,CP *.;< •UNIV. OPAIJCM, ,' OCT 141905 No. 26.— DECEMBER, 1904 DEPARTMENT OF THE INTERIOR BUREAU OF GOVERNMENT LABORATORIES BIOLOGICAL LABORATORY The Clinical and Pathological Signifi- cance of Balantidium Coli Richard P. Strong, M. D. MANILA BUREAU OF PUBLIC PRINTING 1904 25822 PREVIOUS PUBLICATIONS OP THE BUREAU OP GOVERNMENT LABORATORIES. No. 1, 1902, Biological Laboratory. — Preliminary Report of the Appearance in the Philippine Islands of a Disease Clinically Resembling Glanders. By R. P. Strong, M. D. No. 2, 1902, Chemical Laboratory. — The Preparation of Benzoyl-Acetyl Peroxide and Its Use as an Intestinal Antiseptic in Cholera and Dysentery. (Prelim- inary notes.) By Paul C. Freer, M. D., Ph. D. No. 3, 1903, Biological Laboratory. — A Preliminary Report on Trypanosomiasis of Horses in the Philippine Islands. By W. E. Musgrave, M. D., and Norman E. Williamson. No. k> 1903, Serum Laboratory. — Preliminary Report on the Study of Rinderpest of Cattle and Carabaos in the Philippine Islands. By James W. Jobling, M. D. No. 5, 1903, Biological Laboratory. — Trypanosoma and Trypanosomiasis, with Special Reference to Surra in the Philippine Islands. By W. E. Musgrave, M. D., and Moses T. Clegg. No. 6, 1903. — I. New or Noteworthy Philippine Plants. II. The American Element in the Philippine Flora. By Elmer D. Merrill, Botanist. No. 7, 1903, Chemical Laboratory. — The Gutta Percha and Rubber of the Philip- pine Islands. By Penoyer L. Sherman, jr., Ph. D. No. 8, 1903. — A Dictionary of the Plant Names of the Philippine Islands. By Elmer D. Merrill, Botanist. No. 9, 1903, Biological Laboratory. — A Report on Hemorrhagic Septicemia in Animals in the Philippine Islands. By Paul G. Woolley, M. D., and J. W. Jobling, M. D. No. 10, 1903, Biological Laboratory. — Two Cases of a Peculiar Form of Hand Infec- tion (Due to an Organism Resembling the Koch- Weeks Bacillus). By John R. McDill, M. D., and Wm. B. Wherry, M. D. No. 11, 1903, Biological Laboratory. — Entomological Division, Bulletin No. 1, Preliminary Bulletin on Insects of the Cacao. (Prepared especially for the benefit of farmers.) By Charles S. Banks, Entomologist, Bureau of Government Laboratories. No. 12, 1903, Biological Laboratory. — Report on Some Pulmonary Lesions Produced by the Bacillus of Hemorrhagic Septicaemia of Carabaos. By Paul G. Woolley, M. D. No. 13, 190k, Biological Laboratory. — A Fatal Infection by a Hitherto Undescribed Chromogenic Bacterium : Bacillus aureus foetidus. By Maximilian Herzog, M. D. No. Ik, 190Jf. — Serum Laboratory: Texas Fever in the Philippine Islands and the Far East. By J. W. Jobling, M. D., and Paul G. Woolley, M. D. Biological Laboratory: Entomological Division, Bulletin No. 2, The Australian Tick (Boophilus australis Fuller) in the Philippine Islands. By Charles S. Banks, Entomologist. No. 15, 190^, Biological and Serum Laboratories. — Report on Bacillus Violaceus ManilaB : A Pathogenic Micro-Organism. By Paul G. Woolley, M. D. No. 16, 190k, Biological Laboratory. — Protective Inoculation against Asiatic Chol- era : An Experimental Study. By Richard P. Strong, M. D. (Continued on third page of cover.) No. 26.— DECEMBER, 1904 DEPARTMENT OF THE INTERIOR BUREAU OF GOVERNMENT LABORATORIES BIOLOGICAL LABORATORY The Clinical and Pathological Signifi- cance of Balantidium Coli Richard P. Strong, M. D. MANILA BUREAU OF PUBLIC PRINTING 1904 *' 25822 LETTER OF TRANSMITTAL Department of the Interior, Bureau of Government Laboratories, Office of the Superintendent of Laboratories, Manila, November 29, 190Jf. Sir : I have the honor to transmit herewith for publication an article entitled "The Clinical and Pathological Significance of the Balantidium Coli." Very respectfully, Eichard P. Strong, Director Biological Laboratory, Acting Superintendent Government Laboratories. Hon. Dean C. Worcester, Secretary of the Interior, Manila, P. L 3 CONTENTS. Page. Introduction 7 Historical review 8 Geographical distribution 10 Synonymy 10 Zoological description 10 Modes of infection 15 Animal experiments 16 Clinical histories and autopsies 20 Clinical summary 53 Prognosis 56 Treatment 56 Pathological significance 57 Summary of gross lesions 57 Histological studies _ 58 Conclusions 66 Addenda 67 Bibliography 70 Plates I-IX 77 5 THE CLINICAL AND PATHOLOGICAL SIGNIFICANCE OF THE BALANTIDIUM COLI. By Richaed P. Steong, M. D., Director of the Biological Laboratory. INTRODUCTION. There apparently exists to-day, both in American and English medical literature, considerable obscurity regarding the pathogenic importance of the Balantidium coli in man. Most of our recent text-books of medicine either fail entirely to mention this infusorium or only refer to its occasional occurrence in the large intestine in certain cases of diarrhea or dysentery, where it is often assumed to be an accidental invader of little importance, and its injurious influence is usually doubted. Nevertheless, it seems probable that this parasite is not only harmful to man, but one that is capable of giving rise to a specific diarrhea which is often persistent in its course and not infrequently of a serious nature. Since the first definite description of the Paramecium coli and the report of a case by Malmsten and Loven in 1857, 1 a considerable number of other instances of human infection with this organism have been published. The list which I have been able to collect up to this date 2 (including Malmsten's first case) now numbers 117. In 1891 Mitter could collect only 28 cases from the literature, and in a number of these the data are very incomplete. It is from his dissertation that many authors have obviously formed opinions regarding the Balantidium coli. Yet Mitter, in his paper, 1 The references to authors are arranged in chronological order at the end of the article. 2 August, 1901 ; see also Addenda. draws no very definite conclusions regarding the pathogenic import- ance of the parasite. However, from an analysis of the entire number of cases in man, I believe that more definite ideas regarding this infusorium may be arrived at. During the summer of 1900, while investigating the intestinal diseases of the Philippine Islands, I encountered an instance of infection with this parasite. 1 The case came to necropsy where definite gross and microscopical lesions were observed. The study of this case and of the literature regarding the Balantidium coli furnished the opportunity for the present paper. In this inquiry I shall, after reviewing briefly the history of the parasite and its zoological properties, next ask attention to a survey of the cases of human infection ; and finally, after summariz- ing the gross pathological changes, shall endeavor to emphasize certain microscopical lesions attributed to this infusorium and which, in so far as I have been able to ascertain, are hitherto undescribed. HISTORICAL REVIEW. Stein has suggested that it is probable that the Balantidium coli was first seen by the discoverer of the infusoria, Leeuwenhoek. The latter, at least, reported that when about 30 years old he began to be troubled with loose, painful, and frequent stools. This condition continued for some time and led him to a micro- scopical examination of his excrement, where he observed delicate motile organisms mostly the size of a red blood corpuscle, but some larger, which moved about with the aid of a little foot-like hook. In portions of the feces as large as a grain of sand there was at least one of these little animals, but generally more — four or five, or even eight. They never occurred in the normal excrement. Leuckart has pointed out that since the Balantidium coli is con- siderably larger than a red blood cell, Leeuwenhoek's description seems but slightly applicable, but that probably the report was based merely on a subsequent estimate in which a mistake might easily have been made, and he further remarks that it would have been indeed impossible for Leeuwenhoek, with the optical means at his disposal, to have seen the movement of cilia which he % A preliminary report of this case has already been published. (See Bibliography. ) 9 evidently described in an infusorium only the size of a red blood corpuscle. However, as has been referred to above, the parasite was first observed definitely and described by Malmsten in 1857 in Stock- holm. The investigation of the infusorium was undertaken at this time with the assistance of the celebrated zoologist, Loven, who recognized it as new, made drawings, and prepared a description of the parasite for Malmsten. This author also finally concluded that the parasite was, from its structure , more like Paramoecium colpoda (Ehrenberg) ; he therefore referred it to Ehrenberg's holotrichous genus, Paramoecium, and suggested the name of Paramoecium. coli for it, Claparede and Lachman, in 1858, confirmed mainly the researches of the Swedish investigators, and assigned the parasite as a member of the genus Plagiotoma (Plagiotoma coli), although no traces of adoral cilia were demonstrated. Stein, in 1860, pointed out that the parasite described by Malm- sten according to published data was one of the true Leucophrys patula and denominated it as Leucophrys coli. He maintained that is could not be a true Paramoecium. In 1861-1863 Leuckart found and studied the parasite in pigs. He thought the oral cavity quite different from that described by the Swedish investigators, and pointed out that the terminal mouth did not lead into a longitudinal fissure in the lateral border of the body, but was found in the middle line — that is, on the anterior surface — in the form of a three-sided opening. He suggested that the parasite should be placed in the genus Holophrya, if it was not assigned to a new one of its own. In 1862 Stein, from his studies made on the parasites from swine, pointed out that Leuckart also had not correctly recognized the oral structure of the parasite — that what he held to be the mouth was the dilated anterior part of the peristome, and the esophagus lying next to it was only the posterior end of the same. Stein also showed that the oral orifice was surrounded by a left-sided zone of adoral cilia. It became clear that this represented the peristome which was quite of the form found only in Balantidia; he therefore assigned it to the genus Balantidium (Balantidium coli, Stein, 1862). Leuckart, in the next edition of his work, admitted that Stein 10 was the first to recognize the true nature of the peristome, and from further studies on the parasite from hogs confirmed Stein's views. In the earlier days of the history of the parasite Wising, Grassi, and Calandruccio maintained that the species of Balantidium found in man was different from that observed in the hog. Wising based his arguments chiefly upon the fact that the parasite in man was somewhat smaller than that of the hog and that the former did not become encysted. The other authors referred chiefly to the fact that they were unable to infect themselves by the ingestion of Balantidium cysts derived from the hog. Among more recent observers, however, the Balantidia of man and of the pig are usually regarded as identical. Geographical distribution. — The infusorium has to-day an extended geographical distribution, as the table of the cases of infection in man on page 18 will show. As to its distribution in hogs, we may mention here that since Leuckart's discovery of the parasite in these animals in Germany it has been observed in the hogs of Sweden by Stein, Ekecrantz, and Wising, in those of Italy by Grassi, of St. Petersburg by Eepchevski, of the United States by C. W. Stiles, 1 and of Manila by the author. Blanchard states that in a few examinations of the hogs in Paris he did not find this parasite. He admits, however, that his observations were not very extended, and Neumann has, moreover, since found it in pigs in Toulouse, and Eaillet in those of Alf ort. ZOOLOGICAL DESCRIPTION. SYNONYMY. Paramecium { ?) coli, Malmsten, 1857, Leuckart, 1861. Plagiotoma coli, Claparede and Lachmann, 1858. Leucophyrs coli, Stein, 1860. Balantidium coli, Stein, 1862. Holophyra coli, Leuckart, 1863. Balantidium coli. fiaXdyridioy (diminutive of paXdynoy, a bag). Class, Infusoria; subclass, Ciliata; order, Heterotrichida; family, Bursaridne. The body is usually somewhat oval-shaped, measuring from about 0.07 to 0.1 mm. in length by 0.05 to 0.07 mm. in breadth. The anterior end is a little truncated with a short peristome, which is generally funnel-shaped, and opens externally near the anterior pole, When the parasite is feeding, however, the peristome becomes 1 Personally communicated. 11 broadened out and triangular in form, and one may see then that it is not simply a furrow. The peristome gradually narrows, extends obliquely toward the median plane, and leads by its posterior end into the short gullet. While it appears that the peristomal region itself is destitute of cilia, the left border of the funnel is beset with them, and they are longer and stronger here than over the general body surface. These adoral cilia, when in motion, give something of the appearance of a paddle wheel revolving in the liquid media which surrounds the parasite. The gullet continues and runs obliquely through the cortical layer and enters the medul- lary substance. The posterior end is rounded and contains the anus, which at times is almost imperceptible. However, particles may be frequently observed to pass from it. The interior structure of the parasite consists of a finely granular substance in which we may distinguish at times fat and starch granules, and even occa- sionally red and white corpuscles. Limiting the granular endosarc is a clear, almost transparent layer of protoplasm, which is striated with spiral lines extending from the peristome to the posterior extremity. (See PL IX.) The surface of the cortical layer is surrounded by a cuticle covered with cilia. The nucleus lies on the ventral surface either anteriorly or posteriorly; it is usually kidney-shaped. It stains readily and intensely with ordinary dyes. There are generally two contractile vacuoles whose position is variable, though usually the larger one lies near the posterior ex- tremity. Sometimes only one is present, or, according to Leuckart, as many as three may be observed. Their contractions are made rather slowly. Stein states that the two vacuoles are connected by a lacuna and the contents of the anterior one may sometimes be seen passing to the posterior. The body exhibits greater permanence of form than we usually see in the naked infusoria. Nevertheless, it is able to change its shape and may appear quite round. In passing between obstacles and in breaking through the tissues it may become considerably flattened out, (See PL IX.) The parasite has the property of moving rapidly forward and apparently . with some force. It also has a rotary motion. In dying the organisms generally stop their forward motion and begin to rotate; the form becomes rounder and the movement of the cilia slower. Spherical masses, which gradually increase in size, are next pushed out from the anus. Smaller ones may issue 12 from the oral orifice and from other parts of the body. Finally the parasite becomes a granular mass, and is soon unnoticed in the surrounding media. Gurvich has described a rarer mode of death in which the con- tents of the body are discharged with great rapidity from the oral opening, the organism is reduced to one-half its size, the cilia stop moving, and the parasite shortly appears as a granular mass. REPRODUCTION. Reproduction has been described in three ways, viz, by division, by budding, and by conjugation. Division is apparently the most common method of reproduction. It has been noted by Stein, Ekecrantz, Wising, Leuckart, and others. According to Leuckart, the first step in the division is the formation of a ciliated circle around the middle of the body. These cilia are as long and as active as those in the adoral region. However, they do not at first encircle the parasite completely, but are absent on the dorsal surface for a considerable space. It seems, therefore, that it is primarily and especially on the ventral surface that they originate, but whether from a new formation of cilia or from outgrowths of former ones Leuckart was unable to say. At this stage of the division the two vacuoles are widely separated, and the nucleus has grown comparatively little. The girdle of cilia is nothing but the first outline of the subsequent adoral zone, as the further course of the process shows. One can very easily recognize close beside the girdle of cilia a construction which is at first shallow and easily overlooked, but which after a short time almost separates the two halves of the parasite from one another, so that the connecting part is restricted to a small band. The granular substance in each half is often drawn back from the line of construction. The arch of the cilia gathers more closely around the anterior pole of the posterior half, and is continued inward into a short, flat, but already triangular protuberance formed close behind the extremity of the ventral surface. At this stage the nucleus has already divided into two parts which lie one in each half. We have not infrequently observed this method of reproduction in our specimens and sections. In stained sections containing the parasite the nucleus usually shows a homogeneous appearance, except in those in which the proc- ess of division is apparent, when the nucleus appears granular. No star formations were observed, and division is apparently by direct mitosis. 13 Sometimes, when found dividing, the organisms are all but sepa- rated, being united only by a thin connecting thread. Leuckart once observed this thread rolled into a ball, which resembled a ball of dung the animal was about to drop. Ekecrantz, having also seen these formations, recorded them as buds, and was therefore led to believe that the parasite reproduced by budding. Leuckart stated that although he had actually observed a small vacuole inside of one of these balls, he was far from being inclined to consider that the parasite reproduced by budding. Many other authors are also not convinced that reproduction takes place by this method. Madame Lavrovskaya, Bushuyeff, Zhegaloff, and Ortman have, however, described reproduction by this manner. The process as recorded is in general as follows: Budding. — The parasite turns on its axis several times; the move- ments of its cilia stop, except at one place where they continue to move rapidly. After awhile in this place a protrusion of the proto- plasm occurs, which gradually increases in size, and later on takes a spherical form. From the body of the first cell one or two nuclei enter the new body and the protruded form begins to rock to and fro from the mother cell. The little bridge of protoplasm connect- ing the two gradually becomes thinned, finally ruptures, and the young body becomes free. Bushuyeff further states that these young specimens were of various forms and resembled somewhat the amoebae described by Loesch; their movements were slow and amoeboid-like. To his regret, he was not able to observe their transition to adult, rapidly moving specimens. Lavrovskaya ob- served the separation of the protoplasm, but likewise not the development to full-grown organisms. She also observed forma- tions four times the size of white blood cells which were surrounded by a membrane and inclosed a granular nucleus and vacuoles as in developed Balantidium coli, but these forms possessed no cilia and were not motile. Not having followed their transition to full- grown parasites, she could not speak definitely regarding their importance or of their significance in the life history of the parasite. GKirvich, while he did not observe budding, saw such formations half the size of fully developed Balantidium coli supplied with cilia and moving, though not very rapidly. He suggests that this is perhaps another step in the transition to the fully developed parasite. Vlayeff also observed young forms immovable and without cilia. Zhegaloff was able to observe the movements of the separated * 14 protoplasm after it had left the mother cell, but no further develop- ment was noted in these new forms, and after an hour they had all died. In PL VII may be seen examples of the so-called "budding forms." We were not able to satisfy ourselves definitely that the parasites really multiplied by this manner. In the stained sections of the large intestine of our case, however, smaller forms of the parasite were occasionally observed. Sometimes these were from one-third to one-half the size of full-grown Balantidia. Conjugation was first described and pictured by Wising in 1871. According to this author, in the- first stage the two individuals become united by their peristomal folds, while the bodies lying with the surface of the abdomen to each other remain quite separate. The conjugated individuals presented exactly the same appearance seen in Balantidium entozoon except that the changes of the nucleus and nucleolus, which occur normally in the latter, were not observed by Wising. Examples of the first stage may probably be seen in PL VIII. The prominence of the peristomal fold in each parasite is to be noted. In none of the other single specimens is it so well marked or so distinctly seen. Woit and Gurvich have also noted conjugation. According to Gurvich the process is continued as follows: The two parasites become fused together and a double contoured coating forms. The encysted form then appears as a colorless oval body clearly dis- tinguished from the surrounding feces. Its size is from two to three times that of an ordinary Balantidium coli. In this capsule the process of segmentation may at times be observed when several spherules are seen to be formed. From these spherules Gurvich supposes new individuals may be produced under favorable circum- stances. Chichulin observed ovoid forms with a double contoured layer. Their size was several times that of the parasite. Their con- tents consisted of separate round bodies like segmented spherules, with very granular protoplasm. He considered these transitional encysted forms. The change to fully grown parasites was not observed. Ency station. — I was not fortunate enough to observe encysted forms. Leuckart, however, described ency station as follows: The parasite gradually loses its cilia, except a few adoral ones. The interior granular mass becomes gathered together into a heap, from 15 which some large drops of fat shine out. Later still the cilia and the epistome disappear, and the body finally appears as a ball (0.08-0.1 mm.), which is surrounded on all sides by a capsule-like, thickened cuticle, but still incloses, as before, a clear peripheral layer and a dark central mass with fat drops. He states the origin of the cysts could admit of no doubt, for he observed in their early stages the nucleus and vacuoles. These observations have been con- firmed by Stein and others. The conditions under which eneysta- tion occurs are complicated, as drying does not always suffice. The encystation after conjugation, as described by Chiculin, has already been noted. MODES OF INFECTION. As has been pointed out before, man is not the only host of the Balantidium coli. It seems that the hog is its proper entertainer, and the parasite is in fact found very frequently in great abundance in the colon and caecum of this animal. Further, it is probable that man only occasionally derives it from the hog. As to the way human infection occurs, it appears not unlikely that this infusorium sometimes obtains admission to its host in an encapsulated state. It is not probable that the freshly voided parasites in the feces often gain access to the human alimentary tract. The encysted forms, however, when the feces become dried and broken up, are scattered about and may come into contact with the food or drinking water. It is interesting to note, however, that Klein has recently stated that Paramecium coli is almost always present in the sewage as it passes out of St. Bartholomew's Hospital. In a sample of sewage bottled for over thirteen weeks he still found living Para- moecium coli. The parasite has also been found in London drinking water. Leuckart pointed out that it preserved its motility for long periods in water of ordinary temperature, and that it was much less sensitive to cold than other monads. However, even if drinking water might offer a means of conveyance of the fresh forms into the alimentary canal of man, yet it is a question whether the parasites, if introduced in this way, would survive in the normal stomach or be destroyed by the gastric juice. We must remember, however, that the disease frequently occurs shortly after the preparation of sausage or the ingestion of uncooked sausage meat, and we can not be certain that such infection is due to encysted forms only. There is the probability that a few parasites might pass through the stomach under certain conditions unharmed, particularly when 16 the number introduced has been large. . Swine, however, are prob- ably not infrequently infected with the freshly voided forms, on account of their dung-eating habits ANIMAL EXPERIMENTS. Attempts to infect animals have usually been unsuccessful. Ekecrantz and Wising's experiments, in which attempts were made to inoculate dogs and rabbits with feces containing the para- site, both by the mouth and rectum, were negative. Eapchevski repeated these experiments on dogs, introducing on several occasions fresh feces containing large quantities of Balan- tidium coli into the intestine of these animals! The parasites did not live and multiply, but died and produced no disturbance. This author also performed experiments on dogs, in which colitis was artificially produced by means of repeated enemata of emulsions containing croton oil; fresh feces containing living parasites were then introduced into the rectum, but the results were here also negative. Vlayeff performed four experiments on rabbits. In two he introduced 15 c. c. of feces containing Balantidium coli — in one into the rectum and in the other into the stomach. The first died in a few hours; the second died after a week. In both he found catarrh of the intestine, especially of the lower part. In the other two rabbits he introduced feces of the same patient, but containing no Balantidium coli; both of these animals remained alive. It is not stated whether the parasites, either alive or dead, were present in the first two rabbits at autopsy. Apparently they were not found. Cassagrandi and Barbagallo maintained from numerous experi- ments that the parasite could sometimes live in the intestine of cats if catarrh was first produced, but that it was incapable of producing independent disease there. ChigayefT, however, obtained negative results in two cats into which 200 grams of feces containing Balantidium coli were injected per rectum, and which were also fed fresh meat over which the infected feces had been poured. Both remained healthy. Chiculin also failed to infect two cats which were fed with meat covered with feces containing Balantidium coli. In two other cats the dejecta were introduced per rectum. One of these cats escaped from captivity and could not be caught; the other was killed after two weeks. There was catarrh in the lower part of the intestinal 17 canal, with several small erosions of the mucosa, whose edges were eaten out, thickened, and hypergemic. No parasites were found in the ulcers or around them. The necropsy was performed while the cat was still warm. The author thinks the ulcers were due to traumatic injury on the injection of the feces. Two jack rabbits were also infected per rectum. On necropsy little ulcers of the same character were found, and slight catarrh, but none of the parasites could be found on the mucosa in spite of the fact that the autopsy was perfectly fresh. Chiculin also examined the intestine of two hogs in the dejecta of which during life he had observed Balantidium coli. He found pathologic changes in one hog, but only of the lower part of the intestine. There were no ulcerations, but the mucosa was greatly furrowed, intensely hyperasmic, and abundantly covered with mucus. However, the mucus did not contain parasites. The intestine of the other pig was completely normal. Lavrovskaya experimented with guinea pigs, injecting the feces containing the parasites into the intestine in the healthy state as well as after it had been inflamed with ammonia and potassium hydroxide. Her results were negative. AfanasyefFs experiments on these animals also failed. ZhegalofT thought that perhaps the negative results of these experiments were due to the choice of the animals. He selected young pigs, 1|, 4, and 5 weeks old. These he fed for one week with large quantities of feces containing Balantidium coli and blood, No positive results were obtained. No diarrhoea was produced and no parasites were found. Later he added dried feces to their food; but still the results were negative. Lastly he tried to inoculate by enemata into the healthy intestine and into this organ inflamed with croton oil He continued such experiments for two weeks, but the results were likewise negative. In the author's hands, experiments on monkeys have also failed. While it seems that the parasite is not pathogenic for pigs, it is worthy of observation that the feces of these animals are generally soft and diarrheal-like, and it is usually in the soft stools of hogs that the infusorium is found. VIABILITY. The parasite has not been grown or isolated in pure cultures, though attempts have been made on hard and liquid media. It, 25822 2 18 however, is probable that it may be grown on special media in the presence of certain bacteria. Usually it dies shortly after being removed from the intestine or after the death of its host. The time it may live, however, is variable. Thus, in feces where the parasites are numerous, all may die in from one to two hours. According to Zhegaloff, if placed in the cold they cease to move after from ten to fifteen minutes. In other specimens of feces they may live from ten to fifteen hours, or even longer. Vlayeff has stated that at 20° C. he once succeeded in keeping them alive for three days. So likewise a few hours after the death of their host all the parasites may have disappeared, or only a few dead ones may be found, but on one occasion Chigayeff found them alive one and one-half days after the death of his patient. The body lay in the cold; when the specimens from the intestine were examined the parasites began to move. For the preservation of specimens of Balantidium coli in the feces, Yakimovich and Eomanovski have both described methods. That of the former, which consists essentially of a gelatin mass, preserves the cilia admirably. Table of cases and necropsies. Case No. Country and author. Date. Cases. Nec- rop- 3 4 9,10 31-33 40 42 46 47 54-65 67 73-79 80 81 82,83 85 84 86 87 88-90 91 92 106-109 110 116 117 Russia: Stieda Stieda, Wachsmuth Loesch Rapchevski Afanasyeff Madam Lavrovskaya. Afanasyeff Janowski Lobas Fadieyeff Gurvieh Trzhetsieski Janowski Bushuyeff Lang Chigayeff Vlayeff Dehio Woit Zhegaloff _'„_. Solovyeff Chiehulin Collman Solowiew Ssaweljew 1866 1866 1870 1880, 1882 1888 1890, 1891 1891 1891 1894 1895 1896 1896 1896 1897 1898 1898 1898 1898 1898 1899 1899 1900 1900 1901 1901 J 1 12 1 1 10 1 1 1 1 2 20 Total . U death; no necropsy. 2 2 deaths; no necropsy. 19 Table of cases and necropsies — Continued. Case No. Country and author. Date. Cases. Nec- rop- sies. 1.2 7 5 6 8 11-13 14-16 17-21 36 37-39 41 98-105 49 50 51 53 66 68 71,72 93^97 28 29,30 69 70 34 45 52 111-114 43 115 44 22-27 35 48 Sweden: Malmsten _ _ 1857 1869-70 1869 1869-70 1871 1873 1874 1874-75 1885 1885 1890 1899-1900 2 1 1 1 1 3 3 5 1 3 1 8 1 ----- -- ___ ___ 1 Winbladh Ekecrantz _ . _ Belgrage _ _ _ _ Wising _ _ _ Peterson __ Peterson. __ Henschen Edgren____ Wising . Edgren _ Henschen Total _ 30 6 Finland: Runeberg 1892 1893 1893 1894 1895 1896 1896 1899 2 5 Runeberg _ _ __ Gruner Blomberg . _ _ Patiala _ Sievers DelaChapelle _ __ __ Runeberg, reported by Sievers Total _ _ _ _ __ 13 Italy: Graziadei _ _ 1880 1880,1882 1896 1 2 1 1 Perroncito Cassagrandi and Barbagallo__ - _ Grassi ____ Total 5 Germany: Zurnieden , 1881 1891 1893 1900 1 1 1 4 Pfeiffer Roos _ Collmann Total 7 1 1 1 6 1 1 1 North America: Mitter 1891 1900 1891 1875 1884 1892 Philippine Islands: Strong and Musgrave _ _ South America: Ortman _ Cochin China: Trielle _ Stockvis 1 Africa: Maggiori Grand total 1117 32 1 Deaths, 35. 20 ANALYSIS OF THE CLINICAL CASES AND AUTOPSIES Cases 1 and 2. [Malmsten, Stockholm, 1857.] Case 1. — Malmsten (2) x described the first case in man, which was observed in 1856 in Stockholm. The patient, a male, 36 years old, had suffered from an attack of cholera two years before which left him with chronic intestinal catarrh. On admission he was extremely emaciated and complained of digestive disturbances, colic, diarrhea with tenesmus, and some blood in the stools. The latter also often contained undigested particles. The frequency of the stools was increased as soon as the patient ate anything. The examination of the rectal mucosa showed an ulcer with raised borders which produced a purulent excretion mixed with blood. The exudate con- tained large numbers of infusoria which were later designated as Paramwcium colt. The ulcer was touched daily with silver nitrate, and enemas of quinine sulphate were administered. Under this treatment the strength of the patient improved and the ulcer was completely healed in eight weeks. Nevertheless, he still suffered from colic, and while the stools became more consistent they were more frequent. His condition remained stationary for a long time. The stools were now examined microscopically, and large numbers of Paramwcium coli were found. They contained, how- ever, no pus and blood and the author concluded from this fact that there were no more ulcers in the intestines, He also thought for this reason that the parasites were not the cause of the original rectal ulcer. The patient was then treated with enemas of muriatic acid, and the number of the stools became reduced to about two per day. The health of the patient also improved. After six months only an occasional parasite could be found. The study of the infusorian in this case was undertaken with the aid of Loven. Case 2. — In 1857 Malmsten (2) observed the second case, also in Stockholm. The patient, a woman, aged 35 had suffered from colic and severe diarrhea off and on for two years. The stools were usually watery and contained at times blood and fragments of indigested food. Shortly after her entrance to the hospital tenesmus appeared with bloody mucous excre- tion at the end of each stool. On entrance she was extremely emaciated. The stools were frequent, watery, yellowish, and of a gangrenous odor. Microscopically pus cells and Paramwcium coli were present. The weak- ness of the patient increased, the stools became involuntary, and she sank and died. On necropsy the mesenteric glands were swollen. In the large intestine there were numerous small gangrenous ulcers about the solitary follicles; from the sigmoid flexure to the caecum the intestine was filled with foul pus. A small number of Paramwcium coli were found in the ulcers and in the foul pus, but over the whole surface of the normal mucous mem- brane of the large intestine, caecum, and appendix they were very numerous. In the lower portion of the rectum there was an extensive diphtheritic 1 These figures refer to the bibliography. 21 inflammation with large ecchymoses. The solitary follicles of the small intestine were swollen, the mucous membrane of the stomach injected. No parasites were found in the small intestine or stomach. Case 3. [Stieda, Dorpat, 1863.] In the stools of a typhoid fever patient Stieda (8) found on one occasion several specimens of a Paramwcium which in its appearance resembled that described by Malms ten. As he could not afterwards find these parasites he could not investigate them further. The patient, who had severe diarrhea later, left the hospital as cured. Case 4. [Stieda, Wachemuth, Dorpat, 1866.] This case was observed by Wachsmuth and reported by Stieda (8) from the former's notes after his death. The patient, a woman aged 40, had suffered from diarrhea and tenesmus for eight years. For a week previous to entering the hospital she noticed that her feet began to swell and she suffered from palpitation of the heart. On admission she was well nourished, although anemic. The legs were edematous to the knees. The lungs were normal. A feeble, systolic murmur was heard at the apex of the heart, and the liver was slightly enlarged. The urine was normal. An examina- tion of the fluid stools showed undigested food, red blood corpuscles, and Balantidium coli. After dieting and treatment with sulphate of iron and opium the patient improved and was able to leave the hospital, as she felt well. Though the stools became more firm, Balantidium coli was still present. Case 5. [Ekecrantz (10), Upsala, 1869.] The patient, aged 57, had suffered off and on for twenty years from diar- rhea, tenesmus, and cramps. At times the stools were bloody. On admission the patient was emaciated. The tongue was coated and the abdomen distended. The stools were grayish yellow and of thick consistency, con- taining undigested food. Microscopically, large numbers of Balantidium coli were present. Under the administration of carbolic-acid pills the patient improved and the diarrhea increased. The number of Balantidium coli was also greatly reduced. Later the diarrhea gained in severity and at the same time the parasites greatly increased in number. One week later the stools were less frequent and had regained their normal consist- ency without the number of parasites being decreased. The patient refused to remain longer under treatment and left the hospital. Case 6. [Bellfrage (11), Upsala, 1869.] The patient, aged 42, as a child suffered from gastro-enteritis. Later he was healthy until 20 years of age. Then he began to suffer from 22 attacks of diarrhea. A short time before entrance to the hospital the diarrhea grew worse, with severe abdominal pain and tenesmus. One week before entrance blood appeared in the stools. On admission the patient was extremely emaciated and complained of great thirst and abdominal pain. The abdomen was tender, particularly over the epigastrium and in the vicinity of the descending colon. Nausea and vomiting were present. The stools were very thin and contained blood and Balantidium coli. Later they became involuntary and the patient died. Necropsy (fifteen hours after death). — The mucosa of the stomach and small intestine was pale and the solitary follicles of the latter were swollen. There was a mucous polyp in the pylorus. The hepatic flexure of the colon was adherent to the liver. On the peritoneal surface of the transverse colon there were a number of blackened hemorrhagic spots. The mucosa of the caecum and first part of the intestine showed a grayish-green discoloration with red areas here and there. In the caecum there were large and small ulcers of irregular shape, frequently girdled; their floors were formed of the submucosa, which presented a dark, slaty, hemorrhagic appearance. In the large intestine there were also found ulcerations, more frequent and most extensive in the sigmoid flexure and rectum. Here and there were diphtheritic areas over the mucosa of the large bowel. In spite of diligent search in different parts of the intestinal tract, no Balantidium could be found at necropsy. Case 7. [Winbladh (12), Upsala, 1870.] The patient, a laborer, had pneumonia six years before entrance to the hospital. About one and a half years before entrance he gave a history of a severe attack of diarrhea which came on at Christmas time. For nearly a year after this attack he was well. Three months before entrance the diarrhea began again with some blood. On entrance the patient was weak and emaciated. Microscopical examination of the liquid stools showed great numbers of Balantidium coli, but no red blood cells. Under treatment with quinine enemas and sulphuric acid the parasites became fewer in number and as the passages became formed their number still further decreased. Case 8. [Wising (13), Stockholm, 1871.] The patient, aged 62, was employed by a butcher and ate what was left over after slaughtering pig3 and other animals. He also lived in the corner of a stable. About a month before entrance the patient was taken sick with diarrhea and severe colic. His condition gradually grew worse and blood appeared in his stools. There was no tenesmus at first, but later this developed. On admission the patient was extremely emaciated and pale; the stools were often pea-soup-like and contained mucus. Micro- scopically, white and red cells, vibrios, and Balantidia were present in large numbers. The patient was treated with carbolic-acid pills and 23 enemas of carbolic solution, but lie grew worse. Under tannin enemas and tannin and opium suppositories he decidedly improved. After eleven months' treatment with various other drugs he insisted on leaving the hospital. He had gained in strength and flesh and said he was well; however, he still complained at times of "gripes." Occasionally the stools were w T ell formed and contained no Balantidium coli. At other times they were diarrhea-like, containing mucus, red blood cells, and Balantidium coli in large numbers. Cases 9 and 10. [Loesch, St. Petersburg, 1874.] These cases are briefly reported by Rapchevski (21). They were observed by Loesch in Prof. W. E. Ecks's clinic in 1870 and reported orally at the meeting of the society of practicing physicians of St. Petersburg (20). Only symptomatic treatment was used. In one the patient soon died under symptoms of complete exhaustion, and on necropsy there were extensive ulcerations of the large intestine. In the second case, under the use of astringents the diarrhea diminished somewhat but did not disappear, and the parasites were still found in the stools. The patient left the clinic before she had recovered. Cases 11, 12, 13, 14, 15, 16. [Peterson (14), Upsala, 1873-74.] Case 11. — The patient, a workman, gave a history of diarrhea of several months' standing. A short time before admission he noticed blood. On entrance he was considerably emaciated. The cornea of the right eye was ulcerated. There was no history of syphilis. The abdomen was not tender on pressure. The stools were from eight to eleven in twenty-four hours, loose and yellow. Balantidium coli and blood were present. Under treatment with oil, opium, chalk, and enemas of infusion quassiae the appetite improved and the stools contained firm lumps, but the Balantidium coli was unchanged in number. The patient left the hospital in this condition. Six months later his discharges were from two to six daily and contained a little blood. Case 12. — The patient, aged 46, a laborer, had severe diarrhea fifteen years before entrance. Since this he has also had several slight attacks of the same trouble. About three months before entrance he was attacked with diarrhea and colic. The stools were very thin but were said to contain no blood at first. The patient grew gradually worse, and finally blood appeared in the stools with pain in the anus. On entrance he was very weak; the mucous membranes were pale; edema of the legs and feet was present; he complained particularly of gripes in his stomach; the abdomen was swollen and tender; the passages were one to two per hour and passed with pain and tenesmus. Microscopically, large numbers of Balantidium coli and red blood corpuscles were present. The urine showed a trace of albumen and hyaline cylinders. Specific gravity, 1,017. Two days after 24 entrance severe hiccough appeared and persisted in spite of treatment up to the time of the death of the patient, which occurred two days later. The urine and feces were passed involuntarily before death. Necropsy {twenty-four hours post-mortem). — The lungs showed a few T nodes of catarrhal pneumonia. Both kidneys were firm, the cortex of each anemic. The suprarenal capsules were thickened and showed amyloid degeneration. There were some old adhesions about the large intestines. The interior of the stomach was bathed in mucus. In the ileum was found an ulcer which was reddened; its margin was not raised. The mucus in the ileum was in general pale gray, but showed here and there small hemor- rhagic flakes. The walls of the large intestine were considerably thickened, due to the edema of the submucosa. In the caecum and transverse colon were numerous ulcerations, some with irregular borders, others with slightly raised edges and slightly undermined. Their floors were formed sometimes of mucosa and sometimes of muscular coat. The mucosa between the ulcers was very hypersemic. There was some diphtheritic inflammation in the sigmoid flexure. The lower part of the rectum was only reddened. In the small intestine ascaris ova were found, but no Balantidium coli. In the caecum, transverse colon, and sigmoid flexure a few Balantidia were found, but only one with feeble ciliary movements. Case 13. — A stable man, aged 70 years, was troubled with a cough four years prior to admission to the hospital. Later he suffered from gastric catarrh. Three months before entrance diarrhea began and edema of the ankles appeared. On admission he was much emaciated. There was some ascites and the legs were edematous. The stools were yellow gray and contained large numbers of Balantidium coli, but no blood or pus cells. There was no tenesmus. Over the left lung coarse and fine rales were heard. The radial arteries were thickened. The urine contained no albumen. Specific gravity, 1,008. He was treated with Dover's powders, chalk, and opium. Three days before death the diarrhea increased. He died twenty-one days after admission. Necropsy {thirty-four hours post-mortem). — There was edema of the hemispheres of the brain and of its membranes. Atheroma of the aorta and pulmonary arteries. The lungs were congested and edematous. The pleurae thickened at the apices. In the lower lobe of the right lung was found a thrombus. The mucosa of the jejunum and ileum was pale, but in some places in the latter hypostatically congested. In the large intes- tine there were ulcerations with their edges and bases formed of muscular coat. The small ulcers had an irregular form. The ulcers were most numerous in the colon. There were also pigmented and slate-colored patches present. No Balantidia were found at the necropsy, but they were plentiful just before death. Cases 14, 15, and 16. [Peterson.] These cases of diarrhea and Balantidium coli infection were, according to Sievers, reported orally to the society of physicians in Upsala in 1874. 25 Although Peterson promised to publish them, he has apparently not yet done so. Cases 17-21. [Henchen (15), Upsala, 1874.] Case 11. — The patient, a woman aged 45, had always been well until her present illness, which began at Christmas time, 1873. She was then attacked with severe diarrhea, chills, and vomiting. She also suffered from colic and pain along the sigmoid flexure. There was no tenesmus. She gradually lost strength and became confined to her bed. An examina- tion of the bloody stools showed innumerable Balantidia. After treatment with large enemas of acetic and tannic acid the patient improved. She was discharged after two weeks, convalescent, with no abdominal disturb- ance and no Balantidium coli in her stools. Three months later she was well, with no parasites in the feces. Case 18. — The patient, aged 54, gave a history of diarrhea for over two years. He suffered also with abdominal pains and increasing colic. The stools were very thin, pea-soup-like, but not bloody. They contained numerous Balantidia. Under the same treatment as case 17, the Balan- tidium greatly diminished and the patient improved and w r as able to leave the hospital. One month and a half later he appeared in perfect health. Case 19. — The patient, aged 14, a daughter of case 17, had always been strong and healthy until her present illness, which began some months before with symptoms of acute gastritis. Diarrhea began shortly after- wards, with frequent bloody stools. The feces showed numerous Balan- tidia. After nineteen days' treatment with tannin enemas the unfavorable symptoms disappeared and the patient returned to her home, though there were still a number of parasites present in her feces. The diarrhea reappeared with great severity, and she returned and was again treated with tannin enemas. She improved and left the hospital. For some time afterwards the stools were normal and contained no Balantidium coli; at times they were thinner at the end of the motion. Her general condition was good. Case 20. — The patient, aged 33, had previously always been healthy. Her present illness began with diarrhea and abdominal pain. Her appetite failed and she gradually lost strength. The stools showed numerous Balantidia. After treatment with tannic-acid enemas the parasites were reduced to very few in number and the stools became normal. The appetite and strength also returned. The patient returned home and was well for fourteen days, but the diarrhea broke out anew. The stools again showed very large numbers of Balantidia. Under the same treatment as above the parasites disappeared and the patient returned home, convalescent. Case 21. — The patient, aged 45, had alw T ays been well until eight years ago, when he began to have numerous thin stools without other symptoms. One year ago he grew worse; the stools became thinner and more numerous. Tenesmus also developed. He lost strength and appetite. The stools showed large numbers of Balantidia. After tannin enemas the patient improved. The stools had not become of normal consistency and the 26 Balantidia were still present, though in small numbers, when the patient left the hospital. He was well for one week, when his former symptoms all reappeared. Cases 22-27. [Treille (17), Cochin China, 1875.] While on a voyage between China and Cochin China, Treille observed a small epidemic of fifteen cases of dysentery of a very mild type. In six of these cases he found numerous Balantidia in the stools. The clinical history of the cases is very brief; it is merely mentioned that the stools in all contained blood in addition to the parasites, and that the latter were found particularly in the beginning of the disease and at the time of the appearance of the first blood in the stools. The feces of the other cases which showed no blood also showed no Balantidium coli. In most of the cases the parasites disappeared after a few days' treatment, usually with ipecac. Robin confirmed the diagnosis of the parasites in these cases. Case 28. [Graziadei (19), Turitio, 1880.] In a patient received in the clinic at Turin and affected with severe anemia of the Gotthard tunnel, Graziadei found in the fresh feces, together with uncinaria, ascaris lumbricoides, and tricocephalus ova, always numer- ous Balantidia. This was the first time the parasite had been reported from Italy. As the patient had the common form of Gotthard anemia, it was difficult for Graziadei to tell the significance of the Balantidium coli. He states, nevertheless, that the patient suffered with intermittent diarrhea and that there was a small amount of blood in the stools and that this was the only case of the Gotthard anemia where he found blood in the feces. Cases 29, 30. [Perroncito, 1880 (22) and 1882 (25).] Perroncito found the parasite in two cases of dysentery — in the first in Torino and in the second in an epidemic of dysentery in Vereellese in connection with the cercomonas. He also found the parasite in the muddy water in the St. Gotthard tunnel. No other clinical data of the cases are given. Cases 31-33. [Rapchevski (21 and 24), 1880-1882.] Case 31. — The patient, 23 years old, was well until about three weeks before he came to Rapchevski for treatment. Then he was attacked with diarrhea and colic, chiefly in the region of the umbilicus. The diarrhea grew more severe and resisted all treatment by the mouth. On admission the patient was thin and pale and the tongue coated. The abdomen was tender. The stools were liquid and grayish yellow in color, containing mucus, red blood corpuscles, pus cells, and a mass of Balantidium coli. 27 For the first week, under indifferent treatment, the disease showed no change and the Balantidia had not diminished in number. Under treat- ment with salicylic acid (15 grams) and sodium sulphate (one-half ounce) morning and evening and two high enemas of salicylic- acid solution, 1-1,000, for four days, the patient felt much better and the parasites disappeared from the stools, though the latter were, of course, frequent. The above treatment was then stopped and treatment by astringents begun by the mouth. After one week the stools became regular once or twice a day and formed. For the last two weeks in the hospital there were no Balantidia in the stools. The patient left the hospital well. Case 32 (1882). — The patient was 21 years old. Ten days before entrance he was taken sick with diarrhea and pain in the abdomen, headache, and fever. On admission the symptoms of typhoid fever were definite and the case was apparently in the second week of the disease. The course of the typhoid was light, and after three weeks the temperature became normal. Besides bronchial catarrh and diarrhea, there were no complications. The diarrhea was constant, however, and though the temperature was normal, it continued. The stools were liquid and, contained mucus, red blood corpuscles, pus cells, and Balantidium coli. No improvement took place until the same treatment as in case No. 31 was used. After six days the treatment was stopped. The stools were normal for two days and then the diarrhea began again and on examina- tion large numbers of Balantidia were again found. The treatment was then resumed for five days. After this there were no parasites and the diarrhea stopped completely. The patient left the hospital, well, two weeks later. Case 33 (1882). — The patient, aged 23 years, entered the hospital November 14, 1881. In the spring of 1881 he was taken sick with inter- mittent fever, which lasted four or five weeks. In September he was attacked with diarrhea and severe pain in the abdomen. The latter improved, however, but grew worse just before entrance. On admission the abdomen was tympanitic and painful on palpation; the tongue was coated and the appetite decreased. The stools were very frequent and liquid. He was treated by astringents and opiates until January 8, but did not improve. He then came under Rapchevski's care, suffering with severe colic in the lower part of the abdomen and considerable distension. The stools contained mucus, red blood corpuscles, pus cells, and a mass of Balantidium coli. Loesch called attention to this case in his clinic and stated that probably salicylic acid would not do as well in this case, as probably the lesions of the intestines were further advanced and that ulcers were already present. The salicylic treatment was, however, begun. After five days the parasites had apparently disappeared from the stools, but the diarrhea continued. As there was more blood in the stools, however, the salicylic acid was stopped. The day after the Balantidia appeared and the other symptoms grew worse. Salicylic acid without sodium sulphate was tried but had to be given up on account of the weak state of the patient. Cough, nausea, and hiccough appeared and the patient died February 10 from exhaustion and collapse. 28 At necropsy the walls of the heart were flaccid and thin. There was an area of solidification in the upper portion of the left lung. On section its surface was smooth and reddish in color. The liver on section gave a nutmeg appearance. The kidneys were atrophied. The cortex of each was thin and contained several small cysts. The mucosa in the ileum was dis- tinctly hypersemie, thickened, and here and there were minute extravasa- tions of blood. The follicles were enlarged and pigmented. In the large intestine there were throughout numerous ulcerations, many having a transverse direction. Some of these reached almost to the depth of the muscular layer. Their edges were slightly thickened, undermined, and ragged. The follicles were swollen and many showed crater-like ulcera- tions. In the upper part of the large intestine the mucosa between the ulcerations was thickened, dark, livid, and covered with extravasations; in the descending colon and especially in the sigmoid flexure it was thickened and slate colored in places. The mesenteric glands were enlarged and some deeply pigmented. It is merely stated that the microscopical examination of the large intestine showed changes proper to ordinary chronic ulcerative inflammation. Case 34. [Zur Nieden (23), Freiburg, 1880.] This was the first reported occurrence of infection with the parasite in Germany. The patient, a woman aged 27, had been employed in cleaning pigs' intestines for sausage making. She had suffered with continuous diarrhea for three years (since her second delivery). Four months before admission the diarrhea became painful and blood appeared in her stools; later pain and colic in the abdomen were present. On entrance she was extremely emaciated and moderately anemic. A rectal examination showed an inoperative carcinoma of the rectum with deep crater-shaped ulcers. The feces showed red and white blood cells, cylindrical cells, and numerous Balantidia. Under treatment with enemas of one-half per cent carbolic- acid solution for eight days the frequency of the stools was somewhat decreased, but no reduction in the number of parasites could be observed. Case 35. [Stockvis (27), Sunda Isles, 1884.] The patient, aged 46 years, a riding master from the Sunda Isles, gave a history of an attack of irregular fever and of chills the year before. Later he began to cough, but without much expectoration. On one occasion, how- ever, the sputum was light red and of an offensive odor. The further course of the disease lasted six weeks; there was irregular fever, some cough, and a small quantity of sputum. The physical examination of the chest showed in the right axillary region over the fourth and fifth inter- costal spaces a small area over which coarse rales could be heard. The middle lobe of the right lung was certainly affected at this time, but what the process was originally the author could not definitely say, though it suggested a rupture of a liver abscess into the right lung. The urine was 29 normal. In some of the last sputa the patient coughed up were found one living and several dead specimens of Balantidium coli. The parasites agreed with the description of Malmsten. The sputum had a foul odor and was coffee-brown in color. Leucin and tyrosin and fatty acid crystals were not found in it. The patient completely recovered and the author thought the trouble was due to Balantidia. Case 36. [Edgren (29), Stockholm, 1885.] The patient was admitted to the Seraphim Hospital suffering with chronic nephritis and diarrhea. She stated she was well until one year before admission, when the diarrhea began. On entrance she was much emaciated. The stools showed masses of Balantidium coli. The urine showed considerable albumen and hyaline cylinders. Its specific gravity was 1,012. The patient was treated with naphthalin, and after several days no parasites were found in the stools. Vomiting set in and the patient died suddenly. At the necropsy, sixteen hours after death, no parasites were found in spite of a very careful search for them. However, the author admits that they might have been still present and yet died in sixteen hours. The diagnosis of nephritis was confirmed at necropsy. The large intestine showed only inflammatory thickening. Cases 37-39. [Wising (28), 1885.] In 1885 Wising reported three more cases in addition to his first one in 1871. Case 31. — The patient was extremely emaciated; the passages were very numerous and contained many Balantidia. He was treated with enemata and improved for a time, and after several months he was well enough to be discharged. His stools were thin but regular in number, one or two in twenty-four hours, and he was healthy in appearance. He remained in this condition for one and one-half years, but during the whole time Balantidium coli was found in his feces. When seen the last time by this author he still complained of having intermittent diarrhea. No treatment seemed efficacious. Cases 38 and 39. — These cases were also seen in Seraphim Hospital. The first one ended in death, and at necropsy it was shown that the parasites were found not only in the colon but also 2 or 3 feet above the ileocecal valve in the ileum. The author called attention to this fact because he thought it was advisable in these cases to use some remedy by the mouth and also to try to disinfect the upper portion of the intestinal tract. He suggested naphthalin for this purpose, and tried it on his last case. The patient was given V gr. three times a day. After some days Balantidium coli disappeared from the feces, but returned later. The patient left the hospital while the naphthalin treatment was being pursued again. The author thought that the results from the use of the naphthalin in this case Avere very encouraging. 30 Case 40. [Afanasyeff (31), 1888.] The patient was observed at the Nipolai Hospital. He suffered from persistent diarrhea, anemia, and general emaciation. The stools contained considerable mucus and blood and large numbers of Balantidium coli. After treatment, both by the mouth and by enemata, the parasites dis- appeared from the stools and the patient recovered. Case 41. [Bdgren (35), 1890.] The patient, aged 57 years, entered the hospital September 12 and was discharged December 14. There was a family history of tuberculosis. He had always lived in poor hygienic conditions. Of late years he had suffered from intermittent diarrhea. Four months before entrance the diarrhea became very severe and vomiting appeared. He then grew very weak. On admission he was much emaciated and pale. There was tenderness on pressure over the abdomen. The stools were frequent, very thin, and watery; many Balantidia were present. The lungs were apparently emphy- sematous. The blood examination showed red blood corpuscles, 4,900,000, and about 1 white to 200 red cells. Haemaglobin, 55 per cent. Under tannin enemas, tannin, and napthalin by the mouth the parasites dis- appeared from the stools and the diarrhea improved; the patient was also perceptibly better. The diarrhea had not completely stopped when the patient left the hospital. Case 42. [Lavrovskaya (36), 1890-91.] The patient, aged 70, w T as afflicted with chronic nephritis and entered the hospital October 14. She was fairly healthy, but had become exhausted from constant diarrhea. There was considerable tenesmus and pain in the abdomen. The stools were semiliquid and dark yellow. Micro- scopically, they contained blood, pus cells, red blood corpuscles, and Balct/ntidia. Enemas of salicylic acid, boracic acid, naphthalin, and salol by the mouth were given. Under this treatment there was success in reducing the abdominal pain and the stools to two or three per day, but the para- sites did not disappear. As soon as the treatment was stopped the parasites rapidly increased in number, and the diarrhea and pain reappeared. Finally, after treatment at intervals with salol internally and salicylic enemas for over four months, the patient was thought much better and left the hospital February 14, 1891. However, an occasional parasite was found in the stools. She was seen again March 5, and was apparently well. Lavrovskaya, later in 1891, observed the case still further. On March 15 renewed diarrhea appeared and Balantidium coli was found pres- ent. She was put on the same treatment, and by April 2 the diarrhea had stopped and the parasites disappeared. She was then free from parasites 31 for a month, and as she was apparently well, she was discharged. At the end of August diarrhea reappeared, and the patient entered the hospital in a very weak condition on September 25. Numerous Balantidia were pres- ent. Under the same treatment the parasites disappeared on October 18 and were not found up to November 18, when the patient again left the hospital. On January 4 the patient had a slight attack of influenza and entered the hospital, remaining until January 25. No parasites were observed and her stools were normal. Case 43. [Mitter (41), 1891.] The patient, aged 39, was born in Germany, but had emigrated to America. He lived in Iowa, where he was employed in raising pigs and making sausages. While in Iowa he suffered with fatigue and weakness and depression in the morning. His appetite was fairly good. There was no diarrhea at the time and his stools were fairly solid and regular but showed fragments of undigested food. No blood was present and he had no tenesmus or colic. The patient traveled to his home in Germany, and felt well until his return to Iowa, when his former symptoms returned ; but in addition he suffered with pain in the left side below the umbilicus and in the vicinity of the sigmoid flexure, which was greatly increased by pressure. Also the fragments of food in his feces occurred in extremely large quantities. Finally he returned to his home again for treatment. On the voyage he again improved, but he consulted a physician, who examined his stools and sent a specimen of them to Professor Heller in June, 1890. The latter found numerous Balantidia in them. Mitter examined the patient February 24, 1890, and found the skin pale and the conjuntiva? very anemic; the tongue was coated, the abdominal walls were tense, and there was no pain on pressure. On examining the stools, which were of fairly solid consistency but still contained fragments of indigested food, he found dead Balantidia. On the following day he found numerous parasites and leucocytes in the stool. The patient's entire illness was of about fifteen years' duration. He refused all medical treatment, because, while he did not feel well, his only complaint was of pain and weakness. Case 44. [Ortman (42), 1891.] The patient, aged 48 years, a pilot, had been in Brazil in June, 1888. On his last voyage from this country in October, 1888, he was attacked with diarrhea, which continued with intermissions for over a year. From Easter of 1890 until September 15 his stools numbered from three to six a day, were of yellow color, and contained mucus. On admission, September 15, he was cachetic. The abdomen was not painful, but there was considerable gurgling on pressure, A provisional diagnosis of chronic intestinal catarrh ^nd possibly intestinal tuberculosis was made. Under diet and tannic-acid enemas and naphthalin for about fifteen days the patient improved. But when this treatment was stopped the stools took on gradually the same 32 character. On microscopical examination large, numbers of Balantidium coli were found in a floccule of mucus. In order to exclude tuberculosis of the intestine, 5 milligrams of tuberculin were given the patient. There was, however, no trace of a reaction. Under enemas of tannic and muriatic acid, quinine, and Emms salt crystals for four months, the patient finally improved; and from January 21 to February 6, when the patient left the hospital, no more Balantidia were found. His appetite was then good; his stools regular and formed. General diet was well supported. He was seen again about four months later; his stools were then regular and normal. In the fresh stool, after prolonged searching, in some mucus a single specimen of Balantidium coli was found. Case 45. [Pfeiffer (43), Wiemar, 1891.] The patient had suffered from diarrhea for three years. At the time when the diarrhea was most severe, in each microscopical preparation of the stools Pfeiffer found 10 to 25 Balantidia. At other times the parasites seemed to be completely wanting. There was no pus in the stools, but during the severe attacks of the diarrhea there was bloody mucus, and then the parasites were most numerous. Under treatment with quinine pills improvement followed for a short time only. Case 46. [Afanasyeff (38), 1891.] This second case of Afanasyeff was demonstrated in a lecture. The patient suffered with severe dysentery, general marasmus, and anemia. In the stools were found large numbers of Balantidium coli. Rational treat- ment could not be applied on account of his weakness and he succumbed. At necropsy there were found very severe hemorrhagic and ulcerative changes in the large intestine. This patient probably became infected from contact with pigs. Case 47. [Janowski (39), 1891.] The patient, aged 25 years, had suffered from persistent intermittent diarrhea for a year and a half. He was much emaciated; the skin and mucous membranes were pale; the abdomen was drawn in, the walls tense; there was tenderness on pressure, especially over the iliac fossa. On palpation the walls of the caecum were thickened. The stools contained a little mucus and blood and many Balantidia. They numbered from 1 to 13 per day. He was in the clinic two and one-half months, but neither treatment by the mouth nor enemas did any good, and the patient finally died from exhaustion. The necropsy showed nothing of importance except what is usually seen in catarrh of the intestines. There were neither ulcers nor any change in the sacular glands. The parasites were more numerous nearer the rectum. 33 Case 48. [Maggiora (44), 1892.] Maggiora, in an epidemic of dysentery in Africa, studied 26 cases. The stools of all showed considerable mucus and white and red blood corpuscles in large numbers. In one case he found amebse and in another the Paramcecium coll. As he found each of these parasites in only one case, he therefore did not attribute much significance to either. Case 49. [Runeberg (45), 1892.] The patient, 41 years old, ate considerable pork. For two years he had suffered from acute attacks of vomiting and severe diarrhea. The stools were thin and contained mucus mixed with blood and numerous Balantidia. Treatment with naphthalin, calomel, tannic and acetic acid enemas, and many other drugs was unsuccessful. On the other hand, after several days' treatment with quinine sulphate by the mouth and in enema ta the Balantidia disappeared from the stools and the diarrhea stopped. For two months the stools were examined but no more Balantidia were found. The general condition of the patient was perfectly satisfactory. Case 50. [Runeberg (46), 1893.] The patient, aged 55, had recently been employed in slaughtering pigs. On admission he had a cachetic appearance, and therefore a malignant tumor was at first expected. In the mucus from the rectum very large numbers of Balantidia were found. The patient was first treated with naphthalin, but it did not give good results, and after its administration the Balantidia were even more numerous than before. A favorable result was obtained only after quinine enemas and calomel internally had been given. The diarrhea and the parasites disappeared completely, and during two months, while the case was continually under observation, the Balantidia were not found any more. The patient gained 17 kilos in weight. Case 51. [Gruner (47), 1893.] This case was reported orally by Gruner at a meeting of the society of physicians and naturalists at Abo in 1893. The case has been published more at length by Sievers (64) from Gruner's notes. The patient, aged 46, a woman, had lived in a shed with pigs. She was taken sick two years before entrance with diarrhea and abdominal pain. On admission she was emaciated; the stools were thin and watery and excreted with pain. They contained blood and Balantidia in large numbers. Ihe patient was treated with quinine and creoline enemas and with 25822 3 34 quinine internally. After several weeks' treatment her condition improved and she gained in weight. The stools became formed and no parasites could be found. For several weeks before the patient left the hospital her stools were normal. One year later she was seen and found healthy and well. Case 52. [Roos (48), 1893.] The patient, aged 30 years, had suffered with severe diarrhea for about four months. There was little abdominal pain and tenesmus. On admission he was much emaciated. On palpation there was pain in the epigastrium and ileocoecal region. The stools were frequent, thin, and contained blood and mucus with many Balantidia. Under treatment with quinine inter- nally and by enemata the stools became more solid and the Balantidia diminished but did not disappear. Calomel was then given for nine days (1 decigram three or four times a day), and, although the patient became salivated, no more Balantidia were found in the stools up to the time he left the hospital six days later. The stools, however, still remained gruel-like, and the urine showed considerable indican. About three weeks after leaving the hospital the diarrhea again became severe and the patient again entered the hospital with diarrhea and colic. However, no Balan- tidia could be found. After tannin enemas and tannin and charcoal the stools became solid and there was but one movement a day. The patient left the hospital well. Case 53. [Blomberg (50), 1894.] At a meeting of the medical society of Abo December 3, 1893, Blomberg stated that he had treated a case of diarrhea infected with Balantidium coli with quinine and opium, obtaining satisfactory results. He did not publish the case further. Cases 54-65. [Lobas (51), 1894.] Lobas studied sixteen cases of dysentery in Sakhalin Prison, all of which died. In the first four cases no microscopical examinations were made. In the remaining twelve examination of the stools showed numbers of a ciliated infusorium which from Lobas's description were evidently Balan- tidia. The stools, in addition, all contained blood and pus cells. In all the cases extensive ulcerations of the large intestine were found at necropsy. Case 66. [Patiala (52), 1895.] In the proceedings of the medical society of Finland for May 18, 1895^, it is merely mentioned that Patiala showed a case of diarrhea infected with the Balantidium coli. He did not publish the case further. 35 Case 67. [Fadieyeff (53), St. Petersburg, 1895.] The patient, a sailor, aged 25 years, began to have severe diarrhea before entrance. On admission the lungs showed slight dry bronchitis. The abdo- men was a little swollen and tender on pressure. Vomiting and moderate fever were present. Cholera was suspected, as it was present in the city at the time, but cultures from the stools showed no comma bacilli. The diarrhea and nausea continued at intervals for about a month, then the fresh stools were examined and Balantidium coli found in large numbers. The author tried all remedies recommended, but the parasites were always found living. Tannin enemas gave only a temporary relief. The patient weakened and died thirty-eight days after entrance. Necropsy (forty-two hours post-mortem). — There were found adhesions to the lungs anteriorly. The kidneys were somewhat increased in size; the tissues of the cortical layer of each were waxy and contained several infractions. On section the kidneys, heart, and liver showed fatty degenera- tion. There was chronic catarrh in the small intestine. The large intestine showed chronic catarrh with considerable hyperemia and four ulcerations. The long diameter of the ulcers extended transversely to that of the lumen of the intestine; their floors were formed of muscular tissue or serosa. Sections of the large intestine were studied microscopically. (See "Histological studies." ) Case 68. [Sievers (54), Finland, 1896.] The patient, a gardener, aged 19 years, had suffered from attacks of vertigo, diarrhea, and dyspepsia. He had passed segments of Bothrio- cephalus latus for a year. On admission he was very weak; the mucous membranes were pale ; there was a soft, systolic murmur over the heart and jugular veins. The red blood cells numbered 1,500,000; the haemoglobin registered 40 per cent. The abdomen was swollen and painful on pressure. The examination of the liquid stools showed mucus, red and white blood cells, many Balantidia, Megastoma entericum, and segments of Bothrio- cephalus latus. The patient was apparently suffering from anemia due to Bothriocephalus latus. This parasite was expelled under treatment and the condition of the patient improved. He gained in weight and the anemia lessened. The diarrhea, however, continued, with mucus in the stools, and the Balantidium coli and Megastoma were still present. Under treatment for three weeks with quinine internally and quinine and Emms salt enemas the diarrhea finally disappeared, and there was one natural stool daily besides those passed when enemas were given. Occasionally after the enema a few dying Balantidia were found. The patient insisted on leaving the hospital. The abdomen was no longer tender and he felt per- fectly well. 36 Case 69. [Cassagrandi and Barbagallo (55), Catania, 1896.] According to Janowski, the authors cited above described a case of diarrhea in the stools of which they found the Balantidium colt. They were of the opinion that the parasite has no pathological effect on the intestinal canal. They also mention a case communicated to them by Grassi (case 70, Grassi ) , observed by the latter in Catania, the case having become infected with Balantidium coli in Massava. I did not succeed in obtaining the original monograph of Cassagrandi and Barbagallo in America. Cases 71, 72. [De la Chapelle (56), Finland, 1896.] Case 11. — The patient, aged 66, worked on a farm and occasionally killed and cleaned pigs. He had suffered previously from infection with Bothriocephalus latus and for about a year with severe diarrhea, pain in the abdomen and tenesmus. The stools contained blood and numerous Balantidia. The patient was much emaciated and was afflicted with arterio schlerosis. He was treated for five weeks with quinine internally and with large quinine and Emms salt enemas. The enemas were always almost immediately expelled. However, no improvement followed, and the patient left the hospital with severe diarrhea and a large number of Balantidia in the stools. Case 12. — The patient, aged 56, was a farmer who raised and killed pigs. He had passed Bothriocephalus segments previously; four months before entrance to the hospital diarrhea began with abdominal pain and tenesmus. After treatment directed against the taenia, the diarrhea became better, but later worse than before. On admission he was much emaciated and the mucous membranes were pale. The stools were numerous and contained mucus and Balantidium coli. He was treated in the same manner as in Case LXXI. After three weeks no parasites could be found, the diarrhea disappeared, and the patient gained in weight. One month later he left the hospital. Balantidium coli was not found and the stools were well formed. He was well for two years, then he began to suffer from severe diarrhea again, and lost much flesh. On examination of the stools Balantidium coli was again found in large numbers. After treatment as above for several weeks the stools became normal, the parasites disappeared, and he left the hospital well. Cases 73-79. [Gurvich (57), 1896.] Case 13. — A male; complained of severe diarrhea. Microscopical examina- tion of the stool showed the ova of Bothriocephalus latus and Balantidium coli. The patient disappeared and the author did not see him again. Case 7 f f. — A woman; complained of severe diarrhea. In the feces were found large numbers of Balantidium coli. The patient left the clinic and never returned. 37 Case 75. — The patient, a peasant, aged 60 years, had suffered for about a month with severe diarrhea, tenesmus, and vomiting. The feces contained a small amount of blood, many Balantidia, and ova of Bothrio- cephalus latus. The patient also suffered with hemorrhoids. He was treated with croton oil, bismuth, tannin, and felix mass, but the diarrhea became very severe, the Balantidia very numerous, and he died in collapse. Necropsy (forty-eight hours post-mortem, of the abdominal cavity). — There was about 200 cubic centimeters of cloudy, chocolate-colored fluid in the peritoneal cavity. The mucosa of the caecum and ascending colon was pale and covered with multiple round ulcers penetrating to the muscular coat; their edges were infiltrated. In the descending colon and sigmoid flexure the mucosa was infiltrated and covered with hemorrhages; there were some ulcerations. None of the ulcers had perforated. No parasites were found in the contents of the intestine or in preparations from the scraped mucosa. Microscopical examination was made of sections of the large intestine. Case 76. — The patient, a laborer, aged 58 years, took care of four pigs. He had previously passed segments of tapeworm and suffered with painful diarrhea. On admission the abdomen was drawn in and there was slight pain over the caecum. The stools showed mucus and numbers of Balantidium coli. The patient was treated for five days with tincture of valerian without change. Under treatment with enemata he improved, and the parasites had disappeared when the patient left the hospital. Case 77. — The patient, aged 65 years, at Christmas time, 1895, killed a hog and made and ate sausage. Following this he had severe diarrhea. On microscopical examination the feces showed Balantidium coli. The diarrhea finally became intermittent. He was seen only once in the dispensary. Later it was learned that under diet and enemas of water the diarrhea had slightly diminished. Case 78. — The patient, aged 55 years, a cook, had suffered for thirty- six years from indigestion and at times suffered from nausea. He had three attacks of pneumonia. Four years before entrance he gave a history of an attack of diarrhea, from which, however, he soon recovered. Two years later he became a cook and used to prepare sausages and would often blow into the pig's intestines, taking them unwashed into his mouth. Shortly after diarrhea began and later tenesmus appeared. On admission a few rales were heard over the lungs. The sputum was purulent and abundant. There was pain on palpation over the large intestine. On microscopical examination a mass of ova of taenia and Balantidium coli were found in the stools. There was also some mucus present. The red blood cells counted 1,200,000. The haemoglobin registered 40 per cent. Under treatment with felix mass, quinine enemas, and flores cinae the patient improved somewhat, the stools became gruel -like, and no parasites were found for three days before the patient left the hospital. There were then many rales in the lungs and severe anasarca was present. Case 79. — The patient, aged 68 years, had been in good health until Christmas, 1895, when she prepared sausage from fresh pigs' intestines, blowing into them with her mouth. Severe diarrhea with pain in the 38 abdomen followed shortly afterwards. The stools contained blood, mucus, and numerous Balantidia. The case is not reported further. Case 80. [Trzhetsieski (60), 1896.] The patient, a young soldier, gave a family history of tuberculosis. He had suffered with gastric dyspepsia for about fifteen years. He stated that his intestines had always been normal until three years ago, when he sustained an accidental trauma of the abdomen. Since that time he has had continuous diarrhea. While in the hospital the sputum examination showed no tubercle bacilli. The abdomen was painful on pressure. A test breakfast showed but slight disturbance of the stomach. The stools were very thin, contained mucus, trichomonas intestinalis, megastoma entericum, asearis ova, and enormous numbers of Balantidium coli. The patient remained under observation for two months, but the normal functions of the intestines were not restored, though he gained one kilo in weight. He- was treated with salicylic acid, quinine and calomel, and enemata of sali- cylic acid and quinine. The diarrhea and the parasites diminished only at intervals. Case 81. [Janowski (58), 1896.] The patient, aged 48 years, had suffered from diarrhea for four and a half months. The attack began three days after the ingestion of pork and sausage at a wedding celebration. After defecation there was pain in the region of the rectum. The feces were liquid, containing mucus, pus cells, and numerous Balantidia. Treatment with opium and bismuth gave only temporary relief. Treatment with quinine internally and in enemata for five days caused improvement, as four days later no Balantidia were found in the feces and the pus had also disappeared. The stools were, however, still semifluid and numbered three per day. Cases 82, 83. [Bushuyeff (62), 1896.] Case 82. — The patient, aged 62 years, was admitted to the hospital complaining of diarrhea, weakness, and loss of appetite. He was emaciated arid anemic, and the feet were at first edematous. The patient stated that the diarrhea followed on drinking water from a dirty well. The abdomen was swollen and painful on pressure, and the walls of the caecum thick- ened. The feces were watery and contained epithelial cells and Balan- tidium coli, and later blood. The urine also afterwards showed a trace of albumen and hyaline cylinders. He was treated with various drugs by the mouth and with tannin enemas. Under the latter the Balantidium coli diminished, and just before leaving the hospital typical ones were not found, but instead young bodies resembling the amebse of Loesch, which the author thought were young Balantidia. The patient left the hospital and 39 the author did not follow him further, but ascertained later that he died of his nephritis several months after leaving the hospital. Case 83. — The patient, a soldier, aged 46 years, had suffered from diarrhea for three years. For the past four months there was mucus and blood in his stools and recently the rectum prolapsed. The stools were passed with pain and gurgling in the abdomen. Microscopically they showed megastoma entericum, ascaris ova, and Balantidia. Treatment by sodium sulphate and salicylic enemas and other remedies gave no good results, though it was continued for one week. The parasites were still present in the feces w T hen he was last observed. Case 84. [Chigayeff (63), 1898.] The patient, a guardsman, aged 25 years, entered the hospital com- plaining of pain in the abdomen and of diarrhea of two weeks' duration. One week before entrance he had an attack of vomiting. On admission there were loud rales heard over the lungs, though percussion was normal. The abdomen was retracted and painful on pressure along the course of the large intestine. The stools were liquid and painful. After the patient had been under observation a week the feces were examined and found to contain numerous Balantidia. He was treated with bismuth, salol, and opium, and enemas of salicylic, acetic, and boric acids and quinine. The Balantidia still remained present and the diarrhea continued. The rales in the lungs were still present, but there was no fever. Albumen appeared in the urine, but no blood cells or casts. The pulse gradually weakened, the pain in the abdomen increased, hiccough appeared, and the patient died. Necropsy (one and one-half days after death). — The pia mater of the brain was congested. The heart muscle was reddish brown with a yellowish tinge (fatty and brown degeneration). The lungs were in places emphy- sematous and showed areas of broncho-pneumonia. The mucosa of the stomach was covered with mucus. The kidneys showed fatty degeneration. The mucosa of the small intestine was pale; in the lower part it was also bathed in mucus. In the caecum and throughout the large intestine there were numerous ulcers, many irregular and undermined. The lymphatics in the region of the large intestine were the size of a pea and of a grayish- red color. Notwithstanding the fact that the autopsy was performed one and one-half days after death and that the cadaver lay in the cold, Balan- tidia were still found alive in the mucus (after it had been warmed) from the large intestine. Case 85. [Lang (65), St. Petersburg, 1897.] The patient, a peasant, aged 40, entered the hospital November 5, 1897. He had always been well until March, 1897, when a persistent diarrhea began. He lost appetite, and edema of the feet appeared. On admission he was thin, the feet and hands cyanotic. The abdomen was collapsed and not painful on pressure. The feces were liquid; microscopically they contained 40 mucus, red blood cells, and Balantidiwn coli. The patient was treated with tannigen and opium, and tannin and boric enemata. But the diarrhea continued; pain and gurgling increased in the abdomen, the pulse became thready, and the patient died. Clinical diagnosis : Chronic enteritis. Necropsy {thirty-seven hours post-mortem) . — There were old adhesions of the pericardium, right-sided catarrhal pneumonia, brown atrophy of the cardiac muscle. Chronic gastro-enteritis. Ulcerative colitis. Two small fibromata of the right kidney and edema of the pia mater of the brain. The mucous membrane of the large intestine was in places slate colored, in others ulcerated. The ulcers had an irregular form with undermined edges. They corresponded to the solitary follicles. The mesenteric glands were enlarged; some were slaty and others hyperamiic in appearance. No Balantidia were found in the intestines. Case 86. [Vlayeff (66), St. Petersburg, 1898.] The patient, aged 32 years, had for seventeen years taken care of pigs. In 1897 he became ill with persistent diarrhea. On admission his general nutrition was poor and there was edema of the face and feet. There was slight ascites. The liver extended two fingers' breadth below the cestal margin. There was pain on palpation about the umbilicus. The stools were watery, bloody, and purulent, and contained numerous Balantidia. Tenesmus was present. The urine showed traces of albumen. The patient was an alcoholic. He was treated by three enemas of iodine solution, 1-10,000 and 1-5,000, and under this treatment the parasites disappeared and were not found any more up to the time of the death of the patient ( one month later ) . The patient was also given silver nitrate and opium and starch enemas, but he grew steadily worse and the diarrhea increased. Pleurisy began on the left side and the patient died. On necropsy there was found ulcerative polypus catarrh of the large intestine, infarction of the lower left lung, and fibrinous, hemorrhagic inflam- mation of the left pleura. In the right ventricle an embolous was attached to the wall. On microscopical examination of the contents of the intestines Balantidium coli was not found. Case 87. [Dehio (64), 1898.] The patient was a peasant, aged 45 years. He worked on a farm and cleaned pig sheds. About two weeks previous to entrance he had an attack of nausea followed by diarrhea. The abdomen became swollen and painful and severe tenesmus developed. On admission he was extremely emaciated. The stools were fluid and brownish in color and numbered fifteen to twenty a day. Microscopically, many white and red blood corpuscles and numerous Balantidia were present. He was treated with opium and enemata of boric acid for three days, but gradually weakened and died. Necropsy ( seventeen hours after death ) . — The muscles were pale. The aortic valves were thickened. On opening the abdominal cavity there were 41 thin, peritonitic adhesions in the neighborhood of the large intestine, particularly in its lower part. The kidneys were anemic. In the small intestine there was no change except near the caecum, where there were a few small hemorrhages. The caecum was not particularly altered. In the large intestine there were numerous ulcerations usually w T ith irregular borders and with the longer diameter perpendicular to the length of the intestine. Many were undermined. Their floors were formed of muscular coat or sometimes merely of the serosa. But no perforation had occurred. These areas corresponded to the peritonitic adhesions. In the sigmoid flexure and rectum nearly the whole mucosa was necrotic. Although the necropsy was performed seventeen hours after death and the body lay in the cold, the Balantidia were found living in the mucus from the large intestine. Cases 88-90. [Woit (67), 1898.] Case 88. — A farm laborer, aged 31 years; had good health and no intestinal disturbances until forty days before he entered the dispensary as a patient. He was taken ill then with severe abdominal pains and diarrhea. The diarrhea continued and mucus and blood appeared in the stools. The feces were purulent and contained mucus and numbers of Balantidium coll. The patient declined to enter the hospital and was not seen further. Case 89. — The patient, a woman, aged 47, became ill in February, 1897, with digestive disturbances and intermittent attacks of diarrhea. Two months before these symptoms developed a pig was killed and she made fresh sausage. On September 3, 1897, she w T as suddenly taken ill with pains in the abdomen and chills. The abdomen became swollen, but there was no vomiting. Five days later she entered the hospital. On admission the mucous membranes were pale and the abdomen swollen and tender. A diagnosis of peritonitis was made. The stools were liquid and contained large numbers of Balantidia. The weakness of the patient increased and the stools became more frequent. The abdominal symptoms grew worse and the patient died September 24. Clinical diagnosis: Peritonitis and colitis due to Balantidium coli. Necropsy {September 25, at 10 a. m., by Afanasayeff) . — Anatomical diagnosis : Colitis e Balantidium coli; peritonitis fibronis purulenta second- aria; pleuritis adhesiva circumscripta utriusque laterus; nephritis inter- stitialis gradi parvi; degeneratis parenchymatosa renum; cystitis necro- tica; prolapsus vaginae partialis. In addition, the heart was somewhat small and atrophied. The abdominal cavity contained foul-smelling gas and about 5 liters of fluid greenish-yellow pus. The entire serosa of the mucosa was covered with the same exudate. In the lower end of the ileum the Peyer's patches were pigmented and of a slate color. In the caecum, colon, and rectum there were a large number of ulcers, from 1 to 2 millimeters to three-fourths of a centimeter in diameter. The major- ity were rounded, the minority "oval. Many of the ulcers were fused 42 together. Their edges were without special traces of reaction and were pale and undetermined. In depth the majority reached the muscularis mucosa, though some extended into the muscular coats. The shallower ulcers w r ere covered with gray necrotic material, while the deeper ones were relatively cleaner. The longitudinal muscular coat was infiltrated and hemorrhagic in places. No distinct perforation could be found, though the intestine tore easily on being removed. The liver tissue was soft, anemic, and grayish yellow in color. Balantidium coli or its encysted forms could not be found at the autopsy. The author concluded that death was due to peritonitis, secondary to Balantidium coli colitis, and that probably perforation had taken place, although the place of perforation was not found. Histological examinations were made. Case 90. — The patient, a peasant, aged 59, used to sleep in the stable where the sheep and cows were kept, but no pigs. He said he had never had anything to do with hogs. For several years he suffered from indiges- tion, pain in the abdomen, and fluid stools. The attacks were intermittent. At times severe tenesmus and colic were present. On several occasions he noticed segments of taenia in his feces. On admission he was weak and emaciated. There was slight edema of the legs, and the arteries were schlerosed. The cardiac sounds were faint. The liquid feces showed ova of Bothriocephalic latus and Balantidium coli. "Under treatment with felix mass the taenia was driven out. For six days after this treatment the Balantidia also disappeared and the stools were formed. Then, how- ever, they became liquid and the Balantidia were found in large numbers. Later the feces contained both blood and mucus. Anasarca appeared and disappeared several times. He remained in the hospital for nearly six months, then he was seized with an epileptic contracture which lasted one hour. He did not regain consciousness and died soon after. He had become extremely emaciated. The treatment consisted of many remedies; among them were calomel, flores cinae and oleum ricini, enemas of acetic, tannic, and boric acids, and silver nitrate. The enemas of silver nitrate seemed to do the most good. The parasites were found in the intestine until two weeks before the death of the patient. From this time on he was given daily the enemas of silver nitrate until he died. Clinical diag- nosis: Colitis e Balantidium. coli et arterio sclerosis. Necropsy {fourteen hours after death). — Anatomical diagnosis: Colitis chronica e balantidia coli; pneumonia lobularis, lob. inf. sin.; degeneratio parenchymatosa, myocardii; nephritis interstitialis arterio schlerotica; arterio sclerosis; oedema cerebri. In addition, on the surfaces of the kidneys there were small infarcts and retention cysts. The cortical layers were atrophied with yellowish striae. The mucosa of the small intestine was pale, but in some places numerous punctate hemor- rhages had occurred. The mucosa of the large intestine in general was pale, but there, were numerous hemorrhages, especially on the folds; in places there were many superficial epithelial defects, but large defects or ulcers of the mucosa were nowhere present. Microscopical examination of the small and large intestine was apparently negative for Balantidia. The author thought the immediate cause of death of his very 43 . cachetic patient might be looked for in the edema of the brain, particularly on account of the advanced arterio sclerosis. He expected to find ulcers in the intestines on account of the blood in the stools, the pain in the abdomen, and the persistent prolongation of the intestinal disease, but instead he found a catarrhal condition. He concluded that the parasites had not been present long enough to produce ulceration. Histological studies were made of the large intestine. Case 91. [Zhegaloff (72), 1899.] The patient was a child, aged 5 years and 4 months. In the latter part of its fourth year it ate pork. The stools were normal imtil seven months before the parents consulted the author; then the child was attacked with diarrhea, which became intermittent. Later edema of the face and feet, headache, and abdominal pain appeared. On admission the mucous mem- branes were pale; the abdomen swollen and tender on pressure. The stools were liquid, containing mucus and Balantidia. The blood count showed 3,800,000 red cells; leucocytes, 13,400; haemoglobin, 50 per cent (Fleichel). The patient was under observation for eighty-eight days. For twenty-eight days there was fever; afterwards this disappeared. The edema of the face and feet disappeared after one week. The anemia also lessened. The Balantidia diminished under treatment, and on the fortieth day none could be found. On the sixtieth day diarrhea began and Balantidia were again present. Whenever the stools became regular and formed the parasites were not found. The author thought the fever due to increased intestinal fermentation. A virulent colon bacillus was isolated from the stools. He was treated with oleum ricini, tann albin, carbonate of iron, and enemas of tannic and acetic acid. This was the first reported case of Balantidium coli infection met with in a child. Case 92. [Solovyeff (71), 1899.] The patient, aged 70 years, entered the clinic complaining of a per- sistent diarrhea which had lasted for four weeks. He lived generally in unhygienic places, and slept frequently in sheds where animals, such as sheep and hogs, were kept. On admission the feet and ankles were swollen. The stools numbered from twenty to twenty- five per day. On microscopical examination they showed red blood corpuscles and numerous Balantidia. He was treated with enemas of 1 per cent tannic, 2 per cent boric, and 1 per cent salicylic acids. Under the treatment he improved considerably. The stools decreased to two or three a day, and the appetite improved. Cases 93-97. [Runeberg. These cases were published by Sievers (70) from Runeberg's notes.] Case 93. — The patient, aged 31 years, did farm work and looked after a pig. For two or three years she had suffered off and on from 44 diarrhea. She had often passed segments of Bothriocephalus latus. Two and one-half months before entrance she became suddenly ill with diarrhea, tenesmus, vomiting, and severe pain in the abdomen. On admission she was weak and had vertigo and ringing in her ears. The stools numbered from ten to twenty per day. An examination of the feces showed mucus, blood, and large numbers of Bothriocephalus latus ova and Balantidium coli. The Bothriocephalus was driven out with felix mass. She was then placed on Emms salt enemas followed by quinine enemas. After eleven days' treatment the stools became of normal consistency and no Balantidia were found in them. The patient remained in the hospital one and a half months longer, but the parasites were not found again. She left, well. Case 9J{. — The patient, a laborer, aged 57 years, had good health until four months before admission. He was then taken ill suddenly with diarrhea and abdominal pain. He lost strength and found it necessary to go to bed. In the thin stools mucus and numerous Balantidia were found. The patient was first treated with naphthalin internally and in enemata and also with tannin enemas; after this for several weeks with enemas of soda solution, followed by quinine enemas. His condition improved con- siderably, the diarrhea stopped, and he left the hospital well. After several weeks an examination of the stools showed no Balantidia. Case 95. — The patient, aged 39, frequently killed swine and other domestic animals. Three months before entrance he began to suffer from diarrhea, pain in the region of the umbilicus, and tenesmus. The stools were thin and watery and contained numerous Balantidia. Under enemas of Emms salt followed by quinine ones he improved and gained three kilograms in weight. The diarrhea stopped and during the last portion of his stay in the hospital no Balantidia could be found in the stools. Case 96. — 'The patient, a woman, aged 35, had to take care of a pig in addition to performing other farm work. Until two years ago she was in good health; then she suffered from swollen and suppurating tuber- culous glands of the neck. For six months she had been afflicted with diarrhea. On entrance the stools were semifluid and contained numerous Balantidia. She was treated for five days with quinine enemas and quinine internally. On the sixth day the stools were half formed but no Balantidium coli was found in them. The patient would not remain longer in the hospital. Case 97. — The patient, aged 69 years, for two months had his dwell- ing "w r all to wall" with pigs without taking care of them directly. He had a weak constitution and w T as at times addicted to alcohol. He had suffered from cough and difficulty in breathing for four years. Three months before entrance he was taken ill with diarrhea, tenesmus, and burning pain in the abdomen. On entrance the stools were watery and bloody and contained many ova of Bothriocephalus latus and Balantidium coli. The former parasites were driven out with felix mass. After calomel the patient was treated with quinine internally and in enemata, preceded by Emms salt enemas. The Balantidia decreased in number and at times disappeared entirely from the stools, but afterwards returned again. Finally they disappeared for some time and the patient left the hospital 45 August 21, with the diarrhea considerably reduced and only from one to two stools a day. His general condition was somewhat better. Improve- ment, however, only continued for a week and a half, and on September 15 he returned with severe diarrhea and numerous Balantidia in the stools. He Avas still under treatment when the case was reported. Cases 98-105. [Henschen (73), 1899-1900.] Cases 98-102. — These five cases were observed by Henschen in the summer of 1900 at Darlane. In all, Balantidia were found. In four of the cases as soon as the parasites were more or less completely removed the patients recovered in a very short time. One case, however, that had suf- fered diarrhea for seven years soon got better, but when he had been under treatment for a few days he was again attacked with this symptom. The number of parasites, however, stood in direct relationship to the intensity of the disease in this case. Case 103. — The patient worked at a sawmill. He often caught cold at his work. He generally had good health. Sometimes he had attacks of diarrhea, but they always passed in a couple of days. His present illness began with severe cold, swelling of the abdomen, and severe diarrhea. The diarrhea continued for seven weeks, when he entered the hospital. The patient did not have syphilis or phthisis. He was much emaciated. The abdomen was much contracted and tender on pressure. The stools showed mucus and numerous Balantidia. After treatment with enemas of acetic and gallic acids for several days the Balantidia for the most part disappeared and the passages became formed. The enemas, after being stopped for one day, were then resumed. For the next ten days, January 31 to February 9, very few Balantidia (and then usually only dead ones) were found, and the passages were firm. On February 10 there were three stools and the Balantidia were numerous. From February 11 to 14 no parasites were found, and the stools numbered one each day. The patient left the hos- pital February 14. Case 104- — The patient, a woman, had generally had good health and had not been troubled before with either constipation or diarrhea. She was taken suddenly ill about two and a half months before entrance with pain in the abdomen followed the next day by diarrhea. The diarrhea con- tinued with short intermissions (due to treatment) until she was admitted to the hospital. On entrance she was very weak and emaciated. The stools were green yellow in color and contained blood and Balantidium coli. A blood examination showed red blood cells, 5,900,000; haemoglobin, 60 per cent. She was treated with enemas of tannic and acetic acids for about a month. The parasites finally disappeared twelve days before the patient left the hospital and were not found during this time in daily examination. The stools were then normal. Case 105. — Henschen, in addition to the preceding seven cases, merely mentions that a case infected with Balantidium coli had been seen and treated by Dr. Linah in Upsala. 46 Cases 106-109. [Chichulin (74), 1900.] This author reports a family epidemic of intestinal catarrh due to Balantidium coli. Case 106. — The patient, a well-to-do farmer, applied for treatment for a persistent diarrhea of four months' duration. Before this he was in very good health. Rarely after continuous drinking, gastro-intestinal dis- turbances appeared, such as diarrhea and pain in the abdomen. He had had syphilis. His present illness began after a Christmas celebration, when he ate sausages which he had made himself. In the preparation of the sausages he took the intestines into his mouth and blew into them. On admission the abdomen was swollen and tender. The stools were frequent, thin, and contained mucus, pus cells, and large numbers of Balantidium coli. He was treated with enemas of sodium bicarbonate followed by enemas of salicylic acid. After four days there was marked improvement in the patient's condition. After one month's treatment the patient had completely recovered. The diarrhea had ceased and the Balantidia had disappeared. Four months afterwards he was also perfectly well. Case 107. — The patient, the wife of case No. 106, applied to the author, complaining of a severe cough, general weakness, and constant diarrhea. There was a familiy history of tuberculosis. The patient had suffered from bronchitis as a child and 'pneumonia three years before. At Christmas time diarrhea began after she had helped her husband to make sausage and after eating the pork so prepared. Before this she had no diarrhea and was usually constipated. On admission she was emaciated and very anemic. There was a systolic murmur over the heart and the second pulmonic sound was accentuated. Percussion and auscultation showed the right lung diseased. The sputum contained tubercle bacilli. The abdomen was drawn in. The stools were liquid and contained large numbers of Balantidium coli. The treatment consisted of creosote and kaphir inter- nally and enemata", as in case 106. The patient's strength fell pro- gressively, however, and after three weeks the enemas were changed to a watery solution of iodine, 1 to 10,000. After seventeen days the Balan- tidium coli disappeared from the feces and the latter became of a gruel- like consistency. The general condition of the patient was not, however, markedly improved. Eleven days later the lung symptoms became aggra- vated and the patient died of sudden prolonged pulmonary hemorrhage. The husband declined to allow an autopsy. Case 108. — A servant to the above case had previously had good health. Her diarrhea appeared almost simultaneously with that of her mistress. Defecation was often accompanied with colic. After suffering in this manner for over two months she became very thin and pale. On admission the abdomen was contracted. The whole colon was dilated, however, and painful on pressure. An examination of the feces showed undigested food particles, mucus, * pus corpuscles, epithelial cells, and Balantidium coli in large numbers. The patient was treated with enemata as in case 106 and with salol, benzol, naphtho-amagdalin by the mouth. 47 Five times the diarrhea stopped and the parasites disappeared. But each time the diarrhea recurred and then numerous Balantidia were found. Finally, after the fifth seance of treatment, there was no recurrence. The stools were examined two and a half months after the complete dis- appearance of the Balantidia and the diarrhea, and were found normal. Case 109. — A boy, aged 4 years, a son of patients Nos. 100 and 107, was brought complaining of bloody diarrhea which had lasted for two weeks. The child had gradually become weak and irritable, and according to the father's statement had recently begun to eat pork. On admission he was anemic and there was general reduction of nutrition. The abdomen was distended and tender. The stools were painful and contained blood, mucus, pus, ova of ascaris lumbricoides , and numerous Balantidia. Edema of the ankles was present, and some fever. He was given calomel and santonin and the lumbricoids were expelled. But the character of his stool and his general condition did not at all improve. Then he was given opium and finally enemata of sodium benzoate alternating with 1 per cent solution of boric acid. This treatment was continued for one week, but the condition of the child grew gradually worse and the Balantidia increased enormously in numbers. The entire field of the microscope was filled with them. The child died in collapse and the father would allow no necropsy. Cases 110-114. [Collmann (75), 1900.] Case 110. — The patient was a workwoman from Laptau. She entered the clinic complaining of severe diarrhea which had continued for a long time. In the very thin and liquid stools Balantidia were found in large numbers. The patient was given aqua calcis and was not seen again. Case 111.- — The patient, a young woman, entered the clinic complaining of a persistent diarrhea. A diagnosis of Balantidium coli enteritis was made; flores cinse was prescribed for her. She also did not return to the dispensary again. Case 112. — The patient, aged 50 years, had for nearly ten years off and on passed segments of taenia. He also suffered from nausea and vomiting at times. For four weeks prior to entrance he had diarrhea. On admis- sion there was slight edema of the legs and a soft, systolic murmur could be heard over the apex of the heart. The abdomen was soft and not swollen or tender on pressure. The urine was normal. The stools were very thin and greenish. Microscopically they contained leucocytes, epithelial cells, Bothriocephalus ova, cercomonas intestinalis, and Balantidium coli. The latter was present in large numbers. On June 3 taenia treatment was prescribed and one specimen of Bothriocephalus latus was passed with the head. On June 5 the stools were thin but contained no Balantidium coli or Bothriocephalus ova. On June 10 there were also no parasites present in the feces, and the patient left the hospital at his own request. Case IIS. — The patient, aged 22 years, had for ten years off* and on noticed taenia segments in his stools. He had been troubled since a child with attacks of diarrhea, but had otherwise been in good health. 48 Four months before entrance the diarrhea became severe and cramps and pain in the abdomen developed. Later he had attacks of vomiting. On admission he was pale, weak, and emaciated and suffered with diarrhea, headache, vertigo, and pain in the abdomen. There was palpitation of the heart. The fundus of the eye showed small retinal hemorrhages. There was a soft, systolic murmur over the heart. The second pulmonic sound was not accentuated. The red cells showed 1,024,000, white cells 4,000 to the cubic millimeter; haemoglobin, 30 per cent. The stools were very thin and contained numerous Bothriocephalus ova and many Balantidia. Taenia treatment was prescribed, but the head was not obtained. After he had been in the hospital for about a month bronchitis developed. No' tubercle bacilli were found in several examinations of the sputum, and the lung symptoms disappeared shortly afterwards. He was given boric enemas daily. After this treatment for about five weeks the Balantidia disappeared from the stools. Taenia treatment was then given and a chain of Bothriocephalus latus passed, though the head was not found. Two weeks later the patient left the hospital greatly improved. No Balantidia or ova had been found for tw r o weeks; the stools numbered two or three a day; the lungs and the fundus oculi were completely normal. Case 1U{. — The patient, a woman, aged 48 years, was taken sick six months previously with tenesmus, diarrhea, and abdominal pain. These symptoms continued and she lost flesh rapidly. On admission she was markedly emaciated. Over both lungs were heard quite a number of dry rales. The abdomen was painful on pressure. The urine showed a trace of albumen and hyaline casts. The stools were liquid and contained mucus and large numbers of Balantidia and ova of the tricocephalus dispar. Tubercle bacilli were sought for in the stools and sputum but were not found. A blood examination showed red blood corpuscles 4,000,000, white cells 12,800. A differential count showed — Per cent. Polynuclear leucocytes 57. 4 Mononuclear leucocytes 3. 1 Eosinophils 5. Lymphocytes 31. 5 The patient was given tann-albin, and the diarrhea became better. When she left the hospital one and a half months later the stools were formed and contained no Balantidium coli. During the summer of 1900, as stated above, the author observed and reported with Dr. Musgrave a case of infection with this parasite. I shall report this case here with fuller details : Case 115. [Strong and Musgrave (76), Manila, 1900.] Chronic diarrhea; Balantidium coli in enormous numbers in the dejecta; death; autopsy. — The patient, a soldier, aged 26 years, 49 was admitted to the hospital June 9, 1900, complaining of severe diarrhea and of pain in the rectum. The family history was good. There was no history of pulmonary trouble or of hereditary disease. Personal history. — He suffered from scarlet fever and measles as a child. He had always lived in the northern New England States until September, 1899, when he enlisted in the United States Army and went to San Francisco, Cal. In December, 1899, he came to Manila. He states that, except as noted above, he had always been perfectly well until coming to the Philippine Islands. Present illness. — The patient went into active service in the field in January and felt perfectly well until the latter part of February. While on this service he often drank water from streams and marshy places. He ate the usual army ration and had not come into contact with pigs in any way. In April he was attacked suddenly with diarrhea and the stools became thin and watery. The diarrhea continued until entrance to the hospital, but at times varied in severity. Sometimes there were as many as twenty-five stools in twenty-four hours. Occasionally he passed some mucus and blood. Shortly before admission there was considerable pain in the rectum after going to stool. His appetite was good at first, but a short time before admission it decreased considerably, and at about this time he became troubled with attacks of vertigo. Physical examination on entrance. — The patient was considera- bly emaciated and the malar bones stood out prominently. The cheeks were flushed and the conjunctivae pale; the tongue was moderately coated. Examination of the heart and lungs was negative. The liver was not increased in size and the spleen not palpable. The abdomen was drawn in, its walls were thin, and the pulsations of the abdominal aorta could be easily felt. There was tenderness on pressure, especially over the transverse colon. The pulse was 86 to the minute and the temperature 99.2° F. Microscopical examination of the thin liquid stools showed mucus, epithelial cells, leucocytes, red blood corpuscles, and very large numbers of Balantidium coli. No amoebae or other parasites than the Balantidia were present. A blood count showed 4,200,000 red blood cells and 7,000 white corpuscles. The urine contained no albumin, but a few cylindroids were present. The patient remained in the hospital up to the time of his 25822 4 50 death, which occurred on August 11. During this period he was seen on a number of occasions by the author. The diarrhea was continuous ; the stools varied from three or four to twenty in twenty- four hours and were always thin, containing mucus and microscop- ically epithelial cells, Balantidia, and blood cells. The parasites were very numerous; often from 100 to 200 could be counted in one field with a low power of the microscope (Zeiss A A, ocular No. 2). No tubercle bacilli were found in the stools. The temperature was usually normal or slightly subnormal. On one occasion (June 22) it reached 101° and on another (July 12) 101.4°. He complained considerably at times of general weakness and of pain in the abdomen and in the rectum after going to stool. He was treated with various remedies, such as salol, thymol, mor- phia, bismuth subnitrate, and santonin by the mouth and by quinine and nitrate of silver in enemata. None of these remedies seemed particularly to influence the course of the disease. There were usually fewer living parasites present shortly after the enemas were given. The latter were finally discontinued on account of the weakness of the patient and the discomfort they caused him. A second blood count on August 9, two days before death, showed 2,300,000 red blood corpuscles and 14,000 leucocytes. A differential count of the leucocytes showed — Per cent. Polymorphonuclear leucocytes 66.6 Small mononuclear leucocytes 21.4 Eosinophils 9.1 Large mononuclear and transitional leucocytes 2.9 The patient grew extremely emaciated. The first sound of the heart became prolonged, and he gradually sank and died. Necropsy (five hours post-mortem). — The body measured 144 centimeters long and was extremely emaciated. There was very little subcutaneous fat present. The circumference of the arm in its greatest diameter over the biceps was 15 centimeters; that of the forearm at its upper third, 13f centimeters ; of the thigh at the middle, 22| centimeters; the calf of the leg, 17^ centimeters. There was no rigor mortis or livor mortis present. The intercostal muscles were pale in color. Heart and pericardial cavity. — The cavity contained a small amount of clear fluid. Both layers of the serosa were smooth. The heart was small and the valves normal; the right chamber 51 contained a small amount of fluid blood ; the arch of the aorta showed early atheroma and the coronary arteries early sclerosis; the muscle was soft and pale and cloudy; the organ weighed 125 grams. Lungs and pleural cavities. — The latter were dry and free from adhesions. Both lungs were moderately pigmented and everywhere crepitant. There was no bronchitis present. Abdominal cavity. — The omentum contained very little fat; it was adherent to the abdominal parietes just external to the coecum and to the caecum itself; the appendix 5 millimeters from its tip was sharply flexed upon itself and the tip" was hard and fibrous ; there were no evidences of any active inflammation; no other adhesions were present in the cavity. The mesenteric lymphatics were somewhat swollen, and many of them were hyperemia The small intestine in the lower part of the jejunum and ileum was contracted. The csecum, ascending and transverse colon were moderately distended ; at the splenic flexure the caliber of the bowel was much reduced and continued so for about 15 centimeters, when it again became moderately distended ; the mesocolic glands close to the bowel were moderately swollen and felt hard and shot-like. The spleen weighed 110 grams; its surface was smooth and the structure well preserved ; the pulp was dark in color ; the trabecule and malpighian bodies were visible. The liver weighed 1,110 grams; its surface was smooth and the cut section appeared normal ; the gall bladder contained no stones ; it was moderately distended with greenish fluid bile ; the common duct was patent. The kidneys together weighed 255 grams; the capsules stripped easily ; the surface vessels were somewhat injected. On cut section they were pale and cloudy ; the pelves and ureters appeared normal, the adrenals showed no pathological changes. The bladder was considerably distended with clear urine. The esophagus and pancreas were also normal. The stomach was small and contracted ; the mucosa not thickened ; there were a few diffuse, reddened patches of the mucous membrane. Intestines. — In the small intestine there was no apparent catarrh of the duodenum; the mucosa of the jejunum was bathed in yel- lowish mucus; the mucous membranes beneath appeared normal; in the lower portion of the ileum the mucosa was reddened in places, 52 particularly on the summits of the rugse; Peyers patches and the solitary follicles were not swollen ; just above the ileocecal valve the mucosa was much reddened. The mucosa of the large intestine near the rectum was covered with an abundant bloody mucus exudate which was easily washed off. The mucosa itself was reddened throughout. About 36 cen- timeters above the anus there was an old, healing ulcer in the mucosa; it was not particularly undermined and had a blackish, pigmented base and margins. Over some areas the hyperemia of the mucous membrane was not so marked, and the mucosa in these portions seemed thinned. In the transverse and ascending colon and caecum there were a number of old ulcerations similar to the one described above. Anatomic diagnosis. — Chronic ulcerative colitis; extensive infec- tion of the large intestine with Balantidium coli ; chronic localized adhesive peritonitis ; cloudy swelling of the kidneys and heart muscle. Microscopical examination of the scrapings from the mucosa and from the contents of the large bowel showed many motile Balan- tidia coli. In the lower end of the ileum a few parasites were found. They were not, however, observed elsewhere in the intestinal tract. Fresh smears from the spleen were negative for malarial parasities. Bacteriology. — Agar-plate cultures from the heart, spleen, liver, and kidneys were negative for organisms. Histological studies were made. Since the preliminary report of case 115 was made and before the completion of this article Solo w jew and Ssaweljew both reported cases. The observations of the former author have an important bearing upon our own studies, so these cases will therefore be added. Case 116. [Solowjew (78), 1901.] The patient was 54 years old and entered the hospital clinic complaining of bloody diarrhea, tenesmus, and abdominal pain. For the past year he had looked after cleaning pigpens. He did not remember just when the diarrhea began ; the periods had been intermittent. Shortly before entrance he suffered from attacks of vomiting. On admission he was anemic and very weak. Over the lungs fine rales were heard. The pulse was weak. The abdomen was swollen and the large intestine painful on pressure. The 53 stools contained blood and Balantidia in large numbers. The treatment consisted of tannin internally and in enemata. No new symptoms devel- oped, but this condition gradually grew worse and he died. Necropsy (seven hours after death, by F. J. Romanon) . — Anatomical diag- nosis: Colitis ulcerosa e Balantidium coli; perihepatis et peri splenitis adhesiva; emphysema pulmonum, oedema piae matris; arterio sclerosis. The serosa of the small intestine was rose-colored. The mucosa was swollen throughout and dull looking. In the ileum it was covered with a thick, whitish mass mixed with blood. No parasites were found in it. The serosa of the colon was markedly hypersemic, especially in the trans- verse and descending colon. The walls of the large intestine were slightly thickened, edematous, and hyperarmic. There were many ulcerations present. Their forms were round or oval and they measured from 1 milli- meter to 1 centimeter in diameter. The greatest diameter of the ulcers corresponded to the transverse section of the intestine. The ulcers were often fused together. Their edges were blood-red, quite smooth, and usually slightly infiltrated. Their floors were formed of muscular coat, submucosa, or sometimes by serosa. In some of the large ulcers the floors were slaty-gray. The mucosa between the ulcers appeared swollen and hypersemic. The mesenteric glands especially above Bauhini's valve were swollen and reddened. Microscopical examination of the contents of the large intestine showed nonmotile Balantidia coli. Histological studies were made. Case 117. [Ssaweljew (79), 1901.] The patient, aged 61 years, had taken care of pigs. For four weeks she had pains in the abdomen; following this diarrhea and tenesmus began and continued until her admission to the hospital. On entrance the abdo- men was swollen and there was pain over the large intestine on pressure. An examination of the feces showed mucus, blood, and numerous Balantidia. She was treated with enemas of calcium chloride and sublimate solution of 1 to 3,000. The author does not state what became of the case. CLINICAL SUMMARY. From the foregoing histories of the 117 cases it may be seen that in all but two (Nos. 35 and 43) either diarrhea or dysentery existed. Case 35 had apparently no intestinal symptoms, and the parasites were found in the sputum. In case 43 (Mitter's) there was no diarrhea and the stools were of fairly solid con- sistency but contained undigested food, and there was abdominal pain below the umbilicus, which was increased on pressure. Of the 117 cases tuberculosis of the lungs existed in two (Nos. 78 and 107), tuberculosis of the glands of the neck in one (No. 96), 54 tuberculosis of the intestines in one (No. 115) (see histological examination), typhoid fever in two (Nos. 3 and 32), chronic nephri- tis in six (Nos. 12, 36, 42, 82, 90, 114), uncinaria infection in one (No. 28), carcinoma of the rectum in one (No. 34), and Bothrioce- phalus latus infection in ten (Nos. 68, 71, 72, 73, 75, 90, 93, 97, 112, 113). In these twenty-three cases, therefore, it might be difficult to say just what influence the parasite played in the production of the diarrhea. In case No. 32, however, the diarrhea continued after the fever had disappeared and until treatment was directed against the parasite. In case No. 12 there was ulceration of the intes- tine at necropsy, and in case No. 90 there was chronic colitis, and there were epithelial defects, though no ulcerations were present. Therefore the intestinal lesions could not be attributed to the nephritis. In case No. 71 there was no infection with Both- riocephalus latus at the time the patient was under observation, and in case 75 there were ulcerations in the large intestine at autopsy. In cases 68 ? 72, 90, 93, and 97 the diarrhea continued after the Bothriocephalus latus had been driven out of the intes- tines. As there might appear some doubt as to the origin of the diarrhea in the other fourteen cases, it would be wrong to draw conclusions from them, but there still remain 103 cases in which its etiology must be explained. An attempt has therefore been made to arrange all of the cases in tabular form as below with regard to the relationship between the parasite and the diarrhea. While it has sometimes been dif- ficult to decide into which column a number of the cases should be placed (and perhaps here the reader will not always be willing to abide by the author's decision), effort has been made to place no case in Column II in which the relationship between the parasite and diarrhea (as borne out by the clinical history and the necropsy) did not seem definite. In Column I have been placed those cases in which it seemed that the diarrhea was probably dependent upon the presence of the parasite; in Column II those in which the diar- rhea was almost certainly dependent upon the parasite ; in III those cases in which, from the incompleteness of the clinical histories, we are not able to decide ; in IV those in which, on account of the coexistence of other diseases or from other causes, we can not determine the relationship ; in Column V those cases in which, from 55 the histories, the diarrhea seemed to depend not upon the presence of the parasite but upon other influences: Table showing relationship between Balantidium coli and diarrhea. I. II. III. IV. V. No. 1 No. 17 No. 10* No. 3 No. 4 2 20 14 11 5 6 31 15 18 37 7 44 16 28 43 8 49 22-27 34 48 9 50 29 36 86 12 51 30 41 13 68 38 42 19 91 39 52 21 93 53 71 32 94 54-65 75 33 95 66 76 40 98-101 69 78 44 104 70 80 45 106 73 81 46 108 74 82 47 109 75 83 67 116 77 86 72 105 88 79 110 88 84 111 92 85 117 96 87 112 98 113 90 114 97 102 103 107 115 Therefore, from a consideration of the clinical data, one may seem justified in emphasizing the following conclusions : The pres- ence of Balantidium coli in the stools is usually associated with diarrhea, in which the feces are generally liquid, often contain mucus, sometimes undigested food, and frequently blood. The diarrhea is usually particularly persistent in its course until treat- ment is directed immediately against the parasite. Colic is a frequent symptom, and nausea and vomiting may occur. The abdomen may be swollen. It is . frequently painful on pressure, particularly along the course of the large bowel. The colon on palpation is often thickened. Tenesmus is common. When the parasite has been present for long periods of time there is usually general weakness, exhaustion, and emaciation ; more or less anaemia is then generally found and edema of the feet and ankles may appear. The disease has been seldom met with in children (in but two reported, cases). Twenty-five per cent of the patients gave a history of having either associated with pigs or eaten or prepared fresh 56 PROGNOSIS. In regard to the prognosis we must draw our conclusions from 111 cases, as in the remaining the data are insufficient to decide from. In 32 cases (29 per cent) recovery took place, the diarrhea stopped, and the parasites disappeared. In two cases, which were greatly improved and in which the diarrhea disappeared, after several months only an occasional parasite could be found. In eleven other cases there was considerable improvement. The mortality was 30 per cent, but, as already stated, in a number of cases death occurred from other diseases. The prognosis seems to depend upon the general condition of the patient and upon whether he has sufficient strength to undergo the local treatment, the extent to which the disease has progressed, and upon the coexistence or nonexistence of other diseases. TREATMENT. In the treatment of the disease quinine enemas have given satisfactory results in some cases, in the hands of De la Chapelle, Euneberg, Janowski, and others. Quinine enemas preceded by Ems salt-water enemas (15 grains to 1,500 grams of water) were used with good results by Sievers. Winbladh found enemas of quinine and sulphuric acid of benefit. With Eoos quinine failed, but calomel in doses of 1 decigram three times daily removed the parasites. Edgren recommended naphthalin internally and tannic acid in enemata. Wising advised the employment of the same with also acetic-acid enemas. Bushuyeff obtained the best results with salol administered by the mouth and tannin in enemata. Zhegaloff and Woit, however, found enemas of acetic and tannic acid of but little benefit. Vlayeff reported that iodine solution (1-5,000) drop for drop of feces killed the parasite at once. Iodine (1-10,000) killed it in two minutes. Silver nitrate (1-3,000) soda solution 2 per cent and quinine (1-700) all acted in a weaker manner toward the parasite. Waldenstrom and Henschel, after trying a large number of drugs, decided that enemas of 50 grains of acetic acid and 5 grains of tannic acid to one-half gallon of water at 37° C. were the best remedies. Eapchevski recommended salicylic acid (15 grains) and sodium sulphate (one-half ounce) morning and evening, and enemas twice 57 a day of salicylic acid (1-1,000). He admits that in hopeless cases this treatment only increased the irritation of the intestine. Lavrovskaya advised, for patients too weak to use Kapchevski's treatment, salol by the mouth and salicylic enemata preceded by Ems salt enemata. Solowjew claimed that boric and salicylic enemas gave good results. Chichulin obtained good results with sodium-bicarbonate enemas followed by salicylic-acid enemas (1-1,000) and (1-2,000) slightly acidified with hydrochloric acid and by salol tann-albin, etc., administered by the mouth. On the other hand, the various remedies mentioned above, when employed by other observers, have frequently failed. It appears probable that, in cases in which the lesions are not too far advanced and in which the strength of the patient is such that the local treatment may be pursued for long periods of time, the patient may be freed from the parasite. In other words, the same class of cases may be expected to yield to treatment and to recover from Balantidium colitis as from amoebic dysentery. PATHOLOGICAL SIGNIFICANCE. SUMMARY OF THE GROSS LESIONS. Among the thirty-five deaths there were thirty-two necropsies. In twenty-eight of these cases there was ulceration of the large intestine. In one (No. 38) the condition of this organ is not stated. In three cases (36, 47, 90) there were no ulcerations of the large intestine, but only chronic catarrh. Case 36 died of nephritis, and the bowel showed only inflammatory thickening. Case 90 died of arterio sclerosis, edema of the brain, and pneu- monia; it also showed hemorrhages and superficial defects of the mucosa of the large bowel. The author thought the patient died of a complication before the ulcerations of the intestines had taken place. In two cases (75 and 89) there was general peritonitis, though in neither was the point of perforation ascertained. The type of intestinal ulcer described in the cases is not perfectly distinctive. The old ulcers were blackish or slate-colored ; the edges of the more recent ones were frequently slightly undermined and irregular, with sometimes the greatest diameter lying trans- versely to -the lumen of the intestine. In some cases there were 58 diphtheritic patches present. The mucosa between the ulcers was usually reddened and often hemorrhagic. In the small intestine the lower end of the ileum occasionally showed hyperemia. Peyer's patches were sometimes swollen. In only one case was there an ulcer in the ileum (No. 12). The mesenteric glands were at times swollen or pigmented. There were no other constant changes in any of the other organs. The parasites were found at necropsy in 21 cases. In three it is not stated whether they were present or absent. Of the remaining eight cases in which they were not found, in seven the time the necropsy was performed after death was probably too great for one to expect to find the parasites living. In the remaining case the time the autopsy was performed after death is not known. In only two of the cases were the parasites found in the lower end of the ileum. HISTOLOGICAL STUDIES. In but seven cases were histological examinations made. Case 33. — Rapehevski merely states that the microscopical examina- tion of the large intestine showed changes proper to ordinary chronic ulcera- tive inflammation. The time after death of the necropsy is not given, and it is not stated whether the parasites were found at the autopsy, but they were present just before death. Case 67. — Fadieyeff found on section of the large intestine that the floors of the ulcers were formed of muscular and serous coats. At the edges of the ulcers there was necrosis, infiltration with round cells and hyper- trophy of the fixed tissue cells. Balantidiwm coli was not discovered in the sections, but an abundant accumulation of fungi and bacteria were found in the mucous coat. The author admits that, as the time was summer and the necropsy was not performed until two days after death, the growth of fungi and bacteria was probably post-mortem, and that the Balantidia could have easily disappeared and become disintegrated within this time. Case 15. — Gurvich found that microscopical examination of sections of the large intestines showed inflamed purulent ulcerations. The floors of the ulcers were formed of muscular coat. The edges were undermined and surrounded by a small-celled infiltration. In this case the necropsy was performed forty-eight hours after death and no parasites were found in the intestine at autopsy, though they were present shortly before death. Case 89. — Woit found, on histological study of sections of the large intestine, that the mucosa was greatly altered in places, and was sometimes deprived of the epithelium. Here and there Lieberktihn's crypts were still visible, and there was then moderate atrophy of the epithelial cells. Where the glands were relatively well preserved interglandular and subglandular inflammatory infiltration had occurred. In the places where the glands 59 had disappeared the infiltration was less marked. Infiltration was present, but only to a slight extent, in the smaller ulcers (which reached only to the submucosa) and along their undermined edges. To sum up, an inflam- matory small-celled infiltration of the mucosa existed, with the borders of the ulcers not very markedly infiltrated with round cells. Case 90. — In Woit's other case, on microscopical examination of the large intestine, the mucosa was in general well preserved; only in places were there slight superficial defects which did not pass through the entire glandular layer. Lieberkuhn's crypts were clearly distinguished, and although greatly altered, were still present. There was marked inflammatory infiltration of the interglandular and subglandular portions of the mucosa. In the latter large numbers of round cells were found. The submucosa was somewhat swollen and edematous; it was also infiltrated inflammatorily, but to a less degree. The blood vessels in this layer were markedly dilated; in places in the submucosa hemorrhages had occurred. The muscular coats were unaltered. In case 89, while the exact time after death the necropsy was per- formed is not known, the patient died September 24 and the necropsy was performed at 10 a. m. September 25. In case 90 the necropsy was not performed until fourteen hours after death. In neither of these cases were there Balantidia found at the autopsy, though in case 89 they had been present shortly before death. Therefore, from the literature of the first 114 cases, it may be seen that while the Balantidium coli had never been found in a normal intestine at necropsy, and while the appearance of the large intestine in these cases had been usually similar, there had been no distinctive and specific pathologic lesions which could be ascribed to this parasite until my preliminary report with Musgrave of case 115, in October, 1900. The changes found in the histological sections in this case will now be repeated and described more fully. It is to be noted that the necropsy was performed five hours after death and the parasites were found living at this time in all portions of the large intestine and in the lower four to fiNe centimeters of the ileum. The tissues were placed at once in alcohol or Zenker's fluid. Sections were stained in hematoxylin and eosin, saffranin, Unna's alkaline methylene blue, Ziehl-Neelson's solution, and by the Gram-Weigert stain. I shall describe the lesions of the large intestine in the order in which from a study of the tissues I believe they progress. Sections of the early lesions show above the surface of the glands of Lieherhuhn a layer of desquamated epithelial cells, leucocytes, and altered red blood corpuscles. The cell bodies usually stain lightly, but many of the nuclei still stain well. A number of them 60 are, however, fragmented. Balantidia are fairly numerous in this exudate. The layer passes gradually into and infiltrates the adja- cent portion of the mucosa. The upper surfaces of the glands are eroded and their cells in places are desquamated. Large numbers are swollen and have undergone mucoid degeneration. In places, the layer is extensively infiltrated with round cells. Eosinophiles are fairly numerous and an occasional plasma cell may be seen. A number of epithelial cells, some proliferating, are also present. Many of the capillaries are dilated, and there are numerous small hemorrhages, in other places the hemorrhages are much more extensive. In the areas where the glands are pressed apart, thb round-celled infiltration is not so marked, but the epithelial cells show marked mucoid degeneration. Balantidia are found in con- siderable numbers all through the mucosa, lying in the crypts, or breaking through different portions of them. A number may be seen half way through the walls of the glands of Lieberkuhn where the basement membrane has ruptured. The parasites are numerous at the bases of the glands, sometimes lying four or five together. Here the subglandular infiltration is more marked. Often from twenty to thirty parasites may be counted in one field. (Zeiss AA, ocular No. 4). Sometimes from eight to ten eosinophiles may be seen about a parasite, while others show none of these cells in the immediate neighborhood. One finds a gradual continuation of the morbid process as follows : The altered mucosa becomes thinner and the limits between one gland and another are little by little lost and finally one finds areas in which the glands are no longer distinguishable, or in which only the remains of an altered gland occur here and there. The whole portion is infiltrated and there are many altered blood corpuscles and much blood pigment scattered through it. There are also a number of epithelial cells, some showing karomitosis. The edges of these areas are formed of more or less altered glands. The parasites are not usually numerous in the interior of these portions, but one is apt to find them deeper in at the base of the mucosa and also along the margins of these areas. When the process is continued until ulcers are formed, sections of these ulcers show the mucosa completely destroyed in the center; near the surface there are no traces of cells remaining. The whole necrotic portion takes a diffuse pale stain and contains no visible parasites. Scattered through it is considerable black pigment. These necrotic areas 61 extend as deep as the upper portions of the submucosa. Surround- ing them are areas of infiltration in which leucocytes showing karyorexis and lysis are numerous. Still farther outside the edges of the ulcers are areas of round-celled infiltration and the remains of glands appear, together with the parasites, as described above. As we go deeper, parasites may be seen in places passing through the muscularis mucosae in large numbers. Here and there round cells occur grouped about them, but at other times single parasites are found without any infiltration in the neighborhood. Eosino- philes are numerous in the muscularis and submucosa. The para- sites push the connective tissue fibers apart in their passage. At times the anterior extremity seems drawn out almost to a point. The blood vessels are much hypertrophied and increased in number. Sections of many of the veins, arteries, and lymph vessels show one or two parasites in the lumina. Occasionally about the thin-walled vessels infiltration is found. In one section nine eosinophils were counted about a section of a vein which contained two parasites. Other vessels, particularly those with thick walls, show no infiltra- tion around them. The thinner-walled and smaller vessels which do or do not contain parasites often show small hemorrhages in their regions. We have not succeeded in finding any parasite lying in the vessel wall, and it is doubtful whether they enter the large vessels in the submucosa directly or are carried there by the larger capillaries from the mucosa. There are certain portions of the submucosa which stain poorly and which contain no parasites ; also infiltrations of round cells occur about these areas in which no parasites are found. Other portions are more hyaline and contain few cells, while near at hand there are areas containing fibrous connective tissue which show infiltra- tion here and there. The parasites are found in all depths of the submucosa. Deeper in, they are seen passing along the intermus- cular septa and occasionally lying in groups of ten or twelve between the two layers of the muscle. Here there seems to be at times some attempt on the part of nature at encystation, as a single layer of epitheloid cells was found partially enveloping one nest of thirteen parasites. These parasites all contained leucocytes in their interior. There was no apparent infiltration with round cells about the group. Other parasites show slight infiltration about them as they pass into the muscle layer. The Balantidia do not seen to be able to wander freely through the muscle 62 bundles, which generally seem little altered: In the serosa also the parasites are frequently fo^nd in the blood vessels. The latter are hypertrophied, increased in number, and crowded with red blood cells. Occasionally' there are minute hemorrhages about the smaller vessels. There is an occasional eosinophile in the stroma. In a number of the larger veins which contain the parasites in their centers there is a mesh wcrk of fibrin about the parasite. The fibrin is arranged in rather coarse bands and with wide mesh. All about the parasite, lying in the fibrin, are numerous cells con- sisting of polymorpho-nuelear leucocytes and round cells with an occasional eosinophile. Outside of these areas there are com- paratively few leucocytes among the blood cells. While this change is not constant in all of the veins which contain parasites, it frequently occurs, and about parasites which show no signs of degeneration. Sections stained in Loeffler's methylene blue and hematoxylin and eosin and with Ziehl-Neelson's solution show that the bacteria are plentiful in the necrotic areas, particularly on the surface, but also extending into the submucosa as far as the limits of the necrosis. Both bacilli and cocci are found. The bacilli which generally decolorize by Gram's stain are more numerous in the depth than cocci. No tubercle bacilli were found in several sections. It must be admitted that in places the microscopical lesions of the large intestine suggest strongly those of an old or healing tuberculosis as seen by the homogeneous appearance of the connective tissue in certain portions of the submucosa which stained rather poorly, by the more hyaline portions poor in cells, by the fibrous connective tissue containing here and there foci of inflammatory activity, by the infiltration of round cells in other places where parasites were absent, and by the numerous hemorrhages due to erosion of the vessels. Indeed, after more careful study of the sections, we finally became convinced that such a process actually existed even though no tubercles or tubercle bacilli were encountered; and obviously while these features were not necessary for a diagnosis, yet in this case they were extremely desirable; but, as stated, no tubercles could be found in sections of the large intestine. Finally, however, on making other sec- tions of the intestinal tract, several tubercles were discovered in a section of a portion of the ileum, one containing a giant cell. The mesocolic lymph glands lying close to the serosa show areas of necrosis and of hemorrhage. The lymph sinuses are crowded with red blood cells. The remains of many distorted and shrunken nuclei and chromatin granules are present. The sinuses are closely packed in places with round cells. There is apparently a slight increase in the eosinophiles. A small amount of. fibrin may sometimes be seen. A section of the small intestine made just above the ileocecal valve shows a picture similar to that seen in the preparations from the large 63 bowel. In sections made higher up in the ileum there are areas of round- celled infiltration in the mucosa and submucosa and no parasites present. In places, however, tubercles are found, some containing giant cells and others showing fibrous degeneration. The liver sections show in places granular and fatty degeneration of the hepatic cells. A few small areas composed of round cells with a little fibrin lying between them are present. The other organs reveal few changes of importance to us. The heart muscle and kidneys show cloudy swelling and granular degeneration of some of the cells. Therefore, the entire pathological picture in this case can not be ascribed to Balantidium coli. That some of the changes of the large intestine were dependent upon the presence of this parasite, however, seems unquestionable. For example, in the sections the parasite may frequently be seen pushing itself through and ruptur- ing apparently normal glands. Again, in places where the round- celled infiltration is marked, one or more parasites are usually near. Also, the collection of leucocytes often seen about the parasites lying in the blood vessels and the fibrin network about them almost cer- tainly depend upon the presence of the Balantidia. In addition, the extensive eosinophilia in the tissues is perhaps due in larger part to the parasite. Case 116. — The histological studies of case 116 as yet remain. Not long after the study of the case reported by Musgrave and myself, Solo jew made careful histological studies of the intestine from his case (quite independently of our work). The conditions he found are very similar to those described above and confirm our observations. The parasites were found invading the mucosa, submucosa, and muscular layers. They were less numerous in the areas which showed marked necrosis and were found in the margins of more healthy tissue which surrounded these areas. The capillaries and veins of the submucosa were dilated, contained parasites, and often showed hemorrhages about them. Often the amount of infiltration was small about single parasites in the tissues. However, when the parasites were found in large numbers, the infiltration was very marked. The ulcerations extended in places down to the muscular coat, and their edges were usually undermined. The lymph glands were hypertrophied and hyperemic. No parasites were found in any other organ than the large intestine. In the mesenteric glands, spleen, liver, and kidneys there was considerable pigment inside the leucocytes in the blood vessels. No tubercle bacilli were found in the sections. The histological examination of these seven cases, as far as they go, show a general similarity. The resemblance between Woit's 64 second case, Solo Jew's, and my own is striking. In all there was catarrh of the mucosa, infiltration of the muscularis and submucosa with round cells, and dilatation of the vessels of the submucosa with numerous hemorrhages. In Solo Jew's case and mine the changes are almost identical. In but two cases were the parasites found in the tissues, and it seems not unlikely that in the remaining number the Balantidia might have died and become disintegrated in the time that elapsed between the death of the patient and the preservation of the tissues. The parasites, as one knows, become very quickly disintegrated after death. Though occasionally they have been found living for long periods in the dead body, yet in Solo Jew's case, performed only seven hours after death, the parasites were already immotile. As in the cases of Fadieyeff, Gurvich, and Woit, the parasites were not found at necropsy — perhaps one could hardly expect that they should have been discovered in sections. At any rate, ulcers in the large intestine were present in all of the seven cases, and it seems difficult to explain why the parasites had not invaded the tissues through these lesions. That they do always invade the intestinal coat can, however, be definitely decided only by future observations. The invasion of the Balantidia post-mortem in our case does not seem likely, judging from the short time after death the necropsy was performed, from the position which the parasites occupied in the tissues, and from the occasional attempt at encystation and from the other histological changes about them. We are unable to decide in regard to the fate of the numerous parasites found in the blood vessels and lymph spaces. A careful search for them in the sections of other organs of our case was unsuccessful. Solo jew also met with none elsewhere than in the sections of the large intestine. In this connection it is interesting to recall case No. 35, in which the parasites were found in the sputum and in which the author thought that either an abscess of the lung or liver had existed. Manson, in his Text-Book on Tropical Diseases, also reports that in the expectorated pus from a liver abscess discharging through the right lung he found a ciliated infusorium resembling Balantidium coli. Willach's studies of pigeons are also suggestive in this respect, as he encountered small, hepatized areas in the lungs of two of these animals. The areas were congested, grayish red, and contained oval infusoria (Balantidium viridi) covered with closely placed cilia and with a peristome and triangular oral opening. The protoplasm 65 was a greenish color and there was a granular nucleus. The mucosa of the intestinal canal in the pigeons was reddened, spotted;, and slightly swollen, and the liver and muscles (in the second pigeon) showed small yellow areas in which these parasites were also found. Paulich observed similar infusoria in the lungs of an orang-outang in the zoological garden at Hamburg. Perroncito fqmd other infusoria in the lungs of a sheep. As to the role that the intestinal bacteria play in producing the necroses and ulcers of the intestine in cases of infection with Balantidium coli, it seems undoubted that they assume a very important part here just as they probably do in producing the lesions of amoebic dysentery, and indeed many of the ulcers described are not very dissimilar to amoebic-dysentery ulcers. The Balantidia are found far ahead of the bacteria in the tissues, and it seems that their action is chiefly mechanical and that after they have made openings in the mucosa they pass in and the bacteria follow. In favor of this is the fact that in the most necrotic portions of the mucosa the parasites are not found, while bacteria are plentiful. It must be admitted, however, that many of the cases have not been studied as carefully as we should hope for, as shown by the few histological examinations reported, and it occurs to us that possibly the ulcers in a number of the other cases were of other than balantidial origin. The question therefore arises, Can this parasite invade primarily a normal or nearly normal mucosa ? Though from places in our own sections, as we have stated, and from those of Solo jew, this would seem probable, the question can not yet be regarded as definitely proved. There is no positive evidence to show that the parasite secretes a toxic substance. The presence in my case of an eosinophilia (also noted in the blood in case No. 114, Collmann), 1 which was greater in the various coats of the intestines than in the circulating blood, and which, while not nearly so marked as in severe uncinaria infections, was more apparent than in strongyloides intestinalis infections and greater than one usually sees in tuberculosis of the intestines, suggests the question whether these cells originated in the tissues locally (as Brown in his studies on trichinosis has suggested) under the irritation of the parasites or whether they arose elsewhere (in the circulating blood or from other tissues) and were attracted there x Also see "Addenda," Askanazy's case. 25822 5 66 by some positive chemotactie substance. If by the latter way, then the origin of such a substance might be either the degenerating cells or a secretion of the parasite. Before concluding it is interesting to review the ideas of other investigators in regard to the role played by the Balantidium coli in man. While the whole list of opinions is too great to be con- sidered here, among the more recent observers who have studied the parasite in man since 1895, Fadieyeff, Sievers, Gurvich, W. Jan- owski, Vlayeff, Dehio, Henschen, Woit, Chichulin, and Solojew all recognize the pathogenic action of the parasite and believe that it is capable of producing at least chronic diarrhea and catarrh of the large intestine. On the other hand, Trzhetsieski, Bushuyeff, Chiga}^eff, and Collmann are rather undecided about its primary pathogenic action, but think that it may sustain or render worse an already existing diarrhea or intestinal catarrh. Zhegaloff con- siders that the pathogenic action is not proved, and that it probably only develops on an already diseased or injured intestine, while Cassagrandi and Barbagallo believe that it has no pathological effect on the intestinal canal and is an innocent commensal of man. However, from the investigations of Solojew and of myself, it seems that we may be justified in maintaining that the large number of parasites continually moving over the surface of the mucosa, breaking through the glands, and wandering through the submucosa and finally passing between the muscular coats and reaching even to the serosa itself, as well as the presence in the blood vessels of all the layers of the intestine of large numbers of the Balantidia, must cause considerable irritation in the intestinal tract. The situation of the parasites in the tissues would also account for the persistence of the diarrhea and for its difficult cure. I wish to express my thanks and appreciation to Dr. W. M. Gray, of the Army Medical Museum, Washington, for most of the accompanying photomicrographs, which were prepared at the Army Medical Museum in the summer of 1901. CONCLUSIONS. In 99.1 per cent of the cases of human intestinal infection with Balantidium coli diarrhea has been a prominent symptom. In two cases histological studies have shown that the parasites have invaded the coats and vessels of the large intestine. Both human beings * and hogs have been found infected with the parasite in Manila. A more careful study in the future of fatal cases of Balantidium ccli infection with early necropsies and histological examinations is desirable. Manila, P. I., October, 1901. ADDENDA. The above paper was completed in the early autumn of 1901. At that time we were not prepared in Manila to publish articles with illustrations, and upon the request of the Journal of Experimental Medicine it was sent to that periodical for publication. However, shortly after this time the Journal of Experimental Medicine was discontinued and the article in question has not yet appeared. Since, however, no extensive work has been printed in English upon this subject, and since the literature, a great deal of which is only in Eussian and Swedish, has been extensively reviewed in this article, it has been thought advisable to publish it as it stands, but, in order to bring the work more completely up to date, to add below the several other investigations which have been performed by various observers since the original article was written. For this reason these additional researches will be here briefly reviewed. Harlow Brooks, 2 in January, 1902, in a study of an epidemic of dysentery among the orang-outangs of the New York Zoological Park, concluded that the Balantidium coli was the etiologic factor in the production of the epidemic. The Balantidia were found in large numbers in the feces of the animals. Several of them died, and on post mortem examination practically the same lesions, both gross and microscopical, were encountered in the large intestine as have been described above in cases 115 and 116. In the sections the parasites were found extending through all the coats of the large bowel. This is the first report of the pathogenesis of the parasite for lower animals. 1 Since the completion of this article several other cases infected with Balantidium, coli have been encountered in Manila by Drs. Webb, of the United States Army; Williams, of the Civil Hospital, and Clegg, of this laboratory. 2 Netv York University Bulletin of Medical Sciences, January, 1902. Missing Page Missing Page 70 will dispel any doubt there might be as to whether these bodies are really Balantidia, Solowjew's illustrations were also perfectly con- clusive. It is quite evident that Ehrnrooth has never seen the Balantidium coli in sections, as this parasite stains very well here and is easily recognized. However, he believes that the Balan- tidium has a pathogenic significance chiefly through the mechanical irritation which it causes. Klimenko ? s * case showed at autopsy ulcerations in the colon and rectum. The living parasites were found in the intestine at autopsy, which was performed eight and a half hours after death. However, many of the parasites were already at this time dead. Microscopical study of stained sections which had been fixed at the time of the necropsy showed the Balantidia in greater or smaller numbers through all the layers of the large intestine. They were numerous in the blood vessels of the submucosa. The epithelia of the mucosa showed mucous degeneration. The larger the number of parasites in the tissue the greater was the amount of round-cell infiltration present. Balantidia were not found in the walls of the appendix nor in any other part of the body than the large intestine. These additional cases in which histologic examinations have been made of the freshly preserved tissues are of considerable importance, since they all support the idea of the pathogenesis of this parasite. Personally I believe that we should attribute the same significance to its presence in the stools in cases of intestinal disturbances as we do to the presence of amoeba? in cases of dysentery. Whether the Balantidium coli is capable of producing a primary erosion in the intestine has not been conclusively demonstrated. However, if such an erosion of the mucosa exists from any cause, the parasite is certainly capable of continuing the process and of modifying and producing in connection with the bacteria which accompany it, more or less characteristic pathologic lesions. BIBLIOGRAPHY. (1) 1722. Leeuwenhoek. Opera Omnia 1722 Anatom. et contemplat. 11, p. 37. (2) 1857. P. H. Malmsten. Infusorier sasom intestinaldjar hos men- niskan. Hygiea, Stockholm, 1857, XIX, 491-501. Also transl. Allg. med. Centr. Ztg. Berl, 1858, XXVII, 81-89. Also Virchow's Archiv. 12 Bd., 1857, p. 302. 1 Beitrag zur Pathologie des Balantidium ( Paramecium ) coli. Beitr. z. path. Anat. u. z. allg. Path. Jena, 1903, XXIII, 281. 71 (3) Clapargde et Lachmann. Etudes, Vol. I A, 1858, p. 241, and pi. 11, fig. 10 (Copie Malmsten). (4) 1860. F. Stein. Sitzung 56 der Bohmisch Gesellsch. der Wissen- schaften. 1860, I., p. 47. (5) 1861. Leuckart. Weighman's Archiv. I., 1861, p. 80, Tafel V, fig. AB. (6) 1862. F. Stein. -JLmtl. Ber. d. Karlsbader Naturforschersver. 1862, p. 165. ( 7 ) 1863. Leuckart. Die menscftlichen Parasiten. Band I, 1863, p. 146, fig. 21, and p. 744. (8) 1866. L. Stieda. Ueber das Vorkommen von Paramaecium coli beim Menschen. Arch. f. path. Anat etc. Berl., 1886, XXXVI, p. 285> Stieda-Wachsmuth. Ibid. (9) 1867. F. Stein. Der Organismus der Infusorionsthiere, fol. Leipz., 1867, II, p. 3?0, (10) 1867. W. Ekecrantz. Bidrag till kannedomen om de i menniskans tarmkanal forekommande infusorier. 8°. Stockholm, 1869. Also Nordisk medizinskt Archiv. Stockholm, 1869, Bd. 1, No. 20, p. 1. (11) 1869-70. F. Belfrage. Fall af Balantidium Coli. Upsala Lakaref, Forh. 1869-70, Bd. V, p. 180. (12) 1869-70. J. T. Winbladh. Fall af Balantidium Coli. Upsala Lakaref. Forh. 1869-70, V., p. 619. (13) 1871. P. J. Wising. Till kannedomen om Balantidium Coli hos menniskan. (Reprint.) 8°. Stockholm, 1871. Also Nord. emd. ark. Stockholm, 1871, III, No. 3, p. 1, 1 pi. (14) 1873. O. V. Peterson. Nya fall af Balantidium coli. Upsala Lakaref, Forh. 1872-1873, VIII, p. 251. (15) 1874-75. S. Henschen. Fern nya fall af Balantidium coli behand- lade med stora rattenlavemanzer hollande attiksyra och garfsyra. Upsala Lakaref, Forh. 1874-75, X, p. 120. (16) 1874. J. A. Waldenstron och S. Henschen. Bidrag till kannedomen om nagia medels inverkan pa Balantidium coli samt ett nytt satt alt redan i tarmkanalen sakert doda detsomma. Ibid. Upsala Lakare, Forh. IX, 1874-75, p. 579. (17) 1875. G. Treille. Note sur Paramecium coli observe" dans la dysenterie de Cochinchine. Archiv de Med. Navale, Bd. 24, 1875, p. 129. (18) l§79-86. Leuckart. Parasiten des Menschen, III, Aufl. 1879-1886, Bd. 1, p. 321. (19) 1880. B. Graziadei. II paramrecium coli umano in Italia, notizia parassitologica, Osservatore Torino. 1880, XVI, 609, 613. Also Archivio per le scienze mediche, Vol. IV, No. 21, 1880-81, p. 437. (20) 1880. Loesch. Vratch, I, p. 505 (Meeting of Practicing Physicians, St. Petersburg). (21) 1880. Rapchevski. Sluchai khronieheskavo katarra tolstikh kishek s prisutstviem balantidii coli. Vratch, St. Petersburg, 1880, No. 31, p. 505. 72 (22) 1880. Perroncito. Lanaemia dei contadini fornaciai e minatori in rupporto coll attuale epidemia negli operai del Gottardo. Annali delta R. accademia d'agricoltura di Torino, XXII, 1880, p. 228. (23) 1881. P. Zur Nieden. Balantidium coli bei einem Falle von Carci- noma recti. Gentralbl. Klin. Med. Bonn, 1880-81, 1, p. 769. (24) 1882. I. F. Rapchevski. Ob upotieblenii salitsilovoi kisloti protiv Balantidium coli. Med. Vestnik. St. Petersburg, 1882, XXI, pp. 361, 377, 393. (25) 1882. Perroncito. Paramecio dell' uomo. J Parassite delV uomo e degli animali utili. 8°. Bologna, Milano, Napoli. 1882, pp. 104- 105. (26) 1822. B. Grassi. Intorno ad alcuni protisti endoparassitici. Atti. Soc. Ital. Sci. Natur. Vol. XXIV. (27) 1884. B. J. Stockvis. Paramecium in sputa. Weekblad van h. Nederl. Tijdschrift voor Genesk. Nov. 20, 1884, p. 4. (28) 1885. Wising. Balantidium Coli. Forhandlingar den 24 Februari. Svens Lak. Sallsk. Handl. Stockholm, 1885, p. 48. (29) 1885. J. G. Edgren. Fall af Balantidium Coli behandladt med naftalin. Svens. Lak. Sallsk. Handl. Stockholm, 1885-86, p. 45. (30) 1886. Railliet. Bull. Soc. Centr. de Med. Veterinaire. 1886, p. 161. (31) 1888. M. M. Afanasyeff. Uspiekhi bakteriologii zaraznokh bolieznei za postiedniye dva goda. Kalendar Alya Vrachei, 16 St. Petersburg, 1888, p. 205. (32) 1888. Neumann. Trait 6 des Parasites et des Maladies Parasitaires des Animaux Domestiques. (33) 1888. Grassi and Calandruccio Att. Ace. Line. Roma, 1888. (34) 1889. R. Blanehard. Balantidium Coli. Traite de Zoologie Medi- cale, Paris, 1886-89, p. 108. (35) 1890. J. G. Edgren. Ytterligare ett fall af Balantidium Coli behandladt med naphthalan. Hygiea Stockholm, 1890, LII, p. 44. (36) 1890, 1891. Lavrovskaya. Sluchai Balantidii Coli. Bolnitsch Gaz. Botkina St. Petersburg. 1890, 1, pp. 302, 342. (37) 1890. N. N. Yakimovich. Zhelatinnaya massa v. histologicheskoi tekhnikie. Trudi Vrachei Peterb. Nikolayer voyenn. Hosp. 1890, 1, pp. 394, 397. (38) 1891. M. M. Afanasyeff. Novieshiye uspiekhi bakteriologii zaraz- nikh bolieznei i. parazitologii. Kaendar dyla vrachei 16°, St. Petersb., 1891, p. 177. (39) 1891. Th. Janowski. O sluchaye dlitslnano katarra tolstikh kishek. Vratch. St. Petersburg, 1891, XII p. 279. (40) 1891. Yubov Lavrovskaya. Sluchai Balantidium Coli. Bolnitsch Gas. Botkina, St. Petersburg, 1891, 11, p. 304. (41) 1891. J. J. Mitter. Beitrag zur Kenntnis der Balantidium coli in menschlichen Darmkanale. 8°. Kiel, 1891. (42) 1891. K. Ortman. Ueber Balantidium coli. Berl. Klin. Wochnschr. 1891, XXVIII, p. 814. (43) 1891. L. Pfeiffer. De Protozoen als Krankheitserreger. Wiemar, 1891, p. 215. 73 (44) 1892. Maggiora. Einige mikroskopische und bakteriologische Beob- achtungen wahrend einer epidemischen dysenterischen Darmerkran- kung. Gentralb. f. Bakt. etc., Bd. XI, 1892, p. 173. (45) 1893. J. W. RunSberg. Ett fall af Balantidium coli med enoist diane\ Finska Ldkeresallskopets Hand., Bd. XXXVII, 1892. (46) 1893. RunSberg. Ett nytt fall af Balantidium coli. Finska Ldk eresdllskopets Hand., Helsingfors, 1893, XXXV, p. 494. Transl, abstr. Vratch, St. Petersburg, 1894, XV, p. 237. (47) 1893. Gruner. Finska Laker esallskopets Hand., B. XXXV, 1893 p. 845. (48) 1893. E. Boos. Ueber Infusoriendiarrhoe. Deutsche Arch. f. Klin, Med. Leipz., 1893-94, LI, p. 505. (49) 1893. Willach. Eine durch Infusorien verursaehte Tauben Epi zootie. Arch. f. wissensch. u. prakt. Thierh. Berl., 1893, XIX, p. 36 (50) 1894. Blomberg. Finska Ldkaresallskopets Hand., Bd. XXXVI, p. 239. (51) 1894. N. S. Lobas. K. Kazuistikie amebvukh enteritov. Vratch, St Petersb. 1894, XV, p. 845. (52) 1895. Patiala. Finska Ldkaresallskopets Hand., Bd. XXXVII, 1895 p. 26. (53) 1895. A. A. Fadieyeff. Balantidium Coli pri yazoennom Vospalenii tolstikh kishek. Med. Pribav. k. Morsk Sbomiku. St. Petersb, 1895, p. 339. (54) 1895. R. Sievers and A. von Bondsdorff. Balantidium Coli, Megas- toma entericum, Bothriocephalus latus hos samma person. 8°. Helsingfors, 1895. Repr. from Finska Ldkeresallskopets Hand. Helsingfors. 1895, XXXVII, Ibid. Ztschr. f. klin. Med. Berl., 1896, XXX, p. 25. (55) 1896. Cassagrandi and Barbagallo. Balantidium Coli. A proposito di un caso di diarrea con Balantidium coli riscontrado dagli autori in Cantania nelV Ottobre (1894). 8°. Cantania, 1896, 22 pp., 1 pi (56) 1896. A. de la Chapelle. Tvenne nya fall af Balantidium Coli hos menniska. Finska Ldkeresallskopets Hand. Helsingfors, 1896 XXXVIII, p. 1041. Also reprint Eria Stockholm, 1897, XXI p. 264. (57) 1896. M. J. Gurvich. Balantidium Coli v kishechnikie chelovieka Russk. Arch. Patol. Klin. Med. i. Bakteriol. St. Petersb., 1896, II p. 804, 1 pi. Also transl. (Abstr.) Ibid., p. 840. (58) 1896. W. Janowski. Przypadek obecn6sci Balantidium Coli w stol each oraz uwagi o wplywie tego pasozyta na zalburzenia w prze wodzie pokarmowym. Gaz. Ck. Warszawa, 1896, 2 S. XVI, pp. 683 Also Zeitschr. f. Klin. Med. Berl., XXXII, 1887, p. 415. (59) 1896. E. Klein. Balantidium Coli in sewage. Brit. Med. Jour. Part I, Vol. II, 1896, p. 1852. (60) 1896. A. A. Trzhetsieski. Kvoprosu o znachenii prostielshikh zhi votnlkh organizmov i spetsialno Megastoma entericum pri Khroni cheskom katarrie kishek. Russk. Arch. Patol., St. Petersburg, 1896, p. 192. 74 (61) 1897. W. Janowski. Ein Fall von Balantidium Coli in Stuhle. Ztschr. f. Klin. Med. Berl., 1897, XXXII, p. 415. (62) 1897. V. F. Bushuyeff, Kvoprosu o bolieznetvornosti, Balantidium Coli. Voyenno-med. J., St. Petersburg, 1897, CLXXXVII1, Med. spec, pt., p. 167. (63) 1898. N. F. ChigayefT. Sluchai yazvennavo vospaleiiiya tolstikh kishek s balantidio coli v isprazhneniyakh. Vratch, St. Petersburg, 1898, XIX, p. 1441. (64) 1898. K. Dehio. katarralnikh i yazvennikh protsessakh, vizi- vayemikh mikroparazitam (Balantidium Coli) v tolstoi Kishkie chelovieka. Russk. Arch. Patol., Klin. Med. i. Bakteriol. St. Petersburg, 1898, VI, p. 113, 1 pi. (65) 1898. G. F. Lang. Sluchai yazvennavo vospaleniya tolstikh Kishek s prisutstviem v isprazknlniyakh Balantidii coli. Bolnitsch Gaz. Botkina. St. Petersburg, 1898, IX, p. 2379. (66) 1898. G. Vlayeff. Sluchai yazvennavo katarra tolstikh kishek s prisutstvieem v isprazhneniyakh balantidii coli. Vratch, St. Peters- burg, 1898, XIX, p. 140. (67) 1898. Oskar Woit. Dfei neue Flille von Balantidium Coli im menschlichen Darm. Deutsch. Arch. f. Klin. Med., 1897-8, LX, p. 363. (68) 1899. M. Jakoby and F. Schaudinn. Ueber zwei neue Infusorien im Darm des Menschen. Centralbl. f. Bakteriol. {etc.). 1 Abt., Jena, 1889, XXV, p. 487. (69) 1899. D. L. Romanovski. Dva sluchaya anchylostoma duodenale. Sposobi sokhraneniya mikroskopicheskikh preparatov glistnikh yaits, ameb i balantidii coli. Vratch, St. Petersburg, 1899, XX, p. 1369. Also St. Petersb. Med. Ges. Sitzung, V. 19 Okt., 1899. (70) 1899. R. Sievers. Ueber Balantidium Coli in menschlichen Darm- kanal und dessen Vorkommen in Schweden und Finland. Arch. f. Verdauunskr., Berl., 1899, V., p. 445. (71) 1899. A. V. Solovyeff. Sluchai Balantidii coli. Vratch, St. Petersb., 1899, XX, p. 1031. (72) 1899. J. P. Zhegaloff. Sluchai Balantidium Coli u duvochki 5 liet. Klin, j., Mosk., 1899, 1, 44-57. Ibid, Jahrb f. Kinderheilk. Leipz., 1889, n. F. XLIX, p. 425. Also Vratsch., 1898, No. 12, p. 361 u $To. 48, p. 1426. (73) 1899-1900. S. E. Hensehem Till fragan om Balantidii Coli pato- genetiska betydelse. Upsala Lakaref. Forh., 1899-1900. N. F. V., p. 444. Also Archiv. f. Verdauungskrankheiten, Bd. VII, 1901. (74) 1900. G. N. Chichulin. Kvoprosu o zuachenii Balantidium Coli dlya kishechnikh razstroistr. Vayenno med. J., St. Petersburg, 1900, LXXVIII, med. spec, pt., p. 2059. (75) 1900. B. Collmann. Fiinf Fiille von Balantidium Coli im Darm des Menschen. I.-D. 8°. Konig^berg, 1 Pr., 1900. (76) 1900. R. Strong and W. Musgrave. Prelim, note of case of infec- tion with Balantidium Coli. Johns Hopkins Univ. Bulletin. Balti- more, February, 1901, XII, p. 31. 75 (77) 1901. R. Strong. Balantidium Coli. Circulars on tropical diseases, No. 1, Manila, February, 1901, p. 11. (78) 1901. N. Solowjew. Das Balantidium Coli als Erreger chronischer Durchfalle. Centralbl. fiir Bakt. Parasitenk., Infektionskrankh. Jena, 1901, XXIX, 1, June 13th and 24th, Nos. 21 and 22, pp. 821 and 849. (79) 1901. N. Ssaweljew. Affektion des Dickdarms, bedinzt durch Balan- tidien. Centralbl. f. Stoffwechsel und Verdauungskrankh. Got- tingen, 1901, p. 11. DESCRIPTION OF PLATES. 1 Plate I. The early lesions of the mucosa, consisting of desquamation of epithelial cells of the glands, round-celled infiltration, etc. About a dozen parasites may be counted in this field. II. Parasites passing from the mucosa through the muscularis mucosae. III. Parasites lying in the submucosa and adjacent tissue. IV, V. Parasites in the blood vessels of the submucosa. About the vessel in PL V nine eosinophiles may be counted. VI. A group of parasites lying between the muscular coats of the large intestine. VII. Parasites in the mucosa showing the so-called "budding forms" and one in which the nucleus is dividing. VIII. Parasites, probably in the first stage of conjugation. The prom- inence of the peristomal fold of each is striking. IX. A parasite passing through the walls of a gland of Lieberktthn rupturing the basement membrane. The parasite shows the striation referred to in the text. X. Parasite more highly magnified, showing flagella. 1 The photomicrographs are all made from sections of the large intestine. Nos. I, II, IV, VI, and X were made by Mr. Martin, photographer of the Laboratory. 77 •- ^#*' ; *'' iv-*^^ ■■■■% ■/ "4i,< *3e " : .* £&**.*• £. '*'■■•• *V . «■ ... *#,mw^%' ■A *%. A me jMW : i fWMJ 111 /# .*•« tf\#" /•'-.. •ft..'. 4Rr'3d£ : ■&jk: PREVIOUS PUBLICATIONS OP THE BUREAU OP GOVERNMENT LABORATORIES. (Continued from second page of cover.) No. 17, 190 4. — New or Noteworthy Philippine Plants. By Elmer D. Merrill, Botanist. No. 18, 1904, Biological Laboratory. — I. Amebas : Their Cultivation and Etiologie Significance. By W. E. Musgrave, M. D., and Moses T. Clegg. II. The Treatment of Uncomplicated Intestinal Amebiasis (Amebic Dysentery) in the Tropics. By W. E. Musgrave, M. D. No. 19, 1904, Biological Laboratory. — Some Observations on the Biology of the Cholera Spirillum. By Wm. B. Wherry, M. D. No. 20, 190k. — Biological Laboratory: I. Does Latent or Dormant Plague Exist where the Disease is Endemic? By Maximilian Herzog, M. D., and Charles B. Hare. Serum Laboratory: II. Broncho-Pneumonia of Cattle: Its Asso- ciation with B. Bovisepticus. By Paul G. Woolley, M. D., and Walter Sorrell, D. V. S. III. Pinto (Pafio Blanco). By Paul G. Woolley, M. D. Chemical Laboratory : IV. Notes on Analysis of the Water from the Manila Water Supply. By Charles L. Bliss. Serum Laboratory: V. Frambcesia : Its Occurrence in Natives in the Philippine Islands. By Paul G. Woolley, M. D. 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