THE INFLUENCE OF ACUTE ALCOHOLISM ON THE NORMAL VITAL RESISTANCE OF RABBITS TO INFECTION BY A. C. ABBOTT From THE JOURNAL OF EXPERIMENTAL MEDICINE Vol. I, No. 3, 1896 THE INFLUENCE OF ACUTE ALCOHOLISM ON THE NORMAL VITAL RESISTANCE OF RABBITS TO INFECTION. By A. C. ABBOTT, M. D., FIRST ASSISTANT, LABORATORY OF HYGIENE, UNIVERSITY OF PENNSYLVANIA. (From the Laboratory of Hygiene, University of Pennsylvania.) During the past six months a portion of the time at my disposal has been occupied with experiments the results of which I propose to embody in this contribution. These studies were made in the Laboratory of Hygiene of the Uni- versity of Pennsylvania under the auspices of the Committee of Fifty to Investigate the Alcohol Question, who generously placed at my disposal the funds necessary to defray the expenses of the work. In the distribution of the several subdivisions of the general ques- tion relating to the influence of alcohol upon the physical and moral well-being of those who use it as a beverage, the committee has seen proper to assign to me for experimental solution one of the most in- teresting and important phases of the subject-viz., that concerning the influence of alcoholism, acute and chronic, upon the normal vital resistance of animals to various forms of infection. In undertaking the work a general scheme of procedure was drawn up that seemed to meet most of the requirements of the prob- lem, but as I now review it I find that it has been possible, in the time at my disposal, to cover only a limited portion of the ground included in this scheme. The lines along which it was proposed to conduct these investiga- tions are as follows: 1. Determine if the normal vital resistance of animals to infec- tion by the common pathogenic bacteria is demonstrably influenced Copybight, 1896, by D. Appleton and Company. 2 Acute Alcoholism on the Vital Resistance of Rabbits to Infection by either acute or chronic alcoholism, induced through the use of known amounts of pure ethyl alcohol. 2. If any or no effect is observed, determine if the same holds good for animals under the influence of the commoner alcoholic bever- ages, as beer, wine, whisky, cordials, etc. 3. Determine if through either acute or chronic alcoholism the germicidal properties of the serum of the blood of animals is materially altered. If so, determine, if possible, the nature of this alteration. Thus far the work has borne upon the question concerning the influence of acute alcoholism upon the resistance of rabbits to infec- tion by the pyogenic cocci-i. e., the streptococcus pyogenes (erysipe- latos) and the staphylococcus pyogenes aureus-and by the bacillus coli communis, and the results are in many ways sufficiently instruc- tive to warrant their report at this time. A difficulty that arose at the outset was in procuring cultures of pathogenic organisms of suitably diminished virulence without their being at the same time totally devoid of this property. As experi- ence has taught us to expect certain deviations from the usual course of infection when normal animals are inoculated with attenuated cultures, such, for instance, as prolongation of the period of incuba- tion and modification of the pathological lesions, the problem under consideration seemed to be in part most easy of solution through a comparison of results obtained by the use of such cultures on groups of alcoholized and non-alcoholized animals. Should such modifica- tions occur in the normal animals, as would be anticipated, and an in- fection not differing from that produced by fully virulent cultures occur in the alcoholized animals, the difference could reasonably be referred to a reduction of vital resistance brought about by the alco- hol administered. To meet the requirements it would perhaps have been best to have employed cultures of organisms that were diminished in viru- lence to definite degrees of attenuation, such, for instance, as the bacillus anthracis attenuated to the degree of virulence represented by its primary and secondary vaccines. As such material was not at my disposal, however, cultures of another sort were used-namely, A. C. Abbott 3 those that were of a low degree of virulence without this degree being definitely determined. Again, cultures of organisms were employed the pathogenic powers of which are usually irregular and uncertain, while in still other tests an effort was made to detect a difference between alco- holized and non-alcoholized animals when inoculated with virulent material but in very small doses, hoping in this way to demonstrate, by a difference in the period of incubation, a difference of resistance in the animals composing the two groups. The experiments were made with cultures of streptococcus pyo- genes of a low degree of virulence, with normal bacillus coli com- munis, and with virulent staphylococcus pyogenes aureus, and, as the results to be reported show, with very diverse consequences. Another difficulty was encountered in regulating the dose of alcohol. The intention was to have the animals daily in a state of intoxication, but it is not easy to decide just when this stage is reached, as the only certain indication of it is inco-ordination of muscular movement. It frequently occurred that when alcohol was given to this stage the direct effect of the drug was such as to gravely im- peril the life of the animal, and in a certain number of instances the animals did not rally from even so few as one or two such administra- tions. If the dose were diminished, then one could often not be sure that the rabbit was intoxicated. On the other hand, one encounters occasionally an individual on which alcoholism to intoxication has apparently no effect upon the general health, and may be prolonged over relatively long periods. One of my animals, for instance, received daily doses of alcohol rang- ing from 5 to 15 cubic centimetres for one hundred and fourteen days. Its weight at the beginning was 1,330 grammes, and at the end 1,350 grammes, while during the interval its weight had been as high as 1,520 grammes and as low as 1,090 grammes. It died under the administration of 15 grammes daily with macroscopic lesions of only the gastric mucous membrane. I believe that the studies upon the effects of smaller, non-intoxicating doses of alcohol will demonstrate the possibility of continuing the administration of the drug over prac- Acute Alcoholism on the Vital Resistance of Rabbits to Infection 4 tically an indefinite period, quite to the stage of chronic alcoholism, in a fair proportion of the animals treated in this way. The individual susceptibility of different animals to the physio- logical action of alcohol differed in such a way as to require at the beginning a special dose for each individual. It is impossible to main- tain throughout a constant relation between body weight and dose necessary to produce the desired effects. For instance, it can not be said if 5 cubic centimetres of alcohol produces intoxication in a rabbit of 1,000 grammes weight, that necessarily 10 cubic centimetres will have the like effect in the next rabbit of 2,000 grammes weight. The dose can only be determined by experiment. It frequently occurred that, when the necessary dose had been determined, its continuous administration over several or more days resulted in very rapid and marked loss in body weight, an indication of the greatest importance, meaning, that if the alcohol be continued the animal is practically certain to die. Under these circumstances it becomes necessary to either diminish the dose or cease the adminis- tration entirely for a time, until the lost weight is partially or com- pletely recovered. During the interval of rest, as it may be called,, the animal is of course not daily intoxicated, and while the records of these experiments refer to animals " daily under the influence of alcohol to the stage of intoxication," it will be borne in mind that with many of these animals such periods of rest, varying in duration, were more or less frequently necessary. As it was impossible to induce the rabbits to take alcohol volun- tarily, either with the food or otherwise, it became necessary to ad- minister it through a soft-rubber catheter passed down the oesophagus into the stomach, and though this was done as gently as possible, the irritation resulting from the repeated passage of the catheter, to- gether with the depressing influence of the drug, was accompanied in a number of instances by intercurrent infections which, from their character and location, I think can be reasonably traced to insignifi- cant wounds of the mucous surface of the oesophagus made when the alcohol was administered. In only two instances was death positively the result of inspira- A. C. Abbott 5 tion of alcohol into the air passages at the time of operation. When such an accident occurs death is practically instantaneous. The most common macroscopic effect of the direct action of the alcohol was erosion and inflammation of the mucous membrane of the stomach, a condition that was unfortunately present in quite a num- ber of my animals, and which complicated matters in such a way as to vitiate considerably the results of the experiments. When the necessary dose of alcohol was determined, it was al- ways given mixed with an equal quantity of distilled water. The dose necessary to positively produce intoxication ranged from 5 cubic centimetres to 15 .cubic centimetres of pure ethyl alcohol, though the usual dose in rabbits of from 1,500 to 1,800 grammesweight was from 7.5 cubic centimetres to 10 cubic centimetres, doses which if taken by a man of one hundred and fifty pounds weight would be roughly equivalent to from two thirds to five sixths of a pint of abso- lute alcohol. Notwithstanding this apparently very large amount, animals have repeatedly been encountered on which from 10 to 12, and even 15 cubic centimetres had no visible influence, though the continuance of these doses in many instances- was followed by death associated with grave lesions of the gastric mucous mem- brane. While rabbits offer conditions in a way favourable to experiments of this character, they are so liable to intercurrent bacterial and protozoal infections as to lead to many irregularities when large num- bers of them are used. In the course of this work a number of ex- periments have been seriously vitiated by reason of such complica- tions. The general plan followed in these experiments was to employ groups of equal numbers of animals. All were inoculated in the same way, then to one group alcohol was given, while to the other no alco- hol was administered. They were all then kept under the same con- ditions of food, etc. Each animal was weighed in the morning before it was fed. In one or two cases the number of " controls " was fewer than that of the alcohol group. Control animals receiving only alco- hol were not introduced into each experiment, as the necessary data on this point could always be had by reference to the records of 6 Acute Alcoholism on the Vital Resistance of Rabbits to Infection preceding experiments in which the different effects of the drug on different animals was recorded. Without going further into the particulars, it will suffice to tabu- late the details and briefly summarize the results of each experiment as follows: Experiment I. Summary of the results of the intravenous inoculation of rabbits receiving daily doses of alcohol to the stage of intoxication, with bouillon cultures of streptococcus pyogenes obtained from a phleg- monous inflammation in man: Of eleven rabbits inoculated intravenously with varying amounts of streptococcus pyogenes, six received daily doses of alcohol for different lengths of time. The remaining five of this group received no alcohol. In addition, two rabbits received only daily doses of alcohol. Of the six inoculated animals that received alcohol, all died after marked loss of weight and all exhibited lesions referable to the inoculation. One re- vealed a condition of the liver probably the result of the action of the alcohol. Of the five inoculated animals to which no alcohol was given, one died, one was killed, and three recovered. The one that died presented no lesions referable to the inoculation. Cultures revealed the presence of streptococci in the liver mixed with another organism, while the other internal organs were sterile. The animal that was killed presented no lesions of importance, and its blood and internal organs were found by culture test to be sterile. Each of the three remaining animals suffered from temporary erysipe- las of the ear at the site of needle puncture. They recovered from this, and at the end of one hundred and twenty days were apparently in good condition, one having gained 330 grammes, the other 110 grammes, and the other 270 grammes in weight. Of the two animals that were not inoculated, but which received alcohol daily, one died after one hundred and fourteen days with a condi- tion of the gastric mucous membrane referable to the alcohol, the other after thirty-four days with no macroscopic lesions to account for death. A. C. Abbott 7 Experiment II. Summary of the results of intravenous inoculation of rabbits, re- ceiving intoxicating doses of alcohol daily, with suspensions of strepto- coccus pyogenes: The eighteen animals employed in this experiment were divided into four groups and treated as follows: Four received intoxicating doses of ethyl alcohol for five days and were then inoculated intravenously with 0.5 cubic centimetre of a sus- pension of streptococcus pyogenes. Five received intoxicating doses of methyl alcohol for five days and were then similarly inoculated. The alcohol was continued in both groups after inoculation until death. Five received, in addition to the inoculation, daily doses of distilled water, injected into the stomach in the same manner as was the alcohol in the other animals, for fifteen days. After this alcohol was given to two of them-to one for two days, to the other for six days-while the remaining three got nothing from the fifteenth day. Four were simply inoculated. One of this group received a single dose of alcohol. The nine latter animals served as controls. Results.-Of nine inoculated animals to which alcohol was given, seven died with suppurative lesions. Of nine inoculated animals that received no alcohol until after the fifteenth day, when alcohol was given to two, five died, three were killed, and one was observed for fifty-two days. In only three of the nine were suppurative lesions detected at autopsy. Of the seven alcohol animals that died, five presented lesions at autopsy that could be attributed to the action of the alcohol. Experiment III. Summary of the results of intravenous inoculation of rabbits receiving alcohol daily to the stage of intoxication, with suspensions of bacillus coli communis from human fasces: Of five rabbits, each of which was inoculated with 1 cubic centimetre of a suspension in bouillon of bacillus coli communis, and all of which had 8 Acute Alcoholism on the Vital Resistance of Rabbits to Infection been receiving alcohol to the stage of intoxication daily for five days, four died in from eighteen to twenty hours and one in eighteen days after inoculation. None presented lesions referable to the inoculation. One revealed a condition of the gastric mucous membrane that evidently resulted from the direct action of the alcohol. Bacillus coli communis was obtained in cultures from the internal organs of all. Five rabbits, each of which had been receiving alcohol in doses rang- ing from 2.5 to 15 cubic centimetres daily for thirty-one days, were in- oculated intravenously with the same material in the same amount that was employed in the preceding group. One died within twenty-four hours after the inoculation. Four died in from forty-three to fifty-five days after the inoculation. Three presented at autopsy lesions referable to the inoculation- viz., the condition of the liver, gall bladder, and bile described by Blach- stein.* Two presented no lesions attributable to the inoculation. Two showed a condition of the liver that may possibly have resulted from the prolonged action of the alcohol, while in the remaining three no results of the alcohol were evident. Two control animals that were inoculated in the same manner with the same material, but which received no alcohol, were alive on the seventy-ninth day after inoculation. By the sixtieth day one had gained 230 grammes in weight, while the other, though apparently well, had lost 200 grammes in weight. Experiment IV. Summary of the results of inoculation of alcoholized animals with suspensions of bacillus coli communis: Three animals received intravenous inoculation of 0.5 cubic centi- metre of a suspension of bacillus coli. Immediately afterward the adminis- tration of alcohol was begun. One died during the night and one on the day following the inoculation. Bacillus coli was found by cultures in the internal organs of both. The third died eight days after inoculation with no characteristic lesions and no colon bacilli in the internal organs. * Blachstein. Intravenous Inoculation of Rabbits with the Bacillus Coli Communis and the Bacillus Typhi Abdominalis. Bulletin of the Johns Hopkins Hospital, vol. ii, No. 14, July, 1891. A. C. Abbott 9 The mucous membrane of the stomach was eroded and there was a fibrino-purulent pericarditis and pleuritis, evidently the result of an intercurrent infection, probably induced by the repeated passage of the catheter along the oesophagus. Three other rabbits that had been getting alcohol for four days were inoculated in the same manner-as the preceding. Two died on the ninth day and one on the eighteenth day following inoculation. In one, dead on the ninth day, were the characteristic lesions de- scribed by Blachstein. There was also present a condition of the stom- ach that was manifestly the result of the action of the alcohol. Of the remaining two, in one death ensued from an intercurrent in- fection, while in the other death was the result of an intestinal intus- susception. This latter animal presented erosion of the gastric mucous membrane that was evidently the result of the action of the alcohol. In both animals that died on the ninth day colon bacilli were present in cultures from the internal organs, while in the one dead on the eight- eenth day the blood and internal organs were sterile. Three control animals were alive and apparently well on the forty- sixth day. One had gained 50 grammes, the other 280 grammes, while the third had lost 120 grammes in weight. In short, of six alcoholized rabbits inoculated with colon bacilli, all died. One presented characteristic lesions at autopsy. Of three non-alcoholized, control animals, none died. Experiment V. Results of intravenous inoculation of rabbits receiving alcohol, with cultures of staphylococcus pyogenes aureus: In this experiment the first inoculation was without effect, and the animals were inoculated a second time after an interval of seven days. Four animals were employed-viz., two alcoholized and two controls. The alcoholized animals died in fourteen and two days, respectively, after the inoculation. Both presented lesions referable to the inocula- tion and neither showed conditions due to the direct action of the alco- hol. One control animal died in four days after the first inoculation, while the second died in six days after the second inoculation. To this latter animal alcohol was administered from the time of the second in- oculation. Both presented lesions referable to the inoculation, and the one that got alcohol presented also conditions due to the direct action of the alcohol. 10 Acute Alcoholism on the Vital Resistance of Rabbits to Infection This experiment does not demonstrate any material difference be- tween the alcoholized and the non-alcoholized animals as regards their susceptibility to this form of infection. Experiment VI. Subcutaneous inoculation of alcoholized animals with cultures of staphylococcus pyogenes aureus: There were four animals in this group, two alcoholized and two con- trols. In all except one, an alcoholized rabbit, the subcutaneous inocula- tion was without effect up to the seventh day. On the seventh day the three remaining animals were inoculated again, but this time intra- venously. Results.-One alcoholized animal died in three days after the sub- cutaneous inoculation. Death was due to pseudo-tuberculosis of the lungs. There was only a trifling area of suppuration at the seat of inocu- lation. The other alcoholized rabbit died four days after the intra- venous inoculation and presented the usual condition of widespread miliary-abscess formation. Both control animals died after the intra- venous inoculation-the one in seven days, the other in twenty-four hours. The former presented lesions characteristic of the inoculation, while the latter presented no macroscopic lesions at all at autopsy. The former control animal had been given alcohol since the date of its sec- ond intravenous inoculation. At autopsy it presented lesions referable to the direct action of the alcohol. Experiment VII. Intraperitoneal inoculation of alcoholized animals with cultures of staphylococcus pyogenes aureus: Four animals were employed; two received alcohol and two served as controls. The animals that exhibited no effects of the intraperitoneal inocu- lation at the end of a week were reinoculated with the same material, but this time the inoculation was intravenous. One alcoholized animal died the day following the intraperitoneal inoerdation, the other two days after the intravenous inoculation. In neither were lesions detected that could account for death, or be positively referred to either the inoculation or the alcohol. A. C. Abbott 11 Both control animals recovered from the intraperitoneal inocula- tion and at the end of a week were inoculated intravenously. One died two days after this latter inoculation and presented neither mycotic nor alcoholic lesions, death being due to rupture of the gravid uterus, while the other died nine days after intravenous inoculation with abscesses in myocardium and kidneys. Experiment VIII. Intravenous inoculation of alcoholized rabbits with bouillon cul- tures of staphylococcus pyogenes aureus: Of the six inoculated animals to which alcohol was given, three died in less than twenty-four hours and three in from forty-eight to seventy- two hours after inoculation. In three, lesions were present that could positively be referred to the inoculation, and in one the condition was doubtful. In two no such lesions could be found. In five of the six animals a condition of the mucous membrane of the stomach was found that was evidently the result of the direct action of the alcohol. Of the six inoculated animals that did not get alcohol three died in less than twenty-four hours, two after five and twelve days, respectively, while the remaining animal was apparently well at the end of forty-three days. Three of these animals presented lesions that resulted from the inocu- lation, in one the lesion was doubtful, in one no lesions were detected, and the sixth is still alive. This experiment demonstrates a slight, though not very important or striking, difference between the course of infection in the two groups. Experiment IX. Subcutaneous inoculation of alcoholized rabbits with cultures of staphylococcus pyogenes aureus: Of the six inoculated animals to which alcohol was given, one died during the night following the inoculation; the remaining five died in from five to fifteen days later. Two of these animals presented no lesions referable to the inocula- tion, one presented an extensive local lesion, and three presented a lesion of the pleurae and pericardium of doubtful significance. This condi - 12 Acute Alcoholism on the Vital Resistance of Rabbits to Infection tion was identical in the three animals and consisted of a fibrino- purulent inflammation of practically all the serous surfaces within the thoracic cavity. Cultures from this lesion revealed the presence of a staphylococcus that grew feebly, producing but a very faint, barely perceptible, cream colour, and in general gave the impression that it might be an attenuated or enfeebled culture of staphylococcus aureus. It was not studied in detail. The animals in which this lesion was found died in five, fifteen, and fifteen days, respectively. The three control animals used in this experiment manifested no ill effects of the treatment. They were alive and well at the end of forty- six days after inoculation. In none of the six animals that received alcohol was there any macro- scopic evidence of the action of the alcohol on the tissues. Experiment X. Intravenous inoculation of alcoholized rabbits with staphylococ- cus pyogenes aureus attenuated (?) by exposure to chloroform: Four animals were used in this experiment. Of the two inoculated animals to which alcohol was given one died on the fifth, the other on the second day following the inoculation. One presented a lesion of the kidney positively referable to the inocula- tion, the other a condition of the peritonaeum that probably, though not certainly, resulted from the treatment to which the animal had been subjected. Both of these animals presented extensive erosions of the gastric mucous membrane that was manifestly the result of the direct action of the alcohol. Neither of the two control animals evinced any ill effects from the in- oculation; both gained in weight, and at the end of twenty-eight days were eliminated from the experiment as not likely to manifest evidences of infection. , Conclusions. The deductions that may be drawn from the results of these ex- periments are as follows: That the normal vital resistance of rabbits to infection by strepto- coccus pyogenes (erysipelatos) is markedly diminished through the A. C. Abbott 13 influence of alcohol when given daily to the stage of acute intoxica- tion. That a similar, though by no means so conspicuous, diminution of resistance to infection and intoxication by the bacillus coli com- munis also occurs in rabbits subjected to the same influences. And that, while in alcoholized rabbits inoculated in various ways with staphylococcus pyogenes aureus, individual instances of lowered resistance are observed, still it is impossible to say from these experi- ments that in general a marked difference is noticed between alco- holized and non-alcoholized animals as regards infection by this par- ticular organism. It is interesting to note that the results of inoculation of alcohol- ized rabbits with the erysipelas coccus correspond in a way with clin- ical observations on human beings addicted to the excessive use of alcohol when infected by this organism. In the course of the work an effort was made to determine if, through the oxidation of alcohol in the tissues to acids of the corre- sponding chemical group, the increase of susceptibility could be re- ferred to a diminution in the alkalinity of the blood as a result of the presence of such acids. The number of experiments thus far made on this point is too small to justify dogmatic statements, but from what we have gathered there is but little evidence in support of this view'. Throughout these experiments, with few exceptions, it will be seen that the alcoholized animals not only showed the effects of the inoculations earlier than did the non-alcoholized rabbits, but in the case of the streptococcus inoculations the lesions produced (formation of miliary abscesses) were much more pronounced than are those that usually follow inoculation with this organism. With regard to the predisposing influence of the alcohol, one is constrained to believe that it is in most cases the result of structural alterations consequent upon its direct action on the tissues, though in a number of the animals no such alteration could be made out by macroscopic examination. I am inclined, however, to the belief, in the light of the work of Berkley and of Friedenwald, done under the direction of Prof. Welch, in the Pathological Laboratory of the 14 Acute Alcoholism on the Vital Resistance of Rabbits to Infection Johns Hopkins University, that a closer study of the tissues of these animals would have revealed in all of them structural changes of such a nature as to indicate disturbances of important vital functions of sufficient gravity to fully account for the loss of normal resistance. The conspicuous influence of the alcohol on the gastric mucous membrane in many of these animals, with the consequent disturb- ance of nutrition, is undoubtedly the explanation of the marked loss in body weight that was observed in many of the animals employed in these experiments. In this light the susceptibility induced by alco- hol to excess is somewhat analogous to that induced by starvation, where we see the resistance of animals to particular forms of infection very markedly diminished. A. C. Abbott 15 TABULATED DETAILS OF FOREGOING EXPERIMENTS. Experiment I. Table showing the Results of Intravenous Inoculations of Rabbits that were receiving Daily Doses of Ethyl Alcohol to the Stage of Intoxication with Bouillon Cultures of the Streptococcus Pyogenes, obtained from a Phlegmonous Inflammation of the Foot of a Man. Bab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to inoculations. + = present. O = absent. Lesions ref- erable to the alcohol. + = present. O = absent. Results and remarks. Begin- ning- End. 1 41 250 c. c. 5 to 10 c. c. 36 days. Was then inoculated with 1 c. c. of bouillon culture of strep- tococcus intra- venously. 1,190 910 + General infection. + (?) (Liver.) Died six days after inoculation. Liver very yellow and friable; contained large numbers of strepto- cocci ; many of the capillaries quite filled with them. Streptococci also present in pure culture in blood, kidney, and bone marrow. No ab- scesses detected. 2 40 240 c. c. 5 to 7 ' 5 c. c. 35 days. Inocula- tion same as that of No. 1. 1,210 880 4" Miliary abscesses in muscles. 0 Died on sixth day after inoculation. Numerous miliary abscesses in muscles along the spine. No abscesses in myocardium or kidneys. Cultures.-Streptococci in pure culture in muscle abscesses, blood, liver, kidney, and spleen. Died on fifth day after inoculation. Miliary ab- scesses throughout the voluntary musculature. Abscesses in myocardium. Pale areas, but no ab- scesses in kidneys. Spleen dark and congested. Cultures.-Streptococci in pure culture and in large numbers in muscle abscesses, blood, liver, spleen, and kidney. 3 49 297*5 c. c. 5 to 7'5 c. c. 45 days. Intrave- nous inoculation of bouillon cul- ture of strepto- coccus 24 hours old. 1,280 960 + Miliary abscesses in muscles. 0 4 47 282-5 c. c. 5 to 7*5 c. c. 45 days. Inocula- tion same as that of No. 3. 1,200 1,040 + Ab- scesses (?) in myo- cardium. General infection. 0 Died on third day after inoculation. No abscesses in muscles. Several pale points in myocardium; these contained streptococci in large numbers on microscopic examination. Cultures.-Streptococci in pure culture from pale points in heart, from blood, liver, spleen, kidney, and peritoneal cavity. 16 Acute Alcoholism on the Vital Resistance of Rabb its to Infection Rab- bits. No of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + = present. O=absent Lesions rei- eiabie to the alcolioi + - presen.. G -aoseni. Results and remarks. Begin- ning. End. 5 16 145 c. c. 7 ' 5 to 10 c. c. Inoculated 3 times. Intervals: First, 2 days; second, 4 days; fhird, 7 days. Last in- oculation (fatal) was 0-8 c. c. of a bouillon culture of streptococcus intravenously. 1,740 1,290 + Miliary abscesses in muscles. 0 Animal had two subcutaneous inoculations, first two days and second four days after beginning of al- cohol. Seven days after beginning of alcohol it received an intravenous injection of 0'8 c. c. of a bouillon culture of streptococcus pyogenes. Died nine days after last inoculation. Sites of subcu- taneous inoculations sterile. As result of intra- venous inoculation the voluntary muscles were everywhere studded with miliary abscesses. Similar abscesses in diaphragm ; none in internal organs. Cultures from abscesses in muscles and from blood show streptococci in pure culture. 6 3 30 c. c. 10 c. c. Both given at same time. Same in- oculations as those for No. 5. J 1,910 1,740 Miliary abscesses in muscles. 0 Died in afternoon of second day after inoculation. Miliary abscesses throughout voluntary muscles, especially those of thorax. Spleen very large, almost black in colour; measured 6'5 cm. long, 2 cm. wide, and 1'5 cm. thick. Numerous abscesses in myocardium. Cultures and cover slips revealed streptococci in muscle abscesses, liver, spleen, blood, and kidney. A 114 845 c. c. 5 to 15 Not inoculated. 1,330 1,350 + The daily dose of 15 e. c. was begun eight davs be- c. c. Mucous membrane of stomach. fore death, after the animal had been getting 10 c. c. daily for the thirty-seven preceding days. Autopsy revealed macroscopic lesions only in the stomach. The walls were thickened and oedema- tous, in some places thin. There was widespread erosion and necrosis of the mucous membrane. B 34 147-5 c. c. 5 to 10 c. c. Not inoculated. 1,030 GOO O The animal was markedly susceptible to alcohol. At autopsy, no macroscopic lesions to account for death were found. Control Animals, received Alcohol, not inoculated. A. C. Abbott 17 c 120 N o <i 1 col iol + In three weeks after inoculation this animal was Con- trol hoi. lated at time as same No. 1, Erysipelas of ear well, having had a local erysipelas of ear at point of puncture of needle. After four months it had for and in same about site gained 330 grammes in weight, and was not ob- No. way. of opera- served further. 1 tion. D Con trol 120 Do. No alcohol. Inocu- lated at same time and in same wav as No. 2. 4- Temporary erysipelas of ear at After about three weeks the animal was well of its local erysipelas in ear. It had recovered its lost weight, and was apparently in good condition. At end of four months it had gained 110 grammes No. 2 site of in weight. Observation discontinued. and No. operation. 6. E Con- trol 120 Do. No alcohol. Inocu- lated at same time and in same + Temporary erysipelas Temporary redness and swelling of ear at site of operation. At end of four months had gained 270 grammes. Observation discontinued. for No. way as N 3. 3. ■ of ear. 3. F 16 Do. No alcohol. Inocu- 1,220 800 + Died after sixteen days. For some time had had Con- lated at same time and in same profuse watery discharge from nostrils and mouth. This began on fourth day after inoculation. No for No. way as No. 4. lesions of importance found at autopsy. Cultures.-Blood : pure culture of streptococci. 4. Liver: streptococci, with a large micrococcus. Lung, kidney, and spleen sterile. G 15 Do. No alcohol. Inocu- 1,410 1,590 + Animal killed on fifteenth day-i. e., nine days after Con- lated at same times and in Circum- scribed its last (intravenous) inoculation. No miliary abscesses in muscles and no lesions of internal for No same way 5. as No. pus for- mations at organs found at autopsy. Circumscribed pus formations in stages of healing at both sites of 5. sites of subcutaneous inoculation. subcutane- Cultures from sites of subcutaneous inoculation and ous inocu- internal organs showed them to be sterile. lations. Control Animals inoculated, but received no Alcohol. 18 Acute Alcoholism on the Vital Resistance of Rabbits to Infection Rab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + =present. O-absent. Lesions ref- erable to the alcohol. + = present. 0=absent. Results and remarks. Begin- ning. End. 7 13 142'5 7'5 to 15 5 days. Intrave- 2,010 1,650 O 0 Died eight days after inoculation. c. c. c. c. nous injection of • Autopsy.-No lesions anywhere to be detected. No 0-5 c. c. of a sus- streptococci in cultures. pension of strep- Cultures all contain short oval bacillus. Evidently tococcus pyo- genes. an intercurrent infection. 8 12 142-5 7'5 to 15 Do. 1,600 1,350 + 4- Died seven days after inoculation. Abscesses in c. c. c. c. Musele (Stomach.) muscles of both thighs; none in heart or kidneys. abscesses. Mucous membrane of stomach very much eroded. Cultures.-Streptococci in large numbers and in pure culture from blood, liver, kidney, and mus- cle abscess. 9 10 90 c. c. 7-5 to 10 Do. 1,020 940 + 0 Died fourth day after inoculation. c. c. Strepto- Autopsy.-No abscesses anywhere in voluntary muscles. Several diffuse pale areas in heart; cocci in blood. numerous necrotic areas in liver. Cultures demonstrate a mixed infection ; those from blood and kidney contain streptococci, those from the other organs contain a short oval bacillus. 10 12 132-5 7 ' 5 to 15 Do. 1,860 1,530 0 + Died seven days after inoculation. c. c. c. c. (Stomach.) Autopsy.-Muscle abscesses not detected. Liver contained coccidia nodules. Kidneys presented several small cortical haemorrhages. Mucous membrane of stomach inflamed and eroded. Cultures.-No streptococci in cultures from blood, liver, spleen, kidneys, or peritoneal cavity. In all these tubes was a short oval bacillus. 11 Died on fourth day as result of alcohol. Had not been inoculated. Experiment II. Table showing the Results of Intravenous Inoculation of Rabbits that were receiving Daily Doses of Alcohol to the Stage of Intoxication, with Suspensions of Streptococcus Pyogenes. Ethyl Alcohol. A. C. Abbott 19 12 11 109 c. c. 3 to 15 5 days. Inocula- 1,520 1,260 + + Died six davs after inoculation. C. 0. tion same as in preceding ani- mals of this ex- periment. Strepto- coccus septi- caemia. (Stomach.) Autopsy.-No muscle abscesses detected. Liver studded with minute yellow points. Mucous mem- brane of stomach very much reddened and eroded. Cultures.-Streptococci in pure culture and in large numbers from blood, liver, and spleen. IS 7 54 c. c. 3 to 10 c. c. Do. 1,200 1,110 + Strepto- cocci in blood and internal organs. O Died on day after the inoculation. Autopsy.-Liver contained psorosperm nodules, in which streptococci in large numbers were found along with the characteristic parasite. Kidneys pale; presented numerous minute cysts (?) over entire cortex. No abscesses anywhere. Cultures.-Streptococci in pure culture and in large numbers from blood, liver, spleen, kidney, and peritoneal cavity. 14 12 109 c. c. 3 to 15 c. c. Do. 1,000 1,040 + Abscess in muscle; strepto- cocci in blood. + (Stomach.) Died on seventh day after inoculation. Autopsy.-A single abscess in muscle of the thigh was detected. Slight excess of moisture in peri- toneal cavity. No abscesses in myocardium or kidneys. A widespread area of erosion and in- flammation of the mucous membrane of the stomach. Cultures -Streptococci in pure culture from spleen, liver, blood, kidney, and peritoneal cavity. They were present in only small numbers. 15 13 124 c. c. 3 to 15 c. c. Do. 1,440 1,420 + Abscess on leg; strepto- cocci in blood. '+ (St macli.) Died on eighth day after inoculation. Autopsy.-On right leg, near axilla, between skin and muscles, was a circumscribed collection of pus of about the size of an almond. No miliary abscesses detected. Several necrotic areas in liver. Mucous membrane of stomach very red and eroded. This animal had a very acute and painful erysipelas of the ear for several days after inoculation. Cultures.-Streptococci from blood, liver, and large abscess on leg. 16 8 46'5 c. c. 3 to 10 c. c. Do. 1,240 1,140 + Muscle abscesses; streptococci in blood. 0 Died on second day after inoculation. Autopsy.-Muscle abscesses in left thigh and in abdominal muscles. Several abscesses in myo- cardium. Cultures.-Streptococci from blood, liver, kidney, and muscle abscesses. Animals receiving Commercial (Pure) Methyl Alcohol. 20 Acute Alcoholism on the Vital Resistance of Rabbits to Infection Control Animals for this Experiment. These Animals were inoculated with the Same Material, at the Same Time, and in the Same Way as the Ten Preceding Animals. For Fifteen Days Each received SO c. c. of Distilled Water daily, injected into the Stomach through a Soft-rubber Catheter. Rab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + = present. O=absent. Lesions ref- erable to the alcohol. + = present. 0=absent. Results and remarks. Begin- ning. End. 17 21 20 c. c. of water daily for 15 days. Alcohol was then begun. In 6 days 30 c. c. of alcohol given. Water, 20 c. c. Alcohol, 10 c. c. 3 days, nothing. 5 days from the beginning of wa- ter. Inoculation same as preced- ing animals. 1,010 860 °(?) Condition of the ear of this rab- bit was evi- dently ery- sipelatous. Unfortu- nately it was not examined at autopsy. 0 Died on fifteenth day after inoculation and on fifth day after alcohol was begun. Autopsy.-For five days before death this animal has had very sore ear. It was thick, painful, and dependent. Beyond a slight diminution in colour, internal organs were normal. No lesions of muscles. Cultures-Blood, liver, and kidneys sterile. 18 18 Water as in No. 17. One day, nothing; then got 10 c. c. alcohol on each of 2 days. Water, 20 c. c. Alcohol, 10 c. c. 5 days from begin- ning of water. Inoculation as above. 1,130 1,020 0 O Died after second dose of alcohol-i. e., thirteen days after inoculation. Autopsy-Neither recent nor remote suppurative lesions anywhere. Small area of consolidation in left lung (inspiration pneumonia (?)); no bac- teria found in cover slips from this. Cultures.-Blood, liver, and kidneys sterile. 19 52 No alco- hol. 20 e. c. water daily for 15 days. Then got nothing for 37 days. None. 5 days from begin- ning of water. 1,650 1,500 O The weight of the animal ran up as high as 1,710 and down as low as 1,450 grammes while in the experiment. At end of fifty-two days it was apparently well. Observation was discontinued. Showed no signs of sickness at any time. A. C. Abbott 21 20 16 Do. Do. 1,120 1,130 0 The weight of the animal went up to 1,200 grammes 21 16 Do. Do. in course of the experiment. It was killed on sixteenth day. Autopsy.-Neither recent nor remote lesions any- where. Viscera apparently normal. Cultures.-Blood, liver, spleen, and kidney sterile. 1,010 1,030 0 Weight was up to 1,080 grammes at one time. Killed on sixteenth day. Autopsy.-No lesions of any kind anywhere. Ani- mal apparently normal. Cultures.-Blood, liver, spleen, and kidney sterile. 22 11 No alcohol, lated on Inocu- same 920 960 + Abscesses. Weight was up to 1,030 during experiment. Died five days after inoculation. date and in same way as preceding Strepto- coccus Autopsy.-Abscesses in voluntary muscles, in myo- cardium, and in right kidney; none in left kidney. animals. septicae- mia. Cultures.-Streptococci in pure culture for blood, liver, spleen, kidney, and peritoneal cavity. 24 Do. Intercurrent infection before it was inoculated. Excluded from the experiment. 25 1,320 1,040 + (?) Caseous gland in Died on twenty-fifth day. For some days before death there was profuse watery discharge from mouth and nose. axilla. Autopsy.-A small caseous gland in right axilla. Did not contain streptococci on microscopic ex- amination. No other lesions noted beyond nu- 25 17 None un- til 16th Do. 1,480 1,250 4- merous minute petechia; over cortex of kidneys. Cultures.-Blood, liver, kidney, and peritoneal cavity sterile. Died on second day after its dose of alcohol-i. e., Abscesses on twelfth day after inoculation. day, when 1 dose of 10 e. c. was given. in muscle. Autopsy.-Evidence of healed peritonitis. Two large abscesses in left pectoral muscle; no ab- scesses in myocardium or kidneys. The muscle abscesses were apparently of long standing. Cultures.-Streptococci from muscle abscesses. Blood and kidney sterile. Control Animals getting Nothing but the Inoculation. Acute Alcoholism on the Vital Resistance of Rabbits to Infection 22 Fab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + = present. O=absent. Lesions ref- erable to the alcohol. + = present. O=absent. Results and remarks. Begin- ning. End. 26 16 No alco- hol. Do. 1,490 1,090 0 Killed on sixteenth day after experiment was be- gun-i. e., eleventh day after inoculation. Autopsy-Suppurative -lesions, neither recent nor remote, were anywhere to be detected. Cultures.-No streptococci in either the blood or the internal organs. Experiment III. Tabic showing the Results of Intravenous Inoculation of Rabbits receiving Daily Doses of Ethyl Alcohol to the Stage of Intoxication, with Suspensions of Bacillus Coli Communis from Human Ececes. 27 6 55 c. c. 7'5 to 10 5 days. Intrave- 1,990 1,970 0 + Died about five hours after inoculation. c. c. nous injection of I c. c. of opaque suspension of b. coli 52 hours old. (Stomach.) Autopsy.--Mucous membrane of stomach red; slight congestion of spleen and kidneys. Cultures.-A few colonies of bacillus coli from liver. Blood sterile. 28 6 55 c. c. 7'5 to 10 c. c. Do. 1,890 1,800 O O Found dead on morning following the injection. Autopsy-About 3 c. c. of reddish fluid in peri- tonaeum. One or two dark areas in lungs. No other lesions. Cultures.-Liver, blood, and peritoneal cavity gave bacillus coli in pure culture. 29 23 240 c. c. 7'5 to 10 Do. 1,400 920 0 0 Died on twenty-third day-i. e., eighteen days after inoculation. Autopsy.-Pseudo-tuberculosis of apex of left lung. Liver pale and tough. Gall bladder distended with dark-green bile. Cultures.-Peritoneal cavity, five colonies, and bile, one colony; all were of bacillus coli. 30 6 55 c. e. 7'5 to 10 Do. 1,690 l,77o 0 0 Found dead on morning following the inoculation ; had evidently been dead some time, as post-mor- tem changes were in progress in all the organs. Cultures.-Bacillus coli in pure culture from spleen, kidney, liver, and blood. A. C. Abbott 23 31 6 55 c. c. 7-5 to 10 c. c. Do. 1,710 1,470 0 0 Found dead on morning following the inoculation. Post-mortem decomposition more or less advanced in all the viscera. No lesions discernible to naked eye. Pure cultures of bacillus coli obtained from blood, liver, spleen, kidney, and peritonaeum. 32 32 112-5 2'5 to 31 days. Same 1,130 1,070 O + (?) This animal was so susceptible to alcohol that it c. c. 7 • 5 c. c. inoculation as above. (Liver.) could not be given regularly. Found dead on morning following the inoculation. The only lesions found at autopsy were very pale liver and a circumscribed oedematous patch in the lung. Colon bacilli in pure culture from blood, liver, spleen, and kidney. 33 75 440 c. c. 2-5 to 10 c. c. 33 days. Inocu- lated as above. 2,000 1,310 + (Bile.) O Died on seventy-fifth day-i. e., forty-three days after inoculation. Autopsy.-Moderate emaciation. Liver so thickly studded with coccidia that nothing could be de- tected as to presence of other lesions. Gall blad- der very much distended with clear, pale bile in which floated amorphous flakes that could be seen through the walls of the organ. These con- sisted of leucocytes, epithelium, blood corpuscles, and bacteria. Cultures.- Pure cultures of bacillus coli from bile and blood. Cultures from liver contained colon bacilli with another bacillus (bacillus pyogenes). 34 88 580 c. c. 5 to 15 c. c. Do. 1,560 1,330 + (Liver and bile.) O Died on eighty-eighth day-i. e., fifty-five days after inoculation. Autopsy.-Slight emaciation. Several irregular necroses in liver. Very great distention of gall bladder with clear, pale-greenish bile, in which was an amorphous sediment. Cultures.-Colon bacilli in pure culture from the bile. Liver and blood sterile. The Following Animals were inoculated at the Same Time as the Preceding, with the Same Amount of the Same Material. They differed from the Preceding in having received Alcohol daily for a much Longer Time before the Inoculation. 24 Acute Alcoholism on the Vital Resistance of Rabbits to Infection Rab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + = present. 0=absent. Lesions ref- erable to the alcohol. + - present. O=absent. Results and remarks. Begin- ning. End. 35 87 560 c. c. 2'5 to 15 c. c. Do. 1,620 1,220 0 + (?) (Liver.) Found dead on eighty-seventh day-i. e., fifty-four days after inoculation. Autopsy.-Liver large, tough, rough on its surface. On section, the open mouths of vessels are very conspicuous. Gall bladder filled with normal dark-green bile. Cultures demonstrated the blood, liver, and bile to be sterile. 36 84 537'5 c. c. 2*5 to 10 c. c. Do. 1,570 1,070 + (Liver and bile.) 0 Found dead on eighty-fourth day-i. e., fifty-one days after inoculation. Autopsy.-Both lungs in part affected with pseudo- tuberculosis. Liver presented several irregular parts of yellowish superficial necroses. Gall bladder very large, distended with pale, clear bile, in which floated flakes of amorphous mate- rial ; these could be seen through the walls of the distended organ. Cultures.-Bacillus coli was obtained only from the bile. It was here in pure culture. From lungs bacillus pyogenes (?) was obtained in pure culture. 37 38 79 79 Injected as above. a a 1,290 1,820 Seventy-nine days after inoculation this animal is still alive. Had gained by sixtieth day 230 grammes. Observation discontinued. Seventy-nine days after inoculation the animal is alive, is apparently well, though it had lost 200 grammes in weight by sixtieth day. Controls. Injected at Same Time as the Others, but received no Alcohol. A. C. Abbott 25 Experiment IV. labie giving the Results of Intravenous Inoculation of Rabbits that were receiving Daily Doses of Ethyl Alcohol to the Stage of Intoxication, with Suspensions of Bacillus Coli Communis from Human Faeces. 39 11 90 c. c. 10 c. c. Simultaneous. In- 1,540 1,180 0 + Died eight days after inoculation. Had been under 40 oculated with 0'5 c. c. of a suspen- sion of bacillus coli from agar culture 24 hours old. (Stomach.) observation for two days before any treatment was begun. Autopsy.-Acute fibrino-purulent pleuritis and peri- carditis, due to intercurrent infection. Mucous membrane of stomach slightly eroded. No colon bacilli found in the cultures from blood and internal organs. 2 20 c. c. 10 c. C. Do. 1,330 1,190 0 O Died on the day following inoculation. Autopsy.-The only lesion found was an intussus- ception of the colon involving about 12 cm. of the length. It was very acutely congested, and evidently recent. Cultures.-Blood sterile. Liver: a few colonies of bacillus coli. 41 1 10 c. c. 10 c. c. Do. 1,760 0 O Died during night of the day on which it was in- oculated. Autopsy.-No macroscopic lesions. Cultures.-Blood and liver contained large numbers of bacillus coli. 42 9 47 ■ 5 c. c. 5 to 7 • 5 c. c. 4 days. Inoculated as above. 1,180 950 0 + (Stomach.) Died on ninth day-i. e., five days after inoculation. Autopsy.-Liver presented several areas of super- ficial necrosis. Gall bladder filled with normal bile. A recent volvulus, with intussusception of small intestine. Lymphatic apparatus of intes- tine enlarged, but not congested. Mucous mem- brane of stomach eroded. Cultures.-Colon bacilli in small numbers were ob- tained from liver, blood, bile, and spleen. 43 18 177-5 c. c. 7'5 to 10 c. c. Do. 2,110 1,780 0 0 Died on eighteenth day-i. e., fourteen days after inoculation. Autopsy.-Death ensued from intercurrent infec- tion. No colon bacilli found in cultures. 26 Acute Alcoholism on the Vital Resistance of Rabbits to Infection Rab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + = present. O=absent. Lesions ref- erable to the alcohol. + = present. 0=absent. Results and remarks. Begin- ning. End. 44 9 87'5 c. c. 7'5 to 10 Do. 1,520 1,180 4- 4" Died on ninth day-i. e., five days after inoculation. c. c. (Liver and (Stomach.) Autopsy.-Moderate emaciation. Several irregular bile.) necroses in liver. Gall bladder distended with pale bile, in which amorphous flakes could be seen through the wall of the distended organ. Amorphous matter consisted of leucocytes, blood corpuscles, and bacteria. Mucous membrane of stomach red and eroded. Cultures.-Bacillus coli in blood, liver, bile, and spleen. 45 46 47 No alcohol. Intra- venous inocula- tion of 0'8 c. c. of the same sus- pension used in preceding rab- bits of this ex- periment. 1,560 -1,960 1.510 After forty-six days animal apparently well. Weight, 1,610 grammes. After forty-six days animal apparently well. Weight, 1,840 grammes. After forty-six days animal apparently well. Weight, 1,790 grammes. Controls ; inoculated, in the Same Way but with a Larger Dose of the Same Material as the Preceding Animals, but received no Alcohol. 27 A. C. Abbott Experiment V. Table showing the Results of Intravenous Inoculation of Rabbits receiving Daily Doses of Ethyl Alcohol to the Stage of Intoxication, with Bouillon Cultures of Staphylococcus Pyogenes Aureus. 48 49 24 12 200 c. c. 110 c. c. 10 to 15 c. c. 10 c. c. 3 days. Intrave nous inoculation of 0'3 c. c. of 24-hour bouillon culture of S. au- reus. After 7 days, similar in- jection of 0'5 c. c. Do. 1,900 1,360 1,250 1,160 + (Kidneys.) + (Abscesses in kidneys and mus- cle.) O 0 Died on twenty-fourth day-i. e., twenty-one days after first and fourteen days after second inocu- lation. Autopsy.-Several old abscesses in the kidneys; gave appearance of being encapsulated; none in myocardium or voluntary muscles. Widespread pseudo-tuberculosis of right lung. -This is evi- dently the cause of death. Cultures.-Staphylococcus aureus from kidney. Blood, liver, and bile sterile. A long, slender bacillus growing in felt-like, tenacious colonies from the diseased lung. Died on twelfth day-i. e., nine days after first and two days after second inoculation. Autopsy.-One small abscess in voluntary muscles. Numerous small abscesses in kidneys. None in myocardium. Cultures.-Staphylococcus aureus in very small numbers from blood and kidney. Peritonamm sterile. Controls. 50 13 None un til 7th day of ex- periment, then al- cohol was begun. Total amount, 50 c. c. 10 c. c. Alcohol given sim- ultaneously with the second inocu- lation ; first inoc- ulation as above; second inocula- tion on seventh day consisted of 0-5 c. c. of a bouillon culture of S. aureus in- travenously. 2,430 2,250 + (Abscesses in kidneys.) + (Stomach.) Died on thirteenth day-i. e., ten days after first and six days after second inoculation. Autopsy.-Mucous membrane of stomach very much inflamed and eroded. Several conglomer- ate abscesses in kidneys, none in myocardium or in voluntary muscles. CWfwres.-Staphylococcus aureus from kidney. Blood and liver sterile. 28 Acute Alcoholism on the Vital Resistance of liabbits to Infection Rab- bits. No. of days ob- served. T tai amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + =present. 0=absent. Lesions ref- erable to the alcohol. + = present. O--absent. Results and remarks. Begin- ning. End. 51 4 None. One inoculation of 0'3 c. c. of bou- illon culture of S. aureus intrave- nously. No alco- hol. 1,170 920 + (Abscesses in myocar- dium and muscles.) 0 Died four days after inoculation. Autopsy.-Abscesses in myocardium and kidneys. None in voluntary muscles. No cultures. 52 14 125 c. c. 10 to 15 3 days. Subcutane- 1,350 930 + O Died on fourteenth day-i. e., eleven days after first and four days after second inoculation. Autopsy.-Typical disseminated miliary abscess formations in muscles and internal viscera. No cultures. c. c. ous inoculation of 1 c. c. of a 24-hour bouillon culture of S. aureus; 7 days later intravenous inoculation of 0'5 c. c. of simi- lar culture. (Dissemi- nated mili- ary abscess formation.) 53 6 55 c. c. 7'5 to 10 c. c. 3 days. One sub- cutaneous inocu- lation as above. 1,380 1,080 + (Site of in- oculation.) 0 Died on sixth day-i. e., three days after inocula- tion. Autopsy.-Small purulent mass at site of inocula- tion. No abscesses anywhere. Large part of both lungs affected with pseudo-tuberculosis. Cultures.-Staphylococcus aureus from site of in- oculation. The slender bacillus referred to in protocol of Rabbit 48 obtained from lung. Experiment VI. Table showing Results of Subcutaneous Inoculation of Rabbits receiving Daily Doses of Ethyl Alcohol to the Stage of Intoxication, with Cultures of Staphylococcus Pyogenes Aureus. A. C. Abbott 29 54 14 60 c. c. 10 c. c. 7 days after first 2,390 2,080 + + Died on fourteenth day-i. e., seven days after sec- Alcohol was be- gun 7 days af- ter first inocula- tion- i. e., with the sec- ond in- oculation. for 6 days after second inocula- tion. inoculation ; first inocidation was 1 c. c. of a bouillon culture of S. au- reus subcutane- ously ; second was 0 5 c. c. of similar cultures intravenously. (Abscesses in kidneys.) (Stomach ) ond inoculation. Autopsy.-Post-mortem decomposition advanced. Straw-coloured fluid containing fibrin-like strands in pleural cavity. Abscesses in kidneys. Stom- ach injected. Cultures.-Staphylococcus aureus from kidney, liver, and pleural cavity. Bile, spleen, and peri- tonaeum sterile. 55 8 No alco- hol. First inoculation as above; second as above. No al- cohol. 1,940 1,890 O O Died on day following last (second) inoculation. Autopsy.-Beyond a slight distention of the peri- cardial sac with fluid, there were no lesions any- where to be detected by the naked eye. No abscesses anywhere. Cultures.-Staphylococcus aureus in moderate num- bers from blood and kidney. Pericardial sac sterile. 56 4 40 c. c. 70 c. c. 3 days. Inoculated 1,050 880 O 0 Died on dav following inoculation. into peritonaeum Autopsy.-Beyond a few c. c. of reddish fluid in with 0'5 c. c. of peritonaeum, there was no evidence of peritonitis. 24-hour bouillon No other lesions. cultures of S. Cultures.-Staphylococcus aureus in pure culture aureus. from peritonaeum. Blood and liver sterile. Experiment VII. Table showing Results of Intraperitoneal Inoculation of Rabbits receiving Daily Doses of Ethyl Alcohol, with Cultures of Staphylococcus Pyogenes Aureus. Controls. 30 Acute Alcoholism on the Vital Resistance of R abb its to Infection Rab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + = present. O=absent. Lesions ref- erable to the alcohol. + = present. O=absent. Results and remarks. Begin- ning. End. 57 12 110 c. c. 10 c. c. 3 days. First inocu- lation as in No. 56, second inocu- lation on seventh day. Intravenous injection of 0 5 c. c. of bouillon culture of S. aureus. 1,590 1,430 0 0 Died two days after second inoculation. Autopsy.-Small purulent nodule at point of punc- ture of first (intraperitoneal) inoculation. No peritonitis. Pericardium roughened, but con- tained no bacteria microscopically. It had not the appearance of recent inflammation. Minute red points over the surface of kidneys. No ab- scesses detected anywhere. Cultures.-A few colonies of staphylococcus aureus from blood and liver. 58 3 No alcohol. Inocu- 0 O Died on second day after inoculation. lated as No. 56. A utopsy.-Ruptured uterus, with three dead foetuses lying in abdominal cavity. Cultures.-Blood sterile. Staphylococcus aureus and short bacilli in peritoneal cavity. 59 16 No alcohol. 7 days 1,000 after the intra- peritoneal inocu- lation an intra- venous inocula- tion of 0'5 c. c. of bouillon cul- ture of S. aureus was given. 870 + (Abscesses in kidneys and in myocar- dium.) O Died nine days after second inoculation-i. e., the intravenous injection. Autopsy.-Kidneys and myocardium studded with abscesses. Lung presented several caseous or suppurating nodules that contained cocci. Cultures.-Staphylococcus aureus in liver, kidney, and bile. Controls. A. C. Abbott 31 Experiment VIII. Table showing Results of Intravenous Inoculation of Rabbits receiving Alcohol daily to the Stage of Intoxication, with RouiUon Cultures of Staphylococcus Pyogenes Aureus. 60 2 12-5 c. c. 12'5 c. c. Simultaneous. In- + Died on second dav. 61 3 22-5 c. c. 10 to travenous inocu lation with 0'4 c. c. of a 24-hour bouillon culture of S. aureus. Do. 1,990 1,860 (Heart and kidneys.) + (Stomach.) 4" Autopsy.-Very delicate network of lymph over surface of heart. Numerous very minute yellow points in kidneys. Mucous membrane of stom- ach red and eroded. Cultures.-Staphylococcus aureus in small numbers from blood, in very large numbers from kidney. Died on third dav. 62 63 1 2 12-5 22-5 c. c. c. c. 12'5 c. c. 10 to Do. Do. 2,000 2,050 (Myocar- dium, kidneys.) O + (Stomach.) + (Stomach.) + Autopsy.-Animal died as result of an accident. A small amount of alcohol was inspired into lungs. Death followed at once. Several yellow points in myocardium, and numerous similar points in kid- neys. None seen in voluntary muscles. Mucous membrane of stomach very red and eroded over large part of its surface. Cultures.-Blood sterile. Kidneys gave staphylo- coccus aureus in very large numbers. Died fifteen hours after inoculation. Autopsy.-Entire cardiac two thirds of stomach in- tensely reddened and mucous membrane eroded. Cultures.-Blood sterile. Kidney, four colonies of staphylococcus aureus. Died forty-eight hours after inoculation. 64 1 12-5 c. c. 12'5 c. c. Do. 1,390 (Kidneys.) + (?) (Pericar- dium.) (Stomach.) O Autopsy.-Conglomerate and single miliary ab- scesses in both kidneys. Walls of stomach very much thickened, oedematous, and acutely red- dened over about half its surface. Stomach con- tained small amount of dark grumous material. Cultures.-Blood sterile. Kidney contained staph- ylococcus aureus. Found dead fifteen hours after inoculation. Autopsy.-Pericardium filled with bloody serum Small amount of fluid in peritonasum. Cultures.-Blood, twenty-one colonies. Kidney, one colony of staphylococcus aureus. 32 A cute Alcoholism on the Vital Resistance of Rabbits to Infection Rab- bits. No. of days ob- served. Total amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + =present. 0=absent. Lesions ref- erable to the alcohol. + = present. O=absent. Results and remarks Begin- ning- End. 65 1 12'5 c. c Do. 1,790 0 + (Stomach.) Found dead fifteen hours after inoculation. Autopsy.-Small amount of fluid in peritonaeum. No peritonitis. Mucous membrane of stomach red and eroded. Cultures.-Staphylococcus aureus in blood and kidneys. 66 11 No alcohol. Inocu- lated as above. 2,150 1,530 + (Abscesses in muscles, kidneys, and joint.) Died on twelfth day after inoculation. A utopsy.-Numerous old abscesses in muscles, many almost as large as a pea. Purulent suppuration about the joint of right hock. Numerous old abscesses in kidneys. None in heart. Cul'.ures.-Staphylococcus aureus from kidney and 67 1 Do. 2,110 0 suppurating joint. Blood sterile. Died twenty hours after inoculation. Autopsy.-Numerous extremely minute white points in myocardium. Several pale, circumscribed, and also diffuse points in kidneys. Mucous membrane of stomach normal. Cultures.-Blood and kidneys sterile. 68 1 Do. 1,720 (Heart, muscles, Died twenty-one hours after inoculation. Autopsy.-Pericardium distended with serum. Heart covered with a delicate network of fibrin. kidneys.) Myocardium studded with minute pale points. Voluntary muscles presented numerous small lens-shaped pale points. Kidneys presented nu- merous pale areas that dipped into the cortex in a wedge-shaped manner. Cultures.-Staphylococcus aureus from kidney. Blood sterile. Controls-Inoculated, but received no Alcohol. A. C. Abbott 33 69 70 36 1 Do. De. 1,730 1,350 + (?) (Pericar- After forty-three days animal is apparently well. Weighs 1,560 grammes. Died twenty hours after inoculation. Autopsy.-Pericardium filled with serum, in which dium.) was a colourless clot and a few strands of fibrin. Diffuse pale areas in cortex of kidneys. Cultures.-Blood, one colony of staphylococcus aureus. Kidney sterile. 71 4 Do. 1,970 1,780 + (Abscesses in heart, Died on fifth day after inoculation. Autopsy.-On inner aspect of left thigh was a col- lection of pus about the size of a chestnut. Nu- kidneys, merous abscesses in muscles. Several abscesses and mus- in myocardium. Numerous abscesses in both cles.) kidneys. Small area of peritonitis in left iliac region. Cultures.-Staphylococcus aureus from blood, kid- ney, and abscess in thigh. n 11 55 c. c. 5 c. c. Simultaneous. Sub- 2,520 2,140 + O Died on twelfth day after inoculation. cutaneous inocu- lation of 1 c. c. of a bouillon cul- ture of S. aureus. (Site of in- oculation.) Autopsy.-At site of inoculation in the left groin the tissues were dissected apart, leaving a moder- ately large excavation. This contained neither serum nor pus. About the borders of this the tissues were very oedematous, the oedema extend- ing up into the neck and into the thighs of both sides. Middle lobe of right lung consolidated. Cultures.-Staphylococcus aureus from blood, from site of inoculation in large numbers, and from kidney. Lung also contained them, but associ- ated with a short bacillus. 73 14 75 c. c. 5 to 10 c. c. Do. 1,690 1,460 + (?) (Pericar- ditis and pleuritis.) 0 Died on fifteenth day after inoculation. Autopsy.-A trace of suppuration only at site of inoculation. Fibrino-purulent pleuritis and peri- carditis. Moderate amount of blood-stained purulent matter in pleural cavities. Cultures.-From pleural cavity a feebly growing staphylococcus was obtained. Can not say that it was or was not staphylococcus aureus. Experiment IX. Table showing the R< suits of Subcutaneous Inoculation of Rabbits receiving Alcohol to the Stage of Intoxication daily., with Cultures of Staphylococcus Pyogenes Aureus. 34 Acute Alcoholism on the Vital Resistance of Rabbits to Infection Rab- bits. No. of days ob- served. Tctal amount of alcohol received. Daily dose of alcohol. Interval between the beginning of alcohol and time of inoculation. WEIGHT IN GRAMMES. Lesions ref- erable to in- oculations. + = present. 0=absent. Lesions ref- erable to the alcohol. + = present. 0=absent. Results and remarks. Begin- ning. End. 74 5 30 c. c. 5 to 10 c. c. Do. 1,720 1,400 + (?) (Pericar- ditis and pleuritis.) O Died on fifth day as direct result of last dose of alcohol, from under the influence of which it did not recover. Animal was very susceptible to al- cohol. By mistake its last dose was 10 c. c. in- stead of 5 c. c., as had been the case. Autopsy.-Slight purulent reaction at site of inocu- lation. Purulent pericarditis and pleuritis. No abscesses. Slight peritonitis. Cultures.-Blood, left pleura, kidney, and spleen gave a feebly growing staphylococcus identical with that found in No. 73. Site of inoculation gave typical staphylococcus aureus. 75 1 10 c. c. Do. 1,590 0 0 Died during night of day of inoculation. Autopsy.-No macroscopic lesions anywhere to ac- count for death. Stomach normal and filled with partly digested food. Cultures.-Staphylococcus aureus from site of in- oculation. Blood and kidney sterile. 76 14 140 c. c. 10 c. c. Do. 2,420 2,050 + (?) (Pericar- ditis and pleuritis.) 0 Died on fifteenth day after inoculation. Autopsy.-At site of inoculation was circumscribed collection of cheesy pus of about size of an alm- ond. Fibrino purulent pericarditis and pleuritis. Both thoracic cavities filled with purulent matter. Cultures.-Staphylococcus aureus in large numbers from the site of inoculation. A few colonies of cocci from liver. Thoracic cavity gave large numbers of slowly growing micrococci that gave the impression of an enfeebled culture of staphy- lococcus aureus (see Nos. 73 and 74). 77 9 90 c. c. 10 c. c. Do. 1,660 1,260 O 0 Died on tenth day after inoculation. Autopsy.-Only slight reaction at site of inoculation. No lesions on macroscopic examination to account for death. Cultures.-Blood, liver, and kidney sterile. A. C. Abbott 35 78 46 r 1 2.130 0 . Apparently well after fortv-six days. Weighs 1,850 grammes. Apparently well 79 46 No alcohol. Inocu- 1,560 0 after forty-six days. Weighs lated as above. 1,780 grammes. 80 46 1,490 0 Apparently well after forty-six days. W eighs -J 1,570 grammes. Experiment X. Results of Intravenous Inoculation of Rabbits that were receiving Alcohol daily to the Stage of Intoxication, with a Culture of Staphylococcus Pyogenes Aureus attenuated (?) by Exposure to Chloroform. 81 82 1 4 45 c. c. 22'5 c. c. 5 to 7 • 5 c. c. 5 to 7'5 c. c. 2 days. Intrave- nous inoculation with 0'6 c. c. of a chloroformed culture of S. aureus. Do. 1,200 1,630 1,050 1,640 + (Pelvis of kidney. Thoracic cavity (?).) + (?) (Peritoni- tis.) + (Stomach.) + (Stomach.) Died on fifth day after inoculation. Autopsy.-Pleural cavities and pericardium filled with clear serum. Purulent inflammation of pel- vis of right kidney; no cortical lesions. Urine contained microscopically numerous micrococci. Mucous membrane of stomach eroded. Cultures.-Blood, left kidney, peritonaeum, and liver sterile. Pelvis of right kidney and urine con- tained staphylococcus aureus in large numbers. Died on second day after inoculation. Autopsy.-General acute peritonitis, with deposit of lymph over coils of intestines. Mucous mem- brane of stomach very red and eroded. Cultures.-Blood, kidney, and peritonaeum all con- tained a pure culture of a staphylococcus that grew slowly and suggested an attenuated staphy- lococcus aureus. Controls. 83 ■- 28 .....J No alcohol. Inocu- lated as above. 1 1,350 1,530 The observation was discontinued at twenty-eighth day. The animals had gained in weight, and had at no time shown effects of the treatment. 84 ( ) 1,410 1,750 Controls.