with colon bacillus and streptococcus. There is rapid infiltration of the wall of the gall bladder with exudate and infective thromboses of the veins. This leads to a necrosis. At the same time there is an extensive involvement of the peritoneum, as shown by the mass of organized lymph surrounding the gall bladder.

Dr. Ransohoff mentions a case of rupture of the common bile duct as a consequence of gangrene of the wall, followed by a peculiar sign to which attention had never been called before; there was a localized jaundice affecting the area of the navel only. At the operation bile was found staining the peritoneal fat. He considered that this jaundice was the result of inhibition. It makes itself manifest first in the integument of the navel, as this part is thinner than the rest of the abdominal wall. He remarks that total gangrene of the gall bladder has not as yet been observed, except in the case he presents, as an affection independent of gallstones, and he considers total gangrene of the gall bladder a very rare condition. Czerny ascribes gangrene of the gall bladder to pressure on the cystic artery, which, except for a very insignificant anastomosis along the attached surface of the gall bladder, is practically an end artery. In Czerny's case the gangrene was limited to the mucosa of the gall bladder; in Ferguson's case most of the gall bladder came away as a slough five weeks after the operation.

When this subject was discussed in New York after the presentation of Dr. Hotchkiss' paper in 1894, Dr. Gerster said that he had never had an opportunity of observing a case of gangrenous empyema of the gall bladder. Dr. McBurney said he had operated a number of times on the gall bladder and had never yet seen a case of gangrene. He had met with many cases of gangrenous inflammation of the vermiform appendix. contrasts the two organs and says that while one is frequently gangrenous the other is very infrequently so. He suggests as an explanation the toughness and non-vascularity of the gall bladder walls in contradistinction to the soft and vascular walls of the appendix, the vessels of which become rapidly plugged with bacteria. As an active feature in each case we have the interference with drainage.

In the same discussion Dr. Abbe stated he had seen a case of acute phlegmonous inflammation of the gall bladder, and when he operated he found that the mucous membrane, the cellular tissue and the peritoneal layer of the gall bladder slipped up and down upon each other so as to be readily dif

ferentiated. He thought there was less tendency to gangrene. from interference with the arterial supply in the gall bladder than in the appendix. In the case mentioned by Dr. Hotchkiss a circular constriction had taken place that was evidently sufficient to choke off the blood supply from the extremity of the viscus. He thought it unwise to burden the nomenclature of liver surgery with the name "gangrenous inflammation." With an experience of five cases, I am of the opinion that the disease is a distinct and definite one, accompanied by very distinct and definite symptoms. The condition has been diagnosed by more than one observer.

Mayo Robson considers gangrene of the gall bladder as only an extreme degree of phlegmonous cholecystitis. In the Museum of Guy's Hospital he found a well-marked specimen of the condition, and, later, reported a case of his own.

Symptoms. I find that the symptoms of the disease are of a very marked type. The patient, perhaps in the midst of health, is seized with sudden acute pain in the right hypochondrium, which may be so severe as to cause collapse, faintness and prostration. The constitutional disturbance is very alarming. The most peculiar symptom I have observed is the condition of the pulse, the rate of which varies very quickly from 70 beats to the minute to 130 to 140 to the minute, when it becomes feeble and running, and is accompanied by lividity of the face, blueness of the hands and feet, and the body surfaces become cold, clammy and covered with sweat. There is always an elevation of temperature and sometimes a rigor. When such a condition present and a mass is found in the right hypochondrium, beneath the edge of the liver, extremely sensitive to the touch, we are justified in diagnosing gangrenous cholecystitis, and immediate operation is indicated. By early operation and open drainage I have been able to save 100 per cent. of my cases.

A DEPARTMENT OF INOCULATION AND

IMMUNIZATION.

BY DR. J. N. E. BROWN,

Superintendent Toronto General Hospital.

GENESIS OF THE DEPARTMENT.

The reason the Toronto General Hospital was fortunate in being able to undertake the work of an inoculation department so soon after the discovery of opsonins was due to the fact that when the discoverer, Sir Almroth Wright, visited America the authorities of the Toronto General Hospital enjoyed the privilege of listening to him speak of his work. In this address at the hospital he advised us to undertake the work and to secure the services of Dr. Ross, one of our own students and internes, who had spent nine months in the laboratory in St. Mary's Hospital, London, working at the new therapy with him, and who was about to practice his profession in our city.

The services of Dr. Ross were secured, the board agreeing to pay a salary of $1,000 per year. To fit him up a laboratory, one room, about 24x15, equip it with the necessary apparatus and the first quantity of the necessary stains, etc., cost $826. The work has now been carried on most enthusiastically for a period of five months, though for some months previously the opsonic work had been carried on to a limited extent by our resident pathologist, who had received some instruction in the subject some months before.

St. Mary's Hospital of London, the one in which Sir Almroth Wright works, was the first institution to give assistance to this new means of diagnosis and therapy. The London Hospital was second, and, as far as I know, the Toronto General Hospital was third.

THE RATIONALE OF THE ACTION OF OPSONINS.

Wright found that when he mixed healthy washed white blood corpuscles with a pure culture of some micro-organism, such as the staphylococci (the causative agent in boils), no phagocytosis took place, but upon the addition of blood serum the white blood corpuscles would gobble up the micro-organisms. It was then quite patent that something in the blood serum either first

stimulated the white cells to greater activity in the ingestion of the germs, or that something in the blood serum acted in such a way upon the microbes as to make them more palatable to the white blood corpuscles. He found that the latter was the case by another experiment. He incubated the micro-organisms with blood serum, after which he washed free every trace of the serum. Washed white corpuscles were then added to the microorganisms. These they engulfed with avidity.

This substance, which added such piquancy to the microorganisms that the white blood corpuscles devoured them, Wright called an "opsonin" (from the Latin word "opsono" I prepare a feast for). As he found that for each of the several micro-organisms infecting the human system and causing disease, there was a corresponding something in the blood which tended to make them palatable to the white cells, he came to the obvious conclusion that there was an opsonin in the blood to correspond with each micro-organism which had become peccant in the human system. Hence the plural form, "opsonins."

While speaking of this I may point out that in Wright's work, and also in Dr. Ross', numerous cases have presented themselves where a mixed infection was present. For example, a patient would present himself, suffering from a tubercular lesion, in which a secondary infection had occurred, due to the staphylococcus, the streptococcus or some other organism; all of which infections in succession called for such treatment as would bring about an increase in opsonins to combat their particular invasions.

METHOD OF EXAMINING THE BLOOD OF PATIENT.

A patient, suffering from furunculosis (boils) is brought to the laboratory for treatment. A sample of his blood from the vicinity of the lesion is examined; and the micro-organisms, staphylococci, are found. The next step consists in taking a measured quantity of white blood corpuscles, an equal quantity of an emulsion of these living staphylococci and an equal portion of the patient's serum. These are collected in an instrument like this (instrument shown) in this way (demonstration). These three substances are then thoroughly mixed together and incubated fifteen minutes, preferably in a special incubator made for the purpose. While this incubation is taking place, a second experiment is going on which consists in taking white blood corpuscles, as in the previous experiment, the same quantity of staphylococci as in the previous experiment,

and an equal portion of the serum of a normal individual. These are mixed together and incubated fifteen minutes. A smear of the first incubated mixture is then taken and examined under the microscope, stained, and the number of staphylococci in each of fifty or more white corpuscles are counted. Suppose there be found 250-that is 5 germs in each blood corpuscle. A similar procedure is taken with the second incubated mixture, which contains the normal serum. In this case the number of germs in the 50 corpuscles will be, say, 500-that is, 10 germs ingested by each white corpuscle. From these two experiments the investigator concludes that the patient's power of battling with these particular micro-organisms is only one-half of what it should be, and decides, to say in inoculation parlance, that the patient's opsonic index is one-half or .5. This index is taken from time to time during the course of treatment, and is an indication of the progress the patient is making.

TREATMENT.

The treatment of these bacterial diseases, whether due to the staphylococcus, streptococcus, gonococcus, the tubercle bacillus or some other micro-organism, consists in making a vaccine of the organism which has caused the disease. The technique of this I will not describe, but will simply say that the vaccine is made up of devitalized (dead) micro-organisms suspended in the form of an emulsion in salt solution. To see that the vaccine is perfectly safe to administer, some of it is put in a suitable medium, and if there are no signs of growth we may conclude that it is safe to inoculate the patient. To make assurance doubly sure, a guinea pig may be inoculated with the vaccine; if he survive the vaccine may be pronounced safe to administer to the patient.

A certain measured dose of a standardized emulsion is giventhat is to say, an approximate number of dead micro-organisms are injected hypodermically into the system, say 2,000,000 to 200,000,000, depending on circumstances. The number of these in any given emulsion may be counted by means of making a comparative count of the number of these micro-organisms which are found in association with a certain number of counted red blood corpuscles present in a cubic millimetre.

As a rule, immediately following the injection, the patient's opsonic index becomes lowered, but, succeeding this negative phase, the index steadily rises, passes its old mark and exceeds the opsonic index of the normal individual. This upward movement is termed the positive phase. Subsequent to this, from

*Chart shown.

*