of apt to be diagnosed as "chloroties."-as "neuras- two days. They are like urticarial wheals, and Fever: there is nothing characteristic about the fever, it may be of a very varying type, it may be high or low, intermittent or remittent, with high or low oscillations, it may have the typhoid curve, or the malarial index,-it may be absent for quite a time, with a bacteriemia present, it can come and go, therefore it must be looked for every day, for at some time during the disease it is present. Chills, chilliness, and sweating:-there is more often a feeling of chilliness than a pronounced chill. Sweating may be present at any stage of the disease. Weakness and pallor:-are usually progressive with the disease. Loss of weight:-is sometimes slight, again quite marked and then it is usually associated with fever and heart involvement. Pains:-in joints, in muscles, and in bones are quite a feature throughout the disease, they are of a rather indefinite character, but of a tearing, breaking type, sometimes referred to the back, then again to the abdomen, and may thus be due to emboli in spleen or liver. Sometimes associated with these pains (which often disappear spontaneously), is swelling of the joints, the knee, wrist, ankle, hip, shoulder, and sternal ends of the clavicle. (Libman.) 31 Liver:-may be enlarged at any stage of the disease, and if late in the disease, it is probably due to an embolis. Spleen-may be, may not be enlarged, if enlarged, it is due to a peri-splenitis or to emboli, and if the latter, there is pain referred to the left lumbar or hypochondriac region. 32 Painful nodes:-this feature of the disease was first noted by a French observer, then by Huebner, as far back as 1879, and accentuated by Osler,3 as pathognomonic of the disease, specially if endocarditis is present, These nodules may be described as tender areas of raised red ness, with a white central point, about the size of a pea, appearing suddenly in the skin of the lateral aspect of the ends of the fingers and the toes, at times, in other parts of the body. They may be one or many, and remain from one to Sternal tenderness:-tenderness, even on slight pressure, of the lower part of the sternum, is pathognomonic of the disease, according to Libman. Color: pallor, changing to a peculiar dirty waxy shade, is considered a noteworthy feature of the infection. (Libman.) If Kidneys: it is said that every case nearly Paresis: this may occur, though not in the Retinal hemorrhages:-are not infrequent,-it Blood:-it presents no invariable change, there may be, or not a marked leucocytosis, the more chronic the case, the less the leucocytosis, and it may vary, from time to time in the course of the disease. With a pronounced anemia, or a severe toxaemia, both the hemoglobin and the red corpuscles may be diminished. Delirium:-is usually in proportion to the toxaemia. Heart: the clinical picture of the heart has been left to the last, as the writer seeks to justify, by quotations from different authorities, the assertions made in the early part of this paper, namely, "endocarditis in streptococcus viridans infection may play no role, or only a very insignificant role, and when it does exist, it is often, although not always an old endocarditis activated anew by this organism in the blood stream." This organism, as already mentioned, has a special affinity for diseased endocardial tissues. Schottmuller 37 says: "finding a bacterium proves to me only that here is an organism that under certain conditions can provoke an infection, but if an infection will result depends upon the disposition of the patient, the condition of the tissues as regards trauma, etc.,— in fact examination of the bacterium does not tell what will result clinically." But the writer says when clinical symptoms are already present, no time should be lost in seeking, in some open or hidden focus, and in the blood for a bacterium, and its specificity carefully studied. Murmurs: Schottmuller says, "if a murmur is present, it may be an old one, or a new one,there may be none, or there may be many,-- in the early stage a heart murmur can hardly be heard." Fraentzl, "there are cases that run a subacute course, and give no heart symptoms till shortly before death." Simon, "a murmur may be absent, or it may be slight, resembling a febrile muscle murmur. 7370 Lenhartz, "though at times there is a marked murmur, again it may be only a slight blowing sound, due to enfeebled heart muscle, and still again no murmur can be detected, even on most careful examination" (see writer's case reported later). Libman, "in sonie cases the primary focus is very minute, or where none is demonstrable, there may be a bacteriemia, and the endocardium may not be involved." Janeway,38 "very difficult to diagnose an endocarditis, when по heart murmur is heard." Horder, "reports three cases that during life showed no murmur, absolutely, but post-mortem showed valvular vegetations. Osler, "streptococcic endocarditis presents a picture, as a rule, in which heart symptoms are in the background, -again, there are cases in which, from beginning to end no murmur is heard, or it may be too slight to be heard, or it may be an old murmur. Cases of infection with these organisms may run an identical course, except with no endocarditis.' Pain, palpitation, oedema, dyspnoea, cough,-expectoration, all symptoms associated with valvular trouble, more or less, as well as with anemia, are mentioned by different writers, but not much stress is laid on them, except by Osler who says, "if a murmur is detected, often there is no symptom referable to the heart, such as palpitation, pain, dyspnoea, or oedema,-except towards the end. Decompensation:-Simons claims this is very rare, even in chronic cases,--while Libman asserts it is a very frequent cause of death. Emboli:-occur causing, from slight to fatal symptoms, and forcibly suggest when they do occur, endocarditie origin, in fact, the final symptomatic outcome, so often corroborated by the post-mortem findings, leaves no doubt that endocarditis is of frequent occurrence. ENDOCARDITIS. It has already been shown that streptococcus viridans can be present locally without causing endocarditis, 39-also, it has been shown that many authorities admit its presence in the blood with a clinical picture of none or very slight cardiac symptoms. Now, only a very few words will be devoted to the endocarditis resulting from this organism after it has found its way into the blood stream. It seems justifiable to believe, specially bearing in mind Rosenow's mutation theory, that in many instances the organism, isolated from the blood, by Kraus, Canon, Gravitz Lenhartz, Horder, and others, and called by different names, may be the same as accepted today as so so frequently causing endocarditis, namely, "the streptococcus viridans,""the modified pneumococcus, "the endocarditic coccus. In fact, as it is conceded that the short-lived, acute cases, the severe cases, were the formerly so-called "ulcerative," "malignant," "septic, while the prolonged, chronic cases were more of the vegetative, proliferative type, it might be that the former were due to the more virulent, unmodified pneumococcus, and the latter to the Rosenow's "modified pneumococcus, "" of recognized low virulence. Capsule germs are most virulent in the capsule stage. (Zinnser.) 390 Up to rather recent date we have been accustomed to consider only two types of endocarditis: : A-, a simple, non-infectious type, mostly due to rheumatism, to scarlet fever, measles, etc., and we did not think it serious, if the patient recovered from the original disease, and led a quiet, non-strenuous life, under proper observation. - B-, an infectious, septic, severe type, due to some virulent, supposedly, pyogenic organism, and called "malignant,' " "ulcerative,' "septic" endocarditis. From this generally accepted classification of endocarditis, we have gradually passed through a succession of discussions as to type "A" not only being due to an organism, but also being at times malignant, ulcerative, to type "B" not being always due to an organism, nor always malignant, ulcerative, septic,-to the acceptance, finally, of the terms, "endocarditis lenta" (Schottmuller),-"acute, subacute, chronic bacterial endocarditis" (Libman),"infectious endocarditis" (Rosenow), because "we now know that all cases of so-called malignant endocarditis are not fatal,-or, that all die directly from the endocarditis, or the concomitant toxaemia,-healed. cases have been described,-many cases are not associated with pus,-the type or organism is not pyogenic,--many cases are not of the ulcerative type, but the vegetative, proliferative type. "'40 PROGNOSIS. The prognosis is most discouraging,—while the course of the disease may extend from weeks to years, many claim there is no recovery. Schottmuller says "all cases are, practically, uniformally fatal. Horder-recovery is very rare,-in his 150 cases he had only one recovery and in this case the blood cultures were negative. Oille-recovery does take place, but it is rare. Billings-as far as I know, no case has recovered, some do improve under rest, some under autogenous vaccines. Libman:-"it is only a question of time when all succumb, the late cases to uraemia and to heart decomposition. He intimates that if the blood cultures remain positive, all cases die. Even in cases where the blood cultures become negative, these eventually die, the fibrous or calcareous changes in the heart interfere. not only, with the proper function of the heart, but emboli are carried to different parts of the body, and the glomerular kidney affection and the disturbance in the blood-forming organs, are all inimical to the preservation of life." "Cases may apt to be diagnosed as "chlorotics,"-as "neurasthenics"- as "obscure tuberculars"- sometimes with no fever, no heart murmur. Even if slight fever is present, with above symptoms, still not much attention may be given the case, so that this early stage is apt to be prolonged, without any care, till all these symptoms become intensified, and then it is the fever, the chill or chilliness, the sweating, the prostration which compel a careful examination. The symptoms then suggesting a typhoid fever, this is eliminated after a few days, by observation and Vidal tests, then malaria is tested for, and no plasmodia are found, rheumatism, incipient tuberculosis, miliary tuberculosis, glandular, pulmonary, kidney tuberculosis, each one in turn is eliminated by proper examinations,- Hodgkins may be the next possible diagnosis, this failing to clear up the case, colon bacillus kidney infection is considered, and found not present Thus the diagnosis is still obscure, because no blood culture has been made. So by this time we may have a part of, or a fully developed picture (clinical) of the disease, as follows: Fever: there is nothing characteristic about the fever, it may be of a very varying type, it may be high or low, intermittent or remittent, with high or low oscillations,-it may have the typhoid curve, or the malarial index,-it may be absent for quite a time, with a bacteriemia a bacteriemia present, it can come and go, therefore it must be looked for every day, for at some time during the disease it is present. Chills, chilliness, and sweating:-there is more often a feeling of chilliness than a pronounced chill. Sweating may be present at any stage of the disease. Weakness and pallor:-are usually progressive with the disease. Loss of weight:-is sometimes slight, again quite marked and then it is usually associated with fever and heart involvement. Pains:-in joints, in muscles, and in bones are quite a feature throughout the disease, they are of a rather indefinite character, but of a tearing, breaking type, sometimes referred to the back, then again to the abdomen, and may thus be due to emboli in spleen or liver. Sometimes associated with these pains (which often disappear spontaneously), is swelling of the joints, the knee, wrist, ankle, hip, shoulder, and sternal ends of the clavicle. (Libman.) 31 Liver:-may be enlarged at any stage of the disease, and if late in the disease, it is probably due to an embolis. Spleen: may be, may not be enlarged,-if enlarged, it is due to a peri-splenitis or to emboli, and if the latter, there is pain referred to the left lumbar or hypochondriac region. Painful nodes:-this feature of the disease was first noted by a French observer, then by Huebner, as far back as 1879, and accentuated by Osler,32 as pathognomonic of the disease, specially if endocarditis is present, These nodules may be described as tender areas of raised redness, with a white central point, about the size of a pea, appearing suddenly in the skin of the lateral aspect of the ends of the fingers and the toes, at times, in other parts of the body. They may be one or many, and remain from one to two days. They are like urticarial wheals, and are looked upon as a painful nodular erythema. Petechiae: these may be seen frequently in the skin and the mucous membranes of any part of the body, but rarely on the palms of the hands, or the soles of the feet. They may be few or quite many, appear late or early in the disease, and last from one to several days, fading from red to a dull brown, looking so much like freckles that if found on a part of the body not exposed to conditions favoring the development of freckles, they are to be taken into consideration in making the diagnosis. Sternal tenderness:-tenderness, even on slight pressure, of the lower part of the sternum, is pathognomonic of the disease, according to Libman. Color: pallor, changing to a peculiar dirty waxy shade, is considered a noteworthy feature of the infection. (Libman.) Kidneys: it is said that every case nearly shows some symptom of disturbed or diseased function,-increased or diminshed quantity of urine, albumen with or without casts, and from a few red corpuscles to marked hematuria. If the organism is present in fairly large amount in the blood, it may be found in the urine, disappearing in this secretion before it disappears in the blood. in the blood. (Libman.) 33 A special form of nephritis is attributed by Lohlein 34 and Baehr 35 to the "viridans," called "glomerular nephritis,' but the clinical symptoms do not differentiate it, only the post-mortem study shows it to have been this special form. Paresis:-this may occur, though not in the early stage of the disease, and it may pass away completely, or pass into paralysis, causing internal or external strabismus,-ptosis of the upper lid,-dilation of the pupil,-deafness,— hemiplegia, etc., all due to emboli, therefore undoubtedly associated with endocarditis. Retinal hemorrhages:-are not infrequent,-it is said that there is no case of bacterial endocarditis without this secondary lesion, and it is to be found if the eyes are carefully examined.36 Blood:-it presents no invariable change, there may be, or not a marked leucocytosis, the more chronic the case, the less the leucocytosis, and it may vary, from time to time in the course of the disease. With a pronounced anemia, or a severe toxaemia, both the hemoglobin and the red corpuscles may be diminished. Delirium:-is usually in proportion to the toxaemia. Heart: the clinical picture of the heart has been left to the last, as the writer seeks to justify, by quotations from different authorities, the assertions made in the early part of this paper, namely, "endocarditis in streptococcus viridans infection may play no role, or only a very insignificant role, and when it does exist, it is often, although not always--an old endocarditis activated anew by this organism in the blood stream." This organism, as already mentioned, has a special affinity for diseased endocardial tissues. Schottmuller 37 says: "finding a bacterium proves to me only that here is an organism that under certain conditions can provoke an infection, but if an infection will result depends upon the disposition of the patient, the condition of the tissues as regards trauma, etc.,— in fact examination of the bacterium does not tell what will result clinically." But the writer says when clinical symptoms are already present, no time should be lost in seeking, in some open or hidden focus, and in the blood for a bacterium, and its specificity carefully studied. Murmurs: Schottmuller says, "if a murmur is present, it may be an old one, or a new one,there may be none, or there may be many,- in the early stage a heart murmur can hardly be heard." Fraentzl, "there are cases that run a subacute course, and give no heart symptoms till shortly before death." Simon, "a murmur may be absent, or it may be slight, resembling a febrile muscle murmur. Lenhartz, "though at times there is a marked. murmur, again it may be only a slight blowing sound, due to enfeebled heart muscle, and still again no murmur can be detected, even on most careful examination" (see writer's case reported later). Libman, "in some cases where the primary focus is very minute, or where none is demonstrable, there may be a bacteriemia, and the endocardium may not be involved." 37a Janeway,38 "very difficult to diagnose an endocarditis, when no heart murmur is heard." Horder, "reports three cases that during life showed no murmur, absolutely, but post-mortem showed valvular vegetations.' Osler, "streptococcic endocarditis presents a picture, as a rule, in which heart symptoms are in the background, -again, there are cases in which, from beginning to end no murmur is heard, or it may be too slight to be heard, or it may be an old murmur. Cases of infection with these organisms may run an identical course, except with no endocarditis.' Pain, palpitation, oedema, dyspnoea,cough,-expectoration, all symptoms associated with valvular trouble, more or less, as well as with anemia, are mentioned by different writers, but not much stress is laid on them, except by Osler who says, "if a murmur is detected, often there is no symptom referable to the heart, such as palpitation, pain, dyspnoea, or oedema,-except towards the end.' Decompensation:-Simons claims this is very rare, even in chronic cases,--while Libman asserts it is a very frequent cause of death. Emboli: occur causing, from slight to fatal symptoms, and forcibly suggest when they do occur, endocarditic origin, in fact, the final symptomatic outcome, so often corroborated by the post-mortem findings, leaves no doubt that endocarditis is of frequent occurrence. ENDOCARDITIS. It has already been shown that streptococcus viridans can be present locally without causing endocarditis,also, it has been shown that many authorities admit its presence in the blood with a clinical picture of none or very slight cardiac symptoms. Now, only a very few words will be devoted to the endocarditis resulting from this organism after it has found its way into the blood stream. It seems justifiable to believe, specially bearing in mind Rosenow's mutation theory, that in many instances the organism, isolated from the blood, by Kraus, Canon, Gravitz Lenhartz, Horder, and others, and called by coccus. different names, may be the same as accepted today as so frequently causing endocarditis, namely, "the streptococcus viridans," "the modified pneumococcus," "the endocarditic In fact, as it is conceded that the short-lived, acute cases, the severe cases, were the formerly so-called "ulcerative," "malignant, "septic," while the prolonged, chronic cases were more of the vegetative, proliferative type, it might be that the former were due to the more virulent, unmodified pneumococcus, and the latter to the Rosenow's "modified pneumococcus," of recognized low virulence. Capsule germs are most virulent in the capsule stage. (Zinnser.) 39o Up to rather recent date we have been accustomed to consider only two types of endocarditis: A, a simple, non-infectious type, mostly due to rheumatism, to scarlet fever, measles, etc., and we did not think it serious, if the patient recovered from the original disease, and led a quiet, non-strenuous life, under proper observation. B- an infectious, septic, severe type, due to some virulent, supposedly, pyogenic organism, and called "malignant," "ulcerative," "septic" endocarditis. From this generally accepted classification of endocarditis, we have gradually passed through a succession of discussions as to type "A" not only being due to an organism, but also being at times malignant, ulcerative,-to type "B" not being always due to an organism, nor always malignant, ulcerative, septic,-to the acceptance, finally, of the terms, "endocarditis lenta" (Schottmuller),-"acute, subacute, chronic bacterial endocarditis" (Libman),"infectious endocarditis" (Rosenow), because "we now know that all cases of so-called malignant endocarditis are not fatal,-or, that all die directly from the endocarditis, or the concomitant toxaemia,-healed. cases have been described,-many cases are not associated with pus,-the type or organism is not pyogenic,-many cases are not of the ulcerative type, but the vegetative, proliferative type. PROGNOSIS. 9740 The prognosis is most discouraging,-while the course of the disease may extend from weeks to years, many claim there is no recovery. Schottmuller says "all cases are, practically, uniformally fatal. Horder-recovery is very rare, -in his 150 cases he had only one recovery and in this case the blood cultures were negative. Oille-recovery does take place, but it is rare. Billings-as far as I know, no case has recovered, some do improve under rest, some under autogenous vaccines. Libman"it is only a question of time when all succumb,-the late cases to uraemia and to heart decomposition. He intimates that if the blood cultures remain positive, all cases die. Even in cases where the blood cultures become negative, these eventually die, the fibrous or calcareous changes in the heart interfere. not only, with the proper function of the heart, but emboli are carried to different parts of the body, and the glomerular kidney affection and the disturbance in the blood-forming organs, are all inimical to the preservation of life." "Cases may 9941 seem to have recovered, from a pathological, bacterial and clinical standpoint,-healing may take place in these cases of bacterial endocarditis, but the complete recovery from a clinical standpoint is still meagre. He bases the above assertions, partly, on cases examined post-mortem, called by him "bacteria-free healed or healing endocarditis," in which during life no organisms were found in the blood, and post-mortem none were found either in the blood or in the valvular vegetations, but, because the clinical picture while under observation, and the post-mortem findings were similar to positive cases of streptococcus viridans infection which had come to post-mortem after his clinical observation, the special glomerular pathology of the kidney being for him, proof positive of this form of bacterial infection,-involving the kidney as no other infection does. Of these 18 cases post-mortemed, they had all been found bacteria free during his observation. This observation varied from a few days to months, the shortest observation was 3 days, the longest was 10 months,-in most cases one to three blood cultures were made, and all cases gave a history of previous illness, dating back, at least, three years.* 42 43 RECOVERY. Abrahams, reports a very typical case follow ing tonsillitis, with carefully made blood cultures found to be positive streptococcus viridans, in the cultures, and case made a perfect recovery, three years ago. Warren and Herrick, in an analysis of 134 cases of bacteriemia, reported ten (10) recoveries of positive streptococcus viridans in blood cultures, the symptoms in some of these ten (10) cases indicating a very serious condition. This report, although up to date, does not mention date of onset of disease, but that endocarditis was present in only one of the cases. 45 Oille, in his published report (and later in a personal communication, May 28, 1916), of 16 positive streptococcus viridans cases, only one died, though several of them gave a history of intermittent illness dating back more than three years. This careful observer says "if every case of simple endocarditis be bacterial in origin, then all are not of fatal outcome, for it is certainly safe to predict that all of these (abovementioned) cases are not going to end fatally in two, or even in twenty years." 46 Cecil, does not report a single fatal outcome in any of his cases not even in the three (3) cases associated with endocarditis. And the writer adds her own case (a full report of which follows later) which, owing to the unusual "intravenous" administration of the auto-vaccine, and the very successful result, was the cause of writing this paper. DIFFERENTIAL DIAGNOSIS. It is evident from what has gone before, that while in the acute cases diagnosis must present little difficulty, as either the cases die before time has been given to make a diagnosis, or the cases are so specially those of infection, there is no doubt of the diagnosis, it is the more or less subacute or chronic cases that present difficulties. Enough has been presented, in the way of the different diseases for which it may be taken, to make consideration of differential diagnosis here unnecessary,-sufficient to say it may simulate most any disease in any part of the body, specially the most common-place, every-day complaints. In the writer's opinion there are three means of making the diagnosis,-three means that will make evident, not only that an infection is present, but also the nature of the organism causing the infection, thus assisting the prognosi and the therapy. The writer is very earnest in urging that these three means be resorted to at the earliest date, not waiting for danger signals which may mean, "too late." These three means are very simple: 1, a very careful and complete investigation as to a past or present focal lesion in some part of the body,specially in the mouth and throat. 2- cultures of smears taken, as early as possible, and frequently repeated, from the local lesion. 3, very careful, technically complete blood cultures made by an experienced worker,-not by a young laboratory student, and at as early a date in the disease as possible. "An early discovery of the organism is of the greatest importance as to diagnosis and prognosis.' "Blood cultures are a means second to none of diagnosing this interesting and important disease, 47 indeed, in a few cases it has been the only evidence obtained, even before a murmur was heard, and in the absence of all temperature."' 48 That some blood cultures have proved negative in some cases, only emphasizes the fact, that, either they were not made as intelligently as some authorities dictate, or they were not made at the right time, not early enough, or at a moment when the organism was absent, owing to high temperature possibly,49 or to some other cause, leaving behind its fatal imprint. As Horder says, "it is the disintegration of the vegetations forming fatal emboli that are to be feared, and our aim should be to control the growth of the organism which causes them,and our chief hope of accomplishing this would seem to lie in an early diagnosis, so as to use means which promise success in overcoming the organisms themselves, and in thus preventing these vegetations from attaining any size. TREATMENT. In view of the fact that so many claim that recovery seldom results, it seems like begging the question to consider if there is not some therapeutic measure or measures to be used. Let us consider what we have to treat, an infection,and an infection is a local or a systemic invasion of the body by an organism foreign to the blood and other tissues, provoking phenomena, more or less harmful to the host. What is the biochemical principle underlying the treatment so successfully worked out by Mechnikoff, Wright, Koch, Jenner, Pasteur, and their followers? That the human body in health generates in itself |