An eye once subjected to tuberculin without any ensuing reaction should not be used again for the test, as the eye becomes sensitized and will give positive reaction without tuberculosis being present in the subject under examination.

Patients recovering from typhoid fever occasionally show the Calmette reaction, probably because typhoid fever patients in the convalescent stages show a hypersensibility to bacterial albumins, as suggested by Cohn. According to Comby, in children, tuberculin solution of 1⁄2 per cent. should be used. In children less than one year of age this author found nc reaction, and in those below two years the reaction was of doubtful value. The Von Pirquet cutaneous reaction proved of special value in the first two years of life. In advanced tuberculosis the ophthalmic reaction often fails, because of the low opsonic index, the latter indicating that there is no resistance to the tuberculin introduced from without. Children afficted with phlyctenular keratitis generally give positive reaction, and the existing corneal affection is often aggravated or a recent one caused to reappear.

Most observers agree that the reaction should be made only on sound eyes, i. e., eyes free from lesions of the conjunctiva, sclera or cornea. Granular or follicular conjunctivitis gives a light reaction, while trachoma a more severe one, with increased number of follicles. This would strongly suggest the possibility of a distinct relationship between the so-called follicular conjunctivitis and trachoma.

The test is of great diagnostic value in differentiation between keratitis parenchymatosa luetica, or keratitis parenchymatosa on a tubercular basis. In those cases where an inflammation of one or both eyes is present, either the Von Pirquet cutaneous inoculation or the subcutaneous injection of tuberculin is indicated in preference to the ophthalmo-reaction.

Most reports show that from the eye reaction no appreciable response is obtained at the site of the tubercular focus, but in one case in my practice, that of a small tumor in the inter-arytenoid space, where the 1 per cent. Calmette solution was instilled, I observed hyperemia of the tumor and larynx, causing some discomfort and lasting about three hours. Another patient showed engorged lower and middle turbinated bones on the side of the local eye reaction. In this case there was a patulous nasal duct. I also obtained ophthalmo-reaction in several patients who had been apparently cured of tuberculosis of the apex for more than a year. These were cases that had not shown any bacilli for a long time. The tuberculin used in my test was obtained from the H. K. Mulford Co. I found their ophthalmic tuberculin tablets very efficient and easily applied.

If the amount of the solution to be used is small, it should be prepared at the time when it is to be used. The old tuberculin of Koch contains glycerine and peptonates, which in themselves cause irritation to the eye and give rise to what might be mistaken for a positive reaction. For the cutaneous or subcutaneous reaction the latter (old tuberculin) is to be recommended.

I trust that this short résumé of the rather extensive literature of the subject, in conjunction with my own experience, will be of some benefit in doubtful cases of tuberculosis.

was the immortal Virchow, assisted by Klebs, who first announced the new theory that all functions of the body are but manifestations of activity or dormancy of the cells of the organism.

with cultures from tuberculous products produced similar lesions to those following the direct injection of tuberculous tissues themselves. This work, persisted in by Klebs, led eventually to the discovery by Koch of the tubercle bacillus, the real cause of the disease, the essence of which constitutes the vaccine in tuberculin therapy.

Hammerschlag is credited with having first made investigations regarding the nature of extractives of the tubercle bacilli, but to Robert Koch is due the honor of discovery of the principles and preparation of an emulsion of the powdered dead bodies of the tubercle bacilli (T. B.) and old tuberculin, which has stood the test of time in its therapeutic application in the diagnosis and cure of tuberculosis.

This leads us to inquire into the principles which underlie the vaccine or tuberculin therapy of tuberculosis.

What is vaccine therapy? It is the treatment of infectious diseases by the inoculation of the patient with the product of the dead bodies of the microrganisms of the same species that has caused and is maintaining the morbid process in the organism. This method consists, essentially, in the exploitation and increased activity of the protective machinery whereby the 'anti-bacterial power of the blood is increased to such a degree as to successfully protect the organism from further invasion of pathogenic organisms.

Two elementary contents of the blood necessarily come into consideration as protective agents against the invading microorganism. "The leucocytes constitute one of these, and the anti-bacterial substances in the blood constitute the other."

It is true that to Metchnikoff belongs the discovery of the phagocytic power of the blood, and Koch discovered the principles, to a great degree, of tuberculin therapy; but it was left to Almoth T. Wright to show to the world how and why phagocytosis is accomplished in bacterial diseases. This he has done in a most lucid manner in his exposition of the opsonic index.

What, then, is an opsonin? It comes from the Greek word opsono, "I convert into palatable pabulum," or "I prepare the banquet." Opsonins are substances formed in the blood fluids which prepare and render micro-organisms susceptible of being ingested and digested by the leucocytes.

The technique by which the amount of

opsonins present in the blood may be determined need not be repeated here, but suffice it to say that it is the chemical union between the opsonins contained in the blood plasma and the pathogenic organisms that render the latter susceptible to the white blood cells. Therefore the gauge of phagocytosis does not depend on the activity of the leucocytes, but upon the quantity and increased power of opsonins in the blood fluid. Wright says: "Increased opsonic phagocytic response is associated with successful immunization or cure, and this increased phagocytic response is dependent on an increase of the opsonic power of the blood fluids, and not on the increased capacity for spontaneous phagocytosis on the part of white corpuscles."

Now if these things are so, if the machinery of immunization is understood and correctly interpreted by Wright, there ought to be a better way of measuring the immunizing effects of vaccine than by the old method of test inoculation of animals. Wright and Douglas have clearly demonstrated that by placing in a pipette an equal quantity of serum to be tested, of blood cells, and of bacillus emulsion, and incubating for twenty minutes the contents of the pipette, then staining and examining under the microscope, the average_number of bacilli taken up by the leucocytes may be accurately counted. gives the phagocytic index. The opsonic index is obtained by comparing this phagocytic index with that of healthy subjects.

This

We learn from these experiments that the serum profoundly influences the phagocytosis, that the increased power of the serum depends upon the opsonin therein. contained. In short, the whole experiment teaches that the changes which are associated with the acquirement of immunity are changes in the blood fluids and not in the white blood cells. That the phagocytic reaction of the leucocytes and the contents of the blood in anti-bacterial substances can be measured with a degree of accuracy sufficient for all practical purposes. And if by these methods it is possible to measure the changes by charts and curves showing the negative and positive. phase in each, which are superinduced by bacterial inoculation, it must be possible by curves to gauge in a more accurate manner than by a test inoculation the immunizing effects of a vaccine, and what should be the dose in any given case.

We have not time to go into a detailed

account of the curves of immunization which are obtained by inoculation of tuberculin vaccine and the laws which govern the output of the opsonins, but we should learn in a general way that the opsonic index varies very little in a healthy man from day to day, but in tuberculosis the index fluctuates considerably; that the depressions or "negative" phase is due to a natural inadequacy of the organism in her protective machinery of immunization or to the overwhelming doses of tuberculous matter by auto-inoculation; "that the positive phase results from auto-inoculation or artificial inoculation just sufficient to act as a stimulus, and that the essence of the vaccine therapy consists in so timing and graduating a series of inoculations as to perpetuate the positive phase at high tide, and therefore maintain the antitoxic activity of the organism."

Up to the present we have been dealing only with the physiology of immunization, showing how the opsonins are preformed in the blood; that they are not bacteriolysins, agglutinins or antitoxins, but are the physiological products of the tissues of the body, and are in the highest degree a specific, whose special function is to render all bacteria fit for ingestion and digestion by the leucocytes, whereby the immunizing response is increased.

If we are to successfully treat the bacterial diseases in general and tuberculosis in particular by this method, something more is to be learned. We should know how the bacteria find lodgment and growth in the tissues. We should understand how bacteria or their products find their way from the focus of infection into the blood stream; how the organism reacts to autoinoculation, and how to bring the bacteriotropic substances and leucocytes into action upon bacteria which are cultivating themselves in the body but outside of the blood stream.

We know, therefore, that the rational application of this treatment can be had only in strictly localized processes where the focus of infection is cut off from the lymph and blood streams. This class comprises almost all chronic infections, including all localized tubercular processes and early pulmonary tuberculosis. In this class the opsonic index is persistently low, owing to the absence of the immunizing stimuli. In the formation of tubercle there is lowered vitality in the focus of infection caused by absorption of the bacteriotropic substances by the tubercle bacilli,

and because there is a deficit of anti-bacterial substances in the foci, owing to the fact that their conveyance through the lymphatic glands is greatly hindered by the barriers thrown up and around the tubercle in the form of a fibrous capsule.

Next in order, we must notice the general principles which should underlie all our therapeutic measures:

First, we must provide for the conveyance of bacteriotropic substances into the focus of infection."

Second, "In case there is stagnant fluid in the focus of infection, which prevents the entrance of bacteriotropic substances into the infected area, we must draw off the fluid in the focus." (Wright.)

The anti-bacterial fluid can be drawn fresh from the blood stream through the lymphatics into the focus of infection by the application of heat, or by Bier's method of stasis-hyperemia, which is effected by backing up the blood in the veins, which increases the hydraulic pressure in the capillaries. illaries. This is effected, as we know, by the application of elastic bandages to the parts in such manner as to cause congestion in the focus of infection, thereby tarrying an excess of anti-bacterial substances to the bacteria, which by increased leucocytosis are destroyed and the disease is healed. This method controverts the old method of treatment of inflammatory processes in the limbs and joints by rest, ice and elevation.

Willy Meyer, of the New York PostGraduate, in a recent article speaks in the highest praise of this method of treating tuberculous joints and limbs. He says that "of course, hyperemia is not a panacea, but experience has shown that this conservative treatment is far the best method of treatment at our disposal for the treatment of tuberculous joints and bones."

To corroborate Meyer and others, let me quote from Bier's book, in which it is stated that in seventeen consecutive cases of tuberculosis of the wrist treated at his clinic, fifteen, or 88 per cent., were cured. Of the elbow 72 per cent. and of the foot 61 per cent. resulted in a cure. The very hyperemia we have all along been combating with our treatment of rest, ice and elevation, he now teaches as being an etiologic factor-a wise arrangement of nature in its fight against an invading foe, which has not to be reduced, but increased, in order to check the infective process and its deleterious results. He certainly has

demonstrated beyond the shadow of a doubt that his method is far superior to those formerly in vogue.

In the second instance, where there is an accumulation of stagnant fluid in the focus of infection, as in tubercular peritonitis, the indications are for operative interferênce, by which we achieve many times wonderful results; but it is not the surgeon's knife that does the good, but it is the access gained by the bacteriotropic substances to the infecting bacteria which will inhibit their further growth and cause their destruction. In other words, we have an artificially induced auto-inoculation.

Now in regard to inoculation of bacterial vaccine. If, as it is admitted, the reason every case of tuberculosis is not cured is on account of a deficiency of anti-bacterial substances of opsonins — in the blood, can this be remedied, and how? This was the great problem that concerned. Professor Wright, and he has apparently solved it by the "renascence of a once discredited method," which, illumined by his own genius, bids fair to become one of the most valuable assets in medicine, and that method is nothing more nor less than Koch's method of treatment by tuberculin or by the watery extract of Von Ruck. Koch's method failed because the requisite knowledge did not exist for its intelligent administration. "The main thing, the doses prescribed, were enormously too large and given too frequently, and through the union of the opsonin with the tuberculin terribly reduced the patient's power of resistance to the infection within him."

Under Koch's treatment from five to ten milligrammes were given; whereas Wright administered as a dose only 1-1,000 of a milligramme. We knew nothing then of the opsonic index or negative phase or positive phase; that the giving of an injection during the negative phase would still increase further that negative phase and drive the resistance down to zero; but now, thanks to Wright, a new era has dawned in bacterio-therapeutics, whereby it is made possible to administer tuberculin and other vaccines in an intelligent and safe manner both in diagnosis and

treatment.

Wright, in speaking of single species of micro-organisms found in the body when giving his personal experience of vaccine. therapy, goes on to say that "typical examples of this type are found in cases where tubercle bacilli have effected lodg

ment in lymphatic glands. In this type of infection all but uniformly successful results have been achieved in my experience by vaccine therapy. What applies to tuberculous infection of lymphatic glands applies also to tubercle infections of the kidneys and other urinary organs, and also to early cases of tubercle of the lungs."

The fundamental facts demonstrated by Wright and Douglas supply a firm basis for the extension of the therapeutic lines in a definite and scientific manner, whereas before it had been entirely tentative and fraught with risks. By this treatment Wright seeks to obtain the maximum amount of protective subtances from the minimum inoculations, and he found that doses held by Koch and his disciples to be inoderate were more toxic than curative, and produced the negative phase. The positive phase, which lasts about two weeks, is strongest when produced by tuberculin injections in infinitesimally small doses without producing any constitutional disturbances-1-1,000 to 1-600 milligramme-but Koch taught that five milligrammes was the proper dose—5,000 times as much.

Urwick, who lucidly expounds Wright's theory, sums up the whole question by saying that as the attempt to free the organism from the bacteria by antiseptics is recognized to be hopeless, the only other chance we have of destroying them is by the injection of vaccine, which forms protective, or, in Ehrlich's language, 'bacteriotropic substances."

In conclusion, I have refrained from entering into detailed statistics, but have confined myself to the discussion of the main principles of vaccine therapy, hoping that by any means we may here and there induce scientific workers to embark on this task of mastering this somewhat difficult technique, which shall vindicate the efficacy of vaccine therapy.

Although this is a new and practically untried method with the general practitioner, yet the opsonic theory has demonstrated that tuberculin as a therapeutic remedy in tuberculosis has passed beyond the experimental stage and rests on the firm basis of clinical as well as therapeutical facts. In regard to this treatment, Trudeau lately states that in tuberculosis the more chronic the type of the disease the better adapted to tuberculin treatment the case seemed to him, and that all cases of the common type, whether incipient or of long standing and advanced, provided