THE LIBRARY OF THE UNIVERSITY OF CALIFORNIA LOS ANGELES GIFT OF SAN FRANCISCO COUNTY MEDICAL SOCIETY =^.^ <=M. )iiR A^ V «f> X! if^ LELAND STANFORD JUNIOR UNIVERSITY PUBLICATIONS UNIVERSITY SERIES TheJPathology of Nephritis as illustrated by thirty-two consecutive cases BY WILLIAM [OPHULS Professor of Pathology From the Division of Pathology Stanford University Medical School STANFORD UNIVERSITY, CALIFORNIA PUBLISHED BY THE UNIVERSITY 1916 UNIVERSITY SERIES Inheritance in Silkworms, I. Vernon Lyman Kellogg, Professor of Entomology. 89 pp., 4 plates. 1908. Price $1.00. The Opisthobranciiiate Mollusca of the Branner-Agassiz Expe- dition TO Brazil. Frank Mace McFarland, Professor of His- tology. 105 pp., 19 plates. 1909. Price, $1.00. A Study of the Normal Constituents of the Potable Water of the San Francisco Peninsula. John Pearce Mitchell, Assis- tant Professor of Chemistry. 70 pp., i map. 1910. Price, 50c. Synopsis of the True Crabs (Brachyura) of Monterey Bay, Cali- fornia. 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(Continued on third page of cover.) 571ti LELAND STANFORi:) JUNIOR UNIVHRSITY PUBLICATIONS UNIVHRSITV SHRIES The Pathology of Nephritis as illustrated bv thirtN'-two consecutive cases WILLIAM OfHULS Professor of Pathology From tlie Division of Pathology Stanford University Medical School STANFORD UN'IVERSITY, CALIFORNIA PUBLISHED BY THE UNIVERSITY 1916 Stanford University Pkess 353 TO ALL THOSE WHO CONTRIBUTED IN THE COLLECTION OF THE CLIN- ICAL DATA UTILIZED RY THE AUTHOR 7n(;n^D THE PATHOLOGY OF NHPHRIUS AS II.I.DSTRATED BY miR I'lTWO CONSECUTIVE CASES It may seem ]iresum|ilii(iii> mi the ipatt cil' a |)alli()Iii,i;i>t to atlempl to write a treatise on the I'atholoj^y of W-iili litis inchi(lin|L;- a resume of tlie symptomatology of the disease, hecause the evidence collected from the histories of tlie patients i^ necessarily second-hand and incomjilete and the author i> not iraiiud in the interpretation and evaluation of clinical phenomena. It may Ijc coiiteiuled. however, that the careful judicious contemplation of a clinical liistory liy some one not connected with the case and not interested in the matter of clinical diaifnosis — ])rovided he has the necessary knowledge of .Medicine in general — may bring out the salient points in the biology of the disease with greater clearness. 1 lowever that may be. since it became necessary to consult the records in trying to solve the etiological (|iiestions involved, an at- tempt has been made to give an outline of the progress of the disease in each individual case as brielly as i)ossible. without entering into aii\ of the many details that are chiefly of clinical importance. The aim has been to collect in each case all relevant data which migiit have any bearing on the etiology, progress and termination of the disease.' To this was added an abstract of all autoi)sy findings which might be of interest, and an esjjecially careful descri])tion of the findings in the kidneys, both in the gross and microscopically. Since no mere descri])tion in words can convey an adec|uale conception of the fmdings. photograjihs of the gross specimens have been added wherever feasible, and in all cases photomicrograjihs of the diseased kidneys. The latter, of course, reproduce only a very small area of the tissues e.xamined ; but an attempt has been made to show as much as ])ossible without • The results of functional tests li.ivc not hci-n considered, vvilli the exception (jf an occasional reference to the phenolsulphone-plitlialein lest. 'I his has been done, not because their great scientilic interest and practical value is not fully recognized, but because many cases antedated the use of such functional tests, so that the evidence in the few recent cases is hardly sufticieiit to warr.uit any pened up such a large field for little xohinie should jirove to be useful for teacliin_a; purposes. THE I'ATIIOI.OCV Ul- NHI'IIKITIS I. Acute Glomerulo-Xephritis (Cases 1-4). The first two patients were males of over 50 years of age. with old infectious endocarditis of the aortic orifice. According to the histories, and also according to the anatomical findings, the original infection dated back many years ; in the first case, at least eight, and in the second altogether twenty years. The course of the disease in both cases was quite the usual one for chronic endocarditis, and the patients died in one of the exacerbations. The nephritis in both cases was terminal and incidental to the main disease. In the first case it revealed itself clinically by \ery definite urinary findings, and by a slowing of the phenolsulphone-phthalein secre- tion. In the second case the urinary changes were very slight — so much so that the condition might very well have been overlooked clinically. In both cases diplostreptococci were found in the lesions in the heart valves, and in the first case also in the urine, and in the spleen at necropsy. The kidneys in these two cases were not as yet very much swollen : the cortex was somewhat opaque, the seat of petechial haemorrhages. The glomeruli showed the very earliest lesions: hyaline necroses of some of the loops, and a very marked infiltration with neutrophilic leucocytes. In case 2 there was some extra-capillary proliferation in the glomeruli, and a slight infiltration of the adjoining connecti\e tissue with neutro- philic leucocytes. There had been much bleeding irom the diseased glomeruli, and also escape of some leucocytes into the tubules. There were as yet few casts, and the epithelium was nearly unaltered. In the case ( i ) in which the bacteria were found in the urine, no bacteria were found in sections of the kidneys either in the glomeruli or in the tubules ; but there were many capillary diplostreptococcic emboli between the tubules, some with beginning suppuration about them. This is one of the cases which so strongly suggest that in glomerulo-nephritis coccus embolism does take place in the glomeruli, but that in these struc- tures the bacteria are rapidly dissolved, in this way causing the hyaline thrombosis and necrosis of the vascular loops. It is interesting to note that in both of these cases there were quite a few small foci of old focal nephritis, such as have been described in diplostrei)tococcus endocarditis by previous observers. This was also the case in observation 3. Evidently for many years the kidneys with- stood the effect of continued bacterial embolism fairly well, until in the end they more or less suddenly gave way. It is difficult to say whether ACl'TK C.I.OMKKri.O-MCI'HUI I l> *) this slimilil lie ascrihcd t(i an iiurcaseil vinilfiuc on tlic ))art nf tin- in- fectious organism or to tlie (K\ flopniint of a liyperscnsitivencss in the organ. It appears to nie tliat mi tlie wliolc the last view is the more likely one. The third case is remarkable hecause, in spite of tiie fact that an old endocarditis was found at autojjsy, there were no clinical symiitoms to suggest it. The fourth case is one of cirrhosis, with the usual clinical manifestations. In both of these last cases the acute nephritis devcloi)ed in the last three weeks. In case 3 there was a very suggestive history of a sudden breakdown, with characteristic disturbances in urination three weeks before his death. The patient suddenly had to urinate very frequently, and developed oedema. In case 4 there is no such detinile history of the onset, but about a month before her deatii she liccame much worse, this being some time after tl-.e development of se])tic ulcers on her legs, which were probably the cause of her nephritis. The ne])hri- tis in these cases is therefore probably about three to four weeks old. Clinically it showed by the develojiment of oedema. .Some jjuffiness of the face is recorded in case 4. The urine in both cases containeil much albumin, many hyaline and gr.iiuilar casts, and some leucocytes. The kidneys were greatly swollen. They were hyiwraemic and oedematous. The cortex was wide, more or less yellowish, and o]ia(|ue. It contained petechial haemorrhages. Histologically there was somewhat more evidence of extracapillary proliferation in the glomeruli: otherwise the lesions were similar to those observed in the earlier cases. Many tubules were filled with blood and with neutrophilic leucocytes. The epithelium was swollen, somewhat granular, and in one case fatty de- generation had occurred. The interstitial tissue in both cases was heavily infiltrated with neutrophilic leucocytes and with lym|)hocytes. In case 4 there was already evidence of a beginning jiroliferation of the connective tissue cells. That this proliferation was of inflammatory origin is so evident that it docs not admit of any discussion. In some of the glom- eruli also a beginning organization of the necrotic material had set in. In the one case in which the tissues examined were sufficiently well jire- served for bacteriological examination no bacteria were found, in sjiite of long continued search with the mechanical stage through several sections. In all four cases of acute glomerulo-ncphritis the etiology was clearly evident. There was streptococcic infection with bacteriaemia in all, and in three the nephritis occurred in the final stages of an old dijilo- streptococcic endocarditis. The death of these four patients is largely attributable to their ])re-existing disease, and it was for this reason that 10 Till-: rATIlnl.OG'i' OF NICPIIRITIS there was an oppDrlunity of stiulsinn' llie alterations in tlie kidneys at this early stage. In the very beginning the lesions are practically confined to the glomeruli, the initial change being a hyaline thrombosis of some of the vascular loops, followed by necrosis and an infiltration of tlie entire glomerulus with neutrophilic leucocytes. Naturally in ordinary sections not all affected glomeruli show the necrotic loops, but my impression is that in a series one can always find them in each affected glomerulus. The diseased glomeruli bleed and permit of the passage of albumin and leucocytes — w-hich explains the material found in the ca])sular spaces, in the tubules, and in the urine. Sometimes the exudate has a tendency to spontaneous coagulation in the capsular spaces and in the tubules. \'ery soon these glomerular lesions are followed by a general hyper- acmia and oedema which causes considerable enlargement of the organ. Tile oedema often is very pronounced. The hyperaemic blood-vessels show a marked local leucocytosis, numerous venules in the region of the vasa recta being especially engorged and full of various types of leucocytes. The congestion is soon followed by a general extravasation of leucocytes into the tissues, the intensity of the reaction naturally depending on the severity of the process. Among the leucocytes that find their way into the tissues there are many neutrophilic cells, together with lymphocytes and plasma cells, as can easily be seen in sections stained with Giemsa's stain according to Schridde's method. The amount of epithelial degeneration also naturally varies with the intensity of the process. In some of our cases it is noted as slight, in others it is ciuite considerable. There is no question that the disturbance in circulation and the oedema as such must be important factors in the development of these degenerative lesions ; still one can hardly escape recognizing also the importance of a toxic factor. The possible epithelial lesions at this time consist in swelling, with slight granular degeneration, fatty degeneration, and scattered necroses. As a result of the inflammatory oedema the connective tissue cells of the interstitial tissue become swollen. After a few weeks, evidences of proliferation may be observed on their part. As has been stated above, of the inflammatory nature of this proliferation there can be no doubt. In the glomeruli also proliferative changes occur quite early in the process. The capsular epithelium swells, is partly detached, and pro- liferates somewhat. My impression, however, is that the majority of the new cells in the glomeruli which become so plentiful in the later stages are derived from the connective tissue, both of the capsule and of the ACL'Ti-; (;i.n)tocols. are naturally purely incidental. I ni.iy state at this ])oint that for brevity's sake in the protocols I ha\e \i^fd tlie terms "arteriosclerosis" and "endarteritis" in the sense of Jores. employing "arteriosclerosis" when there was a notable hy|)erplasia of the elastic elements of the intima. The distinction, however, is meant to be a ])urely morphological one. not implying the deejier --ignificance attributed to it by Jores. 12 Till-; I'ATUOl.OGV 01' NICIMIRITIS II. SuiiACUTF, (Ii.omkkulo-N'ki'iikitis (Cases 5-12). Naturally, there exists no sharp line of division between the acute, subacute, and chronic cases. Cases 5 and (\ for instance, might just as well have been classified with the acute, and cases 11 and 12 with the chronic types. The beginning" and the course of the disease were very cliaracter- istic in case 5. The patient's trouble commenced with an attack of tonsillitis about nine months before she died. Soon symptoms of acute polyarticular rheumatism made their appearance, and continued inter- mittently for about six months. The severe endocarditis, which evidently developed simultaneously, was overlooked until the patient entered the hospital in the last stages of the disease. At that time she already showed evidence of severe renal involvement. It is not apparent from the history when her renal disease started. How far her oedema was as- sociated with her nephritis is difficult to tell : but there are certain symp- toms recorded in the history, like frequent vomiting, restlessness, drow- siness, muscular twitching, which arouse the suspicion of a uraemic condition. Her blood pressure, in spite of the severity of her renal com- plication, was not afifected, possibly on account of the severe sejJtic in- volvement of the heart muscle. Diplo-streptococci were recovered during life from blood and urine, and after death from the infected heart valves. The following case (6) is an interesting one on account of the fact that the infection which caused the nephritis was apparently caused by colon bacilli, no evidence of streptococcus infection being discovered either during life or at necropsy. On account of the fact that the child had congenital syphilis, it might be suggested that the lesions in the kidneys also were of syphilitic origin ; but so long as we know so little of the histology of acute and subacute syphilitic nephritis, I believe we would hardly be warranted in making this assumption. In other words, I do not believe that the proof has yet been furnished that spirochetes can produce lesions in the kidneys similar to those observed in ordinary bacterial infections. The next case (7) is a good example of how inattentive some patients are to the state of their health. The first symptom that attracted this patient's attention was a hemiplegia and aphasia as a result of embolism from a severe diplostreptococcus endocarditis. The urinary findings were unusually slight for the severe lesions in his kidneys. Except for the general oedema, which of course may be attributed to his cardiac disease, there were no other general symptoms of nephritis. SUUAITTK f.l.OMKKll.O-NKl'MKITIS 1.^ Ill paiicin S. wliu liad an ohj streptococcus infection of a compound iraclure of the lc,n. the urinarv tindings made the diagnosis of nephritis eviilent. I "here was some oedema, but it was not very marked at any time. C)ther "nephritic" symptoms were cnm])lctely absent, in s])ite of \ ery severe lesions in the kidneys. In case 9 the renal disease was only a minor incident in tlie typical clinical develo])ment of a severe septic endocarditis, iirobal)ly arisinjj ei,c:ht months before death from infected wounds on the lins^ers. Still, the urinary tindintis were unmistakable and the phenolsulphone-phthalein excrelion was distinctly slowed. Three months before his death the patient liad noticed some oedema at ihe ankles, increased thirst, and in- creased urination. The oedema at no time was a prominent symptom. and was absent at death. Case 10 is notewnrthy in several particulars. The patient, a nouul; woman, liad h,id an unusually severe long-continued infection, develop- ing from a decayed tooth about one \ear before her death. .\n abscess e\entiially formed at the lower jaw which had to be drained from the outside. I-'ollowing the operation the abscess healed, and at necropsy a small scar only could be found at the place where it had been. Several decayed teeth, however, remained in her mouth. .After the healing of the abscess she was apparentlx' well until four weeks before her death, when she developed a painless oedema of the legs. Ten days later the right leg. which was still oedematous, became infected with streptococci, from which infection she died within a short time. The histological picture of the lesions in tlu- kidneys in this case differs from that of other cases of this series by the lack of evidence of actively progressive inflammation. The alterations were very extensive, but ai)parently not very severe, and almost (|uiescent. .Almost all of the glomeruli were diseased. They showed development of fibrous tissue Iietween the vascular loops, making the tufts thick and heavy. There was also some little proliferation in some of the capsules and in the capsular spaces. Although so many glomeruli were diseased, one did not receive the impression that theymajority were functionally badly dam- aged. The newly formed fibrous tissue was found on the inside of the tufts, and did not therefore apparently interfere much with the secretion of the urine-water: and the vascular looi>s themselves, although some of them showed a slightly thickened hyaline wall, ai)peared otherwise nor- mal. Many tubules were filled with hyaline casts, and some of them with neutrophilic leucocytes. The epithelial degeneration which was jireseiit in the tubules was probably recent, and to be attributed, at least in jiart, to the streptococcus sepsis from which the patient died. The 14 Tin-; I'A'IIKll.UC'i- (IF MJMIKITIS arteries were ])raclic:ill\ iKirmal. except the main stems of the renal ar- teries, which were moderately sclerosed. On the whole, therefore, the histological picture would suggest that the process was fairly well healed, at any rate rather (|uiescent. Clinically, however, the evidences of renal disease were well marked. Her first symptom, the oedema, was evidently a "renal" oedema, because there were no signs, either clinical or anatomical, of cardiac decomjjensation. There was also distinct hyper- tension, and a slight but unmistakable hypertrophy of the left ventricle. The urinary findings also were well marked. Although the urinary production was diminished, the specific gravity was fixed at about loio; there was much albumin in the urine, and many formed elements in the sediment. Symptoms of uraemia, however, were altogether absent. In the following case ( 1 1 ) we have subacute nephritis in an indi- vidual suffering at the same time from old diplostreptococcic endocardi- tis and syphilitic aortitis with aneurysm. The time when the diplo- streptococcus infection took place cannot any more be established exactly, but the patient complained of heart trouble for at least four years before his death. As shown by a history of extreme polyuria half a year before his end, his nephritis must have dated back before this time. The polyuria in this case was a striking and constant symptom, and possibly accounts for the comparative absence of oedema. His symptoms were largely those of endocarditis, complicated naturally by the co-existing aortic aneurysm. His blood pressure was high and rising. His heart was twice normal size, an enlargement partly due to aortic regurgitation. His urine, on account of the polyuria, naturally had a constant low specific gravity ; it contained much albumin and many formed elements. While he was at the hospital there was practically no excretion of phenol- sulphone-phthalein. The pericarditis which he developed eventually was due to an extension of the dijilostreptococcic infection from the heart valves to the pericardium. In the last case ( 12) the nejihritis is evidently much older than in the others of this series. This patient had had numerous attacks of tonsillitis from infancy. Six years before death her nephritis had been first noticed. For the last five years she had had definite "uraemic" symptoms (headache and vomiting), and occasionally slight oedema. The most interesting feature in this patient's history was that she had associated with her nephritis what appeared to be typical symptoms of "Raynaud's disease," attacks of syncope and cyanosis in fingers and toes. Eventually she developed an anaemic ( ?) contracture of her left arm and a dry gangrene of her left foot. This symptom-complex was probably due to a o-radual closing of, her peripheral arteries by lateral thrombosis and endarteritis. I'n fortunately we were not permitted to verify this sup- SUUAl ITI-: (J.dMl-.Kll.lP-M-.l'IIKIllS 15 position at aiitoi)s\ ; l>ut uc lia\c I'vidiiut- that Ikt internal arteries, more especially those in the heart and kidneys, were fjraduaily i>eing closed hy such a process. In hotii of these ortjans. as a conse<|nence, small multiple necroses resulted, which in the heart were irrei^ularly scattereil, and in the kidney were situated in the pyramids, liacteria were not found in the small arteries which were the seat of the throm- bosis. Towards the end a similar thrombotic obstruction took ))lace in some of the arteries of the sigmoid flexure, with much bleeding and ex- tensive sloughing. .Ml these processes naturally at first suggested the occurrence of multiple embolism: but no source of embolism was dis- covered in the pulmonary vein, left heart, or the aorta: besides, tlie gradual development of the conditions in the extremities speaks very much against embolism as the causative factor, and favors the idea of their origin by gradual thrombosis. The case, 1 believe, is of unusual imixirtance. because it seems to furnish the proof that tin- Literal thrombosis followed by endarteritis, which is so frequently observid in llu- kidneys in these cases of glom- erulo-nephritis (see below), may involve arteries in other parts of the body, and may in this way give rise to symptoms resulting from a more or less gradual obstruction of them. .\"o doubt sometimes the cerebral arteries may be involved in the same way. That this i)atient, in spite of the absence of an infectious endocarditis, suffered from a chronic di])lo- streptococcus bacteriaemia, at least as long as she was under clinical observation, seems evident. She had a septic temperature all the time. Her pulse rate varied between 80 and 130, and the blood culture was positive. In fact, clinically there seemed to be no doubt that the patient had a septic endocarditis, and the absence of this condition at autopsy was a great surprise. In fortunately, a thorough search for another chronic septic focus could not be made. It is possible that in this in- stance the urinary tract itself may have harbored the diplococci, because there was evidence at necro])sy of a slight chronic sujipurative ])yelitis and cystitis with positive finding of diplostreptococci. This, however, may have been merely the conse(|uence of the constant elimination of diplostrejJtococci by way of the kidneys. This jjatient's "nephritic" complications were uiuuistakable. .She had headaches and vomiting: she had albuminuric retinitis: she had comparatively little oedema : she had a high blood (iressure with clinical signs of excessive heart action, but without gross hyijcrtrojihy : she died in uraemic coma. The urinary findings also were very well marked. She had some symptoms suggesting jjolyuria. a fixed low si)ecific gravity. The urine contained much albumin, and at times there were large show- ers of casts. Red blood cells were also commonlv found. 16 Till': ^ATll()l,(l(;^ oi' xkimikitis To sum u|>: In all these cases of siiliaciitc nephritis, except in case 6, there can hardly be any question of the etiology; and in this one I am inclined to believe that the nephritis was due to a colon bacillus septi- caemia arising from the infected urinary tract. In the cases with endo- carditis ( 5, 7, <;. Ill chronic diplostreptococcus septicaemia existed, without doubt ; in case 8 a chronic streptococcus septicaemia from the infected bone is also ver)- likely; and in case 12 the clinical symptoms and the positive blood culture proved the existence of a chronic septi- caemia, at least as long as the patient had been under clinical observation. The source of the continued infection in this case was possibly in the urinary tract. The only somewhat questionable case is case 10, where the original septic infection was present in the region of the jaw, where, however, after long treatment the lesion eventually healed. \o ])ersist- ing septic focus was definitely made out, although she still had several decayed teeth ; and it is possible that the histological evidence of com- parative quiescence of the process in the kidneys might indicate that whatever infection remained was not very active or extensive. The clinical symptoms of nephritis were quite definite in all cases. All of them had oedema at one time or another, the amount of oedema and its distribution varying very much in different cases. One early case (S) had somewhat indefinite symptoms of uraemia; otherwise the others were free from it, except the most chronic case, which was much older than the rest, in which there were observed very definite uraemic symp- toms and a well marked retinitis albuminurica. Case 8, of about six months' duration, already showed a beginning hypertrophy of the left ventricle ; and the last three cases had a definite rise of systolic blood pressure to between 170-200 mm. mercury, and two of them a noticeable hypertrophy of the left ventricle. In the case (ill with very marked hypertrophy of the heart, the hypertrophy w-as probably largely due to valvular disease. The urinary findings were striking in all cases. The urine at all times contained much albumin. Casts ( hyaline, granular and epithelial ) were almost just as constantly present, although sometimes they were not found at all times, but in showers. Leucocytes and erythrocytes, either free or as blood casts, were also commonly encountered. Two cases (9 and II) had a definite polyuria, which was extreme in case ir. In the more chronic cases (10, 11, 12) the specific gravity was fixed at a low point, not always apparently as a result of polyuria, the condition being suggestive of a true hyposthenuria. In case 9 the phenolsulphone-phthalein excretion was somewhat slowed, in case 11 entirely, suppressed, and in case 12 very much delayed. si'hai r ii-. i;i.(iMKKii.i)-M;niKiris 17 III tlu- ^ross, tlu- kidiR'vs were smootli, conj^cstcil, (n.'(leiiiat>piis anil swollen, or already contracted to about normal size. Tiic cortex was either dilTuseJy opac|ue or contained small opaque spots. Petechial cort- ical haemorrhai:jcs were often seen. They were most numerous in case 5 (see fig. 7). Histologically, in the more acute cases the tissues were still much infiltrated with neutrojihilic leucocytes, to which were ni)earance of tlie .y;lomeriilar remnant one cliritis which really belong; to "glomerulo- nephritis. The local condition of the arteries again xaried reiiiarkablv in this short series. In case 1.^ tliey were entirely normal. In case 14 the small arteries showed a well marked "endarteritis," and in some of the larger ones the internal elastic membrane was split up into several thick super- imposed layers. gi\ing the typical picture of a hyperplastic develojiment characteristic of true arteriosclerosis according to Jores. In case 15 the lesions in both small and larger arteries were in the nature of a very jiroiiouuced "endarteritis." THE PATIIor.o(',^■ or NF.niRiTis r\'. Chronic Gi.o.mkrulo-Nkphritis (Cases 16-32). in order to avoid tedious repetition the cases of tliis last scries will We taken up in a more summary fashion. Ever since the disease has been recognized the etiology of these chronic cases has been a most vexing problem. Whereas in the acute and even the subacute cases the history of some septic infection can usually be obtained and a persisting septic focus can often be demon- strated fairly easily, in the chronic cases the history of the original in- fection dates back so far that it often is entirely forgotten by the patient, especially by patients who are more or less indifferent in regard to the state of their health ; and the persisting focus apparently may be so insignificant that an unusually careful clinical examination and even an unusually carefully performed necrojisy may fail to reveal it. In these cases the original infection is probably often due to organisms of a low degree of virulence which provoke very slight symptoms, and the bacteri- aemia also is comparatively slight and intermittent, as one would expect from a comparatively insignificant and hidden focus. In searching for the time and character of the original infection the question, how far one is able to communicate with the patient and his family, is of great importance; so that in patients able to speak foreign languages only, especially such languages as Chinese and Japanese, it is often a i)racticaliy hopeless task. Many of these patients arrive at the hospital in a comatose condition, and, unless close relatives or friends are accessible, very little or nothing can be made out about their ante- cedents. Among our sixteen cases there were seven (cases 16, 18, 20, 25, 27, 29, 32) in which for one reason or another the history is imperfect. Of the other nine patients one (17) had scarlet fever as a child and rheu- matism at twenty years of age. another (19) claimed to have been healthy all his life. He even denied having had any diseases in child- hood, which makes his statements somewhat improbable. Patient 21 had had a severe infection, "a touch of typhoid," as she said, at the age of 22, and her symptoms dated from the time she was 23. Patient 22 had had a long continued suppuration of the neck due to chronic tuberculosis, necessitating twelve operations. In such a case the existence and persist- ence of mixed infection with septic organisms is, of course, not at all unlikely. In the history of patient 23 we read of repeated attacks of tonsillitis and several attacks of polyarticular rheumatism. Patient 24 also has a history of rheurnatism. In case 26 we encounter once more a LllRoNK CI.O.MMUfl.o-NI'.niKms 2^ general denial oi" all diseases except measles in infancy. In case JS also there is no statement in regard to the original infection. I'aiieTit ,^o had had trec|uent attacks of sore throat, and patient ,^i had had what she called "l,a Grippe" as a girl and an attack of acnte api>eiidicilis nine years before her death. .\ direct relation of the original infection to the following nephritis is traceable only in one case (21 ) ; still the investi- gation shows that in fully six of the nine cases the existence of some in- fection ]5receus |)ockets in the tonsils with considerable scarring in case 20: an old healed scar at the base of the aorta and an old septic infarct of the spleen full of influenza bacilli in the patient (21 I who had had a "touch of typhoid" thirteen years before her death : an old ulcerative endo- carditis in the i)atient (231 w'ho had a history of tonsillitis and rheu- matism: an old ulcerative endocarditis in case 28; an old ulcerative tonsillitis and an ajJiJarently old mild suppurative pyelitis in the patient (31 I who had had the attack of "La Grippe," The long continuance of the rheumatic infection in case 17 is shown by the fact that many years after his original trouble he developed a pleurisy, evidently on a rheimiatic basis, because there was no evidence of tuberculosis found at autojisy. It is also to be noted that during the last years of his life he complaineil for several years of chills in the evening and night sweats. In case 32 there is a history of "malaria." so frequently wrongly diagnose