TUBERCULOSIS. By H. C. PARSONS, B.A., M.D., L. R.C.P., M.R.C.S., OWEVER suggestive may be the symptom group presented by an early case of pulmomary tuberculosis, failure to demonstrate the tubercle bacillus in the sputa postpones a positive diagnosis. The presence of the organism in discharges implies a full development, degeneration, and ulceration of the tuberculous focus, so that during this development, that is in the early stage of the disease, our most valuable diagnostic measure fails us; and though the presence of tuberculosis is not proved, it is not disproved. If this difficulty exist in disease of organs having a natural outlet for their discharges, how much greater the obscurity in those not accessible from without, as bones, joints, secous sacs, glands, etc. Of this, A. Frænkel,(1) says, " it is evident that the practitioner has an urgent need in such cases of some diagnostic resource which will as far as possible take the place of the actual demonstration of the bacillus." 'Such a resource "-he adds-" is found in Koch's tuberculin." The condemnation heaped upon tuberculin after its apparent failure as a curative agent was so sweeping that any other virtue it possessed was for a time overlooked. Its selective power as applied to cattle was later recognized, and the analogy presented by human tuberculosis invited a similar application for diagnostic purposes, and today there is substantial evidence as to its utility in this respect. Vaughan,(2) speaking of tuberculin says "here is a body that has (1) Albert Fränckel, Zeitschrift für Tuberculosi und Heilstatlenwesen and Journal of Tuberculosis, Vol. iii, No. 1. (2) Vaughan, 20th Century Medicine, Vol. xiii, p. 104. (3) Trudeau, Medical News, May 29th, 1897. (4) Von Jaksch, Verhand der Congress, and Junere Med. 1891, (quoted by Trudeau). (5), (6), (7), (9), quoted by Trudeau. (8) Heron, Journal of Tuberculosis, Vol. iii, No. 4. (10) Elder, Montreal Medical Journal, Vol. xxx, Oct. 1901. (11) Casselberry, Medical News, Oct. 12th, 1901. (12) Otis, Medical Record, June 17th, '99. (13), (14), (15), (16), quoted by De Renzi and by Trudeau, Medical News, May 29, 1897. (17) Kabler and Wien, Klin Wochen, Nov. 30, 1891, (quoted by Trudeau). (18) Linoir Progrès Med., Nov. 30, 1893, (quoted by Trudeau). (19) Brit. Medical Journal, Feb'y 21, 1891, (quoted by Trudeau). (20) Deutch Archiv and Klin Med., 1894, (quoted by Trudeau). (21) Quoted by Heron, Journal of Tuberculosis, Vol. iii, Nov. 4, 1901. (22) Moorehouse, Cleveland Med. Jour., Aug., 1900. (23) Maragliano Berlin, Klin Wochen Nov. 19-20, 1896, (quoted by Trudeau). (24) Goetsch, Deutsch Med. Wochen, Nov. 25, 1901, and Journal of Tuberculosis, Vol. iii, No. 3. (25) Journal of Tuberculosis, Vol. iii, No. 3. a specific action, a chemical substance, by the effects of which one can distinguish a tuberculous from a non-tuberculous individual." Franckel" draws attention to the striking effects produced by tuberculin in true lupus and the absence of such in erythematous lupus. Trudeau) speaks of the accuracy of the test in cattle, and in other animals artificially inoculated-as shown by post mortem examination-and thinks it remarkable that the application of its diagnostic use in man should have been so long neglected. Von Jaksch) attributes to it a higher diagnostic value, and similar experience is reported by Reazi,(5) Grasset,(6) Vedel,(7) Heron,(8) Maragliano,(9) Moorehouse, Elder,(10) Casselberry,(11) Otis(12) and others. Peiper,(13) Reitzkow,(14) Senn(15) and Verueuil,(16) are reported as having found it unreliable, and it must be admitted that there are instances in which the reaction has failed in undoubted cases of tuberculosis, but the weight of evidence is in favour of the test and its value in diagnosis. Possibly when certain points in technique are settled, as for instance a standard concentration of tuberculin, and a more uniform dosage, an explanation of these errors may be forthcoming. The element of danger in the use of tuberculin appears to have proved a barrier to its more general acceptance. There are two questions. Is there any immediate danger as a result of the injection? And secondly is there a risk of aggravation or dissemination of the disease? Both have a certain amount of excuse for their existence. The early cases treated with tuberculin were unselected; the dose was large and frequently repeated, under which the reactions were violent and the strength of the patients severely tried. Such are now carefully avoided. The cases are selected, and in the earliest stage of the disease; in advanced cases the test is unnecessary, as the diagnosis is made clear by other means; the dose is small, just sufficient to produce a reaction, and one reaction is all that is called for. No unfortunate results have been recorded. Regarding the aggravation and dissemination of the disease. Shortly after the introduction of the tuberculin treatment when large doses and violent reactions were in order, some of the cases died during the course of the treatment. At autopsy Virchow reported the finding of numerous apparently new foci of disease at a distance from those recognized during life, these were interpreted as evidence of the disseïrination of the disease. A condition of softening was also described in the tissues about the older tubercular areae, which was construed as having broken down the natural barrier of encapsulation set up by nature, and a resulting liberation of the bacilli to invade the surrounding tissues. As a more definite knowledge was gained of the local changes produced by tuberculin, these disseminated lesions were, and are now looked upon as local reactions about foci of disease unrecognized during life, and not as any evidence of a new infection. Broden's observations on the use of tuberculin in peritoneal tuberculosis of dogs, (Archives de. Med. Exper., Vol. x, No. 1, 1899, quoted by Trudeau), supplies experimental confirmation in favor of this. Tuberculin is regarded as the specific chemical poison of the bacillus tuberculosis. Certain rules govern the production of tuberculin, virulent tubercle bacilli are used; the tubercle bacillus substance is required; the presence of tubercle bacilli intact results in the formation of abscess and is to be avoided; the centrifrige has superceded the porcelain filter, as it was found that the latter withheld, in addition to the bacilli, certain other substances considered necessary to the filtrate. The object is to obtain an extract of the bacilli. A concise description of the production of tuberculin is given in 20th Century Medicine, Vol. xiii. As to dosage. The fact that doses from 25 to 2 milligrammes of tuberculin have been employed for diagnosis, and with equally satisfactory results, would imply that the concentration of the substances in use at the present time varies in a marked degree. Moorehouse, in his series, gave 7 mgm., Elder 24, Casselberry 3 to 6. In order to avoid violent reactions in the more susceptible, Trudeau advises that the initial dose be small. i mgm. is given, and if no result, 2 mgms. are given after an interval of 2 or 3 days, and a third injection of 3 mgms. if necessary. This is the maximum dose. The patient is kept under observation for three or four days prior to the administration of tuberculin; the temperature must be running a normal course. The injection is made with every antiseptic precaution, beneath the skin of the back, and the patient confined to bed, temperature and pulse being recorded every 2 hours for 24 or 36 hours. The reaction occurs in from 6 to 32 hours. It is characterized by an elevation of temperature, malaise, sensations of chilliness, but rarely a chill, headache, nausea, sometimes vomiting, there is frequently also a moderate amount of pain according to the seat of the lesion. The pulse rate is proportionate to the rise of temperature. The temperature may range from 100 to 104. The duration of the reaction, as shown by the temperature curve, varies from 20 to 30 hours. The local reaction, as seen in lesions, on or near the surface, consists of redness, swelling, pain and tenderness and elevation of surface tem perature. In pulmonary cases, pain in the chest has been noted in some in others an increase of physical signs, which, however, rapidly disappear. This reaction is explained by a certain affinity possessed by tuberculin for tuberculous foci (Frænkel). Trudeau describes tuberculin as a partly specific irritant, both to tuberculous foci, and to the susceptible organism in general. The local reaction is an active hyperæmia about the focus of disease such as one sees in the initial stage of inflammation. Baumgarten describes it as an exudative inflammation in the vascular tissue about the tubercles. In a well marked reaction the changes are so profound that it would seem hardly possible that they result from the toxin contained in the minute dose of tuberculin. It is shown by Kabler (17) and Lenoir (18) that tl.e urine secreted during the reaction contains albumose in greater quantity than is represented by the injection material. It is further known that from caseous tuberculous material may be obtained albuminous substance which give the tuberculin reaction. (Crookshank, Herroun, (19) Matthes.)(20) The deductions from this are, that the tuberculin by its action upon the tuberculous foci sets free toxines stored up within them, which, by their action, either alone or in conjunction with those of the tuberculin, give rise to the general reaction. In bovine tuberculosis Frankel shows that in 8,000 tests the error was between two per cent. and three per cent. The proof of the test was the gross appearance of the organs at autopsy. Frænkel thinks that in the absence of gross lesions, nothing short of a microscopic examination, especially of the lymph glands, can be considered absolute proof. man. A synopsis of a few series of cases will serve to show the results in France (21) reports 55 tests; 45 were positive, 10 negative. 34 of the former eventually died, and 29 were submitted to autopsy and all showed active tuberculosis. Five of the negative cases died and postmortem examination failed to show any trace of the disease, the remaining five are living and well. Moorehouse (22) reports a positive result in 13 cases, (12 suspected and one undoubted case) of tuberculosis. In 14 cases, Trudeau, (3) seven gave the reaction, seven were negative. Casselberry reports nine cases, four positive, five negative. The subsequent records of these (23) cases are given and appear to prove the accuracy of the test. Elder (10) gives results of eleven tests, four were positive, seven negative. Three of the four positive were proven tuberculosis by examination of the tissues after operation, the fourth refused operation. Of the seven negative, three were cases of enlargement of the testicle, which later cleared up under antisyphilitic remedies. Two were undoubted cases of tuberculous peritonitis, as subsequently proved at operation. One case of tuberculosis of the elbow joint and one of tuberculous adenitis did not give the reaction. The writer, however, questioned the value of the tuberculin used in these last two instances Maragliano (23) and Guttsdat (3) report reactions in 9 per cent. and 8 per cent. respectively of apparently healthy persons. In view of the present knowledge of tuberculosis and its behavior, its talency in many cases, and the post-mortem findings in persons dying of various diseases, and in whom tuberculosis was not suspected, it is not surprising that such results are obtained from time to time. Again it is said that cases of carcinoma, sarcoma, syphilis and actinomycosis have reacted to tuberculin, but in these the possibility of associated tuberculous disease was not excluded. Of this Trudeau says: "Before condemning the test as at fault when reaction occurs in apparently healthy individuals, it should be borne in mind that autopsies made on persons dying of other diseases show some unsuspected tuberculous focus to exist in from thirty to forty per cent." In summing up the results of his observations Elder says that the reaction does not appear to be constant, even when tuberculosis is undoubtedly present, but contra, in no case did he get any reaction, when tuberculous, so far as could be determined, was not present. The only unequivocal proof of the correctness or otherwise of the test is a complete autopsy with special reference to the lymph glands (Frænkel). This being true there will necessarily be an element of doubt in some cases of human tuberculosis, in the absence of more searching investigation than clinical methods afford. Apart from the diagnostic use of tuberculin evidence as to its curative value is on the increase, this is both experimental and clinical, and, though not generally accepted, has made such marked strides of late that it is well worthy of careful study and trial. The advocates of tuberculin as a curative measure are unanimous in condemnation of the course followed in earlier days, when large doses were given and their violent reactions produced, and these in unselected cases. These points are established, that the cases should be carefully selected; the temperature should be normal for 24 or 48 hours previous to the administration of a dose; when the injection is followed by a rise of temperature the dose should be diminished rather than increased, as was the former custom; mixed infection is a contraindication. The injections are made beneath the skin of the back. The initial dose is This is rarely followed by a reaction; should there be a reaction the dose is reduced. Koch repeats the injec ion every second day, gradually increasing the dose, but avoiding elevation of temperature. 005 mgm. |