Chicago School of Medicine and Surgery - Medicos Yearbook (Chicago, IL)

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LITERATURE Zimmunn- iagnustits in iinternal Mzhitinef W1L1.1AM BUTLER, A.lVI., lVI.D. Attending Physician to Cook County and Frances VVillard Hospitals, Professor and Head of Depart- ment of Medicine, Chicago College of hledicine and Surgery CMedical Department of Valparaiso Universityj CHICAGO In the presence of infection certain reaction products are developed in the infected individual. Their development is excited by the infective bacteria. This immunizing process may be due to the action of the cells or of the fluids or of both. If the process more particularly affects the cells the result is termed cellular immunity, if it affects the fluids, humoral immunity. Some of the substances formed are pro- tective to the individual, others apparently have little demonstrable protective inHuences, and still others sensitize the subject. The substances formed in humoral immunity may be divided into: CID agglutinins, Czj precipitins, C3D complement-binding substances and Q4j opsonins. The demonstration of these substances forms the basis of the serum reactions which have attained so much importance in recent years. The detection of agglutinins attained its greatest importance in the diagnosis of infections caused by typhoid, paratyphoid, and colon bacilli, in which they are specific. Strictly speaking, the latter term must be used in a relative sense, as normal serums possess a certain amount of aglutinins and it is only their demonstration in relatively high dilution that renders the reaction specific. The complement-binding principle of Bordet has received many applications to diagnosis, the most important of which is the serum diagnosis of syphilis. While numerous modifications of this method have been proposed, the original method of Wassermann still remains the most reliable. While the test requires for its proper performance the skill of a trained laboratory worker, the interpretation of the results should always be in the hands of theclinician, who should possess for this purpose a broad knowl- edge ofimmuno-diagnostics. This test is not only useful for the initial diagnosis of syphilis or for deter- mining the presence of that disease in doubtful cases, but it has many applications as an aid to prognosis and treatment during the course of the affection. It is quite remarkable that this reaction is not more frequently employed in controlling the treatmen t and management of syphilitics. One of the strongest claims for the specificity of salvarsan was the fact that it converted positive Wassermann reactions into negative ones. I am fully convinced that if syphilitics were properly managed in this age, serious recurrences and parasyphilitic diseases would be reduced to a minimum. ' ' f However, when used to control the treatment of syphilitics, this reaction should be properly under- stood. One negative reaction does not mean that the patient has been curedof syphilis. This, unfor- tunately, has been considered sufficient, especially since the introduction of salvarsan. just how often a patient should be examined after giving a negative reaction will of necessity remain more or less speculative. In the first year I should not regard a negative reaction as an indication to suspend treat- ment, but I should wish to know by an occasional examination, say every other three months, whether the reaction was still negative, in other words, whether the treatment was being pushed sufficiently. This would apply equally in the second year, with but few and short intermissions of treatment. The intermissions might be lengthened in the third and fourth years. Every time the reaction is found it means, as pointed out in my first paper, active syphilis, and calls for specific treatment. When the reaction persists under treatment over an indefinite period, it means active lues with all its possibilities and its resistance to treatment. Passing over the various applications of this and similar principles to the diagnosis of such diseases as echinococcus infection, cancer, etc., I wish to take up the consideration of the diagnosis of tuberculosis by means of immuno-reactions and particularly by an application of the complement-binding principle. Interest in the tuberculin reaction has been materially increased since the discovery of Pirquet, who found that individuals who had once suffered from a tuberculous infection or were at the time affected with tuberculosis, would react locally to the application of Old Tuberculin by the method of vaccination. 'Read in the Section on Practice of Medicine of the American Medical Association, at the Sixty-Second Annual Session, held at Los Angeles, June, 1911. I 1. Butler: Serum Diagnosis of Syphilis, New York Med. Jour., Nov. 30, 1907. Page 178

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.15 ',-.S ln ,,.I.- ,..- -4,v.-we--Q 'WF Y---l- - I LITERATURE X' Mfrs 0305, 9 I kallli' li RSE TKKFYOUR FE. T DFP , NAI-RAIL WE PKVIENT ,- .. MIGHT GET AW: -VL-f4,Jie...f:-N -fx fr 1 E ffh, fm- Q? xii? 2157 TET NUS 1' - '27,-.X I E, -X. 7 annulfs il-Blaswt igirh I know a little bird, And I think you know it too, i ForrI'm sure youlve seen it many times Since you have been to school. Now this little bird Is such a condescending thing With itls characteristic attitude And cane beneath it's wing. He may herald votes for women And with penant proudly stand Or with gun chase greasers Through the burning desert sand But now this little bird Has changed his habit oer True to his class he wears a gown And a cap does his head adore His b ll may be long, his knees big, His name you never heard But you have got to hand it to oseph For his Flu Flu mascot bird f K Youns F by EL NDES A BRBQQTTES 2-L ,LL 3'l.P: WRC GY-I MEJqQo BUST Page I77 CC 77 7 7- 7 ff, 582 an W, M 'E li tg 0 . 0 oo X OR ,': 0 H if Q .21-3 oi 'ii if D 6 I xff :-' f ,x - Q ,-, N I W if ..51,,A3-iff xc' Q -' E5 - 'N-'HSE

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, ,,,, . Y Am... . ...A .,.., .z ,. .,,.,, .Mu ...M ,W M, .-. ,,,..- ....,....,.:..e,u 1...:u:a::.. . Y ' . -':w- csvgrfsszn-:M 11.1, ' : :m:.nz-:Tm-f-:n::.v ...ww z.4.f,1.m.maatza.:gm..ww--1 1.1,m.as:ge ..n.mp.:,f-saw. 1 . ,ue rg zL.4...g.-41: -f.:-lawn, -.fp-...m :u.v-v-.a-.-'.'..m.a.:-....'-- :nuvJLvn:m.'nm4-x1 LITERATURE, This reaction is the first exam-ple of the use of such immuno-diagnostic methods for the diagnosis of tuberculosis.. Following this discovery of Pirquet, a variety of vaccination methods have been devised, such as vaccination in the conjunctiva, hence the ophthalmic reaction, the percutaneous method, etc. In regard to the subcutaneous reaction, some interesting observations were published by Franz. He found, on examining 40C men of a Bosnia regiment which came from a tuberculous district and whose members were in the first year of the service, that 61 per cent reacted positively to Old Tuberculin. He examined a Hungarian regiment from a section with little tuberculosis and found that 38 per cent of them gave positive results. Only a small number of the reacting individuals were demonstrably tuber- culous, while a number of the non-reacting individuals were tuberculous. While these statistics might argue strongly against the specificity of the tuberculin subcutaneous reaction, there is no doubt of its value in suspected tuberculous cases in the hands of competent observers. We may say that whatever the subcutaneous method lacks in decisive diagnostic value for tuberculosis, the other methods do not possess, notwithstanding this, great claims are made for the efficiency of the ophthalmic reaction in active tuberculosis. There is, likewise, no doubt of its being a valuable aid in the diagnosis of tuber- culosisg that it is not a decisive differential diagnostic recourse is generally recognized. The skin reaction of Pirquet is a specific tuberculin reaction, but the tuberculous process may have healed out. years before, as a consequence, this test is of little value in diagnosing an active process, except during infancy, although a strong reaction may at times lend additional weight to a diagnosis. The occasional unfavorable effects of the subcutaneous injection of Old Tuberculin, together with the uncertain value of tuberculin reactions, show the desirability of a test devoid of these two objections. Efforts have already been made in this direction. They have been directed toward the demonstration of specific substances in the blood of tuberculous patients. The antibodies that have been investigated are agglutinins and complement-binding substances. Arloing and Courmout werethe first to report that the serum and serous exudates ofmany tuberculous patients agglutinated tubercle bacilli. This serum test has not been much tried out, evidently because it has fallen short of tuberculin reactions. Bordet, in his studies of Pfeifferls phenomenon, discovered a new principle in immunity, namely, that of complement fixation. He was able to show by an indirect method, in which a hemolytic system was antigen and bind complement. The discovery of Bordet opened up a great field for investigation into the presence of antibodies in body fluids bv this method, and from this investigation the syphilis reaction ultimately developed Wassermann and Bruck investigated extracts of tuberculous tissue for tuberculin and antltuberculin and found both They believed that there existed a direct association between tuberculin treatment and antituberculln in the blood of tuberculous patients They observed that tuberculous individuals who had no complement binding antibodies reacted strongly to tuberculin, while those that had them failed to do so From this W'assermann originated an ingenious theory in explanation of the tuberculin reaction He asserted that wh n antituberculin was present, it neutralized 1nJected tuberculin and consequently no reaction occurred If it was not present the circulating injected tuberculin was attracted into the diseased focus by antituberculin with which it united and took up complement, thuis causing local congestion and the general reaction Wassermann s and Bruck s experiments were confirmed bv Ludke and Citron other workers how ever, were unable to do so W eil and Strauss, Czastl a lVolff Fisner and Ascher, Cohn and Butler and Vlefford were unable to find any parallelism between complement binding antibodies and tt berctlin reactions, or between opsonius and the latter All seem agreed however that they vt ere able in a con siderable number of cases to show complement binding antibodies in the serum of tuberculous patients In association with my assistants, Drs William E Putz and Nora ohnson I have undertaken an investigation into the serum diagnosis of tuberculosis on the basis of ctmplement deviation The majority of the patients were selected from the second and third stages of the disease, including how ever a number of suspected cases The technic employed in this work IS that used for complement deviation reactions for antigens, the various tuberculins were used including bacilli emulsion Old human tuberculin was chiefly used My previous experiences with it were not satisfactory in fact its action at times was so erratic as to raise the question of specificity of the reaction To avoid this difficulty in subsequent experiments we used human bacilli emulsion as antigen It is necessary tc titrate it carefullv and also to repeat titiations before each test in order that it shall not be used in more than half the amount of inhibiting quantities We also used bovine bacilli emulsion titrating in the sa me manner The serums are obtained in the usual way and inactivated to 56 C for one half hour This is abso lutely essential as we convinced ourselves that active serums could not be used for this ieaction And as a matter of fact the original reaction calls for inactivation Active serums frequently contain anti complementary substances They may show inhibiting properties without the antigen In the presence of antigen this may be increased evidently fiom a summation oi inhibiting factors ln regard to the employment of active sei ums for their complement we can also state from experience that the content in complement of different serums is variable 'ind absolutelv unsuitable for the reaction P6106 IfQ ' , . . . 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