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TUBERCULIN TREATMENT IN PULMONARY TUBERCULOSIS
1357 In case 1, however, no treatment was given which could account for the subsequent development of amyloidosis. A hyperglobulinaemia is commonly found in many of the primary neoplastic diseases of the reticuloendothelial
system-for example, myelomatosis,
chronic
lymphatic
leukaemia, Hodgkin’s disease, and the reticuloses.
It is of considerable interest to know what proportion of these develop amyloidosis and whether treatment with nitrogen
mustards, irradiation, cortisone, *
or
corticotrophin
was
sriven.
Department of Pathology, University of Manchester.
B. J. LEONARD.
DIAGNOSIS OF ACUTE STAPHYLOCOCCAL ENTEROCOLITIS SiR,-It was with great interest that we read the article by Dr. Matthias and his colleagues1 in which they drew attention to a method of diagnosing acute staphylococcal enterocolitis. We are glad that they have been able to confirm our findings2 that a gram film made of the faeces is a test, both simple and rapid, that can be used routinely on patients receiving antibiotic therapy. One of us (B. R. F.) emphasised the value of the method during a discussion at the recent symposium on hospital coccal infections.3 A. ELLIOT-SMITH Radcliffe Infirmary, B. R. FRISBY. Oxford. PORPHYRINS IN BACTERIOLOGY on atypical acid-fast certain whether these emphasises yet or a several diforganisms comprise homogenous group ferent types. You also mention their chromogenic properties, and that made me wonder why bacteriologists have not studied the porphyrin production of these bacteria under varying cultural conditions as a means of classification.
SiR,ŅYour annotation of May 25
bacilli
.
that it is not
That tubercle bacilli produce porphyrin under certain conditions has long been known,4 5 and the same can be said of many cutaneous myeetee.6But these properties have never been subjected to systematic bacteriological study. Only investigators primarily interested in porphyrins have studied8 these questions-e.g., in diphtheria bacilli,7 Bacillus cereus,8 and rhodopseudomonas species 9-while the bacteriologists seem to have overlooked the possibilities of systematic porphyrin studies under varying cultural conditions. This is presumably because porphyrin analysis is difficult ; but modern techniques of micro-analysis, paper chromatography, &c., have largely overcome this. Recently the possible role of porphyrins in destruction of viruses in vitro has also been pointed out.’° Direct study of the fluorescence of the culture with a portable source of Wood’s light is very cheap and easy,l1 although such simple studies will not be sufficient, since comparatively large amounts of porphyrin may be present without visible fluorescenceand even porphyrin chromogens may be present. The difficulty of obtaining adequate supplies of porphyrin markers for paper chromatography seems on the way to
being conquered.12 Modern porphyrin techniques certainly offer a new field of development for the bacteriologist, especially
where there
are
difficulties of classification.
TORBEN K. WITH. 1. Lancet, June 8, 1957, p. 1172. 2. Cooke, J., Elliott, C., Elliot-Smith, A., Frisby, B. R., Gardner, Brit. med. J. March 9, 1957, p. 542. A. M. N. 3. J. clin. Path. (in the press) ; see Lancet, Jan. 12, 1957, p. 92. 4. Fischer, H., Fink, H. Z. physiol. Chem. 1925, 150, 243. 5. Dhéré, C., Rapetti, L. Bull. Acad. Méd. Paris, 1935, 114, 96. 6. Carrié, C., von Mallincrodt-Haupt, A. S. Arch. Derm. Syph., Wien. 1934, 170, 521. 7. Hale, J. H., Rawlinson, W. A., Gray, C. H., Holt, L. B., Rimington, C., Smith, W. Brit. J. exp. Path. 1952, 31, 96. 8. Schaeffer, P. Biochim. biophys. acta, 1952, 9, 261, 362. 9. Lascelles, J. Biochem. J. 1956, 62, 78. See also Ciba Symposium on
Porphyrins. London, 1955 ; p. 265.
10. Kradolfer, F., Wyler, R. Z. Hyg. 1957, 143, 416. 11. With, T. K. Scand. J. clin. Lab. Invest. 1957 (in the 12. Jørgensen, S. K., With, T. K. Nature, Lond. 1955, With, T. K. Ibid, 1957, 179, 824.
press). 176, 156.
TUBERCULIN TREATMENT IN PULMONARY TUBERCULOSIS SIR,-We should be grateful for an opportunity to comment on your timely annotation of June 8. It seems wise to draw a clear distinction between the methods and aims of the two schools. One (ourselves) seeks to desensitise completely with total antigens and to
maintain desensitisation for many months ; generalised tuberculin reactions are avoided by the choice of dose and increment, and minimised by adjuvant therapy, yet are encountered at one stage in our course in about half of those desensitised. The other school (Smith and Vollum,l Howells and Swithinbank 2) used purified protein derivative, attempt the induction of repeated generalised tuberculin reactions, and encounter some amount of desensitisation. Both court the hazard of the delayed anaphylactic reaction. This needs careful management. If the capacity of the tubercle bacillus first to sensitise, then to cause hypersensitivity, and finally destruction is a dominant aspect of tuberculosis of the lungs then current chemotherapy with adjuvant treatment provides the opportunity to test this thesis. There are two adclitional reasons why these inquiries should be encouraged. The first is the limitations of classical chemotherapy in this disease, and the need to augment them. The second is the need to uncover substances which block the sensitising reaction at different stages ; already some are known3 and as more effective ones are discovered they must be tested in the clinic. We have shown that desensitisation with the total antigens of the tubercle bacillus 4 is, in experienced hands, a safe and practical procedure in the presence of chemotherapy and we now have evidence that desensitisation to challenge with undiluted old tuberculin may be maintained by weekly, two-weekly, or monthly injections. While most patients who present with pulmonary tuberculosis today fall into that favourable prognostic group which responds successfully to chemotherapy, perhaps assisted by surgery, there remains a residue to try the ingenuity of the chest physician. They are those who lack host resistance, and by our reasoning are likely to benefit by desensitisation. Experience has reduced this group to the following : (1) The severe post-primary attacks of children and adolescents (12-19) with gross mediastinal glandular enlarge-
-
ments. (2) Those in whom chemotherapy and surgery have failed. (3) Those with extensive chronic pulmonary bilateral disease unsuited to surgery, with a record of institutional treatment and relapse. (4) Those who on admission show extensive bilateral cavitating disease unlikely to be suitable for surgical treatment. (5) Those whose bacilli are partially resistant to one or
drugs. (6) Those
more
with extensive acute Department of Pharmacology, King’s College, London. Tuberculosis Chemotherapy Unit,
Farnborough Hospital, Farnborough, Kent.
pneumonic tuberculosis. GEORGE BROWNLEE. D. G. MADIGAN.
SiR,-ŅMay I underline a few points in your excellent annotation. The deliberate provocation of focal tuberculin reactions in cases of pulmonary tuberculosis has produced no adverse results either in the series presented by Howells and Swithinbank2 or in the pilot survey in Oxford which preceded it. In tuberculous meningitis, on the other hand, intrathecal tuberculin should be used with the greatest care and with a full appreciation of its potential dangers. Dosage must be closely controlled by full examination of the c.s.F. each-day. Facilities must be 1. Smith, H. V., Vollum, R. L. Lancet, 1950, ii, 275. 2. Howells, C. H. L., Swithinbank, J. Tubercle, 1957, 38, 1. 3. Mongar, J. S., Schild, H. O. J. Physiol. 1957, 135, 301. 4. Brownlee, G., Madigan, D. G. Ciba Foundation Symposium
Experimental Tuberculosis, 1955, p. 211.
on
1358 available for the immediate relief of any undue rise in intracranial pressure. The tuberculin courses given by Smith and Vollum 15 in meningitis and by Howells and Swithinbank2in pulmonary tuberculosis were designed specifically to provoke as many focal reactions as possible before the development of desensitisation. For this reason injections of tuberculin were spaced at intervals of 5 or 7 days. These series were not designed to study the significance of prolonged desensitisation and in neither instance was there any plan to continue tuberculin therapy as a longThe detailed daily c.s.F. term outpatient measure. examinations which are an essential part of Smith and Vollum’s routine give a quantitative picture of the focal reaction in the tuberculous theca. In pulmonary tuberculosis the focal reaction can only be presumed from the presence of a mild general reaction characterised by fever, malaise, and, in some cases, brief increase in local symptoms and signs. These reactions, it is true, cause the patient some inconvenience. Not one of my 78 has asked to discontinue the course on account patients of unpleasant reactions. In one of the Oxford cases, tuberculin reactions provoked haemoptysis from a giant
cavity, and the treatment had to be stopped for this reason. The focal tuberculin reaction is, as you say, a hyperaemic phenomenon designed to carry the antimicrobial drugs to the place where they will do the most good. It must be emphasised, however, that it is the inaccessible and not the resistant bacillus at which the reactions are aimed. There is little, sense and there may be real danger, in provoking hyperaemia in tuberculous tissues if the bacilli are thereby exposed only to drugs to which they are resistant. The Churchill Hospital Oxford.
F. RIDEHALGH.
PRIMARY HEPATIC CARCINOMA SiR,ňYour annotation of April 6 draws certain conclusions which do not appear altogether justified. While it is true that primary carcinoma of the liver is
in oriental countries and parts of Africa, there is insufficient evidence to justify the conclusion that the incidence is highest among the Bantu Negro. The older reports from this Institute refer to highly selected groups of young adult males in whom liver cancer is the most common tumour. While there is some evidence that the Bantu tribes in Portuguese East Africa may have a much higher incidence than those of the Union of South Africa,6 comparison with the West African Negro is as yet impossible in the absence of incidence studies, which are only now being initiated. Visits to Uganda, the Belgian Congo, and French West Africa, however, have given me the impression that carcinoma of the liver is at least as common if not more frequent in some of these areas than in South Africa and what statistics are available support this view.7 In a series of necropsies from a general Bantu hospital in Johannesburg, primary carcinoma of the liver constituted slightly more than 2% of all necropsies. In a rate study, we found, however, that the incidence of primary carcinoma was 22% of all carcinomas in males.88 While this relatively high frequency is mainly due to a high absolute incidence, it is accentuated by the composition of the population at risk which includes a high proportion of young adult males. The reduced incidence of cancer of the skin and of the gastro-intestinal tract in the local African also increases the relative frequency. It is difficult to compare the frequency of cirrhosis in different populations, since we are dependent chiefly on post-mortem studies. In the United States the frequency of cirrhosis usually varies between 2 and 5% common
H. V., Vollum, R. L., Taylor, I. M., Taylor, K. B. Tubercle, 1956, 37, 301. 6. Berman, C. Primary Carcinoma of the Liver. London, 1951. Schweiz. Z. Path. Bakt. 1955, 18, 564. 7. Denoix, P. F. 8. Higginson, J., Oettlé, A. G. Acta Un. int. Cancr. (in the press). 5.
Smith,
of all necropsies,whereas the frequency of cirrhosis at post mortem in Johannesburg in the Bantu is approximately 9-1% in males and 4.0% in females.1O On the other hand, for 1947-54, at the Boston City Hospital, in the series quoted by your editorial, the frequency was 13.93%.11 While this hospital may not be representative of the United States as a whole, it is probably similar to those hospitals serving the Bantu population of South Africa. These observations should cast some doubt on the statement that the high incidence of primary liver cancer in Africa is mainly attributable to a higher frequency of cirrhosis. There is evidence on the other hand, however, to suggest that the high incidence of liver cancer in the African Negro and in other countries with a high incidence, may be dependent on the high frequency with which cirrhosis undergoes malignant change.12 Approximately 54% of cirrhotic livers in males at post mortem in Johannesburg show malignant change. You also state that the relationship of dietary deficiency to cirrhosis in both man and laboratory animals is now well established. While this may be true for animals, the role of nutrition in liver disease in man is far from clear. The only relatively well-documented nutritional " liver disease in man is the fatty liver of kwashiorkor, in which cirrhosis is a very rare sequel. In European practice the term " nutritional cirrhosis is applied to the common " alcoholic " or Laennec’s cirrhosis although the nutritional aetiology is by no means universally accepted. Livers of this nature, although common among the white races of South Africa, are exceedingly rare in the indigenous and poorer Bantu population.1O In contrast the common cirrhosis in which carcinoma develops in South Africa is not of this type, but usually has the features of a post-necrotic or posthepatitic cirrhosis. The aetiology is definitely unknown, but according to French studies, this cirrhosis may be viral in origin 13 and our experience supports this view. Nutrition as a direct factor in this type of cirrhosis has not been demonstrated. I would therefore like to suggest that (i) a high frequency of cirrhosis has not yet been shown to be the cause of the high incidence of liver cancer in underprivileged communities ; (ii) the relationship of diet to liver cancer and cirrhosis is by no means satisfactorily proven; and (iii) that the term " nutritional cirrhosis " in man be dropped until it can be used with greater knowledge of the aetiological background. "
"
South African Institute for Medical Research,
Johannesburg.
JOHN HIGGINSON.
THE WORD " ISOTOPE " now so familiar, was introduced in about 1912 by a medical woman-Margaret Todd, who was also a novelist writing under the name Graham Travers-to fit the concept of elements occupying the same place in the periodic table. The occasion was a social gathering at 11, University Gardens, then the home of Sir George Beilby (the father-in-law of the late Frederick Soddy, who originated the concept of isotopes and other achievements in radiochemistry including the first approach to atomic numbers). Having been obliged to use awkward periphrases to express his " isotopic " ideas, Soddy said he needed a word for the concept; Dr. Todd immediately suggested isotope—iso, the same, topos, place. The word had indeed been published a few years before in a context of organic chemistry ; but there is no reason to suppose that Dr. Todd was aware of that.
SIR,—This word,
Glasgow
9. Lichtman, S. S. Diseases of the Liver Gall Bladder and Bile Ducts. Vol. 2. London, 1953 ; p. 613. 10. Higginson, J., Grobbelaar, B. G., Walker, A. R. P. Amer. J. Path. 1957, 33, 29. 11. MacDonald, R. A. New Engl. J. Med. 1956, 255, 1179. 12. Higginson, J. Schweiz. Z. Path. Bakt. 1955, 18, 625. 13. Charnot, R., Camain, R., Guidicelli, P. Bull. Soc. Path. erot. 1953, 46, 847.
system-for example, myelomatosis,
chronic
lymphatic
leukaemia, Hodgkin’s disease, and the reticuloses.
It is of considerable interest to know what proportion of these develop amyloidosis and whether treatment with nitrogen
mustards, irradiation, cortisone, *
or
corticotrophin
was
sriven.
Department of Pathology, University of Manchester.
B. J. LEONARD.
DIAGNOSIS OF ACUTE STAPHYLOCOCCAL ENTEROCOLITIS SiR,-It was with great interest that we read the article by Dr. Matthias and his colleagues1 in which they drew attention to a method of diagnosing acute staphylococcal enterocolitis. We are glad that they have been able to confirm our findings2 that a gram film made of the faeces is a test, both simple and rapid, that can be used routinely on patients receiving antibiotic therapy. One of us (B. R. F.) emphasised the value of the method during a discussion at the recent symposium on hospital coccal infections.3 A. ELLIOT-SMITH Radcliffe Infirmary, B. R. FRISBY. Oxford. PORPHYRINS IN BACTERIOLOGY on atypical acid-fast certain whether these emphasises yet or a several diforganisms comprise homogenous group ferent types. You also mention their chromogenic properties, and that made me wonder why bacteriologists have not studied the porphyrin production of these bacteria under varying cultural conditions as a means of classification.
SiR,ŅYour annotation of May 25
bacilli
.
that it is not
That tubercle bacilli produce porphyrin under certain conditions has long been known,4 5 and the same can be said of many cutaneous myeetee.6But these properties have never been subjected to systematic bacteriological study. Only investigators primarily interested in porphyrins have studied8 these questions-e.g., in diphtheria bacilli,7 Bacillus cereus,8 and rhodopseudomonas species 9-while the bacteriologists seem to have overlooked the possibilities of systematic porphyrin studies under varying cultural conditions. This is presumably because porphyrin analysis is difficult ; but modern techniques of micro-analysis, paper chromatography, &c., have largely overcome this. Recently the possible role of porphyrins in destruction of viruses in vitro has also been pointed out.’° Direct study of the fluorescence of the culture with a portable source of Wood’s light is very cheap and easy,l1 although such simple studies will not be sufficient, since comparatively large amounts of porphyrin may be present without visible fluorescenceand even porphyrin chromogens may be present. The difficulty of obtaining adequate supplies of porphyrin markers for paper chromatography seems on the way to
being conquered.12 Modern porphyrin techniques certainly offer a new field of development for the bacteriologist, especially
where there
are
difficulties of classification.
TORBEN K. WITH. 1. Lancet, June 8, 1957, p. 1172. 2. Cooke, J., Elliott, C., Elliot-Smith, A., Frisby, B. R., Gardner, Brit. med. J. March 9, 1957, p. 542. A. M. N. 3. J. clin. Path. (in the press) ; see Lancet, Jan. 12, 1957, p. 92. 4. Fischer, H., Fink, H. Z. physiol. Chem. 1925, 150, 243. 5. Dhéré, C., Rapetti, L. Bull. Acad. Méd. Paris, 1935, 114, 96. 6. Carrié, C., von Mallincrodt-Haupt, A. S. Arch. Derm. Syph., Wien. 1934, 170, 521. 7. Hale, J. H., Rawlinson, W. A., Gray, C. H., Holt, L. B., Rimington, C., Smith, W. Brit. J. exp. Path. 1952, 31, 96. 8. Schaeffer, P. Biochim. biophys. acta, 1952, 9, 261, 362. 9. Lascelles, J. Biochem. J. 1956, 62, 78. See also Ciba Symposium on
Porphyrins. London, 1955 ; p. 265.
10. Kradolfer, F., Wyler, R. Z. Hyg. 1957, 143, 416. 11. With, T. K. Scand. J. clin. Lab. Invest. 1957 (in the 12. Jørgensen, S. K., With, T. K. Nature, Lond. 1955, With, T. K. Ibid, 1957, 179, 824.
press). 176, 156.
TUBERCULIN TREATMENT IN PULMONARY TUBERCULOSIS SIR,-We should be grateful for an opportunity to comment on your timely annotation of June 8. It seems wise to draw a clear distinction between the methods and aims of the two schools. One (ourselves) seeks to desensitise completely with total antigens and to
maintain desensitisation for many months ; generalised tuberculin reactions are avoided by the choice of dose and increment, and minimised by adjuvant therapy, yet are encountered at one stage in our course in about half of those desensitised. The other school (Smith and Vollum,l Howells and Swithinbank 2) used purified protein derivative, attempt the induction of repeated generalised tuberculin reactions, and encounter some amount of desensitisation. Both court the hazard of the delayed anaphylactic reaction. This needs careful management. If the capacity of the tubercle bacillus first to sensitise, then to cause hypersensitivity, and finally destruction is a dominant aspect of tuberculosis of the lungs then current chemotherapy with adjuvant treatment provides the opportunity to test this thesis. There are two adclitional reasons why these inquiries should be encouraged. The first is the limitations of classical chemotherapy in this disease, and the need to augment them. The second is the need to uncover substances which block the sensitising reaction at different stages ; already some are known3 and as more effective ones are discovered they must be tested in the clinic. We have shown that desensitisation with the total antigens of the tubercle bacillus 4 is, in experienced hands, a safe and practical procedure in the presence of chemotherapy and we now have evidence that desensitisation to challenge with undiluted old tuberculin may be maintained by weekly, two-weekly, or monthly injections. While most patients who present with pulmonary tuberculosis today fall into that favourable prognostic group which responds successfully to chemotherapy, perhaps assisted by surgery, there remains a residue to try the ingenuity of the chest physician. They are those who lack host resistance, and by our reasoning are likely to benefit by desensitisation. Experience has reduced this group to the following : (1) The severe post-primary attacks of children and adolescents (12-19) with gross mediastinal glandular enlarge-
-
ments. (2) Those in whom chemotherapy and surgery have failed. (3) Those with extensive chronic pulmonary bilateral disease unsuited to surgery, with a record of institutional treatment and relapse. (4) Those who on admission show extensive bilateral cavitating disease unlikely to be suitable for surgical treatment. (5) Those whose bacilli are partially resistant to one or
drugs. (6) Those
more
with extensive acute Department of Pharmacology, King’s College, London. Tuberculosis Chemotherapy Unit,
Farnborough Hospital, Farnborough, Kent.
pneumonic tuberculosis. GEORGE BROWNLEE. D. G. MADIGAN.
SiR,-ŅMay I underline a few points in your excellent annotation. The deliberate provocation of focal tuberculin reactions in cases of pulmonary tuberculosis has produced no adverse results either in the series presented by Howells and Swithinbank2 or in the pilot survey in Oxford which preceded it. In tuberculous meningitis, on the other hand, intrathecal tuberculin should be used with the greatest care and with a full appreciation of its potential dangers. Dosage must be closely controlled by full examination of the c.s.F. each-day. Facilities must be 1. Smith, H. V., Vollum, R. L. Lancet, 1950, ii, 275. 2. Howells, C. H. L., Swithinbank, J. Tubercle, 1957, 38, 1. 3. Mongar, J. S., Schild, H. O. J. Physiol. 1957, 135, 301. 4. Brownlee, G., Madigan, D. G. Ciba Foundation Symposium
Experimental Tuberculosis, 1955, p. 211.
on
1358 available for the immediate relief of any undue rise in intracranial pressure. The tuberculin courses given by Smith and Vollum 15 in meningitis and by Howells and Swithinbank2in pulmonary tuberculosis were designed specifically to provoke as many focal reactions as possible before the development of desensitisation. For this reason injections of tuberculin were spaced at intervals of 5 or 7 days. These series were not designed to study the significance of prolonged desensitisation and in neither instance was there any plan to continue tuberculin therapy as a longThe detailed daily c.s.F. term outpatient measure. examinations which are an essential part of Smith and Vollum’s routine give a quantitative picture of the focal reaction in the tuberculous theca. In pulmonary tuberculosis the focal reaction can only be presumed from the presence of a mild general reaction characterised by fever, malaise, and, in some cases, brief increase in local symptoms and signs. These reactions, it is true, cause the patient some inconvenience. Not one of my 78 has asked to discontinue the course on account patients of unpleasant reactions. In one of the Oxford cases, tuberculin reactions provoked haemoptysis from a giant
cavity, and the treatment had to be stopped for this reason. The focal tuberculin reaction is, as you say, a hyperaemic phenomenon designed to carry the antimicrobial drugs to the place where they will do the most good. It must be emphasised, however, that it is the inaccessible and not the resistant bacillus at which the reactions are aimed. There is little, sense and there may be real danger, in provoking hyperaemia in tuberculous tissues if the bacilli are thereby exposed only to drugs to which they are resistant. The Churchill Hospital Oxford.
F. RIDEHALGH.
PRIMARY HEPATIC CARCINOMA SiR,ňYour annotation of April 6 draws certain conclusions which do not appear altogether justified. While it is true that primary carcinoma of the liver is
in oriental countries and parts of Africa, there is insufficient evidence to justify the conclusion that the incidence is highest among the Bantu Negro. The older reports from this Institute refer to highly selected groups of young adult males in whom liver cancer is the most common tumour. While there is some evidence that the Bantu tribes in Portuguese East Africa may have a much higher incidence than those of the Union of South Africa,6 comparison with the West African Negro is as yet impossible in the absence of incidence studies, which are only now being initiated. Visits to Uganda, the Belgian Congo, and French West Africa, however, have given me the impression that carcinoma of the liver is at least as common if not more frequent in some of these areas than in South Africa and what statistics are available support this view.7 In a series of necropsies from a general Bantu hospital in Johannesburg, primary carcinoma of the liver constituted slightly more than 2% of all necropsies. In a rate study, we found, however, that the incidence of primary carcinoma was 22% of all carcinomas in males.88 While this relatively high frequency is mainly due to a high absolute incidence, it is accentuated by the composition of the population at risk which includes a high proportion of young adult males. The reduced incidence of cancer of the skin and of the gastro-intestinal tract in the local African also increases the relative frequency. It is difficult to compare the frequency of cirrhosis in different populations, since we are dependent chiefly on post-mortem studies. In the United States the frequency of cirrhosis usually varies between 2 and 5% common
H. V., Vollum, R. L., Taylor, I. M., Taylor, K. B. Tubercle, 1956, 37, 301. 6. Berman, C. Primary Carcinoma of the Liver. London, 1951. Schweiz. Z. Path. Bakt. 1955, 18, 564. 7. Denoix, P. F. 8. Higginson, J., Oettlé, A. G. Acta Un. int. Cancr. (in the press). 5.
Smith,
of all necropsies,whereas the frequency of cirrhosis at post mortem in Johannesburg in the Bantu is approximately 9-1% in males and 4.0% in females.1O On the other hand, for 1947-54, at the Boston City Hospital, in the series quoted by your editorial, the frequency was 13.93%.11 While this hospital may not be representative of the United States as a whole, it is probably similar to those hospitals serving the Bantu population of South Africa. These observations should cast some doubt on the statement that the high incidence of primary liver cancer in Africa is mainly attributable to a higher frequency of cirrhosis. There is evidence on the other hand, however, to suggest that the high incidence of liver cancer in the African Negro and in other countries with a high incidence, may be dependent on the high frequency with which cirrhosis undergoes malignant change.12 Approximately 54% of cirrhotic livers in males at post mortem in Johannesburg show malignant change. You also state that the relationship of dietary deficiency to cirrhosis in both man and laboratory animals is now well established. While this may be true for animals, the role of nutrition in liver disease in man is far from clear. The only relatively well-documented nutritional " liver disease in man is the fatty liver of kwashiorkor, in which cirrhosis is a very rare sequel. In European practice the term " nutritional cirrhosis is applied to the common " alcoholic " or Laennec’s cirrhosis although the nutritional aetiology is by no means universally accepted. Livers of this nature, although common among the white races of South Africa, are exceedingly rare in the indigenous and poorer Bantu population.1O In contrast the common cirrhosis in which carcinoma develops in South Africa is not of this type, but usually has the features of a post-necrotic or posthepatitic cirrhosis. The aetiology is definitely unknown, but according to French studies, this cirrhosis may be viral in origin 13 and our experience supports this view. Nutrition as a direct factor in this type of cirrhosis has not been demonstrated. I would therefore like to suggest that (i) a high frequency of cirrhosis has not yet been shown to be the cause of the high incidence of liver cancer in underprivileged communities ; (ii) the relationship of diet to liver cancer and cirrhosis is by no means satisfactorily proven; and (iii) that the term " nutritional cirrhosis " in man be dropped until it can be used with greater knowledge of the aetiological background. "
"
South African Institute for Medical Research,
Johannesburg.
JOHN HIGGINSON.
THE WORD " ISOTOPE " now so familiar, was introduced in about 1912 by a medical woman-Margaret Todd, who was also a novelist writing under the name Graham Travers-to fit the concept of elements occupying the same place in the periodic table. The occasion was a social gathering at 11, University Gardens, then the home of Sir George Beilby (the father-in-law of the late Frederick Soddy, who originated the concept of isotopes and other achievements in radiochemistry including the first approach to atomic numbers). Having been obliged to use awkward periphrases to express his " isotopic " ideas, Soddy said he needed a word for the concept; Dr. Todd immediately suggested isotope—iso, the same, topos, place. The word had indeed been published a few years before in a context of organic chemistry ; but there is no reason to suppose that Dr. Todd was aware of that.
SIR,—This word,
Glasgow
9. Lichtman, S. S. Diseases of the Liver Gall Bladder and Bile Ducts. Vol. 2. London, 1953 ; p. 613. 10. Higginson, J., Grobbelaar, B. G., Walker, A. R. P. Amer. J. Path. 1957, 33, 29. 11. MacDonald, R. A. New Engl. J. Med. 1956, 255, 1179. 12. Higginson, J. Schweiz. Z. Path. Bakt. 1955, 18, 625. 13. Charnot, R., Camain, R., Guidicelli, P. Bull. Soc. Path. erot. 1953, 46, 847.