Volume 1 — GENERAL DISEASES. (continued 7)

Rupture of the spleen occurs occasionally, and is usually attended with sudden pain, collapse, and speedy death. Murchison refers to two examples recorded by Zuelzer and one by Hudson; Petersen reports fifteen cases, in seven of which sudden rupture occurred with speedy death, while in the other eight the rupture followed local softening from infarction, and resulted in death in a few days from purulent peritonitis.

In one of our cases, where death occurred on the sixteenth day, apparently from double pneumonia and heart-clot, it was found that there was a rupture in the enlarged spleen near its upper end, recent plastic peritonitis in the region of the spleen, and a moderate amount of bloody pulpy fluid throughout the peritoneal cavity.

As we have seen, disturbances within the respiratory tract occur with very different frequency in different epidemics. In many they are rare, while in 1870 we noticed cough and other evidences of respiratory trouble in no less than 90 out of 200 cases.

Severe catarrhal laryngitis is a rare and dangerous complication. It did not occur in our cases, but both Begbie and Paterson report cases of it which required tracheotomy, and Wyss and Bock met with ulcerative laryngitis with perichondritis.

Bronchitis of moderate severity, although rare in many epidemics, occurs so frequently in others, as in Philadelphia in 1870, as to rank as a symptom of the disease.

Pneumonia is one of the most fatal complications. The results of our own observations agree with the statements of Jenner and of Carter, that it is the next most common lesion after enlargement of the liver and spleen. On the other hand, Murchison noted it only in 4 or 5 out of 600 cases. It occurred in at least 11 of our cases, 8 of which were fatal; and unquestionably less extensive inflammation was present in other cases which recovered, in view of the marked respiratory disturbances frequently present. Both lungs were involved in 4 cases; of the remainder, the right and left were about equally divided. Out of 23 autopsies, the lesions of pneumonia were found 8 times. The lower lobes were affected in every case. The form of this disease was croupous in 9 cases; in 1 it was that of metastatic suppuration, and in 1 it was more properly described as splenification. The amount of plastic pleurisy associated with it was usually great, and in one case there was also severe pericarditis. In another case the disease advanced to the stage of gangrene of a circumscribed area of the pleura and of the superficial layer of the lung. In only one instance was albuminuria present. In two cases the pneumonia occurred so late in the course of the disease that it might be regarded as a sequel. Death occurred in one of these on the thirtieth day, and in the other (that in which gangrene ensued) it ran a subacute course, and death did not take place until the fortieth day. In the other cases the disease began at the close of the initial paroxysm, during the intermission, or early in the relapse. As would be expected, the sympathetic fever due to this complication modified and obscured the characteristic course of the specific pyrexia.

This rare termination in gangrene has been noted by other observers; in all five or six times. Parry met with a truly remarkable case of double pneumonia, followed by gangrene, and yet resulting in recovery. Jaundice is apt to attend cases of relapsing fever which are complicated with pneumonia.

Pleurisy is an almost constant accompaniment of pneumonia, and frequently occurs in marked degree. It may also be present in cases of severe splenic inflammation. In all probability, localized plastic pleurisy is not infrequent, and may cause some of the severe thoracic pains so frequently present.

Metastatic abscesses of the lung occur occasionally as a result of the profound toxæmia, and are apparently preceded by patches of infarction, which soften in the centre, as in the usual development of pyæmic abscesses. This condition was found in one of our cases in conjunction with suppurative parotitis. It has been included among the instances of pneumonia.

Acute miliary tuberculosis, involving chiefly the lungs and intestinal canal, occurred as a sequel in one case under our observation, and phthisis has been found to follow by other observers (Carter). It is to be expected that if the patient did not so quickly pass from under observation it would be found that an affection so gravely complicating nutrition as does relapsing fever is frequently followed by serious organic disease.

Parotitis is mentioned by so few authors as to show that it is a rare complication in most epidemics, varying from 1 in 600 to 1 in 50 cases. One gland only is affected at a time as a rule, though both may be involved successively. The inflammation begins either during the intermission or the relapse, and may terminate by resolution or by suppuration. Although a painful and severe complication, it is followed by recovery in a considerable proportion of cases. Carter²³ states "that in some degree it was noted in 2 or 3 per cent. of all cases, and nearly as often amongst survivors as in the casualties." It occurred in three of our cases (185); once it underwent resolution; once suppuration occurred in the parotid and in the masseter muscle, with metastatic abscesses in the lungs, and death; and once the patient, who had previously existing amyloid degeneration of liver and spleen without albuminuria, had severe relapsing fever with two relapses, in the first of which parotitis occurred in both glands, successively terminating in suppuration, after which he did well through an apyretic period of six weeks, when sudden high fever appeared, followed by speedy death.

²³ Op. cit., p. 210.

Pharyngitis and tonsillitis of mild grade occur in from 3 to 25 per cent. of the cases in different epidemics.

Hiccough deserves to be ranked among the complications, because it is of frequent occurrence, obstinate and annoying. It occurred in a considerable proportion of our cases, and much more frequently in those who had jaundice. It was often present both in the initial paroxysm and in the relapse, but disappeared soon after the end of the pyrexia. It bore no constant relation to the severity of the vomiting. Not rarely it lasted several days and nights, causing exhaustion and interference with sleep and proving rebellious to treatment. Hypodermic injections of morphia and atropia, chloroform internally, and extremely careful alimentation proved most serviceable.

Hemorrhage from the stomach has already been spoken of (see above).

Diarrhoea, as already stated (see above), occurs much more frequently than in typhus fever, varying from 1 per cent. (Murchison) to 15 per cent. (Scotch epidemics) or 33 per cent. (Philadelphia), or even 50 per cent. (Königsberg). It is usually of moderate severity, but occasionally is so profuse and intractable as to constitute the main cause of death. In some epidemics the attacks of looseness occur almost exclusively after the relapse, but in others the bowels are frequently loose during the febrile stages. In our cases there were not infrequently from three to eight thin, dark, bilious or light yellowish stools daily after the second or third day of the initial paroxysm, and then the looseness would stop during the intermission, probably to recur in the relapse. Occasionally diarrhoea with very frequent liquid stools occurs at the close of one or both of the febrile stages, assuming a critical character, and substituting more or less of the sweating which is the common mode of crisis, although in several such cases quoted by Murchison from Douglas the sweating, despite the critical diarrhoea, was usually profuse. It can scarcely be said that there is any relationship between diarrhoea and vomiting; both are frequently present, and may even be severe and persistent in the same case, though either may be marked while the other is moderate or slight. Abdominal pain and tenderness in the epigastrium and hypochondria are constant symptoms, but when diarrhoea is marked there are apt also to be griping pains and tenderness in the lower segment of the abdomen. When diarrhoea occurs as a sequel, either beginning after the close of the relapse or continuing in cases where the bowels have been loose during pyrexia, it is apt to prove obstinate and intractable, or even to lead to a fatal result.

The character of the stools varies much; usually thin and dark, they may be light yellowish or even whitish. Thus, in a severe case with deep jaundice we observed seven liquid and decidedly whitish stools in twenty-four hours. In such instances there is undoubtedly more or less complete closure of the biliary ducts by plugs of mucus or by swelling of the mucous membrane. On the other hand, the stools may be inky black from admixture with altered blood, or, lastly, they may consist of mucus and blood, in which event the complication assumes the form of actual dysentery and is attended with increased abdominal pain and with tenesmus. Dysentery was, as would be expected, quite frequent in the Indian epidemics studied by Carter.²⁴ It is usually of moderate severity, but occasionally it runs into gangrenous inflammation, is attended with perforation of the bowel, or is followed by hepatic abscess. In one instance we noticed a peculiarly fetid puriform discharge from the anus, which occurred during the relapse and persisted for several weeks, gradually subsiding, as though from some unhealthy ulceration which slowly healed.

²⁴ Op. cit., p. 218.

Jaundice is of frequent occurrence, but has been sufficiently discussed above.

Peritonitis is not rare in its circumscribed form. This statement is based on the comparative frequency with which localized splenic peritonitis, of varying degrees of severity, is found after death in relapsing fever from various causes, and from the great frequency of severe pain and tenderness in the region of the enlarged spleen in favorable cases. In its lesser degrees it may not add materially to the danger of the patient, but in more severe forms, associated with serious splenic lesions, it may run a protracted subacute course and maintain irregular fever.

General peritonitis is, on the other hand, a rare complication, occurring not more than once in several hundred cases. It results from dysenteric perforation of the bowel, from rupture of a splenic abscess, or from rupture of the spleen itself. An example of this latter accident which occurred under our observation has already been given. Speedy death invariably follows, though in the case just referred to the symptoms of peritonitis were totally masked by those of the coexisting double pneumonia, which seemed to be the immediate cause of death.

Suppuration of the mesenteric glands is a rare complication, mentioned especially by Wyss and Bock. As these glands are not usually found enlarged, there being no irritative lesion of the intestines of common occurrence in relapsing fever, it is probable that the collections of pus which have been found were metastatic in origin.

Dyspepsia is not an infrequent sequel, as would necessarily be the case after a disease characterized by so much gastric irritation and by such serious lesions of the liver and spleen. As a consequence, care in diet is often required for a considerable period after the course of the disease has ended; dyspeptic symptoms are frequently complained of, and marked emaciation and anæmia often protract convalescence.

It may be observed that a striking appearance of emaciation is often developed shortly after the crisis of the first paroxysm, or, more particularly, of the relapse. It is partly due to the actual loss of weight during the high pyrexia, but even more to the abrupt transition from a state of extreme febrile turgescence to one of equally extreme relaxation and maceration of the surface.

The amount of urine has been seen (above) to vary greatly in cases distinguished by no special disorder of the kidneys; the extremes in ordinary cases being from twelve or fifteen ounces just before the crisis to from eighty to one hundred and twenty within forty-eight hours after the crisis. Suppression is, however, sometimes noted, and is always a grave symptom, though Parry²⁵ reports more than one case in which on several successive days there was not more in twenty-four hours than one fluidounce of non-albuminous urine, and in which no symptoms of uræmia occurred, and the sweat had no urinous odor. In one of our fatal cases, with intense jaundice, hematemesis, inky black stools, and oedema of the feet and of the lungs, there was not a drop of urine secreted during the last four days of the initial paroxysm; death occurred on the eighth day, and the kidneys were found intensely engorged, of a deep blackish-blue color, with numerous ecchymoses in the cortex, due to impaction of the convoluted tubules with blood, while the renal epithelium was granular and swollen, and many tubules were filled with epithelial cells and granular matter. At the autopsy the urinary bladder was firmly contracted and contained a very small amount of bloody liquid.

²⁵ Op. cit.

More frequently, incontinence of urine, with or without retention, occurs during the febrile stages—according to our observation, most commonly in cases attended with mental disturbance and tending to a typhoid condition. The symptom was not of very grave significance, however, and after the use of the catheter for a few days the bladder regained its tone.

Albumen is quite frequently present in small amounts during the pyrexia of relapsing fever. Thus, in 18 cases of ordinary severity, which all recovered, and in which the urine was carefully examined daily, a trace of albumen was found in 5; in 2 cases it appeared both in the initial paroxysm and in the relapse, but in all instances its presence was of brief duration. In one of these five cases the albumen appeared at both critical periods, when the amounts of urine in twenty-four hours were respectively 150 ccm. and 250 ccm.; but in the other cases the transient albuminuria coincided with free secretion of urine (1250 ccm., 1850 ccm.). It is probable that were the same careful search to be made in all cases the presence of albumen would be detected in fully 20 to 25 per cent. On the other hand, in fatal cases the occurrence of albuminuria is by no means constant, although undoubtedly it is present in a larger proportion of such cases than of those of ordinary severity.

Our experience does not confirm that of Murchison, who states that he never met with typhoid symptoms in relapsing fever without albuminuria or some other evidence of retarded elimination by the kidneys. In several of our cases where the typhoid state was developed in the highest degree repeated examination of the urine failed to discover albumen.

Most observers have been struck with the comparative immunity of the kidneys from serious disturbance in a disease presenting such complicated morbid processes and widespread lesions as relapsing fever. To show, however, that these organs suffer specially in certain epidemics, it may be mentioned that Obermeier²⁶ reports having found albumen with tube-casts of various kinds in 32 out of 40 cases of relapsing fever, thus showing that, in the particular epidemic he was studying, catarrhal nephritis was of almost uniform occurrence. It is true that serious interference with the elimination of urea and other nitrogenous matters may occur without the coexistence of albuminuria, so that it is impossible to deny that severe nervous symptoms may result from impaired renal activity even when the urine contains no albumen.

²⁶ "U. d. wiederkehrende Fieber," Arch. f. path. Anat. u. klin. Med., Bd. xlvii. p. 170.

Attention has already been called to the variations presented in the amounts of urea, but more extended observations are required to show the precise relations of these variations to the graver nervous phenomena. It will be found, we venture to opine, that, while in one group of relapsing-fever cases of grave type, cerebral symptoms are dependent upon the retention and accumulation in the system of urea and other effete nitrogenous products, owing to interference with renal activity from pre-existing organic disease of the kidneys or from an exceptional degree of congestion of those organs, there are other groups where similar typhoid cerebral symptoms are more directly dependent upon the specific toxæmia, upon the hyperpyrexia, upon exhaustion of the nerve-centres by intense peripheral irritation, or upon congestion or other morbid conditions of the nerve-centres themselves.

In all cases where cerebral symptoms manifest themselves in relapsing fever the daily examination of the urine—which here, as in other zymotic diseases, is a duty in all cases—becomes of extreme importance. Three conditions should be borne in mind in such examinations. In the first place, the attack of fever may have occurred in one already the subject of organic kidney disease, and, considering the classes from which the majority of the cases of relapsing fever are drawn, this possibility cannot be of rare occurrence. Out of eighteen post-mortem examinations in which the kidneys were studied with especial care we found positive evidence of pre-existing organic disease four times. In these cases the albuminuria was marked and persistent, though tube-casts were rarely found, and severe cerebral symptoms of typhoid type were prominently present. In another highly interesting case the patient, who had amyloid disease of the liver, spleen, and kidneys, contracted severe relapsing fever; he had increased albuminuria during both febrile stages, suppurative parotitis, but no grave cerebral symptoms, and apparently recovered. After an apyretic period of six weeks, during which the symptoms of the amyloid visceral disease persisted, a sudden and rapidly fatal pyrexia occurred. Unfortunately, the existence of spirillar infection of the blood was not known at the time.

In the second place, the attack of fever may become complicated with acute nephritis from special localization of the poison, as in Obermeier's cases, or from vulnerability of the kidneys. In such cases careful study of the urine should indicate the event, and the prognosis, though grave, is not so hopeless as in the first instance. An interesting example of this occurred under our observation, where the patient, who had apparently an ordinary attack, was seized with acute catarrhal nephritis, with temporary uræmia, during the relapse, but after a dangerous illness recovered without any organic renal disease as a sequel.

In the third place, may be found the more usual and more readily-determined condition of slight and transient albuminuria (with variations in urea excretion) which has already been discussed, and which has no serious prognostic significance.

The following very interesting case deserves special mention: The patient, a man aged thirty-six, was admitted on the fifteenth day of an attack of acute catarrhal nephritis, with slight ascites, marked oedema of the feet and legs, and highly albuminous urine. In the course of ten days the oedema and albuminuria were much diminished, when on the thirteenth day after admission he was attacked with relapsing fever, the ward in which he lay containing a number of persons ill with that disease. The initial paroxysm was severe, but without any grave cerebral symptoms; the urine grew scanty, dark, and bloody, and the oedema increased and invaded the pelvis. Crisis occurred on the fifth day, temperature falling 9°, sweating copious, urine 473 ccm. in twenty-four hours, color of porter, highly albuminous, and depositing blood, renal epithelium, hyaline, granular and epithelial casts, all stained reddish. Two days later, urine 1600 ccm., light colored, with only a small amount of albumen.

A slight and brief relapse (101° for two days) occurred after an interval of four days; a second imperfect relapse (100.5° for three days) after a further interval of six days; and finally, after a further interval of only two days, a violent relapse (temperature rising rapidly to 106°) with crisis (fall of 8° in twelve hours) at close of fifth day. The oedema gradually diminished from the time of the first crisis, did not increase in the relapses, and disappeared completely and finally about ten days after the last relapse. The urine was very free after the first paroxysm, averaging from 2000 to 2300 ccm. During the subsequent febrile periods it did not decrease, and indeed on the second day of the last relapse, with the temperature at 105°, the amount in twenty-four hours was 3200 ccm. Four days subsequently, during crisis, the amount was only 350 ccm.

The albumen disappeared entirely from the urine in two weeks from the close of the last relapse; there had then been no tube-casts for some days, and the patient was discharged entirely well a short time afterward. The treatment consisted of hot vapor-baths, repeated dry cupping over the kidneys, infusion of digitalis with acetate of potash during pyrexia, and Basham's iron mixture in the intermissions. It seemed that the occurrence of the relapsing fever interfered wonderfully little with the recovery from nephritis.

Hematuria is a comparatively rare and very grave complication. It may occur as an additional evidence of the dyscrasia of the blood in connection with hemorrhages from other surfaces, or as in the case we have before referred to or in that reported by Murchison,²⁷ it results from intense engorgement of the kidneys. In Murchison's case hematuria, with much albumen and tube-casts, occurred in both paroxysms without any uræmic or typhoid symptoms, and was followed by satisfactory recovery.

²⁷ Op. cit., p. 370.

Sugar is sometimes present in small quantity as a transient symptom; and diabetes has been observed as a sequel.²⁸

²⁸ Tyson, Phila. Med. Times, 1871, i. 418.

Metastatic inflammation of the kidneys, with centres of suppuration, was observed by Wyss and Bock.

When menstruation occurs during relapsing fever, as it may do at any time, it is apt to be excessive, and may amount to severe hemorrhage. Crisis has been known to occur in this manner.

The numerous cases reported by various observers of relapsing fever occurring in pregnant women establish the rule that abortion almost invariably occurs, whatever may be the stage of the pregnancy. In a large majority of cases the mother recovers, but the child, if viable, is stillborn or dies in a few hours. Only two of our patients were pregnant women, and the result in each was unusual. In one, the patient, already the mother of several children, was in the fifth month of gestation; the initial paroxysm was severe, with delirium, but no symptoms of abortion occurred; the intermission lasted six days, during which she felt very well; the relapse was also severe, and crisis occurred on the fifth day, the temperature falling below normal, and the case promising to do well; but on the following day there was a sudden rebound of temperature, pulse 140, severe præcordial pain, and death occurred in twenty-four hours, the contents of the uterus being partially expelled during the act of dying. In the other case, a girl of eighteen years, who had aborted at the third month of gestation eight months previously, and who was again three months advanced in pregnancy when attacked with relapsing fever, went safely through a bad attack and carried her baby successfully to full term.

MORBID ANATOMY.—The surface of the body often presents patches of livid discoloration, and jaundice persists in cases where it has been present during life. There is but little appearance of emaciation, except in cases where it has been present before the attack.

When death occurs while the temperature is high the body remains warm an unusual length of time. Thus, in one case where death occurred at 11.30 P.M., the temperature at 12 was 103°, and at 1 A.M. it was 101.6°, that of the room being 73°; at 6 A.M. it remained at 93°, the room being at 73°; between 9 A.M. and 2 P.M. the room was kept at 55°, but the body was still at 82° at the latter hour.

The voluntary muscles are often jaundiced, and in prolonged cases they may be found flabby and having undergone marked granular degeneration. In many cases, however, they remain quite dark and firm. Ecchymoses of the muscular substance are met with occasionally.

In one case, where during life there had been painful swelling of the left parotid region, with fistulous openings on the cheek, and where death occurred on the twelfth day of the disease, the masseter muscle was swollen, with patches of dark, almost black, discoloration from ecchymosis, and was studded throughout with small collections in its substance. The fluid from these contained very numerous cells indistinguishable from leucocytes. The muscular fibrils were friable and granular, and there was multiplication of the nuclei of the sarcolemma. These unusual lesions seemed to have originated in interstitial disintegrating thrombi, with consequent inflammation of the muscle.

The muscle of the heart is more frequently affected, and in the fatal cases our attention was particularly drawn to those lesions. Ponfick²⁹ has also described them minutely. The degree of change varies from a partial loss of transverse striation, with slight granular appearance, up to a very high degree of granulo-fatty degeneration. The organ is then flabby, its substance pale gray or brownish, either wholly or in streaks, and microscopic examination shows an extreme degree of fatty granular change. It must not be forgotten, however, that many of the subjects of relapsing fever have been leading irregular and dissipated lives, and that in some instances the lesions of fatty degeneration detected in their organs may have been the result of their previous habits.

²⁹ Virchow's Archiv. f. path. Anat., Bd. lx. Hft. 2, p. 162.

Lesions of the cardiac muscle were most marked in those of our patients who had been intemperate, and in whom fatty degeneration of the viscera (chiefly liver and kidneys) was also found. They were most fully developed in cases where death occurred at a comparatively late period, while in some very severe cases, in which death occurred as early as the fifth day, the cardiac fibre presented merely faintness of striation without actual granular degeneration.

Ponfick in particular notes that the great majority of the bodies he examined were of persons who had been habitual drunkards.

Pericarditis is occasionally present, and is marked by the usual lesions. In a very severe case in which it contributed largely to the production of the fatal result it was associated with pneumonia. In addition to this, effusions of blood beneath the endocardium and pericardium are not rare; and we have seen them quite large and numerous in cases where the muscular fibre was firmly contracted and the cavities contained quite firm decolorized clots.

Thus in our case No. 62, Series C., "the heart was normal in size, with no appearances of previous disease. There were numerous ecchymoses of both layers of the pericardium. The right cavities contained large, firm, yellowish, fibrous clots, forming a cast of the upper part of the ventricle and of the auricle, and extending both into the pulmonary artery and back into the veins, and so firm that by gentle traction a complete cast of these vessels was drawn out. The clot in the pulmonary artery was throughout firm, fibrous, and yellowish. There were numerous ecchymoses of the pleura and of the mucous membranes of the stomach and urinary bladder, hemorrhagic infarctions in the kidneys and lungs, and granulo-fatty degeneration of the cardiac muscle." Death had occurred in this case about the close of the third week, and was preceded by hematemesis and suppression of urine. We must note in this connection the tendency to embolism that exists in this disease.

Especial interest attaches to the condition of the blood in relapsing fever. Usually it presents no abnormal appearance if drawn during life, though in grave cases it may coagulate imperfectly. We have no knowledge of its minute chemical characters, save that in several cases where there was great diminution in the amount of urine, with uræmic symptoms, urea has been found in considerable amount in the blood (Murchison, p. 368). The red globules present no definite or characteristic changes. In some of our examinations they appeared of light color and became crenated very quickly on exposure. On the other hand, the white corpuscles have repeatedly been observed to be increased in number, at times considerably so (Cormack, Thompson, Zuelzer, Carter, Boeckmann, and ourselves), though this change is not regarded as constant or essential. It has, however, a very great interest in connection with the characteristic lesions of the spleen which will be described hereafter. In several cases we observed that many white corpuscles were small and apparently imperfectly developed. Boeckmann³⁰ concludes that they increase in number during the febrile paroxysm, reaching their highest number at the crisis, and then diminishing gradually to the normal. The red globules are much decreased during the fever, and return to the normal slowly during convalescence.

³⁰ Deutsch. Arch. f. klin. Med., Sept. 1881, p. 513.

In addition to these changes, various abnormal elements have been observed more or less constantly. By far the most important of these is the spirillum or spirochete of Obermeier, which has been already carefully described. In proportion as this organism has been carefully looked for it has been found constantly, so that the evidence has become very strong in favor of its uniform presence in the blood of relapsing-fever patients during the febrile stage of the disease.

Ponfick in 1874³¹ called attention to the occurrence of large granule-cells in the blood in this disease. They are found during life as well as after death, when they exist in largest proportion in the blood of the splenic, hepatic, and portal veins. Their shape is spherical, ovoid, or elongated; the basis of the cells is a delicate, translucent, albuminous substance; and the granules are of a fatty nature, as shown by the action of reagents. These cells have been found by other observers, and the view is generally received that they are derived from the lymphoid elements of the spleen, and perhaps of other portions of the lymphatic system; and Carter, who has studied them carefully, is inclined to think there is some connection between them and the development of the spirillum.

³¹ Centralbl. f. d. med. Wissensch., 1874, p. 25.

Ponfick also first described³² certain other large, irregularly-shaped, pale, granular, nucleated cells, which occur in smaller number in the blood in relapsing fever, and which he regarded as altered endothelium, derived from the lining of the blood-vessels, of the lymphatics, or of the lacunar spaces of the spleen. Occasionally these cells are found with such highly granular contents as to make them closely simulate the large granule-cells described above. These results of Ponfick have been confirmed by other observers.

³² Loc. cit.

In several of our reports of examinations of blood there is mention made of quite abundant, free granular matter—an appearance also observed by Carter. Finally, the latter describes the occurrence of thread-like filaments and of short, rod-like bodies.

There are no characteristic lesions connected with the gastro-intestinal canal. The mucous membrane of the stomach may be normal or merely injected, though where there has been much vomiting, and especially bloody vomiting, there is marked injection, and not rarely ecchymosis and submucous extravasations of blood, with softening of the membrane. These extravasations are usually small, but Cormack reports a case where one-third of the mucous membrane of the stomach was the seat of ecchymosis and extravasation. In one of our own cases the extravasations occupied an area of four inches square.

The small intestines exhibit patches of congestion or ecchymosis less frequently than the stomach, though it is usual to find injection of the mucous membrane, especially of the lower portion, in cases where there has been diarrhoea. Carter, observing the disease in India, found in one-half of all autopsies some amount of congestion, hemorrhage, or inflammation of the ileum. In two instances he found a layer of diphtheritic deposit over the mucous membrane of the lower part of the ileum.

There are no special alterations of the solitary or agminated glands, and ulceration never occurs. Even in cases where the constitutional infection is severe, whether diarrhoea has been present or not, it is noteworthy that there is rarely any swelling of the solitary glands or Peyer's patches, such as is met with in many other acute specific diseases. It was not present in any of our autopsies.

The large intestine in like manner exhibits no characteristic lesions. Patches of congestion and occasionally submucous ecchymoses may be observed, and croupous exudation occurs here somewhat more frequently than in the small intestine.

Wyss and Bock³³ speak of enlargement of the mesenteric and retroperitoneal glands as of frequent occurrence, but we did not observe it, and Murchison states that these glands present no abnormal appearance.

³³ Op. cit., p. 223.

Alterations of vascularity of the brain or its membranes are met with, but they are variable and bear no definite relation to the precedent symptoms. Ecchymoses of the membranes are occasionally observed, and in one of our cases extensive meningeal hemorrhage was found. Murchison reported a case in which embolism of the left femoral artery occurred, and subsequently of the left middle cerebral artery, inducing death. The suggestion may be hazarded that in some of the cases where there is severe delirium ending in stupor and death there has been multiple capillary embolism of the cerebral vessels.

There is occasionally the evidence of catarrhal inflammation of the upper air-passages, and in some epidemics diphtheritic exudation in the pharynx and larynx has been noted (Wyss and Bock); and Ponfick found acute oedema of the glottis in a considerable proportion of the fatal cases at Berlin. The lesions of pleurisy are met with in a small proportion of cases; in our own autopsies this complication was more frequent than in most epidemics.

The lungs may be normal, and Murchison concludes that they are more frequently so than in typhus. Still, they often present congestion or oedema, and subpleural ecchymoses, hemorrhagic infarctions, and pneumonic consolidation are not rare. Lobar pneumonia was present in 33 per cent. of our own autopsies, in 28 per cent. of Carter's, and in 20 per cent. of those conducted by Ponfick. The inflammation usually presents the regular stages, and is associated with a moderate degree of plastic pleurisy; but occasionally, as in one of our cases, it terminates in gangrene. In the instance referred to there was an area of gangrene about three inches square and one inch in depth, involving the pleura and a superficial layer of lung on the antero-lateral aspect of the left lower lobe. In another remarkable instance, already referred to on account of the suppurative inflammation of one masseter muscle, the lungs, which were stained yellow throughout, presented numerous deep purplish patches, which on section altogether resembled the secondary metastatic deposits of pyæmia, with yellowish softening or even puriform centres surrounded by a rim of purplish livid discoloration. Very numerous similar patches, varying from the size of a pea to that of a hazel-nut, and presenting every stage of development, were found throughout both lungs. In a few instances we found the lesions of chronic phthisis, which had, of course, existed before the attack of relapsing fever. The bronchial glands were found swollen and infiltrated in cases where inflammatory processes in the lungs have existed.

Much interest attaches to the state of the genito-urinary organs in relapsing fever, but caution is required to distinguish lesions that have existed prior to the attack from those properly referable to it.

Owing to the intemperate and exposed lives of many of the patients, renal lesions might reasonably be expected in no small proportion. The comparative rarity of albuminuria (see above), even in severe cases, is suggestive of the view that when it is present it may at least sometimes be due to pre-existing lesions aggravated by the acute infectious process, and further that the extreme gravity generally presented by such cases may be in part due to the impaired condition of the kidneys.

The morbid changes most frequently referable to the fever are moderate enlargement and congestion, occasionally very intense so that we find it described in our notes as deep blackish-purple or blue; ecchymoses of the capsule or of the mucous membrane of the pelvis; small hemorrhagic infarctions, usually in the cortex; and cloudy swelling of the glandular cells. Less commonly are found hemorrhagic infarctions, or small embolic patches advanced to various stages of disintegration, even to the formation of small puriform collections. In quite rare cases the lesions of acute nephritis are present, while caution must be used in interpreting other changes occasionally met with, such as pallor with granulo-fatty degeneration or other advanced alterations of the glandular cells, or hyperplasia of the intertubular connective tissue, with or without contraction of the kidneys.

The mucous membrane of the bladder, as already mentioned, may present ecchymoses, or, more rarely, croupous exudation (Wyss and Bock). The urine contained may be bloody, or, as in one of our cases where there had been total suppression of urine for over seventy-two hours before death, there may be but a small amount of almost pure blood, containing a few phosphate crystals, but no tube-casts. In this case there were also ecchymoses of the bladder and of the pelvis of the kidneys, with intense congestion and numerous small hemorrhagic infarctions of the kidneys.

The liver is constantly though variously affected. It is found enlarged in the great majority of cases, especially if death has occurred during the febrile stage. The ordinary degree of enlargement in our cases was from four to four and a half pounds, but in a few instances the liver weighed one hundred or one hundred and two ounces, though in most of these extreme cases the patients had been drunkards, and there was such advanced fatty alteration of the liver as to make it probable that the organ had been diseased previously. These figures correspond with the results of other observers.

In many cases, especially when death occurs early and during the febrile stage, the capsule and substance of the liver are congested, at times intensely so; and when ecchymoses are found elsewhere they are apt to be present here also, appearing as purplish patches dotted over the capsule and extending into the superficial layer of hepatic tissue. Not rarely, however, the liver substance is paler than normal, and presents a yellowish tinge, apart from the decided yellowish staining present in cases attended with jaundice. Carter describes a partial mottled paleness of the liver as having been frequently observed in his cases, the circumscribed pale areas presenting a corresponding localized degeneration of the cells, as though from some local interruption of circulation.

Cloudy swelling and fatty degeneration of the liver-cells are indeed very often present, and in some epidemics with preponderance of bilious symptoms are constantly found (Ponfick). The degree of the cell-alteration varies from a slight granulo-fatty change to an advanced fatty degeneration, even with a marked tendency, in rare cases, to disintegration of the cells, so as to produce lesions analogous to those of acute yellow atrophy (St. Petersburg epidemic).

The whitish deposits described by Küttner as due to albuminous or fibrinous infiltration are probably referable to transformed hemorrhagic infarctions, and the minute puriform collections that have been observed at the centre of the acini (Wyss and Bock) may have been metastatic in origin, or attributable to the disintegration of minute thrombi associated with irritative hyperplasia of the adjacent lymphoid elements. The consistence of the liver varies: when death occurs early and bilious symptoms have not been marked, it may be even firmer than normal, but more frequently it is softer, and it may be relaxed, flabby, and friable.

The condition of the bile-ducts is of great interest in view of the frequency of jaundice as a symptom in relapsing fever, and most authorities unite in saying that they present no lesions capable of explaining it.

The gall-bladder is usually found full of dark bile, but there is no such degree of inspissation, except in rare instances, as could interfere with its passage through the ducts. Murchison quotes the statement of Peacock that in some instances the bile was thick and viscid, so as apparently to cause obstruction, but all observations agree in showing that this is exceptional. The mucous membranes of the larger ducts may present evidences of slight catarrhal inflammation, but in nearly all cases where they have been carefully examined, even when jaundice had been marked, they have been found patulous and free, so that the jaundice cannot be regarded as due to obstruction of the larger ducts save in rare instances (Pastau). In further confirmation of this may be stated the fact that there is no want of bile in the duodenum and feces.

On the other hand, a careful consideration of the lesions of the substance of the liver will show that it would be most improbable that the minute biliary ducts in the areas most affected should escape implication. Münch, who investigated this subject carefully, found that there was a catarrhal state of the fine bile-ducts in every case of relapsing fever with jaundice; and Litten found the smallest ducts plugged with bile-stained pellets of mucus. It would appear, therefore, that in many cases at least the jaundice is really obstructive in its origin, the seat of the obstruction being in the too-rarely examined minute bile-ducts, though further investigation of this interesting question is required.

The clinical bearing of these conditions has been fully discussed in the appropriate section.

The changes in the spleen are constant, and even more remarkable than those in the liver. It is enlarged with rare exceptions, and especially so if death has occurred during the febrile stage. Upon the subsidence of the fever the spleen probably returns to its normal size more rapidly than the liver. The more common extent of the enlargement in our own cases was from ten to eighteen ounces, though we found the spleen in one case weighing twenty-nine and a half ounces and in another forty-four and a half ounces. In neither of the latter instances was there any reason to suspect malarial complication. The most extensive enlargement we have found recorded is sixty-eight ounces in a case reported by Küttner.³⁴

³⁴ Schmidt's Jahrb., 1865, vol. cxxvi.

There is usually a correspondence between the stage and extent of the splenic and hepatic lesions, but this is not invariable, and one or the other organ may present a far higher degree of enlargement or much more intense interstitial changes. It may be mentioned, moreover, that in some unusual cases the lesions of the lungs, such as ecchymoses and hemorrhagic infarctions, may be disproportionately marked as compared with those of either the liver or spleen.

The capsule of the spleen often presents a mottled look, with at times large purplish ecchymoses; it is apt to be more or less opaque, and local peritonitis, with thin layers of plastic exudation often forming friable adhesions with the abdominal wall, may exist.

In one of our cases the capsule presented a small perforation or rupture, with an exudation of plastic lymph over an area of four by six inches, and diffuse peritonitis, with effusion of bloody liquid with shreds of lymph throughout the abdominal cavity. This fatal termination is fortunately rare, but there are several other instances on record. The splenic pulp may retain its consistency and firmness, even in cases that have run a long course; but more frequently it is softened, and may be almost diffluent. The pulp is often swollen, so that when cut it projects above the section. The color is darker than normal, and often is of a deep maroon color. This swelling is due to enlargement of the blood-vessels, associated with great increase of the cellular elements of the pulp and with enlargement of the Malpighian corpuscles.

When death occurred early in the disease we found these bodies grayish or grayish-yellow in color and of the size of hempseed, so that the section very thickly studded with them closely resembled shad-roe, and this stage of the lesion is frequently described in our notes as the shad-roe spleen. Subsequently, the Malpighian bodies enlarge still more, and stand out above the section a line or more in diameter, and of a lighter color; not rarely, several of them come in contact, and thus form a considerable mass of irregular shape, resembling the infarctions described below.³⁵ It is probable that central softening may occur later in the Malpighian bodies, though we are inclined to regard the puriform collections frequently found as chiefly due to the disintegration of hemorrhagic infarctions or of embolic patches. Of these, hemorrhagic infarctions are by far the most common and present the familiar appearances. They may be quite numerous, superficial, or deep-seated, and of variable shape and size. At first dark reddish, firm, and sharply separated from the surrounding pulp, they grew reddish-yellow or yellowish later, softened in the centre, and eventually were transformed into puriform collections. Doubtless, in a large proportion of cases that recover such infarctions exist and are slowly absorbed. Ponfick has shown that these are venous infarctions, the arterioles leading to them being patulous. True arterial embolism does, however, occur, though much more rarely (Ponfick, Murchison), giving rise to firm, wedge-shaped infarctions at the periphery of the spleen, which may undergo degenerative changes similar to those above described. The resulting abscesses may burst into the peritoneum, pleura, lung, or bowel. The microscopic appearances have been most fully described by Ponfick, our own comparatively meagre observations having accorded entirely with his subsequent accurate description. The cells of the swollen pulp contain red blood-discs and pigment, and some present collections of bright granules. The lymphoid cells of the Malpighian corpuscles are at first in a state of cloudy swelling with multiplication of their nuclei, and later show marked granular fatty degeneration.

³⁵ Thus, Wyss and Bock describe "multitudes of minute abscesses as large as poppy or hempseed, and containing a single drop of pus."

The lymphatic glands present no lesions, and the pancreas is normal.

The peritoneum is not affected as frequently as other serous membranes in this disease. Superficial ecchymoses are, however, quite common, especially so over the solid viscera; and more rarely effusions of blood have been found in the subperitoneal connective tissue, involving the muscular or glandular tissues beneath. We have already mentioned (above) the occasional occurrence of local peritonitis, most frequently of the splenic capsule, and also the rare accident of diffuse inflammation from rupture of the spleen.

The marrow of the bones was carefully examined by Ponfick, who first called attention to the presence of important changes in relapsing fever, which have since been confirmed by other observers. These changes consist in proliferation and subsequent degeneration of the lymphoid cells of the marrow, with multiplication of the nuclei in the walls of the minute vessels and fatty degeneration of their coats. As a result of these changes, spots of puriform softening may form, chiefly in the cancellous tissue of the extremities of the long bones, with the production of localized necrosis, and possibly with extension of inflammation to the neighboring articular cavity.

Considerable space has been devoted to the detailed consideration of the pathological changes in relapsing fever, partly because we believe the fact has not been sufficiently recognized that the disease is constantly attended with important and characteristic lesions. These consist, in brief, of remarkable changes in the blood; of widespread ecchymoses and infarctions, which not rarely undergo puriform disintegration; of hyperplasia and subsequent degeneration of the Malpighian corpuscles of the spleen, with changes in the cellular elements of the splenic pulp; of cloudy swelling of the gland-cells of the liver and kidneys, with a marked tendency to fatty degeneration; of changes in the marrow of the long bones; and, finally, of granulo-fatty degeneration of the muscles, and especially of the heart.

DIAGNOSIS AND RELATION TO OTHER DISEASES.—The entire question of the diagnosis of relapsing fever is dominated by that of spirillar infection. Before Obermeier's discovery the differential diagnosis of the initial paroxysm, and to a less extent that of the subsequent events of a case of relapsing fever, was attended with considerable difficulty. But if, as now seems established, immediately before and throughout the initial paroxysm and subsequent relapses a characteristic spirillum is to be detected in the blood upon proper examination, while it rapidly disappears after the crisis, it is evident that as soon as a suspicion is aroused as to the possible presence of relapsing fever the question may be settled conclusively by the microscope.

None the less is it important to consider carefully, but briefly, the symptoms by which relapsing fever is to be distinguished from various affections which may simulate it, because even the most experienced observers admit that the spirillum cannot be invariably detected; because it is not yet known that a similar organism may not be found in some other affections; and, finally, because on the outbreak of an epidemic of relapsing fever, especially in America, where its occurrence has hitherto been so rare, there is strong probability that the nature of the early cases will not be even suspected until the relapse occurs.

Typhus fever often prevails in an epidemic form simultaneously with relapsing fever, so that it was inevitable they should have been for a time confused. Their essential non-identity is, however, now too well recognized to require any lengthy demonstration. The following statement of the heads of the argument may therefore suffice.

In typhus there is no characteristic spirillum, and the lesions which are truly characteristic of relapsing fever are totally wanting. There are convincing differences in the symptoms, course, and results of the two diseases. There is no evidence to show that when fever has been imported into a locality by a single case, typhus fever has ever produced other than typhus, or relapsing other than relapsing fever. The two diseases often prevail together, and may coexist in the same house, each preserving its own distinct characteristics; and persons exposed to the double contagion may contract one or the other, or first one and then the other at a shorter or longer interval, so that an attack of either exerts no protective power against the other. It must be noted, however, that in a large majority of such cases of successive contagion it is relapsing fever which has been followed by typhus, while the reverse has been observed much more rarely.

In 1869-70 the two diseases were prevalent in Philadelphia, and the wards of the municipal hospitals constantly contained a considerable number of cases of both. Three instances came under our care in which after recovery from relapsing fever the patient contracted typhus. All of these patients were employed as assistant nurses, and were continuously under observation from the early part of their attack of relapsing fever to the end of the attack of typhus. In one case the interval of health between the close of the relapse and the onset of typhus was forty-four days; in the second it was thirteen days. In both cases the original disease was thoroughly characteristic and the subsequent attack of typhus was typical. In both death followed, and the post-mortem examination verified the above statement. The third patient had severe relapsing fever, from which he recovered and returned to work, though with pains in the legs, shoulders, and forehead. After an interval of apparent health of eleven days he developed a well-marked attack of typhus, which terminated on the twelfth day in recovery. It may be added that although typhus is not of frequent occurrence in any portion of North America, there have been a number of epidemics unattended with a single case presenting the features of relapsing fever.

Between well-marked cases of the two diseases there should be no difficulty in making a prompt diagnosis. Relapsing fever is distinguished from typhus clinically by the severity of the initial chill; the rapid elevation of the pulse and temperature; the comparative infrequency and mildness of cerebral symptoms, despite the intense fever; the severity of the gastric symptoms, nausea and vomiting; the enlargement of the liver and spleen, with marked abdominal pain and soreness; the frequency of jaundice, of epistaxis, and of other hemorrhages, and of anæmic murmurs over the heart and large vessels; obstinate insomnia; vertigo; peculiar rheumatoid pains and perversions of sensation; the frequency of sweating during the high pyrexia; by the occurrence of crisis, subnormal temperature, apyretic interval, and relapse; the rarity of measly eruption and of bed-sores; the frequency of pneumonia, diarrhoea, ophthalmia, oedema, and desquamation as complications and sequelæ; the usual occurrence of abortion in pregnant females; the protracted course of the disease, and its remarkably low mortality despite the severity of the symptoms, except in cases of complicated or typhoid type; and, finally, by the modes in which death occurs. Of course to this must be added the specific result of examination of the blood in relapsing fever.

Doubt will arise only in very rare cases where a measly eruption appears on or before the fifth day of relapsing fever, with headache and mild delirium, but without severe gastric symptoms, epistaxis, or jaundice. If no relapsing fever were prevalent at the time, such a case might well be regarded as one of mild typhus until the crisis and the relapse disclosed its real nature. But if the two diseases were known to be prevalent in the community, examination of the blood would properly be made at once and the diagnosis be established.

The diagnosis between ordinary cases of relapsing fever and typhoid is readily made by the gradual onset and peculiar course of the pyrexia in the latter disease, as well as by the frequency of delirium, of abdominal distension, and of diarrhoea, and by the characteristic eruption. The occurrence of epistaxis, bronchial irritation, and splenic enlargement is common to both, and an eruption of small rose-pink spots has been noted by some observers (Carter, pp. 194, 317). But jaundice, enlargement of the liver, hypochondriac pain and soreness, excessive nausea and vomiting, severe rheumatoid pains, and numbness and tingling of the extremities, are very significant symptoms of relapsing fever. Attention has already been called to the grave type of relapsing fever in which the typhoid state is fully developed, and to the fact that in such cases the pyrexia is often modified, the onset less abrupt, the crisis imperfect, and the interval occupied by an irregular post-critical symptomatic fever. It is altogether probable that such cases have not rarely been regarded as of true typhoid character; and indeed the attempt has been made by Griesinger to establish as a separate and independent affection, under the name of bilious typhoid fever, a group of cases which close examination seems to show to be chiefly composed of grave complicated relapsing fever with a certain proportion of true typhoid fever, complicated with jaundice.

The recognition of the bilious typhoid type of relapsing fever is based upon the history of the case; the mode of onset; the greater severity of the pains, arthritic and abdominal; the early appearance and intensity of the jaundice; the more marked enlargement of the liver and spleen; the marked tendency to hemorrhages from various surfaces; the peculiarities which careful study of the temperature curve will show, especially about the time of crisis; the rarity of eruption; the characteristic spirillum;³⁶ and the totally different anatomical lesions, which are, unfortunately, often demonstrable, as this form of relapsing fever is fatal in from 33 to 50 per cent. of cases.

³⁶ As first demonstrated by Motschutkoffsky.

Since the discovery of the spirillar test for relapsing fever it may be said that Griesinger's bilious typhoid must be stricken from medical nosology as an independent affection.

The case of Charles Hood, above, is a good example of the bilious typhoid form which occurred not rarely in the Philadelphia epidemic.

Murchison points out that, owing to the frequent occurrence of jaundice in relapsing fever, this disease has been mistaken for yellow fever by such good observers as Graves, Stokes, and Cormack. Difficulty in diagnosis would be likely to arise only in regard to the bilious typhoid type of relapsing fever, and since its clinical history has become so well known, a mistake is not likely to occur. The geographical distribution of the diseases is widely different. Yellow fever is influenced powerfully by season and temperature, while relapsing fever is independent of both. Negroes are but slightly liable to yellow fever, while relapsing fever attacks them with special violence. Yellow fever is not contagious, but infectious, and second attacks are extremely rare; relapsing fever is one of the most contagious of the zymotic diseases, but one attack does not protect against a subsequent one. The mortality, the anatomical lesions, the course of the pyrexia, the leading clinical symptoms, are all widely distinct in the two affections; and, finally, no spirillum has been found in the blood in yellow fever. Yellow fever is an extremely fatal disease; the ordinary form of relapsing fever has a mortality of 2 to 10 per cent.; the bilious typhoid form, one of 33 to 50 per cent. In yellow fever the spleen is but slightly enlarged, and the liver is pale and softened; in relapsing fever the liver and spleen are greatly enlarged, and there is great tenderness over the hypochondriac region. In yellow fever albuminuria is much more common, and the urine more frequently suppressed, than in relapsing fever.

The sudden onset, the severe headache and pains in the limbs, the vomiting, jaundice, epigastric tenderness, enlargement of the liver and spleen, occasional epistaxis, hematemesis, or hematuria, absence of characteristic eruption, liability to herpes facialis, pneumonia, and diarrhoea; the occasional occurrence of remissions in the pyrexia, and even of more or less fully-developed chills for several successive days during the initial paroxysm or the relapse, suffice to explain the difficulty which may arise in distinguishing the bilious form of relapsing fever from bilious remittent fever. But the latter disease arises exclusively from malaria, and is therefore powerfully influenced by season and locality; is not contagious; does not present anything approaching to the crisis, the apyretic interval, or the abrupt relapse of relapsing fever; presents pigmentary changes in the blood, instead of the spirillum; and lesions of the spleen and liver totally unlike those characteristic of relapsing fever; can be promptly controlled by antiperiodic doses of quinine, and therefore should have a mortality far less than that of the grave form of relapsing fever. It is not necessary to pursue this subject further, but a reference to the temperature charts of Carter³⁷ or of Litten³⁸ will show that in some epidemics single paroxysms resembling those of quotidian ague might occur during the interval between the initial paroxysm and the relapse, or a series of two, three, or more such paroxysms of quotidian or tertian type might represent an entire relapse. Such phenomena are wholly uncontrollable by quinia, and are presumably dependent upon irregularities in the specific infection, instead of upon a blending of malaria with the poison of relapsing fever. There is some ground for believing, however, that those who have recently passed through an attack of the latter are highly, perhaps unusually, susceptible to malarial infection, as we have already seen they are liable to contract typhus.

³⁷ Op. cit.

³⁸ Deut. Arch. f. klin. Med., xlii. 1874.

The chill, the sudden and high fever, the acid sweat, the high-colored urine, the intense pains and soreness, and the occasional murmur over the heart, will in some cases of relapsing fever suggest the idea of severe rheumatic fever, with illy-developed articular inflammation and with a tendency to hyperpyrexia. The urgent danger presented by the latter condition and the necessity for immediate recourse to cold baths and large doses of quinine or of the salicylates, render it highly important that no such error of diagnosis should be made. It will usually be avoided readily by observing that in relapsing fever there are great nausea, repeated vomiting, insomnia, peculiar formication of the extremities, jaundice, early enlargement of the liver and spleen, with abdominal pain and soreness, and a tendency to epistaxis; and, further, that despite the high temperature, cerebral symptoms such as result from rheumatic hyperpyrexia are not threatened, except in grave typhoid cases or just preceding the crisis.

The onset of relapsing fever may suggest forcibly the invasion period of small-pox, with its marked rigors, high fever, lumbar pain, aching in the head and limbs, nausea and vomiting, and if the patient is known to have been exposed to the contagion of both diseases a diagnosis would be impossible until the third day. But such a dilemma can rarely occur, and under ordinary circumstances the patient's antecedents will enable a correct opinion to be formed.

Severe cases of simple febricula with marked gastric disturbance may, as remarked by Jenner, closely simulate relapsing fever; and the same is true of attacks of acute gastro-hepatic catarrh, with severe headache, sharp fever, cholæmic eye, epigastric tenderness, and frequent vomiting. Of course there is no danger under ordinary circumstances of these simple conditions being regarded as relapsing fever, but when the latter is prevalent in epidemic form it is probable that the mistake is frequently made. Although an immediate diagnosis might be possible only by microscopic examination of the blood, the peculiar clinical symptoms of relapsing fever would soon be found wanting, and suitable treatment would bring the simpler affection under control.

Acute yellow atrophy of the liver occurs chiefly in pregnant women, though it is also met with in men and children; but it is so rare that should a case of it come under observation during the prevalence of relapsing fever there is considerable danger that its nature would be overlooked. It resembles relapsing fever in the occurrence of jaundice and other signs of hepatic disorder, of delirium, and of a tendency to hemorrhage from various surfaces. The temperature, however, is more moderate, and does not exhibit the sudden remission of relapsing fever; the liver is usually demonstrably diminished in size; severe nervous disturbances, such as convulsions followed by stupor and then by coma, are more constant; while the occurrence of spirilla in the blood of relapsing fever and of leucin and tyrosin in the urine of acute yellow atrophy serves to distinguish completely the two diseases. Acute yellow atrophy is, moreover, invariably fatal.

With ordinary care there is but little danger that any of the local complications of relapsing fever will so absorb attention as to lead to a neglect of the specific general disease, so that the cerebral symptoms should be readily distinguished from the onset of any acute intracranial affection; the parotitis which occasionally appears early in the disease should not be confounded with idiopathic mumps; and so for other complications. There is far more danger, indeed, lest some of the complications may be overlooked; and this is especially true of pneumonia, one of the most frequent and most important of them all. Its occurrence is the cause of the supervention of grave typhoid symptoms or of the modification of the normal course of the pyrexia in so many cases that nothing but a systematic daily examination of the lungs will avert serious oversights.

MORTALITY AND PROGNOSIS.—The rate of mortality has varied in different epidemics from 2 or 3 to 24 per cent. Murchison shows that out of 2115 cases admitted to the London Fever Hospital during a period of twenty-two years, and embracing two distinct outbreaks, only 39 proved fatal, making 1.84 per cent. mortality. Adding to these the results of Scotch and Irish epidemics, a total of 18,859 cases, with 761 deaths, is reached, giving the rate of mortality for Great Britain as 4.03 per cent. The great Indian epidemics studied by Carter gave 111 deaths out of 616 cases, equal to 18.02 per cent. Recent German epidemics have given from 5 to 10 per cent. The above rates are obtained where all the cases observed during an epidemic are included. If, however, the mortality of the ordinary form of relapsing fever is computed separately from that of the bilious typhoid form, it does not exceed 2 to 5 per cent., whilst the mortality of the latter form rises to from 33 to 50 per cent., or even higher.

In the Philadelphia epidemic, out of a total of 1174 cases there were, as nearly as can be ascertained, 169 deaths, giving a rate of mortality of 14.4 per cent. Taking all the cases admitted to the hospital under our observation, many of which entered at a late period of the disease and not a few when moribund, the mortality was not less than 13 per cent. The mortality among the negroes who were attacked with the disease was considerably greater than among the whites. Finally, if the mortality of the bilious typhus form be considered separately—although from the frequency of jaundice in this epidemic and the numerous gradations of severity presented it is difficult to form a sharply defined group of this character—it was certainly not less than 50 per cent.

The date of death varies with the epidemic, the form of the disease, and the previous condition of vitality of those attacked. Ordinarily, by far the larger proportion of deaths occur during the first relapse or the second interval, but in bilious typhoid cases, presenting grave complications, especially pneumonia or severe hemorrhages at an early date, or in cases occurring in intemperate subjects, or in those previously in impaired health, the mortality is much heavier in the initial paroxysm or the first interval than at later periods.

Youth exerts the same favorable influences upon the result of relapsing fever as it does in the case of typhus and typhoid. Murchison states that of 717 male patients under twenty-five years of age admitted into the London Fever Hospital, not one died, and in most epidemics similar, though not equally marked, results have been noted. In some epidemics the mortality among young children has been considerable. As a rule, the percentage of deaths increases with each decade after thirty years.

Sex does not exert any definite or constant influence upon the mortality. The number of males affected is far greater; they are liable to be exposed to the contagion in its most concentrated form; a larger proportion of them are probably the subjects of intemperance than in the case of females; and thus most statistics agree in making the mortality somewhat greater in the male sex; but, all things being equal, there is no good reason for holding that sex itself has any value in determining the result.

As in other zymotic diseases, the mortality from relapsing fever is highest during the early period of an epidemic, and the type of the disease grows milder as the epidemic declines. Cases of the bilious typhoid form have become notably less frequent during the later stages of some epidemics than at an earlier period.

Marked difference has been observed also as to the action of remedies at different stages of epidemics, the early cases exhibiting an extraordinary resistance to remedies, and especially to anodynes, which passes away later. When typhus and relapsing fevers have prevailed together, and a clear discrimination between the two sets of cases has not been made, it has appeared that the mortality increased as the epidemic advanced, but this apparent exception has been due to the fact that at first the cases of relapsing fever were in the majority, while later those of typhus, the much more fatal disease, preponderated.

Epidemics of relapsing fever prevail at all seasons, but more commonly they are at their height during the colder months of the year. The total mortality will of course correspond, but the actual percentage is not constantly greater during any one season, although it is probable that the greater liability to chest complications during the colder months will render the disease more fatal then.

The gravity of relapsing fever has varied so greatly in different epidemics that it is very difficult to determine what influence upon the mortality has been exerted by mere difference of race. A further source of difficulty is found in estimating the differences in the physical conditions of the poorer classes in the various communities affected. The mortality has been exceptionally high in the Russian and Indian epidemics and in some of the German ones, while in the British epidemics it has uniformly been light. It is interesting to note that in the Philadelphia epidemic, where the great majority of patients were Irish or negroes, the mortality was high, over 14 per cent. The previous condition of the Irish patients must certainly have contrasted favorably with that of the individuals attacked in the Dublin and Belfast epidemics, so that the difference in result seems attributable only to a greater virulence of the disease. As an ample opportunity was here afforded to judge of the relative severity of relapsing fever in the negro and white races when the cases occurred at the same season, at the same stage of the epidemic, and in individuals living under nearly similar conditions, it may be stated that the conclusion of all who studied the question closely was that the disease was much more severe among negroes, and in particular that they displayed a greater tendency to serious complications and to the bilious typhoid form.

Although the degree and virulence of the infection undoubtedly constitute the most important elements in determining the mortality, the previous health and habits of those attacked with relapsing fever exert an influence upon the result. This is especially true of habitual intemperance, which, by disposing to disease of the liver and kidneys, greatly increases the liability to a fatal result. It has been seen (above), however, that even when acute catarrhal nephritis existed at the time of the attack severe relapsing fever might terminate favorably. Another observation which we made frequently, and which coincides with what is well known in regard to typhoid and typhus, is that improper exertion and exposure during the stage of incubation and immediately after the invasion produced a highly unfavorable effect on the subsequent course of the disease, and seemed in particular to dispose to dangerous or fatal collapse at the critical periods.

Apart from these general considerations, there are many special points to be considered in regard to the prognosis of relapsing fever:

If after the crisis of the invasion there is not rapid and decided improvement, complications should be suspected.

A sharp rebound of temperature quickly following crisis may be followed by speedy death.

Mere elevation of temperature during the invasion and the relapse, even though to an extreme height, is not attended with the danger which even a somewhat lower degree would indicate in other zymotic diseases.

Increased elevation toward the expected time of crisis should arouse anxiety, as sudden and dangerous cerebral symptoms may occur.

Prolonged duration of the pyrexia, or the substitution of irregular gradual defervescence (lysis) for the characteristic crisis often associated with typhoid symptoms as are these conditions, is significant of complications and of danger.

Wild delirium during the pyrexia, or transient active delirium about the time of crisis, is not necessarily unfavorable, but continuous low delirium, with disposition to stupor, is associated with a typhoid tendency and is frequently followed by death. Excessive muscular tremor or convulsions are highly unfavorable, but not necessarily fatal, symptoms.

Cardiac murmurs are not of serious import. The pulse is not usually as rapid in proportion to the temperature as in typhus or typhoid, and an excessively rapid pulse toward the expected time of crisis, especially if associated with feebleness of the heart's action, points to the danger of sudden collapse at or soon after that time. Previous cardiac disease, especially fatty degeneration in habitually intemperate persons, increases this danger. Continued frequency of pulse after the crisis indicates some complication or the danger of some accident.

Cough of a bronchial origin is not a specially unfavorable symptom, but if associated with the physical signs of pneumonia and with marked disturbance of respiration it indicates extreme danger.

Epistaxis, even when copious, often occurs in favorable cases, but hemorrhage from the stomach or the kidneys is usually, though not invariably, followed by death.

An eruption, measly or of pink spots, with or without minute petechiæ, is rare, and usually occurs in severe cases, but is not of specially unfavorable significance unless associated with the typhoid state or with patches of purpura.

Hiccough is a much less unfavorable symptom in relapsing fever than in typhoid or typhus, and vomiting, even frequent and persistent, may occur in cases of ordinary severity.

Enlargement of the liver and spleen indicates special risk only when persistent for some time after the relapse, in connection with persistent irregular fever. Jaundice has no necessarily unfavorable signification, is frequent in ordinary cases in some epidemics, but when it is associated with the other features of the bilious typhoid form the danger is extreme, at least 33 per cent. of such cases proving fatal.

Slight transient albuminuria may exist without special danger, but if associated with evidences of catarrhal nephritis, or if extreme diminution of urine, with or without albuminuria, exists, cerebral symptoms are apt to ensue, with a high degree of danger.

All serious complications—parotitis, erysipelas, dysentery, abortion, pneumonia, and, above all, peritonitis—greatly increase the risk.

It is not possible to determine in what cases the relapse will fail to occur. Motschutkoffsky's statement, that when a slight post-critical rise occurs a relapse will follow, must be applicable only to a limited number of cases.

In all cases at least one relapse must be expected; the patient in the interval must be regarded as still sick, and after the close of the relapse he must still be treated with rigid care until convalescence is permanently established. It must be remembered in hospital practice that many patients enter toward or after the crisis of the first paroxysm, so that caution is needed in estimating the effect of remedies and the period of the disease.

The undue prominence of certain conditions during the course of the disease is apt to be followed by corresponding sequelæ, and emaciation, anæmia, dyspepsia, diarrhoea, dysentery, enlargement of the spleen and rheumatoid pains may then be anticipated. The liability to ophthalmia and affections of the middle ear is not to be forgotten.

CAUSES OF DEATH.—In fatal cases death occurs from exhaustion dependent on the protracted and severe sufferings of the patient; from cerebral symptoms; from hyperpyrexia; from the virulence of the toxæmia; from uræmic poisoning; from sudden collapse; or from some complication, such as hemorrhagic meningitis, hemorrhages, pneumonia, dysentery, rupture of the spleen, peritonitis, or abortion.

TREATMENT.—The indications for treatment presented by regular cases of relapsing fever seem to be—to moderate the pyrexia; to relieve distressing symptoms, especially pain, insomnia, and gastric irritability; to sustain the strength of the system; to prevent or modify the relapses; and to avoid complications and sequelæ.

It is needless to observe that until the nature of the specific cause of relapsing fever is fully determined, whether the spirillum occupy that relation or not, it is impossible to direct our efforts rationally toward its neutralization or elimination. The various remedies which have been employed for these special purposes have no clinical support to recommend them. And while experiment has shown that the activity of the spirillum is readily destroyed by the direct action of various weak solutions, as of quinine, carbolic acid, iodine, and mineral acids, no special curative effect follows the internal administration of these remedies, even in the largest doses consistent with safety. In fact, there can scarcely be any disease in which treatment is less satisfactory or its results more difficult to estimate. The marked difference between various epidemics, and the wide variation presented by the development of individual symptoms in different cases of the same epidemic, fully account for this.

Quinine, as might be expected, has been largely used, in the hope that it might control the pyrexia or prevent the relapse. Murchison³⁹ quotes a considerable amount of evidence from various sources to show that it does not possess either of these powers. It was administered to a considerable number of our cases, either in small and frequently repeated doses during the pyrexia or the intermission, or else in large doses repeated several times in immediate anticipation of the expected time of the relapse. Thus in some cases three grains of sulphate of quinia were given every two or three hours until tinnitus was produced, and then this was maintained during the remainder of the pyrexia and of the intermission. The amount given daily was from thirty to forty-two grains. It seemed to rather increase the discomfort in the head, and in some cases it aggravated the irritability of the stomach. The pyrexia was certainly not controlled by it. Given in the same manner during the intermission, it was usually well borne, but was not effectual in preventing the relapse. It is true that in some cases the subsequent relapse seemed to be somewhat modified.

³⁹ Op. cit., p. 408.

Thus in one case 30 grains were given on the 6th of April; 39 grains on the 7th; 39 grains on the 8th; 42 grains on the 9th; and 60 grains on the 10th; the critical fall had occurred during the night of the 7th, and the relapse began on the evening of the 9th, but the rise in temperature was less abrupt than usual, and the relapse lasted less than five days. It was quite severe, however, so that it is doubtful whether the apparent modification was anything more than is frequently observed in cases where no quinine has been administered.

In another case the fall in temperature at the end of the first paroxysm was from 105.5° to 97° on March 26th: 35 to 40 grains of sulphate of quinine were given daily on April 4th, 5th, 6th, 7th, and 8th; the temperature began to rise on the 3d, but the severe pyrexia and the usual symptoms of the relapse were limited to a period of less than thirty-six hours. This is a less common irregularity, and yet does not afford sufficient evidence of the efficiency of quinine. In other cases, however, as already stated, no appreciable effect followed its administration in this manner.

To illustrate the other method of giving quinia, a case may be quoted in which 20-grain doses every three or four hours were given from April 25th to April 29th, so that in four days 575 grains were taken. The initial paroxysm was of average severity, and terminated at the end of the seventh day, April 20th. The quinine did not postpone the relapse, which occurred on April 28th, but was of much less than the usual duration.

In no other case in which these large doses were given was there even as much reason as in the above instance to attribute to quinine any positive influence upon the course of the disease.

In order to demonstrate that the failure of quinine was not dependent upon a want of absorption, Muirhead injected large amounts subcutaneously with no better results.

In conclusion, it may be said that the evidence shows positively that quinine possesses no specific influence whatever upon relapsing fever; that in only occasional cases, if at all, will even enormous doses given during the intermission postpone or modify the subsequent relapse; and that it is not effective in reducing the temperature. In view, therefore, of the usual gastric irritability and tendency to vertigo and headache, which seem to be increased by large doses of quinine, and, further, in view of the small mortality, and of the fact that when death occurs it usually comes from causes over which large doses of quinine could exert no influence, it seems clear that this drug should be prescribed only in tonic doses and only in cases where it is well tolerated by the stomach.

Arsenic was used in a considerable number of our cases with the view of determining if it possessed any power of relieving the severe pains or of influencing the relapse. It was administered in the form of Fowler's solution (Liq. potassii arsenitis), and was given exclusively by the mouth. If given during the intermission, it was well borne in doses of five to ten drops every four or even every three hours, given freely diluted with water and immediately after food. In several cases it quickly induced puffiness about the eyes, but no effect whatever was produced on the pains or on the succeeding relapse. In more than one such case there was an unusually profuse crop of sudamina during the relapse, many of the vesicles breaking and being followed by brownish stains. When given during the pyrexia it aggravated the nausea and vomiting, so that it had to be suspended. In one unfortunate case, indeed, although promptly suspended, the arsenical solution seemed to have assisted in the establishment of vomiting and purging, which proved uncontrollable and contributed greatly to the fatal result. Hypodermic injections of arsenic have been used considerably with no better results. There seems, therefore, to be no reason whatever for any further use of this drug in relapsing fever.

The high pyrexia and the severe rheumatoid pains have naturally suggested the use of salicylic acid and the salicylate of soda. We were not sufficiently aware of their antipyretic properties in 1869-70 to have recourse to them, but in more recent epidemics Unterburger⁴⁰ and Riess⁴¹ have found that large doses of the latter substance (one hundred grains or more daily) will reduce the temperature either in the initial paroxysm or in the relapse, but that the disease is not cut short nor are the lesions of the blood or solids prevented.

⁴⁰ Jahrb. f. Kinderheilk., v. x., 1876.

⁴¹ Deutsch. Med. Wochnsch., Dec., 1879.

It must be borne in mind here, as in connection with the action of quinine, that apparent modifications of the relapse are to be viewed with great distrust, since such great irregularities therein naturally present themselves. Care must further be taken lest such attempts to reduce the temperature aggravate the irritation of the stomach, and by lessening the power of taking food induce more serious exhaustion than would have resulted from the unchecked pyrexia. The evidence in our possession is not sufficient to justify a positive decision as to the therapeutic value of the salicylates in relapsing fever, but, apparently, they are applicable to only a portion of the cases, and in these are of but limited utility.

The same failure which has followed the use of quinine, of arsenic, and of salicin and the salicylates has attended the effort to prevent the relapse by berberine, benzoate of soda, tincture of eucalyptus, and other reputed antiperiodics.

Digitalis, veratrum viride, and aconite were used by us quite freely as antipyretics. The first two of these were often suspended on account of the irritability of the stomach, and no valuable results followed their use when well tolerated. Aconite in small doses, frequently repeated, as one drop every two hours, seemed to aid in allaying nausea and to exert some slight influence upon the fever. In cases where there was a distinct tendency to heart-failure, digitalis was given freely with advantage.

Cold baths were not used to reduce the temperature in any of the cases under our observation. They have been employed in other epidemics, but, as far as we know, with no other effect than to cause merely temporary lowering of temperature, without any decided relief to the other symptoms and without any apparent influence upon the course of the disease. Frequent spongings with cool water and the application of ice to the head gave only slight and temporary relief.

Simple febrifuge remedies, such as effervescing draught or spirit of nitrous ether with solution of acetate of ammonium, were well received by the stomach, and appeared to promote perspiration and the more free secretion of urine.

Finding all our efforts to control the pyrexia so unsuccessful, recourse was had in a large proportion of our cases to the hyposulphite of soda, given, dissolved in two ounces of water, in doses of twenty grains every two or three hours. In two cases it seemed to increase nausea, and at times it caused some purging, but otherwise it was well borne by the stomach, and, indeed, frequently appeared to aid in controlling vomiting. The records show that this drug was given in only two or three of the fatal cases, so that although the patients who took it regularly presented every grade of severity of the disease, they did well uniformly. It is certain, however, that the hyposulphite of soda exerted no specific effect upon the disease; it did not reduce temperature, it did not prevent or modify the relapses nor relieve the severe pains; it may have promoted more free and healthy secretions, and, by tending to prevent vomiting, may have aided in maintaining nutrition; but, on the whole, it may fairly be doubted whether this remedy merits any more extended trial.

One chief reason of the failure of antipyretics in relapsing fever is to be found in the existence of widespread irritative lesions of the glandular and mucous tissues, which combine with the specific blood-changes in causing and maintaining the high temperature. It is not surprising, therefore, that the remedies which afford the greatest relief in this disease are opiates and sedatives to the gastro-intestinal mucous membrane. Opium, or morphia, must indeed be regarded as the basis of the rational treatment of relapsing fever. It is called for by the insomnia, the severe headache and the pains in various parts of the body, the nausea and vomiting, and the pyrexia. It does not appear to have been as prominent a feature in the treatment of other epidemics as we found it necessary to make it in Philadelphia. Parry⁴² used it very freely, chiefly in the form of opium, by the mouth, and found a singular tolerance exhibited by his patients, several of whom took as large a dose as three grains every two hours during the afternoon and night without producing any sleep or even any contraction of the pupils. This resistance to the action of opium was observed chiefly in the early part of the epidemic, and we may add that it was exhibited chiefly when opium was given by the mouth. When morphia was used hypodermically we found that one-fourth of a grain, given at intervals of six to twelve hours, afforded very great relief to the pains, aided and relieved vomiting, and often induced quiet, refreshing sleep. Its use was not contraindicated by jaundice, by cough or pulmonary congestion, or by moderate contraction of the pupils. It was frequently given so as to maintain decided drowsiness throughout the pyrexia. When the pains persisted during the intermission the morphia was continued in smaller doses or at longer intervals. It occasionally happened that when patients were thus kept continuously under opium influence no relapse occurred; but here, as in regard to the action of quinine, it may safely be asserted either that what was regarded as the initial paroxysm was in reality the relapse, or else that the absence of a relapse was a mere irregularity, and in no way to be attributed to the action of the opium. On the other hand, in cases presenting a tendency to the typhoid state, with a disposition to stupor, or where the urine was scanty and albuminous, no opiate was administered.

⁴² Loc. cit.

We have already stated that in our cases quinine in acid solution was frequently ordered, and it answered very well to add to each dose of this a suitable amount of morphia.

Atropia, in the dose of gr. 1/60 to gr. 1/40, was usually associated with the hypodermic injections of morphia. This was done particularly in cases where the pains were very severe, when the pupils were disposed to be contracted, or when there was continued profuse sweating. In addition to this, atropia was continued without morphia during the intermission in a few cases. The patients proved susceptible to its influence, and dryness of the mouth with dilatation of the pupils was readily produced by gr. 1/60 every six hours. In one case gr. 1/40 every four hours for two days caused delirium, with the usual symptoms of belladonna action, all of which passed away quickly after withdrawal of the drug. But in none of these cases was the relapse influenced in the least.

Other remedies may be used for the relief of the insomnia, which is always one of the most distressing symptoms. Chloral and bromide of potassium have been found serviceable in various epidemics, and some observers have preferred them to opium for the relief of headache and insomnia. They did not prove reliable in the Philadelphia epidemic of 1869-70. Bromide of potassium, even in large doses, produced scarcely any effect, and, while in a few cases chloral in doses of gr. xx. gave positive relief, in the majority of instances 40 grains failed to cause sleep or relieve suffering. It must not be forgotten also that, as there is a special tendency to cardiac failure in this affection, the action of chloral must be closely watched.

In a small series of our cases where muscular pains, hyperæsthesia, and twitching were marked succus conii was given quite freely, but without any apparent benefit.

The condition of the stomach required attention in almost every case. Nausea, vomiting, and epigastric and hypochondriac soreness were the prominent symptoms. Anorexia was usually complete during pyrexia, and not rarely patients were admitted to the hospital who asserted that for one or more days they had not taken any nourishment whatever. Under such circumstances, and in a disease where the tendency to prostration and cardiac failure calls for stimulants and food, it is evident that strict care must be given to the diet. In many cases skimmed milk with lime-water, meat broths, arrowroot, or gruel, could be taken in small amounts at short intervals, and retained. But whenever these are rejected, no attempt should be made to persist in their use, but koumiss, whey, or chicken-water should be substituted, and continued until the stomach grows retentive. Equal care must be paid to the selection of a suitable form of stimulus. It may be proper to employ a mild and relaxing emetic if the patient be seen at the onset of the disease and if there is reason to suspect the presence of indigested food in the stomach, but under any other circumstances there seems no reason for its use in a disease where vomiting is so common and gastric irritability one of the most troublesome symptoms. Nor should purgatives be given save when very positive indications exist for their use.

Constipation is rarely obstinate; the amount of nourishment taken is very small; in a considerable proportion of cases there is diarrhoea, or at least a sensitive state of the bowels; and as a consequence it is preferable in nearly every case to dispense with laxatives entirely, and, if the bowels must be opened by assistance, to administer a simple enema.

When irritability of the stomach is marked, benefit may be derived from very small doses of calomel frequently repeated, as, for example, gr. 1/8 or 1/4 every one or two hours. Subnitrate of bismuth may be used in combination with this or as a substitute for it. In several instances more prompt relief was obtained from nitrate of silver given in the dose of gr. 1/12 every three or four hours, dissolved in thin mucilage of acacia.

Stimulants were remarkably well borne, and their administration in such form as was acceptable to the stomach was clearly of service, even from an early period of the disease. As a rule, whiskey was employed, given in the form of milk punch. By carefully graduating the amount of alcohol, and when necessary diluting the milk freely with lime-water, the stomach usually received it well. If circumstances favored, dry champagne, or brandy or sherry in carbonated water would often prove preferable. The exhausting nature of the disease, the marked tendency to cardiac failure, and the inability to digest an adequate amount of nourishment, all indicate the early use of stimulants. In cases where a tendency to the development of the typhoid state existed alcohol was freely given, even to the extent of sixteen ounces of whiskey in twenty-four hours. Other stimulants were usually given in these cases, such as carbonate of ammonium, especially if pulmonary congestion existed; turpentine, especially if tympany was marked; or Hoffmann's anodyne or spirit of chloroform, if muscular twitchings, hiccough, or insomnia with wandering delirium were prominent symptoms. In all cases of severity the use of tonics and stimulants should be maintained in reduced doses during the intermission and for some days after the final fall of temperature.

It remains to allude briefly to certain special remedies and to certain symptoms requiring special treatment. Formerly, much diversity of opinion existed as to the propriety of venesection or local depletion in relapsing fever, but Murchison concluded, after a careful examination of the evidence, that it had not been shown to be of service; and certainly the disease as it occurred in Philadelphia in 1869-70 presented no indication whatever for even the mildest depletory measures. This corresponds with the recognized plan of treatment in all the specific fevers.

Blisters are not so objectionable in relapsing fever as in either typhus or typhoid, and there are several conditions in which they have been found decidedly useful. In cases where the headache has obstinately resisted cold applications, bromide of potassium, and opiates, a blister to the back of the neck has afforded marked relief, with no unfavorable result. Again, in cases where the vomiting and epigastric distress were severe and obstinate the application of a blister three inches square to the epigastrium is to be recommended.

Chloroform has proved of value for the relief of various symptoms in relapsing fever. As already stated, it was found the most useful remedy for the hiccough which was so troublesome in a number of our cases, and especially in those where jaundice was pronounced. It also seemed serviceable in controlling the peculiar chills which in varying degrees of severity were present in a few cases, recurring at about the same hour on successive days. These rigors or chills were uninfluenced by very large doses of quinine or other antiperiodics, but were apparently controlled by full doses of chloroform given in advance of the expected hour of recurrence.

Jaundice, which, as has been stated, is partly of hæmic origin, but is probably also due in part to obstruction from catarrhal swelling of the mucous membrane of the bile-ducts, is not influenced by mineral acids, and still less should mercurials or purgatives be administered for its relief. It would seem proper, in cases where this symptom is marked, to observe special care in diet and the use of stimulants, and to employ local sedative astringents, such as small doses of nitrate of silver combined with opium and belladonna.

Muscular soreness, pains, and tremor may call for special treatment on account of their severity. The only remedy which has proved useful in relieving the first two of these symptoms is opium, conjoined with the external use of anodynes. Iodide of potassium fails even in doses as large as can be borne, and the same is true of muriate of ammonium and cimicifuga, which we used thoroughly without any effect. In the muscular pains, however, which torment the patient during convalescence, the ammoniated tincture of guaiacum was found of service. Atropia hypodermically and chloroform internally have been found useful for the relief of severe muscular twitchings.

Upon the whole, therefore, it will be seen that in ordinary cases a supporting and expectant plan of treatment is all that is required. Abandoning the idea of forcibly controlling the fever or of preventing the relapse, care should be given in the first place to the diet and to judicious stimulation.