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Blood pictures in tuberculosis
234
TUBERCLE
abnormalities not visible on the straight x-ray. T h e extent of lesions noted on bronchography can be appreciated. I t is helpfifl in planning treatment particularly when surgery is being considered. Progress of disease m a y be watched and results of treatment and operation noted. T h e irregular irregularities of the bronchial changes in pulmonary tuberculosis m a y help in the differential diagnosis with other chest conditions. In outlining cavities bronchography is unreliable, though when filling is obtained it is most convincing. Used in conjunction wlth tomography the value of both is enhanced. It has proved to be helpful in having the bronchograms to hand before deciding where to make tomographic cuts. At present there is no direct correlation between the bronchographic appearances and the histological findings. I t is not possible to differentiate between a non-specific and a tuberculous bronchitis, or active disease and a burnt-out fibrotic lesion. Using comparative inspiratory and expiratory films functional bronchial changes can be noted. Although the interpretation of abnormal bronchial changes is uncertain, it should be assumed that the)" are associated with disease or its effects. THE PATHOGENESIS AND PROGNOSIS OF TUBERCULOUS PLEURAL EFFUSION By JAMES J. XVARINO, M.D.
Professor of 2tiedicine, University of Colorado Professor XVaring in a most agreeable paper said that simple pleural effusions had been classed as h a p p y accidents, in that-the), healed quickly and warned the patient to bc careful about tuberculosis. This was only truc when thcy occurred bcforc the age of 7. Then they did appear to be truly bcnign. At later ages thcre was a 2o per cent relapse into chronic pulmonary tuberculosis. As to pathogenesis he thought it likely that effusions were associated with hypersensitivity and haematogenous dissemination. There were probably tubercles scattered all over the body at the time of a pleural effusion. He then examined the histories of cases of pleural effusion occurring in American army men. T h e immediate results were all good whatever the treaffnent but the later incidence of parench)anatous disease seemed to depend on two factors: (I) the length of the rest period during treatment, and (2) T h e sort of work to which the m a n returned: the harder the work the greater the n u m b e r of relapses. Those who returned to full combat duty had a veD, high rate of relapse indeed. It appears that pleural effusions must be taken vex3" seriousIy.
September 19~4
D E C O R T I C A T I O N OF T H E L U N G By O. S. Tunus, F.mc.s.
Surgeon to St Bartholomew's and Brompton HoSpitals The modern operation of decortication aimed a removal of all scar tissue from the surface of the hmg so that the lung was free to expand and also from the chest wall and diaphragm so that respiratory movement might be restored. There were numerous reports in the literature to show that in cases where the lung has been collapsed for more than a few months oxygen uptake m a y not be improved in spite of complete reexpansion of the lung and restoration of respiratory movement: it was therefore important to operate early in all patients where re-expansion of the lung was hindered by a chronic pleurisy. Nevertheless late operations might serve a valuable purpose in allowing the lung to expand and so obliterate a fluid- or air-containing space. Chest radiographs were shown demonstrating the use of decortication in the treatment of haemothorax, acute and chronic pyogenic empyema, and chronic pleurisy in patients with tuberculosis. Simple drainage of an acute pyogenic empyema was preferred to decortication unless the empyema was massive or tuberculous infection could not be excluded with certainty. Decortication was undoubtedly the ideal treatment of all but the smallest chronic pyogenic empyemas which had failed to heal w i t h proper and prolonged dependent drainage. Several cases of persistent pleural effusion .and fibrosis due to 'primary' tuberculous infection had been treated by decortication with good results. In patients with a known puImonary lesion of the adult type, decortication might be necessary in order to obtain expansion of the lung after artificial pneumothorax therapy had been employed and been complicated by a chronic pleurisy. The risks of operation were considercd to be less than the ultimate hazards of leaving a patient with a persistent pleural space containing fluid. I f the stability of the lung lesion was in doubt, decortication might be accompanied by resection or followed by thoracoplasty.
Correspondence Blood Pictures in Tuberculosis To the E d i t o r - 'TUBERCLE'. S I R , - An article by F. Kneller in the February I954 issue of 'TUBERCLE' on the above subject was of special interest to us at Grassington Hospital, as, for some )'ears now, we have found the blood picture of great help in the assessment
September 1954
TUBERCLE
of o u r cases, chiefly from the prognostic point of view and particularly since the advent of c h e m o t h e r a p y and thoracic surgeD-. H a v i n g recently studied this article again, I feel p r o m p t e d to write regarding a m e t h o d of computing an ' I n d e x ' which is not mentioned and which seems to have been forgotten. I refer to that described by D r Frimodt-M611er and Barton in the September I933 issue of 'TUBERCLE'. Dr Donaldson, Medical Superintendent at Grassington Hospital, was m u c h interested when he was in India in the work of Frimodt-M611er w h o was then Medical Superintendent of the Arog)azaram Sanatorium in South India. W i t h Barton, his pathologist, Frimodt-M611er worked out his Index and D r Donaldson who was using this method w h e n I came to Grassington explained it tO me and gave me the literature. For some years now I have done both the H o u g h t o n a n d the FrimodtM611er meth6ds and I find the latter easier and less time-consuming than the H o u g h t o n . Moreover, the results of the two Indices seem to be quite comparable. Tile H o u g h t o n formula is as follows (Tubercle, N o v e m b e r I953) : V . B . - - [ S . R . + (P. + M . - - 2 L ) ]
I n this the.normal is 26o to 300. T h e higher the I n d e x the better the prognosis. Frimodt-M611er modified the H o u g h t o n Index b y using the 'Schilling' Division of the neutrophils instead of the V o n Bonsdorff count. I n the Schilling count the 'Stabkernige' cells (Stabs.) are o f great importance. T h e y arc juvenile cells with non-segmented nuclei shaped like a O or an S. Their increase points to toxaemia and causes a bad index. While a high V o n Bonsdorff count goes to the credit side, a high 'Stabs' count has to be p u t on the debit side. Frimodt-M611er points out that objection m a y be raised that the n u m b e r o f neutrophils in which we calculate the percentage of Stabkernige cells is not constant as in the V o n Bonsdorff count which always uses Ioo neutrophils; but as in our investigation never less than ooo leucocytes are counted the n u m b e r of neutrophils from which the percentage is calculated is almost always m o r e than IOO, and the general effect of this is a more accurate percentage. Furthermore, Frimodt-M611er halved the sedimentation r a t e - ' T h i s reduction places the sedimentation rate more on a level with the other parts of the formula preventing the S.R. from having u n d u e weight'. T h e F.M. formula is therefore as follows: N + ( S _ ~ _ bI. o×o ) + M + S . R . - - 2 L . 2 N - neutrophil polys. M - monocytes. L - lymphocytes.
235
T h e average I n d e x in this formula in healthy people is - - 5 and + I 2 is the u p p e r limit of w h a t is considered to be normal. T h e lower the index, the better the prognosis. W h a t matters v e r y m u c h in both the H o u g h t o n and the Frimodt-M611er formulae is the increase in the lymphoctyes which, as is well know, points to healing. T h e n u m b e r o f monocytes is also o f i m p o r t a n c e in both and their increase means the formation of new tubercles. T h e following examples show the parallelism between the two methods. T h e y are representative of very m a n y which have been done and exemplify various points to which H o u g h t o n called attention such as a high E.S.R. with a normal Index or a low E.S.R. with a high Index. T h e y serve to show that the FrimodtM611er Index is comparable with the Houghton. (I) This shows the blood picture in an ordinary straightforward case where the E.S.R. and the Indices are in keeping. T h e patient was a y o u n g m a n (C. B.) aged x7 with a l a n e cavity in the left u p p e r zone. At three points in his treatment, as improvement continued, it will be noted how the Frimodt-M611er I n d e x reflects the improvement in the patient's condition in the same w a y as the H o u g h t o n Index. 30.5.52 xm4.53 27.3.52 % % % % % % Neulros. Juveniles ½~ Stabs. 5z 61½ 3 Segmented 55 ) 28 45 Lymphos .. 43~ 55~ 1½ Eosinos. .. 2 4½ z½ Basos. .. x 3~ Monos. .. 7½ 4½ 3 228 Von Bons... 264 269 xi E.S. rate .. 4 2 007 H. Index 297 "5 35o'5 F.M. Index +26- 5 --25- 5 --66 (2) This example shows the 'Bronchitic Blood Picture' where, according to H o u g h t o n , there is a relatively high V.B. count coupled with a relatively rapid S.R. I n other words, the final Index appears good but tile S.R. is not in keeping. I n our case the patient was a w o m a n (D. H.), 35 years of age, who had bilateral p u l m o n a r y tuberculosis and had also suffered from chronic bronchitis for very m a n y years. T h e following was the blood picture and again the Indices are comparable. % Yo Neutros. Juveniles I Stabs. 3½ •. 45 Segmented 4o.~ Lymphos. •. . . . . . 44~ Eosinos. . . . . . . x½ Basos. . . . . . . Monos. . . . . . . 1 Von Boris. . . . . . . 257 E.S. rate . . . . . . 39 H. Index .. .... ~59 F.M. Index ....
) )
..
2
• .
- - I O
TUBERCLE
236
(3) The last example is to demonstrate how, in certain cases, the E.S.R. shows a normal figure but the Index is not good. A woman (C. W.) of 28, with a minimal lung lesion, complained persistently of backache and pain in both arms. No spinal lesion could be found but a few months later, x-ray revealed spinal disease. Here again the Frimodt-M611er method showed an unsatisfactory Index in the same way as the Houghton one, whde the E.S.R. was normal.
% Neutros.
Juveniles ;~ Stabs. Segmented 57~J L) mphos. . . . . Eosinos... .. Basos. . . . . Monos. . . . . Yon Buns. . . . . E.S. rate .... H. 'Index . . . . F.M. Index ..
% ..
66.~ -'24½ I
-8 242 3 215"5 +38
Quite apart from the work done an comparing the two Indices, one very interesting feature has 'been the marked and rapid improvement shown in the blood pictures following chemotherapy with or without thoracic surgery, anajor or minor. At Grassington we have noticed a particularly satisfactory trend in the Indices following combined chemotherapy and pneumoperitoneum. The most markedly good results as reflected in the Indices are to be seen, of course, following chemotherapy and major surgery. In all I have done over i,ooo counts and compared the Houghton Index and the FrimodtM611er Index in over 3oo, and for anyone who has not the requisite laboratory help and who would like to gain the further information which an Index of this type gives, I feel that the Frimodt-M611er might be tried. Yours faithfully, The Hospital, Lomsz E. SA.~ISON, ~t.I).
Grassinglon, Wr. Skipton, Turks.
Thirty Years Ago (Extract from TUBERCLE, September r 9 2 4 Atypical Tubercle Bacilli in H u m a n and Animal Tuberculosis with Special Reference to those Occurring in Lupus, by A. Stanley Griffith, ~LD.) W h a t is the explanation of this frequent modification of the pathogenic properties of tubercle bacilli in lupus? It has been suggested that the action of
September 1954
daylight, subnormal temperature, local treatment, etc., might bring about the change. I f daylight cansed an attenuation of the virulence of tubercle bacilli in the cutaneous tissues we should expect lupus lesions which are most exposed to daylight to contain attenuated tubercle bacilli more frequently than lesions which are concealed from light. There is, however, no demonstrable relation between attenuation and the degree of exposure to light. Fully virulent h u m a n and bovine strains have been obtained from lesions on the face and neck which had been in existence m a n y )'ears. In one case a fully virulent bovine strain was obtained from facial lupus of thlrty-three years' duration. In another case of five )'ears' duration a strain from" the face was fully virulent while one from the buttock, obtained, it is true, eleven months after the face strain, was much less virulent. On the other hand, h u m a n and bovine strains with modified virulence were obtained in 12 cases in which the lesions were on the trunk and legs. Lupus is very commonly situated on the face, neck and extremities, parts of the body which are relatively cool, and the possibility cccurred to me some time ago that subnormal temperaturc might have an influence on the virulence of bacilli multiplying slowly in unfavourable surroundings. With a view to testing this hypothesis I began a passage experiment in toads. A .bovine strain h,'ls now been passed through six toads in succession and the total duration of residence in toad tissues is seven )'ears. This prolonged residence in a coldblooded host has not caused any, decrease in the virulence of the strain or alteration in cultural characteristics. T h e experiment incidentally gives no support to the view that m a m m a l i a n tubercle bacilli can be readily modified in the tissues of cold-blooded animals. Treatment of the lesions with antiseptics, Finsen light, etc., was certainly not the cause of the modifications in the majority of the cases under consideration, since the lesions filrnishing the original material had not been treated in any way. lkIoreover, lupus produced by modified tubercle bacilli is not a milder process than lupus from which fully virulent tubercle bacilli are obtained. O n the contrary', the disease in these cases is characterized by" persistence, intractability and tendency to spread. Although the tubercle bacilli have lost virulence for experimental animals there is no loss, rather is there an increase, in the virulence of the bacilli for the individual affected with lupus.
TUBERCLE
abnormalities not visible on the straight x-ray. T h e extent of lesions noted on bronchography can be appreciated. I t is helpfifl in planning treatment particularly when surgery is being considered. Progress of disease m a y be watched and results of treatment and operation noted. T h e irregular irregularities of the bronchial changes in pulmonary tuberculosis m a y help in the differential diagnosis with other chest conditions. In outlining cavities bronchography is unreliable, though when filling is obtained it is most convincing. Used in conjunction wlth tomography the value of both is enhanced. It has proved to be helpful in having the bronchograms to hand before deciding where to make tomographic cuts. At present there is no direct correlation between the bronchographic appearances and the histological findings. I t is not possible to differentiate between a non-specific and a tuberculous bronchitis, or active disease and a burnt-out fibrotic lesion. Using comparative inspiratory and expiratory films functional bronchial changes can be noted. Although the interpretation of abnormal bronchial changes is uncertain, it should be assumed that the)" are associated with disease or its effects. THE PATHOGENESIS AND PROGNOSIS OF TUBERCULOUS PLEURAL EFFUSION By JAMES J. XVARINO, M.D.
Professor of 2tiedicine, University of Colorado Professor XVaring in a most agreeable paper said that simple pleural effusions had been classed as h a p p y accidents, in that-the), healed quickly and warned the patient to bc careful about tuberculosis. This was only truc when thcy occurred bcforc the age of 7. Then they did appear to be truly bcnign. At later ages thcre was a 2o per cent relapse into chronic pulmonary tuberculosis. As to pathogenesis he thought it likely that effusions were associated with hypersensitivity and haematogenous dissemination. There were probably tubercles scattered all over the body at the time of a pleural effusion. He then examined the histories of cases of pleural effusion occurring in American army men. T h e immediate results were all good whatever the treaffnent but the later incidence of parench)anatous disease seemed to depend on two factors: (I) the length of the rest period during treatment, and (2) T h e sort of work to which the m a n returned: the harder the work the greater the n u m b e r of relapses. Those who returned to full combat duty had a veD, high rate of relapse indeed. It appears that pleural effusions must be taken vex3" seriousIy.
September 19~4
D E C O R T I C A T I O N OF T H E L U N G By O. S. Tunus, F.mc.s.
Surgeon to St Bartholomew's and Brompton HoSpitals The modern operation of decortication aimed a removal of all scar tissue from the surface of the hmg so that the lung was free to expand and also from the chest wall and diaphragm so that respiratory movement might be restored. There were numerous reports in the literature to show that in cases where the lung has been collapsed for more than a few months oxygen uptake m a y not be improved in spite of complete reexpansion of the lung and restoration of respiratory movement: it was therefore important to operate early in all patients where re-expansion of the lung was hindered by a chronic pleurisy. Nevertheless late operations might serve a valuable purpose in allowing the lung to expand and so obliterate a fluid- or air-containing space. Chest radiographs were shown demonstrating the use of decortication in the treatment of haemothorax, acute and chronic pyogenic empyema, and chronic pleurisy in patients with tuberculosis. Simple drainage of an acute pyogenic empyema was preferred to decortication unless the empyema was massive or tuberculous infection could not be excluded with certainty. Decortication was undoubtedly the ideal treatment of all but the smallest chronic pyogenic empyemas which had failed to heal w i t h proper and prolonged dependent drainage. Several cases of persistent pleural effusion .and fibrosis due to 'primary' tuberculous infection had been treated by decortication with good results. In patients with a known puImonary lesion of the adult type, decortication might be necessary in order to obtain expansion of the lung after artificial pneumothorax therapy had been employed and been complicated by a chronic pleurisy. The risks of operation were considercd to be less than the ultimate hazards of leaving a patient with a persistent pleural space containing fluid. I f the stability of the lung lesion was in doubt, decortication might be accompanied by resection or followed by thoracoplasty.
Correspondence Blood Pictures in Tuberculosis To the E d i t o r - 'TUBERCLE'. S I R , - An article by F. Kneller in the February I954 issue of 'TUBERCLE' on the above subject was of special interest to us at Grassington Hospital, as, for some )'ears now, we have found the blood picture of great help in the assessment
September 1954
TUBERCLE
of o u r cases, chiefly from the prognostic point of view and particularly since the advent of c h e m o t h e r a p y and thoracic surgeD-. H a v i n g recently studied this article again, I feel p r o m p t e d to write regarding a m e t h o d of computing an ' I n d e x ' which is not mentioned and which seems to have been forgotten. I refer to that described by D r Frimodt-M611er and Barton in the September I933 issue of 'TUBERCLE'. Dr Donaldson, Medical Superintendent at Grassington Hospital, was m u c h interested when he was in India in the work of Frimodt-M611er w h o was then Medical Superintendent of the Arog)azaram Sanatorium in South India. W i t h Barton, his pathologist, Frimodt-M611er worked out his Index and D r Donaldson who was using this method w h e n I came to Grassington explained it tO me and gave me the literature. For some years now I have done both the H o u g h t o n a n d the FrimodtM611er meth6ds and I find the latter easier and less time-consuming than the H o u g h t o n . Moreover, the results of the two Indices seem to be quite comparable. Tile H o u g h t o n formula is as follows (Tubercle, N o v e m b e r I953) : V . B . - - [ S . R . + (P. + M . - - 2 L ) ]
I n this the.normal is 26o to 300. T h e higher the I n d e x the better the prognosis. Frimodt-M611er modified the H o u g h t o n Index b y using the 'Schilling' Division of the neutrophils instead of the V o n Bonsdorff count. I n the Schilling count the 'Stabkernige' cells (Stabs.) are o f great importance. T h e y arc juvenile cells with non-segmented nuclei shaped like a O or an S. Their increase points to toxaemia and causes a bad index. While a high V o n Bonsdorff count goes to the credit side, a high 'Stabs' count has to be p u t on the debit side. Frimodt-M611er points out that objection m a y be raised that the n u m b e r o f neutrophils in which we calculate the percentage of Stabkernige cells is not constant as in the V o n Bonsdorff count which always uses Ioo neutrophils; but as in our investigation never less than ooo leucocytes are counted the n u m b e r of neutrophils from which the percentage is calculated is almost always m o r e than IOO, and the general effect of this is a more accurate percentage. Furthermore, Frimodt-M611er halved the sedimentation r a t e - ' T h i s reduction places the sedimentation rate more on a level with the other parts of the formula preventing the S.R. from having u n d u e weight'. T h e F.M. formula is therefore as follows: N + ( S _ ~ _ bI. o×o ) + M + S . R . - - 2 L . 2 N - neutrophil polys. M - monocytes. L - lymphocytes.
235
T h e average I n d e x in this formula in healthy people is - - 5 and + I 2 is the u p p e r limit of w h a t is considered to be normal. T h e lower the index, the better the prognosis. W h a t matters v e r y m u c h in both the H o u g h t o n and the Frimodt-M611er formulae is the increase in the lymphoctyes which, as is well know, points to healing. T h e n u m b e r o f monocytes is also o f i m p o r t a n c e in both and their increase means the formation of new tubercles. T h e following examples show the parallelism between the two methods. T h e y are representative of very m a n y which have been done and exemplify various points to which H o u g h t o n called attention such as a high E.S.R. with a normal Index or a low E.S.R. with a high Index. T h e y serve to show that the FrimodtM611er Index is comparable with the Houghton. (I) This shows the blood picture in an ordinary straightforward case where the E.S.R. and the Indices are in keeping. T h e patient was a y o u n g m a n (C. B.) aged x7 with a l a n e cavity in the left u p p e r zone. At three points in his treatment, as improvement continued, it will be noted how the Frimodt-M611er I n d e x reflects the improvement in the patient's condition in the same w a y as the H o u g h t o n Index. 30.5.52 xm4.53 27.3.52 % % % % % % Neulros. Juveniles ½~ Stabs. 5z 61½ 3 Segmented 55 ) 28 45 Lymphos .. 43~ 55~ 1½ Eosinos. .. 2 4½ z½ Basos. .. x 3~ Monos. .. 7½ 4½ 3 228 Von Bons... 264 269 xi E.S. rate .. 4 2 007 H. Index 297 "5 35o'5 F.M. Index +26- 5 --25- 5 --66 (2) This example shows the 'Bronchitic Blood Picture' where, according to H o u g h t o n , there is a relatively high V.B. count coupled with a relatively rapid S.R. I n other words, the final Index appears good but tile S.R. is not in keeping. I n our case the patient was a w o m a n (D. H.), 35 years of age, who had bilateral p u l m o n a r y tuberculosis and had also suffered from chronic bronchitis for very m a n y years. T h e following was the blood picture and again the Indices are comparable. % Yo Neutros. Juveniles I Stabs. 3½ •. 45 Segmented 4o.~ Lymphos. •. . . . . . 44~ Eosinos. . . . . . . x½ Basos. . . . . . . Monos. . . . . . . 1 Von Boris. . . . . . . 257 E.S. rate . . . . . . 39 H. Index .. .... ~59 F.M. Index ....
) )
..
2
• .
- - I O
TUBERCLE
236
(3) The last example is to demonstrate how, in certain cases, the E.S.R. shows a normal figure but the Index is not good. A woman (C. W.) of 28, with a minimal lung lesion, complained persistently of backache and pain in both arms. No spinal lesion could be found but a few months later, x-ray revealed spinal disease. Here again the Frimodt-M611er method showed an unsatisfactory Index in the same way as the Houghton one, whde the E.S.R. was normal.
% Neutros.
Juveniles ;~ Stabs. Segmented 57~J L) mphos. . . . . Eosinos... .. Basos. . . . . Monos. . . . . Yon Buns. . . . . E.S. rate .... H. 'Index . . . . F.M. Index ..
% ..
66.~ -'24½ I
-8 242 3 215"5 +38
Quite apart from the work done an comparing the two Indices, one very interesting feature has 'been the marked and rapid improvement shown in the blood pictures following chemotherapy with or without thoracic surgery, anajor or minor. At Grassington we have noticed a particularly satisfactory trend in the Indices following combined chemotherapy and pneumoperitoneum. The most markedly good results as reflected in the Indices are to be seen, of course, following chemotherapy and major surgery. In all I have done over i,ooo counts and compared the Houghton Index and the FrimodtM611er Index in over 3oo, and for anyone who has not the requisite laboratory help and who would like to gain the further information which an Index of this type gives, I feel that the Frimodt-M611er might be tried. Yours faithfully, The Hospital, Lomsz E. SA.~ISON, ~t.I).
Grassinglon, Wr. Skipton, Turks.
Thirty Years Ago (Extract from TUBERCLE, September r 9 2 4 Atypical Tubercle Bacilli in H u m a n and Animal Tuberculosis with Special Reference to those Occurring in Lupus, by A. Stanley Griffith, ~LD.) W h a t is the explanation of this frequent modification of the pathogenic properties of tubercle bacilli in lupus? It has been suggested that the action of
September 1954
daylight, subnormal temperature, local treatment, etc., might bring about the change. I f daylight cansed an attenuation of the virulence of tubercle bacilli in the cutaneous tissues we should expect lupus lesions which are most exposed to daylight to contain attenuated tubercle bacilli more frequently than lesions which are concealed from light. There is, however, no demonstrable relation between attenuation and the degree of exposure to light. Fully virulent h u m a n and bovine strains have been obtained from lesions on the face and neck which had been in existence m a n y )'ears. In one case a fully virulent bovine strain was obtained from facial lupus of thlrty-three years' duration. In another case of five )'ears' duration a strain from" the face was fully virulent while one from the buttock, obtained, it is true, eleven months after the face strain, was much less virulent. On the other hand, h u m a n and bovine strains with modified virulence were obtained in 12 cases in which the lesions were on the trunk and legs. Lupus is very commonly situated on the face, neck and extremities, parts of the body which are relatively cool, and the possibility cccurred to me some time ago that subnormal temperaturc might have an influence on the virulence of bacilli multiplying slowly in unfavourable surroundings. With a view to testing this hypothesis I began a passage experiment in toads. A .bovine strain h,'ls now been passed through six toads in succession and the total duration of residence in toad tissues is seven )'ears. This prolonged residence in a coldblooded host has not caused any, decrease in the virulence of the strain or alteration in cultural characteristics. T h e experiment incidentally gives no support to the view that m a m m a l i a n tubercle bacilli can be readily modified in the tissues of cold-blooded animals. Treatment of the lesions with antiseptics, Finsen light, etc., was certainly not the cause of the modifications in the majority of the cases under consideration, since the lesions filrnishing the original material had not been treated in any way. lkIoreover, lupus produced by modified tubercle bacilli is not a milder process than lupus from which fully virulent tubercle bacilli are obtained. O n the contrary', the disease in these cases is characterized by" persistence, intractability and tendency to spread. Although the tubercle bacilli have lost virulence for experimental animals there is no loss, rather is there an increase, in the virulence of the bacilli for the individual affected with lupus.