affected. Lesions have been found in the esophagus, stomach, vermiform appendix, and not infrequently in the large intestine.

For convenience of description the inflammatory changes may be divided into four stages, each lasting about a week: (1) The stage of infiltration; (2) the stage of necrosis; (3) the stage of ulceration; (4) the stage of healing.

The first stage, that of infiltration, may involve the whole or a part of the Peyer's patch. It is elevated, indurated, and of a gray color. Hyperemia may be noted around the infiltrated area. The surface of the infiltrated area is often irregular and contains darker areas, and is sometimes spoken of as the "shaven-beard" appearance.

The swelling of the Peyer's patch is due to the inflammatory exudate. The area contains numerous polynuclear leukocytes and round cells, many of which result from the proliferation of the fixed connective-tissue elements. There may be some red cells in the perivascular tissues, and the bacillus typhosus is also present. The blood-vessels show marked dilatation.

The infiltrated area rarely extends deeper than the muscular coat; in some instances, however, this is involved. The solitary lymph-follicles frequently reveal similar changes.

The second stage, that of necrosis, is due to the cutting off of the blood supply to the involved area, and the action of a specific poison. As the necrotic substance is discharged the

ulcer is formed, giving rise to the next stage. The necrotic process sometimes involves the walls of the blood-vessels, and when the necrosed area is discharged, hemorrhage is produced. The hemorrhage may be either open or concealed. If the ulceration be deep and the influence of the toxins upon the muscular coat of the bowel be pronounced, paralysis of the coats may take place; this is often the cause of concealed hemorrhage.

In the third stage, that of ulceration, the ulcer more or less conforms to the Peyer's patch. It is oval or circular in outline, the greater diameter being in the long axis of the intestine, opposite the mesenteric attachment. The floor is usually smooth, and formed by the muscular coat. Sometimes it is roughened, as necrotic tissue still adheres to the floor.

The edges may be somewhat overhanging and elevated. The great resistance of the muscularis mucosæ to the action of irritants gives rise to the overhanging character. The process may extend deeper, so that the muscular coat becomes necrotic; or in some cases the peritoneum may form the floor of the ulcer, and this may be involved, giving rise to perforation, which may be either circular or oval (punched out), the size varying from that of a small opening to two centimeters in diameter.

The perforation may be a slit-like opening, and results from the action of a peristaltic wave upon a scybalous mass lodging in the ulcerated area, the bowel becoming tense and the inelastic floor of the ulcer rupturing. When perforation occurs, the peritoneum invariably becomes inflamed, general peritonitis and death often following. If adhesions of neighboring coils of intestines are formed, a localized process results: frequently an abscess.

The fourth stage, that of healing or cicatrization, follows the stage of ulceration. Granulation tissue is formed, and finally the fully developed fibrous tissue, over which the epithelium ultimately spreads. The scar is smooth. It may be somewhat depressed, but does not show marked tendency of contraction; therefore, strictures of the bowel are almost unheard of in this disease.

The mesenteric glands are enlarged in all cases of enteric fever. They are soft and friable, and rarely ulcerate. The spleen is enlarged in about 90% of the cases. The capsule is tense, and the splenic pulp is soft and friable; in rare instances rupture has been found.

Granular degeneration of the voluntary and involuntary muscles of the internal organs, especially of the heart, is present. Hyaline degeneration of blood-vessels has been noted. Catarrhal inflammation of the gastro-intestinal mucous membrane occurs.

The specific organism has been found in the feces (rarely before from the tenth to the sixteenth day), in the urine, in the spleen, and in other internal organs.

The constitutional manifestations are due largely to the typhotoxins.

Period of Incubation.-This is from two to three weeks. Symptoms. The onset of the disease is insidious, and is preceded by prodromes, these consisting of malaise, vague pains in the limbs and back, headache, epistaxis, and slight evening fever. These symptoms continue until the patient is compelled to remain in bed. Diarrhea may be present, or may be easily invoked by a mild laxative. It is convenient to divide the symptomatology into periods of weeks, corresponding to the pathologic changes.

First Week. At the end of the period of prodromes, which may be variable, the disease may be ushered in by chilliness or, rarely, by a distinct rigor. The pupils are dilated, appetite is lost, and the tongue is covered by a dry, white fur, and its edges and tip are red. Diarrhea continues; headache is increased, especially at night; the pulse is frequent, and its volume is good, but later it becomes dicrotic. The temperature is characterized by a gradual rise, being higher each evening by about a degree and a half, until the fifth or seventh day, when the fastigium is reached.

Toward the end of the week some tympanites occurs, and at this time a few scattered rales may be heard posteriorly over the chest. There is usually pallor of the face, with flushing of cheeks. The urine shows the changes of febrile conditions. At the end of the first week the spleen is perhaps slightly enlarged, and the characteristic eruption may be noticed.

Second Week.-The symptoms just described now become aggravated, with the exception of headache, which commonly disappears. The eruption, if not previously noticeable, now shows itself, perhaps on the abdomen, chest, or back, but rarely appears upon the extremities, and exceptionally upon the face. It consists of slightly elevated, rose-colored spots, from one to four millimeters in diameter, disappearing on

pressure, and reappearing when the pressure is relaxed. They appear in successive crops, which last from two to three days. The spleen is now found to be enlarged; the fever high and subcontinuous in type; the pulse weaker, from 90 to 120, and dicrotic. Occasionally, the hearing is dull. There may be low, muttering delirium. The intestinal symptoms are more pronounced than during the first week. In favorable cases defervescence may set in.

Third Week.-The symptoms become more severe; asthenia and emaciation are pronounced; fresh crops of the eruption may appear. At this time, which corresponds to the stage of ulceration, such complications as hemorrhage and perforation may be noticed. The temperature-curve becomes remittent in type; the pulse is feeble, and the first sound of the heart may be inaudible. Among the symptoms are excessive sweating and sudamina; dry and coated tongue, with brownish fur upon it; collection of sordes upon the teeth; and probably involuntary evacuation of urine and feces. The delirium now becomes more marked and perhaps violent in character, or there may be stupor, coma, carphology, or subsultus tendinum.

Fourth Week.-The symptoms ameliorate, the temperature becoming intermittent and the sordes disappearing as the tongue clears and the spleen contracts to its normal size. The urine increases in amount, and if there has been presence of albumin, this disappears. The mind clears, and great hunger develops. Convalescence is protracted, but may be interrupted by complications, relapses, and sequels.

The temperature during convalescence is very unstable, running a subnormal course; recrudescences may occur through constipation, excitement, improper food, etc.

Special Symptoms.-Temperature. The temperature rises, gradually reaching its fastigium in from five to seven days. During the second week the course of the temperature is subcontinuous, falling each morning a degree or a degree. and a half, and rising each evening to the same height as on the previous evening. This continues another week. During the third week there are greater remissions in the morning, the temperature assuming a decided remittent type until the fourth week, when it falls to or below the normal, giving an intermittent type. During convalescence the temperature is frequently subnormal, being labile and easily disturbed. Indiscretions in diet, visits of friends, excitement, mental emotions,

and constipation frequently produce a rise, called a recrudescence.

Departure from the type may occur. There may be a sudden rise at the onset, beginning with a chill, running a brief course, and ending by crisis. This is known as the abortive form, and takes place particularly in the enteric fever of children, showing a decided remittent range, thus giving rise to one of the synonyms called "infantile remittent fever." It is common for the typical curve to be interrupted by intercurrent diseases or complications. Hyperpyrexia, called the pre

agonistic rise, occasionally occurs, especially in fatal cases, just before death. The fever-curve of relapse corresponds to the original attack, but the fastigium is more quickly reached, defervescence taking place sooner.

Circulatory System.-As is usual in febrile diseases, the pulse frequency corresponds to the intensity of the fever, although this disease is one of relatively slow pulse. At the onset the pulse is of full volume and the tension is low, and soon in the process of the disease becomes dicrotic; this is an important diagnostic phenomenon in enteric fever. The pulse