, etc. Mucins are not coagu- lated by heat, are slightly soluble in neutral or alkaline solutions and are soluble in lime water. The methods commonly employed to isolate mucin are to pre- cipitate them by adding alcohol, in various proportions, from equal parts of each to five parts of alcohol to one of the solution, filter, wash the precipitate well with alcohol and then allow to dry. Or it may be purified by redissolving in lime water and again precipi- tating with acetic acid. The above methods have been used many times. Both the fil- tered and unfiltered urines were studied. Upon the addition of the alcohol, a copious, white, flocculent precipitate appeared. When the precipitate is purified, as is explained above, it becomes lighter in color and more flaky. The separation was continued until a quantity of the material was obtained. Portions of this were treated with dilute sulphuric acid. It was not readily soluble but dissolved upon boiling, giving a clear, yellowish brown liquid, resembling, in color, the urine of the horse. Solutions were boiled for twenty minutes and at the end of that time tested for syntonin and reducing substances. For syntonin, the method followed was to add a little litmus to the solution and an excess of a dilute solution of potassium hydrate. The contact method was employed and a precipitate at the line of the two fluids indicated acid albumen. It was not possible to obtain positive results in each case, but in many cases they were 30 obtained. For reducing sugars, Trommers test and Fehlings solu- tion were used. The precipitate from the alcohol was but slightly soluble in water and but little in alkaline solutions. Indeed, not enough of it could be dissolved to obtain any appreciable amount in a iiuid. Neither would solutions of it give positive reactions to any of the so called mucin tests. The test most commonly used to detect mucin m human urine is to dilute with an equal amount of water, and then add acetic or citric acid. The contact method is the one most commonh' used, and acid being introduced first. If mucin is present, a more or less pronounced precipitate appears at the line of contact. Acetic acid saturated with salt has been advocated by some, using the same method as the above. Some, also, advise making more alkaline before testing. Horse urine treated as above does not give veTy satisfactor}' results. Acetic acid has been used in various proportions, thus : glacial, commercial, commercial saturated with salt. Citric was used in twenty per cent, ten per cent, five per cent, and a two and one half per cent solutions. The more favorable results were obtained with the stronger acids. No precipitate was obtained with the weaker acids. As a rule, if the solution was made more alkaline with ammonium hydroxide, the tests were more satisfactory and the precipitate more distinct. Conclusions. The mucin in the urine of the horse comes, in the main, from the mucous glands situated in the pelvis of the kidne}'. A very small amount comes from the glands in the upper part of the ureter ; none of it comes from the bladder. That while suitable means have not yet been devised for isolating and detecting mucin in horse urine, yet, without doubt, the substance is mucin, as is proven by the tests described above. That of the tests described, the one in which the urine is made more alkaline before testing is the most satisfactory. 31 Bibliography. But few articles were found bearing upon the subject of mucin in the urine of the horse. The following text-books have been drawn from quite freely : Meade Smith. — Physiology of the Domestic Animals. Capt. Fred Smith. — A Text-book of Veterinar;' Physiology. James Law. — Veterinarj' Medicine. Vol. III. Hammarsten. — Physiological Chemistry. Allen. — Commercial Anal3'sis. Salkowski. — Chemical Physiology. Heitzman. — Urine Analysis and Diagnostics. Tyson. — Practical Examination of Urine. Bensley, R. R. — Structure of the Glands of Brunner. (Bulletin, Univer- sity of Chicago.) THE EFFECT OF CERTAIN DRUGS UPON METABOLISM AS DETERMINED BY URINARY EXAMINATION. J. A. .AIADDEN. The drugs investigated were : salicylic, benzoic, sulphurous, and boric acids, also borax and echinacea. The doses in all cases were minimum and the results obtained may, on this account, vary somewhat from those of other investigators. The methods adopted in the urinary examinations were those commonly used in clinical work and are believed to be sufficiently accurate for comparison of the normal and drug periods. The centrifuge was used for the de- termination of the chlorides, phosphates and sulphates. The tests were, at first, checked by the volumetric determinations commonly in use and the value of each o. i cc. of ppt. in the centrifuge deter- mined on the basis of parts per looo. As a great many examina- tions were to be made, it was believed that the centrifuge method would be the most expeditious and accurate enough for ordinary purposes. For the urea determinations, the Doremus Ureometer, as modified by Hinds, was used with the sodium hypobromite solu- tion. The apparatus was tested with a solution of urea of known percentage and was found to be accurate within a slight fraction of a gram. No uric acid determinations were made and in none of the tests were albumen or sugar found to be present. The general plan of the investigation was, in each case, to col- lect the total amount of urine for twenty-four hours and take from this a sample for analysis. Seven days (one week) was the limit of each period. Before the drug was taken, seven analyses of the urine were made. This may be referred to as the normal period. Following this, the drug was taken for one week and this will be designated as the drug period. The average of each seven ex- aminations is taken as representative of the condition of the urine 33 for that period — say the normal ; and this average is compared with that obtained from the drug period, the amount of the constituents in all cases being determined in grams or cubic centimeters for the twenty-four hours. Except in the case of sulphurous acid, five grains of each drug were taken three times a day before meals for one week with a nor- mal period between the use of each drug. Sc!//cy//c Aiid. iAccording to Rideal, (i) this drug is not a harmless remedy and may produce a disintegrating effect upon the blood corpuscles. The salts of salic^dic acid may cause albuminuria, indicating an irritating effect upon the kidney, perhaps on account of the forma- tion of phenol (2). H. Leffman, (3) after a number of experiments, concluded that salicylic acid in all forms, natural, crude or refined, is distinctly antagonistic to most enzymes, especially those that convert starch. He showed that in the proportion of i to 20000 it retarded the con- conversion of starch in the ratio of 245 to 174, while i to 1000 entirely prevented conversion, both with diastase and pancreatic ferments. Chittenden (4) found that salicjlic acid and salicylate of soda greatly retard peptic digestion. Rideal (i) thinks that if the drug is allowed to mix or pene- trate the food, that chronic dyspepsia and other symptoms would appear by the relatively large amounts that would accumulate in the svstem. There seems to be evidence, that like lead and arsenic it has a cumulative action. Bronacdel (5) especially characterizes salicylic acid as being injurious in cases of weak or diseased kidneys, by its cumulative action in the system. Luthye investigated the action of the salicylates on the urinarj' tract, and found in every case, evidence of desquamative irritation in the kidne>s, urinary passages and the bladder appeared inflamed. The urine contained tubular casts and its condition did not return to normal for two or three weeks. 34 Experiments (6) on calves bj' feeding them milk without sali- cylic acid and milk containing the drug in the proportion of i to looo, there was found a difference of 3.4S'.'ti protein and 4.56;u fat, in favor of the untreated milk. Antiseptic and Preservative Uses. The strength of salicylic acid required for killing bacteria has been variously given by different observers. Vallin claims "that its action on ferments and microbes is often only temporary ; the ferments and bacteria rapidly become used to their new surroundings and the following generations that succeed, resist doses that have been fatal to their ancestors. For this reason alcoholic beverages which can only be preserved by the aid of salicylic acid require large amounts, as high as 1.5 grams per liter. Salicylic acid is considered a convenient an- tiseptic, but it gives no absolute guarantee, and its power is limited. This drug has been largely used for preserving perishable foods in the proportion of four to eight grains to the pint or pound. It is used to aid the preservation of fruit, beverages, milk, fish, meats and eggs. Experivie7ital. After six urinary examinations to determine the average for the normal urine, as previously explained, the writer took five grains of salicylic acid in capsules before meals ior seven da}'S. The urine was collected and examined as before and the average taken for the Salicylic period. An unpleasant and somewhat burning sensation in the stomach was noticed soon after taking the drug. The appetite and general system appeared to be somewhat depressed and there was a continuous but not severe pain in the region of the kidneys. The following table shows the effect upon the urine. Normal Period Amount Sp. gr. Solids Chlorides Sulphates Phosphates Urea Dec. 29-Jan. 3, '04 Average of 6 Examinations 991 1027.6 63.169 7.563 1.927 2.0S4 2S.22 Salicylic Period Jan. 4-10 Average of 7 Examinations 841 1028.5 53-903 7.200 2.292 1-957 27.494 Maximum of Normal Period 1220 1030, 69.900 9-333 Maximum of Salicylic Period 1 150 1032. 69-570 15.8S4 Minimum of Normal Period 830 1024. 57-510 5-780 Minimum of Salicylic Period 485 1026. 36.132 3-378 35 2.500 2.415 32.00 4.025 3.220 36..80 1.927 1.830 23.24 1-350 1-35S 17.46 A comparison of the two averages shows a decreased amount of urine, a higher specific gravit}' and a decrease in all of the con- stituents except in sulphates, during the drug period. Borax. Lubrech (7) experimented upon dogs, by giving them five grams of borax per day. After the sixteenth day, the dogs showed symptoms of violent intestinal inflammation with hemorrhage ; appetite being diminished. There was howling and whining indicating severe pain. This showed that borax in two great concentration is liable to excite intestinal symptoms and irritation. Henry Leffman (8) claims that borax in very large doses tends to retard the assimilation of proteid and fattj^ food, increasing notably the weight of feces and their contents of nitrogen and fat. Excessive doses cause diarrhoea. In moderate doses, borax showed little or no interfering action with either starch or proteid digestion. Chittenden and Gies (9) experimented on dogs with borax and analyzed both urine and feces. They arrive at the following con- clusions : I. That the animal increased in weight, not from the laying on of fat, but to the diminished secretion of water. 2. The specific gravity of the urine was increased, rising from 1017-1018 to 1022-1027, dropping back as the experiments were discontinued. 3. The reaction of the urine, after the first day of borax, changed from an acid to an alkaline reaction. 4. The salt was rapidly elim- inated, for thirty-six hours after close of borax period no trace of it could be found. 5. Has no cumulative action in the system. The amount daily per dog was five grams. Experiments in feeding calves (6) on milk with and without 36 borax. The amount of borax given was i of borax to 675 of milk. The determinations showed there was 1.3 per cent protein and 0.2 per cent fat gain in amount in favor of the untreated milk. The borax appeared to prevent digestion to a slight extent. Preservative Uses. Borax is used in the preservation of milk, cream, marjorine and butter principally. It is also used in the pre- servation of meats and fish. Experimental. Five grains of borax were taken three times a day, before each meal, for a week. An occasional headache, some pain and uncomfortable feeling over the region of the kidneys were experienced. Micturition occurred during the night in this period. This had not been experienced before and did not occur later. The bowels appeared looser and a larger quantity of feces was passed. The appetite was in no way affected. The ef- fect upon the urine is shown in the subjoined table : Normal Period Amount Sp. gr. Solids Chlorides Sulphates Phosphates Urea Jan. 11-17 Average of 7 Examinations 9S9 1027. 62.10 6.84 1.89 1,81 29.30 Borax Period Jan. 18-24 Average of 7 Examinations 982 1025.7 58.42 6.39 1.26 1.74 26.61 Maximum of Normal Period 1200 1030. 72.60 7.65 2.25 2.13 33.70 Maximum of Borax Period 1325 1028. 74.06 9.01 2.00 2.3 Minimum of Normal Period 800 1024. 55.90 6. [2 1.71 1.62 33-tJO 24. CO Minimum of Borax Period 700 1024. 45.64 4.76 0.70 1.35 19.60 A comparison of the averages shows there is a slight decrease in all of the constituents during the borax period. Boric Acid. Dr. J. J. Evans, (10) in treating a case of cystitis with boric acid, and increasing the dose from ten to twenty grains three times a day, concluded that the drug had a toxic effect. After three weeks of treatment, an erythematous rash spread over the man's face, neck and head. This was followed by a sub- 37 cutaneous oedema and scah- dermatitis : the salivary glands becoming enlarged, eventually the hair of the face and head fell off, inside a fortnight. In treating similar cases later, the same symptoms resulted. Von Noorden, (ii) shows that a 3.5 per cent solution of boric acid gave rise to a stomatitis, characterized by swelling of lips, gum, border of tongue, salivation, tenderness, and now and then superficial ulceration. G. Merkel, (12) administered boric acid internally to thirteen patients for its assumed action, in doses of from one to two grams daily, in aqueous solution, for eight days. The polyuria that followed, even small doses, surpassed twice and even three times the normal amount, and boric acid could be detected for seventeen days after it had been discontinued. Seven of the patients com- plained of various gastric disturbances, colic and diarrhoea, while taking the drug, another of the patients who used insufflation of boric acid, was, after several days, affected with erythema. Metabolism experiments (13) in which respiratory products were taken into account, indicated that boric acid increased the pro- duction of COj and water vapor, and increased the clearage of fat, or carbohydrates in the body. In experiments, (6) in feeding calves with milk containing pre- servatives, it was found that there was a difference of 2.52 percent protein and 0.19 per cent, fat in favor of the untreated milk, against that containing boric acid. Boric acid appears to prevent digestion. Chittenden and Gies (g) performed experiments on dogs with boric acid, from which the urine and feces were analyzed, and they drew the following conclusions : I. Moderate doses up to five grams per day, even when con- tinued for some time, does not influence proteid metabolism. 2. There was no specific influence on the general nutrition of the body. The body weight did not tend to increase. 3. Large doses 5-10 grams per day directly stimulates proteid metabolism, increases the excretion of nitrogen, also the sulphates and phosphates. 4. Ex- cessive doses tend to cause an increase of mucus and diarrhoea. 38 Preservative Uses. Boric acid is used as a preservative for butter, cream, milk, hams and fish. Some writers think that meat preserved by boric acid is not diminished in nourishment and is more readily assimilated ; others disagree and arrive at an opposite conclusion. Lehmann infers that it is not the boric acid that acts as the preservative, but rather the substances produced by it, i.e., acid phosphates. Experimental. Five grains of boric acid were taken three times a day just preceding each meal. The urine was collected and examined as in the preceding cases. Aside from some diuresis, no physical effects whatever were felt. Urinary Tabi^e. Normal Period Amount Sp. gr. Solids Chlorides Sulphates Phosphates Urea Jan. 25-31 Average of 7 Examinations 732 102S.3 45.650 11.960 1.056 1.360 20.57 Boric Acid Feb. 1-7 Average of 7 Examinations 859 1026. 51.262 16.396 1.246 1.3SS 20.97 Maximum of Normal Period 850 1030. 55.920 14.790 1.300 1.760 25.60 Maximum Boric Acid Period 1030 1030. 62.592 22.200 1.545 1.72S 23.25 Minimum of Normal Period 625 1022. 41.400 9.900 0.425 0.9 15.60 Minimum Boric Acid Period 525 1022. 36.720 S.790 0.780 1.05 14.70 A comparison of the averages shows a lower specific gravity but an increased quantity of urine with higher constituents during the boric acid period. This indicates increased metabolism. Benzoic Acid. Julan de la Croix (14) in seventy-four ex- periments, with varying quantities, found that the least quantity that would prevent bacterial growth in fresh beef tea was i to 2800. To kill bacteria it required i to 410 and to sterilize spores i to 50. Graham Brown (15) stated that sodium benzoate was superior to 39 quinine hydrochlorate and sodium salicylate in destro>ing the virus ot diphtheria. He believed even that by saturating the human sys- tem with benzoic acid, by repeated hypodermic injections, the system was rendered almost insusceptible to inoculation with diphtheria. Gosslin and Robin, (i6) proved that in disorders of the bladder attended with ammoniacal urine, that benzoic acid taken internally rendered the urine acid, preventing the precipitation of insoluble phosphates and the formation of carbonate of ammonium and poisonous salts by the urinary bacteria. They used it in uremia successfully, in amounts of i to 4 grams daily, dissolved in glycerine and water. Wernitz, (17) declares that pepsin is neutralized by i to 200 and others by i to 300 of benzoic acid or benzoate of soda. In order to determine whether benzoic acid increased the acidity of the urine, Dr. William Ashhurst, (18) experimented upon dogs. The urine of the dogs was tested for a number of days previous, afterwards the dogs received hypodermicalh- i gram and finally 2 grams daily. From the experiments he drew the following conclusions; i. It had an inconstant diuretic effect, accompained by a slight diminution of the acidit}' of the urine. 2. Retardation or absolute prevention of the occurrence of alkaline fermentation. 3. It had a germicidal and inhibitory action on the growth of certain micro-organisms, either within the bladder or introduced from without into the urine after voiding. Preservative Uses. A saturated solution in water delay's the putrefactive changes taking place in animal matter. It is used in preventing fats from becoming rancid as in "adeps benzoinatus." Added to milk in small quantities, it prevents coagulation, but its action is not as lasting as the fluorides, probably owing to the benzoic acid being more easily decomposed by some of the organisms. Experimeyital. Five grains of benzoic acid were taken three times a day in capsules before each meal. A general feeling of de- pression appeared to result from the use of this drug. There was a dull headache and dull but rather continuous pains over the region 1-39 23-75 I.S5 30.00 1-53 2S,90 1-35 1 7- 50 40 of the kidneys. The appetite and tone of the stomach appeared to be lessened. Urinary Table. Normal Period Amount Sp. gr. Solids Chlorides Sulphates Phosphates Urea Feb. 22-2S Average of 7 Examinations 846.4 1026.85 52.27 15.25 1.37 1.51 26.54 Benzoic Acid Period Feb. 29-Mar, 6, '04 Average of 7 Examinations 824.2 1026.85 51.52 13.68 1.44 Maximum of Normal Period looo. 1030. 64.65 18.46 2.30 Maximum Benzoic Acid Period 1070. 1030. 59-81 18.19 1.70 Minimum of Normal Period 700. 1022 45-37 12.44 0.90 Minimum Benzoic Acid Period 700. 1024 42.35 10.35 1.05 1.12 19.50 The average periods show a gain in sulphates for the benzoic acid period. For the other constituents there is a slightl}' higher amount for the normal. Sulphurous Acid. Sulphurous acid and the bisulphites are widely used for preserving foods. They act i, by abolishing the oxygen and 2, by suspending the growth of moulds and ferments like those of the viscous, acetous, lactic and butyric fermentations. It has been used as a preservative for milk intended for butter and cheese making. It is used extensively in beer, wine and fruit syrups to absorb the oxygen and prevent secondary fermentations. Sulphurous acid is used by refiners of beers and making of lime juice and vinegars. It is also used in the preservation of meats. In canned goods it is objectionable as it may dissolve the lead and tin from the metallic envelopes. Experimental. Fifteen minims of sulphurous acid were taken three times a day, after each meal for the period of one week. In this experiment five examinations of the normal urine were made twelve days before the drug was taken. In addition to the drug 41 period, seven examinations were made during the following week, making three series of examinations in this experiment. Urinary Table Normal Period Amount Sp. gr. Solids Chlorides Sulphates Phosphates Urea Apr. 13-17 Average of 5 Examinations 826 1022.6 45.22 13.48 Sulphurous Acid Period Apr. 29-May 5 Average of 7 Examinations S75 1026. 8 53.43 i4-7i After Period May 6-13 Average of 7 Examinations 757 1026.5 46.57 12.52 Maximum of Normal Period 9S0 1024. 47.92 15.98 Maximum of Drug Period 1150 1030. 59.41 21.95 Maximum of After Period 850 1030. 51.42 15.02 Minimum of Normal Period 800 1020. 44.27 9.48 Minimum of Drug Period 750 1020. 39.46 11.33 Minimum of After Period 1.38 1-75 i-^i 1.60 2-33 650 1024. 44.72 9-^5 1. 16 1.60 1.87 2-33 2.09 2.23 3.01 2.28 1-57 1.55 i.q8 21-73 27,90 24.28 24.70 33-IO 2550 19.20 24.70 A comparison of the averages shows that there was an increase of all constituents during the drug period as compared with the normal and that the after period corresponds more closely with the normal than the drug period, except in specific gravity and in the amount of sulphate which curiously enough, is in greater quantity than during either of the other periods. The increased elimination would indicate a greater metabolism. KcHiNACEA. This drug is obtained from the root oi Echmacea Angustifolia and various claims are made for it. It is especially recommended in blood depravation and is useful in anemia. All 42 glandular organs are said to undergo a stimulating influence with increased functional activity. Digestion, absorption, assimilation, and general nutrition is improved. It is said to stimulate, mar- kedly, retrograde metabolism, influence the lymphatic system and stimulate the capillary circulation. This drug was experimented with for the purpose of determin- ing its effect on metabolism. Five grains of the extract in tablet form were taken just before each meal. Urinary Tabie. Normal Period Amount Sp. gr. Solids Chlorides Sulphates Phosphates Urea Feb. S-14 Average of 7 Examinations 873.5 1025.1 50.5S9 13.15 1.25 1.37 26.45 Echinacea Period Feb. 15-21 Average of 7 Examinations 907. 1024.8 51.97 13.18 1.16 1.61 21.51 Maximum of Normal Period 1140. 1030. 58.368 17.44 1.40 1.87 29.75 Maximum of Drug Period 1050. 1030. 63.52 15.93 1.57 2.52 31.50 Minimum of Normal Period 700. 1022. 47.50 10.47 iio 0.6S 23. So Minimum of Drug Period 750. 1022. 4537 11.94 0.75 1.14 16.50 A comparison of the averages shows that there was some diur- esis and a slightly greater elimination of solids during the drug period, except in sulphates and urea. The difference in the latter is quite marked and is contrary to the results of some other investi- gators. (19). The drug appeared to act as a tonic ; increased the appetite considerably and appeared to give better tone to the system generally. 43 BIBUOGRAPHY. 1. Rideal S. Disinfectants and Preservatives, 1903. 2. Lancet. Dec. 20, 1879. 3. Journal of Franklin Institute, Dec, 1898. 4. Journal of Physiology, 1898. 5. Hyg. Congress. Geneva, 1882, II. 352. 6. Bulletin 86. Maryland Experiment Station. 7. Cornell Expt. Sta. Report 1899-1900. 8. Journal of Franklin Institute, 1S99, Vol. 147. g. American Jour. Physiol, 1898, Vol. I. 10. British Medical Journal, 1889. 11. Zentralblatt fiir innere Medizin, 1903. 12. Jour. Med. Ass'n, 1903, Vol. 40. 13. Hygiene Rundschau, 1902. 14. Archive Expt. Path., 18S1, Vol. XIII, p. 175. 15. Klebs Archives Vol. VIII, p. 140. 16. Archive Ginirale de Medicine, 1874, Vol. XXIV, p. 566. 17. Dorpot Essays, 1880. 18. Philadelpeia Medical Journal, 1900, Vol. V, p. 456. 19. P. A. Fish. American Veterinary Review, 1903, Vol. XXVII. GouipliriientB of PIERRE A. FISH, ABSTRACTS OF WORK DONE IN THE LABORATORY OF VETERINARY PHYSIOLOGY AND . . . .PHARMACOLOGY . . . , UNDER THE DIRECTION OF P. A. FISH NO. 3 NEW YORK STATE VETERINARY COLLEGE CORNELL UNIVERSITY • ITHACA, N.Y. 1906 TABLE OF CONTENTS PAGES 3 Urethral Calculus in the Dog P. A. Fish Arecoline Hj'drobromate H J. Milks g The Effect of Sulphurous Acid upon Peptic and Tryptic Digestion P. A. Fish 14 Ergot as an Abortifacient A.J. Bjirley 22 The Status of Therapeutics P. A. Fish 30 The Structure and Function of the Digestive Tract of the Chicken F. H. McNair 35 The Effect of Sulphurous Acid upon the Urinary Con- stituents P. A. Fish 43 URETHRAL CALCULUS IN THE DOG. PIERRE A. FISH. The patient, a male coach dog, four years of age, weighing about fiftj' pounds was brought to the clinic *, May i, 1905. The history, as given by the owner, was to the effect that the dog appear- ed to be in a normal condition up to within about 24 hours of the time that he reach the clinic. Attempts at micturition were un- successful although the animal used his best efforts. An examination of the urethral tract was made externally and a small movable mass was detected at the proximal end of the bone of the penis. A small sized catheter was also passed but met an obstruction, easily distinguished by a peculiar grating sound and by the fact that the catheter would go no farther. The use of the cath- eter confirmed the external examination and as it was quite evident that the mass could not be forced out through the urethra, the pa- tient was prepared for an operation. Anesthesia was effected by the injection of one half grain of morphine sulphate hypodermically and the inhalation of ether. The operative area was shaved, disinfected and a longitudinal incision was made on the left side of the sheath at the proximal end of the penal bone. The cut was continued through the urethra directlj' to the obstruction and a calculus of irregular form and about the size of a small pea was removed. It was planned to draw the accumulated urine from the bladder with a catheter after the calculus was removed, but before this could be accomplished, the patient passed a considerable quantity of urine without assistance, through the urethral incision. The wound was disinfected with sublimate solution and the urethral incision sutured with catgut ; the dermal incision was also loosely sutured with the same material. *N. Y. State Veterinary College. The following day the stitches were removed from the external wound and some clots of blood removed. The sheath and testicles were considerably swollen. Thermofuge was applied locally and eight grains of Ichthyol were given internally three times a day to relieve the inflammation. Urination occured in a normal manner except that the urine last expelled was of a bloody character. The wound was dressed daily with sublimate .solution and dusted with compound alum powder. The swelling of the sheath soon yielded to the treatment, but the orchitis continued. After a few days more of the same treatment, this condition also improved. The tempera- ture hung about 103°. The highest temperature recorded was 103.8°. Two weeks after the operation, 5 grains of Sodium Benzoate were administered three times daily and the Ichthyol discontinued. The dog was discharged May 16, and the owner advised to continue the Sodium Benzoate and to dress the wound, which was not quite healed, with the sublimate solution. On June 10, the dog was returned with symptoms similar to those exhibited May i. The dog could pass only a few drops of urine at a time. The catheter showed an obstruction at the base of the bone of the penis as before. An operation was immediately performed similar to that of May i, except that the incision was made upon the right side of the sheath. The calculus this time was not much more than half as large as the previous one, and with it came a still smaller one. In both operations, there were in addition to the larger calculi a few smaller ones of about the size of a pin head. In this operation the urine was not passed through the wound as before and there was doubtless less infection, because there was scarcely any swelling of the sheath and the wound appeared to be in a healthy condition. There was some orchitis, however, which gradually improved without special treatment. The procedure and treatment in the second operation were very similar to that of the first, except that Ichthyol was given for a shorter period and a tablet of Calcalith. three times a day was substituted for the Sodium Benzoate. The Calcalith (a combination of Calcium, Lithium and Colchicine) was given with the idea of its forming combinations with the phosphates and ehminating them through the intestinal canal thereby decreasing the elimination through the kidneys. Shortlj' after the first operation the urine was examined for phosphates and the normal amount was found to be more than doubled. A partial analysis of the calculus was made. Phosphates and carbonates were found to be present, probably in combination with lime as a base. For three months there was no return of the trouble and the owner reported the dog to be in as apparently a normal condition as ever. On September 13, the dog was returned by the owner. (The dog was exhibited at the State Meeting, then in session). There was considerable orchitis and swelling of the sheath. On the left side of the sheath near the scrotum there was an opening in the skin from one to two centimeters in diameter. It appeared as if some urine escaped through this orifice, but an attempt to pass a catheter through it was not successful. An attempt to pass the catheter through the penis was likewise unsuccessful at first, although it was passed later. The swollen condition of the parts made an external examination for calculus ver^' difiicult. The dog was placed under morphine-ether anesthesia and the skin orifice enlarged and the incision carried down to the urethra. A catheter was easily passed through this orifice into the bladder. A catheter was also passed the full length of the penis without ob- struction, indicating that no calculus was present in the urethra and probably no stricture. The wound was dressed antiseptically but not sewed. On the day after the operation, there was no trouble in passing a catheter and drawing some of the urine. A small opening now appeared in the skin upon the right side of fhe sheath as if there might be pus present, although none was seen. Temperature 101°. The wound was dressed and injected with Compound Iodine Solu- tion (Lugol's). The swelling of the sheath soon decreased as did that of the scrotum, although more slowly. The urine at first passed through the wound but on the sixth day after the operation it was observed to pass normall}' through the penis. Within two weeks the swelhng- and orchitis had disappeared and the wound was healing nicely : but at this time the dog was not teeling so lively as heretofore and soon gave evidences of sick- ness by refusing his feed and developing a slight rise in temperature. The treatment consisted of tonics and antipyretics without much apparent change in his condition. Although not improved in health, he was taken home by the owner after the third week and the treatment kept up. The dog, however, grew weaker, and two weeks after he was taken home he wandered awaj' and never re- turned. It is much to be regretted that an autopsy could not have been held. It was brought out later, that just previous to the last attack the owner had washed the dog in a creek and he believed that the dog had taken cold at this time. The swelling of the sheath and scrotum may have been caused by this cold bath, as the tissues in the above named parts were probably weakened from the previous operations and therefore more susceptible — the effect ultimately ex- tending through the whole system and being more or less responsi- ble for the fatal ending, notwithstanding the fact that the wounds were healing nicely and that the surgical part of the case was apparenth- successful. There is some variance in opinion as to the frequency and treatment of such cases as shown by the following extracts : Ashmoat ''Joseph F. Perry , Jr, ;, "Dogs; Their Management and Treatment in Disease" (1886;, states regarding cystic calculi that "a cure is out of the question" and that ''the symptons must indicate the line of treatment to be followed." J. H. Steel, "A Treatise of the Diseases of the Dog" ^1888), states that cystic calculi must be considered as frequent in the dog, and that cases are also on record in the bitch. With regard to the urethral calculus he says this "is generally a small cystic stone im- pacted in its passage Turethra;. Manipulation may enable us to bring it down to the orifice of the canal and there grasp it with the forceps and so aftord relief otherwise an incision must be made on it, where it can be felt in the urethra, and removal so effected." J. Woodroffe Hill, "The Management and Diseases of the Dog" (1900, 5th Edition), states that in June, 1S81, he performed the first recorded case in English literature of canine lithotomy- on a St. Bernard bitch. Miiller, "Diseases of the Dog" translated by Glass, recognizes four types of urinary calculi : urates, oxalates, phosphates and cystic stones. The latter being soft, wax-like bodies with a shiny, crystalline, irregular surface. The composition of the other types is indicated by the names. He also reports a calculus weighing 490 grams fabout one pound) having been taken from a German boar- hound. The origin of the calculi is generally in the pelvis of the kidney, according to Miiller, usually from some foreign bod}-, as a blood clot, a piece of mucus, epithelium, etc., around which the sediment in the urine forms and gradually the crystalline elements accumu- late. This deposit is especially favored in cases of cystitis, where the urine is undergoing alkaline fermentation and produces a copious sediment in the urine. Where there is ischuria (retention or sup- pression of urine) relief by operation or drawing off the urine must be reasonably prompt. If the urine is not drawn off in three days the bladder is ruptured and it may burst in two days. When the rupture occurs, death takes place in a few hours. Miiller states that it is well established that it is impossible to produce any good results from the injection into the bladder of anj' of the various agents that are supposed to have the property of dis- solving calculi ; as for instance acids for dissolving phosphatic cal- culi, alkalies for breaking up uric calculi, or the drinking of mineral waters, such as Vichy, Wildung, Carlsbad. He recommends the operation of urethrotomy if the calculus is located in the urethra, or cystotomy if located in the bladder. In his operation in urethrotomy, he recommends that the wound be left open unless it be large, in which case only one stitch is em- ployed. The urine escapes through the wound for two days, but the wound soon closes, and in eight or ten days, he states, the urine is passed in the natural way. 8 Frederick T. G. Hobday, "Surgical Diseases of the Dog and Cat" 2d Edition. 1906. In the dog and cat, particularly in the male animals, small calculi are frequently met with in the urethral canal. In one instance Dr. Hobday removed eleven calculi at one ure- throtom}' operation, the patient being a St. Bernard dog. On each of two other occasions he counted more than fifty small calculi in the urethra and bladder. Relief from distended bladder due to calculi may be obtained either by puncture of the bladder or ure- throtomj'. In the former case a trocar and cannula, with due antiseptic precautions, are inserted into the bladder through the linea alba from i to 3 inches behind the brim of the pelvis, so as to pierce the bladder where it is tense and fairly close to the neck. One patient was operated upon in this via.y five times in three months with no bad results. The operation for urethrotomy is to remove the stone. Dr. Hodbay recommends an incision in the median line directly over the calculus and the stone remo^-ed with any others within reach, and the parts thoroughly washed with a fluid antiseptic. In some cases he thinks it wise to leave the catheter hi situ for some hours after the operation. If the wound is small he recommends suturing and covering with Iodoform and Collodion ; but if of some length, a small orifice should be left for drainage, as otherwise the urine will find its way through and disturb all the sutures. In any case it does not much matter, and many operators advise using no sutures at all, but treating the place as an open wound. In the female the shorter urethral canal does not offer quite so many difBculties. "The Prognosis of these cases is excellent except where the patient has been left until almost in a state of collapse before sur- gical aid is attempted. The internal administration of bladder and urethral sedatives, such as urotropin, hyoscyamus, buchu, pearl- barley-water, etc., afterwards are useful aids to convalescence. The chief dangers in the future are those of stricture or the presence of another stone which may escape from the bladder." ARECOLINE HYDROBROMATE. HOWARD J. MILKS, WATERTOWX, X. Y. Arecoline is the alkaloid of Areca nut. The nut has been for a long time in use as a remedy for tapeworms and other worms of the intestinal tract. The alkaloid has been employed as an active ptirgative in colic and laniinitis. It is claimed that it is more active as a purgative than eserine or pilocarpine or both. It is also said to be a remedv for tapeworms and has been used for its effects upon the eye as a myotic. Before beginning a description of its propei- ties, some references may be noted as to the characteristics of the drug. U. S. Dispensatory. Areca nut, or Betel nut as it is sometimes called, is the product of an East Indian tree belonging to the family of palms. The fruit, which is about the size and shape of a small egg, and of an orange color, contains the nut imbedded in a fibrous fleshy envelope, and invested with a brittle shell which adheres to the exterior flesh. The Betel nut of commerce is of a roundish conical shape,, rather larger than a chestnut, externally of a deep brown, diversified with a fawn color, internalh- brownish red, with whitish veins, very hard, of a feeble odor when broken and of an astringent taste. It abounds in tannin and also contains gallic acid, a fixed oil, gum, a little volatile oil, lignin and various saline substances. E. Bombalon obtained from it a volatile alkaloid, resembling nicotine, which he named Arecaine. It is left from an ethereal so- lution in the form of a colorless, oih' liquid smelling like weak meat broth and having a strong alkaline reaction. With tartaric, citric, hydriodic and salicylic acids it Ibrms varn- ish like salts, the salicylate having a tobacco-like odor. Its taste is, at first, imperceptible but later acrid. It increases the secretion of saliva, lessons the pulse and has a purgative action. lO E. Jahns has found three alkaloids : Arecoline C^ H,3 NO^, identical with the Arecaine of Bombalon, Arecaine C,H„N02+HjO which occurs in colorless crystals, permanent in the air, soluble in water but not in absolute alcohol, chloroform, ether or benzol; thirdly an alkaloid which exists in quantities too minute to analyze. Jahns considered Arecaine the active principle and pronounced it a powerful teniacide resembling Pelletierine. It also resembles Muscarine but depresses both the heart and respiration ; causes te- tanic convulsions and increases peristalsis extraordinarily. It con- tracts the pupil. Arecoline is a volatile oil, miscible in all proportions in water, alcohol, ether and chloroform, forms crystalline salts and is pro- nounced very toxic. It exists in the nut in the proportion of 0.1%. The hydrobromate is the form in which it is used: The dose for the horse being one- half to one grain. It is a more powerful stimulant of the salivary glands than Physostigma and is especially used in colics in horses in the above doses and for tapeworm in man in 1-15 — i-io grain doses. It is also used as a myotic. A 1% solution in the eye profluces strong myosis. It has been pronounc- ed superior to Physostigma in glaucoma, though less enduring in effect. E. Frohner finds that it increases secretions and peristalis act- ing similarly to a combination of eserine and pilocarpine. The first passage from the intestines takes place in from one fourth to one half hour after the injection. The laxative effect is followed by slight colicy symptoms. Large doses are diaphoretic. Poison- ous doses bring about an irregular condition of the heart, lessen blood pressure and slows the heart. Five grains kills a horse. As a therapeutic agent he has employed it on account of its action, stability of preparation and cheapness. It has proven valuable in colic and laminites. Dr. W. L. Bell recommends its use in colic and laminitis. The treatment in laminitis consists of injecting one grain daily subcutem, along with applications to the feet. He states that before using Arecoline he could not get such good results although the other parts of the treatment were as rigidly adhered to. A Belgian veterinarian reports a series of cases of laminitis in which recovery took place very promptly. The animals were fully recovered and put to work on an average of about six days. I have experimented upon several dogs to ascertain the effects of the drug in different doses. Case Xo. i. Fox Terrier weighing iS lbs. One half grain of Arecoline Hydrobromate was administered subcutaneously. In three minutes he was dull and weak. He leaned against the cage, then pitched headlong to the floor. He was thrown into convulsions at each attempt to move. In a short time he was quiet, lying upon his side ; his breathing was irregular and his mouth*was wide open. At times his breathing was labored and difficult, then quiet as if in deep sleep. The pupils were dilated. The bowels moved m fifteen minutes and again in one and a half hours. Case Xo. 2. Weight about 25 lbs. The doses were given on alternate days, beginning with 1-20 grain. This had no effect except to accelerate the breathing, A dose of i-io grain produced salivation and passages from the bowels in i '; hours. Upon giving a dose of i gram the bowels moved twice very copiously within eight minutes. The pupils were dilated. The animal was weak, de- pressed, breathing irregular and he layed upon his side with legs extended. The following day the dog was as well as usual. Upon giving a dose of 2 grains, the feces were passed in six minutes, also the urine. Another passage of feces in five minutes. He was very weak and irritable. The pupils were dilated and he rested upon his side. There was a third passage of feces in ten minutes. In one hour he was resting easily and took note of his surroundings. The next morning he was better but would not eat. The bowels were still loose and blood was passed with the feces. He gradually grew better for the following six days, when he had apparently recovered. Later he was given 3 grains with essentially the same sj-mptoms as were secured with the former dose, except that they were more severe. He was injected at 2:30 p. yi, and died the following morning at 9 a. m. The post mortem showed : lungs normal ; spleen slighth' congested ; stomach full of a dark green liquid. The small intestines 12 were con>^esteil iu areas '--2 inches long. Cecum congested. Liver, pancreas and kidneys normal. Bladder congested. Auricles empty. Ventricles full of dark blood. The mucosa of the ileum was very much congested and showed a bloody exudate. The contents of the intestine were bloody. Seven tapeworms were found in the small intestines. This fact was interesting, since the dog had been repeatedly dosed with the drug and in quantity sufficiently to purge and finally to kill, yet the worms had not been expelled. Several kittens were used. Doses of /s to^2 grain proved toxic with the following symptoms : Feces in about three minutes. Signs of illusions. Ran about cage with tail bristled and spitting at imaginary objects. Very irritable. Pupils dilated. Lying upon its side in 8 to 10 minutes. Soon the respirations ceased but the heart did not stop until one or two minutes later. A dose of 1-16 grain produced no symptoms in a cat of 5 or 6 pounds. To test the keeping qualities of the solution, one fifth grain that had been in solution for two weeks was injected. This seemed as powerful as a fresh solution, killing the cat in a few minutes and with the usual symptoms. In a dog under chloroform anesthesia, jV grain was injected into a loop of the intestine and the loop ligated at either end. An adjacent loop was kept as a control. In three fourths of an hour the different segments were examined. The segment receiving the arecoline appeared harder and firmer than the control. Upon cutting open both segments, congestion was found in the one con- taining the arecoline but not in the other. No difference in the amount of secretion could be noticed. Salivation did not occur. In each segment living tapeworms were found. To try the effect of the drug upon the heart, experiments were performed upon the horse and frog. In the case of the former, intravenous injections were used and a blood pressure tracing taken. In each case a very rapid fall in blood pressure was obtained. In the case of the frog a minim of the solution was dropped upon the heart. It was found that i"o would stop the heart within one beat and more permanently than stimulation of the vagus. Solutions of o. 1^0 acted nearly as strongly as the i"o. If a drop of strychnine or 13 atropine solution were applied before the arecoline, the action of the drug was not very marked. As a curative agent, I have not had much opportunit}' for exper- iments. In one case of impaction colic in a mare possessing an enormous ventral hernia, I gave Yz grain and secured no action other than salivation. Half an hour later ify grain was given and a copious discharge was secured from the bowels in about 20 minutes. The salivation was very marked. In about ten minutes the animal opened its mouth and a mouthful of saliva fell out. The saliva kept dropping for about 15 or 20 minutes. During the action of the drug the animal was quite restless and colicy. In one stable in which laminitis occured at the same time, are- coline was given to two horses and an aloes ball to the third; in other respects the treatment was the same. The two receiving the arecoline were worked on the second day and were examined in the evening. Thejr were found entirely recovered. The third case also worked ■on the second day but was pretty sore at the time of examination. The following conclusions as to the action and uses of arecoline TOAy be drawn from the preceding experiments and the literature upon the subject; that it is a rapid intestinal evacuant, increasing both peristalsis and the secretions. That its action is accompanied by colicy symptoms and profuse salivation. That its action upon the eye is two-fold, locally it is a myotic and internally a mydriatic. That the chief dangers in its use are on account of its action upon the heart and respiration. Indications for its use are in cases of colic, laminitis or wherever a rapid evacuant is desired. That as a remedy for worms, especialh' as a teniacide, it can- not be relied upon from the facts that solutions of it have failed to expel the worms when given in doses sufficient to produce purga- tion and finally to kill the dog, nor did the solution kill the worms applied to them directly, as in the case where the bowel was ligated. Its chief advantages over eserine and pilocarpine are that it is more permanent in solution, and is cheaper especially if pur- chased in bulk. THE EFFECTS OF SULPHUROUS ACID UPON PEPTIC AND TRYPTIC DIGESTION. PIERRE A. FISH. The more closeh' digestion experiments can be made to approx- imate normal conditions the more reliable they are. Normally the digestive products are absorbed soon after they are formed. In test tube experiments no absorption occurs and the accumulation of the digestive products may interfere with the complete digestion of the food stuil. In the following experiments the sulphurous acid was, in most instances, added to the artificial digestive fluids at the same time the substances to be digested were added. Possible explanations for negative results would be that the acid might have an inhibitory action upon the enzyme, or change the constitution of the food stuff, or both effects might occur coincidently. Experiment i. A solution was prepared by dissolving i cen- tigram of scale pepsin in loo cc of a 0.2",, solution of hydrochloric acid. Tube i served as control and contained i gram of dry fibrin in 20 cc of the above fluid. Four more tubes were prepared in the same way ; but varying proportions of sulphurous acid were added. Tube 2 contained i minim : tube 3, 2 minims ; tube 4, 5 minims and tube 5, 10 minims of sulphurous acid. All of the tubes were placed in the incubator for 24 hours at a temperature of about 40° C. ^^ery good tests were obtained from all of the tubes showing the presence of soluble and acid albumin, albumose and peptone. The undis- solved residues were dried to constant weight and the weight taken to determine the amount of the substance which had gone into solution as shown in the following table : Dried Percentage Residue. Dissolved. Tube I Control i7-5o"o 82.50 " 2, I minim H, SO3 18.00% 82.00 " 3, 2 " t ( 10.20Q5 S9.80 " 4, 5 " (( 16.900-0 83.10 " 5. 10 " " 20.7oQ'o 79-30 15 Tube 3, with the greatest solubility, gave the least satisfactory peptone test ; while tube 5 with the least solubility gave a good peptone test. Experiment ii. 3 35 milligrams of scale pepsin were dis- solved in 100 cc of o.2 9o hydrochloric acid. The whites of freshly boiled eggs were passed through a number 40 sieve. Ten grams of this finely divided albumin were placed in flask i with 30 cc of the above solution. Flask 2 was prepared in the same way except that 10 minims of the undiluted sulphurous acid were added. Both flasks were placed in the incubator at 40° C for 48 hours. Dried Percentage Residue. Dissolved Flask I, Control 6.25% 93-75 " ,2, 10 minims H., SO, 9-78% 90.22 Peptones were found in both flasks, but No. i was more satis- factory. A greater part of the albumin also went into a solution. Experiment hi. A pepsin solution similar in strength to Experiment 11 was used. Two grams of finely divided lean meat were used in each flask in this experiment. Flask I, Control Meat. + 30 cc of pepsin solution. " 2, 5 minims H, SO;, " " " " " " 3, 5 minims H„ SO, " " " " " " 4, 2 gms. meat placed in 30 cc of undiluted H, SO, for 48 hours. After draining it was put in 30 cc of the pepsin solution. " 5, Same as No. 4, except that after draining it was fried in a spider with a little lard for a few minutes. It was then placed in 30 cc of the pepsin solution. " b, 2 gms. of normal fresh meat fried in spider as No. 5. Then placed in 30 cc of the pepsin solution. All flisks were placed in the incubator at 40° C and digestion allowed to continue for 48 hours. Flask I, Control " 2,5 minims H„ SO, " 3, 5 minims H, SO., " 4, undiluted H, SO,, . " 5, H, SO3 cooked " 6, normal, cooked Dried Percentage Residue. Dissolved. 10.00% 90.00 10.65% 89.35 ' 11.10% 8S.90 15.50% 84-50 23-95% 76.05 45.80% 54.20 i6 Soluble allniiuiu, acid albumin, albumose and peptone were found in all the flasks : the least satisfactory peptone test being obtained from flask 5. No. 6 gave marked peptone tests but was poorest in solubility. Cooking very evidently retards solution of the meat. Experiment iv. The pepsin solution consisted of 2 centi- grams of scale pepsin in 100 cc of 0.2^0 hydrochloric acid. Tube I, a bit of fibrin -|- 30 cc of pepsiu solution 2, " •' •■ •< .' .1 j^ 4 minims H.^ SO.J 3, " 4, " + 8 ' H., SO., + 15 ' H., SO,, + 30 " H, SO,, + 45 " H, SO3 + 60 " H., SO;, 7, " The temperature of the contents of the tubes, at the beginning of the experiment was 30° C : this was raised to 40° C and digestion continued for two hours. At the end of that period, peptones and all of the intermediate products were found in all of the tubes. In tubes Nos. I and 2 the reactions did not appear to be as strong as in the remaining tubes. Experiment v. One centigram of scale pepsin was dissolved in 100 cc ot undiluted sulphurous acid. In 20 cc of this solution was placed a half gram of fibrin in a moist condition. Digestion pro- ceeded for 24 hours. Good peptone tests were obtained. There was not the usual swelling and translucency of the fibrin as when hydrochloric acid was present. The fibrin remained opaque ; diges- tion occurred by erosion with slow disintegration of the mass. ExPERiJiENT VI. An artificial digestive fluid was made by macerating a portion of the raucous membrane of the stomach of a cat in chloroform water. The extract was filtered and i part of it was added to 9 cc of 0.2'^' 0' hydrochloric acid for the digesting fluid in each tube. Three tubes were used : No. i containining i gram of fibrin which had previously been soaked in water for 4 hours, and then allowed to dry again. No. 2 was treated similarly to No. I except that the fibrin was soaked in a solution consisting of sul- phurous acid I cc, water 29 cc, for 4 hours. No. 3 was the same as No. 2 except that the fibrin was immersed for 4 hours in undiluted 17 sulphurous acid. Digestion was allowed to go on for about lo hours at the usual temperature. Peptones and all of the intermedi- ate products were found. In No. 3 the fibrin had practically all disappeared : in No. 2 there was but little, while in No. 3 there was the largest amount of fibrin. The sulphurous acid had appar- ently increased the solubility of the fibrin. Experiment vii. Each flask contained 2 grams of broiled beef fineh' divided, immersed in 30 cc of a o. i°o solution of pepsin in the usual percentage of hydrochloric acid. Flask No. i served as control and was prepared as above described. Flask No. 2 was similar except that previous to broiling the meat had been preserved by immersion for a few hours in a 2%* solution of sulphurous acid. In flask No. 3, the meat had been preserved in a 5%' and in No. 4 a loS'o solution of sulphurous acid. Digestion proceeded for 24 hours. Dried Percentage Residue. Dissolved. Flask I, Control 19.10% So. 90 " 2, 2% preservative 16.85% 83-15 " 3, 5% ifi-gs'-'o 83-05 ■' 4, IO»,j 14.15;',, 85.85 Digestion had apparently been very thorough as all of the flasks gave excellent tests for albumoses and pepsin. TRYPTIC DIGESTION. Experiment viii. Five hundred milligrams of trypsin were dissolved in 123 cc of 1% sodium carbonate. Flask i contained 2 grams of flnely divided raw beef in 30 cc of the trypsin solution and 30 cc of water. Flask 2 was similar to No. i except that 5 minims of sulphurous acid were added. Flask la similar to No. i except in the amount of the trypsin solution and water. This flask con- tained in addition to the meat 60 cc of the trypsin solution and 60 cc of water. Flask 2a was prepared similarly to la but with the addition of 10 minims of sulphurous acid. *These figures do not refer to the amount of absolute acid, but to the percentage of the commercial solution dissolved in water. i8 Dried Percentage Residue. Dissolved. Flask I, Control I2.40",, 87.60 " 2, 5 minims H^ SO, 14-65% 85-35 " la, Control 15-95% 84.05 " 2a, lo minims H., SO, 14-50% 85-50 Digestion continued for 48 hours. Flask i gave a slight indol reaction and only faint traces of albumose and peptone. Flask 2 gave neither indol nor albumose nor peptone reactions. Flask la gave only a trace of albumose and a fair test for peptone. Indol was absent. Flask 2 a, indol absent. Traces of albumose and peptone. The sulphurous acid restrained putrefactive processes as shown by the absence of indol in Nos. 2 and 2a. Experiment ix. This experiment was similar to No. vii in peptic digestion. The trypsin solution was the same as used in No. viii. Flask No. i was control and contained 2 grams of broiled beef, finely divided, with 30 cc of the trypsin solution. Flask No. 2 was similar except that previous to broiling the meat had been preserved by a few hours immersion in 2% sulphurous acid. In fiask No. 3, a s'-'o and in No. 4, a 10% solution of sulphurous acid was used to preserve the meat. Digestion continued for 24 hours at 40°C. Flask I, Control " 2, 2% preservative " 3, 5% " 4, 10% All the flasks showed good peptone tests indol. Experiment x. The solution was prepared by dissolving 0.28 gram of pancreatin in 100 cc of a 1% solution of sodium car- bonate. Flask I contained 2 grams of finely divided raw meat in 30 cc of the above solution and 30 cc of distilled water. Flask 2, the same with the addition of 5 minims of sulphurous acid. Flask la contained 2 grams of finely divided raw meat in 60 cc of the pan- creatin solution and 60 cc of water. Flask 2a, the same as la with the addition of 10 minims of sulphurous acid. Dried Percentage Residue. Dissolved. 25-70% 74-3° 26.60% 73-40 20.00% 80.00 17-90% 82.10 Dtone tests ; they also showed 19 Dried Percentage Residue. Dissolved. 1S.50",, Sr.so iS.05% 81.95 22.35% 77-65 i4.85;'o 85-15 he flasks. Very faint tests for t No. 2. Alkali albumin and Flask I, Control " 2, 5 minims H„ SO., " la, Control " 2a, 10 minims H., SO; No indol was found in an}' of the flasks, peptones were obtained from all but No. 2. albumose were found in all. Digestion occurred for 24 hours at 40°C. Experiment xi. This experiment was in line with Nos. vii and ix. The paucreatin solution being the same as in No. x. Flask No. I was Control and contained 2 grams of broiled beef, fineh' divided, and 30 cc of the paucreatin solution. Flask No. 2 was similar except that previous to broiling the meat had been pre- served b}' a few hours immersion in 2% sulphurous acid. In flask No. 3, a 5%, and in No. 4, a io'^!'o solution of sulphurous acid was used to preserve the meat. Digestion proceeded 24 hours at 40°C. Peptones and intermediate products were found in all of the flasks. Dried Percentage Residue. Dissolved Flask I, Control 40-35% 59-65 " 2, 2% preservative 3'-05% 68.95 " 3, 5;^,-, 31-50% 68.50 " 4, lopo 30. 10% 69.90 This series gives a lower percentage of solubility' than any hith- erto encountered, but as in the case of the pepsin and trypsin ex- periments the solubility is in favor of the acid treated meat. No. 3 gave a pronounced test for indol ; in No. 2 there was a suspicious trace but it was entirely absent from Nos. i and 4. Experiment xii. A 0.25*6 solution of paucreatin was pre- pared by adding 0.5 gram of pancreatin to 250 cc of i9o sodium carbonate. The solution was quite turbid and filtration did not remove the turbidity completely. Tube I, a bit of fibrin — 20 cc pancreatin solution. Control. " 2, " " ' " " " + 15 minims H, SO " 3. " + 30 " 4, " + 60 " 5. " + 90 " ■ " '■ 6, " " " " -f- 120 " " 20 Digestion was allowed to proceed for 50 or 60 hours at 40° C. The addition of the acid would neutralize a certain amount of the alkali of the pancreatin solution. The first three tubes gave an alkaline reaction. Tube 4 was near the neutral point but weakly- alkaline. Tubes 5 and 6 were distinctly acid. No i showed the presence of alkali albumin and a slight amount of albumose and peptone. None of the other tubes showed any signs of albumose or peptone. Nos. 2 and 3 showed alkali albumin. No 4 only a trace of the alkali albumin ; while Nos. 5 and 6 showed no evidence whatever of digestion. Experiment xiii. As meat contains a considerable percent- age of water, it seemed desirable, in connection with the experi- ments, to determine this percentage. Two grams of fresh raw beef were finely divided and dried to constant weight. The dry residue weighed 0.612 gram ; or the original 2 grams of meat consisted of 30.60 % dry material and 60.40 % of fluid. In the majority of the experiments the percentage of dry residue was less than in this case, showing that some of the material must have actually dis- solved. In experiment xi, however, the percentage of dried resi- dues is greater ; nevertheless, good peptone tests showed that digestion had occurred. The cooking of the meat would also retard any tendency to dissolve. CONCLUSIONS. In peptic digestion a slightly greater percentage of solubility was obtained from the controls in the case of raw meat and boiled egg, where the normal percentage of fluid is rather high. In the tryptic digestion of raw meat the evidence was more favorable to the preparations containing a slight amount of sulphurous acid. In both peptic and tryptic digestion the evidence was uniformly in favor of the meat preserved in the acid before cooking. This was true of fibrin as well as meat. The development of peptone was not necessarily correlative with the solubility of the substance. In some instances where there was great solubility there were poor or negative peptone tests, 21 while in other cases with a low percentage of solubility excellent peptones were obtained. Peptic digestion was retarded but not checked by substituting undiluted sulphurous for the normal 0.2% hydrochloric acid. Peptones apparently develop as quickly in the acid preparations as in the controls. In tryptic digestion sulphurous acid completely checks action if enough of it be added to render the medium acid. vSmall amounts of the acid with the medium still alkaline do not appar- ently interfere with digestion. ERGOT AvS AN ABORTIFACIENT. ARTHUR J. BURLEY, ANGOLA, N. Y. HISTORICAL. The medicinal uses of ergot date back some centuries. Some of the earhest references during the sixteen century, show that some of its virtues were already known to the masses, and that it was used extensively in obstetric practice. Numerous epidemics due to ergot are reported during the eighteenth century. Salerne proved the poisonous effects of ergot on pigs, ducks and fowls ; the animals dying of gangrene. He corroborated the statement that the fresh ergot was the most virulent and that, after some months it sweated and lost its poisonous properties. Allusions to ergot were quite numerous during the eighteenth century, it being used mainly by the lower classes and by charlatans with criminal intent. In France, its use was interdicted in 1774. Its reputation declined but was later revived by the efforts of American physicians. Drs. Stearns, 1807, Akerly, Prescott 1813, Chapman, Dewees (1817-1818) and Altee in 1821 largely con- tributed to turn the tide in its favor. European physicians com- bated the idea of its efhciency, but ergot was finally admitted to the L,ondon Pharmacopoeia in 1836. PHYSIOLOGIC ACTION. DiGESTivR System. — In large doses ergot is a gastro-intes- tinal irritant, occasioning considerable heat and dryness of the throat, accompanied by thirst and succeeded by pain in the stomach and bowels, vomiting and occasional purging, with violent peri- stalsis, although constipation is the common sequence. Circulatory System. — Repeated medicinal doses increase the blood pressure, although rendering the pulse slower and smaller, the result primarily of stimulation of the vaso-motor center, followed 23 by peripheral action causing a tonic contraction of the small nn- striped muscle fibers. A poisonous dose lowers arterial tension, causing the pulse to beat faster and softer — an effect due to the exhaustion from over- stimulation or to direct depressant action upon the heart muscle. It is claimed by competent authority that there is no active and actual contraction of the arteries as a result of stimulation of the vaso-motor system, but that the arteries contract because of the fullness of the veins, there not being sufficient blood to fill both systems — marked arterial anemia resulting. .Some difference of opinion exists as to the effects upon the circulatory s}'stem. Experiments by the writer on the heart of a frog show tliat the force of the contraction is increased. m(\mmmi mmrnrnm The first line is a tracing from the normal heart beat of the frog. The fol- lowing tracings are from the same specimen after the afiplication of ergot. It is claimed by Willebrand that the normal or hypertrophied heart so contracts under the action of ergot that tl'ie difference in size is appreciable by r>ercussion. No specific tffe'ls ujjon the blood have been described. Nervous System. — Medicinal doses have no especial action though excessive doses sometimes depress the sensory mechanism producing general cutaneous anesthesia. Among the physiologic effects of toxic doses is stimulation of the organic motor centers. RESPiKATrjKv Syste.m. — Medicinal doses produce no particular effect. Large doses depress the resfjiratory center rendering the breathing shallow. This action is manifest from the first there 24 being no primary stimulation of the respiration. Death from an overdose of ergot usuall}' results from paralysis of the respiratory center. Temperature;. — No special action has been observed. Toxic •doses cause cold skin ; the limbs, ears, horns and tail lose their natural warmth. Eye. — The caliber of the retinal and nutrient optic blood ves- sels is reduced resulting in marked pallor of the disk, transitory amblyopia and papillary anemia. Uterus. — In some respects the most important action of ergot is upon this organ. Except in labor no appreciable effects are pro- duced by very small doses although large doses are said to produce contraction. In therapeutic doses the principal action of the drug is on unstriped muscle fibers. It causes especially the contraction of the blood vessels and contraction of the uterus. Its action is most strikingly exemplified during pregnancy. It produces, in full doses, tetanic, tonic contraction of the uterine muscle, the uterus being hard and pale, forcing the blood out of the uterine arterioles. The uterine contractions are attributed, in part, to stimulation of the parturition center in the lumbar portion of the cord. The precise manner in which ergot affects the uterus is still a matter of discussion. It is fairly well demonstrated, however, that the drug acts both centrally and peripherally owing to its different constitu- ents, cornutin acting centrally and sclerotic acid peripherally. Ergot has been studied as much or more than any drug in the materia medica and if opinions vary as to its modus operandi, it is because a very complex substance is dealt with, the nature and «ven the number of its constituents being as yet inadequately known. Some of the principles of the drug are unstable, and vari- able in their influence. Tanret's ergotinine, for example, is said to be without effect upon the uterus. Bonjean's ergotin is a powerful ecbolic and has marked action, moreover, upon the vascular system. Bladder. — In animals poisoned with ergot, the bladder may be found distended with urine or empty and firmly contracted. In the first instance there is a spasmodic contraction of the vesical 25 sphincter ; while in the latter case the entire muscular structure of the organ is under the influence of ergot. Peton noticed soon after an injection of ergot the appearance of fibrillary contractions re- sulting in the complete evacuation of the organ ; in other cases the contractions alone were seen. Wernich observed the same phe- nomena and recommended close attention to the regularity of micturition in patients treated with ergot and, should retention occur, the use of the catheter. (Evetzky). Absorption and Elijiination. — The active constituents of ergot are rapidly absorbed into the blood and are eliminated princi- pally by the kidneys, increasing the urinary flow. It is well established that ergot does not pass into the milk. Evetzky dis- covered a substance resembling ergot in a womb discharge of a woman treated with ergot for a uterine fibroid tumor. Muscle. — In therapeutic doses the principal action of ergot is on unstriped muscle fiber. It causes especially the contraction of the blood vessels and of the uterus. Some experiments made by the writer indicated that the gastrocnemius muscle of the frog' contracted somewhat more forcibly under the influence of ergot. EXPERIMENTAL. The action of ergot upon the uterus is quite fully described in the text books on materia medica, but any literature bearing upon direct experimental evidence of this action, the writer was unable to discover. The experimental work was, therefore, confined almost entirely to a study of this drug upon the uterus of pregnant cats. I am indebted to Dr. P. A. p-ish for the data of two experiments upon pregnant cats, which he carried out in the Spring of 1904. On April 16, he injected hypodermically [ cc of aseptic ergot (Parke Davis) at intervals of about one hour until five doses had been ad- ministered. On the following day April 17, it was found that the cat had given birth to three living kittens which were well enough developed to nurse from the mother. The mother appeared bright and did well afterwards. Cat number 2 was experimented upon the same day ; but in 26 this instance the fluid extract of ergot (Parke Davis) was used. One dram of the fluid extract diluted with two drams of water, was administered through a rubber tube, directly into the stomach. Five doses were administered in all at about one hour intervals. On the following day (April 17) it was found that two dead but quite fully developed kittens had been born. On the morning of April 18, another dead kitten was found and the mother seemed to be in considerable distress. At 2 p. m. she was found dead. The postmortem showed two more kittens in the uterus. One with head presenting in the vagina and badly squeezed out of its natural shape. The uterus was much congested and appeared to be almost gangrenous, with considerable bloody exudate in the abdominal cavity. The remaining experiments were carried on under the direction of Dr. Fish, the special object being to note the oxytocic properties of the drug and incidentally the after effects upon the mother and fetus. In the majority of cases the fluid extract of ergot (Parke Davis) was used ; the dose being one dram diluted with two drams of water introduced directly into the stomach through a rubber tube. Cat No. 3. On March 21, 1905, four doses of the fluid extract were administered as above described at intervals of two hours. On the following day no signs of abortion were observed although the cat seemed slightly indisposed. On March 23, five doses of the drug were given at similar intervals, but no symptoms were observed on the following day. On April 8, the experiment was repeated but the ergot was given at intervals of one hour instead of two. On the following day at 10 a. m. the cat seemed uneasy, looking around at the flank and appearing as if to make preparation for the act of parturition. At 10:45 she gave birth to four kittens, two of them dead. At 2 p. m, she gave birth to another live kitten. The following day all of the kittens were dead except one and this lived only twenty-four hours longer. The kittens seemed quite well developed although small. They were not seen to suck nor did mammitis develop in the mother. Cat No. 4. On April 22, one dram doses of the fluid-extract were administered every half hour up to five doses. No symptoms 27 were observed on the following day except slight muscular trem- blings. On April 25, four doses were given at half hour intervals. Shortly after the fourth dose she gave birth to a kitten (10:30 A. m.). At 2 p. M. another kitten was born. These kittens were smaller and possessed less hair than those of No. 3. The cat was more indisposed and did not recover so rapidly as No. 3. Cat No. 5. The experiment was carried out as on No. 4. Emesis occurred after the third dose. Dosage was begun at 4 p. m. Maj' 3 and at 9 a. m. the following morning she gave birth to a kitten quite immature and less than half grown. It measured onlj' 5.6 centimeters in its fetal membranes. No other kittens were observed. On May 9 the cat was killed and a postmortem held. The uterus showed that four kittens had been present and it was assumed that the mother ate up the remaining immature kittens as she was not constantly observed during the whole of the experiment. The mother's health had been excellent up to the time ofthe postmortem. Cat No. 6. On May 19 four doses of ergot were administered at half hour intervals. There were no results on the following day. Similar doses were administered May 22, with emesis after the third dose. No abortion or other symptoms were observed. The cat was killed and four kittens near term were found in the uterus. Three other cats were experimented upon, but the postmortems showed they were not pregnant. SUMBIARY AND CONCLUSIONS. Ofthe six pregnant cats experimented upon, five gave birth to their young within a reasonable time after the administration ofthe ergot. Some of the kittens were probably near term, because of this it may be suggested that normal labor may have occurred independently of the ergot. In the absence of any data relating to the time of impregnation absolute proof is impossible ; but the fact that cats i to 5 inclusive gave birth to their kittens within twenty- four hours after the last dose of ergot, renders it highly probable that the act of parturition was not a coincidence correlated with normal labor, but was due to the action of the ergot. 28 Tn cats i and 2 the treatment was simultaneous (except for the form of the preparation of the drug); the act of parturition was also simultaneous. This fact, it seems to us, is deserving of more weight than that the kittens were near term. Cat No., 3 required three sets of experiments at intervals of a few daj'S before parturition effects were produced. The kittens although apparently quite well developed were small. Two of them were born dead. The remaining three were unable to nurse and soon died ; and the conclusion was reached that they were born prematurely. On cat No. 4, two sets of experiments were tried within an in- terval of three days. Shortly after the last dose the act of parturi- tion set in. The kittens were even more immature than those from cat No. 3, and their birth is quite reasonably attributed to the action of the ergot. On cat No. 5, the ergot unquestionably produced abortion, as the kitten was not more than half its term and measured only 5.6 centimeters in length. This experiment emphasized the necessity of close observation because of the tendency of the mother to eat the immature young. If the act of parturition is not observed and if no fetus is found (because of its having been eaten), the conclu- sion would be reached that the drug had exerted no action. Two sets of experiments, within an interval of three days, were performed upon cat No. 6 without result. It is possible that more of the drug was needed in this case as in cat No. 3, or that the cat was less susceptible than the others. The effect of the ergot upon the mothers was apparently not harmful except in cat No. 2 where there was a fatal termination and in cat No. 4 where there was some indisposition for a time, but ultimate recovery ensued. In some cases a few of the fetuses were born dead, and others died soon after birth, while a few survived. The former conditions might be expected if the birth was premature. From these experiments the conclusion seems reasonable that ergot has the power of stimulating the gravid uterus to the extent of emptying it of its contents, in the cat. 29 Some difference in susceptibilit}' was noted. Cats Nos. i and 2 required only five doses. Cat No. 3 required fourteen doses in three series of experiments and Nos. 4 and 5 nine doses in two series of experiments. The doses should be rather large and administered with due frequency in order to produce abortion. THE STATUS OF THERAPEUTICS. PIERRE A. FISH. ITHACA, N. The veterinarian who has merely a financial interest in his patients, is unworthj- of the name. The highest aim of the true practitioner is to cure disease and alleviate suffering. In addition the thinking practitioner seeks to know how and whjr the results are effected. Therapeutics is not an exact science ; it is slowly struggling toward that goal. Ignorance of causes retards therapeutic effic- iency. Therapeutics has kept pace with the wonderful progress of pathology in the last few decades, and new treatments have been worked out to correspond with the increased knowledge of the origins of morbid effects. Most of the glory for these discoveries has gone to pathology' but, richlj' as she deserves it, therapeutics should not be forgotten. Therapeutics is ancient ; she was born in mysticism, has develop- ed into science, and is the keystone of practice. She has brought surgery out of the dark ages by bestowing upon her the blessings of anesthesia and asepsis. The brilliant and radical operations that may now be performed with comparative safety, were undreamed of some years ago. The result has been that, in the ej'es of some, such a glamour has encompassed surgery that therapeutics has become hidden in obscurity. In certain cases, surgery may with a few strokes of the knife, as in the removal of a benign tumor, dissect out the disease and cast it away. Just as brilliant an operation, to my mind, is, with purely therapeutic measures, to convert a patient rolling in the agonies of colic into a quiet, peaceful, normal, and contented frame of mind with little prospect of recurrence of the trouble under proper conditions of care. But there are major operations which may be complicated with infection, where recovery is slow and prolonged, or where death 31 occurs. Similarly in a medical case the practitioner may be groping- in the dark, or the drugs are not potent enough to set up the proper reaction in the affected tissues. Yet, equal in glory and compara- ble to the most successful major operation, it seems to me, is the res- toration to a normal condition of a lung or a portion of it, which has become consolidated and therefore practically functionless for respiratory purposes. The regulation of the heart and circulation, breathing, peristalsis, the increase or decrease of the various secretions of the body by therapeutic measures, is as wonderful to me as any surgical operation that has ever been devised. Surgery, however, has the advantage of being able to cut her way to the foe and can sec more or less clearly its nature and the extent involved. Medicine cannot do this ; her foe is concealed and must therefore be fought in the dark, with the result that very often the various stages in the fight cannot be seen clearly at a given time. It is natural that one should expect more from him that fights a visible enemy than from one who attacks a hidden foe ; but in the event of victory for the latter the glory should be greater. A^eic Remedies. The number of new remedies discovered each year is surprising. But a small fraction of them come into practical use and that often for only a shprt time. The great majority have no superior merit over the old ones and are no more heard of. It is safe to say that many of the old and experienced remedies will never be superseded, and that there is still much to be learned of their virtues, there can be no doubt. The scriptural saying, "Prove all things and hold fast to that which is good" applies with more or less force here. Conservatism is the safer procedure. Undue eagerness is to be deprecated. Wait until some of the merits of the new drug have been demon- strated ; but having once decided to try it, give it a faithful, fair, impartial and sufficiently prolonged test to determine conclusively in your own mind its value or its uselessness. Secret Remedies. This term is used advisedly as against /fli'^ grams of starch were boiled in 60 cc, of water. To this was added 1 gram of sodium benzoate dissolved in 30 cc. of water. This mixture was allowed to stand 17 hours and then 30 cc. of filtered saliva were added and digestion allowed to continue for one hour at a temperature of 38° to 40° C. Qualitative tests showed the presence of sugar within 25 minutes. Experiment 1-a. This was similar to No. 1 in every way except that no sodium benzoate was present. Sufrar was also found in this Mask within 25 minutes. Quantitative tests of the contents of the two llasks showed that S cc. from flask No. 1 were sufficient to reduce the l<^ehlin^'s or that each 5 cc. of the beuzoated flask contained 0.05 g-ram of reducing- sugar. In No. 1-a only 4.3 cc. of the solution were required to reduce the Fehling's so that the evidence was in favor of the latter or normal flask. Experiment 2. This was similar to No. 1, except that the saliva was kept in the ice chest for 17 hf^mrs and then at room temperature for 7 hours before dig-estion began. Sug-ar was found in this flask within 10 minutes. Experiment 2-a. Similar to No. 2, except that no sodium benzoate was present. Sugar was also detected in this flask within fO minutes after the beg"inning of digestion. At the end of the hour, quantitati\-e tests showed that only 4.8 cc. of the solution from flask 2 were required to reduce the Fehling-'s Solution ; while in the normal flabk No. 2-a only ,3.7 cc. were required. Experiment 3. In this experiment the same amount of sodium benzoate was used. Its solution was added to the saliva and the mixture kept in the ice chest for 17 hours, and later 7 hours at room temperature, before mixing- with the starch and beg-inning- digestion. Sugar was found to be present within 5 minutes. Experiment 3-a. Similar to No. 3, except that no sodium benzoate was present. Sugar was also found in this flask within 5 minutes. Quantitative tests showed that 5.1 cc. of the benzoated mix- ture were required to reduce the Fehling's Solution ; while in the normal mixture (No. 3-aj only 3.9 cc. were required. The following summary of the experiments is useful for comparison : SoDium Benzoate. Nopaui,. No. 1. 5 cc. No. 1 -a. 4.3 cc. No. 2. 4.8 cc. No. 2-a. 3.7 cc. No. 3. 5.1 cc. No. 3-a. 3.9 cc. Average 4.96 cc. Average 3.96 cc. The evidence in these experiments is uniformly in favor of the normal flasks. Experiment 4. In this experiment the saliva was diluted one-half with distilled water. Digestion was allowed to continue 3% hours at a temperature of 38° to 40° C. The starch mixture and the sodium benzoate solution were mixed shortly before add- ing- the saliva. Flask No. I (Normal). 2J grams starch -|- 60 cc. water -|- 30 cc. diluted saliva. Flask No. 2. 2| grams starch -{- 60 cc. water + l gram sodium benzoate in }0 cc. water -|- 30 cc. diluted saliva. Flask No. 3 (Normal). 1 gram starch -\~ 50 cc. water -|- 25 cc. water -|~ 25 cc. diluted saliva. Flask No. 4. 1 gram starch -|- 50 cc. water -|- l gram sodium benzoate in 25 cc. water -|- 25 cc. diluted saliva. Flask No. 5. l gram starch -|- 50 cc. water + 0.5 gram sodium benzoate in 25 cc. water -|- 25 cc. diluted saliva. The proportion of sodium benzoate in the benzoated flasks was as follows : No. 2, 1 to 120 or f % ; No. 4, 1 to 100 or l'/„ ; No. 5, 1 to 200 or 0.5%. The flasks were submitted to the same experimental conditions and when digestion was discontinued the quantitative tests showed the following results : No. 1 (Normal). Only 2.5 cc. of the mixture were required to reduce the Fehling's solution. No. 2. 4.5 cc. of the mixture reduced Fehling's. No. 3 (Normal). 7.2 cc. reduced Fehling's. No. 4. 7.2 cc. reduced Fehling's. No. 5. 7.8 cc. reduced Fehling's. In all of the flasks, there was present the same amount of saliva, but there was a variation in the amount of starch ; two of the flasks having 2}4 times as much as the remaining three. It seems reasonable, therefore, to infer that a greater amount of sugar had been formed in those flasks where there was the great- est amount of starch. As reg-ards flasks 1 and 2, the evidence is decidedly in favor of No. 1 ; there being more sugar in the normal than in the benzoated flask. In the three flasks contain- ing the smaller proportion of starch, the results were much alike and would lead to the inference that the presence of the benzoate in the flasks 4 and 5 had but little if any influence upon the sali- vary dig-estion. The evidence as a whole, however, seems to be more favorable to the normal than to the benzoated flasks. Gastric Digestion. Pepsin. The experimental work with the enzyme pepsin included such food stuffs as egg- albumin, raw meat and fibrin. Experiment 5. An artificial dig-estive fluid was prepared by dissolving 0.0535 gram of scale pepsin in 1000 cc. of 0.2 /( hydro- chloric acid. Portions of this stock solution were used in the experiments on albumin. The albumin was obtained from hard boiled eg-g-s. The whites of the eg'g-s being forced through a finely meshed sieve in order to g^et them in a finely divided state. Flask No. 1. Control. 10 grams of egg albumin + 30 cc. of the pepsin solution. Flask No. 2. 10 grams of egg albumin + 30 cc. pepsin solution -|- l gram sodium benzoate in 30 cc. of water. Flask No. 3. Second control, 10 grams of egg albumin + 50 cc. of the pepsin solution. Flask No. 4. 10 grams of egg albumin -\- 50 cc. pepsin solution -|- 1 gram sodium benzoate in 50 cc. of water. Flask No. 5. 10 grams of egg albumin 4- 50 cc. pepsin solution -)- 0. 5 grain sodium benzoate in 50 cc. of water. Flask No. 6. 10 grams of egg albumin + 50 cc. pepsin solution -f- 0-25 gram so- dium benzoate in 50 cc. of water. Flask No. 7. 10 grams of egg albumin -;- 50 cc. pepsin solution -)- 0.125 gram so- dium benzoate in 50 cc. of water. Flask No. 8. 10 grams of egg albumin -|- 50 cc. pepsin solution + 0.0625 gram sodium benzoate in 50 cc. of water. On mixing the ingredients, the contents of flasks 2 and 4 became turbid and a precipitate formed ; the other flasks re- mained comparatively clear. The formation of the precipitate was probably due to the action of the hydrochloric acid upon the sodium benzoate, causing the production of benzoic acid, which is not readily soluble in water. All of the flasks were allowed to digest for 22 hours at a temperature of SS"^ to 40^^ C. At the end of digestion, each of the flasks was tested for the intermediate and end products of digestion. Peptones were found in all of the flasks but numbers 2 and 4. Intermediate products were also absent in these two flasks. After the filtering of the contents of the flasks, the undissolved residues were dried to constant weight and then weighed. The following table shows the results : Percentage of Percentage of Albumin Dissolved. Undigested Residue Flask No. 1. Control. 91.87% 8.13% Flask No. 2. lf% Benzoate. 83.99% 16.01% Flask No. 3. 2d Control. 98.12% 1.88% Flask No. 4. 1% Benzoate. 84.50% 15.50% Flask No. 5. O.Sfo Benzoate. 91,37% 8.63% Flask No. 6. 0.25% Benzoate. 98.20% 1.80% Flask No. 7. 0.125^ Benzoate. 98.27% 1.73% Flask No. S. 0.0625% Benzoate. 98.63% 1.37 f„ In flask No. 2 which contained sodium benzoate to the extent of 1|% and No. 4 which contained 1% no digestion occurred as shown by the absence of peptones. Although the table shows that approximately 84^ of solid material had disappeared in each case, it must be remembered that the original 10 grams of &gg albumin contained a large percentage of water and that when dried to constant weight and with no digestive action, there would be a large decrease in weight on account of the loss of water. In flask No. 5, which contained 0.5% of benzoate, peptones were present but the relatively large amount of undi- gested residue would indicate that digestion had been retarded. In flask No. 3 (control) and in numbers 6, 7 and 8, containing 0.25% or less of benzoate, the results were very similar to each other and would indicate that 0.25% or less of the benzoate had no interference with the digestion. Incidentally the antiseptic effects of sodium benzoate were noted in this experiment. The filtrates from the flasks were retained five weeks. At the end of this period the controls Nos. 1 and 3 showed a profuse growth of mould while the benzoated flasks remained clear. Experiment 6. This experiment was the same as No. 5 ex- cept that raw beef finely divided was substituted for the egg albumin. Flask No. 1. Control. 2 grams raw meat -j- 30 cc. water -|- 30 cc. pepsin solution. Flask No, 2. 2 grams meat -|- 30 cc. pepsin solution + 1 gram sodium benzoate in 30 cc. water. Flask No. 3. 2d control. 2 grams meat + 50 cc. pepsin solution -f 50 cc. water. Flask No. 4. 2 grams meat -|- 50 cc. pepsin solution -|- l gram sodium benzoate in 50 cc. water. Flask No. 5. 2 grams meat -|- 50 cc. pepsin solution -[-0.5 gram sodium benzoate in 50 cc. water. Flask No, 6. 2 .grains meat -|- 50 cc. pepsin solution -)- 0.25 gram sodium benzoate in 50 cc. water. Flask No. 7. 2 yranis meat -\- 50 cc. pepsin solution -)- 0.125 gram sodium benzoate in 50 cc. water. Flask No. S. 2 grams meat -|- 50 cc. pepsin solution -[-0.0025 gram of sodium ben- zoate in 50 cc. of water. Flasks Nos. 2 and 4 showed a precipitate of benzoic acid as did the similar flasks in the preceding experiment. Dig-estion was allowed to g-Q on for 15 hours at a temperature of 38° to 40° C. No peptones nor intermediate products were found in the con- tents of flasks 2 and 4, showing that no digestion had occurred here. In No, 5 there was only a faint test for peptone and fair tests for the intermediate products. In the remaining flasks very good tests were obtained for the peptones and intermediate pro- ducts. The amount of dissolved material and undig'ested residue is shown in the following" table : Percentage of Percentage of Meat Dissol ved. Undigested Residue Flask No. 1. Control. 93.00%, 7.00% Flask No. 2. If Benzoate. 62.25 % 37.75% Flask No. 3. 2d Control. 94.10% 5.90% Flask No. 4. I'/o Benzoate. 55.65% 44.35% Flask No. 5. 0.5;^, Benzoate. 83.25% 16.75% Flask No. 6. 0.25 ;>^ Benzoate. 91.30% 8.70% Flask No. 7. 0.125% Benzoate. 90.30% 9.70% Flask No. S. 0.625 y{i Benzoate. 90.90% 9.10% This series in connection with the tests for the products of dig-estion shows that 1%' or more of sodium benzoate is sufficient to prevent digestive action in this experiment ; O.S^/o materially retards digestive action ; while 0.25% and less have but slight effect on digestion although the controls showed a slightly higher degree of efficiency. In the following experiment an artificial gastric juice was made by removing the mucous membrane from the stomach of a dog. Forty grams of this was ground up in a mortar with 40 cc. of 1% acetic acid. After standing for a short time it was added to some chloroform water in the proportion of 40 to 100. After a few days it was Strained through cloth and diluted with an equal volume of 0.2% hydrochloric acid and was then ready for use. Dry fibrin was also used in this experiment because it is a proteid substance, easily dig-ested and the lack of water in the fibrin gave more approximately accurate results in determining' the undigested residues. Experiment 7. Digestion continued for 18 hours at a tem- perature of 38 to 40 degrees C. Flask No. 1. Control. 1 gram dry fibrin in 50 cc. water -j- 50 cc. gastric extract. Flask No. 2. 1 gram fibrin -f- 50 cc. gastric extract -|- 1 gram sodium benzoate in 50 cc. water. Flask No, 3. 1 gram fibrin -|- 50 cc. gastric extract -(-0.5 gram sodium benzoate in 50 cc. water. Flask No. 4, 1 gram fibrin -f- 50 cc. gastric extract -|- 0.25 gram sodium benzoate in 50 cc. water. Flask No. 5. 1 gram fibrin -|- 50 cc. gastric extract -|- 0.125 gram sodium benzoate in 50 cc. water. Flask No. 6. 1 gram fibrin -|- 50 cc. gastric extract -|- 0.0625 gram sodium ben- zoate in 50 cc. water. The tests showed that no digestion took place in flasks 2 and 3. A trace of peptone was found in No. 4 ; a fair test in No. 5 ; a good test in No. 6 and the strongest in No. 1, the control. A small amount of hydrochloric acid was added to the contents of the flasks at intervals during digestion. Some cloudiness result- ed in Nos. 2 and 3, when this was done, but the other flasks remained clear. Percentage of Percentage of Fibrin Dissob ved. Undigested Residue, Flask No. 1. Control. 81.10% 18.90% Flask No. 2. 1 fo Benzoate. plus 72 mg. Flask No. 3. 0.5% Benzoate. plus 23 mg. Flask No. 4. 0.25% Benzoate. 17.60% 82.40% Flask No. 5. 0.125% Benzoate. 52 10% 47.90% Flask No. 6. 0.0625;;^ Benzoate. 64.90^ 35.10% A glance at the table shows that in none of the benzoated flasks were the results as good as in the control ; even with the smaller percentages of the benzoate, digestion had been mater- ially retarded. In Nos. 2 and 3 the results show that there was absolutely no solution of the fibrin, but that at the end of the experiment there was an actual increase in weight. In the case of No. 2 there was a gain of 72 milligrams and in No. 3 of 23 10 milligrams. This gain in weight was undoubtedly due to som.e precipitation of benzoic acid when the gastric extract and solu- tion of sodium benzoate were mixed and the precipitate remained upon the filter with the fibrin. The antiseptic action of sodium benzoate was also shown in this experiment. The flasks were allowed to stand 2 months. At the end of that time No. 1 showed a profuse fungus growth. There was some sediment in the bot- tom of No. 6 but the others were as clear as crystal. Reiiniu. An experiment was also carried out to determine if the presence of sodium beazoate hindered in any way the action of the milk curdling enzyme of the stomach. For this purpose 25 grams of the mucous membrane of the fourth stomach of a sheep were removed. After trituration in the mortar with 25cc of 1% of acetic acid for a half an hour, 250cc of chloroform, water were added and the whole was allowed to stand for two days. It w-as then neutralized with a solution of I'/c sodium car- bonate, strained and filtered and was then ready for use. Experiment 8. In all cases the milk and sodium benzoate were mixed for an hour before adding the digestive extract. Temperature 3S degrees C. Flask No. 1. Normal. 10 cc. milk. Flask No. 2. Control. 10 cc. milk + 1 grain commercial rennin. Flask No, 3. 2d Control. 10 cc. milk + 2 cc. of above extract. Flask No. 4. 10 cc. milk -j- 1 gram sodium benzoate + 2 cc, extract = 10, '^f sodium benzoate. Flask No. 5. 10 cc. milk + 0,5 gram sodium benzoate +2 cc extract = 5 ;i sodium benzoate. Flask No. 6. 10 cc. milk -|-0.2 gram sodium benzr.ate + 2 cc. extract = 2ff sodium benzoate. Flask No. 7. 10 cc. milk -|- 0.1 gram sodium benzoate + 2 cc. extract = 1 ff sodium benzoate. Flask No. 8. 10 cc. milk + 0,05 gram sodium benzoate -\- 2 cc. extract = O.Sfc sodium benzoate. Flask No. 9. 10 cc. milk + 0.02 gram sodium benzoate + 2 cc. extract = 0.2^ sodium benzoate. Flask No. 10. 10 cc. milk + 0.01 gram sodium benzoate -|- 2 cc. extract = 0.1% sodium benzoate. Flask No. 11. 10 cc. milk + 0.005 gram sodium benzoate -\- 2 cc. extract = 0.05 5J sodium benzoate. 11 Within IS minutes after the beg-inning of digestion moder- ately firm clots had formed in Nos. 2 and 3 — the controls. At the end of 40 minutes some whey was forming in No. 2 and moder- ately firm clots were found in 9, 10 and 11. The contents of 4, 5, 6, 7 and 8 were still fluid. At the end of one hour and 40 minutes, clots appeared in Nos. 7 and 8 and some whey was showing' in those which had previously dotted. After 5 hours a soft clot appeared in No. 6. Nos. 4 and 5 were still fluid. The normal milk in No. 1 had undergone no change. The flasks were put in the incubator over night at a temperature of 40 degrees C. In the morning the clots had contracted still more and there was a greater abundance of whey, especially in the controls 2 and 3. In 9, 10 and 11 the clots were a little larger than in the controls. In 6, 7 and 8 the clots were still larger and irregular and a smaller quantity of whey. Nos. 4 and 5 were still fluid. In No. 1 the normal milk had undergone the natural process of souring. In Nos. 4 and 5 there was sufficient sodium benzoate present to inhibit the action of the enzyme rennin and was also sufficiently antiseptic to prevent the natural souring of the milk. Another control experiment was carried out by boiling some of the rennin extract from the sheep's stomach and adding 2 cc. of it to 10 cc. of milk as in No. 3. Observations were carried on for 2j4 hours but there was no evidence of clotting, showing that the boiling had killed the enzyme. The flask was then put in the incubator for over night and in the morning it was found to have undergone the natural process of souring. In none of the benzoate flasks did the clots form as quickly as in the controls. Sodium benzoate to the extent of 0.2% or less appeared to have but slight effect on the action of rennin ; 0.5% to 1% materially retarded its action and 2% very nearly prevented any clotting. Syo and 10% inhibited clotting altogether. Experiment 9. In this experiment commercial rennin was used in the form of tablets, each tablet containing 1 grain of rennin. Flask No. 1. Control. 10 cc. milk -|- 1 grain rennin. Flask No. 2. 10 cc. milk-|-l gram sodium benzoate -|- l grain rennin = 10^ ben- zoate. Flask No. 3. 10 cc. milk + 0.5 gram sodium benzoate -|- l grain rennin — S% benzoate. 12 Flask No. 4. 10 cc. milk -^ 0.2 gram sodium benzoate -)- 1 grain rennin = 1% benzoate. Flask No. 5. 10 cc. milk -(-0.1 gram sodinm benzoate -|- l grain rennin = 1^ benzoate. Flask No. fi. 10 cc. milk -f- 0.05 gram sodium benzoate -|- 1 grain rennin = 0.5^ benzoate. Flask No. 7. 10 cc. milk -|- 0.02 gram sodium benzoate + l grain rennin = 0.2^ benzoate. Dig"estion was allowed to continue for half an hour at 36 to 37 degrees C. At the end of that time it was found that firm clots had formed inNos. 1, 5, 6 and 7, the others remaining" fluid. The flasks were put in the incubator over nig-ht and examined again the next morning-. In 1, 5, 6 and 7 the clots were cylin- drical and well formed ; considerably contracted and a large pro- portion of whey was present. In No. 4 there was an irregular mass at the bottom of the flask with some whey around it. In Nos. 2 and 3 there were some irregular masses at the top and bottom of the milk as if there had been some attempt at clotting-. The result was best in the control for here was the smallest clot and the greatest amount of whey. As compared with the pre- ceding experiment each flask in the last experiment undoubtedly contained a larger amount of rennin, and this helps to explain why clotting- might occur within half an hour in the presence of sodium benzoate to the extent of 1%. Pancreatic Digkstion. Experiments were made with all of the enzymes of the pancreas e. g. amylopsin, trypsin, steapsin and milk curdling. Amylopsin. This enzyme was studied by preparing an alka- line solution of pancreatin as follows : Pancreatin 5 grams, So- dium Carbonate 10 grams, Distilled Water sufficient to make 1000 cc. Experiment 10. In this experiment digestion was allowed to continue for three hours at a temperature of 41 degrees C, the starch having previously been boiled in the water. Flask No. 1. Control. 2-i grams starch + 60 cc. water + 30 cc. pancreatin solu- tion. Flask No. 2. 2i grams starch + 60 cc. water + 30 cc. pancreatin solution + 1 gram sodium benzoate in 30 cc. water. 13 Flask No. 3. 1 gram starch + 50 cc. water + 25 cc. pancreatiii solution -\- 2 grams sodium benzoate in 50 cc. water. Flask No. 4. 2d Control, l gram starch + 50 cc. water -|- 25 cc. pancreatin solu- tion ^- 25 cc. water. Flask No. 5. 1 gram starch -'r 50 cc. water + 25 cc. pancreatin solution + 1 gram sodium benzoate in 25 cc. water. Flask No. 6. 1 gram starch + 50 cc. water + 25 cc. pancreatin solution | 0.5 gram sodium benzoate in 25 cc. water. Flask No. 7. 1 gram starch + 50 cc. water + 25 cc. pancreatin solution J 0.25 gram sodium benzoate in 25 cc. water. Flask No. S. 1 gram starch -|- 50 cc. water + 25 cc. pancreatin solution -j 0.125 gram sodium benzoate in 25 cc. water. Quantitative tests with Fehling's solution gave the follow- ing- results : Number of cc. of solution equal to 0.05 gram sugar or to reduce 10 cc. Fehling's. Flask 1. Control. 4. cc. Flask 2. -(;% Benzoate. 5.3 cc. Flask 3. 1,6% Benzoate. 10.4 cc. Flask 4. 2d Control. 10.5 cc. Flask 5. 1% Benzoate. 11.0 cc. Flask 6. 0.5 C(, Benzoate. 9.7 cc. Flask 7. 0.25;^ Benzoate. lO.l cc. Flasks. 0. 125 fp Benzoate. 9.9 cc. It will be noted that in flasks 1 and 2 where there was 2}^ times as much starch present as in the other flasks, the greatest amount of sugar was found whether sodium benzoate was pre- sent or not, but such difference as there is, is in favor of the nor- mal. With regard to the remaining flasks with the smaller quantity of starch, there is proportionately less sugar and it would be difficult to determine from the results that the benzoate had any special effect, except perhaps to slightly favor the diges- tion ; because with the exception of No. 5, all of the others from 3 to 8 inclusive show that slightly more sugar was produced in the benzoated flasks than in the 2nd control. The difference is so slight however, that it may well come within the limits of error. Trvpsiii. Experiment 11. This experiment was concerned with the pancreatic digestion of proteids. A solution of pan- creatin was prepared as described for Experiment 10. Raw meat was used for the proteid. Digestion continued for 15>^ hours. 14 Flask No. 1. Control. 2 grains meat -|- 30 cc. water + 30 cc. pancreatin solution. Flask No. 2. 2 grams meat - 1 30 cc. pancreatin solution + 1 gram sodium benzoate in 30 cc. water. Flask No. 3. 2d Control. 2 grams meat -j- 50 cc. water -|- SO cc. pancreatin solution. Flask No. 4. 2 grams meat | 50 cc. pancreatin solution + 1 gram sodium ben- zoate in 50 cc. water. Flask No. 5. 2 grams meat -|- 50 cc. pancreatin solution ^- 0. 5 gram sodium ben- zoate in 50 cc. water. Flask No. 6. 2 grams meat ■- 50 cc. pancreatin solution +0.25 gram sodium ben- zoate in 50 cc. water. Flask No. 7. 2 grams meat -| 50 cc. pancreatin solution + 0.125 gram sodium ben- zoate in 50 cc. water. Flask No. S. 2 grams meat ' 50 cc. pancreatin solution -f 0.0625 gram sodium benzoate in 50 cc. water. Peptones and intermediate products were found in all of the flasks. The strongest tests for peptones, however, were obtained from flasks 2 and 4. Percentage of Percentage of Meat dissolved. Undigested Residue. Flask No. 1. Control. 83.85;^; 16.15;^ Flask No. 2. If Benzoate. 83.55% l(iAS% Flask No. 3. 2d Control. 92.40% 7.60% Flask No. 4. 1% Benzoate. 86.65% 13.35% Flask No. 5. 0.5% Benzoate. 92.95% 7.05% Flask No. 6. 0.25% Benzoate. 90.50% 9.50% Flask No. 7. 0.125% Benzoate. 92.60% 7.40% Flask No. S. 0.0625% Benzoate. 89.15% 10.85% In Nos. 1 and 2 the results are nearly the same. In the series 3 to 8 inclusive there is greater variation. In this series there was a greater amount of the pancreatin solution present — about 40^j more, which undoubtedly accounts for the higher per- centages of the meat dissolved. In Nos. 3, 5 and 7, the figures compare very closely and although there is more difference be- tween the remaining figures, the inference may be justified, in connection with the peptone tests, that the benzoate did not materially hinder the digestion of the meat. Experiment f 2. In this case dry fibrin was used in connec- tion with an extract made from the pancreas of a horse. Diges- tion for IS hours. In all cases the fibrin was allowed to soak in the sodium benzoate solution for three hours before the pan- creatic extract was added and digestion begun. 15 Flask No. 1. Control, l gram fibrin -\- 50 cc. water -\- 50 cc. pancreatic extract. Flask No. 2. 1 gram fibrin -|- 50 cc. pancreatic extract |- 1 gram sodium benzoate in 50 cc. water. Flask No. 3. 1 gram fibrin -|- 50 cc. pancreatic extract -| 0.5 gram sodium benzoate in 50 cc. water. Flask No. 4. 1 gram fibrin + 50 cc. pancreatic extract -| 0.25 gram sodium ben- zoate in 50 cc. water. Flask No. 5. l gram fibrin ^ 50 cc. pancreatic extract -\- 0.125 gram sodium ben- zoate in 50 cc. water. Flask No. 6, l gram fibrin J- 50 cc. pancreatic extract -|- 0.0625 gram sodium ben- zoate in 50 cc. water. Good peptone tests were obtained from all the flasks. Percentage of Percentage of Fibrin dissolved. Undigested Residue. Flask No. 1. Control. 56.00,9/' 4i.00fc Flask No. 2. ly^ Benzoate. 55.50% 54.50% Flask No. 3. 0.5% Benzoate. 51.10% 48.90% Flask No. 4. 0.25% Benzoate. 53.10% 46.90% Flask No. 5. 0.125%, Benzoate. 52.50% 47 50% Flask No. 6. 0.0625% Benzoate. 60.80% 39.20% The results show that digestion was not prevented in any of the flasks, as demonstrated by the peptone tests. From the amount of fibrin dissolved, it would appear that the benzoate re- tarded dig-estion in all but No. 6, where the very slight amount present apparently favored digestion. The contents of the flasks ■were kept one month after making the digestive tests in order to note any antiseptic effects of the benzoate. At the end of the month all of the flasks had a putrefactive odor and there was some scum or sediment in each, indicating that sodium benzoate was not as efficient as an antiseptic in an alkaline medium as in the acid gastric experiments already noted. Milk Curdling Enzyme. Experiment 13. The milk curd- ling enzyme of the pancreas was experimented with in this case. A small piece of dog pancreas was placed in each flask with the milk, and although it was questionable if the other pancreatic enzymes would not overshadow the action of any milk curdling enzyme, the work was carried through although somewhat un- satisfactory in results. 16 Flask No. 1. Control. to cc. n Flask No. 2. 10 cc. milk 1 Flask No. 3. to cc. " 0,5 Flask No. 4. to cc. " 0.2 Flask No. 5. 10 cc. " 0.1 Flask No. 6. to cc. '■ 0.05 Flask No. 7. 10 cc. " 02 milk - a small piece of fresh pancreas, ram sodium benzoate --- pancreas. The contents of the flasks were allowed to digest for 2 hours at 36 to 37 degrees C, with no apparent change. The flasks were then put in the incubator over night. The next morning the cream had risen to the surface in all. In No. 1 there was a mass of cream and the piece of pancreas at the top, and some whey- like liquid below. In No. 7 the conditions were similar but not so marked. In No. 6 the pancreas was suspended in the fluid and there was but a slight separation of the whey-like fluid. In No. 5 the pancreas was at the bottom and but a mere trace of whey. In 2, 3 and 4 the pancreas was also at the bottom and the fluid was of a uniformly milky appearance. It appeared as if tryptic digestion had gone on simultaneously and this was shown to be the fact ; for on making the peptone test peptones were found in all flasks except No. 2 in which they were entirely absent, and in No. 3 in which only a very faint trace was obtained. The inference formed from this experiment was that 0.2% of sodium benzoate caused but slight interference with any milk curdling action, but that more than that amount inhibited it. With regard to the tryptic digestion of milk, 2'/r, of sodium ben- zoate did not materially interfere, 5% caused marked retarda- tion and 10% entirely inhibited it. Experiment 14. This experiment was introduced in order to obtain, if possible, a purer milk curdling action without special interference of the other emzymes. Thirty grams of the pancreas of a sheep were triturated in a mortar with the addition of 150 cc. of brine. The mixture was allowed to stand for a day or two with occasional stirring. The reaction became slightly acid ; this was overcome or neutralized with \'/,_ sodium carbon- ate. The mixture was thea strained and filtered. Flask No. 1. Normal, to cc, milk. Flask No, 2, Control, 10 cc. milk 2 cc. brine solution. 17 Flask No. 3. 2d Control. 10 cc. milk + l grain rennin. Flask No. 4. 3d Control. 10 cc. milk + 2 cc. brine extract of pancreas. Flask No. 5. 10 cc. milk -|- l gram sodium benzoate + 2 cc. pancreas extract = 10% sodium benzoate. Flask No. 6. 10 cc. milk -[■ 0.5 gram sodium benzoate + 2 cc. pancreas extract = S% sodium benzoate. Flask No. 7. 10 cc. milk -| 0.2 gram sodium benzoate + 2 cc. pancreas extract = 2% sodium benzoate. Flask No. 8. 10 cc. milk + 0.1 gram sodium benzoate + 2 cc. pancreas extract = Ifi sodium benzoate. Flask No. 9. 10 cc. milk -|- 0.05 gram sodium benzoate -|- 2 cc. pancreas extract = 0.5% sodium benzoate. Flask No. 10. 10 cc. milk + 0.02 gram sodium benzoate -|- 2 cc. pancreas extract = 0.2% sodium benzoate. Flask No. 11. 10 cc. milk + O.Ol gram sodium benzoate -|- 2 cc. pancreas extract = 0.1% sodium benzoate. Flask No. 12. 10 cc. milk + 0.005 gram sodium benzoate -| 2 cc. pancreas extract = 0.05% sodium benzoate. After dig-esting 5 minutes in the incubator at a temperature of 38 degrees C. it was found that numbers 1, 2 aad 5 were still fluid, while numbers 4 and numbers 6 to 12 inclusive showed mod- erately firm clots. In No. 3 the clot was very firm. Ten minutes later there was no further change. After thirty minutes from the beginning of the experiment No. S clotted. One hour and a half from the beginning of the experiment numbers 4, 9, 10, 11 and 12 lost the coagulated condition and became quite fluid again , indicating the beginning of tryptic digestion. Nos. 5, 6, 7 and 8 were still clotted. Five and a half hours from the beginning of the experiment the normal and control flasks, Nos. 1 and 2, were still fluid having undergone no change ; numbers 5 and 6 were a little firmer than the others, except No. 3, in which there was a good clot and considerable whey. The flasks were all put in the incubator over night. In the morning it was found that No. 1 (normal) had undergone natural souring. No. 2 was apparently the same as the day before, the brine solution having probably prevented the souring. In No. 3 the clot had become much con- tracted and there was considerable whey. In Nos. 4 to 12 inclu- sive — the flasks containing the pancreatic extract — tests were made and peptones were found to be present in all, showing that tryptic digestion had not been prevented. The presence of 18 sodium benzoate to the extent of W^/o did not prevent clotting:, but delayed it for 30 minutes, nor did it prevent tryptic digestion. A control experiment was introduced by boiling some of brine extract of the pancreas to destroy the enzymes. 2 cc. of this boiled extract were added to 10 cc. of milk and the flask kept as the others had been. After 2/4 hours no changes were observed. The flask was then kept in the incubator over night, but no fur- ther changes were observable. There was no evidence of clotting and no peptones were found. Steapsiii. The fat splitting enzyme of the pancreas which plays such an important part as an aid in the emulsification of fats was used in the following experiment by placing a piece of fresh pancreas of a dog in some neutral fat (cream) which had been colored with litmus solution. The cream was found to be of neutral reaction as was also the sodium benzoate. When the litmus solution was mixed with the cream a neutral or light blue color resulted. If the steapsin was active and the fat acted upon by it, then the neutral or blue color of the mixture would be changed to a red on account of the presence of fatty acids formed by the action of steapsin upon the fat of the cream, splitting it up into fatty acids and glycerine. Experiment 15. Flask No. 1. Normal. 1 cc. cream — 1 cc. litmus solution + 1 cc. water. Flask No. 2. Control. 1 cc. cream -^ 1 cc. litmus solution + 1 cc. water + small piece of pancreas. Flask No. 3. Pancreas + i cc. cream + 1 cc. litmus + 1 cc. 10% sodium benzoate = 1 — 30 of sodium benzoate. Flask No. 4, Pancreas + l cc. cream — 1 cc. litmus + 1 cc. 5% sodium benzoate = 1 — 60 sodium benzoate. Flask No. 5. Pancreas + l cc. cream ^- 1 cc. litmus -r l cc. 2.5% sodium benzoate = 1 — 120 sodium benzoate. Flask No. 6. Pancreas + 1 cc. cream + 1 cc. litmus -|- 1 cc. 1% sodium benzoate = 1 — 300 sodium benzoate. Flask No. 7. Pancreas H- 1 cc. cream -f- 1 cc. litmus -\- 1 cc. 0.5% sodium benzoate = 1 — 600 sodium benzoate. Flask No. S. Pancreas— 1 cc. cream— 1 cc. litmus J- 1 cc. 0.25% sodium benzoate = 1 — 1200 sodium benzoate. Flask No. 9. Pancreas — l cc. cream + 1 cc. litmus + 1 cc. 0.125% sodium ben- zoate = 1 — 2400 sodium benzoate. 19 Flask No. 10. Pancreas -\- l cc. cream 4 1 cc. litmus -|- 1 cc. 0.0625,^iJ sodium ben- zoate = 1 — 4S00 sodium benzoate. Flask No. 11. Pancreas + 1 cc. cream -| 1 cc. litmus + 1 cc. 0.03125% sodium benzoate = 1 — 9600 sodium benzoate. The cream, litmus and sodium benzoate were all mixed to- gether and allowed to stand for 2}^ hours before adding the pan- creas. The flasks were kept in the incubator at 37 degrees C. and were observed at intervals. A red color soon appeared in the litmus surrounding the pancreas. Within twentj- minutes this had appeared in all the flasks but the normal — No. 1. The red color was best developed in Nos, 2 and 8. In No. 3 there was some fatty acid as shown by a slight red, but this flask was the poorest of the series. Nos. 4, 5, 6 and 7 did not show much difference between themselves but all were better than No. 3. No. 8 was nearly as good as No. 2. There was not much differ- ence between Nos. 9, 10 and 11 but none of them were as good as No. 8, although they were slightly better than 4 to 7 inclusive. They were all left in the incubator over night and examined the next morning when it was found that the best development of fatty acids had occurred in Nos. 2, 8, 9, 10 and 11 ; Nos. 6 and 7 were next in order, while 3, 4 and 5 were the poorest of the series. No. 1 had also turned red on account of the development of the acids incident to the natural souring of cream. It would appear, therefore, that the presence of sodium benzoate in proportion of 1 to 1200 did materially affect the action of steapsin. In the proportion of 1 to 300 and 1 to 600 the action was somewhat re- tarded. The action was still more retarded by the proportion of 1 to 120 and 1 to 60 ; but 1 to 30 did not stop the action of the enzyme. Two other tests were carried out with a larger proportion of sodium benzoate present. In these tests the ingredients were all mixed together at the same time. Flask No. 12. Pancreas + 1 cc. cream + 1 cc. litmus + 5 cc. W/r sodium ben- zoate = 1 to 14 of sodium benzoate. Flask No. 13. Pancreas + 1 cc. cream -|- 1 cc. litmus -f- 5 cc. water + 1 gram sodium benzoate = 1 to 7 of sodium benzoate. In No. 12 there was a slight evidence of fatty acid in 20 min- utes. Two hours later this was somewhat increased, and there 20 was a faint trace of red color in No. 13. After remaining in the incubator over night there was not much change. On shaking the flasks No. 12 became slightly red while No. 13 remained blue, although some red was present around the piece of pancreas itself, indicating traces of fatty acids, but these w^ere not strong enough to overcome the blue color. Another control was prepared by placing a piece of the pan- creas in some litmus and water. This was left in the incubator over night. In the morning it was found that no change had occurred. Iiivcrliu. A study was also made of the action of the enzyme of the succus entericus (intestinal juice). A preparation was made by removing 40 grams of the mucous membrane of the small intestine of a dog ; triturating" it in a mortar with 40 cc. of 1''/' acetic acid and then adding 400 cc. of chloroform water. After standing for two days this mixture was made slightly alka- line by the addition of sodium carbonate. This enzyme had the power of converting cane sugar into dextrose a reducing sugar. The cane sugar was tested before the experiment began and was found to be free from any reducing sugar. Experiment 16. Flask No. 1. Check. 50 cc. 2'/o cane sugar -|- 50 cc. water. Flask No. 2. Control. 50 cc. cane sugar -\- 25 cc. water -]■ 25 cc. intestinal ex- tracts. Flask No. 3. 50 cc. 2'/r cane sugar + 25 cc. extract f 1 gram sodium benzoate in 25 cc. water. Flask No. 4. So cc. 2% cane sugar -\- 25 cc. extract -]- 0.5 gram sodium benzoate in 25 cc. water. Flask No. 5. 50 cc. 2% cane sugar | 25 cc. extract ] 0.25 gram sodium benzoate in 25 cc. water. Flask No. 6. 50 cc. 2% cane sugar -| 25 cc. extract 1 0.125 gram sodium benzoate in 25 cc. water. Flask No. 7. 50 cc. 2;:'o cane sugar -I 25 cc. extract 0.0(525 gram sodium benzoate in 25 cc. water. The solutions of sugar and sodium benzoate were mixed to- gether and allowed to stand over nig-ht before the digestive ex- tract was added. Digestion was continued 6 hours ; the temper- ature at the outset being 30 degrees C. and rising toward the end of the experiment to 42 ' C. 21 Number of cc. of solution equal to 0,05 gram sugar or to reduce lo cc. Fehling's. Flask No. 1. Check. No reduction Flask No. 2 Control. 37 cc. Flask No. 3. 1 '/n Benzoate. 44 cc. Flask No. 4. 0.5^ Benzoate. 42 cc. Flask No. 5. 0.25% Benzoate. 37.3 cc. Flask No. 6. 0.125% Benzoate, 24.8 cc. Flask No. 7. 0.0625% Benzoate. 35.4 cc. Qualitative tests 1 hour after dig-estion beg-an showed the presence of reducing- sugar in flasks 2, 5, 6 and 7, and after another hour reducing- sug-ar was found in all of them. The quantitative tests indicate that the presence of sodium ben- zoate to the extent of 0.25'/' does not affect the conversion of cane sugar into reducing sugar ; but that 0,5'/; and \''/o mater- ially retarded the action of the enzj'me. SUMMARY. Carbohydrates. The experiments indicate that the diges- tion of carbohydrates, starch and cane sugar, was not much inter- fered with on account of the presence of sodium benzoate. When the benzoate was present to the extent of 0.5'/ to 1'/. there was some evidence that digestion was delayed. In smaller percentage 0.25% or less the digestion, as a rule, seemed to be normal. This statement applies, in general, to the action of the enzymes ptyalin of the saliva, amylopsin of the pancreatic juice, and in- vertin of the succus entericus. Proteids. In the digestion of ^gg albumin and raw meat with solutions of pepsin in hydrochloric acid, \''/o of sodium ben- zoate was sufficient to altogether inhibit the action of the enzyme ; 0. S"}^ did not quite inhibit digestion but very materially retarded it ; 0.25/, and less did not interfere with the digestion of t%^ albumin but did retard it slightly in the case of the meat. In the experiment with the extract made from the mucous mem- brane of the dog's stomach, and fibrin as the proteid to be digested, still more unfavorable results were obtained ; one-half per cent of the benzoate entirely prevented digestion ; 0.25% per- mitted only a trace of digestion, and a percentage as low as 22 0.0625'/; materially retarded the action of the enzyme. The di- gestive fluid in this case contained the pepsin fresh from the g'as- tric mucous membrane and the conditions of the experiment should be regarded as more nearly comparable to normal than where merely a solution of pepsin is used. In the digestion of proteids with the pancreatic preparations, sodium benzoate up to I'/J and 1 = 3'/ did not prevent the forma- tion of peptones, although \'/o retarded digestion in the case of raw meat in a solution of the pancreatin, while in the artificial extract of the pancreas of a horse with dry fibrin as the proteid O.S'/i retarded digestion somewhat, while lower percentages had only a slight effect in this direction. In an experiment on milk it was found that sodium benzoate to the extent of 10'/ inhibited the formation of peptones and that 5'/( permitted only a faint trace of them. Two per cent and less of sodium benzoate appar- ently did not materially interfere with the production of peptones. In another experiment upon milk, in which a brine extract of the pancreas was used, sodium benzoate to the extent of 10'/ did not prevent the formation of peptones. Rennin. In the preparation of rennin made from the fourth stomach of a sheep the presence of sodium benzoate to the extent of 0.057,^ to 0.2% delayed the curdling of the milk for 20 to 25 minutes. Five per cent, and ten per cent, of the benzoate pre- vented the curdling altogether and O.S^r to 2'/^, very materially retarded the process. In another experiment in which commercial rennin, in tablet form was used, sodium benzoate to the extent of 0.2% to 1% did not seem to materially interfere with the curdling of the milk. Even as high an amount as 10 '/o did not inhibit in this case, but caused an irregular mass to form in the milk as if there had been an attempt at curdling. The same results were found in the tubes containing 2'/o and 5%, of the benzoate. Of these two rennin experiments the first is more nearly in accord with normal conditions and should be considered the more reliable. The presence of a milk-curdling enzyme in the pancreas is questioned by some. Experiments were, nevertheless, tried in this direction, and although the results were not so satisfactory 23 as in the case of the gastric and commercial rennin there appeared to be some evidence of a curdling action. In the former case, pepsin did not interfere with the action of the rennin because pepsin does not work in a neutral or alkaline medium. Trypsin is active in a neutral or alkaline medium and therefore inter- fered more or less with the action of any milk-curdling- enzyme that might have been present. In the experiment in which a small piece of pancreas was placed directly into the milk the results were unsatisfactory from a milk-curdling standpoint. No curdling took place after two hours observation. After digestion over night in the incubator no satisfactory clots were found, although there appeared to be a whey-like fluid in some of the tubes. On the basis of this whey- like fluid, 0.2% sodium benzoate, as compared with the normal, interfered somewhat with the production of this fluid. More than 0-2% inhibited this action. Peptones were also found in these tubes, so that assuming an interference on the part of the enzyme trypsin, it is somewhat questionable if a true milk- curdling action occurred. More satisfactory results were obtained in using a brine extract from the pancreas of the sheep. In this case moderately firm clots were found in certain of the tubes within 5 minutes after the beginning of digestion. Later the coagulation dis- appeared and the milk apparently underwent digestion by the trypsin as shown by the presence of peptones. That the co- agulation was not in any way due to the brine solution is shown by the fact that control No. 2 which contained milk and brine only remained fluid throughout the experiment. As much as 10% sodium benzoate did not prevent the coagulation but delayed it for 30 minutes. The brine extract apparently hastened the action of the milk-curdling enzyme or delayed the action of the trypsin ; for in this experiment there was good evidence of the activity of both enzymes. Fat. The enzyme which has most to do with this food sub- stance is steapsin which is developed in the pancreas. Steapsin is a most important factor in promoting the emulsification of fats. Sodium benzoate in the proportion of I to 1200 or about 0.08%., or less amounts did not appear to materially affect the 24 action of steapsin. In the proportion of 1 to 600 (0.16'7, ) or 1 to 300 (0.33'/ ) the action was somewhat retarded. Higher percent- ages caused still more retardation ; but a proportion as high as 1 to 7 (14y, ) did not quite inhibit the action of the enzyme. The presence of sodium benzoate to the extent of 0.2'/ did not appear to interfere with the digestion of carbohydrate food. Higher amounts did not always interfere ; but in some cases they did retard the action of the enzymes, and the percentage above mentioned may be regarded as being within safe limits. Sodium benzoate seemed to exert a more direct inhibitory action upon pepsin than any of the other enzymes studied. Al- though 0.2'/. of sodium benzoate did not interfere with the diges- tion of egg albumin, as little as 0.06'/ did materially retard the digestion of fibrin. The nature of the proteid may have some influence upon its digestibility in the presence of sodium ben- zoate. The digestion of proteids, in the presence of sodium ben- zoate, by the pancreatic enzyme trypsin, was more readily accom- plished than by pepsin. This was shown by the fact that 1% sodium benzoate usually inhibited the action of pepsin, while trypsin was still able to produce peptones in the same percentage of benzoate. With 0.2'/ and less of the benzoate there was practically no injurious effect upon the trypsin. The nature of the proteids, as already mentioned, may have some influence upon their rate of digestion with sodium benzoate. In one experiment with milk, 5'/ of the benzoate permitted a faint trace of peptones. In an- other, 10'/ did not completely inhibit their production, while 2'/; apparently did not interfere with the digestion of the milk proteid. The enzyme rennin, as prepared from the mucous membrane of the stomach, was found to be quite sensitive to the presence of sodium benzoate. The lower percentages ( 0.1 '/i) retarded the action of the enzyme, while 5'/ and over completely inhibited it. With regard to the milk-curdling enzyme of the pancreas, sodium benzoate also caused a retarding effect, but not so marked as in the case of the gastric enzyme. Steapsin, the fat splitting enzyme of the pancreas, was mod- 25 erately sensitive to sodium benzoate ; 0.089?! or less of the ben- zoate did not appear to interfere with its action. Higher per- centages caused some retardation, but as high a proportion as 1 to 7 (,14'/( ) of the benzoate did not cause complete inhibition. Sodium benzoate caused less interference with digestion in a neutral or alkaline medium than in an acid medium. From the evidence of the experiments it seems reasonable to conclude that the presence of sodium benzoate to the extent of 0.1 '/( or less exercised no specially harmful effects upon the digestive enzymes. A higher percentage than this, in some cases, did retard the dig-estive processes, and a continuation of such condition might, in time, effect the general health of the individual. It should be remembered, however, that in natural digestion the benzoate, mixed with the food, passes from the action of one digestive fluid to that of another. The benzoate, having been first concerned in the alkaline salivarv digestion, may, as a result, produce a less profound effect upon peptic digestion than in the conditions of the experiments where the benzoate was introduced de novo in each digestive fluid. EXPERIMENTS WITH NUCLEIN. LEE SBLDON BACKUS It has long- been known that all animal or vegetable sub- stances are made up of histolog'ic units known as cells ; that these cells possess the power to develop and reproduce themselves and the constituent which makes this possible is the nuclein which they contain. Chemically the nucleins are complex pro- teid bodies, notable for their large amount of phosphorus. Quite recently it has been found possible to separate this nuclein from the other substances contained in the cell body, and in view of the important function which it normally performs it was thought that it might perhaps have important therapeutic effects as a tonic to the system and by increasing natural resist- ance to disease. Nuclein is present in, and obtainable from, a number of sources. The thyroid glands, liver, kidneys, lungs, testes, ovar- ies, spermatozoa, brain, spinal cord, etc., have all been examined chemically with the result that nuclein has been found to be the most abundant as well as the most important proteid substance present. It has not been found advisable, however, to obtain the nu- clein from any of the above sources. It has been found that it can be most easily derived from the yeast plant and is put on the market both in the form of a solution and in tablets. As seen in solution it is a reddish brown liquid, slightly saline taste, with an odor not unlike that of beef bouUion, and of neutral reaction. As a therapeutic agent, although it has some antiseptic power, it is supposed to act by multiplying and stimulating the natural resisting forces or the phagocytes. Such a physiologic action would refer us at once to morbid blood states and their consequences. Such defects generally being due to blood toxicity. The former includes impoverished conditions of the blood in which the circulating fluid is lacking in those qualities which 27 are necessary to the performance of its proper functions. Nuclein is also claimed to be indicated wherever cell integ^rity and cell activity are lacking-, whether due to insufficient reinforcement from the blood or to inhibition of toxins residingf in the blood. And likewise in such conditions of toxicity in which the system has been invaded by pathogenic germs and the defensive proteids tind themselves impotent to meet functional demands m conse- quence of systemic infection, and it is in the hope of gaining some insight as to the real therapeutic vakie of nuclein that the following experiments have been conducted. With onl}^ a small number of animals (all of which were dogs) and the length of time for experimenting necessarily limited, the results are not fully conclusive, but might serve a useful purpose, as a hint, in further investigation along the same line. As the white blood corpuscles are among- the most active of the phagocytes, and the primary action of nuclein is the sup- posedly rapid increase of these bodies, most of the examinations have been upon the blood. In some cases both red and white cells were counted. In these cases dilution was made with Toisson's fluid, using Thoma's apparatus. Where only the leucocytes were counted a }j7( acetic acid solution was used. In every case one hundred squares were counted for the red corpuscles and the en- tire field for the white. In any count if anything happened which might cause an error, the preparation was discarded and a new one prepared. In getting an estimation of the hemoglobin Tallquist's hem- oglobinometer was used. I found it most convenient to obtain the blood from the inside of the ear, selecting a spot void of hair and puncturing with a sharp lancet one of the small vessels which can be readily seen throug-h the integument in this part. In preparing to make a count, the ear is first washed with water, then wiped off with alcohol and dried. A quick thrust of the lancet brings the blood, the first drop being discarded and the succeedino- used. It is well to have an assistant to keep the ani- mal quiet at this stage, as a slight jerk of the head may easily cause a failure in filling the pipette. Having obtained the re- quired amount of blood, the end of the pipette is wiped off, then 28 immediately filled with the diluting fluid and revolved for one minute, holding the pipette in a horizontal position. This serves to thoroughly distribute the corpuscles. A drop of suitable size is then placed upon the counting chamber, the cover glass placed over it and the preparation examined. The first case on which we used nuclein and which was accurately recorded entered the College Clinic October 30th. '^' The animal was a male collie, six inonths old, and weighing about fifty pounds. The history of the case, as given by the owner, was that the dog had been running about the house and barn and went under the latter in the afternoon of September I5th. As he failed to come out by the following morning, some boards in the barn floor were raised and the animal was taken out of a privy pit, covered with the filth. The dog was washed and ffiven good care but did not appear normal. In a few days he began to show symptoms of paralysis in the right hind leg and in two weeks the paralysis had extended to the opposite side and he was then brought in for treatment As seen by us on October 30th there was paraplegia, extreme nervousness, and the head kept drawn toward the right side. When disturbed by being handled, as in giving medicine, the dog would suddenly give two or three turns and then, bringing- the head down against the bedding with a quick jerk, would lie quiet for a time. The first blood count, 4 P. M., October 30th, resulted as fol- lows : Erythrocytes 5,000,000 ; Leucocytes 4,900. This shows a normal count for the red cells but a marked deficiency in the white ; the normal for the dog being about 10,000. As soon as the blood was taken for this count, twenty minims of nuclein were injected hypodermically. At 4:30 P. M.: Red cells, 5,628,000; White, 6,402. At 5:30 P.M.: " " 5,620,000; " 8,444. In addition to the nuclein treatment, which consisted of 20 minims three times daily, he was given a laxative of calomel gr. ss., sodium bicarbonate gr. ss. Also mixed treatment, two tablets thrice daily, then twice daily. * Published as Case Report "Canine Toxemia," Amer. Vet. Review, Nov. igo6. XXX-g66. 29 No. 1 : Strych, Arsenate, - - - J-!; grains Quinine " - - 1 srain Echinacea Ext. - - - 16 grains Glycerine Water - - aa q. s. - - 2 ounces M. Sig. Teaspoonful twice daily for three days, then thrice daily. The laxatives which were given caused a slight movement of the bowels. On November 2ud a blood count was made showing- Erythro- cytes 6,000,000, Leucocytes 6,000. November 4th omitted treatment No. 1 and substituted tab- lets of digitalis and aconite — one tablet three times daily. November 6th. Red cells 6,880,000, White cells 7,500. November 9th. An abscess was found under the integument in front of the shoulder. The hair was sheared from the red, fluctuating swelling and slight pressure sufficed to break it. There was discharged a thin bloody pus from which a smear was made and examined microscdpically. Rod-like org-anisms were found, each bearing a capsule. November 10th. Up to this time the patient had been fed milk from a bottle in the form of a drench, about two ounces three times daily. On this date he seemed in better spirits and was able to use the legs to a limited extent and lapped some milk from a basin. He also ate a dog biscuit with apparent relish. Leucocytes 9,000. One dram of nuclein was given once daily b}^ hypodermic injections from now on. The mixed treatment was dropped and a small dose of Epsom salts was given. November 12th another abscess was ruptured on the right abdominal wall and an organism similar to the one found on the ninth was isolated. Every day or two an enema of warm water was given which usually resulted in the free passage of feces mixed with hay which the dog had eaten from his bed. On November 15th an examination of the urine was made with the following- results : Specific gravity .... 1030 Urea - - - 39 grams per 1000 cc. Albumin - _ . . . None Sugar ----- None Phosphates - - - 2.6 grams per 1000 cc. Chlorides - - .94 grams per 1000 cc. 30 Beg-inning November 20th one dram of nuclein was given twice daily by mouth. December 2i3d. The dog- had continued to improve and could now walk, though with some difficulty. As there was extreme nervousness bromide was given to quiet him. On December 10th the dog was led outside for a little exer- cise which appeared to be of much benefit. The nuclein was now reduced to one-half dram twice daily. December 20th. Red cells 6,000,000, White cells 12,500. On December 23rd he was thought to be sufficiently conval- escent to be discharged and went home. The following table shows the pulse and temperature while undergoing treatment : DATE. PULSE. TEWPERATURE. 102.5 102.5 102.4 102.0 102.6 104.0 101.5 102.7 103.0 103.4 102.4 102. S 103.0 103.0 On January 9th the case was returned. While away there had been a rapid increase in flesh but otherwise he was much the same as when first brought to the clinic. Head drawn to the right side, rolling over and over when excited, and appearing to suffer greatly. He was put on treatment of triple arsenates, with nuclein and mixed treatment. As there was not much im- provement shown it was thought best that the animal be chloro- formed and a post-mortem held. This took place January iSth. A blood count was made January 7th and showed leucocytes 9,000. Autopsy. Lungs — right anterior lobe two-thirds hepatized ; principal and middle lobe entirely hepatized ; both lobes of the Oct. 30, '05 120 Oct. 30, '05, (4 P. M.) 130 Oct. 31, '05 120 Nov. 1, '05 120 Nov. 2, '05 120 Nov. 3, '05 130 Nov. 4, '05 Nov. 6, 'o5 Nov. 7, '05 Nov. 8, '05 120 Nov. 9, '05 Nov. 10, '05 Nov. 12, '05 Dec. 2, '05 31 left lung- were coag-ested approaching hepatization. Heart — right auricle in diastole ; valves and heart muscle normal ; left heart in systole ; thoracic cavity normal. Liver — congested ; bile cyst well filled and normal in appearance. Spleen normal. Stomach filled with gas. Small intestines normal. Large intestines nor- mal and filled with semi-dry dark green ingesta. Kidneys normal. Bladder filled with urine. The brain was somewhat congested, but otherwise normal. Some sections of the brain were made but no lesions found. Cultures were made from the blood of the lungs and liver. From those obtained from the lung the culture was mixed. Those from the liver gave a pure culture which in all characteristics corresponded with those found in the abscesses previously examined. The case had been diagnosed as toxemia, which appears to have been correct, and from the post-mortem cultures it would seem that there was a general infection and a condition of an- emia as shown by the blood count. It was just such a case as would indicate a nuclein treatment and, although it ended fatally, there are a few points which would go to show that the nuclein was of considerable value. On the first day that the drug was administered there was an increase of over three thousand white cells or 73.77%, an increase which should be of great benefit in ridding the system of micro-org-anisms. The total increase be- tween October 30th, when the dog entered the clinic, and Decem- ber 20th, which was three days before the animal went home, was 7,600 leucocytes, (Oct. 30, 4,900— Dec. 20, 12,500), or in other words the resistance of the animal to infection had been more than doubled and I think it quite possible that if the animal. had remained in the clinic it would have recovered. The rapid in- crease in flesh as seen on being returned January 9th would give rise to the suspicion that the animal had been immediately put on rich food, thereby clogging the channels of elimination and producing such a condition as would greatly favor the repro- duction of toxemia. It might be argued that the other treatment had something to do with the increase of leucocytes and this is quite possible. It must not be overlooked, however, that nuclein gave a rapid increase of leucocytes when first used and a gradual increase 32 during the entire time the case was under observation, and that it was the only agent which was given uninterruptedly during the entire period. Case II. This was an experimental case. The animal selected was a small dog of mixed breed, weight about thirty pounds. It was in good condition and in every way appeared to be normal. When the dog was wanted for examination, he was taken from the kennel into the research laboratory, a distance of about two hun- dred feet. Date. Time. Respiration. Pulse. Temp. Erythrocytes. Leucocytes. Hemog. Oct. 24, 4:00 p.m. .. 5,008,000 11,440 85% " 25,10:00 a.m. .. 120 102.5 4,800,000 9,000 80% " 28, 4:00 p.m. .. 120 102 5 4,900,000 12,333 Feb. 13, 9:30 a.m. 20 120 102.6 4,900,000 Gave one dram nuclein at 10:00 a. m. (hypodermic). Feb. 13, 10:15 a. m. 25 132 101.9 11:00 a. m. . . ... 102.2 1:00 p. m. ... 102.3 Feb. 17, 8:30 a. ni. 24 120 102.9 11,111 Injected 40 minims of nuclein at 10:00 a. m. 10:15 a. m. 24 135 102 10:45 a.m. .. ... 102.2 14,058 11:40 a. m. . . ... 102.5 1:00 p. m. . . ... 102.6 Feb. 20, 9:30 a.m. 24 120 102.8 13,844 100% Injected thirty-five minims nuclein at 10:30 a. m. 10:45 a.m. 30 140 102.1 16,222 (11 a.m.) 11:15 a. m. 36 140 102.4 11:45 a.m. 26 140 102 1:00 p. m. . . ... 102 Feb. 24. In the preceding tests the initial temperature had been taken in the labor- atory. 1 now began taking it in the kennel so that the exercise of the dog might not be the cause of an error. 8:45 a. m. 22 124 102 9:00 a. m. Taken in laboratory. 24 125 102.9 9:30 a. m. 24 124 102 Feb. 27, 9:30 a.m. .. (in kennel) 102 9:45 a.m. 19 (in labor'y) 102 6 12,550 100% 10:00 a.m. 48 130 102.7 10:25 a. m. Gave twenty minims of nuclein (hypodermic). 33 Date. Time. Respiration. Pulse. Temp, Eiytlirocytes. Leucocytes. Hemop;. Feb. 27, 11:30 a. 111. .. ... ... 16,666 12:00 m. 40 lj;o 102,3 15,333 Mar. 12, 9:30 a.m. .. 120 lOl.S 11,333 Gave ten minims of nuclein at 10:00 a. m. 10:00 a.m. .. 120 101. S 10:45 a. m. . . 13,300 11:15 a. m. . . 13,000 Mar. 17, 8:00 a.m. .. 120 102 S:l5 a. m. . . 13,111 100% 8:20 a. m. Injected twenty minims of nuclein. 9:45 a. 111. .. 115 102 14,100 .... 10:00 a. m. Injected forty minims more of nuclein. 10:30 a. 111. . . 15,205 Case No. III. Experimental dog, mixed breed, weight about eig-hteen pounds. Date. Time. Respiration. Pulse. Temp. Erythrocytes. Leucocytes. Hemog. Mar. 5, 9:00 a. m. .. 140 104.8 11,222 100% 9:30 a. m. Gave thirty minims of nuclein. 9:30 a. m. . . ... 102.2 10:30 a, m. .. 6,300,000 15,333 11:30 a.m. .. 13,200 Mar. 6, 9:l5 a. m. .. ... 101.6 9:45 a.m. .. 9.222 100% 10:15 a. 111. Injected twenty minims of nuclein. 10:30 a.m. .. ... 102.2 9,000 10:50 a. m. . . S,000 11:30 a. m. . . , 9,000 Mar, 10, 8:00 a. m. .. ... 101.6 8,333 Injected twenty minims of nuclein at 9:00 a. in. 9:30 a. m. . , 8,330 ... In case No. 2 every experiment gave a rapid leucocytosis after the injection of nuclein. The highest being that of Feb- ruary 27, where there was an approximate increase of 4,000 white cells in about an hour. The respiration and pulse did not show any variation that could be considered due to the drug. In the earlier experiments it appeared that there was a fall in tempera- ture of about one degree after the injection of the nuclein. But on taking the initial temperature in the kennel it was found 34 that the animal's temperature rose about one degree in trans- ferring- him to the laboratory and the apparent fall was probably only the return to normal when he again became quiet. The red cells or hemoglobin did not appear to offer any variation from the normal. Case No. 3 did not give conclusive results in any direc- tion. It would be well perhaps to state that this animal was very timid and so frightened when injected or otherwise experi- mented upon that it is quite possible that the virtue of the agent was more than overbalanced by the dog's mental condition. In the Clinic of 1905, a case of mange was brought in for treatment. Along with the external treatment, nuclein was administered internally. The outcome was a complete and rapid recovery. Considering the severity of the case when it entered and contrasting it with similar cases we feel that no little credit was due to the nuclein treatment. The Gekmicidai. Properties of Nuci^ein. For this I took a twenty-four hour culture of micrococcus pyogenes aureus, and from this inoculated two cubic centimeters of nuclein with one loopful of the organism. I then took six tubes of boullion and inoculated them with one loopful of the nuclein culture in the following order. First tube inoculated at the end of 1 minute. Second tube Ttiird tube Fourth tube Fifth tube Sixth tube 3 5 10 20 30 Examined after twenty-four hours and found no growth in any of the tubes. In the next experiment 2 cc. of nuclein were diluted with an equal amount of sterile water. This was then inoculated with two loopfuls of the culture. Again six tubes of boullion were used, this time transferring two loopfuls of the nuclein culture into the boullion. No. 1. End No. 2. No. 3. No. 4. No. 5. No. 6. 35 Tubes. Time of inoculation. 24 hours later. 1 minute. Growtli. 3 5 10 " No growth. 15 20 " This shows there is quite a marked g-ermicidal action. It must be taken into account, however, that in the preparations used* the nucleiu contains a small amount of trikresol as a pre- servative. Following this a few experiments were conducted with a view to determine if nuclein was converted into peptones when taken into the digestive tract. It would appear that if nu- cleins were changed into peptones bj' the digestive ferments, they would be of no more value as therapeutic agents than pep- tones derived from other sources. The following solutions were made : c- 1 t- n ■ ( Pepsin, .3 gram. Solution Pepsm 3 ^j^ HCl 100 cc. ( r- 1 f n f \ Pancreatin, 1 eram. so ution Pancreatm -' „, c j- .1 r- i „t tn ~„ ( ifo Sodium Carbonate, 40 cc. Prepared four test tubes. Tube 1. Pepsin solution 20 cc, Nuclein 5 cc. Tube 2. Pancreatin solution 15 cc, Nuclein 2 cc. Tube 3. Pepsin solution 25 cc, Nuclein tablets (three). Tube 4. Pancreatin solution 20 cc, Nuclein tablets (three). These were put in an incubator at 40° C for one hour and a half, after which they were tested for peptones by adding an excess of 20% caustic potash solution and a drop or two of a solution of copper sulphate. This test gives a pink color with peptones, but albumose gives the same reaction. To determine if the latter is present some of the solution was saturated with ammonium sulphate, filtered and tested. This serves to precipi- tate and remove the albumose, and if the filtrate gives a pink color we have peptones. Tests were made for syntonin and alkali albumin by the contact method. 1% sodium carbonate solution being used for the former and .2% HCl for the latter. An affirm- ative test is shown in either case by a white precipitate at the neutral zone. ♦Parke Davis. 36 No. Tu ibe. Peptones. Albumose. Syntonin. Alk . Albumin 1 None Present None None 2 None Present None Present 3 None Present None None 4 None Present None Present The tubes were returned to the incubator for forty-eight hours, but when re-examined showed the same results. As a check to this test I prepared some more of the same dig^estive solutions and put them in the incubator for one hour — no nuclein being added. At the end of this time both solutions gave the pink color indicating peptones or albumose. The tubes were then returned to the incubator for twenty-four hours. When tested both were found to contain albumose but no peptone. This concludes my experiments with nuclein and, although the work done is not conclusive in any particular, it would indi- cate that : 1st. Nuclein does cause a rapid leucocytosis, a single dose being sufficient to increase these cells several thousand per cubic millimeter of blood. 2nd. The red cells are affected only to a slight degree. 3rd. It is non-toxic. Dram doses given hypodermically do not effect pulse, respiration or temperature in the normal animal. 4th. It does possess germicidal properties to a considerable extent. 5th. It is not converted into peptones by the digestive fer- ments. In conclusion I desire to acknowledge my indebtedness to Ward Giltner for assistance freely given in many of the blood counts, and to Dr. Fish for suggestions and use of drugs from the Department of Physiology and Pharmacology. REFERENCES : Haru— Practical Therapeutics, ^tl.i edition. Potter — Materia Medica, Pljarriwcy and nerapentics. United States Dispensatory, iStlj edition. Butler — Materia Medica, nerapentics and Pliarmacology . Parke, Davis cS; Co. — Nuclein, its Origin, Nature and nerapentics. Metchnikoff — Immunity in Infective Diseases. ARECOLINE HYDROBROMIDE. PIERRE A. FISH. Arecoline is the alkaloid obtained from the Betel or Areca nut. Pure arecoline is a colorless oily fluid, miscible with water, alcohol, chloroform and ether. It is present in the areca nut to the extent of about 0.1%. The alkaloid is very toxic and forms crystalline salts ; the principal one of which is arecoline hydro- bromide, CsH,,NOjBrH. Two other alkaloids have been described, one under the name arecaine and the other, existing- in traces, as guvacine. The investigations of MarmiJ and Frohner point out many resemblances between the effects of arecoline and the combined effects of eserine and pilocarpine. It likewise resembles mus- carine in its action. E. Frohner has noted the following actions of arecoline upon the horse : It is a strong sialagogue. Doses of ^ to f grain (0.01 — 0.05) cause the saliva to flow in about five minutes, reaching the maximum in one-half hour and continuing to flow for about an hour. It produces tetanic contractions of the intes- tinal muscles and excites the intestinal glands. Horses purg-e, on the average, from doses of ;} to i^ grains (0.05 — 0.1), the first dis- charge appearing in from one-fourth to one-half hour after the injection. Purgation is usually accompanied by light colicy symptoms. Earg-e doses of arecoline excite the sweat glands and cause increased perspiration. There have also been observed nasal discharge (from stimulation of the gflands of the nasal mucosa) and urination. The local application of a solution of arecoline (0.1 — 1%) to the eyeball causes marked contraction of the pupil, lasting for several hours. Subcutaneous injections, however, do not produce this effect. Arecoline has a marked anthelmintic action. Cardiac action is slowed (vagus stimu- lation). Toxic doses produce arhythmia of the heart ; fall in blood pressure and temperature as well as a marked acceleration 38 of the pulse (paralysis of the vagus). Large doses are fatal because of respiratory- paralysis with tetanic contractions. Doses of 3| grains (0.25) are toxic for the horse; 7^- grains (0.5) are fatal. Bocquillon-Limousin gives as the fatal closes : for the rabbit I to ;} grain (0.025—0.050) ; for the cat .} grain (0.020) ; for the dog 1}; g-rains (0.075). If. J. Milks, in some experiments at the New York State Veterinary College, using Merck's preparation of arecoline hydrobromide, found that after previous injections of small doses that the fatal dose must thereby apparently be in- creased. A dog, weighing about 25 lbs., received subcutaneously on four successive days doses of j-^. '. y„ and 1 grain. The dog was apparently as well as ever the day following the injection of the 1 grain. Three days later 2 grains were injected and were fol- lowed by toxic symptoms with blood passing in the feces. After six days the dog apparently recovered. Two weeks from the beginning of the experiment 3 grains were injected during the afternoon and the dog died the following forenoon. During the post mortem, several tape worms (seven) were found in the small intestine, indicating that there was no vermifuge effect from the injections, as no segments of the worms were observed to have passed in the feces. In another dog, where some of the areco- line solution was injected into a segment of the intestine, living tape worms were found after having been in contact with the solution for several minutes. In kittens weighing from f to 2| lbs., J- grain was fatal. In a cat weighing 4^ lbs., \ grain was fatal. In general the heart continued to beat for a time after respiration had ceased. Dr. H. E. Titus of Ames, Iowa, experimented with arecoline hydrobromate upon fourteen cases, including horses, cows, dogs and one sheep. The sheep was in an emaciated condition and died shortly after a dose of 5 milligrams (yV grain). One of the cows suffering from parturient apoplexy, died after receiving two doses of 50 milligrams (^ grain) each. He used the drug successfully in cases of colic and laminitis in horses. From a therapeutic standpoint, the drug has proven of con- siderable value in the treatment of colic and laminitis. It has also been recommended in azoturia combined with sedatives ; 39 also where myotics are indicated. Frohner states that, like pilo- carpine, arecoline is a good resorbent for internal and external transudates, especially in cerebral dropsy and phlegmon, and that several cases of blind staggers have been benefitted. The effect of arecoline hydrobromide upon the circulatory system is pronounced. The writer has taken blood pressure tracings from five horses under chloroform anesthesia, following the intravenous and hypodermic injection of the drug and the ' results are briefly summarized as follows : Horse No. 30 was badly affected with the heaves. Weight 910 lbs. (413 kilograms). The normal blood pressure was found to measure 116 mm. of Hg. Twenty and six-tenths cc. of a 0.2% solution of arecoline hydrobromide, the equivalent of 0.1 mg. per Kg. or a total of about fr grain, were injected into the right jug- ular vein. The effects were almost immediate. There was pro.- fuse salivation ; slowing of the heart, with some irregularity in its beat and a fall in blood pressure to 62 mm. (Fig. 1). The pupils became dilated and the blood was very dark indicating an excessive amount of CO.^. The horse showed toxic symptoms and the same amount of atropine sulpbate was injected into the jugular as an antidote. Improvement resulted as shown by the more rapid beat of the heart and an increase of blood pressure to 108 mm. and later to 130 mm. No more atropine was given and the horse died later, something within two hours after the experiment. Horse No. 31. Weight 1084 lbs. (492 kilograms). 12.3 cc. of a 0.2% solution of arecoline were injected (0.05 mg. per Kg.) or a total of about 1 grain. The blood pressure ranged from 98 to 84 mm. before, but after the injection soon fell to 66 mm. The amplitude of the beat was more than doubled with the corre- sponding slowing of the beat. A moderate electrical stimulus applied to the vagus produced but slight effect. In this case the drug also produced very pronounced effects. Marked salivation soon occurred and profuse sweating around the anus and flanks. The nasal mucosa became cyanotic and this condition persisted after the use of the antidote. The condition of the horse became quite serious as to breathing and a tracheotomy tube was intro- duced into the trachea with benefit. It is doubtful if the horse 40 would have survived without the use of the tube. One and one- third grains of atropine sulphate (four times the dose of the are- coline) was injected into the jugular. The beat of the heart soon increased in frequency and the blood pressure rose to 114 mm. No. 32 was a mare weighing- 790 lbs. (359 kilograms). She had been spayed just previous to the experiment. One grain of the arecoline hydrobromide (0.19 mg. per Kg.) was injected sub cutem. The effect was slower than when used intravenously and the first indication of its action was a lowering of the blood pres- sure, which fell from a normal of 158 mm. to 134 mm. Then quite suddenly the heart became irregular and slow with the am- plitude of the beat much diminished. The blood pressure fell to 78 mm. and the heart stopped for a short time apparently in systole. The vapor of ammonia was inhaled and this was soon followed by improvement in the character of the beat and a rise in blood pressure to 98 mm. (Fig. 2). There was little or no salivation in this case, but the pupils were dilated and the oral mucosa was somewhat cyanotic indicating an increased amount of CO2 in the blood. Later one-half grain of atropine sulphate was injected intravenously with benefit. No. 49. Mare weighing 815 lbs. (370 5 Kg.). Spayed shortly before the experiment. Thirty-seven-sixty-fourths of a grain of arecoline hydrobromide (0.1 mg. per Kg.) was injected into the jugular. The blood pressure fell quite rapidly from 164 mm. to 102 mm,, and a little later to 90 mm., with a considerable increase in the amplitude of the beat or slowing of the heart. An injec- tion of ff grain of atropine sulphate (0.15 mg. per Kg.) caused a rapid rise in blood pressure with a decreased amplitude or quickening of the beat. The blood pressure finally rose to 190 mm. No. 55 was also a mare, spayed just before the experiment. She weighed 910 lbs. (414Kg. ). In the same dose, there was administered one-half grain of arecoline hydrobromide and one- half grain of atropine sulphate intravenously (0.077 mg. of each per Kg.). The arecoline effect was produced first as shown by a slowing and slight irregularity of the heart, with a fall in blood pressure from 114 mm. to 68 mm. Then quite suddenly the atro- pine effect appeared, as shown by the quickened heart beat and Fig. 1. Horse No. 30. The short tracing to the left is the normal. The left vertical arrow shows when the arecoline was injected. Note the fall in blood pressure. The second vertical arrow shows when the atropine sulphate was injected followed by a rise in blood pressure and more rapid heart beat. Fig. 3. Horse No. 55. The vertical arrow indicates when the combined arecoline and atropine were injected into the jugular. Note the slowing of the heart beat and fall in pressure — the arecoline effect. Later the pressure rises and the heart beats faster under the influence of the atropine. (- s S o 5 S -a o ^fl rt ^^ r OJ c o D o f- ■^ ~ i: ^ +1 a rise in the blood pressure to 88 mm. (Fig-. 3). The blood pressure gradually fell again to 68 mm. and the amplitude of the beat increased, but the heart did not beat as slowly as before the injection. In all five cases there was a uniformity in lowering blood pressure and increasing the amplitude or slowing of the heart beat. In numbers 30, 31 and 49, the atropine caused the blood pressure to rise a point higher than normal and in all cases accel- erated the action of the heart. In No. 32 no tracing was taken after the injection of the atropine. In No. 55, with the simul- taneous injection of equal amounts of arecoline and atropine, the arecoline effects were apparently the stronger in that there was slowing and irreg-ularity of the heart, with a fall in blood pres- sure. The atropine seemed to successfully counteract the irreg- ularity and to a large extent the slowing of the heart, but the blood pressure gradually fell to that caused by the arecoline. A larger amount of atropine or repeated doses of it might have counteracted the arecoline more completely. As an antidote to arecoline, atropine seems to be quite successful. In routine practice, as in colic, etc., the atropine may be used in small dosage in combination with or following the areco- line to guard the circulation and respiration against the depress- ing effects of the latter. BARIUM CHLORIDE IN NUX POISONING. H. B. TILLOU ANT3 L. S. BACKUS. The subject was a horse about fifteen years old, weighing' about 1000 lbs. Was lame in the near fore leg, caused by badly contracted flexor tendons. As an experiment, February 14, 1907, we gave four drams of powdered Nux Vomica at 1:30 P. M. One hour later he be- gan to show symptoms of poisoning, as evidenced by restlessness, colicy pains, hurried, difficult breathing, muscular spasms, excess- ive perspiration. Pulse 120, temperature 102. In one of the spasms he fell to the floor and was unable to rise. As an antidote he was given 20 cc. of Lugol's solution in a pint of water, and three ounces of chloroform by inhalation. At 3:35 the horse was showing no signs of improvement. The pulse was 104 and the respirations 54. He was then given 15 grains of barium chloride hypodermically. At 3:43 P. M. the pulse was reduced to 84, was more regular and strong. At 3:50 P. M. the pulse was 72. At 3:57 P. M. the pulse was 60. The respirations at 3:50 P. M. had been reduced to 42 and were deeper and not so labored. At 4:30 P. M. the animal was much im- proved and got upon his feet. At 5:00 P. M. the pulse was 50, regular and full ; the respirations were 28 and normal. The animal began to eat and appeared to be in no pain. After the injection of the barium chloride there were three evacuations of the bowels. February 16, 1907, noon. The same amount (4 drams of Nux Vomica) was again given to the horse. At 1:30 P. M. he began to show symptoms of poisoning, as in the preceding ex- periment. The pulse was 60 and the respirations were 72 per minute. At 2:30 P. M. he was given 15 grains of barium chloride intravenously. At 2:45 P. M., or fifteen minutes after the medi- cine was given, the muscles began to relax and the spasms began 43 to cease. At 2:50 P. M., or 20 minutes after injection, the animal ceased sweating. At 2:40 P. M. the respirations were reduced to 60 per minute, and not so labored. At 3:00 P. M. the pulse was sixty ; respir- ations 25 and normal. The spasms had entirely disappeared. The general appearance was much improved. The patient drank a pail of water and began to eat hay. At 3:45 P. M. the pulse was 55 and the respirations 23. In this experiment the barium chloride produced five evacuations of the bowels. GLANDERS AND BOVINE SERUM. C. I,. KOADIIOUSK AND LEIGH (III.TNRR. Important work in connection with the serum therapy of gflanders has been carried on by Helman, Semmer and Itzkovitch, Pilalvios, Bonome and Vivaldi, Johne, Schindelka, Prieus and Babes. Since bovine animals are immune to the ravages of glanders, it was believed that an immune body or antitoxin mig'ht be found in the blood serum which, when injected into an affected animal, mig-ht neutralize the toxin produced by the in- vading organism and aid in bringing about recovery. The work of Babes, extracts of which appear in the Recueil de Medicine for 1893, and the Comptes rendus de I'academie des Sciences, 12 Decembre I892, was somewhat similar to that which we had planned and a brief reference to his method and results are herewith given. Babes used what he called an extract of beef's blood. It was prepared by collecting- the blood of the ox in sterile flasks and keeping it at a low temperature for several hours. Water and powdered zinc were added and the mixture shaken. The zinc was used to precipitate the solid particles of the blood, including bacteria and serum albumin. The mixture was filtered and a clear fluid obtained, to which was added potas- sium siilphiiret in order to remove any traces of dissolved zinc. The mixture was concentrated to a residue in a vacuum at 35" C. and the residue dissolved in a mixture of equal parts of water and sterilized gh'cerine. This extract Babes used in his experi- ments. Babes injected this e-xtract into glandered and nonglandered horses and guinea pig's. The glandered animals gave a thermal reaction similar to that produced by Mallein. There was no re- action in the non-glandered animals. Babes states: " In my recent experiments I am led to foresee that the beef's serum pos- sesses a specific therapeutic and vaccinal action in glanders." 45 Our own method differed from that of Babes in that the beef's blood received no special treatment further than to collect it in sterile flasks, allow the serum to separate from the clot, remove it and keep it in as aseptic a condition as possible. Babes appar- ently made his extract from the blood as a whole, while in our work the seruna only was used. The question of any hemolytic action of the beef serum was considered early in the work, as this condition would naturally have an important bearing- from a therapeutic standpoint on the continued injection of the serum. The following- statements from Nuttall are interesting- in this connection : 1. The trans- fusion of foreign bloods to man led to the formation of clots, thrombi, serous exudates and hemolysis. 2. Hemolysins act by separating the hemoglobin from the, stroma of the blood corpus- cle, causing the blood with which they come in contact, to lake. fThe hemoglobin is ff)und in the urine). 3. The hemolytic action of the serum is the dissolution of the cell. 4. In IH')H, Grey treated rabbits with increasing doses of eel serum and they gradually developed increasing quantities of antitoxin. Eel serum as a type of hemolytic serum is destructive to red corpus- cles, leucocytes, renal epithelium and nerve cells. 5 Ox serum was found to be injurious to man in the transfusion experiments of Landois, because it hemolysed human corpuscles. Frieden- thal found it to hemolyse the corpuscles of the pig, horse, rabbit, dog, cat and also man. When injected into guinea pigs, it pro- duced inJlltration and necrosis. Two guinea pigs were experimented upon with the bovine serum. Pig No. 1 received subcutaneous injections of the serum from November 22 to December 14, 1905, getting a total of 19>^ cc. There was no abnormal change in temperature during this period. The post-mortem showed an edematous sloughing and hemorrhag"ic condition of the subcutaneous connective tissue at the point of injection. In guinea pig No. 2 the bovine serum was injected intra- peritoneally. Three cubic centimeters of the serum were injected P^ebruary 6th. The temperature of February 5th was 99.4°. From the 6th to the 9th inclusive it was 98.9°. On the 10th, 3 cc. of the serum were ag-ain injected. The temperature on the 10th 46 and nth was 99.4 . On the 12th the o-uinea pig died. The post- mortem showed local inflammation and thickening in the vicinity of the puncture ; also congestion of the liver. According to Uhlenhuth, Roramo, Weiss and Guinard, the lethal dose of ox serum intravenously for the rabbit is (> cc. to ') cc. per kilogram of weight. In the above experiment a total of 6 cc. was fatal to the guinea pig. Experiments upon Horses. Horse No. 1 was in good con- dition, aged about thirty years, and weighed 901 lbs. During the first period, from November 22nd to December 21st, 1905, sixteen injections of the ox serum were made stibciitaneoiisly. The single doses ranged from 10 cc. to 20 cc. and a total of 265 cc. of the serum was injected during this period. The temperature was taken daily at first and then at intervals. It remained nor- mal, ranging from 98,6'^ to 99.6'". On December 22nd, a micro- scopic smear was made and stained by Jenner's method, but nothing abnormal was noticed. In all of the subcutaneous in- jections of the serum, there was a marked circumscribed swelling with considerable soreness at the point of injection, which lasted about two days. From December 22nd to February 22nd the horse received the serum intravenously. At first he received 5 cc, then 10 cc. and finally 20 cc. of the serum at a dose. The total amount injected intravenously for this period was 565 cc. The horse was weighed on January Sth and was found to have lost 70 pounds. An examination of the blood gave the following results : Horse No. 1. Normal. Hemoslobin 65% 94% Erythrocytes 5,000,000 7,900,000 Leucocytes 8,000 5,000 to 10,000 Hh. Index 70% 100% The urine was also examined and gave the following : Horse No. l. Normal. Specific gravity 1050 1025 to 1050 Reaction alkaline alkaline Chlorides 7.7 per 1000 S to 14 per 1000 Sulphates .35 per lOOO 2 to 3 per lOOO Urea 32. per 1000 20 to 40 per lOOO 47 A spectroscopic examination showed the absence of hemog-- lobin, so that, oa the whole, the urine appeared to be in a fairly normal condition. On February 22nd, 1906, horse No. 2 was procured as a check animal. He was ia fair condition and quite spirited, althoug-h about twenty years old. Both animals were tested for glanders by the agglutination method and were found to be free from the disease. Both horses were then inoculated subcutaneously with Zyi cc. of a virulent culture of Bacterium Mallei. A circumscribed swelling with tenderness was produced in each animal. Before the injection, the temperature of horse No. 1 was 99.2" and that of No. 2, 99.6°. After the injection, the temper- ature of horse No. 1 went up to 100.6°, then fell to 100.3° and remaiaed there for a week. In horse No. 2, the temperature re- mained at 99.6° and 99.5° until March 4th, when death occurred. The post-mortem of horse No. 2 showed a local hemorrhagic and edematous condition of the subcutaneous connective tissue and paniculus over an area covering about 4" x 12" in the vicinity of the seat of inoculation. A similar condition existed beneath the scapula and posteriorly across the chest wall to the sternum. The agglutination test on the post-mortem blood gave the reac- tion for glanders. Aside from the local swelling and a slight rise in tempera- ture, horse No. 1 developed no symptoms of glanders. The aggiutinatian test gave no reaction for glanders. On April 2nd, horse No. 1 again received intravenous injec- tions of the serum. Larger doses, ranging from 35 cc. to 65 cc. were given, and during the eight days from April 2nd to 9th, inclusive, a total of 420 cc. of the serum was injected. On April 14th, horse No. 3 was procured as another check animal. He was a large draft animal, about eight years of age, strong and in good condition aside from being affected with par- aplegia which, however, did not interfere with his value for the experiment. The agglutination test showed that he was free from glanders. Horses 1 and 3 were inoculated subcutaneously with 10 cc. of a culture of Bacterium Mallei, which had been grown at 40° C. 4S for three dajs, probably producing- some degree of attenuation. This inoculation produced only slig-ht swelling, which disap- peared after one day. As there were no apparent symptoms from the above inoculation, it was repeated on April 20th, with 10 cc. of a virulent culture of Bacterium Mallei. The following- table shows the temperatures of each horse for five days : Horse No. 1. Horse No. 3. April 20 98.6 degrees 98.5 degrees April 21 102 3 " 101.1 " April 22 104.5 " 101.4 " April 23 105.5 " 102.5 " April 24 96, On April 21, horse No. 3 showed a marked local swelling, with pain at the point of inoculation. On the 22nd there was increased swelling and pain. The horse was in a weak condition. On the 23d there was loss of appetite and greater weakness. On the 24th the horse was down in the stall and died at noon. Blood was drawn from the jugular vein and the serum collected. This was submitted to the agglutination test and a positive ri. action obtained which showed the horse to have been glandercd. Post-iiioiiem, Horse No. 3. At the point of inoculation there was a hemorrhagic area containing serous exudate and extending from the top of the neck to the scapulo-humeral articulation. There was a thickened and hardened condition at the point of inoculation over an area 4" x 6", containing purulent matter. The lungs were filled throughout with miliary nodules. The medi- astinal lymph glands were enlarg-ed, hemorrhagic and dark col- ored. There was a hemorrhagic and edematous condition of the tissue around the trachea and aorta. The splenic pulp was soft. On April 26th, a male giunea pig was inoculated subcutane- ously with nodules from the lung. The guinea pig died May 21st, with orchitis and abscess of the inguinal lymph gland on the same side as the point of inoculation. Pure culture organisms were obtained from the testicle. Horse No. 1 had received no serum for two weeks previous to the inoculation of 10 cc. of the virulent culture on April 20th. On April 24th, fifty cubic centimeters of the serum were injected. Immediately following this injection, the horse showed a marked 49 increase in the number of respirations; the breathing became labored but returned to normal within a few minutes. The re- action from the above injection is given below: April 24. April 25. 4:00 P. M. Temperature 104.0 deg 4;30 p. M. 103.8 6:00 p. M. 104.0 12:00 P. m. 104.7 2:00 A. M. 105.4 4:30 A. M. 105.2 6:00 A. M. 105.3 8:00 A. M. 105.3 11:00 A. M. 104.7 4:00 P. M. " 105.1 At 4:00 P. M. 40 cc. of the serum were injected and the symp- toms of April 24th were not noticed. On April 26th, the temperature at 10:00 A. M. was 103.7° ; at 4:30 it was 105°. At this time 50 cc. of the serum were in- jected. On April 27th, the temperature was 104.5°. The abscess which had formed at the point of inoculation was opened, the pus evacuated, and the area disinfected with strong lysol solution. On April 28th, the temperature was 103.8°. Fifty cubic centi- meters of the serum were injected. There was slight dyspnoea as on April 24. There was a slight serous nasal discharge. On April 29th, the temperature was 103.8°. There was swelling of the nostril, labored breathing and thick mucous discharge. On April 30th, the temperature was 102.5°. There was more pronounced thickening of the nostril ; thick, blood-stained mucous discharge from the nose. The breathing was so labored and the symptoms of suffocation so impending, that tracheotomy was performed. Sevent}^ cubic centimeters of the serum were injected. Blood was drawn from the jugular vein and the serum collected, which by the agglutination test showed the animal to have been glandered. Post-mortem Horse No. i. There was an edematous condition of the connective tissue under the skin above the false nostril and in all the surrounding tissues. The mucous membrane of the nasal septum was dark red in color, infiltrated and showed marked pea-like yellowish elevations with red areola;. On the 50 tloor of the nasal fossa and septum nasi, the mucosa of the facial sinuses was necrotic, and in places the necrosis extended intc> the bone. The sinuses contained a thick, viscid liquid. There was a thickened condition of the mucosa of the turbinated bones. The spleen was enlarged to three times its norinal size and the pulp was soft and dark colored. The kidneys and the liver were enlarg-ed and friable. There was a hemorrhagic and enlarged condition of the anterior mediastinal lymph glands. Summary. Aside from some anemia and a reduced number of red cor- puscles as shown in the blood count, there were no marked or apparent injurious hemolytic effects from the injection of the bovine serum. The evidence is much less complete than might be desired with regard to the effects of the serum upon glanders. Such as it is it seems to be favorable to the belief that the serum imparts some power of resistance to the virus and that it has some value as a diagnostic agent. In the first experiment the horse treated with the serum did not respond to the agglutination test for glanders ; wliile the second horse did, althoug'h both were inoculated with the gland- ers virus at the same time and the agglutination tests were made coincidentl^' at a suitable period after the inoculations. In the second experiment both horses came down with glanders after an inoculation of an unusually large amount of virus. But the serum-treated horse survived for a week longer than the control. In the matter of temperature, the serum- treated horse showed a constantly higher temperature than the control after the virus had taken effect. Succeeding- injections of the serum caused a still higher rise temporarily in the experi- mental horse. HYDKOCYANIC ACID IN CiaOKOFOKM NARCOSIS. I,. S. BACKUS. This ajL^ent was broui^^hl to my attention for the above purpose while readin}^ the work on " Surgical Diseases of the Dog- and Cat," by Hobday. He says : " Hydrocyanic acid first suggested itself as an antidote to chloroform whilst watching the powerful respiratory efforts which it so rapidly causes, when given to ]>ro. duce toxic effects. It is of especial value because it not only stimulates the respiratory center to recommence if once it has ceased, but if given in full medicinal close-;, it maintains the fjreathing until it is able to look after itself, and at the same time by the deep inspirations produced it causes the entrance of a large amount of air into the system. Its effects, too, on the heart are beneficial. The dose recommended of Scheele's strength, to be placed on the tongue averages about one-eighth rif a minim for each pound of body weig-ht." In order to test the value of the above observations the fol- lowing experiments were j)erformed. Exp. 1. Administered chloroform to a full grown cat until respiration ceased, then put two drops of dilute hydrocyanic acid on the back of the tongue and performed artificial respiration. Respirations began at once. Exp. 2. Subject was a male dog, weight about forty pounds. While in chloroform anesthesia the respirations suddenly ceased. Five dr(jps of hydrocyanic acid were put on the tongue and arti- ficial respiration performed. The respiratory function was restored. Exp. .3. Small kitten. Chloroform was administered until there was a cessation of the respirations. One minim of the acid was placed on the tongue and artificial respiration performed. The breathing was at once restored. 52 Exp. 4. Horse. Weighed about lOOO lbs. Completely anes- thetized. Into the jugular was injected one dram of hydrocyanic acid. The respirations immediately became deeper and stronger. The pulse was strengthened. At the outset, It was planned to destroy the horse so ten minutes later two drams more of the acid were injected. This caused an almost instant cessation of heart beat and respiration. SODIUM BENZOATE AND METABOLISM. PIERRE A. FISH. Complete experiments in metabolism were not attempted. The feces were not examined nor was any account taken of the per- spiration or respiration. Careful examinations were made of the urine and changes in the system due to metabolic activity would, it is believed, cause corresponding changes in this excretion. Experiments were tried upon two dogs and upon two men, the dogs being killed at the end of the experiment and certain of their tissues examined for any pathological changes. . As there were a great many urinary examinations to be made, the methods commonly used in clinical work were adopted and are believed to be sufficiently accurate for comparison. Because it is expeditious the centrifuge was used for the determination of the chlorides, phosphates and sulphates after first being checked by volumetric determinations, and the value of each 0.1 cc. of the precipitate in the centrifuge calculated on the basis of parts per thousand. Urea determinations were made with the Doremus ureometer, as modified by Hinds, in connection with the sodium hypobromite solution. For the uric acid test Ruhemann's Uricometer was employed. Dog. No. 1. A black male dog of uncertain breed. Was apparently healthy at the time the experiment began, but had been troubled with a skin affection three months before. The dog was under observation for normal data from March 15th to 27th. During this interval the pulse ranged from 104 to 112 and the temperature from 102.2 to 102.8 F. March 20th the weight was 42 pounds. The diet consisted of Spratt's dog biscuits and plenty of water. On March 27th sodium benzoate was admin- istered in tablet form to the extent of 120 grains (8 grams) a day. This amount was administered in three doses of 40 grains each. After the first day it was given in two doses of 60 grains each. Just before beginning the benzoate the dog was again 54 weig-hed and this time weighed 40.50 lbs. For the first three days, emesis occurred once or more daily, shortly after the ad- ministration of the benzoate. Later the emesis was not observed. The pulse and temperature were noted at occasional intervals and the former was found to rangfe from 98 to 102 and the latter from 101.8 degrees to 102.6 degrees F. From March 31st to April 5th, inclusive, the sodium benzoate was given in solution, 60 grains of the powder being dissolved in 2 fluid ounces of water for each dose twice a da)'. This form of administration caused consider- able coughing and some nausea but no emesis. Later the cough- ing was not so marked and sometimes was not present. The dog was killed April 6th and at his death weighed 41.25 lbs. The urine for the 24 hours was collected and examined on alternate days. Microscopic examinations were made on each occasion and revealed a crystalline deposit. These crystals were soluble in acetic acid and were regarded as phosphates. On two occasions there was some effervescence indicating the presence of carbonates. Small masses of epithelial debris and dandruff scales were also encountered, probabl}' having gotten into the urine, after it was passed, from the skin. The result of the chemical exrmination for the 24-hour urine is shown in the fol- lowing table, the average being taken for the period when no benzoate was taken, followed by the average for the period when the benzoate was taken : Amt. Sp. gr. Solids, Chlor. Phosph. Sulph. Urea. Uric ac. Suj;. Alb. Average of 1 No?m^r -310CC. 1036 26,422 4,168 1.206 1.736 16.87 O.lSlS trace Period. ) Average of i Be''nzo™te -371CC. 1045.5 38.825 4.175 2.163 3.147 18.93 0.234 0.8% pres. Period. ) Maximum i Normal - 400CC. 1042 37.280 7.396 1.995 3.60 24.00 0.261 Period. ) Maximum J Benzoate - 450CC. 1050 45.015 7.766 2.591 5.850 21.60 0.342 Period ) Minimum i Normal V 220CC. 1026 13.327 1.695 0.840 0.825 7.48 0.132 Period ) Minimum / Benzoate - 250CC. 1040 29.125 1,265 1.641 1.937 15.00 0.185 Period. \ 55 The fact that-Some albumin was found during the normal as well as during the benzoate period, although in greater amount during- the latter, would indicate some departure from a true nor- mal condition before the experiment was begun. The day fol- lowing the administration of the benzoate showed the presence of albumin to the extent of 0.375 parts per thousand of urine. After this it fell'to a mere trace. Although sugar is not reported as present during the normal period the tests were somewhat sus- picious, as Fehling-'s solution became opac[ue, but not red, and bismuth was slightly darkened. Glycuronic acid, a constituent of the urine of the dog, has a reducing effect upon copper solu- tions, and it was believed that this substance might have simu- lated the sugar reaction. When, however, the benzoate was administered the tests became more pronounced, the Fehling's solution gave a red precipitate of cuprous oxide, the bismuth be- came black, and to make the result more conclusive in favor of sugar some of the urine caused fermentation with yeast in a fermentation tube. Whatever the substance, sodium benzoate increased its amount and caused decidedly stronger reactions with the reagents. The effect of the benzoate upon the urine as a whole was to increase its amount and to cause a gain in all of the constituents. The constituent least affected was the chlorides ; those most in- creased were the phosphates and sulphates, each of which was nearly doubled in quantity. Dog No. 2. This dog was a female. Her ovaries had been removed a month or two previous to the beginning of the experi- ment. She was under observation from March 15th to May 17th. Her weight on March 20th was 41.5 lbs. Her pulse from March 15th to 17th (the normal period) ranged from 100 to 114. Her temperature rang-ed from 102 to 102.8 degrees F. Aside from an occasional irregularity in the heart beat, the dog seemed to be in excellent health. Her diet was the same as that provided for No. 1. Records of her pulse and temperature were kept through the benzoate period up to April 8th, then they were discontinued. During this period her pulse ranged from 104 to 116 and her temperature from 101.8 to 102.6 degrees F. 56 In this experiment, the idea was to study the effect of smaller doses administered for a longer period of time. With this excep- tion the details of the experiment were practically the same as for Dog" No. 1. According to changes in the dosage, the experi- ment may be divided into live periods : 1st, the normal or fore period, from March 15th to 17th. 2Qd, the 4-g-ram period, during which 4 g-rams of benzoate of sodium were administered daily, (one-half the amount given to dog No. 1), from March 27th to April 17th. 3rd, the (i-gram period, from April 17th to April 23rd. 4th, the 2-g-ram period, from April 23rd to May Sth. 5th, the after period, when no benzoate was administered, from May Sth to May I7th. Just before the administration of sodium benzoate March 27th the dog was found to weigh 40.5 lbs. The 4 grams (or 60 grains) of the benzoate were administered in three doses of 20 grains each. After the first day it was given in two doses of 30 grains (2 g'rams ) each. Emesis also occurred in this dog but not quite as frequently as in No. 1. From March 31st to April Sth, inclusive, 30 grains of the powdered benzoate dissolved in water were administered twice daily. In this dog no coughing, nausea or emesis were observed while the drug was given in solution. The change from the tablet form to the powder in solution was made because the question arose as to whether the milk sugar which probably formed a part of the tablet had any influence upon the production of sugar in the urine. As the urinary re- sults did not change with the change in the form of administer- ing; the benzoate, the tablets, on account of their greater conven- ience were resumed. The total urine for the 24 hours was exam- ined. The microscopic examination showed results similar to that of No. 1., phosphates and occasionally carbonates were pre- sent. Crystals of calcium oxalate, which were not observed in Do,,'- No. 1 were found twice in No. 2 during- the normal period, but only once after the benzoate was begun. During the 2 gram period from April 23 to May 6 the urinary sediment was increased in bulk and appeared to be of a lighter and more flocculent char- acter than before. It was also noted that when the benzoate was discontinued, or (.luring the after period, the urine took on a stronger and more offensive odor than before. 57 The chemical examination, as before, was upon the 24 hour urine and the averag-es of the different periods are shown in the following- table : Amt. Sp. xr. Solids. Chlor. Sulph Hho>ph. Urea. Uric ac. Su>;ar. Alb. Ave. of 3 i exams. - 220cc. 10J4 17.565 2.654 0.616 0.8690 9. .S3 0.0563 nor. per. ) Ave. of 8 i * exams. . 245cc. 1033.8 19.966 2.379 1.133 1.144 8.23 0.0825 0.437;,' trace 4 K'm.per. ) Ave. of 3 J exams. - 293cc. 1036 23.716 2.547 2.188 1.345 7.23 0.088 0.50;,' 6 (im.per. ) Ave. of 6 j exams. |- 379cc. 1026 19.350 2,251 0-725 1.552 7.91 0.083 0.277;,' 2gm.per. ) Ave. of 3 i exams. ^277cc. 1020 12.5 51 1.402 0.72 0.963 6 96 0.062 after per. ) Max. of I25OCC. 1038 22.135 3.2.56 0.875 1.047 10.00 0.06 nor. per. ( '^'"- '''^ t 200CC. 1032 14.91 2 157 (J.475 0.551 9.5 0.529 nor. per. \ Max. of ( 34f,(,j. jfj44 25.24 3.351 2.50 1.733 11.56 0.1128 0.,8;r 4 gm.per. ) 'y''"- °' '■ 130CC. 1025 7.572 0.901 0.42 0.597 3.38 0.0309 0,2;;: 4 gm.per. \ Max. of Ujfj^j ,(,4f; 24.465 3.051 3.850 1.516 7.70 0.110 0.56',' 6 gm.per. | !^'"- '^' '-220CC. 1030 23.113 2.030 700 1.221 6.51 0.074 0.48;,' 6 gm.per. ) Max. of )^^,J^^. ,rj4o 24.232 3.352 1.485 3.355 10.00 0.106 0.37;,' .... 2 gm.per. \ Mm. of I ,j^(j(.(- ,Q,4 ,3r,30 1.386 0.160 0.725 5.40 0.54 0.185?; 2 gm.per. ) a . . . . Max. of |. 35Q^(, ,Q22 14,352 1.618 0.92 0.970 S.40 0.072 after per. j Mm. of /20OCC. 1016 10.252 1.078 0.56 0.955 5.20 0.049 after per. \ It is worthy of note that the normal urine of this dog- con- tained no albumin, but that soon after the administration of the benzoate traces of it appeared upon two occasions, March 31st and April 4th, and then disappeared and was not found again during the experiment. After the benzoate was begun, the tests for sugar became quite j)ronounced ; this substance was evidently correlated with the benzoate, for when the latter was given in 58 decreased amount the sug-ar also decreased, and when the ben- zoate was discontinued the su^ar also disappeared. The effect of the benzoate upon the urine as a whole was to increase its amount and to cause an increase in the solids, par- ticularly in the sulphates, phosphates and uric acid, while on the other hand the urea was decreased, as were also the chlorides to a slight extent. A comparison of the results obtained from the two scries of urinary examinations, shows that there was, at least, a temporary disturbance of metabolism, because in both cases albumin — or in dog No. 1 more albumin — appeared just after the administration of sodium benzoate. The fact that the albumin soon disappeared or diminished would indicate that the metabolic processes soon adjusted themselves to the new conditions. Of mere profound significance, however, was the presence of sug-ar. where a more direct and complete connection with sodium ben- zoate seemed to be established ; the inference being that the benzoate caused an interference with the metabolism of the liver. At any rate sugar appeared while the benzoate was administered, and diminished or disappeared when the benzoate was withdrawn. In dog No. 1 there was not only an increased quantity of urine during the benzoate period but also an increase in the spe- cific gravity and all of the urinary constituents. In dog No. 2 the re was also an increase in the quantity of the urine as well as in the amount of the solids, sulphates, phosphates and uric acid ; but a decrease in the chlorides and urea. The after period, when no benzoate was given, as compared with the normal, showed a slight increase in the sulphates, phos- phates, uric acid and the quantity of urine passed, while the specific gravity, solids, chlorides, and urea were materially de- creased. The weight of dog No. 1 at the end of the experiment was 41.25 lbs. as against 40.50 lbs. the day the benzoate treatment began, showing a gain of 0.75 lb. A week before the treatment, however, the dog weighed 42 lbs. The weight of dog No. 2 at the end of the treatment was 41.50 lbs. On the first day of the treatment it was 40.50 lbs., showing a gain of 1 lb. Like No. 1 a weighing was taken a week before the treatment and was then found to be 41.50. A 59 ■weig-hing- was also made toward the close of the experiment, April 27th, and found to be 41.50 lbs. Prom the end of the treatment May 8th when the weight was 41.50 lbs. to May 17th when the dog' was killed, it was found there had been a gain of 1.25 lbs., as the weig-ht at the time of death was 42.75 lbs. Examination of the blood of the two dog"s was made by Dr. J. Traum. These examinations were made in the normal period, and during- or just after the benzoate period. The following- results were obtained : Red Corpuscles per Leucocytes per Percentage of cubic mm. per cubic mm. Hemoglobin. Dog No. 1. 1 Marcli 24, '05. - 5,600,000 10,987 90 Normal period. \ \pn\ 6, '05. ) End of ben- - 5,804,000 17,345 — zoate period. ) Dog No. 2. I Marcii 18, '05. - 5,988,000 7,499 92 Normal period. ) April 13, '0'5. ) Near end of 4 ^ 6,195,500 7,162 91 gm. period. ) May 9, '05. i 3 days after end V 6,126,000 8,050 100 of benz. period. ) The changes in the blood are not pronounced, except per- haps the leucocytes in dog No. 1 ; but such as they are, they favor the benzoate period. In dog- No. 1 there is an increase in the red corpuscles (204,000) and in the leucocytes (6358). In dog- No. 2 there is an increase in the red corpuscles during- the ben- zoate period (207,500j and a decrease in the leucocytes (336). The after period compared with the normal also shows a slight increase in the red corpuscles (138,000) and something of an in- crease in the leucocytes (551). The post-mortems on the dog-s were performed by Dr. S. H. Burnett, of the Department of Pathology, New York State Vet- erinary College, who has kindly submitted his findings in the following notes : " Post-mortem examination. Dog No. 1. Dog killed by chloroform April 6th, 1905. 60 Skin scurfy, with hair partly fallen out. A few translucent nodules, about 1 mm. in diameter, scat- tered over the surface of the left lung. The right testicle retained in the abdominal cavity, flabby, flattened, size 1 by ZVi cm. The left one normal in appearance, 3 by 3 by 5 cm. The other organs apparently normal. Histological examination : Liver. There is advanced parenchymatous and fatty degen- eration of the liver cells except those in the periphery of the lobules immediately about the blood vessels. Parenchymatous degeneration of the epithelium of the bile ducts. Moderate congestion of the veins and capillaries. Kidney. Extensive parenchymatous degeneration of the epithelium in both cortex and medulla is shown, most marked in the convoluted tubules. There are a few purulent areas in the cortex. Congestion is shown in the glomeruli and capillaries between the tubules in the cortex and in the veins. Lung. The nodules present just beneath the pleura are composed of a center of old connective tissue showing degener- ation, while the outer part is more cellular. The lung near the nodule shows marked congestion ; farther away it is normal. These changes in the liver, kidney and lung are chronic ones, evidently having existed for some time." "Post-mortem examination. Dog No. 2 : Dog, adult female, killed by chloroform May 17th, 1905. Considerable amount of subcutaneous fat. The organs were apparently normal except that there was a cyst ^ by 1 cm. in the anterior end of the left kidney and the duodenum contained four tape worms (Taenia coenurus?) 50 — 75 cm. in length. The dog had been spayed. Histological examination : Liver. All the blood vessels were congested, probably hypos- tatic. There was slight parenchymatous degeneration of the liver cells throughout the lobules. Kidney. There was congestion of the blood vessels, prob- 61 ably hypostatic. There was a slig'ht parenchymatous deg-ener- ation of the epithelial cells in the medulla and in the convoluted tubules." The first experiment on man consisted of the administration of 5 g-raius of benzoic acid io a capsule three times a day before each meal. A general feeling' of depression appeared to result from the use of the drug. There was a dull headache and dull but rather continuous pains over the region of the kidneys. The appetite and tone of the stomach appeared to be lessoned. One week before the benzoic acid was taken, was allowed for the nor- mal period. The urine was collected for each 24 hours and a sample of this was taken for analysis. The same plan, regarding the urine, was pursued the following week when the benzoic acid was taken. The following- averages show the results for the normal and benzoic acid periods : Amt. S46.4 cc. Sp. gr. 1026.S5 Solids. 52.27 Chlor. 15,25 Sulph. 1.37 Pliosph. 1.51 Urea. 26.54 Average of 7 exams, nor- mal period. Average of 7 exams, ben. I- 824.2 cc. 1026.85 51.25 13.68 1.44 1.39 23.75 zoic acid per. Maximum of normal per- \- 1000 cc. 1030. 64.65 lS.46 2.30 1,85 30.00 iod Maximum of benzoic acid \- 1070 cc, 1030. 59.81 18.19 1,70 1,53 28.90 period. Minimum of normal per- |- 700 cc, 1022, 45,37 12,44 0.90 1,35 17.50 iod. Minimum of benzoic acid I- 700 cc. 1024, 42,35 10.35 1.05 1.12 19.50 period, A comparison of the averages of the normal and benzoic acid periods shows that the sulphates were slig-htly increased during- the latter period, but that all of the other constituents and the quantity of the urine were slightly greater during the normal period. The subject of this experiment, Mr. M., was 27 years of age and was apparently enjoying- the best of health. No evidence of albumin nor sugar appeared in the urine either before, during, or after the experiment. 62 The second subject, Mr. F. , was 40 years of ag-e and appar- ently in good health. In this case there was a normal period of 5 days, a benzoate period of i> days, and an after period of 4 days. Ten grains of sodium benzoate were taken three times daily at each meal making the total dosage 30 grains or 2 grams per day. On two of the days 15-grain doses were taken, making a total of 45 grains or 3 grams per day. No physical effects whatever were apparent from the use of the drug. The appetite was in no way affected and the subject appeared to enjoy his usual health throughout. The following table shows the averages for the three periods above mentioned : Amt. Sp. gr. Solids. Chlor. Sulpli. Phospli. Urea. Ur. Ac. Body Ave. of 5 e.xains. ■ l506cc. 1023.6 81.99 19.619 3.222 2.518 31.67 3995 Wt. 1S5 4 r.or. per. \ Ave. of 6 exams. -1745CC. 1023.8 95.11 21.883 3.895 5.244 33.76 0,2902 185.6 ben. per. \ Ave. of 3 e.xanis. after per. - 1425CC. 1024.25 79.19 20.184 2.539 2.585 28,20 3009 185.7 Maximum nor. per. I 1740CC. 1027. 85.13 22.467 3.690 3 390 33,75 540 186 Minimum nor. per. '- 1230CC. 1021. 77.37 17.335 2.610 1.674 29.52 2436 185 Maximum ben. per. '- 2280CC. 1029. 105.40 26.81 4.560 7.432 38.28 0.4700 186 Minimum ben. per. '- 1440CC. 1018. 81.99 17.557 3.360 2.169 29,83 0,2140 185 Maximum after per. - 1590CC. 1029. S3. 88 22.397 3.000 3.130 31,50 0.4698 186,25 Minimum after per. [ lOSOcc. 1022. 72,87 16.642 2.667 1.907 26.01 0.1850 185.25 A daily record of the body weight was also kept throughout the experiment and the results show there was a slight gain (0.3 lb. ) at its termination. No albumin or sugar was found in the urine at any time. A general comparison of the three per- iods of this experiment shows that during the benzoate period there was some diuresis and an increased amount of all of the constituents except uric acid, which was decreased about one- fourth. The phosphates were a little more than doubled in 63 quantity. The results obtained in the after period agreed more closely with the normal than with the benzoate period. In com- paring- the two experiments on man, it is shown that the only re- sult in common during the benzoate period is a slight increase in the sulphates eliminated. In the one case (Mr. M) only 1 gram of benzoic acid was consumed daily while in the other case 2 grams and a portion of the time, 3 grams, of sodium benzoate were taken during the day. The difference in the drug and dos- age may have some influence upon the result, otherwise it may be charged up to personal idiosyncrasy. A somewhat similar but not so marked difference in results is noted in the case of the two dogs. In dog No. 1 with larger dosage, there was, during the benzoate period, an increase in the urine and all of its con- stituents. In dog No. 2 there was a slight decrease in specific gravity, a decrease in the chlorides and urea but all of the other constituents were increased as in No. 1. In the case of Mr. F and dog No. 1 there is a correspondence in the results — an in- crease of the urine and all of its constituents, except that in Mr. F. the uric acid was diminished while in the dog it was increased slightly. This constituent was increased in both dogs. Unfor- tunatel}' the uric acid was not tested in Mr. M. Urea was in- creased in Mr. F. and dog No. 1, while it was decreased in Mr. M. and dog No. 2. Diuresis, increased solids and phosphates occurred in all but Mr. M. The one result in which all four ex- periments agreed was an increased elimination of sulphates. The general results seem to warrant the conclusion that sodium benzoate stimulates metabolism of the body and increases the elimination of the most of the waste constituents of the urine. This effect is probably dependent to some extent upon the dos- age, for in the case of Mr. M. where the smallest amount of the drug was ingested there was a slight decrease in elimination. SUMMARY. The results of the experiments on the dog and man point toward increased metabolism and elimination of urinary pro- ducts after the ingestion of moderately large doses of sodium benzoate. In all there was increased elimination of the sulphates. In three there was diuresis also an increase in the solids and 64 phosphates. In two there was an increase in the chloride and urea, while in the other two there was a decrease in the same constituents. In the two doj^'S there was an increase in the uric acid, one of them showing- at the same time an increase in urea, while the other dog showed a decrease in the same constituent. In one of the men there was a decrease in uric acid; in the other it was not tested for. Both dogs with larger dosage than the men, showed a disturbance in metabolism during the benzoate period by the presence of albumin and sugar in the urine. Sodium benzoate appears to stimulate the liver and general metabolism and increases the elimination of certain of the urin- ary products and causes some diuresis. These effects are undou- btedly correlated with the dosage ; the larger doses producing more marked results and the smaller doses less. The experi- ments showed a variation in the elimination of some of the more important of the waste products; e. g. urea, uric acid and chlor- ides. In some there was an increase and in others a decrease. Similar variations would doubtless exist in the human family due perhaps to personal idiosyncrasy or varying systemic con- ditions. Large amounts of sodium benzoate, sufficiently long con- tinued, may produce a disturbance of health, by interference with the liver ; with the digestive processes or undue stimula- tion or irritation of the kidnej's as shown by its diuretic effect. The effect of sodium benzoate upon the blood is not pro- nounced. The evidence from the experiments is that the red cor- puscles were slightly increased ; the white corpuscles were some- what variable, but upon the whole the number was increased and the hemoglobin was somewhat improved. The total effect is of a favorable character rather than otherwise. The postmortems of the two dogs showed deviations from the normal, especially in connection with the microscopical ex- amination of the tissues. Especial attention was paid to the liver and kidneys, because the most of absorbed material is car- ried through the portal system to the former and the latter are concerned with the elimination of the most of the waste products. The findings in dog No. 1 will, doubtless for the most part, have to be left out of consideration, because in the opinion of the 65 pathologist, the lesions were of a chronic character and antedated the beg-inning- of the experiment. The fact, however, that more albumin and sugar were found in the urine during the benzoate period than before, would indicate that the conditions were made worse rather than better. In dog No. 2, the conditions were not so bad. The conges- tion of the vessels may have occurred as a result of the post- mortem settling of the blood or to the administration of chloro- form in killing the animal. A brief administration of chloroform can hardly be considered as sufficient to produce the degenerative changes found in the liver and kidneys, for which a longer time must have been rec^uired. Although it is impossible to prove that these changes may not have existed before the experiment was begun, it is not improbable that they may have been due to the effects of the sodium benzoate, especially when taken in con- nection with the fact that albumin and sugar were found in the urine shortly after the benzoate treatment was begun. The albumin was found for a short time only ; the sugar persisted as long" as the benzoate treatment was kept up, and disappeared when the benzoate was discontinued. The dosage, averaging 4 grams (60 grains) daily continued for some time, may have been rather large for a dog- of that weight (41 lbs. ), and it is reasonable to assume that smaller doses would have produced less violent changes. The smaller doses, 1 g-ram and 2 grams daily, in the experiments on man, did not cause the appearance of albu- min or sugar in the urine. ALBUMIxsTURIC VARIATION AT THE BEGINNING AND END OF MICTURITION. PIERKie A. FI.SII AND THOMAS SHELDON. The patient, a man of 2') years, had been afflicted with albu- minuria for a number of years. During- the urinary examinations the idea was sua^gested th;it it would be well to determine if the albumin were uniformly distributed throug-hout the urine while in the bladder. The results are shown in the following- table. Variations in the amount of albumin on different days and its complete dis- ap_'earance at the end of the experiments were probably due to treatment for the disorder. No treatment was taken at the beg-inning of the experiment. The ferrocyanide-acetic acid test was used in connection with the centrifug-e. The value of each 0.1 cc. of the precipitate was determined in order to obtain quantitative results. Ten cubic centimeters were taken from the first urine passed, and the same amount was also taken from the last to leave the bladder. This amount was placed in the centrifug-e tube with the ferro- cyauide and acetic acid and both tubes revolved in the centrifuge for three minutes. First Urine. Last Urine. Feb. S, 11:00 A. M. Tube No. 1, .90 gm.— 1000. Tube No. 2, .44 gm.— 1000. Feb. 9, .66 ' " .22 ,. Feb. 11, 1.44 ' ,. 51 ., Feb. 12, 1.22 ' " .44 " Feb. 12, 2:00 P. M. " .22 ' " .22 " Feb. 13, 11:00 A. M. " .33 ' " .22 .. Feb. 14, 12:00 M. .28 ' " .11 ., Feb. 14, 5:00 P. M. .77 ' " .22 ,, Feb. 15, 5:00 P. M. .22 ' " .22 ., Feb. 21, 3:30 P. M. .002 ' fain t trace. Feb. 23, 3:00 P. m. .08 ' " .002 gm— 1000. Feb. 27, 12:00 M. .11 ' fain t trace. Feb. 28, 2:00 P. M. .00 • .00 gni. — 1000. Mar. 2, 3:30 P. M. .02 " .00 .. Mar. 4, 11:30 A. M. ,00 " .00 >. 67 The reason for this variation we do not attempt to explain. In none of the fifteen experiments was a larger amount of albu- min found in the last urine than in the first. In two instances the same amount was found in each urine, but in the thirteen remaining- tests quite markedly larger quantities of albumin were found in the first urine. Diurnal variations in the amount of albumin are very probable, but as shown by the table the tests were made at different hours on different days, and there is, nevertheless, quite constant variations in the amount of albumin in the initial and final urine of each micturition. ABSTRACTS OF WORK DONE IN THE LABORATORY OF ^^ETERINARY PHYSIOLOGY AND . .. .PHARMACOLOGY . . . . UNDER THE DIRECTION OF P. A. FISH NO. 6 NEW YORK STATE VETERINARY COLLEGE CORNELL UNIVERSITY ITHACA, N. Y. 1908 TABLE OF CONTENTS. PAGES Dr. Law's Services to the Veterinary Profession, Pierre zA. Fish. 3 Professor Gage's Work for the Veterinarians, G. S. Hopkins. 6 The New Director of the N. Y. State Veterinary College, P. A. Fish. 8 Observations on the Veterinary Schools in Europe, Pierre A. Fish. 10 Tetanus D. K. Eastman and G. R. Chase. 22 Experiments with Barium Chloride, IV. E. Frink and H. B. Tillou. 27 Rhus Toxicodendron / 5^. Frost. 41 DE. LAW'S SEE VICES TO THE VETERINARY PEOEBSSION. PIERKE A. FISH. When such men as Professors Law and Gage leave the faculty it sets one thmking, especially such of us as have been fortunate enough to have been associated with thorn as students, assistants and col- leagues. A learned judge once said that he believed that it would be for the best interest of all concerned if tlie judge who sentenced criminals should spend a certain time in prison himself before entering upon the duties of his high position. In this way he would more thoroughly appreciate the degree of punishment lie was inflicting and could thereby temper his judgment with mercy as well as justice. I do not fear contradiction when I say that Dr. Law, with his long experience as student and teacher, has never been charged with injustice by any of the numerous students he has taught. When Dr. Law began his career in this country forty years ago he found very few veterinarians, but a large number of horse doctors. No diploma was required in those days. Any stableman or member of the saloon contingent, merely by announcing his intention, could treat sick animals. There were no illegal practitioners, simply because there were no practice laws for them to break. Such a class of practi- tioners, largely illiterate and too indolent to take up any other useful work, were not held in very high esteem by the community. The importance of animal diseases to the stock owner and to the community at large became more and more emphasized, so that the subject was taken up as a part of the instruction in agricultural schools and experiment stations. The evident result of this instruction was to enable the farmer to treat bis own animals. This course may be t-onsidered justifiable under the old conditions when competent veteri- narians were not available. The aim at the present time is to elevate veterinary work to the dignity of the learned professions. In this direction numerous stakes have already been driven along the line of progress. Within recent -years a few of our states have made more or less liberal appropriations for fostering veterinary education. A number of the states hare enacted laws wliich prohibit those not properly qualified from prac- tising veterinar}' medicine. Educational requirements have been raised, so that to enter the veterinary schools in Xew York state as much education is required as to enter many of the medical schools of our country. With the increasing efficiency of the veterinary profession there come increasing problems. One of these is intimately connected with the agriculturalist. It may be said that if it were not for the farmer to breed the domestic animals there would be no veterinarian to treat them. Wliile this is, in a sense, true, it is also true that other pro- fessions and, in fact, all, whatsover their line of life, are dependent for their sustenance upon the soil and the man wdio tills it — upon him who tickles the face of the earth until she smiles back at him with her abundant harvests. Should the veterinary college serve as a bureau for the diffusion of information to the farmers g-enerally for any and all diseases with which their animals may be affected? Should this be the principal function of the veterinary college, or should it send out thoroughly trained men upon whom the fanners may call in case of need ? It is eminently proper for the veterinary school to furnish to the farmer fully and freely all of the information it can in respect to sanitary and preventive medicine, but information relating to infectious and special diseases he should receive through the veterinarian. It would obviously be an absurd procedure for a college to devote its energies to developing professional veterinarians and then put them out of business by encouraging the farmer to be his own veterinarian. "Every man his own doctor" is now an obsolete condition. The veteri- nary college may exercise a dual function. It should serve as a school for the training of professional veterinarians and developing knowledge of sanitary and preventive medicine. We may, then, trace these three phases in the development of the veterinary profession : 1st, the "horse doctor" period, characterized by the absence of legal restrictions, when anyone so inclined might take up the work according to his own desires. 2d, the agricultural period, when the veterinary work was an appendange of agricultural instruction. 3d, the professional period, which we are at present developing into, striving to stand upon the level of the sister pro- fession — human medicine. Our pre.ient director is familiar with all of these periods. His services have been sought by the community, state and nation. The changes wrought in forty years cannot be attributed to any one man, but as much, if not more, of this influence can be traced to Dr. Law as to any other. Not least among his services to the profession is the production of his text books on veterinary medicine, prepared during the strenuoas periofl of organizing and directing the Xew York State Veterinary College. In the words of Horace, he has reared "a monu- ment more lasting than brass." But in the final analysis it seems to me, as a culmination of his services, the chief legacy which he leaves to posterity is his directorship of a .school through which he has empjhasized and dignified the pro- fessional side of veterinary medicine — a school to enter which a person must possess at least a high school education. Aside from character there is no quicker or more satisfactory method of elevating the veteri- nary profession or for the veterinarian to win the esteem of the com- munity than for the public to know that it requires as much education for a young man to enter a school of veterinary medicine as it does to enter most schools of human medicine. The path of the truly great man is not strewn with roses. There are always those who criticize and endeavor to block the wheels of progress, and Dr. Law has not, perhaps, been exempt from trials of this character. The story is told of an officious captain of a small boat plying along the eastern coa.st, who hailed everything in sight, demanding the name and destination of the vessel. One day he sighted a large and stately vessel and true to his instincts he ran alongside, donned Ms gaudy uniform, mounted the bridge of his little boat and got ofE his usual salutation. The reply from the other captain, in his faded uni- form, was to the effect that he was some months out from an Asiatic port on a trip around the world; that his vessel was laden with spices and rich merchandise and that he was homeward bound. Our director is homeward bound, laden with years and his many services to the veterinary profession, ifay the remainder of liis voyage be peaceful. May he finally enter the tome port safely and gently — but not too soon. A toast given at the fifth annual banquet of the Society of Com- parative Medicine, Feb. 30. 1908, upon the approaching retirement of Dr. Law as Director of the New York State Veterinary College. puoFESsor; riAOE's work foe the veterinarians. G. S. HOPKINS. Two years 'ago I liad tlif lioiior of giving a sketch of the alumni of the College. On that ocrasioii I felt free to use as vivid colors a.? I pleased. The aliiiniii u'eie not lueseiit, to pass judgment, and even if they had been aud failed to I'ecogni/e their own li]- "Iv'-*-^ '-"-■.- '■■ ^^^mI"' ■^#>->*' l^eterinary Hospital and Lecture Rooms (upstairs), Utrectjt, Holland. New Judging Pavilion, J^eterinary School, Utrecht, Holland. Institute of Physiology and Chemistry (rear), l^eterinarv School Hanover. Building foi Surgical Clinics, Hanover. 13 in England, it has a four-year course. There are quite extensive grounds with a number of l)uildings. There are about 140 students in attendance. The clinical liours are in the forenoon from 10 to 12. The clinics are free as to consultation and medicine, but there is a charge for the fodder that the animal consumes. I was informed that there was a good demand for veterinarians in Holland and that they did well. Some idea of the work accomplished may be obtained by glancing over the following table, taken from the catalog of this school for 1904-5. The table represents the number of cases treated in each clinic during the period of one year. Stationary Clinic. Consulting Clinic. Ambulatojy Clinic. Total. Horses and Asses . . .. 413 901 89 1403 Cattle Sheep Goats .. 32 260 .. .. 5 .. . 447 1 739 6 . . 12 57 3 11 2 . . . . 72 Varkens (Swine ?). . Dogs 27 38 . . 223 1413 . . . 1638 Cats 296 296 Birds 68 ... . 422 432 Other Animals 68 553 748 3391 4692 At Hanover, Germany, I found a comparatively new and beau- tifully arranged veterinary school in its group of botanical gardens. It was under construction from 1805 to 1899, and I was informed that its cost amounted to 4,000,000 marks ($1,000,000). About twenty buildings are included in these grounds, and it indeed surpasses in beauty and extent some of the smaller universities in the United States. The entrance requirements, as I understand it, are the same throughout Grermany. A student must have passed through a gymna- sium (about nine years), which corresponds to a high school education and that which precedes it in the States. The length of the veterinary course is seven semesters of about five months each, or a total of three and a half years. The tuition per year at Hanover is 160 marks ($40.00). An eighth semester is de- voted to final examinations for those who are eligible and able to com- plete the course. For this semester no tuition is charged. 14 The medical and surgical clinics under Professors Malkmus and Frick, respectively, nnd tjie clinic for small animals under Professor Kunneman are well patronized. The students do not operate upon patients, Init study them, drtws wounds and keep records of their progress. Subjects are purchased for the students to operate upon and these are then utilized for dissection. In the clinic there is no charge made for consultation. Medicines are furnished at about 25 per cent, below the usual rates. A payment of 2 marks (50c.) per day covers everything in the surgical clinic. There are about 240 students in attendance at the Hanover school. JVTilitary service is compulsory in Germany and veterinarians are not exempt from it. Because of their higher education, and this apjDlies to medical and university students also, only one year is required instead of two years as for ordinary individuals. A student must serve out his military term before he can embark in private practice. I was informed that the government would pay the expenses (not personal) of a student at a veterinary school, and in return would require him to serve fi'om seveu to ten yeai'S as an army veterinarian — at least one year for each semester. The veterinary school at Berlin leads all the others in the number of students, there being 335 in attendance. Berlin, I was informed, is a military school and the students attending there are preparing for service as army veterinarians. The grounds of the Berlin school are about as extensive as those of Hanover, and there are numerous new and modern buildings. Some of the older buildings are to be replaced by new ones in the near future. A number of the professors live in a building situated upon the groimds. This is true to a much less extent of the majority of the schools visited in G-ermany — either a professor or some of the assistants being furnished with quarters. In addition to the medical clinic under Professor Frohner and the surgical under Professor Eljerlein, and the clinic for small animals under Professor IiCgenbogen, there is a very large polyclinic under Professor Karnbach. A gr(>at many animals are treated in these clinics. Professor Zuntz, Director of the Agricultural School not far from the Veterinary School, but independent of it, has done some impor- tant work upon the physiology of the domestic animals. The tuition is the same as at Hanover, $40.00. Entrance to the Berlin Veterinary School. Statue of Gerlach. Institute Jor Pathology, Berlin, I BL^i^lSM s, ^.- -^-^, ^.»^ . Department of Anatomy and Clinic for small animals, Dresden. Department of Pathology, Dresden. IS I was told as a matter of historical interest that Virchow as a young student did some u'ork at the Veterinary Seliool, and it was there that he discovered the bacillus of malignant oedema. Also that Koch's discovery of the Bacillus of Tuberculosis and the Comma Bacillus occurred in a building situated near the Veterinary grounds. I am under consideraljle oljligation to Professor Ostertag and his assistant, Dr. Himpel, for courtesies rendered in making it possible for me to attend various lectures and clinics not only in the Veterinary School but in the University of Berlin as well. The following data relating to attendance and cases presented at the clinic-s at Berlin was taken from the Veterinary Journal for September, 1907, and relates to the year 1905-6. "During the summer session 400 and during the winter 416 students were on the roll of the school, and 21 military students. One hundred and ten presented themselves for the final examination, of whom 97 passed. One thousand seven hundred and twenty-seven horses and one donkey were treated in the medical wards under Professor Frohner, and 760 horses in the surgical under Professor Eljcrlein. Six hundred operations were performed; six thousand nine hundred and thirteen large animals were attended as out patients under Professor Karnljach and 1908 minor operations were performed. In the canine ward, under Professor Eegenbogen, 1260 patients were treated and 244 operations were performed. Eight thoirsand dogs, 181 cats and 14 monkeys were attended as out patients, and 632 minor operations were performed. Post-mortem examinations were made l)y Professor Schlitz on 305 horses, 1 donkey, 2 oxen and 113 dogs. Professor Eggeling paid 453 visits and treated 52 horses, 486 oxen, 561 pigs and 3 goats." The grand total of all the animals treated in the various clinics amounts to 20,017. The Veterinary School at Dresden, under the directorship of Pro- fessor Ellenberger, is 'not so extensive as those at Berlin and Hanover; but the buildings are well appointed and conveniently arranged. In a building upon, or adjoining, the grounds reside veterinarians in the military service who take a course of about six months in horse shoeing and the forge under Professor Liingwitz. The clinics are conducted on a plan similar to that at Berlin, but 16 the cliai-ges for the patients are somewhat less. There are about 167 students in attendanee. Tlie tuition is KiO marks ($40.00) per year, with 10 or 13 marks 'additional for special purposes. The Veterinary Scliool at Munich, with Professor Albrecht as director, has buildings somcwliat ohier than the other German schools, but they are well e([uipped ajui arranged. Tlie building containing the patliolwgic collection of Professor Kitt is the most antiquated, but the collection is most interesting. I was informed that Professor Kitt had recently been retired on account of disability. The tuition charges are only 60 marks ($15.00) a year at this school, and the clinical charges were also lower than at the other schools. The attendance is about 320. According to the catalog for 1905-6 the Munich school received the following number of animals in their various clinics: Medical Clinics. Surgical Clinics Large Animals Diseased. (Operated upon) Surgical Clinic Small Animals Diseased. (Operated upon.) Polyclinic Surg- ical Division. Polyclinic Med- ical Division. 312 549 (412) 36 E Di 3 (21) O o > > OE 23 (20) 23 51 (51) Ambulatory Clinic. 194 6l8 lOSl O Q u ■a S o 797 39 59 1233 622 1032 32 1087 (712) 20 1S31 78 52 1967 2419 .... 148 213 2816 Ill 89 2093 The Veterinary School at Stuttgart, under the directorship of Professor Siissdorf, has grounds about as extensive as those ait Dresden and Munich. Some of the buildings are quite antiquated, but the Institute of Anatomy and Pathology and the departments of Medicine and Surgery are well f[uartered in relaitively new and conxmodious buildings. There is (|uite an elaborate system for ventilating the hospital wards of iDoth of these departments. The department of surgery under Professor Hoffman shows a wonderful range of mechan- Entrance io the K'teiinarv School at Munich. Buildings for Medical and Surgical Clinics, Munich. Entrance io the l^eterinaiy School at Stuttgart. ^-i-I^WMMliaa^i-^i-t -■• Building for Anatomy and Pathology, Stuttgart. 17 ical ingenuity in the arrangement and manipulation of its apparatus. There is an elahorate operating table regulated by hydraulic pressure. It may be turned to -a vertical or horizontal position or tilted to any angle and may be raised or lowered by means of a lever. There is also an elaborate apparatus for confining a horse by means of a system of clamps for the head and neck — the feet being fastened to the floor. A large Roentgen Eay apparatus is also included in the equipment. The stalls are most conveniently and hygienically arranged for the comfort of the patients. Water is supplied to each stall automatically through a pipe, so that the patient has always a supply before him. There are from 130 to 150 students at this school, and the tuition is 140 marks ($35.00) per year. It was a matter of much regret that time did not permit me to visit the Veterinary School at Giessen. I was informed that it had quite a close relationship to the medical department of the university — more so than any other school in Germany. ,In Switzerland, the first school that I visited was at Ziirich. Unfor- tunately the season for instruction ended at about the time I was there and I was unable to witness the work and meet as many of the pro- fessors during the remainder of the trip as previously. This school is affiliated with the University of Ziirich, although the school buildings are some distance from it. There is no separate director of the school, the president or director of the university officiating as such. A portion of the course, including botany, zoology, physics, chemistry and physiology, is therefore given at the university. The veterinary faculty is included with that of the university. The school is small, including only 35 students, and the buildings are somewhat old. The entrance requirements for the schools in Switzer- land are similar to those in Germany. There is also compulsory military service in Switzerland. It differs in some interesting ways from that in Germany so far as veterinarians are concerned. As it was explained to me, the j'oung man, while still a student, must serve in the recruit school, devoting eight weeks to military service if in the artillery, or twelve weeks if in the cavalry. If he wishes to maintain some connection with the army he attends the under-officers' school (optional) for five weeks for the artillery branch. Then comes the officers' school (also op- tional) after the state examination, where he spends six weeks. Then 18 he becomes tin officer-lieutenant and must serve eight weeks if in the artillei-}', or twelve weeks if in the cavalry. After the officers' school comes what is known as the "Wiederholens Kurs" (repetition), and the lieutenant must serve everj' second year for tliree weeks until he is 33 years of age. A lieutenant gets six francs, or $1.20, a day while serving. 'J'lio following report of tlie clinical work at Zurich for 1906 wa^ furnislied rue during my visit. Hospital Clinic. Ambulatory Clinic. Consulting Clinic. Total. Horses. , Asses an d Mules . . , . . . 921 1 . . . . 38 2 1089 3474 1 13 f ■■ . . . 5498 Cattle . Swine . 1626 92 8 76 .... 205 .... 3 f ... 1740 299 Goats , Irds Sheep . 1 -f-- 12 Dogs . . , ... 5d3 .... 5 163 1933 . . . 2659 Cats... .... 12 264 281 Fowls . 47 10 1 Pairots Other B 1 1 1 4- 22 ' 10 ^ . .. 84 Rabbits Pigs 1 Gninea 4... 14 Squirrel li :,'; The remaining Swiss V'eterinary School is at Berno and is affil- iated with the university of that city, although the buildings are sep- arate. This school is larger than the one at Ziirich, having 45 students. The grounds are somewhat larger and the buildings are more modern and commodious. The veterinary faculty is included with the university faculty. The Swiss, like the other schools, have clinical periods during the forenoon. The tuition in Ijoth schools is from 200 to 300 francs ($40.00 to $50.00) per year. The course in both schools is four years long. Through the kindness of Dr. Liautard, who accompanied me, I obtained a very fair idea of the school at Alfort, Paris, although the work of instruction had ceased. The grounds with their pleasant groves and numerous Imildings are very extensive and contain statues of Bourgelat and Bouley and a bust of Noeard. A few of the older buildings still remain. yeieriiiary Hospital, Zurich. Administration Building, Lecture Rooms, etc., {rear) ZuricI). yelcrinary School, Berne. Veterinary Hospital and Grounds, Berne. 19 The clinic continues through the vacation and presented a scene of considerable activity at the time of my visit, many of the students remaining to assist. There are between 250 and 300 students in attendanc-e and they take their clinical work during the third and fourth years of their course. The rates are very cheap at this school, as I was informed that a student could get his veterinary education and living on the payment of something like 450 francs ($90.00) per year. There is a dormitory for the students upon the grounds. On a second visit to the school I met a Cihinese student, who informed me that his government sent him there and paid his expenses and that when he returned he would be the first veterinarian in China. I was informed that the Alfort school is supported by the govern- ment under the Secretary of Agriculture and gots an annual appro- priation of $175,000. As in Germany, military service is also compulsory in France, but apparently no allovpance is made for the veterinary education, as I was told ithat the veterinarian must spend two years in the army either as an army veterinarian or common soldier. The veterinary school at Brussels, Belgium, under the director- ship of Professor DeG-ive, is evidently an old school, and there is a larger proportion of old buildings here, with perhaps the exception of Ziirich, than the other schools visited. I was informed that the course in this school is six years in length, the first two years being taken in the university, and tha:t such subjects as botany, physics, zoology and psychology are taken there and the remaining four years are spent in the veterinary school. Or if the four years in the veteri- nary school are regarded as the period of professional work, then it may be accepted that the two years of university work are required for entrance to the veterinary school. The tuition is 300 francs ($60.00) per year, with an additional charge of 20 to 60 francs ($4-$12) for laboratory fees. There are 150 students in attendance. It is entirely optional whether the student shall go into the army or not, as veterinary military service is not compulsory in Belgium. One of the facts, I think, which impresses the American visitor to the veterinary schools on the continent is their extensiveness, the grounds are spacious and there are numerous buildings upon them, a single building for one or two departments, with their laboratories 20 and museums, l)oing larger than the wliolo equipment in some of the American schools. Governmental sui:)port of schools as it exists in Germany is con- ducive to a high degree of cfticienc}'. Some of the advantages are: uniformity of entrance requirements; none but \^•ell educated and qualified veterinarians are in practice. An illegal pi-actitioner is, I judge, a rara avis in that country. With practically the same regula- tions, the system of instruction is interchangeable and a student may transfer from one college to another without loss of time or credit. In some instances living quarters are given to the teachers in addition to their salaries. The methods of instruction of che German schools I visited while in session, attending lectures, clinics, etc., are, I understand, typical of the others. According to the schedule some of the work begins at seven o'clock in the morning and some continues until six P. M. In none of the lectures which I attended, although present promptly on the hour, did any of the lecturers Ijcgin until from fifteen to twenty-five minutes after the hour had struck. This long delay is customary throughout Germany in other branches as well as the veterinary. There is not, as I observed it, the ]iaternal interest in the student as in America. The German system of having the chief examinations at tlie end of the course — apparently on the plan of "pay when you get through" — results in quite a large percentage of students not getting through at the scheduled time, because of dilatoriness and not keeping up to the mark. This again is a custom which is prevalent in Germany in the universities as well as veterinary schools. Although the schools are well provided with laboratories, and they are finely equipped, and although they are irsed for research by assist- ants or advanced students, the idea was impressed u]ion me that the laboratory courses for the undergraduate students could stand a higher degree of development in such branches, for example, as physiology, pathology and bacteriology. In Prance, although the government is generous in its appro- priation to the Alfort school, the conditions surrounding the veteri- narians in practice are not of the most desirable. I was informed that practice in veterinai7 medicine was practically open to anyone who wished to fake it up. Yetej-inarians from other countries may Clinical Area, Alforl, with a view of Slatue of Botirgelal in the distance Entrance to the At fori School, with Administration Building in the distance. Clinical Bnihiing, Brussels. Building for l^elerinarv Anatomy, Brussels. 21 settle in France witliont let or hindrance^ which is no disadvantage if they are properly qualified. But the absence of legal restrictions, except in connection with outbreaks of contagious or infectious dis- eases, against unqualified persons taking up the practice of veterinary medicine is a condition which can have no other effect than to retard veterinary progress in thai country. The veterinary schools in Holland and Switzerland appear to follow more or less closely the methods of Germany; while the school in Belgium is apparently more like those in Prance. The European schools have the prestige of age. The first veterinary school was founded at Lyons, Prance, in 1762. Other schools were established soon afterwards; one appeared at Alfort in IT'GS; others at Copenhagen in 1773; at Dresden in 1774; at Vienna in 1777; at Hanover in 1778; at Buda Pest in 1786; at Berlin and Munich in 1790 ; at London and Milan in 1791 and at Madrid in 1793. Although earlier attempts may have occurred, the first successful establishment of a veterinary school in America was that of the Kew York College of Veterinary Surgeons, which was chartered in 1857. The Ontario Veterinary College at Toronto, C!anada, was established in 1862, and the American Veterinary College in 1875. Since then others have been established, some of them with state support, but the proportion of the number of veterinary schools to that of the general population is still apparently less in America as compared with Europe. Eelatively, veterinary science is young in this countiy, and the prestige of years and adequate financial and government support is still to be attained. Presented at the 44th annual meeting of the American Veteri- nary Medical Association, Kansas City, Mo., Sfept. 10-13, 1907. TETANUS. D. K. EASTMAN AND G. K. CHASE. The synonyjiis of tetanus arc lockjaw and trismus. It is an infectious di.seasc of man and animals in which the specific organisms are localized at the place of inoculation. The disease is characterized by tonic spasms of the voluntary muscles in a given region, or more commonly it affects all the skeletal muscles. It is the result of a specific wound infection. In addition to man it occurs f rc(|uently in horses, asses and mules, and next to them arc small ruminants, such as the sheep and goat. It occurs least often in the dog, and very rarely in birds and fowls. Tetanus is one of the old diseases that was recongnized and described before the Christian era. Though it was not clearly differ- entiated until the discovery of its specific germ in 1884. The cause of the disease is a slender bacillus 2 to 5 microns in length. It forms spores which are at the end of the organism, giving it somewhat the appearance of a pin. It has the distinction of pro- ducing the most powerful poisonous toxin of any of the known bacteria. The shortest period of incubation which seems to be reported is a few hours, and the longest six weeks. In horses the period of incu- bation is from four to twenty days, but inoculating with the pure culture it is from four to five days. In sheep it is from two to four days. In guinea pigs inoculated with the infected soil the incubation period is usually not over forty-eight liours and sometimes less. The common methods of infection are by pricks and nail punc- tures, in which cases the virus can be carried well into the living tissue and there , is little or no bleeding to wash it out. It has been stated that the shorter the period of incubation the more severe the disease, the mortality being more than 90 per cent. The presence of tetanus toxin in the living body causes no symp- toms until it has been absorbed by the peripheral termination of the motor nerves and has passed along their axis cylindera and has reached the motor cells in the spinal cord. While the toxin is in the nerves 23 or spinal cells it apparently remains isolated or unaffected by any therapeutic agent which may be present in the circulating blood or lymph. The chief therapeutic effort is to prevent further absorption of the toxin and antagonize or neutralize that already absorbed. The time required for the toxin to be absorbed and to pass through the nerve represents a large portion of the period of incubation. In the way of treatment serum antitoxin, even in quite large amounts, has not proven very satisfactory as a cure. Borrel, without appreciable success, has employed the intracerebral method of adminis- tering tetanus antitoxin upon experimental animals. The lumbar injection of magnesium sulphate, as reported by S. P. Meltzer, has proved beneficial by relieving the spasms. Bacelli's carbolic acid method, in which one dram doses for the horae, in 5 per cent, solution, administered hypodermic-ally, has been quite favorably reported for the domestic animals. The injection may be made every two hours during the first 24 to 36 hours, and less frequently afterward. Chloral hydrate is widely used for tetanus and is often combined with carbolic acid, especially in rectal injections. Gelsemium and various other drugs have also been recommended with variable success. Experimental. The first subject experimented upon was a black mare weighing about 1000 lbs. She was twenty years old, but in good condition. She was inoculated in the gluteal region by making an incision through the skin and working a pocket under it with the handle of the knife. A piece of agar culture of tetanus was placed in the pocket and the wound left to heal by itself, which it did apparently by first intention. The first symptoms were noted eleven days after the inoculation. They consisted of increased respiration, and pulse and restlessness and protrusion of the membrana nictitans. Circumstances arose which prevented the continuation of the experiment as planned. One dram of dilute hydrocyanic acid was injected intravenously, and although it produced profound results the animal did not die. On a succeeding day another dram of the acid was administered hypodermically and an ounce of carljolic acid and chloral were injected into the rectum. There was no improvement of the symptoms and upon the following day she received three separate one dram doses of hydrocyanic acid, one intravenously and the other two hypodermically. As the symp- toms inerea.sed, instead of decreasing, she was given a three dram dose 24 of the liyJi'ocyanie acid intravenously and a few minutes later died. The second experiment was performed upon a spayed bitch. She was about six months of age and in fine condition. The inoculation was made by making a small pocket in the skin in the gluteal region and introducing therein a small piece of an agar culture of tetanus. As no syjnptoms appeared after an interval of one month the bitch was reinoculated by making a small incision in the pad of the left hind foot and placing a piece of agar culture in the incision. Again there was no effect from the inoculation within a period of one month. A third inoculation was made by preparing an emulsion by triturating a piece of agar culture of tetanus about the size of a pea in two drams of sterile water. This was injected into the peritoneal cavity with antiseptic precautions. In one week the first symptoms of tetanus, in a very mild form, were observed. The neck was somewhat stiff. There was a slight erection of the ears, and wrinkles in the skin of the fore- head. The nienibrana nictitans was protruded and extended half way across the eyes. The eyes were dull and showed an anxious expression. The appetite was good and tlie temperature was 103 degrees F. On the day before the inoculation the bitch received one dram doses of the fluid extract of Ehus Tox twice during the day. The next day the doses were given three times, and this dosage was kept up until the end without other treatment. Mine days after the inoculation the muscles of the neck seemed to he gradually increasing in stiffness; the head was extended and the eyes appeared dull, but in other respects there was no marked change. At no time was there more than a slight trismus of the masseter muscles. There was no change in the symptoms until a week later, when there was quite marked improvement. Treatment was continued for a couple of days longer, l)ut as the Intcli appeared to be in perfect health no further medicine was given. The third experiment was performed upon a bitch which also had been previously spayed. Like the bitch in the preceding experi- ment, she received three inoculations and at the same intervals. One week after the last inoeidation she showed the first symptonrs. The ears were erect and drawn together, the skin of the forehead was drawn up in longitudinal wrinkles. The eyes were retracted and anxious; the membrana nictitans showed slightly and there was some congestion of the mucous membranes. The muscles of the neck were 25 rigidly contractod and the nose extended. She responded readily to calls, but on turning kojDt her head in a straight line with the body. The appetite was good and mastication was not markedly interfered with. The ti-eatment, began as soon as the symptoms appeared, consisted of one-sixth grain of pilocarpine injected subcutaneously three times daily. There was profuse salivation, lasting about twenty- five minutes after each injection. The symptoms soon became more pronounced. There was gradually increasing muscular stiffness; the jaws became partially set and permitted of but slight movement, but she could still make out to eat and drink. She also responded to calls but was stiff and moved with difficulty. Ten days after the appearance of the first symptoms the dosage \\'as increased to four injections daily with the effect of causing the bowels to Ijecoiue looser. As high as one-half grain of the pilocarpine was administered at a single dose, followed by profuse salivation, retching and vomiting and watery evacuations from the bowels. The dose was again reduced to one-sixth of a grain and some one dram doses of rhus tox were also administered. This treatment was con- tinued for a few days and quite marked improvement followed. There was relaxation of the muscles; the nictitans was not so prominent, the eyes were brighter and the wrinkles in the forehead were not so marked. The discharges from the bowels were c[uite free and watery. In a little less than a month from the time of the last inoculation the bitch appeared to be well and further treatment was discontinued. Another experiment was tried upon a small black mongrel dog weighing about 18 lbs. An emulsion containing 1 cc. of the B. Tetani agar culture was inoculated into the peritoneal cavity. The sjonptoms appeared within four days and were well advanced. The pilocarpine treatment was attempted, but the disease advanced so quickly that treatment was given up and the animal chloroformed. The post- mortem showed that the stomach and intestines were normal. The spleen and kidneys were congested and the liver engorged with dark frothy blood. There were petechiae and some congestion in the heart. The sublumbar muscles were rigid and engorged with blood, and there was also some congestion in the meninges of the brain. A black gelding ten years old, suffering from tetanus, was brought to the clinic. The case was in charge of the professor of medicine, anfl the treatment recommended by him was the injection, per rectum, of 26 fi'om one-lialf to one ounce each of carbolic and chloral dissolved in a quart of. water. As a poi'tion of the treatment two-dram doses of li/^ per cent, solution of eosin were injected subcutaneously. The patient recovered in due course of time. The principal object of the experiments wa^ to test the eiiect of eliminative treatment in retarding or checking the course of the dis- ease. Iilius Tox and pilocarpine are both efficient agents for this pur- pose. The dog which received rhus tox from the time of the inocula- tion developed a comparatively mild case of the disease as compared with the dog which received the pilocarpine treatment after the symp- toms had developed. The condition of the second dog became rather serious at one time, and some rhus tox was given along with the pilo- carpine treatment. It is cjuite likely that the combined treatment pulled him through. Both dogs made good recoveries, the rhus dog recovering first and showing less marked symptoms throughout the course of the disease. Other experiments are, of course, necessary, but this preliminary work leads us to think that both rhus tox and pilocai'pine are useful in tetanus largely from the eliminative stand- point. EXPEEIMENTS WITH BABIUM CHLOEIDE. W. E. FRINK AND H. B. TILLOU. Some unpleasant results have occurred from the use of barium cliloride, but, on the other hand, there lia\e also been so many more that were favorable and this, combined with tlie cheapness of the drug, led us to undertake the investigation. It is not unlikely that some of the unpleasant results may have been due to impurities. In the following experiments ilerck's preparations of barium chloride "highest purity" were em^jloyed. The cost was less than forty cents per pound, and there were no effects which we could trace to the presence of any impurity. So far as we can find Percival, in ilarch, 181G. was the first to use the drug therapeutically. He used it in glanders and in one of the cases noticed that there was purging. Labori and others noticed its stimulating effect upon the heart from experiments upon rabbits. Dieckerhoff in 1895 recommended the drug for its purgative effect, and he also used it in a number of cases of colic. The drug was administered intravenously and by mouth, either method producing purging. He noted increased peristalsis and fluidity of the feces. The cow was found to be less susceptible to barium chloride than the horse, and the sheep still less than the cow. The following statistics are interesting concerning the use of the drug. Dieckerhoff published the observations on fifty-one cases in 1895. A few months later Brass published the results of 136 observa- tions, out of wliich twelve animals died, about 9 per cent., as follows: seven with torsion of the large intestine, two of the small intestines, one with hernia through the foramen of Winslow, and one with entero- peritonitis. The doses used by Dieckherhoff and Brass varied from .25 to 1.35 grams. The drug was considered more energetic and more rapid than eserine, pilocarpine or arecoline. It was recommended that the dose be proportioned to the size of the patient, viz., .3 to .6 gram (5 to 10 grains) for small, .5 to .9 gram (8 to 14 grains) for medium, and .8 to 1.2 grams (12 to 18 grains) for large horses. Dahlenburg used it in 32 cases without accident; Griiner in 48, 28 in doses of .75 to 1. gram (12 to 15 grains). In certain eases he in- jected two and three gi'uiiis witliout ill i-esults, except that the syjiip- tonis produced wore intensified. Hutyra at Buda Pest in 1897 used it in .5 to 1.3 grams (8 to 18 grains) in IDl cases without a death. G-riiner, Plattner and Dahlenbui'g point out that fatal accidents arise from the action on the heart of large doses in concentrated form. Ari'iving at the coronary arteries, tetanic spasms of the muscle fibers may result and cause almost instant death. The statistics of a number of published cases show that where dea,th has taken place the attack of colic has lasted for some time, that there was acute derangement of the circulatory system, that the pulse was very quick and feelile, and that the systole was weak. In some cases the patient suffered from old standing heart disease. In all such cases small doses are indicated. M. Cadiot is reported as ti'eating his clinical cases of colic with barium chloride, using a solution of 1 to 30 in tw^o or three injec- tions with intervals of 80 to 30 minutes. In small doses it is still active, prompt in its action and harmless. Brass and Witt at the Berlin school have given three thousand doses without a fatal result. M. Chryet, of the Paris General Omnibus Comjjnny, has treated 4:45 cases with .4 gram (6 grains) doses at intervals of 15 to 30 minutes. Dr. J. C. Callender (American Veterinary Eeview) considers barium chloride superior to eserine in the majority of cases. He has used it intravenously in 10 grain does for all cases of colic from indi- gestion. In some instances the dose was repeated in a half an hour with good results. In ordinary cases evacuation of the bowels in five minutes, with perhaps ten or more in the next half hour. He cautions against its use if there is much hyperthermia or if the pulse is not strong. Dr. Muir, of the University of Pennsylvania, reports the follow- ing observations on the action of barium chloride: Case NO. Dose. ^^, ^yZptn.. Defe^atio height of Feces. 1 15.4 grains 8 min 7 20 lbs. 2 30.8 grains 1 min 24 37f lbs. 3 15.4 grains 3 min 5 14^ lbs. 4 30.8 grains 1 min 42. j yHim^er" } ^'' '"'■ 5 30.8 grains 9 min 20 Died. 29 No dangerous symptoms were shown at any time either of the first four eases. In the fifth or last experiment the animal was a fair sized bay gelding in good condition, pulse 50, full and strong, respira- tion 13, temperature 99 degrees F. Fifteen and four-tenths grains of barium chloride were injected in the jugular at 11 :00 A. M. ; at 11 :31 the feces had passed 11 times. At this time the pulse was full and strong at 48; at 12:07 he had defe- cated 18 times; watery mucus was being discharged from the anus. In order to determine the toxic dose of the drug, 15.4 grains more of the salt was injected in the jugular at 1.43; at 1.49 there was spas- modic contraction of the muscles; he fell, breathing with difficulty, and the heart ceased to beat at 1 :52. The autopsy revealed : the blood cyanosed, riglit heart empty, left side full; lungs normal; contents of cecum fluid; intestines dis- tended with gas; little feces; double colon congested; small intestine normal; cause of death, heart failure. The prominent symptoms were extreme purgation, voiding of watery mucus, only slight pain until the second dose was given, when all the symptoms of asphyxia prevailed, ending in the death of the animal nine minutes aftei' the second dose had been given. Dr. Muir's conclusions are as follows : 1. Barium chloride in doses of 15.4 grains may he safely admin- istered intravenously. 3. It is a prompt and efiicient cathartic in doses of from one to two grams. 3. Its administration is not followed by any severe pain or annoy- ance to the animal. 4. It acts quickly if there is no mechanical oljstruction to the bowel, such as a calculus or volvulus; in the latter case it may cause it to untwist. 5. It has the advantage of being cheap. 6. In doses of 1 gram (15 grains) it causes no pain, while if 2 grams be administered intravenously there is some evidence of pain and distress. 7. It causes little if any swelling and no reduction in tem- perature. 8. Although the number of defecations may be small, the average amount of feces passed is large. 30 In 1898-9 Dr. C. E. Perkins used tlie drug experimentally upon some of the domestic animals. On a number of cases he used it suh- cutaneously in 10 grain doses and obtained evacuations in from three to five minutes and continued at rather frequent intervals for thirty or forty minutes. This method, however, caused, some abdominal pain, manifested l^y the usual symptoms of pawing, uneasiness and rolling. The symptoms persisted for two or three hours; the pulse and temperature remained normal, but the respirations were increased slightly. In some cases the salt was dissolved in distilled water and in others in normal salt solution, but no noteworthy differences were shown in the results. The intravenous injections caused the animal less discomfort. Four cows were also utilized in the experiments. The salt was injected subcutaneously, but the usual dose for the horse produced no result. He found that from 30 to 35 grains hypodermically were required to produce an effect and then it was longer delayed and not so marked as in the horse with a smaller dosage. When the salt was injected subcutaneously without rendering the skin antiseptic there was usually some local irritation and swelling, but this disappeared after a few days without special treatment. The dosage recommended by Dr. Perkins for the horse is 10 grains intravenously for a thousand-pound animal and an additional grain for each additional one hundred pounds in weight. In our own work forty-one experiments were tried, the majority of which were upon horses, the remaining number consisted of a few cows and dogs. The salt was administered intravenously, subcu- taneously, intratracheally, and also in the form, of a bolus and drench. The most of the experiments were confined to animals which were soon to be utilized for anatomical purposes, but in a number of cases the drug was also used upon patients in the clinic. The following examples are taken from each of the different ways in which the medicine was administered to illustrate the symptoms, which may be considered fairly typical of each method. Experiment No. 2. Intravenous method. The subject was an aged bay mare, showing lordosis, but appearing healthy and in fair condition. Her weight was 950 lbs.; pulse 35, and respirations 12 per minute; temperature 99.8 degrees. Fifteen grains of barium chloride, dissolved in 10 ec. of sterile 31 water, were injected into the jugular vein. Champing of the jaws was noticed at once and this continued for about five minutes. The tail was at once raised and there was a passage of a little gas. The first feces, slightly moist, were passed two minutes after the injection. There were slight symptoms of colic and there were more and moister feces one minute later. There was another discharge of feces and liquid two minutes later and some liquid feces and gas within another minute. Still another passage of feces occurred one minute after this. At this time, ten minutes after the injection, the respirations were reduced to six per minute, the pulse was 35 and the temperature 100°. There was excessive rumbling of the bowels. A number of evacuations of soft feces and liquid occurred at intervals from two to six minutes for a period of thirty minutes from the time of the injec- tion. After this period the mare appeared normal and began eating. The first feces occurred within two minutes, and there were ten evacuations within the thirty-minute period. Experiment No. 12. Hypodermic method. The subject of this experiment was an aged gray gelding in poor condition, weighing about 950 lbs. The pulse was 48 and weak. The respirations were 16 per minute. Ten grains of barium chloride were dissolved in 10 cc. of sterile water and injected hypodermically, while warm, into the cervical region. No antiseptic precautions were taken. The animal soon began to shake its head vigorously and at the same time to champ his jaws. The first feces were passed twelve minutes after the injection and consisted of a large amount of hard dry pellets. Four minutes later there was another passage of somewhat softer feces, and six minutes after this another passage of quite soft feces. During this time the animal showed some signs of pain by switching the tail, pawing, etc., but these were not so violent as in some other cases injected in the same manner. The animal soon appeared normal. The pulse was now 36 and strong and full. The respirations were 14 per minute. The first feces occurred in 12 minutes, and there were three evacuations within 25 minutes. Experiment No. 7. Bolus. An aged black horse. The weight ■was estimated at 1050. The animal appeared to be healthy and in good condition. The pulse was 30 and the respirations were 16 per 32 niinnte. A gelatin capsule containing 2 drams of l:)ariuni chloride was crushed in the animal's mouth. As it was believed that he swal- lowed none of the material another capsule containing the same amount was administered. During the action of the drug there was no uneasiness or symp- toms of pain. The first evacuation occurred in twenty minutes. The iirst feces were dry and firm, but later they became quite soft. The animal was obsei-ved foi- two liours, and during that time there occurred 24 evacuations. This number is higher than the average, as in a similar experiment upon another animal there was only one evacuation in an hour. Some flatus was passed at intervals, but no signs of discomfort were shown at any time. One hour after the injection the pulse was 28. The total amount of feces passed was very large, but the animal did not appear weakened. Experiment No. 32. Drench. A drench consisting of a solution of 2 drams of barium chloride in a cpiart of water was administered. The first feces were passed 25 minutes later and were dry and hard; a similar evacuation followed five minutes later. The next feces were passed five minutes later and were softer and moist on the sur- face. The animal appeared to be in no pain, and at the end of the next twenty-five minutes soft feces were passed, followed by evac- uations of soft feces and some fluid at intervals of 10, 10 and 15 minutes. The animal was not observed during the next hour; during that time there had evidently been one or two passages of soft feces. The animal showed no uneasiness at any time. There was no shaking of the head and champing of the jaws as when the drug was given intravenously to the same animal some time previously. Experiment No. 30. Intratracheal method. The subject experi- mented upon was an old brown mare, weighing 1100 lbs., and she appeared to be in good condition. The pulse was 40 and the respira- tions were 14 per minute. A solution of 15 grains of barium chloride in 10 cc. of water was injected into the trachea, the needle being inserted between the rings of the cartilages. Masticatory movements of the jaws were noticed after several minutes. Fourteen minutes after injection there was a discharge of the urine. The pulse was now 34 and the respirations 12 per minute. Twenty-five minutes later more urine was passed and the groom observed that the animal urinated several times during the next hour. This method was tried 33 upon three horses, one of which received 30 grains intratracheally. None of the horses were purged by this method, altliough observed from 40 minutes to 1% hours. The above horse was the only one observed by this method which showed any diuretic effect. In another experiment (Xo. 19) a combination of 10 grains of barium chloride and one-half grain of arecoline hydrobromide dis- solved in 10 cc. of distilled water was injected into tlie jugular vein. The mare had a large evacuation of feces one minute later and began to champ the jaws and kept this up for about three minutes. There were seven evacuations within thirt^'-two minutes. The pulse before the injection was 36 and full and strong. After eight minutes it had increased to 63, but after thirty-two minutes it had fallen to 30 and was full and strong. Except for the champing of the jaws there was no evidence of pain or uneasiness. Another combination (Expt. No. 20), consisting of 10 grains barium chloride, one-half grain escrine and 1 grain of pilocarpine was injected intravenously. A large evacuation occurred witliin five minutes, and there was a total of five evacuations within thirty-five minutes. As in the previous instance, there was champing of the jaws, but no other evidence of pain. Before the injection the pulse was 36 per minute and small. Thirty-five minutes after the injection it was 30 and fuller and stronger. The results obtained by the combinations were apparently in no way especially superior to the barium chloride when used alone by the same method. Some interesting results were obtained upon a patient con- valescing from an attaclv of tetanus. It was noticed one forenoon that the horse was in considerable pain and a diagnosis of spasmodic colic was made. An anodyne drench was administered without apparent benefit. Three hours later an intravenous injection of 15 grains of barium chloride in sterile water were given. In about two miiiutes there was a large evacuation of feces, and this was followed by several more. The colicy symptoms were increased after the injection, and to relieve these 2 grains of morphine were injected subcutaneously, and this soon quieted the animal. [The colicy symptoms seemed to aggravate the tetanus, but the morphine apparently antidoted the effects of the barium chloride quite promptly.] 34 ExiDeriiiu'iits 2G and '^7 wi-i-c ]H'i-foriiiofl upon the same animal at different intervals. The suhjeet was an old buckskin ,<,felding, weigh- ing about 1050 pounds, and was in poor condition. Tlie animal had been given a half ounce of powdered nu.x vomica and an hour later began to sho«- symptoms of poisoning. An ounce of Lugol's Solution was administered and aliout two ounces of chloroform were inhaled without benefit. The pulse rose to 104 and the respiration to 54 per minute and were very laboi-ed. Tlie animal had fallen and could not arise. His recovery was considered hopeless, and as an experiment he was given 15 grains of Isarium chloride subcutaneously two hours after the nux had been taken. Witliin seven minutes the pulse was reduced to 84 and was stronger and not so intermittent. In another seven minutes it was reduced to 73, and still another seven minutes to 60. One hour later it was 50 per minute and regular and sti'ong. Fifteen minutes after the administration of the barium the respirations were reduced to 42: they were deeper and not so labored. One hour and a half after the barium, they were reduced to 28 and appeared quite normal. At this time the animal was found on his feet, eating hay, and three evacuations of feces were found in the stall. Two days later the same horse received a half ounce of powdered nux vomica. Toxic symptoms were shown in about one-half hour. There were muscular spasms, twitching of the eyes and jei'king of the leg muscles. Slight sounds and the presence of persons in the stall made these symptoms worse. There was also profuse sweating. The respirations were 72 per minute, and very labored. The pulse was 60 per minute. An hour and a half after the nux was given, 15 grains of barium chloride dissolved in 10 cc. of distilled water were adnxinistered intra- venously. There were five evacuations of the bowels witliin a half an hour, the first one occurring three minutes after the injection. Ten minutes after injection the drug began to affect the respiration, re- ducing it from 72 to 60 per minute. After 15 minutes the muscles had begun to relax and had stopped the violent twitching; the breath- ing was much more regular and less labored. After 20 minutes the animal ceased sweating and the eyes ceased to roll. After 30 minutes the pulse was 60 and the respirations 25 per minute and apparently unlabored. The muscles had completely relaxed; the general appear- ance was much improved ; a pail of water was taken and some hay was 35 eaten. After an hour and a quarter the pulse was 55 and the respira- tions were 23. It would seem from these two experiments that barium chloride had quite a direct action in antagonizing the action of strychnine. At any rate, it shows very clearly the action of the drug on both the heart beats and respirations, in decreasing the number of each per minute and making the respirations deeper and the puke stronger. In one experiment (33) the animal was killed within an hour after the intravenous injection of 18 grains of the chloride. When the abdominal cavity was opened and the intestines exposed the peristaltic movement was plainly seen, and when a portion of the intestinal wall was removed for sectioning the persistent contraction of the circular muscle fibers caused the tissue to curl up so that it was necessary to pin it to a piece of cork in order to keep it flat for fixing. Seven grains of barium chloride were given in a drench to a yellow bitch weighing about 20 pounds (experiment 36.) Feces and urine were passed soon afterward. The dose was evidently too large. There were marked colicy pains and attempts at vomiting. Vomiting did occur later and nausea was severe. As a mixture containing bis- muth, carbolic acid and hydrocyanic acid did not relieve the nausea, one grain of morphine sulphate subcutaneOusly was admistered. This pri>duced a sedative effect and in a short time the bitch was apparently all right. [In some ways morphine seems to have an antidotal effect to barium chloride.] In another experiment (No. 37)3 grains of the chloride dissolved in a half ounce of water was given to a dog by the mouth. Two copious evacuations occurred, one in the forenoon and one in the afternoon. The animal showed no signs of pain or nausea, and the mild purgative effect of the drug was in this case highly satisfactory. In an experiment (No. 38) one-half grain of the chloride was administered intravenously to a bitch weighing about 25 pounds. The dose was repeated a little later and she died almost immediately. The abdominal and thoracic cavities were opened at once and the heart was found to be still beating and continued to beat several min- utes. The intestines were also noticed to be twitching and jerking. From the fact that in this case the heart continued to beat after the respiration had ceased, it would appear that the animal died from 36 paralysis of i-espii'alion ]'atliei- than from cardiac paralysis. There was no evidence of coagulation of the l)lood, as has been reported by some experimenters. Throughout the experiments it was noticed that, although the feces first passed were relatively dry, those passed subse(juently grad- ually became more moist, and the last ones were usually of a fluid character. The vigor of the peristaltic action was no doubt an impor- tant factor in hastening tlie evacuation of the bowels, and may, to some extent, have interfered with the absorption of the fluid from the feces as they were hurried along and thus increase the fluidity of the later discharges. It was a question if the increased peristalsis would ad- equately explain the increased amount of fluid in the later discharges and if the drug itself might not have a direct action upon the intestinal glands and thus increase the amount of the secretion. The following experiments were performed in order to get further light upon this point. Experiment 39. The subject was a collie dog weighing about 40 pounds. The anim,al was put under complete anesthesia and an in- cision was made through the abdominal wall, through which a portion of the small intestine aliout 15 inches in length was carefully with- drawn. The contents of the intestine were carefully pressed toward either side and a ligature applied at each end sufficiently tight to exclude the passage of fluid through the lumen of the gut. Two other ligatures were applied to this isolated portion, dividing it into three sections as nearly ec|ual in length as possible. The loops were then marked for identification by tying pieces of string loosely around them A solution of barium chloride, one grain to 1 cc. of sterile water, was injected into the intestine in loop No. 1. Two cubic centimeters of a similar solution were similarly placed in loop No. 2. The middle loop was left as a control and 1 cc. of water was injected in this. The in- testine was replaced within the abdominal cavity and the opening closed. Later enough chloroform was administered to stop the heart. The ligated portion was removed from the rest of the intestines. It was at once evident that loop No. 1 was more distended than the control loop and that loop No. 2 was still more distended, its surface being smooth and shiny, while the control loop was collapsed and its surface corrugated. The control loop was found to contain a small amount of ingesta slightly moist, Loop No. 1 contained some ingesta 37 and more fluid, and loop No. 2, which had received 2 grains of the salt, contained only fluid in which particles of ingesta were floating. It was clear that the fluid contents of the intestines had been increased by the action of the salt. The intestinal mucosa appeared quite normal ; loop No. 2 was perhaps slightly liyperemic and there was slight congestion at the points where the ligatures had been applied. Experiment No. 40 was similar to the preceding and similar results were obtained. In Experiment No. 41 the subject was a Jersey cow. The procedure was the same as in the two cases just described. Although the cow died from an overdose of chloroform 20 minutes after the injection had been made, the intestinal loo2>s into which the bariiun chloride had been injected contained a larger amount of the fluid than the controls. Some blood pressure experiments were tried upon the horse to determine the effect of barium chloride upon the heart and circulation. The results showed a marked slowing of the heart beat, with additional force. The blood pressure also rose considerably. STJMMAEY. The results of the preceding experiments we believe justify the following conclusions : I. The drug in the doses recommended acts as a purgative, in degrees according to dosage, producing evacuations varying from mild catharsis to drastic purgation. This is produced by increased peri- staltic movement and increased intestinal secretion. Furthermore the drug acts as a cardiac stimulant and tonic, lessening the number of and increasing the force of the beats, and raising blood pressure. The respirations are also reduced in number, but are deeper and more forcible. We agree with Bartholow that toxic doses when given in proper dilutions 1 :20 kill not by coagulation of the blood, or cardiac paralysis, but by respiratory paralysis. II. That while the intravenous injection is a little more difl&- cult than sub-cutaneous injection, it is more satisfactory, producing quicker results and followed by no greater irritation or other evil results, and can be giren without fear of coagulation of blood or cardiac paralysis. The time after injection by this method to the first 38 passagu feces l)cini;; in most eases from 3-5 minutes, the longest in- terval being ten iiiinntx?s. Symptoms of severe pain were not shown in any ease and the effect of the drug passed in from thirty minutes to two hours, Imt iisually in less than one hour. III. Wien given subcutaneously there was some irritation at the point of injection, also more pronounced symptoms of pain. The effect was not seen as quickly, neither did the animal purge as freely. IV. ^Vhen given by mouth the effect was noted in from twenty minutes to fifty minutes. The animal purged more freely when given in a drench than when administered in a capsule. V. The intratracheal method is unsatisfactory, producing no purgation even when given in doses of thirty grains, but the usual effect on circulation was noted. VI. The dose given intravenously for purgative effects should be fifteen grains for a IOOO-II1. horse, and one additional grain for each 100 lbs. additional. The dose given in the same manner for a cardiac tonic should be five to ten grains, according to the needs of that organ. VII. The subcutaneous and intratracheal methods are unsatis- factory in doses that could be given with safety. VIII. The dose of the drug when by the mouth should be two drams for a 1000-lb. horse and 15 grains should be added to this for each additional hundred pounds weight. IX. Prom the few experiments on cattle it would appear that the dosage in these animials must be larger than for a horse of the same wreight. We would recommend 30 grains intravenously as the mini- mum dose for a 1000-lb. cow for mild purgative action. X. In dogs the dose must necessarily be small, one to four grains may be given by the mouth, according to the size of the animal, or severe nausea will follow. The following tables show some of the more essential results in very concise form : 39 TABLE NO. 1. Case No wt. Method of Administr'n Dose. Pulse Before Pulse After. Time to first Evac'n No. of Evacu- ations. Time obser- ved. Symptoms of Pain. 1 900 Intravenous 10 grains 40 36 4 min 6 48 min Slight. II 950 " 15 grains 35 35 2 min 10 30 min Slight. III 900 " 15 grains 33 40 2 min 17 48 min Slight. IV 1250 " 14 grains 38 50 13 min 2 45 min Colic. V 1000 " 20 grains 34 30 2 min 18 32 min None. VI 900 Bolus 2 drams 30 24 15 min 6 1 hr. None. VII 1050 " 2.5 drams 30 28 20 min 24 2hrs. None. VIII 1000 Hypoderm. 20 grains 42 40 17 min 2 2 hrs. None. IX 800 " 20 grains 40 48 15 min 2 1 hr. Sev're col. X 1000 Intravenous 15 grains X X 3 min 8 33 min None. XI 1100 Hypoderm. 18 grains 50 43 10 min 5 30 min None. XII 950 ■' 10 grains 48 36 12 min 3 25 min Slight. XIII 1000 " 10 grains 50 48 25 min 2 37 min Severe. XIV 1000 Intravenous 17 grains 56 48 2 min 6 25 min Slight. XV 850 Bolus 2| drams 42 37 25 min 1 1 hr. Slight. XVI 850 Intravenous 7| grains 40 38 40 min 1 1 hr. Slight. XVII 850 " 15 grains 41 38 2 min 12 42 min Slight. XVIII 1150 " l5 grains X X 2 min (?) X Colic. XIX 900 " -J gr. ARECOLINE lOgr.BaCla lOgr.BaCU 36 30 1 min 7 32 min None. XX 800 '■ 5 gr. ESERINE 1 gr. piLOCARP 36 30 5 min 5 35 min None. XXI 1100 Bolus 2 drams X X 50 min 7 2i hrs. None. XXII 900 Drench 2 drams X X 25 min 9 2^ hrs. None. XXIII 800 Bolus 2| drams 32 32 23 min 22 ij hrs. None. XXIV 1150 Intravenous 15 grains 49 40 5 min 6 25 min Colic. XXV 1250 " 15 grains 76 60 1 min 8 21 min Colic. XXVI 1050 Hypoderm 15 grains 104 50 X 3 1| hrs. None. XXVII 1050 Intravenous 15 grains 60 55 3 min 5 30 min Slight. XXVIII 950 Intratrach'l 15 grains X X none none If hrs. None. XXIX 950 " 30 grains X X none none l| hrs Colic. XXX 1100 " 15 grains 40 34 none URINE PASSED SEV 40 min None. XXXI 950 '• 15 grains 34 30 none none 50 min Slight. XXXII 1200 Intravenous 15 grains X X 5 min 9 30 min Colic. XXXIIl 950 " 18 grains 40 36 2 min 15 45 min None. • ^ (^ c^ ^ r4 sua ^ 1^ \o r>) Z^ -- O - <'-'-;; VO Ti- rO — n-j (N c :S .y O 2 -^^ o 2 OJ ^ o c7i O z o z a. 5 *- 2 9 o" u^ M Tt- O Q m ro r^ -^ O > Lo ^o f^ p 'S < "=f "^ ro w _ L« — ,—, "^ Xi GC 00 OJ +3 — 3 o O Ci Ci j; 'T- r: c: o -^ o Cl 5<< 3 a rt Lt 3 S 3 _c "3 d 3 a .a a 6i s o :o GQ« ^« ffl ^* — :. — ; Cl c"i o O Cs o- ^^ T— 1 ■^ Zi ■^ -T— 1 It o CO a ^-j o o- -a: O' bJ3 0) -t< -:(< o '^ CO g' a a a a a2 .31 § a a a a a "= aas Ci -H c: LO lo sa^ -^ T-H IB aa ^ o .S a ft? M-S g s a a a ^ ^ s b£ M bO ^ " "^ bo . ^ a -^ J ^5 ^ C? Oi be ■ to a £-/3 2 ^S il) O O rK C'i -?* o IZi 12 Upon the pulse it is noted that it is at first quickened and tlien apparently shows a tendency to fall toward normal. The normal temperature was reduced slightly in each instance, the range being from .2 to 1.3° and then gradually returning to normal. In the ma,iority the respirations were increased slightl}\ In a few of the eases some coughing was noticed after the injection of the drug. The action of the drug upon the bowels was reasonably prompt and there seemed to be l)ut little choice as to rapidity of action whether administered intravenously or hypodermically. The first effect was an increased peristalsis. In most of the cases there was flatus and where there was more than one evacuation of the bowels, the second was softer and more fluid than the first, indicating that tue intestinal glands were active. In half of the eases urination took place, but attempts at mic- turition were frequent in all and seemed to be especially noticeable in the mares. The pupils were contracted to mere slits and the lachrymal secretion was increased, in some instances running over the lower lid and through the nose. The secretion of saliva was always increased, beginning in from 2 to 5 minutes and lasting from 45 minutes to one and a half hours. Experiments Upon the Urine. The first experiments were tried upon human urine. The total amount of urine was collected each day for three days and an examination made each day. Then, for three days, five pills of pilocarpine nitrate, each containing 1-134 grain, were taken daily and the urine collected and examined as before. The average analysis of each of these three day analyses is herewith given. Before taking Pilocarpine (3 days) While taking Pilocarpine (3 d.) Amount 1850 cc Sp. Gr 1016 Solids 37.28 grams— 1000 Chlorides .3.85 " " Phosphates 1.96 " " Sulphates 4.00 " " Urea 15.00 " " Uric Acid 0.7 " " 370 cc. 022 51.26 grams- -1000 7.7 3.15 " 4.00 " 22.00 " 0.48 " 13 The same experiment was repeated later with the following results : Amount 1363 cc. . . 1259 cc. Sp. Gr 1018 . 1024 Solids 41.94 grams— 1000 55.92 grams— 1000 Chlorides . . . 9.4 " " 12.30 " Phosphates . 1.96 " " 3.20 " Sulphates . . . 4.00 " " 3.60 " 11.00 " " 20 00 " Uric Acid . . . 0.35 " '■ 0.30 " The tables show that there was an increased elimination of the solids during the pilocarpine period. The increase in the urea, chlorides and phosphates was especially noticeable. The sulphates varied little but the uric acid was somewhat decreased. The same experiment was tried upon a large maltose cat. The solids were increased as before including in this instance cpiite a decided increase in the sulphates and a slight increase in the uric acid. The urine of some of the horses was tested after the administra- tion of pilocarpine and it was found that here also there was an increase of solids as compared with the average analysis of the normal urine. An effort was made to determine how soon the urea increased in amount after the injection of the pilocarpine, the subject being a mare. Urine was drawn from the bladder at intervals and tested for urea. The following table shows the results : Time 16 min. I14 hrs. 11/2 hrs. 1% hrs. 2 hrs. Amount of Urea .... 19 grams 34 grams 32 grams 28 grams 24 grams A tQst upon another horse was carried out the same way : Time 15 min. 1% hrs. % hr. 1 hr. 1% hrs. 1% hrs. 2 hrs. Amount of Urea 45 gms. 46 gms. 46 gms. 49 gms. 49% gms. 49 gms. 46 gms. It would appear that the maximum amount is reached in from 1 to 1 1-4 hours and then there follows a gradual decline. In summarizing the effects of the drug upon the urine it would appear : 1. The amount of the urine is decreased, probably on account of the loss of fluid through other channels, (especially when sweat- ing occurs). 14 2. The solids of the urine are relatively inereased. 3. The i^rea excreted is inereased in amount, reaching its maxinuiiu in 1 to 1 1-i hours and then gradually decreasing. 4. The desire to urinate is increased after the administration of the alkaloid in both horse and man. Salira. The saliva of the horse does not show much digestive action upon starch under ordinary conditions. Some tests of this character were made to determine if the pilocarpine had any effect upon this action. "While the results were somewhat variable, it appeared that, on the whole, the action was somewhat decreased. Tests were also made to determine if any amount of urea was eliminated by the saliva. The results indicated that a slight amount was thus eliminated up to 20 minutes after the use of the drug and that there was then a decline. The proportion found did not exceed 2 grams per 1000 or 0.2^. So that the elimination of urea by this route would not appear to be of very great therapeutic im- portance. The secretion of the saliva was considerably increased in amount and usually began in from 4 to 7 minutes after the injec- tion of the drug and continued from 3-4 to 1 1-2 hours. CONCLUSIONS There is an increase in the flow of saliva in the horse. The amount of ptyalin in a given cpiantity of saliva appears to be decreased, perhaps on account of dilution. The gastric and intestinal secretions are inereased and the peristaltic movements are accelerated, and because of this combined action aid in overcoming impaction. The blood pressure is lowered temporarily and the amplitude of the heart beat is increased. The erythrocytes and leucocytes are both increased in number. The respiratory movements are slightly increased and the bronchial secretion is augmented. Body temperature is lowered. The pupil of the eyes is contracted. The amount of urine is diminished in ciuantity but the solids are increased, because of the loss of fluid through other channels. MILK SECRETION AND DISEASES TRANSMITTED BY MILK PIERRE A. FISH The mammary glands are derived from the cutaneous glands. In a modified form they show some relationship to both the sweat and sebaceous glands. Toward the end of gestation, the secretory function of the mammae begins with the production of colostrrun or the so-called "beast-milk." The colostrum is a thick, reddish or yellowish fluid with a more salty taste than that of normal milk and may serve as a purge to cleanse the alimentaiy tract of the newly born of the fecal material which has accumulated there previous to birth. This secretion contains numerous free fat glob- ules and a large number of roimd shaped cells — the so-called colostrum bodies more or less filled with fat globules. Some cells are encountered that have a distinct amoeboid movement ; these are leucocytes that have wandered through the epithelium into the glandular ducts and have taken up some globules of fat. In addi- tion there are found some epithelial cells that have undergone more or less degeneration. Colostrum differs from normal milk in its higher percentage of solids and especially in its higher percentage of globulin, albumin, nuclein compounds and lecithin. In a few days there is a decreased amount of globulin and albumin and the secretion of colostrum passes into the true milk secretion with a higher amount of casein so that at the exxjiration of about one week, the secretion possesses the characteristic appearance and composition of milk. An old, but erroneous idea of the formation of milk was that it was simply an excretion — that its constituents were simply elim- inated from the blood, like the urine. Another view was that it was composed of leucocytes which had wandered from the blood into the glands and there disintegrated and set free their contents. Still another view was that the epithelial cells of the gland itself were shed or sloughed off and gave up their contents to form the milk. This view M'ould necessitate the acceptance of the idea that the gland would have to regenerate itself once or twice during the" twenty-four hours. This would mean an unusual activity and burden upon the tissues and is no longer tenable and it further- more is not supported by satisfactory evidence. The modern view is that the mammary glands conform, in general, to the processes that have been worked out in the other glands of the body: that the material for the secretion is brought to the gland by the blood and that the cells elaborate this material and convert it into the constituents of the secretion. The fact that karyokinetic figures, evidencing cell division are occasionally seen indicates that cell destruction does occur to a certain extent and that these cells are reproduced, but this may occur in other glands as well. The milk from animals of different species contains the same ingredients, c.(j. water, proteids (especially casein and albumin), milk sugar (lactose), fat and inorganic salts. Quantitatively, there are marked differences between the milks of different species. Casein is supposed to be the direct product of the gland tissue elaborated from the proteid of the blood by the action of the mam- mary cells, globulin from the serum globulin or the broken down portions of cells and the lactalbumin from the albumin of the blood. As to the lactose or milk sugar there are different opinions as to its formation. The view most commonly accepted is that it is formed in the gland from the sugar (dextrose) of the blood. Milk fat is derived partly from the fat in the food, partly from the fat tissues of the animal and from the mammary cells. These fats undergo a material transformation in the tissues of the gland, so that certain easily recognizable fats, even when taken up in quantity with the food, are either not visible at all in the milk or appear in very small quantit.y or are merely transitory. Doubtless milk fat — like fat tissue — may also be derived from the albumin or carbohydrates of the food. Citric acid, one of the minor constitu- ents of milk does not originate in the food, but results from meta- bolism. There is evidence that the mammary cells react to a number of different influences which may, within rather narrow limits, cause a changed compo.sition of the secretion. On the whole milk is of a 17 rathei" definite chemical composition and this indicates that there is qnite a definite adjustment between the cells of the gland and the secretion they produce. The following limits of the constituents of cow's milk are very rarely exceeded: "Water 83% — 89%, Casein 2% — 5%, Albumin 0.39%— 0.95%, Fat 2.5%— 7.5%, Lactose 4%— 5.8%, Ash 0.35% — 1.21^.. Of these the fat shows a con.siderable range of variation and is commonly considered the most valuable constituent. The term "total solids" includes all of the constituents of milk except the water. The total solids vary somewhat. During the summer months Dr. Van Slyke of Creneva, N. Y., found them lowest in May (12,56% ) and gaining slightly each month luitil they reached their maximum in October (13.45%). The difference in total solids of milk from some of the leading breeds has also been studied by Dr. Van Slyke, and his results are as follows : Per cent, of Per cent, of Breed water Total solids Holstein 88.20 11.80 Ayrshire 87.25 11.75 Shorthorn 85.70 14.30 Devon 85.50 14.50 Guernsey 85.10 14.90 .Jersey 84.60 15.40 In milk from a mixed herd the water seldom falls below 86% and seldom exceeds 88%, although in a very few special cases varia- tions ranging from a little less than 80%. to a trifle over 90% are on record. In the spring of the j'ear, when cows are pasturing on new grass, or feeding on other succulent foods, they may yield milk containing a higher percentage of water as has already been shown by the research of Dr. Van Slyke. Water distilled from milk is clear and colorless and has the same appearance as ordinary distilled water. The chemical reaction is the same (with Phenolphthalein). But there is considerable difference in the taste and smell. This indicates that some of the volatile substances of the milk are distilled over with the water. IS Pat is usually considered the most important constituent of milk. It exists in the milk in suspension. According to numerous authorities, fat globules, at ordinary room temperature, are present in milk in liquid form. Cooling the milk to a low temperature (about 50 degrees P.) renders them firmer. The fat globules are very minute and vary considerably, according to breeds, individual cows, and the stage in the lactation period. The globules in the milk from the same cow also vary a great deal. According to Pleischmann, the size of fat globules varies between 1.6 micromil- limeters and 10 micromillimeters. A Danish investigator finds from 2 1-2 to 11 1-2 million globules in a cubic centimeter of milk. I\Iost authors find little or no difference in the kinds of fat of the different sized globules although some experiments seem to show that the fat of larger globules has a finer flavor, and a little more oily appearance. Casein is the most important of the proteid constituents. It is the substance which forms the curd in cheese making. In fi'esh milk it is in chemical comljination with lime salts. The viscosity of normal millc is lx4ieved ti> be due in a large measure to this condi- tion of casein in milk. Casein differs from allmmin in that tlu' casein contains phosphorus and less siilphur. AVhen rennet is added to the milk of the cow, goat, l)uff'alo and «we the casein coagulates into a firm curd. When added to the milk of woman, mare and ass the casein precipitates as flakes. The former group includes animals with horns, the latter group is without horns. Albiunin or lactalbumin is very similar to the serum albumin of the lilood, but differs in some particulars. It coagulates at about 158 degrees P. (70 degreesC). Lactalbumin occurs in milk in mere traces biit in colostrum it is abundant. It coagulates at 167 degrees P. (75 degrees C.) and is very similar to the serum gloljulin of the blood. J\Iilk sugar or lactose is the most unstable constituent of milk. It quickly and easily decomposes by the action of micro-organisms. If these could be entirely excluded the milk would keep almost in- definitely. As it is difficult under practicable conditions to com- pletely exclude the organisms from the milk, the only way in which 19 their groA^^h can be retarded or prevented, and thereby prevent the changing of the sugar into other products, is to cool the milk to a low temperature (50 degrees F.) (10 degrees C), or to heat the milk to a sufficiently high temperature (180 degrees F.) (82 de- grees C.) to destroy most of the organisms. The sourness of milk is due to the decomposition of the milk sugar into lactic acid. A given quantity of milk sugar produces a somewhat smaller amount of lactic acid. This indicates that there are accompanying by- products during the decomposition of the sugar. Blilk sugar is a white, and not very sweet powder. It is used largel.y in medicine in the preparation of pills and tablets. The ash is obtained from the inorganic salts held in solution by the milk. Although small in amount they are important com- ponents. They consist chiefly of potash, lime, soda, magnesia and iron, combined with phosphoric, hj^drochloric, sulphuric and car- bonic acids. Calcium phosphate constitutes about one-half of all the ash constituents. An enzyme, galactase, discovered by Babcock and Russel, exists in milk. This enzyme slowly peptonizes protein. Its signifi- cance and composition is not well understood. It has been suggested that it may come from the breaking down of the leucocytes. Gases occur in the free state in milk. They consist of carbon dioxide, nitrogen and oxygen. The proportion and relation of the gases vary in freshly drawn niiUv and after it has been allowed to stand for a time. Certain gases are imparted to the milk by the gland and some are formed or absorbed in the milk later. The gases formed by the gland are volatile and by cooling and aerating the milk they can to a large extent be eliminated. Certain taints of, the milk may be due to the formation of gases, as when turnips, onions and garlic are fed to cows a short time before milk- ing. The milk yielded by cows pasturing in the Alps is said to possess a peculiar, though not undesirable spicy odor and flavor. It is maintained by the Swiss that the peculiar flavor of the Em- manthaler cheese cannot be developed anywhere else in the world. This flavor they believe to be due to the kind of vegetation the cows feed upon in the Alpine pastures. Aside from the food, certain physiological disturbances may cause abnormal taints in the milk. 20 Gases or taints are absorbed into milk from its surroundings and great care should be exercised in keeping the utensils clean and the surroundings pure and wholesome. Gases may also be formed in drawn milk as the result of fermentation. Variations in the quantity and composition of cow's milk may be due to numerous causes among which may be mentioned : breed peculiarities, individual peeuliaVities, the age of the cow, the stage of the lactation period, the time and method of milking, the influ- ence of food, estruui, nymphomania, ovariotomy, abortion, exercise, disease and medicines. Excretion of foreign material with the milk occurs to some extent but not so extensively as with some other glands, for example, the kidney. Mercury is easily excreted through the udder either when this substance is taken through the digestive organs or when absorbed after applications to the .skin. Iodine and arsenic also easily enter the milk in considerable quantity. Opinions differ regarding alkaloids. It is a fact, however, that morphine, strych- nine^, atropine, and veratrine are, under certain circumstances, excreted with the milk in such large quantities as to be dangerous to the young. Other substances which can easily be excreted with milk are salicylic acid, carbolic acid, aloes, croton oil and senna, also the active principles of eolchicum, hyoscyamus, and euphor- bium. This is also supposed to be the case with mustard. Strong- smelling medicines (asafetida ether and certain volatile oils) that are given to the cows may impart a taste to the milk. It has been observed that diarrhea occurs in people who have used the milk of cows fed upon food that is moulded or that has undergone putrefactive fermentation. It is supposed that some of the substances which are formed under these conditions in the food materials of the cow may be excreted with the milk. Contamina- tion of the milk and bacterial changes must, however, be always considered in this connection. It is likely that toxic substances formed during disease, and such substances as may be reabsorbed from the uterus, may some- times be excreted in the milk, but there is not much satisfactory information on this subject. On the other hand, we know that antitoxins are in part eliminated from the blood of the mother , 21 animal through the udder and through this channel, they may be vitilized by the young with benefit. The keynote to all hygiene is cleanliness. Good food, pure air, clean surroimdings and proper care are safeguards against disease. Under these conditions specific diseases are not easily introduced and general diseases are conspicuous by their absence. There is probably no food product which should have more hygienic safeguards thrown around it than mill?;. The safety of the human race depends greatly upon it. Statistics have shown an appalling infant mortality when unfit milk has been used. Al- though pure milk is an ideal food for the young, it unfortunately appears to serve also as an ideal food for many of the organisms that prey upon the human race. The problem before the dairyman and the milli consumer at the present time is pure milk and all that it signifies. Upon the veterinarian should fall the duty of adviser as to sanitary conditions. He should be fully cognizant of the infections that can be transmitted by milk to man ; he should advise with the dairyman as to how they may be avoided. In this dual capacity he may serve as a protector of mankind and also guard the interests of the milk producer. There are certain diseases common to cattle and man and there are certain organisms of disease common to man which may be intro- duced into milk and reinfect mankind. Does milk, before it is drawn, contain bacteria that are patho- genic to man ? When the disease affects the udder there is no hesitation in answering in the affirmative ; but when the disease is without this local manifestation the question is not so easily an- swered. Some investigators maintain that such an elimination of bacteria occurs regularly, but others insist that this is not the case and that such an elimination is limited to cases where, during the course of the disease, there are local changes such as hemorrhage or inflammation appearing in the tissue of the udder. In foot-and- mouth disease the milk contains much infectious material ; bi^t the milk from cows with this disease shows a decided departure from normal, and it is not improbable that the elimination of infectious material may be associated with pathological changes in the udder. 22 In certain cattle diseases, ijathogenie organisms may become mixed with the milk during milking, and from a practicable stand- point, this has the same significance as an excretion through the udder. Some of the diseases of cattle which may cause a direct con- tamination of milk with pathogenic organisms is herewith appended: Tuberculosis. Tuberculosis of the udder is of especial interest in connection with milk sanitation, because, when this condition is present, milk is always contaminated with tubercle bacilli. In uterine and intestinal tuberculosis a great number of bacilli are eliminated with the discharges and the excretions that soil the hindquarters, so these forms may easily cause infection of the milk indirectly. This also applies to some extent to animals that have tuberculous broncho-i)neumonia. Tubercle bacilli are sufficiently resistant to live through the souring and other processes necessary in the manufacture of milk into butter and cheese, so that these products nmy contain tubercle bacilli. This has been proven by a comparatively large number of butter tests. The question as to the transmissibility of tuberculosis to man from milk and dairy products is of supreme importance. Koeli, from his researches, has drawn the conclusion that the control of meat and milk, so far as tuberculosis is concerned is unnecessary. He considers that tul)erculosis from food infection is rare in man. He doubts that tuberculosis can be transmitted from men to cattle. He is also doubtful that tuberculosis can be transmitted from cattle to man. Since the paper of Koch much research has been devoted to the points that he has brought to issue. This research has brought out the fact that tuberculosis by the food (primary tubercu- losis of the intestines and mesenteric glands) is more frequent than he affirms, although statistics vary considerably. Furthermore, observations on animals, particularly on swine and monkeys, show that it is not wise to draw definite conclusions in relation to the mode of infection from the gross anatomical lesions. Thus, for example, with swine that are infected almost exclusively through the digestive canal, tul3erculosis of the intestines is an exception, while miliary tuberculosis of the lungs often leads to a rapidly de- veloping caseoiis pneumonia. 23 With regard to the production of tuberculosis in cattle from tuberculous material obtained from man, numerous investigations have shown that such transmission may he effected by inoculation. The transmission of bovine tuberculosis to man seems to have been proven without much question. There are many observations, principally upon veterinarians and butchers, of tuberculous inocu- lation communicated to the hands and fingers through cuts while working with tuberculous organs of cattle. In some cases these were only local lesions that were healed by surgical means ; in others the disease extended to the sheaths of the tendons and glands, and in still others, in the course of time, it appeared to develop into pul- monary tuberculosis. Greater interest is attached to cases of tuberculosis from food, which may with great probability be traced to infection through milk of tuberculous animals. A large number of such cases have been given, of which the following is one of the best proven instances : In a boarding school twelve young girls became ill with signs of intestinal tuberculosis and five of them died. All came from healthy families and no source of infection v/as fomid but one cow which supplied milk for the school and was shown to be affected with tuberculosis of the udder. If one considers that tuberculosis from food is not infrequent in man, and occurs quite frequently in children, that human tuber- culosis is often transmissible to cattle, and that clinical knowledge argues for transmission of bovine tuberculosis to man, and if one considers that tubercle bacilli from cattle have been proven at least as dangerous and generally more virulent for all animals than tubercle bacilli from man, then milk containing tubercle bacilli must be regarded as most dangerous to health and the utmost care should be taken to prevent the sale of such milk. Foot-and-Moutli Disease. It has long been known that milk from cows suffering with this disease is infectious and may carry the disease to man. In the lighter forms of the disease the milk remains unchanged, but with cows badly affected there is not only a decided diminution in quantity but its appearance and composi- tion are changed. In such cases the milk becomes thin, separates a slimy layer of cream of dirty color, and there is quite abundant sediment, or, as happens infrequently, it becomes richer in fat with 24 a simultiineoiis falling i.)if in quantity. Under the microscope, leucocytes and Isroken dt)\vn tissue cells are found in greater quan- titj' than usual, sometimes red corpuscles also. The milk contains a greater quantity of albumin and globulin than usual, so that when boiled, large clumps and flakes separate and the sugar and casein fall off in quantitj^ — all changes which are symptomatic of an admixture of an inflammatory exudate. The virus may, moreover, enter the milk as it is being drawn, if vesicles occur on the teats or udder. The quantity of milk decreases notably during the course of the disease and it seldom reaches its original flow after recovery. This disease is very easily communicated by the milk to other cattle and to swine as well as man. Children are especially suscep- tible. The course of the disease in man may be light or severe and may cause death. The symptoms are : fever and weakness, conjunc- tivitis, formation of vesicles on the mucous membrane of the mouth, the lips, the ears, tlie nose, fingers or, less frequently, on other places on the body; besides nausea, vomiting, diarrhea; sometimes redness of the skin and arthralgia. It is transmissible from man to man. The virus of foot-and-moutli disease may occur in butter, buttermilk and cheese, since it is not killed by the treatment Avhich milk undergoes in their production. This virus, the appearance of which is wholly miknown (prob- ably on account of its ultramiscroscopic size), is not particularly resistant. It has been proven by experiments made during recent years in Germany that the virus dies after 10 minutes' exposure at 158 degrees F. (70 degrees C.) and by being heated at 212 degrees F. (100 degrees C.) for an instant. Cowpox. This disease attacks the teats of the cow particularly and it cannot be doubted that during the milking the virus held in the vesicles sometimes falls in the milk. Since the vaccine virus is kno^^^l to be very potent, and since man is peculiarly susceptible to it, it is evident that the disease is transmissible through milk to man. But, while there are numerous examples of direct infection on the hands and face of the milker, there are only a few observa- tions of an infection through the use of such milk. This is probably due to the fact that most persons are early immunized by compul- sory vaccination and that small children usually drink the milk 25 after it has been boiled or, at least, heated. Stern reports a case in which a large number of children became afEected with an erup- tion on the face, which healed, leaving sears, after using milk from a herd of cows in which cowpox had broken out. Anthrax. During the course of anthrax, the secretion of milk falls off suddenly and decidedly. The milk secreted is thin and its composition is siipposed to be abnormal. Several investigators have observed that the milk of cows affected with anthrax contains viru- lent bacilli. Others have found that this is not always the ease. Because the milk is often mixed with blood, following slight hemor- rhages in the udder, it is probable that the admixture of bacilli occurs chieily when such hemorrhages take place. Raw milk should not be used from a herd in which the disease has broken out as there is danger that the bacilli may enter the milk when it is drawn, be- cause the sick animals excrete bacilli with the bloody excrement and the stable, in spite of all care and disinfection, may be so thoroughly infected that there is the possibility of contaminating the mill?:. Babies. The virus of rabies, yet unknown, is especially asso- ciated with the central nervous system and the salivarj^ glands. Frecjuently it may be found in other glands and even in the udder. A number of observers have proven that the virus may be secreted with the milk. All attempts to convey the disease to healthy ani- mals, through food containing infectious material have thus far been negative, and many hold the view that there is no danger to. man from the use of milk from cows that have been bitten by a mad dog and that are themselves rabid. Since the possibility is always present that infection may occur through a slight lesion of the mouth or pharynx, milk from cows infected with rabies is to be regarded as most dangerous to health. Actinomycosis. There are no recorded observations concerning the changes in milk secretion during this disease, nor have the actinomyses or ray fungi yet been found in milk, in which they probably occu.r. Man may be infected through the digestive canal just as cattle are, and on this account the possibility of contagion through milk should not be disregarded. Milk from cows affected with udder actinomycosis (which is not often diagnosed) should not be used as food for man. 26 Other diseases which may iui'eet the milk sufficiently to make it unsafe for food are: lung plague, mastitis, "calf cholera" septic metritis, sujipurative processes, milk sickness (Central U. S. For- merly confused with anthrax). Jlilk may furthermore he contaminated with organisms of dis- eases specific to man. Serious and extensive epidemics have arisen in this way. Contamination may take place during milking, during its handling on the farm, or later, while it is being handled or stored in the dairy or market place. Sometimes this occurs from sick per- sons coming directly in contact with the milk, sometimes it occurs in an indirect way. The method of contamination differs in respect to different diseases, since infectious material may come not only directly or indirectly from persons luit may also come from the water used for cleansing the milk vessels. The human diseases which may thus be indirectly communicated ta numkind through milk are : typhoid fever, diphtheria, scarlet fever, Asiatic cholera, tuberculosis and there are even reported instances of the transmission of syphilis, and epidemics of sore throat and of erysipelas through milk. The transmission of measles, smallpox, dysentery, or cerebro-spinal meningitis has not been ob- served, but the possibility of such transmission can scarcely be doubted The possibility of so many infections coming directlj^ and indi- rectly from milk illustrates the great importance of dairy hygiene. This importance is becoming more and more appreciated and the da.y is not far distant when the services of cultured and competent men will be increasingly in demand to protect the interests of the dairymen and to safeguard the public health. These men should be veterinarians. PHYTOLACCA DECANDRA ROGER D. HYDE According to the locality in which it grows and the uses to "which it is put Phytolacca has numerous synonyms. The following are those most frequently encoimtered : Poke, poke berry and root, garget, garget berry, coeuni, coaeum, jalap, skoke, scote, scoke jalap, American nightshade, red nightshade, cancer root, jalap cancer root, chougras, red weed, red ink plant, red ink berry, crimson berry plant, pocan bush, Virginia poke, mechoacan, American currant, dyer's grapes. In Germany it is known as the scharlachbeere and kermesbeere. In France it is known as agouman, morelle a grappe. In Spain it is called namoli. jabonera. The word Phytolacca is derived from the Greek word ' ' phyton ' " — a plant — and the Latin word "lacca" — lake — having reference to the crimson color of the juice of the berries. Phytolacca is native to the Ignited States, from ^Maine and northern Illinois to Florida and west to Texas, eastern Kansas and southern ilinnesota. It is also fomid in northern Africa, China, southern Europe, the Azores and Sandwich Islands. In America it grows commonly along fences bordering fields, in rich, moist unculti- vated spots or waste grounds ; also in clearings along roadsides. It has been regarded as a weed in the United States, but in Europe it is valued as an ornamental garden plant. The plant is a smooth, rank, succulent perennial and reaches a height of six to eight feet, although in the Southern States it may grow as high as twelve feet. The root is very long, woody and thick, like the horseradish root. The stems of the plant are purplish green and hollow, with thin transverse partitions at intervals. The leaves are large and alternate. There are numerous clusters of small greenish white flowers, which blossom throughout the summer, and are followed in the autumn by shining purple black berries. From the root is obtained a rich purple juice, which, in Europe, is some- times used to color wines. The root contains numerous starch 28 grains, tannic acid, g'uiu, sugar, resin, a fixed oil, lignin and various: inorganic substances. The root should be gathered in the latter part of the autumn, washed, sliced and carefully dried. It loses strength with age. The leaves make the plant, with its height and purple berries, a very beautiful and striking plant. They should be gathered .just before the fruit ripens. The leaves are said to have the property of destroying epithelioraata. For this purpose they are bruised to a pulpy mass and the juice from them is collected on a plate, evapor- ated to a thick, pasty consistency. It is then spread upon a cloth and laid upon the tumor. It is supposed to have a selective action upon the morbid tissue and to cause its liciuefaction and removal. It then acts as a cicatrizant for the open sore. As soon as all morbid tissue is destroyed a bed of cicatricial tissue begins to form from the periphery towards the center and, as this occurs, the plaster should be cut smaller each day, like the shape of the healing tumor. It is claimed that a large tumor can be cured in a few weeks in this manner. The fruit or Ijerries form close and heavy agglutinated purple black masses. There is little odor but there is an acidulous, sweet- ish, acrid taste. Some claim that the berries are poisonous, others that they are harmless, but that the seeds are harmful. Birds are known to eat the berries without injury. The berries arc said to lose their toxic power somewhat when cooked and some people have made pies of them, but this practice is not to be recommended. Nearly all claim that the juice of the berries is harmless and the Turks are said to have used it for tinting candies. The juice contains sugar, which when fermented yields alcohol by distillation. The chemical composition of Phytolacca is peculiar. Its active and poisonous constituent is a bitter acrid substance, similar to, if not identical with, saponin. The root is remarkable for the great amount of potassium in it. It exists as potassium oxide and nitrate to the amount of 5.56% in the dried root. A splinter gives a violet coloration in the Bunsen flame. A ciuantitative analysis of poke root is given as follows : fatty oil and wax 0.6%; bitter resin 1%.; non-reducing sugar 0.4%,; proteids 1.94% ; amido compounds 1.6%, ; probably free formic acid 29 0.36% ; potassium formate 1.9% ; starch 11.68% ; calcium oxalate 6.2% ; nitrates 2.4:% ; cellulose 16.4%< ; lignin 3.2% ; gum, coloring matter, ash and moisture 42.75%. Claussen obtained from the seeds a neutral principle, which he called phytolaccin. The parts of the plant used officially are the fruit and the root.. The leaves are sometimes used in the form of decoctions and poul- tices, and the .juice in plasters. There are resinoid preparations of the berries which are said to be the basis of the so-called anti-fat cures. Antagonists to phytolaccin are alcohol, ether, opimn, digitalis, strychnine and atropine. The synergists are the motor depressants, emetics and paralyz- ers. Externally the powdered root is irritating to the mucous mem- brane of the nose causing sneezing and burning, and may produce in certain subjects erj^thematous eruptions and excoriations. Digestive System. Phytolacca is an emetic and cathai'tic. It causes great nausea, with much depression, lasting some time before vomiting occurs. Besides being a laxative it augments the secretion of the bile. Brunton claims that it is a powerful hepatic stimulant. Upon the circulatory system, it reduces the force and frequency of the heart's action and lowers arterial tension. Upon the nervous system, Phytolacca is a powerful motor de- pressant. It acts as a direct paralyzant to the spinal cord and medulla. It is said to be somewhat hypnotic. The respiration is depressed and the breathing becomes slow and shallow. Toxic doses cause death by paralysis of the respira- tory center. The drug is readily absorbed by the digestive organs and elimi- nated principally by the kidneys. Poisoning. Most instances of poisoning arise when the plant has been used as a medicine by laymen, but there are also accidental cases due to eating the root which has been mistaken for artichoke, parsnips or horseradish. Some claim that the plant is one of our most violently poisonous plants, especially when fresh. In early 30 spring before the foliage comes, the roots are sometimes grated and eaten, being mistaken for horseradish and toxic results follow. The greens are also sometimes eaten and thorough cooking seems to de- stroy their toxic effects, but if incompletely cooked pois/ming will occur. The symptoms of poisoning are vertigo, swelling of the eyelids, watering of the eyes, photophobia and dimsightedness. There may be the sensation of roaring in the ears. Pain in the muscles and bones of the arms. There is weakness of the heart, intermittent pulse and occasional pain in the cardiac region, There may be coryza, a sen- sation of constriction in the larynx, coughing and difficult breathing. There may be either diminished appetite or unusual hunger, violent thirst, eructations, nausea and repeated and violent vomit- ing, (human) , pain in the stomach and violent pain in the regions of the liver and kidney, colic, frequent discharges of offensive flatus, infrequent diarrhttic stools which may be painless or with tenesmus. There is increased urination with the color considerably dark- ened and with increased deposits. In the Journal of Comparative Medicine and Veterinary Archives for July, 1902, Dr. G. R. White describes a case of poison- ing in cattle by Phytolacca. He found that the cattle had not eaten for four days. They were at first constipated but later passed mucus and clots of blood from the bowel. The animals were spiritless and held their noses close to the ground. Their eyes were sunken, backs arched, high fever and their muzzles were dry and hot and there was also a slight discharge from the nose. There was loss of appe- tite, cessation of rumination and a staggering and weak gait. The disease was at first pronounced hemorrhagic enteritis with dysen- tery, but upon investigation the field where the cattle had run two days, thousands of poke plants were found, hundreds of which had been eaten off even with the ground. The evidence seemed fairly conclusive that the plants were the cause of the trouble. The Treatment is to give absolute repose and warmth, as move- ments are likely to induce retching. The stomach should be emptied by means of a stomach pump and morphine administered hypoder- mically to lessen the pain of the cramps and to support the heart. 31 ._itryclniine may be given to stimulate tlae respiration. Antiemetics are also imlieated. Therapeutics. Pliytolacca is credited with being one of the best remedies for the treatment of mammitis. It may be given both internally and externally for this purpose. It has also been recom- mended for ring worm, ulcers, scabies and favus. Brunton recom- mends its use in the form of a strong decoction or infusion of the root for piles, skin diseases and cancer. It has also been used to allay inflammation, as in follicular pharyngitis, tonsilitis, buboes, burns, abscesses and chronic edema. Its use internally and locally has been recommended for sore nipples, orchitis, varicose ulcers, parasiticide and as a dressing for cancers. It is claimed that birds which ate pliytolacca berries were seen to lose flesh. The drug is said to act upon the lacteal vessels and mesenteric glands so as to retard the taking up of the fatty elements of the food by the lacteals and an insufficient elaboration of their contents by the mesenteric glands, so that this important channel of nutrition is less active. In this way the drug is said to act as an antifat. The drug is contraindicatecl in subacute or chronic conditions, or when the heart's action is weak, or when there are catarrhal con- ditions in the stomach. The contraindications are much the same as for aconite or veratrum viride. Experimental. In order to test the antifat action a fat tom-cat was experimented upon. This cat had been castrated three or four years previously when a kitten, and in the meantime had become cjuite obese. The experiment covered a period of eight weeks and the cat was weighed daily and the average taken for each week. On the second, fourth, sixth and eighth week the cat received increasing doses of the fluid extract of pliytolacca. The range of the dosage was from five minims the first week to twenty minims, twice daily, during the last week. During the odd weeks there was no medicine whatever administered. The average weight for the first week was 9 lbs. 2 ozs. For the next week, while the medicine was administered, the average weight increased 1 lb. 9 ozs. The average for the third week showed a de- 32 crease of 11 ozs. ; for the fourth week ( Phytolacca) a decrease of 10 ozs. ; for the fifth week a gain of 11 ozs. ; for the sixth week (Phyto- lacca) a gain of 7 ozs, ; for the seventh week a gain of 2 ozs. ; for the eighth week (phytolacca) a gain of 2 ozs. At the end of the experi- ment the cat weighed on the average 1 lb. and 10 ozs. more than he did before the drug was administered. The result was unexpected. ISome other preparation than the fluid extract might have been more efficient for fat reduction and the fact that the animal had been cas- trated may also have had some bearing on the result. Another experiment was tried upon a normal kitten which weighed 2 lbs. and 1-2 oz. The kitten was given 10 minims of the fluid extract of phytolacca and on being weighed two days later was found to have lost 2 ozs. Increasing doses were given up to 1 dram and at the end of the experiment the weight of the animal was found to be 1 lb. 12 ozs., a loss of i 1-2 ozs. The larger doses caused restlessness, depression and purging but with eventual recovery. Ten experiments were tried upon horses in order to determine the effect of phytolacca upon the temperature, respiration and pulse. The following details of experiment No. 6 appear to be typical of the most of the experiments and are herewith given. The animal was a light bay gelding weighing about 1000 lbs. One ounce of the fluid extract of phytolacca was administered in a half pint of water at 9 a. m. Temperature Respirations Pul (Normal) 9:00 a. m. 100.4 U 47 9:30 a. m. 100.4 13 46 10:00 a. m. 100.8 14 33 10:30 a. m. 100.9 15 32 11:00 a. m. 100.6 15 37 11:30 a. m. 100.1 15 44 The animal passed wind but suffered no distress. There was no diarrhea and the following day the feces were of normal consistency. The dosage ranged from 1-2 to 2 1-2 ozs. of the fluid extract. In only one case was there diarrhea and this persisted for two days. Two other horses showed evidences of slight diarrhea but it was not at all persistent. In nearly all cases there appeared to be increased peristalsis and more or less flatus. 33 The effects upon the temperature, respiration and pulse were not uniform. In some cases there was a slight increase and in others a decrease, but the variations in all were confined to narrow limits. Experiments upon the heart of the frog showed that the drug had a depressing action and finally caused paralysis of that organ. An experiment was tried upon a human subject in order to de- termine the effect upon body metabolism as shown by variations in the urinary excretion. The experiment covered a period of five weeks, the urine being examined each day for six days of each week. The examinations for the first week were upon the normal urine. In the second week the drug was begun in doses of 10 drops of the fluid extract after each meal. The dosage was increased until in the latter part of the fourth week 50 drops were being taken. None of the drug was taken during the fifth week, but the urinary examinations were continued in order that a comparison might be made between the fore-period (normal), drug period and after-period. During the third week while 35 drops were being taken a slight sensation of dizziness was experienced each time the drug was taken. The medi- cine was, however, continued in increasing doses but there were no further effects of this character. Throughout the entire experiment the drug did not produce an emetic or purging effect, but it seemed to increase the appetite. Average for Average for Average for Fore Period Drug Period After Period Amount for 24 hours 666 pc 740 cc 616 cc. Specific gravity 1025 1025.5 1028.6 Reaction Acid Acid Acid Solids (24 hours) 38.62 43,47 66.8 Chlorides (24 hours) 10.32 13.58 18.74 Phosphates (24 hours) 1.75 1.80 3.32 Sulphates (24 hours) 1.89 2.08 2.2S Urea (24 hours) 17.75 18.37 16.6 Uric Acid (24 hours) 27 .43 .42 There was a trace of indican, a few pavement epithelial cells and crystals of calcium oxalate found throughout the whole experi- ment. In addition to the uses of the drug already enumerated it was 34 used in the form of an ointment upon some dogs suffering from skin trouble. The ointment was made up in the proportion of 1 oz. of the po\vdered root to 7 ozs. of benz(.)inated lard. This was found to be somewhat irritating and the proportions were reduced to 1 to 12. The effect was beneficial in some cases but not in all. The drug is of undoubted value especially as an alterative and. is of considerable use in those cases in which it is especially indicated. TABLE OP CONTENTS. PAGES Canine Tetanus P. A. Fish 3. The Diastases in the Saliva of the Dog and Cat, Charles E. Hayden 5 A Fly-Blown and Distempered Dog P. A. Fish 15 Blood Examination of Dermatoses in Dogs. .Howard Welch IT A Case of Auto-Enterectomy in the Bitch P. A. Fish 35 CANINE TETANUS. Pierre A. Pish. A St. Bernard dog aged nine months was brought to the clinic. The owner stated that the dog had some difficulty in swallowing and as the throat appeared slightly swollen he suspected that the trouble might be sore throat. A calomel jjurge was given without effect. No evacuation of the bowels occurred until the fourth day. vin the meantime, injections of 1/10 grain eserine and 1/6 grain pilocarpine had been administered, accompanied by epsom salt enemas. AA^hen entered, the symptoms of tetanus were not very positive ; but very shortly the stiffness of the body increased quite perceptibly, the membrana nictitans covered a portion of the ej^eballs and the ears were somewhat retracted and drawn toward the median line, causing the skin of the forehead to wrinkle. The nose was some- what uplifted as if the animal were sniffing. This retracted con- dition was probably due to the stiff'ening of the nasal muscles. The dog's condition appeared to remain stationary for a few days. Shortly before the patient was received, the writer had read with much interest an article by Dr. Wilber Fisk Sterman on ' ' The Surgical Treatment of Tetanus." References were made in this article to the cure of some horses by this procedure. The theory of the treatment appeared to be that in addition to, or independently of, any formation of toxin, the cause of the trouble was gas, devel- oped by the organisms, and that the gas was found to be present in unusual quantity beneath the meninges of the brain or, as a later reference intimated, even in the ventricles of the brain. Under these conditions, when the cranium was trephined and the dura penetrated, there would be c[uite an audible hiss from the escaping gas. In some cases this was said to result in quite rapid recovery without further treatment. In other cases it might be necessary to penetrate through the nervous tissue or as one reference put it, to "bore for gas," as far as the ventricle. The case in hand seemed to offer an excellent opportunity for testing the surgical treatment of the disease. The dog was placed under the influence of anesthetics and with a trephine a small button of bone was removed from the cranium just to the right of the longitudinal fissure between the two heniicerebrmns. The dura was ripened but there was no evidence of escaping gas. The surface of the brain was touched and a small portion of the pia loosened but with no trace of gas. The surface of the brain, however, seemed unduly irritable whenever touched. The opening in the cranium was left. The skin was not sutured until a half hour later and then with only a stitch or two, in order that if any gas should perchance be escaping there might still be an exit for it. It was thought that healing might be delayed until all of the gas had escaped. Shortly after the operation the writer was called out of town for a short time. Directions were left for the care of the patient. Two days after the operation the dog was chloroformed to death in order to relieve his suffering. The writer was informed that the dog did not improve after the operation but grew steadily worse until chloroformed. During the course of the treatment a sore was found upon one of the dog's toes, where, probably, the infection began. The wound received the usual carbolic acid treatment. Fig. 1. A photograph of the patioit. The stiffened atlitiide, the lialf elosed eyes, the upraised nose a)id tlie drairinej of ttie ears toward the median line are more or less elearbj shown. Pig. 2. Another case of tetanus i)i the dog. The symptoms and conditions are similar to those in figure 1. The nose is someu'lmt more retracted. The muscles are tense and because of tJie short hair the outline of certain muscles or groups of muscles are quite dis- tinctly visible through the skin, especially in the hind quarters. THE DIASTASES IN THE SALIVA OF THE DOG AND CAT. Charles E. Hayden. Literature. — There is a large amount of literature pertaining to the salivary glands, their secretions and the active principles of these secretions. Conditions which influence secretion have also been given a great deal of attention. Early day investigators dealt with manj' of the same Cjuestions in regard to salivation which are holding the attention of present day workers. Bernard was one of the earliest and foremost to engage in this problem. One paper of indirect interest in connection with this work is that of Carlson, Greer and Becht ^ showing tlie relation of the blood supply to the submaxillary glands and the character of the chorda and sympathetic saliva. Heidenhain's theory of the trophic nerves is here disputed and held to be untenable. They find that decreas- ing the blood supply decreases the quantity of saliva and increa^ es the solid constituents of both chorda and sympathetic saliva. Another paper of like interest is that of McLean - giving evi- dence of vaso dilator fibers to the submaxillary gland of the cat. Still another bearing on the same subject as the preceding is the joint work of Carlson and McLean.^ They present further evi- dence of the relation of oxygen supply to the salivary glands to the composition of the saliva. Their evidence shows that decreasing the oxygen supply increases the solid material in chorda and sub- maxillary saliva. In dealing with the blood supply these papers are pertinent to the subject matter in that they show some of the manifold condi- tions affecting the rate, quality and quantity of the salivary secretions. The diastases in the blood and lymph are showTi to vary in concentration in the following order in the various fluids named: serum, thoracic lymph, neck lymph, leg lymph, pericardial fluid and cerebrospinal fluid. As a supposition the liver is said to be the possible organ of the production of the diastases. The portal and hepatic veins, how- ever, are said to have the same amount of diastatic ferment. Ex- tirpating the pancreas eliminates it as an organ of production, for it does not lessen the amount of diastase in the blood fluids. They are increased under anaesthesia due to possible increased destruc- tion and elimination and decreased production. As a result of elimination the urine often shows a diastatic effect. Numerous experiments made by the authors upon cats, dogs and chickens fed upon a carbohydrate diet show that there is no relation between the concentration of the enzyme and the natural diet. The enzymes of the blood and lymph are stated to be the discards of the tissues in general and of no particular organ of the body. Following the preceding statement that there is no relation between the concentration of the enzymes and natural diet, it is well to consider the results obtained by four different pairs ' of experimenters upon the adaptation of the salivary secretion to diet. Of these, three pairs "^ find results that show adaptation, one pair ^ finds results that do not. Two ^ deal with the human saliva, two " with that of the dog and cat. The last two find results that are of interest in connection with the subject matter of this paper. One pair " maintains that the dog's saliva is inactive under carbohydrate diet, the other ^^ that the saliva is active under the same conditions, and in eight different animals tested, they report sugar ranging' from .0133 to .054 gram. Reducing substances ^- have been demonstrated in the submaxil- lary and parotid saliva of the cat and the substance is shown to be glucose by crystal formation and by the fact that these crystals melt at a temperature very near that of the melting point of glucose. The glucose of the saliva is said to be that of the l)lood eliminated by the salivary glands. The claim is made that the sub- maxillary secretes more sugar than the parotid gland and that the amount is increased under ether anaesthesia. The last fact is ac- counted for by the production of a condition of hyperglycemia. Work has been carried on by A. J. Carlson and J. C. Ryan ^" upon the saliva of the dog and cat. They demonstrated the presence of an enzyme in the saliva of the cat. They say that in all proba- bility there is none in that of the dog. Host of the work was carried! on Avith the saliva of the eat. Only a few experiments with that of the dog. The concentration is found to be greater in reflex or chorda or pilocarpine stimulation under ether anaesthesia than in; any other condition. Concentration is greater in almost every in- stance in the sympathetic than in the chorda saliva. The same con- dition prevails comparing the blood serum with the saliva. Human ptyalin and pancreatin in.jected into the blood increased the enzyme, giving rise to the hypothesis that blood and lymph furnish the enzymes of the salivary gland. Only two of their experiments show a starch splitting ferment in the saliva of the clog. Method. — Seven sets of tests were made in this investigation. Salivary extract was tested qualitatively and ciuantitatively for the presence of sugar. The quantity of reducing sugar in the salivary extract with and without starch digestion ; in the serum under the same condition and the cjuantity resulting from the digestion of starch with saliva have been made the basis for the conclusions drawn in our experiments. The method of obtaining the salivary extract was the same throughout. The glands were macerated in 1% acetic acid, one cc. for each gram of gland substance and then ten cc. of chloroform water was added for each gram of gland sub- stance. The maceration was carried on as carefully as possible and the extract allowed to stand at least twenty-four hours before test- ing. The saliva Avas obtained in several different ways. Pilocarpine was used on two cats anci an attempt made to use arecoline upon another. These two drugs were found unsatisfactory. The animals struggled too much, and since cannulae were not inserted in the salivary ducts they swallowed most of the saliva making it difficult to collect. Both drugs made the eats sick after a short time. The method finally adopted was that of light ether anaesthesia. A few cc. of the saliva were collected. The saliva was always tested at once with 1% starch solution and was incubated for a. period of 120 minutes or longer at a temperature of 37 or 38° C. There were some variations in time and slight ones in temperature in a few of the experiments. The serum was not taken from the animals on the same day as the saliva but it was obtained as clear as possible. The blood in some experiments was taken from that, passing through the heart and in otliers from the carotid artery. As a reagent for reducing sugar we first used Fehlings. It was dif- ticult, however, to standardize for quantitative worlv and proved less isatisf actory than Benedict 's " solution which was tiie one used. It is composed of three solutions. Solution A. Crystalized CuSo, 69.3 gm. Distilled water to 1000 cc. Solution B. Crystallized Rochelle salt 346 gm. Pure anhydrous Na,Co3 200 gm. Distilled water to 1000 cc. Solution C. Potassium sulpliocyanide 200 gm. Distilled water to 1000 cc. The formula for a fourth solution is given by the author. The solution is to alternate with solution C. and its purpose is to make ■the test more sensitive when foreign substances such as chloroform .are found iu-the fluid to be tested for sugar. Solution D. Potassium ferrocyanide 30 gm. Potassium sulpliocyanide 125 gm. Anhydrous Na.COj 100 gm. Distilled water to 1000 cc. A solution containing sodium carbonate is said to have the advantage over one containing sodium hydrate in that it does not decompose so readily. The third solution gives a white precipitate when all the copper in the solution has been reduced. The three solutions are mixed in equal proportions and are more sensitive than Pehling's solution. Prom two to five grams NaaCog are an aid in testing for dilute sugars. Two sets of solutions were used, the first being standardized to .076 gm. sugar for each 10 cc. of copper solu- tion. The second to .078 gm. Our practice when testing for sugar was to add a certain number of cc. of the solution under digestion and then add enough 1% dextrose from a burette to completely reduce the copper solution. The method of computing the number of grams of reducing sugar per cc. in the digested solution was as follows: — Suppose 6.6 cc. of 1% dextrose were added to the reagent mixed in the proper proportions, after adding 10 cc. of the digested product. 9 6.6 cc. of 1% sugar equaled .066 gm. of sugar. .076 gm. minus .066 gm. equals .01 gm. sugar in 10 cc. of the solution and so would show .001 gram to each cc. of serum, saliva and salivary extract used. TABLE I. Animal Dog 1. Dog 2 Dog 3 Dog 4 Polecat Polecat Material used Salivary extract Salivary extract Salivary extract Salivary extract Salivary extract Salivary extract Amt. 1% starch used 25 cc. 25 cc. 25 cc. 25 cc. 25 cc. 25 cc. Time of digestion 90 min. 90 min. 90 min. 90 min. 90 min. 90 min. Test for sugar Pehling's Fehling's Fehling's Fehling's Fehling's Fehling's Results + + + + + • TABLE II. Animal Material tested Amount I per ct. starch used Amount salivary extract used Time of digestion Amount Reagent I per ct. used dextrose used Amount sugar per cc. extract Dogl Salivary ext. 25 CC. 25 CC. 120 m. 4 CC. Benedict's .00144 gm. Dog 3 25 cc. 25 cc. 120 m. 5.6 cc. Benedict's .0008 gm. Dog 8 25 cc. 25 CC. 120 m. 6.6 cc. Benedict's .0004 gm. Dog 4 25 CC. 25 cc. 120 m. 6 cc. Benedict's .00064 gm. Dog 5 25 cc. 25 cc. 120 m. 6.4 cc. Benedict's .00048 gm. Cat 1 25 cc. 25 cc. 120 m. 2 cc. Benedict's .00204 gm. Cat 2 25 cc. 12.5 cc. 120 m. 4.6 cc. Benedict's .0024 gm. Animal Dog 6 Dog 7 Dog 8 Oat 3 Cat 4 Cat 5 Cat 7 Cat 8 Cat 9 ■Cat 10 Cat 11 Substance tested Serum Serum Serum Serum Serum Serum Serum Serum Serum Serum Serum TABLE III. Amt. serum Amt. 1% used dextrose usedcc, 5 cc. 6.4 cc. 5 cc. 5.4 cc. 5 cc. 6.6 cc. 2.5 cc. 6.6 cc. 10 cc. 5.6 cc. 1 cc. 7.8 cc. 1 cc. 7.8 cc. 3 cc. 6.6 cc. 6 cc. 6 cc. 2 cc. 6.6 cc. 3 cc. 6 cc. Amt. sugar per cc. serum .0028 gm. .0048 gm. .0024 gm. .0048 gm. .0022 gm. None None .004 gm. .003 gm. .006 gm. .006 gm. 10 TABLE IV. Animal Snb.^tance tested Amt. I pel ct. starch used - Amt. serum u.sed Amt. I per ct. dextrose used Reagent Amt. sugar used per cc. serum Dog 6 Serum 25 cc. 5 cc. 1 cc. B enedict's .0133 gm. Dog 7 Serum 25 cc. 5 CC. 1 cc. Benedict's .0133 gm. Dog S Serum 25 cc. 5 CC. None Benedict's .078 gm. Cat 3 Serum 60 cc. 2.5 cc. 5.6 cc. Benedict's .0088 gm. Cat 4 Serum 60 cc. 10 CO. None Benedict's .078 gm. Cat 5 Serum 25 cc. 1 cc. 4 cc. Benedict's .038 gm. Cat 7 Serum 25 cc. 1 cc. 4.2 cc. Benedict's .036 gm. Cat 8 Serum 25 cc. 3 cc. 3 cc. Benedict's .016 gm. Cat 9 Serum 25 cc. 6 cc. None Benedict's .013 gm. Cat 10 Serum 25 cc. 2 cc. 2 cc. Benedict's .029 gm. Cat 11 Serum 25 cc. 3 cc. 2 cc. Benedict's .013 gm. Time of digestion 120 min. TABLE V. Animal Substance tested Amt. 1 per cent starch used Amount Time of Antt. I per Reag^ent saliva digestion ct. dextro.se used used used Aral, sugar per I cc. saliva Dog 6 Saliva 25 cc. 5 cc. 120 min. 7.8 cc. Benedict's None Dog 7 Saliva 25 cc. 2 cc. 120 min. 7.8 cc. Benedict's None Dog S Saliva 25 cc. 5cc. 120 min. 7.8 cc. Benedict's None Dog 9 Saliva 25 cc. 10 cc. 17.5 hrs. 5.8 cc. Benedict's .002 gm. Cat 4 Saliva 25 cc. 3cc. 120 min. 6.6 cc. Benedict's .004 gm. Cat 5 Saliva 25 cc. 1 cc. 120 min. 6.8 cc. Benedict's .01 gm. Cat 6 Saliva 25 cc. 2cc. 120 min. 7 cc. Benedict's .004 gm. Cat 7 Saliva 25 cc. 2cc. 120 min. 6.8 cc. Benedict's .005 gm. Cat S Saliva 25 cc. 3 cc. 120 min. 5.8 cc. Benedict's .0066 gm.. Cat 9 Saliva 25 cc. 6cc. 15 hrs. 6.4 cc. Benedict's .0023 gm.. Cat 10 Saliva 25 cc. 2cc. 120 min. 6 cc. Benedict's .009 gm. Cat 11 Saliva 25 cc. 3cc. 120 min. 6.8 cc. Benedict's .0033 gm. TABLE VL Animal Substance te.steJ Amt. extract Reagent used u.sed Amt.l % Amt. sugar dextro.se per 1 cc. used extract Dog 6 Salivary extract 10 cc. Benedict's 7.4 cc. .0004 gm. Dog 7 Salivary extract 10 cc. Benedict's 7.4 cc. .0004 gm. Cat 4 Salivary extract 20 cc. Benedict's 6.6 cc. .0006 gm. Cat 5 Salivary extract 1 cc. Benedict's 7.8 cc. None Cat 7 Salivary extract 10 cc. Benedict's 7 cc. .0008 gm. Cat 8 Salivary extract 3cc. Benedict's' 6 cc. .009 gm. Cat 9 Salivary extract 6 cc. Benedict's 7.6 cc. .0003 gm. Cat 10 Saliv, ary extract 2cc. Benedict's 7.6 cc. .001 gm. Cat 11 Saliv ary extract 3cc. Benedict's 7.8 cc. None 11 TABLE YII. Animal Dog Dog 6 Dog 7 Cat i Cat 3 Cat 7 Cat 8 Cat Cat 10 Cat 11 Substance tested Salivary extract Amt. I per ct. Amt. Time of Amt. I per Reage ice starch extract digestion ct. dextrose used I used used used 9 starch used 60 CC. 23 CC. 25 CC. 60 CC. 25 CC. 23 CC. 25 CC. 23 CC. 25 CC. 25 CC. Amt 2xtra, used 23 CC Reagent CC. 3 CC. 25 CC. 1 CC. 2 CC. 6cc. 6cc. 2cc. 3 CC. 120 min. 120 min. 120 min. 120 min. 120 min. 120 min. 3 hrs. 120 min. 120 min. 120 min. used 6.4 CC. 7.2 CC. 7 CC. 6.4 CC. 7.2 CC. 7.4 CC. 7.4 CC. 6.6 CC. 7.4 CC. 7.4 CC. Amt. sugar per I CC. extract Benedict's 0.00052 gm. Benedict's Benedict's Benedict's Benedict's Benedict's Benedict's Benedict's Benedict's Benedict's 0.0012 gm. 0.0016 gm. 0.00096 gm. o.oos 0.002 0.0016 0.002 0.002 0.0013 gm. gm. gm. gm. gm. gm. Eesults. — 1. The salivarj' extract from all the animals used showed reducing substances present, except in two cats recorded in the sixth table. There is no question in my mind but that there was a reducing substance in these two cases but the failure to notice was in all probability due to the minute amount of extract used, there being only one cc. in one case and three in the other. Ac- cording to the discussion in the literature ^' on the subject the reducing substance is glucose or at least it is to be inferred that it is since the saliva is shown to contain glucose. In the fir.st series of experiments recorded in Table I the salivarj' extract of four dogs and two polecats tested with a fresh Fehling's solution showed sugar to be present in every case. Ac- cording to the results recorded in the second table the extract of five dogs, four of them being the same as recorded in the tirst. sugar was found to be present in quantities as low as 0.00064 gm. and as high as 0.0008 gm. Two eats showed 0.0024 gm. and 0.00204 gm. of sugar. Five of the seven cats and two dogs recorded in Table VI also showed sugar. The average amount is a little higher in the extract from the cat than that from the dog. Comparing the amount of sugar for each cc. of extract used as recorded in Table VI without starch and in Table VII with starch we find that there is more sugar in every case except one recorded in Table VII. The difl:'erence in every instance is marked. The two cases in which no sugar was found in the extract alone showed 0.008 and 0.0013 gm. 12 when digested with starch. The increase in sugar is as high as €.0017 gm. except where no sugar M'as detected in the extract and there it is higher. 2. The saliva of cats after having acted on starch showed a higher i^ercentage of sugar than the salivary extract under the same conditions and a much higher percentage than the extract not having acted on starch. The difference in the first comparison was from 0.0003 to 0.0077 gm. of sugar. Of the four dogs recorded in Table V three produced negative results. Positive results were obtained in one case with a record of 0.002 gm. of sugar but that was after a period of seventeen and one half hours' digestion. These results were more in accord with those of Mendel and Underbill ^^ than those of Neilson and Terry." One of the four ' 'dogs was kept in the kennel for at least five weeks on a diet of dog biscuit and gave a negative result. 3. With one or two exceptions the saliva, serum and salivary extracts were obtained from the same animals. The tests which have laeen made the determining factor are those in which the three substances last named have been taken from the same specimen. The results from serum alone and serum plus starch have been re- corded in tables three and four. In two cases where a small quantity of serum was used it took the full amount of one per cent, sugar solution to reduce 10 cc. of the copper solution. In tliese tests sugar was found after the action of serum upon starch. In the serum we found that sugar was present in a few instances in quantities equal to or greater than the ciuantity obtained from the action of saliva upon starch and in ■every instance the amount obtained after digesting starch with serum was greater than that obtained from saliva and starch. There is more sugar and enzyme in the serum than either salivary •extract or saliva itself. Conclusions. I. The saliva, salivary extract and serum of the cat each con- tain reducing su.gar. 13 II. The sevuiii of both dog and eat eoiitaia a greater quantity of rediieiiig sugar per unit volume than either the saliva or salivarA-* extraet. III. The saliva, salivary extraet and serum of the eat eaeli showed a greater amount of redueing sugar after digesting a one per eent. stareh solution. IV. The diastatic power of blood serum is greater than that of the saliva in the cat and dog. V. The salivary extraet and serinu of the dog showed diastatic power in these experiments but the saliva gave such results in only one out of four tests. YI. The conclusions drawn are similar to those of Carlson and Lnckhardt ^'^ that no enzymes are produced in the salivary glands of the dog and cat but are in all probability discards of the tissiae in general. Bibliography. 1. A. J. Carlson, J. R. Greer, and P. C. Becht : American Journal of Physiology, Oct. 1907. Vol. 20. -. F. C. ilcLean : American Journal of Phj'siology, July, 1900. Vol. -22. 3. A. J. Carlson and F. C. McLean : American Journal of Physiology, January, 1908. Vol. 20. 4. A. J. Carlson and A. B. Lnckhardt : American Journal of Physiology, Dec, 1908. Vol. 23. 5. Hugh C. Neilsou and Oliver P. Terry : American Journal of Physiology. :March, 1906. Vol. 15. ilendel and Underbill : Journal of Biological Chemistry. Vol. III. Xeilson and Scheele. : Journal of Biological Chemistry. Vol V, 1908-09. Xeilson and Lewis : Journal of Biological Chemistry. Vol IV, 1908. 6. X^eilson and Scheele. Neilson and Lewis. Neilson and Terry. Reference V. 14 7. Mendel and UnderhiU. Eeference Y. S. Neilson and Lewis. Neilson and Selieele. Eeferenee V. 9. Neilson and Terry. Mendel and Underbill. Reference V. 10. Mendel and Underbill. Reference V. 11. Neilson and Terry. Reference V. 12. A. J. Carlson and J. C. Ryan : American Journal of Pbysiology, April, 1908. Vol. 21. 13. A. J. Carlson and J. C. Ryan : American Journal of Pbysiology, July, 1908. Vol. 22, 14. Stanley R. Benedict : Journal of Biological Cbeuiistry. Vol. Ill, 1907. 15. A. J. Carlson and J. C. Ryan : American Journal of Physiology, April, 1908. Vol. 21. 16. Mendel and Underbill : Journal of Biological Cbemistry. Vol. Ill, 1907. 17. Neilsou and Terry : American Journal of Pbysiology, Mareb, 1906. Vol. 15. 18. A. J. Carlson and A. B, Luckbardt : American Journal of Physiology, Dec, 1908. Vol. 23. A PLY-BLOWN AND DISTEMPERED DOG. Pierre A. Pish. The subject was a young collie pup four months of age. The owner suspected that the clog might be suffering from rabies from the fact that the dog had been acting in a peculiar manner for some days past. Among the symptoms noted were frothing at the mouth, howling without apparent cause, running about the fields in an excited manner apparently without purpose, and a generally wild appearance and behavior. An examination of the dog showed that in the dense hairs along the spine from the neck to the scrotum there were hundreds of maggots, many of them imbedded in the skin. The dog had evidently been tiy-blown and the rabid symp- toms were undoubtedly due to the pain caused by the burrowing of the maggots into the skin. The treatment consisted in cutting the matted hair away from the infested areas and giving the dog thorough baths in a disin- fectant solution of one of the coal tar products (similar to creolin). After the bath, many of the maggots came to the surface of the skin, as the disinfectant was evidently disagreeable to them. Some had burrowed so deeply or were protected from the disinfectant by the other maggots, that it was necessary to pick them out with a fine forceps to remove them. Each day for a few days, some Sanitas soft soap was applied to the affected areas and allowed to remain for half an hour or more before being washed off. A few applications and baths were suffi- cient to completely remove the maggots. The cutaneous woimds were treated with a powder consisting of iodized starch and boric acid. They took on a cleaner and healthier appearance and eventually healed very nicely. While the hair was being clipped from the body a few cutan- eous eruptions were noticed along the belty. This in connection with a lack of appetite and generally depressed and emaciated con- dition suggested the onset of distemper. The temperature was not found above normal. A good dose of calomel, santonin, podophyllin 16 ami Sddiuiu bicarbonate was given with the idea of thorcmghly cleansing the intestinal tract and removing any worms that might be present. Xo worms were found. Further treatm(mt consisted of the administration of one dram doses of the fiuidextract of Echinacea or Echafolta, twice daily. These preparations are relatively non-toxic and either of them may be administered in dram doses with impunity. The patient received treatment for two weeks and made an excellent and complete recovery. BLOOD EXAillXATION OP DEMIATOSES IN DOGS. Howard AVelch. This work was midertaken with a view to determining- the con- dition of the blood of dogs suffering from the various dermatoses, both parasitic and non-parasitic in nature. Investigations of the various skin diseases in man have estab- lished definite changes in the blood, which can be best illustrated by the following taken from Cabot : Eosinophiles Diseases Leucocj'tes per cent Reporter Psoriasis 8,600 9.8 Zappert Scleroderma 16,690 9.4 Zappert Scleroderma 9,000 7.7 Zappert Chronic Eczema 8,600 9.9 Zappert Chronic Eczema 22 Brown Chronic Eczema 45 Bettmann. Herpes tonsurans 13,000 1.5-24 Andry Pemphigus 5,300 33 Zappert Pemphigus 10,600 14.1 Zappert Pemphigus 1,640 29 Zappert Assiuning that the normal number of leucocytes per cu. mm., is about 7,000 and that the eosinophile percentage is from l%-4%, the above table shows conclusively a leueocytosLs and an eosino- philia in the diseases cjuoted. In work on domestic animals suffering from dermatitis the following cases are cited (Burnett) : Diseases Animal Leucocytes Eosinophilia Reporter Herpes tonsurans Hor,se 8,500 •"■•1?6 Meier Man.°-e Dog 10,888 11 Burnett & Traum Eczema Dog 13,05.5 23 Burnett & Traum Mange Dog 7,899 5.3 Burnett & Traum Here we have similar conditions existing: a leucocytosis and an eosinophilia. To determine whether or not these blood changes were constant, the following cases of dermatitis were examined. The diagnosis of each case was based on a microscopic examina- tion of skin scrapings in 10% caustic potash. A diagnosis of mange was made on fmding the parasite of follicular mange Demodex 18 follieularum. or the sareoptic parasite Sarcoptis squamiferus. In tlie absence of any parasite and the presence of an apparently non- contagions dermatitis, a diagnosis of eczema was made. Any con- dition of the animal that might influence the blood count was noted and a stool examination was made of the j^ounger animals to de- termine the presence or absence of the ova of intestinal parasites. Blood was taken from the inside of the ear, with the usual precau- tions, and counted with Thoma's hemocytometer. using the chamber with the Zappert Ewing ruling. The percentage of the varieties of leucocytes was determined by a count of not less than 500 cells. FOLLICULAB ]\IanGE. Severe Case.s. Case 1. Brindle and white bull terrier, male, 1 j^ear. Large areas on the forehead, cheeks, throat and shoulders were bare and scurfy. The parasite was present in abundance. Patient was very lively and bright. Blood Count Varieties of Leucocytes This count shows a slight leucocytosis and a high eosinophile percentage. Case 2. Brindle bull terrier. 18 mo., female. The areas of in- fection were confined mainly to the head and neck. Patient was in good condition. No pruritus. Blood Count Red Cells 6,860,000 Leucocytes 10,000 1. Lymphocytes 16% 2. Mononuclears 3% 3. Polynuclears 70% 4. Eosinopliiles 11% Red Cells 7,480,000 Leucocytes 8,000 1. Lymphocytes 30% 2. Mononuclears 5% 3. Polynuclears 60% 4. Eosinophiles 5% This blood count is practically that of a normal dog. 19 Case 3. Brinclle English bull, 2 years, male. Badly affected with the pustular form of niauge. The skin on the neck, head, shoulders and flank was thick, bare and suppurating. The patient was marasmie and dull. Three blood counts were taken which show a leucocytosis and persistent eosinophilia. Nov, 19 Nov. 31 Dec. 1 Red Cells 6,185,000 5,800,000 6,200,000 Leucocytes 12,000 12,000 14,000 1. Lymphocytes 23% 19% 26% 2. Mononuclears 4% 6% 2% 3. Polynuclears 60% 66% 65% 4. Eosinophiles 8% 9% 7% Case 4. White English bull, male, 2 years. The areas of in- fection Avere on the cheeks, throat, shoulders, flanks, and interior surfaces of legs. Pruritus was entirely absent. Jan 10 Jan 29 Red Cells 7,200,000 6,000,000 Leucocytes 14,000 9,000 1. Lymphocj^tes 26% 34% 2. Mononuclears .3% 2% 3. Polynuclears 62% 57% 4. Eosinophiles 8% 7.5% This show^ a slight leucocytosis and eosinophilia. Case 5. Foxhound, male, 2 months. Practically the whole body was infested with the parasite, though a case of only two weeks' standing. The parasite, though widespread, was not very abundant. No blood count taken. , 1. Lymphocytes 38% Varieties of Leucocytes J 2- Mononuclears 2% ^ 3. Polynuclears 56% ( 4. Eosinophiles 5% Case 6. Brindle bull terrier, male, 1 year. The forehead, jaws, cheeks and neck were devoid of hair ; the skin was thick and scurfy. Both eyes were involved and suppurating. Feb. 13 Feb. 15 Red Cells 7,020,000 Leucocytes 12,800 1. Lymphocytes 22% 19% 2. Mononuclears 1% 3% 3. Polynuclears 64% 64% 4. Eosinophiles 13% 14% 5. Mast Cells . .4% .2% 1 • 20 In this case there was a pronounced eosinophilia, with a few mast cells which are of rare occurrence in the clog. Case 7 . White bull terrier, 2 years, male. The whole fore part of body was affected badly. Red Cells 7,520,000 Leucocytes 20,000 1. Lymphocytes 30% 2. Mononuclears 5% 3. Polynuclears 59% 4. Eosinophiles 4% A long standing case showing a high leucocytosis. The eosino- phil percentage is normal, but the number of eosin cells per cu. mm. is as high as in the preceding cases. Case 8. Brindle Boston bull, male, 1 j'ear. Practically the whole body was denuded of hair; the skin was thickened and pus- tular. The feet and legs were swollen. A bad case of mange show- ing a typical blood count: a high leucocyte count and an eosino- philia. Blood Count Red Cells 6,582,000 Leucocytes 18,000 1. Lymphocytes 38% 2. Mononuclears 2% 3. Polynuclears 51% 4. Eosinophiles 8% Light Cases. Case 9. Dog, 1 year old, male. Small areas along the lips and on the cheeks were noticeable. Blood Count Red Cells 7,260,000 Leucocytes 8,000 1. Lymphocytes 35% 2. Mononuclears 3% 3. Polynuclears 60% 4. Eosinophiles 2% In this case and the following four we have a practicallj^ nor- mal blood count. 21 Case 10. Scotch collie, female. A small, barely noticeable area existed on the side of the forehead. No other infection was seen. Blood Count Red Cells 6,428,000 Leucocytes 14,600 1. Lymphocytes 21% 2. Mononuclears 4% 3. Polynuclears 73% 4. Eosinophiles 1% The patient was convalescent from an ovariotomy operation which accounts for the leucocytosis. Case 11. Gordon setter, male, 1 year. Small areas were present on the side of the head and jaw. No blood count was taken. Differential Count of Leucocytes 1. Lymphocytes 24% 2. Mononuclears 4% 3. Polynuclears 70% 4. Eosinophiles 2% Case 12. Boston bull, inale, 6 months. Small areas of infection appeared above one eye and another on the cheek. No blood count was taken. Differential Count 1. Lymphocytes 35% 2. Mononuclears 2% 3. Polynuclears 60% 4. Eosinophiles 3% U CO (a 1 o O (D 0) 2i ^ 1| t*, <1 o3 ^5 TS s O m m S m s - d 03 s . tS O o o CZ2 6 O I— I o o m !?0 t-^ CO CO => 00 •^ CO \p o °\ iCO tH t-I to \o O d\CO \p o CO -* \o CO >P 2 \° 2 ^%H lO O (?( CO ^ CO CO t- 0:0 « 05" "^ CO" C'\ CO o\ O c'v O 00 GO ^5 CO „- CO „- o o a 60 o p o ^ 6 ui tn' t>v a CO ;>> X a 1—1 CJ (f) (M 1-H tS ® ^ ^ ^ CI ® yi ^ CC 3 "u 3 H "mi's "bo's CQ is CO CO Cl 02 ^ M « )-H CO M ■TtH j_, 10 M m CQ M on C- Ui CO > ^^ a o ^ cS ^1 -o1 1 " CD C o o ^ "3 .3 S CI < ■^ "2 o 3 3 o s>. w m f^ M E^ f^ H X3 a 1 1 1 1 j > ii 02 O <1 O o J 4J O 1-H 3 ^ O o o iD 00 •r-i 1-* ' C-t CO g p o h- 1 O O H h:; PQ <1 <1 o o CO ot «5 a >P o be ki ^ <1 T— t CO be a; ■2 o p "o ^ O ^ ffl Ol g o 9 -«^ HH hH lO CO 02 d 24 Comparing the severe with the light cases (which we may practically regard as normal animals) the blood counts show a pronounced leucocytosis. Assuming the normal leucocyte count to be 8,000 per cu. mm. (Burnett & Traum), in the eight generalized ■cases in the above table, only one (No. 2) is normal, and the highest is 20,000 (No. 7). The eosinophiles likewise are high. Burnett estimates the normal number at QYr . or 480 cells per cu. mm. In the eight eases, only one (No. 2) is normal. The other seven cases show from two to three times the normal number of eosinophiles. These changes in the blood could not be attributed to anj' cause other than the dermatitis. Saecoptic Mange. Severe Cases. Case 13. Black Persian kitten, 2 months. The head and ears "were badly affected, also slight areas on the neck. The eyes were involved. The patient was very restless and was continually scratching and rubbing the aiiected parts. Three counts were taken. Dec. 1 Dec. 3 Dec. 4 Red Cells 8,300,000 6,500,000 Leucocytes 26,000 25,000 1. Lymphocytes 21% 20% 13% 2. Mononuclears 2% 1% 1% 3. Polynuclears 46% 53% 60% 4. Eosinophiles 30% 27% 25% 5. Mast Cells .5% 1% 1% Case 14. Collie, male, 2 months. The head and ears were badly affected ; the elbows and abdomen were also infected. The ears were devoid of hair and greatly thickened with exudate and scurf. The parasites were readily found. Considerable pruritus was evident. Red Cells 6,500,000 Leucocytes 14,600 1. Lymphocytes 20% 2. Mononuclears 2% 3. Polynuclears 72% 4. Eosinophiles 6% Here we have a leucocytosis and a slight rise in eosinophiles. Case 15. Collie, male, 2 months. The whole body was more or less involved. The legs, flanks, neck and ears were seurfy and the hair quite scant. There was constant rubbing- and scratching. Red Cells 5,576,000 Leucocytes 8,000 1. Lymphocytes 14% 2. Mononuclears 47c 3. Polynuclears 74% 4. EosinopMIes S7o This dog also had distemper, which introduces a new factor to disturb the blood count. However, an eosinophilia was present. Case 16. Scotch collie, male. 6 weeks. The entire body was involved. Intense itching was evidenced by almost incessant scratching and rubbing. A count was taken when the case was first brought in. and another when the patient was discharged cured. Dec. 13 March 1 Red Cells 6,260,000 Leucocytes 13, 000 1. Lymphocytes 36% 32 7e 2. Mononuclears 1% 4% 3. Polynuclears 44% 54% 4. Eosinophiles 17% 7% "VTe observe here, with the removal of the dermatitis, a drop in the eosin count from 17 C^ to 7%. Case 17. ^Maltese cat. female. 1 year. The head and ears were bare and inflamed. The patient continually rubbed and scratched the affected parts. Red Cells 8,992,000 Leucocytes 18,200 1. Lymphocytes 8% 2. Mononuclears 1% 3. Polynuclears 82% 4. Eosinophiles 9% Another case of mange in a eat, showing leueocj-tosis and eosinophilia. 26 Light Cases. Case IS. Eugiish poiuter, female, 2 years. There were scurfy areas on the elbows and flanks. There was a moderate amount of pruritus. (convalescent from operation) Red Cells 7,840,000 Leucocytes 20,000 1. Lymphocytes 23% 2. Mononuclears 2% 3. Polynuclears 72% 4. Eosinophlles 3% Case 19. Foxhound, female, 5 months. A very mild case; there were small areas of infection around the base of the ears. Red Cells 6,182,000 Leucocytes 8,110 1. Lymphocytes 32% 2. Mononuclears 3% 3. Polynuclears 60% 4. Eosinophlles 4% These light eases give the blood counts of normal dogs. Case 20. English bull, male, 1 month. The patient was in very poor condition. The elbows and flanks were scurfy. Examination of the feces showed the presence of large quantities of the intestinal parasite Ascaris. Rachitis was also present. Red Cells 5,696,000 Leucocytes 9,860 1. Lymphocytes 35% 2. Mononuclears 8% 3. Polynuclears 56% 4. Eosinophlles 1%. The eosinoi^hiles were almost absent in this case, which is rather remarkable, as it is usually conceded that intestinal parasites pro- duce an eosinophilia. A subseciuent blood count showed no material change. 27 Cases 21, 22, 23. These three cases were mongrel collie puppies of the same litter, and all similarly affected. There were slight areas of mange at the base of the ears and on the head. Examina- tion of the feces showed the ova of the intestinal parasites Ascaris and the hookworm (Uncinaria). 21 32 23 Red Cells 4,320,000 5,224,000 4,472,000 Leucocytes 6,880 8,220 6,600 1. Lymphocytes 43% 37% 38% 2. Mononuclears 3% 2% 3% 3. Polynuclears 50% 61% 55% 4. Eosinophiles 3% .4% 4% Hemoglobin 45% 27% 54% These counts show an anemia which is similar to that of Uni- cinariasis in man (Stiles), but they lack the eosinophilia conceded to such cases. w CD 5 w "^ H 1^ ifi F^ <| O o HH P4 H K Ph H o >> o CO p^ < m ^0 a n i-t ^-, o CO 00 >0 CO -a c C3 O P5 rt 1=1 TS ta" "o -a ^z; S 01 ja o •a 6 "rt u o w > o M bo a E 5 ^ « « w o b« .- u dj a '2 "S "3 "o I- 1 M ? ^ 4> O O a CTv 3 9 O w w o z; =! m t! a o ■iJ '•^ a u 4J V M a w )-H > s 13 o s?8 \p o 01 ^° O ^ to =\ o ^ 00 o a ^58 o\ o ^ O 10 ir> 00=2 O CO n3 ,_ en a 03 i~t 01 □ rt CJ tA .2 Y^ rt fl en .9 a en 2 P 13 M m Z P4 fO w sKO ° 3 ^o 5^ -I o vo O a\0 o\ O xn ^ 10^ Pi a; v^ M A M HO >> S a ? ^ s < -=5 ir. 10 •a J n ro CO 5? m (U Cfl ^H 1; OJ 4) Q '■S0.2 J3 'Som ^ s n "3 WP^ W (J a ON CT\ 0^ o o .a U < '■J a: u M C "5 a 7i n <^ ^ CO S s Pi 5 ■"d t:! 'd ^ C a ■T^ rt (fl a- k^ (J in ffi s > o ^ o ^_ 1— I :: ^ o - o M3 O o lO "N r- o a; On r^ md" VO" o o CN CO 18 CO oi so < o Q ^ „ ^ ■* l_H cS •^ t— I Z O ^ a; "o O s ffl a u P5 5 a a -2 " ^5 cr* C a^ O^ ON o O 3 o ? O V? M ^ tk tj J3 4< □ ^ a o cc u CC o Oj o p- U to o ON o o > CO > o^ hH w Ci 3.3 This table shows, like the two preceding tables, a leucocytosis and eosinophilia. The leueooytosis is not so pronounced, being almost normal in three cases, 24, 27 and 29, and in no case is it as abnormally high as in the mange cases. The eosin count is, however, luiiformly high. Taking the normal per cent, as 5-6%, nearly every case is double the normal number of eosins, and the more severe the skin irritation, the higher is the eosin count. Ewing, in regard to dermatoses in man, says, "The eosinophiles are affected not so much by any special form of cutaneous lesion as by the extent, intensity and lack of healing tendency on the part of the lesion." This statement is confirmed by nearly every one of the preceding cases, but special stress should be laid upon the "intensity of the lesion," that is, the amount of pruritis and irritation it pro- duces. Referring to the table of follicular mange cases, we find instances where the whole body is involved, the skin thickened, the hair fallen out, yet the animals were in good spirits and condition, at most being a little dull, but in no case suffering to any extent. They seldom showed restlessness or pruritus. In these cases (3, 5 and 8) the eosin per cent, was higher than normal, but not at all in proportion to the extent of the dermatosis. On the other hand, in the sareoptic mange cases, where the pruritus is intense, and we get incessant scratching and great rest- lessness, the eosin per cent, is high, considering the extent of the dermatosis. In cases 13, 14 and 17, where only limited areas of the body were involved, the eosinophilia is as high or higher than in cases of follicular mange where the whole body was affected. This striking difference can only be attributed to the difference in the amount of irritation caused by the two manges. The eczema cases only further confirm this point. In eczema we have usually even more pruritus than in either of the preceding dermatoses, though the skin lesions are relatively insignificant. A glance at the blood counts in these cases shows a more uniformly high eosin coimt than in the mange eases. If we take an average of the blood counts in the tables, the fol- lowing figures result: 34 Disease Red Cells Leucocytes Eosiu Per Cent Follicular Mange 7,006,400 13,400 8.1% Sarcoptic Mange 6,152,000 12,200 10.3% Eczema 6,732.200 10,700 13,6% Normal Dog 6,000,000 8,000 6 % This talDle, while hardly based on enough cases to be of much weight, shows at least for the cases examined, that the eosinophilia is independent of the extent of the skin lesions, and is highest where the intensity of the irritation is greatest. Conclusion. Prom these observations the following conclusions seem war- rantable : 1. That in dermatoses in dogs, the blood shows a leucoeytosis and an eosinophilia. 2. That the eosinophilia depends more upon the intensity of the dermatitis than upon the extent and nature of the disease. In concluding I wish to express my thanks to Drs. P. A. Fish and S. H. Burnett for many valuable suggestions. I am also in- debted to Dr. N. P. Hinkley. of Buffalo, in whose hospital some of the cases were examined. Bibliography. Burnett. — Clinical Pathology of the Blood of Animals. Burnett & Trauni. — Clinical Examination of the Blood of the Dog. Proc. A. V. M. A., 1905. Cabot. — Clinical Examination of the Blood. Ewing. — Clinical Pathology of the Blood. Moore, Haring & Cady. — Clinical Examination of the Blood of the Horse. Proc. A. V. M. A., 1904. A CASE OF AUTO-EXTEKECTOMY IN THE BITCH. Pierre A. Pish. A collie bitch two years old had her ovaries removed through the median line operation. Toward the evening of the second day after the operation it was noticed that the stitches in the w^ound had been removed and two free ends of the intestine were protruding. Immediate prepa- rations were made for suturing the ends of the intestines. The abdominal cavity was irrigated with a dilute solution of adrenalin chloride. The protruding intestines were carefully cleaned. Each end of the intestine had a gangrenous appearance for the distance of about one inch. This tissue was cut away and the ends of the intestine Avere drawn together by means of Lembert's sutures, catgut being used. After thorough cleansing, the parts were carefully placed in the abdominal cavity and the wound on the median line restitched. The patient was watched for a short time after her return to the cage. She soon exhibited signs of nausea and emesis was observed to occur. On close examination the vomitus was found to consist of some blood clots and two pieces of the intestine. One of these pieces measured fifteen inches in length and the other thirteen inches, making with the excised gangrenous portions a total of thirty inches or two and a half feet. The blood clots had undoubtedly formed in the abdominal cavity, when the intestina had been bitten off, and were swallowed along with the pieces of the intestine. In enterectomy operations, the observation has been made by Parkes that there were better chances for recovery if not more than six inches of the intestine had been removed. It is readily obvious that the greater the amount of the intestinal tube removed, the greater would be the interference with digestive pro- cesses and body metabolism and the chances for recovery greatly diminished.