fall in the opsonin to X, the "negative phase." This is followed by a rise to B. After a day or so we give another inoculation, and we get another negative and positive phase. By proper dosage we may be able to raise the index to 1.2 or 1.4-in rare cases even as high as 2.0. As the opsonin falls the patient gets worse, but as it rises he gets better,

" 2

3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 DAYS OF

MONTH

and if we can keep it above 1.0 for a time he will probably get well. The reason that it is necessary to measure the opsonin is this: Should we inoculate a patient during the negative phase, there will be a further fall in the opsonin, or if we give too large a dose the negative phase will be unduly prolonged. This is probably one reason why tuberculin had such a bad effect in the hands of those who first used it. Too much was given at improper intervals, so that there was a cumulation in the direction of the negative phase. When we give too small a dose, we may get no negative and consequently no positive phase, so we have to give the right dose and at the right time. The initial dose can only be determined by trial, but we start with the dose sufficient to give the least negative phase, and reinoculate only when the postive phase begins to diminish.

I will quote a case reported by Wright and Douglas:

The patient was a man who had suffered from boils almost continuously for four years. His opsonic index was 0.6 to staphylococci on the first examination, and 1.1 on the second. He was inoculated with 2,000,000,000 dead staphylococci. On the day after, the opsonins fell to 0.78, negative phase. From this point there was a steady rise. in opsonic power until the original level 1.I was reached a week later. A few days later the index was 1.4, the positive phase. While the

opsonic power was still high another inoculation was given which resulted in, first a negative phase, then a rapid rise for a day or two until the index was 2.0 or twice normal. The clinical result was eminently satisfactory. After several weeks of treatment the boils completely disappeared.

It can be seen, then, that it is of the utmost importance in inoculation to measure the opsonin, for it is only in this way that we can tell the effect of a vaccine and when it is safe to reinoculate. It is believed that the reason why localized infections do not get well of themselves is because insufficient amounts of the bacterial substances are absorbed to cause a rise in opsonic power.

TREATMENT OF TUBERCULOSIS.

For our purpose we divide tuberculous cases into two classes: (1) Those in which the infection is strictly localized, such as lupus, tubercular glands, tuberculosis of subcutaneous tissues, et cetera.

(2) Those which are systemic, as, for example, are most cases of pulmonary tuberculosis-excepting, of course, certain cases of early or quiescent phthisis. The average index to tubercle bacilli in a large series of supposedly healthy persons varies between 0.8 and 1.2. In the class of strictly localized infections the index is almost uniformly low. In cases of lupus the index may be as low as 0.1. This low index is supposed by Wright to antedate the infection and to be the cause. and not the result of such infection. In these cases the vaccine used is Koch's new tuberculin, which is in all respects similar to the other bacterial vaccines, consisting as it does of the finely pulverized bodies of tubercle bacilli.

Many cases of lupus, tubercular cystitis, tubercular glands, et cetera, have been reported as cured or benefitted by the inoculation of tuberculin controlled by the estimation of the opsonic index. The train of events following an inoculation is in all respects similar to that described above. There is the negative followed by the positive phase, just as above. Great care must be taken in the treatment with tuberculin not to reinoculate during the negative phase, and the inoculations have to be given at longer intervals than in the case of staphylococcus vaccine, for the increase in opsonic power is maintained over a much longer period. Wright advises as an initial dose 1-1000 milligram of tuberculin powder and subsequent reinoculation with a slightly larger dose only when the positive phase begins to diminish.

The treatment of active pulmonary tuberculosis is very dangerous, for such a person is constantly absorbing tuberculin from the site of infection. It is for this reason that we find the index fluctuating in these cases. One day it may be 0.4, several days later 1.3, and again the next day as low as 0.6. Since we cannot regulate the amount of tuberculin thus absorbed we cannot estimate our dosage. Wright has suggested that such patients be put to bed until the tuberculo-opsonic index gets to one point and stays there-then one may begin treatment with tuberculin.

DIAGNOSIS.

That the estimation of the opsonic index might be a help in diagnosis is evident, and certain claims have been made for it. I shall not have time to go into this in detail, but one point I wish to refer to. The opsonin in various fluids of the body varies to a certain extent. In tuberculous peritonitis we find that the blood serum contains more opsonin than the ascitic fluid, and the same is true in regard to the chest-serum in cases of tuberculous pleurisy. It has less opsonin than the blood serum of that patient. The conclusion is, that the bacteria growing in a certain focus use up the opsonin in this fluid. Hence the fact that operation so often cures tubercular peritonitis, owing to the fact that the old serum or ascitic fluid low in opsonic power is drawn off and a new fluid richer in opsonin is poured out. By these means some rather remarkable diagnoses have been made. I am sorry that I cannot go more deeply into this part of the subject, but that finally we shall have an aid to diagnosis in the estimation of the opsonic index I do not doubt.

I shall close by quoting from Doctor George W. Ross, of London, a list of bacterial infections that have been successfully treated by opsonic methods. The cases have been reported for the most part by men who are in all respects reliable, and some results claimed are almost marvellous.

BACTERIOLOGICAL CLASSIFICATION.

A.-DUE TO STAPHYLOCOCCUS PYOGENES:

(1) Furunculosis.

(2) Pustular acne.

(3) Sycosis.

B.-DUE TO PNEUMOCOCCUS :

(1) Empyema.

(2) Cystitis.

(3) Suppuration of the antrum.

C.-DUE TO COLON BACILLUS :

(1) Cystitis.

(2) Various local infections.

(3) Sinusitis after gall-bladder operations.

D.-DUE TO GONOCOCCUS:

(1) Gleet.

(2) Gonorrheal rheumatism.

(3) Acute gonorrhea.

E. DUE TO TUBERCLE BACILLUS:

I.-Strictly Localized Tuberculosis:

(1) Lupus and tuberculous ulceration of the skin and subcutan

eous tissues.

(2) Tuberculous disease of bones and joints.

(3) Tuberculous cystitis.

(4) Tuberculous nephritis.
(5) Tuberculous epididymitis.
(6) Tuberculous peritonitis.
(7) Tuberculous adenitis.
(8) Tuberculous laryngitis.
(9) Tuberculous iritis.

II.-Not Strictly Localized Tuberculosis:

Pulmonary tuberculosis.

In conclusion, I wish to say that I have done but scant justice to the subject, and have been able to treat it in only the most superficial manner. For your forbearance I thank you very much.

New York City.

PRIMARY BASAL-CELLED CARCINOMA OF THE APPENDIX; REPORT OF A NEW CASE WITH SOME OBSERVATIONS BEARING UPON ITS HISTOGENESIS.

ALDRED SCOTT WARTHIN, PH. D., M. D.

PROFESSOR OF PATHOLOGY AND DIRECTOR OF THE PATHOLOGICAL LABORATORY IN THE UNIVERSITY OF MICHIGAN.

PRIMARY carcinoma of the appendix is of interest, both to the clinician and pathologist, for a number of reasons. In the first place it is probably of more common occurrence than is at the present time supposed, is usually discovered only on microscopic examination, presents an individual pathologic picture, and is of very slight malignancy, no definite recurrence after operation having as yet been established. It has also been recently suggested that primary carcinoma of the appendix plays an important part in the origin of cecal carcinomas.

In the review of this condition by Rolleston and Jones (American Journal of the Medical Sciences, June, 1906), forty-two genuine cases of primary malignant disease of the vermiform appendix were collected. Of these cases 80.9 per cent have been reported since 1900, and this fact must be taken as evidence that it is not so rare as has been thought. With the increasing routine examination of appendices removed at operation, this number is increasing rapidly, ten or more cases having been mentioned in the literature since last June, and the writer is personally aware of a number of observations that have as yet not been reported. Such a case was discovered in this laboratory, three years ago, in the routine examination of appendices removed in the University gynecological clinic (Doctor Peterson). As this case presents the characteristic and peculiar variety of carcinoma found in practically all of the cases of malignant disease of the appendix, it seems important at this time to add it to the casuistics of this condition, particularly as an unusually thorough microscopic examination was made. The entire appendix was cut in serial sections, and these were studied with particular reference to the relationship of the cell nests to each other and to the various tissues of the appendix.

Further, in connection with this case it is desirable at the present time to call attention to the not infrequent occurrence of epithelial nests and glands in the deeper layers of the appendix wall having no connection with the epithelium of the mucosa. That such snaringoff of mucosal epithelium is not uncommon in the spontaneous healing of ulcerative appendicitis and in chronic obliterative appendicitis is

FIGURE I-LOW POWER VIEW OF APPENDIX, SHOWING LUMEN OBLITERATED BY BASALCELLED CARCINOMA.

clearly shown by our routine examinations, and the question arises as to the part played by this in the origin and development of primary appendiceal carcinoma. It seems probable that there may be a close etiologic relationship between the two conditions. Another observation of epithelial structures in the muscularis and subserosa of an appendix showing no chronic inflammatory changes suggested also a possible origin in a congenital anomaly.