A report on denys’s bouillon filtrate tuberculin in pulmonary tuberculosis (E. G. Rankin)
*The discussion of the revival of tuberculin in the treatment of pulmonary tuberculosis would, doubtless, aptly form part of a paper of this nature, but the limitations of time will not permit. I will, therefore, confine myself to a practical report of the use of the remedy in a certain number of cases, together with the observations deducted therefrom.
The form of tuberculin employed in the following cases was that known as Denys’s Tuberculin Filtrate. This preparation consists of the filtrate from the bouillon culture of the tubercle bacillus, and contains all the soluble products which the bacillus elaborates when cultivated in bouillon. It differs from the old tuberculin of Koch in that no heat is employed in its preparation.
The use of tuberculin filtrate was first employed by Karl Sprengler in 1893, but recently Professor Denys, of Louvain, Belgium, has experimented with the remedy and brought its use prominently before the profession. In a paper presented last autumn before the International Tuberculosis Congress and subsequently before the New York County Homoeopathic Medical Society, Professor Denys announced very successful results.
The tuberculin filtrate is prepared in a decimal series of five dilutions, and is administered hypodermically. The quantity of tuberculin in each two minims in the several dilutions is as follows:
1st. 1-1000 milligrammes.
2d. 1-100 ”
3d. 1-10 ”
4th. 1 ”
5th. 10 ”
The first dose of each series is two minims. Each subsequent dose is increased by two minims until twenty is reached; then the next series is commenced and run up to twenty minims; then the third series, and so on, until the five are administered. The initial dose of the first dilution, it will be observed, is 154/10,000,000 gr.
It is advised that the dose be administered every third day, increasing the interval to a week, as the stronger dilution is reached. Any reaction should be noted, and if that occurs the remedy should not be repeated until all evidences of the same have subsided. Apart from reaction, which is chiefly indicated by rise of temperature, any aggravation of symptoms is an indication for suspension or entire discontinuance of treatment, – namely, increase of malaise, cough, hoarseness, or in the amount of sputum, or any tendency to haemorrhage. After a reaction it is well to repeat the last dose before ascending the scale of dosage.
The smallness of the initial dose is a striking feature and the keynote of the situation. The failure of tuberculin in the past we now know was due to the large size of the dose. Some experimenters administer still smaller doses, namely, .0005 mgm.
An equally important factor is the selection of the cases suitable for tuberculin treatment. Koch says: “I maintain that its efficacy as a cure is completely proved provided its application be restricted to suitable cases, i. e., to those not too far advanced and not complicated by streptococci, staphylococci, pneumococci, influenza bacilli, etc.” The best way of guarding against the misapplication is to employ it only in cases in which the temperature does not exceed 98°. 6+.
Trudeau says: “Denys and some of the Germans claim that even in acute cases good results may occasionally be expected, but my experience, with few exceptions, has been in treating patients who were apyretic or nearly so, – 99.5° to 100°. The more chronic the type of the disease the better adapted the case seems to the tuberculin treatment.” My own experience points to the same conclusion; – namely, that cases with a temperature below 100° are most suitable. In addition, the nutrition must be good and there must be no serious complications.
Between November 12th and 19th, twenty-three cases in the Metropolitan Hospital were placed under this treatment. The pulse, respiration, and temperature in all were taken three times a day for one week before treatment was instituted, and a careful physical examination was made, together with radiographs of the thorax. With one exception these cases all showed advanced changes in the lung. Two left the hospital shortly after commencing treatment. The remaining twenty-one cases will, for convenience, be divided into two classes: 1st, those who were subsequently withdrawn from treatment; 2d, those who continued, and who, with one exception, are still under treatment.
The patients of the first class number ten. All have practically the same histories, – namely, at first there was some slight improvement, but at periods varying from eight to twelve weeks they seemed to lose ground, sometimes with increase of temperature. Treatment for various reasons was suspended. Two of these patients have since died.
The second class, – namely, those upon whom treatment has been systematically continued, – present the following histories:
Case I. – F. McE. Admitted September 29, 1908. American; printer; family history negative. Moderate drinker; gonorrhoea twenty years ago; pneumonia in left side in 1906; has had a slight cough since winter of 1907. About two weeks previous to admission “caught cold,” since which time the cough and expectoration have been much worse. In September, 1908, had a haemorrhage. No night sweats. Lost thirty pounds. Sputum positive. Lungs: Right apex, two inches anteriorly, consolidation and dullness, prolongation of expiratory murmur; crepitant rales in the axillary region in a line with eighth rib; also a few sibilant rales; posteriorly, crepitant rales from ninth rib downward. Left, apex bronchial breathing. Present condition: Right lung still shows the presence of a few crepitant rales, but lower portion has cleared. Left, apex 21/4 inches anteriorly, some bronchial breathing in apex. Has gained 14 pounds. Cough much better. Coughs very little now in the mornings, expectoration being much decreased and general improvement marked. Feels well. Sputum still positive.
Case II. – E. C. Admitted August 10, 1908. Age, 52. Irish; sailmaker. Family history negative. Alcoholic habits. Chancre and gonorrhoea 32 years ago. History of cough and expectoration going back six years. Was able to work up to two months before admission. During this period lost in all 28 pounds. Was in hospital before. So weak had to stop work. Coughs considerably, with profuse expectoration. No blood or night sweats. Lost 13 pounds. Sputum positive.
Lungs: right apex, 13/4 anteriorly, consolidation to third rib, with dullness on percussion. Bronchophony and bronchial breathing posteriorly. Consolidation as far as third rib, with dullness, bronchial breathing, and bronchophony. Left apex 1/4 anteriorly, extensive consolidations. Apex involved downward as far as fourth rib; bronchial breathing apparently all over lung; crepitant rales from second to fourth ribs. Sputum positive. Present condition: General improvement. Much stronger. Cough and expectoration very much diminished. Gained 6 pounds but lost 5. Physical examination shows area of involvement somewhat less extensive, with marked decrease in area of crepitant rales. Sputum still positive.
Case III. – P. F. Admitted July 5, 1905. Age, 35. German porter. Family history negative. Drank quite heavily; gonorrhoea 13 years ago; has had pneumonia and typhoid fever. First noticed loss of health about a year previous to admission, when he “caught cold:” since then has gradually failed. Cough and expectoration, while persistent, have always been moderate. No haemorrhages or night sweats. Dyspnoea on exertion. Lost thirty pounds. Sputum positive.
Lungs: Right, apex 13/4 inches consolidation down to third rib, with dullness and bronchial breathing. Crepitant rales from 3d to 5th rib, extending to axillary region. Vocal resonance increased on entire right side. Posteriorly – dullness to third rib with bronchial breathing, and crepitant rales; apex extending to third rib; posteriorly, negative. Present condition: Increase of strength decided. Cough and expectoration less. Bronchial breathing in right apex less pronounced; crepitant rales disappeared. Left lung also shows improvement. No crepitant rales. Cough remains the same. Sputum still positive.
Case IV. – W. E. Admitted September 25, 1908. American. Upholsterer. Family history negative. Heavy drinker. No venereal history. First noticed loss of health five weeks before admission; loss of appetite and vomiting; cough and expectoration. No haemorrhage or night sweats.
Lungs: right, apex 11/2 inches, anteriorly, dullness to fourth rib. Bronchophony and the crepitant rales to third rib; posteriorly, dullness to fourth rib, with bronchophony to fifth. Left, apparently normal.
Present condition: General improvement very marked. Right lung: rales much less pronounced, being confined for the most part to the expiratory murmur. Coughs and expectorates a little by hawking. Gained five pounds. Sputum still positive.
Case V. – E. D. Admitted September 28, 1907. Age, 37. American. Peddler. Father died of asthma (?); mother, of pulmonary tuberculosis. No other cases of tuberculosis in family. Hard drinker. Scarlet fever in childhood; gonorrhoea six years ago. Has had a cough for the past seven years; has gradually become worse, with moderate amount of expectoration. Haemorrhage four years ago. Has dyspnoea and night sweats. Lost 22 pounds. Sputum positive.
Lungs: right, apex 11/2 inches, anteriorly, consolidation well marked, bronchial breathing to fourth; posteriorly, same. Left, apex, 11/2 inches anteriorly, consolidation down to second rib. Posteriorly, the same, with dullness and bronchophony.
Present condition: Physical examination does not show much appreciable change, but cough has almost entirely disappeared. Slight expectoration. Gained nine pounds. Sputum positive.
Case VI. – M. H. Admitted May 21, 1908. Age, 48. Irish. Clerk. Family history negative. Drinks heavily at times. In October, 1906, “caught cold,” and since then has coughed and expectorated. Has night sweats and dyspnoea, on exertion. No haemorrhages. Lost 28 pounds. Sputum negative.
Lungs: Right, apex 11/2 inches anteriorly, consolidation to fifth rib, with dullness and bronchial respiration, and bronchophony, over entire right side. Crepitant rales from fourth rib to fifth rib; posteriorly, marked dullness down to third rib; bronchial breathing over entire side. Left apex 2 inches. Slight consolidation in apex.
Present condition: Physical examination shows same signs, but not so pronounced in character. Cough much improved; expectoration reduced to about half. General constitution improved. Feels quite well; gained 5 pounds. Sputum still positive.
Case VII. – F. D. Admitted May 10, 1906. Age, 42. American. Laborer. Family history negative. Moderate drinker; no venereal disease. Illness commenced about a month previous to entrance to hospital, after severe cold caused by getting wet. Has had fever and chills occasionally, headache, vomiting and dyspnoea on exertion. Cough, especially at night, with profuse expectoration. Lost 7 pounds. Sputum positive.
Lungs: Right, apex 13/4 inches, anteriorly, consolidation down to third rib, as evidenced by marked bronchial breathing. Posteriorly, consolidation to fourth rib, less degree of consolidation fourth to seventh ribs, Left apex 21/4; apparently normal.
Present condition: Bronchial breathing in involved lung much diminished, – in intensity extends only to the middle of the scapula. Cough gone; expectorates a little by hawking. General condition greatly improved; gained 8 pounds.
Case VIII. – I. H. Admitted July 3, 1908. American. Age, 35. Marble worker. Family history suggests tuberculosis. One brother died of same. Cause of parents’ deaths not known. No alcoholic or venereal history. Illness first appeared two weeks previous to entrance, when he said he had a “severe cold,” with pain in chest and cough. Had headache. Vomiting at times. No night sweats. Coughs mostly in the morning, with profuse expectoration. Says he formerly weighed 57 pounds more than he did on entrance. Sputum positive.
Lungs: Right, normal. Left, apex, 11/2, consolidation of apex with dullness down to second rib anteriorly and to the third rib posteriorly. Prolongation of expiratory murmur and bronchial breathing.
Present condition: Left apex has almost cleared; only discernible. Abnormal condition is slight harshness. Cough has disappeared. There remains, however, a slight hack. Sputum after three examinations negative. Gained seven pounds in weight. Sputum still positive.
Case IX. – A. L. Admitted June 30, 1908. Irish. Laborer. Family history negative. Heavy drinker for past twenty years. Gonorrhoea 15 years ago. First observed loss of health six months previous to admission. “Caught severe cold,” which was followed by haemorrhage. Improved and returned to work for a short time, then came to Metropolitan. Coughs mostly at night. Expectoration not very profuse. No night sweats. Lost 26 pounds. Sputum positive.
Lungs: Right, apparently in good condition; left, apex 13/4 inches anteriorly, consolidation down to fourth rib, as evidenced by dullness on percussion, and bronchial breathing. Posteriorly, crepitant rales in apex down to fifth rib.
Present condition: Cough almost gone; amount of crepitant rales much less. General condition much improved. Gained 15 pounds. Sputum negative.
Case X. – R. A. Admitted October 1, 1909. Age, 55. Irish. Waiter. Hard drinker. Family history negative. Had gonorrhoea and chancre 22 years ago. Pleurisy twice, the last time five years previous to admission. First noticed loss of health about 5 years ago, following last attack of pleurisy, which he said involved both sides. Cough at first dry and hacking, later accompanied by profuse expectoration. Has some dyspnoea now on exertion. No night sweats. Lost 23 pounds in weight. Sputum positive.
Lungs: Right apex 13/4; consolidation with dullness and bronchial breathing down to third rib. No rales. Posteriorly, slight bronchophony over entire lung; left, normal.
Present condition: Lung does not show much change, but there has been a general marked improvement. Cough and expectoration much less, and gain of nine pounds in weight.
Case XI. – I. D. Admitted July 22, 1908. Age, 33. American. Waiter. Family history negative. Moderate drinker; no venereal history. First noticed loss of health eight months previous to admission to hospital. Weakness, accompanied by cough and a moderate amount of expectoration. Sharp pains in chest. Was in another hospital for five months previous to admission to Metropolitan. Has loose cough, marked dyspnoea, and general debility. No chills or fever; no haemorrhage. Sputum positive. Sputum is sometimes bloody. Lost 41 pounds.
Lungs: Right, apex 11/2 anteriorly, dullness to the third rib with bronchial breathing and a few crepitant rales under clavicle; posteriorly, dullness and crepitant rales down to fourth rib. Left, apex, 13/4 inches; anteriorly, dullness and crepitant rales down to third rib; posteriorly, dullness same.
Present condition: General condition very much improved as to strength; cough gone; expectoration – a little in the morning, hawking it up. Crepitant rales have disappeared; bronchial breathing less pronounced in base of right lung. Gained 8 pounds. Sputum still positive.
Case XII. – R. O. Admitted August 19, 1908 Age, 41. German. Coachman. No family history of tuberculosis. Moderate drinker. Gonorrhoea 22 years ago. Two operations for rectal fistulae, five and four years ago, respectively. Illness dates back four years ago when he “caught cold,” accompanied by painful cough with profuse expectoration, followed by the three copious haemorrhages. At present feels weak, has shortness of breath, cough, and expectoration marked. No night sweats. Vomits sometimes after eating and coughing. Has lost 15 pounds. Sputum positive.
Lungs: Right, apex 21/2 inches. Anteriorly, negative. Posteriorly, sonorous rales. Left, apex 2 inches. Consolidation anteriorly, bronchial breathing, sub-crepitant rales to second rib. Exaggerated bronchial breathing in left base.
Present condition: Feels much better, but expectoration not much diminished. Rales in left side have disappeared; on right, there appears to be some harsh breathing sounds. Sputum negative.
Three weeks from beginning of treatment patient had a haemorrhage. Treatment was accordingly discontinued and resumed after an interval of 17 days, commencing with series No. 1. Since then patient has continued to improve.
Case XIII. – T. D. Admitted March 19, 1906. Age, 60. Irish. Laborer. Drinker. Family history negative. No venereal history. About a month previous to admission got wet and had chills, with fever and pain in side. Cough and expectoration followed. Lost 20 pounds. Sputum positive.
Lungs: Right, apex 2 inches, anteriorly feeble respiratory murmurs over surface of chest. Posteriorly, same condition. Left, apex 11/4 inches. Anteriorly, marked consolidation, as evidenced by dullness on percussion; bronchophony, bronchial breathing down to third rib. Posteriorly, feeble respiratory murmur. No rales.
Present condition: Cough better, expectoration less, bronchial breathing about same. Weight same. Patient on May 20th was seized with haemorrhage; tuberculin treatment suspended.
Of these thirteen cases it will be observed that 9 show very decided improvement: 3 much improvement, but less decided; and I manifested no improvement. Six of the much improved class, namely, I., IV., V., VII., IX., X., if kept under proper hygienic conditions, apparently warrant the hope that in them the disease would become arrested. In Nos. VIII. and IX. the disease is nearly arrested. In regard to the others of this class there is no doubt that the process of the disease has been, for a time, at least, retarded.
It is noticeable that even in the cases in the most favorable condition the sputum, with one exception, is positive. The sputum in the other cases is raised by a “hawking” rather than a cough, and that only in the morning. An interesting feature which was observed in all cases was the temperature line. Apart from the reaction elevations which occasionally occurred after injection, the line after the second week became more irregular; this continued for several weeks, and then it became much more regular. After the second dilution of the tuberculin, and in the latter part of the administration of the same, the intervals of injection were increased to four and five days, and finally to a week.
It might, perhaps, be urged that any given number of cases of pulmonary tuberculosis, if placed under improved hygienic condition would show for a time some improvement. While this is true, the criticism would not apply to those cases, at least the greater portion, for the histories show that many had been in the hospital for a considerable time, that is under the same conditions and with the same surroundings before treatment. Thus Nos. VIII. and IX. were each in the hospital one year and four months before treatment, and while they had gained some after entrance they remained in statu quo for a year with a tendency to decline. Nos. II. and III. had been in the institution three years each; No. VII., 3 years and six months; No. IV., 1 year and three months; and No. XIII., the unfavorable case, for 3 years. The cases with the briefest stay before treatment are Nos. I. and IV., 2 months each; XI., four months; and XII., one month.
With so limited a number of cases and so brief a period of observation, – 7 months, – I feel that to attempt to draw positive conclusions would be presumptuous. At the same time, it seems to me that there is sufficient evidence to corroborate the observations of others, – namely, that tuberculin, as Koch says, is effective if restricted to still curable cases. Furthermore, I regard these observations as corroborating the following indications for the use of the remedy:
1. That the initial doses should be small, not more than 1/1000 of a milligramme.
2. That the doses should not be raised too rapidly. The rule of intervals of three days during the first series might be prolonged to four or five days; and after the second series is reached, injections are best given once a week – not more frequently.
3. When there has been a reaction, do not give the next dose until all evidences of the same have subsided.
4. After a reaction, general or local, repeat the last doses before increasing.
5. Malaise, headache, loss of appetite, increase of cough raising blood, are evidences of the limitation of the patient’s tolerance, and call for a suspension of treatment, or limitation of doses. If these symptoms return on the resumption of the treatment even under the minute doses, treatment should be abandoned.
6. Cases suited to treatment are those without fever, or, at least, not above 100 degrees, fair nutrition, and chronic in type.
In closing, I must express my thanks and appreciation to Dr. Charles A. Ley, Dr. W. A. Meierding, and Dr. M. H. Powers, of the Metropolitan Hospital House Staff, for their co-operation and interest.