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BACTERIAL SYNTHESIS OF VITAMIN B12
706
spinal cord ; nor do they help the organism to resist The fact an attack by the lipmolytic streptococcus. that in controlled experiments physiological substances, given in large quantities, may exert a therapeutic influence upon pathological conditions-the recent discovery of the apparent efficacy of A.C.T.H. and cortisone on malignant tumours is an impressive example 8-fits into this concept. Professor Selye deserves the admiration and thanks of the medical profession for presenting so much new experimental evidence. The most effective answer to his critics he has given himself by stating : " Our facts must be correct. Our theories need not be if they help us to discover important new facts." Union Education Department, Pretoria.
ERNST JOKL.
STREPTOMYCIN AND TUBERCULIN
SiR,-I have already reported in your columns certain observations on the effect of streptomycin on the tuberculin reaction in tuberculous meningitis.Further experience has shown that in this respect cases fall into three groups as follows : 1.Moderate cases, in which the reaction increases at the commencement of streptomycin treatment and then falls away as recovery sets in. When the stage of apparent cure is reached, the test again becomes strongly positive and remains so during convalescence. 2. Severe cases, in which the reaction is negative or weakly positive in the early stages and becomes stronger as treatment proceeds. Its subsequent behaviour depends on the course of the disease. 3. Very severe cases with a positive reaction in which the outcome is fatal despite treatment. In these cases, the reaction remains positive throughout.
In the light of the above observations, I have now used subcutaneous or intravenous tuberculin in conjunction with streptomycin for some time, varying the dose according to the strength of the reaction. In three cases I have administered tuberculin intrathecally, but I have now abandoned this route because of the violent reactions which followed. CASE L-Aged 10 years. Admitted April 6, 1947. On Oct. 2, 1947, tuberculin 0-01 ;jLg. was given intrathecally, in view of the persistence of a high level of protein in the cerebrospinal fluid. The reaction was severe. The temperature rose above 39°C, there was violent headache, and the c.s.F. pressure increased. Two days later 0’1 g. was given, and the same reaction was observed, but subsided within 24 hours. The patient was discharged on Dec. 16, 1947, and has remained well since. CASE 2.-Aged 8. Admitted April 11, 1947. One dose of tuberculin 1 g. was given intrathecally on April 20, 1947, but was not repeated in view of the violence of the reaction. Tuberculin was subsequently given subcutaneously. The patient was discharged on Oct. 5, 1947, and has remained well since. CASE 3.-Aged 6. Admitted Dec. 27, 1947. Owing to the prolonged course of the disease, one intrathecal injection of tuberculin 0-01 tg. was given on April 16, 1948. This the temperature was followed by a very severe reaction : rose to over 40"C, the pulse-rate to 150, and the c.s.F. pressure so high as to cause exophthalmos. For two weeks symptoms had to be relieved by drawing off c.s.F. After that time it was found that protein had increased from 1’6 to 4 g. per 100 ml., and cells (mainly lymphocytes) from 30 to 750 per ml. The patient recovered and was discharged on Sept. 20, 1948.
Though
we
cannot
yet draw any conclusions
as
to the
usefulness of tuberculin in
conjunction with streptomycin, it is the general opinion in our clinic that tolerance to tuberculin increases during St. Sophia’s Children’s Hospital, Athens.
streptomycin treatment. K. CHOREMIS.
Spies, T. D., Stone, R. E., Lopez, G. G., Milanes, F., Toca, R. L., Reboredo, A. Lancet, Aug. 12, 1950, p. 241. 9. Choremis, K., Zervos, N., Constantinides, V., Pantazis, S. 8.
Ibid, 1948, ii, 595.
BACTERIAL SYNTHESIS OF VITAMIN B12 SiR,-I have read with great interest the article by Dr. Dyke and his colleagues, in your issue of March 18 ; and I should like to add some comments.
In a bacteriological investigation of the mucosa of fresh pig stomach and of three commercial preparations from different factories of pig stomach against pernicious anaemia, I have constantly found considerable numbers of only two types of bacteria-Bacillus subtilis and one I therefore of the non-pathogenic corynebacteria. presume that one of these bacteria may be identical Later investigations with the " intrinsic factor."1 have shown that both these bacteria synthesise vitamin BIZ in amounts that may be supposed to be important for the concentration of B12 in intestinal mucosa. Clinical investigations with strains of these bacteria in cases of pernicious anaemia have hitherto not given convincing results, but the provisional results indicate that these bacteria, besides producing vitamin BÌ2 by their synthesis of antibiotics, are able to control unwanted bacterial growth in the intestinal mucosa in these cases. This has led to the following working hypothesis of the aetiology of pernicious ansemia: if vitamin B12 is to be absorbed it must be present in intestinal mucosa in a concentration higher than that in the tissues. This is the case in the normal organism, where the intestinal mucosa. is infected with B12-producing strains. In the diseased organism these strains are expelled from the mucosa and replaced by B12-consuming Bact. coli and lactobacilli, and this mucosa forms a barrier to the absorption of B12 from the intestinal contents. Further investigations are being made on the basis of Ibis working- bvnotbesis.
Microbiological Laboratory, Ferrosan Ltd., Copenhagen.
B. NOER Chief Microbiologist.
HOSPITAL ADMINISTRATION
SIR,-It would be difficult to overrate the importance of your correspondent’s article of Sept. 30 under the title Preface to Hospital Administration. It is stimulating chiefly because it insists that hospital administration is one thing, and that the services and crafts which go to meet a hospital’s physical problems are another. These functions are all too frequently confused ; and the confusion has increased because there has been limited experience in procedures for meeting the growing needs of the Ministry of Health for standardised practices and tabulated information. Dr. MacWilliam’s thoughtful letter (Nov. 11) is an evidence that in the present transition in the health services this distinction is likely to be smothered in a welter of administrative conveniences and methods. Readers of the principles set out by Dr. MacWilliam are likely to accept them without, perhaps, realising their far-reaching implications. The questions posed by him focus our attention on some of the difficulties and dangers of the present attempt to weld together two different conceptions of hospital practice and control. But the distinctions between the voluntary hospital and local-authority hospital lay not in accountancy techniques, budgetary controls, and other tools of administration. The distinction was rather in responsibility. On the one hand this responsibility was carried entirely by the hospital board and its administration, and was immediately affected by public reactions to its policies. On the other hand there was an administration responsible in an auditing sense to a financial authority outside the hospital, elected for other than hospital tasks, and having no special sanction or experience in the field of economy consistent with the requirements of the sick. Dr. MacWilliam’s analysis demonstrates some important 1. Nocr, B.
Dansk. Tidsskr. Farm. 1949,
23,
111.
spinal cord ; nor do they help the organism to resist The fact an attack by the lipmolytic streptococcus. that in controlled experiments physiological substances, given in large quantities, may exert a therapeutic influence upon pathological conditions-the recent discovery of the apparent efficacy of A.C.T.H. and cortisone on malignant tumours is an impressive example 8-fits into this concept. Professor Selye deserves the admiration and thanks of the medical profession for presenting so much new experimental evidence. The most effective answer to his critics he has given himself by stating : " Our facts must be correct. Our theories need not be if they help us to discover important new facts." Union Education Department, Pretoria.
ERNST JOKL.
STREPTOMYCIN AND TUBERCULIN
SiR,-I have already reported in your columns certain observations on the effect of streptomycin on the tuberculin reaction in tuberculous meningitis.Further experience has shown that in this respect cases fall into three groups as follows : 1.Moderate cases, in which the reaction increases at the commencement of streptomycin treatment and then falls away as recovery sets in. When the stage of apparent cure is reached, the test again becomes strongly positive and remains so during convalescence. 2. Severe cases, in which the reaction is negative or weakly positive in the early stages and becomes stronger as treatment proceeds. Its subsequent behaviour depends on the course of the disease. 3. Very severe cases with a positive reaction in which the outcome is fatal despite treatment. In these cases, the reaction remains positive throughout.
In the light of the above observations, I have now used subcutaneous or intravenous tuberculin in conjunction with streptomycin for some time, varying the dose according to the strength of the reaction. In three cases I have administered tuberculin intrathecally, but I have now abandoned this route because of the violent reactions which followed. CASE L-Aged 10 years. Admitted April 6, 1947. On Oct. 2, 1947, tuberculin 0-01 ;jLg. was given intrathecally, in view of the persistence of a high level of protein in the cerebrospinal fluid. The reaction was severe. The temperature rose above 39°C, there was violent headache, and the c.s.F. pressure increased. Two days later 0’1 g. was given, and the same reaction was observed, but subsided within 24 hours. The patient was discharged on Dec. 16, 1947, and has remained well since. CASE 2.-Aged 8. Admitted April 11, 1947. One dose of tuberculin 1 g. was given intrathecally on April 20, 1947, but was not repeated in view of the violence of the reaction. Tuberculin was subsequently given subcutaneously. The patient was discharged on Oct. 5, 1947, and has remained well since. CASE 3.-Aged 6. Admitted Dec. 27, 1947. Owing to the prolonged course of the disease, one intrathecal injection of tuberculin 0-01 tg. was given on April 16, 1948. This the temperature was followed by a very severe reaction : rose to over 40"C, the pulse-rate to 150, and the c.s.F. pressure so high as to cause exophthalmos. For two weeks symptoms had to be relieved by drawing off c.s.F. After that time it was found that protein had increased from 1’6 to 4 g. per 100 ml., and cells (mainly lymphocytes) from 30 to 750 per ml. The patient recovered and was discharged on Sept. 20, 1948.
Though
we
cannot
yet draw any conclusions
as
to the
usefulness of tuberculin in
conjunction with streptomycin, it is the general opinion in our clinic that tolerance to tuberculin increases during St. Sophia’s Children’s Hospital, Athens.
streptomycin treatment. K. CHOREMIS.
Spies, T. D., Stone, R. E., Lopez, G. G., Milanes, F., Toca, R. L., Reboredo, A. Lancet, Aug. 12, 1950, p. 241. 9. Choremis, K., Zervos, N., Constantinides, V., Pantazis, S. 8.
Ibid, 1948, ii, 595.
BACTERIAL SYNTHESIS OF VITAMIN B12 SiR,-I have read with great interest the article by Dr. Dyke and his colleagues, in your issue of March 18 ; and I should like to add some comments.
In a bacteriological investigation of the mucosa of fresh pig stomach and of three commercial preparations from different factories of pig stomach against pernicious anaemia, I have constantly found considerable numbers of only two types of bacteria-Bacillus subtilis and one I therefore of the non-pathogenic corynebacteria. presume that one of these bacteria may be identical Later investigations with the " intrinsic factor."1 have shown that both these bacteria synthesise vitamin BIZ in amounts that may be supposed to be important for the concentration of B12 in intestinal mucosa. Clinical investigations with strains of these bacteria in cases of pernicious anaemia have hitherto not given convincing results, but the provisional results indicate that these bacteria, besides producing vitamin BÌ2 by their synthesis of antibiotics, are able to control unwanted bacterial growth in the intestinal mucosa in these cases. This has led to the following working hypothesis of the aetiology of pernicious ansemia: if vitamin B12 is to be absorbed it must be present in intestinal mucosa in a concentration higher than that in the tissues. This is the case in the normal organism, where the intestinal mucosa. is infected with B12-producing strains. In the diseased organism these strains are expelled from the mucosa and replaced by B12-consuming Bact. coli and lactobacilli, and this mucosa forms a barrier to the absorption of B12 from the intestinal contents. Further investigations are being made on the basis of Ibis working- bvnotbesis.
Microbiological Laboratory, Ferrosan Ltd., Copenhagen.
B. NOER Chief Microbiologist.
HOSPITAL ADMINISTRATION
SIR,-It would be difficult to overrate the importance of your correspondent’s article of Sept. 30 under the title Preface to Hospital Administration. It is stimulating chiefly because it insists that hospital administration is one thing, and that the services and crafts which go to meet a hospital’s physical problems are another. These functions are all too frequently confused ; and the confusion has increased because there has been limited experience in procedures for meeting the growing needs of the Ministry of Health for standardised practices and tabulated information. Dr. MacWilliam’s thoughtful letter (Nov. 11) is an evidence that in the present transition in the health services this distinction is likely to be smothered in a welter of administrative conveniences and methods. Readers of the principles set out by Dr. MacWilliam are likely to accept them without, perhaps, realising their far-reaching implications. The questions posed by him focus our attention on some of the difficulties and dangers of the present attempt to weld together two different conceptions of hospital practice and control. But the distinctions between the voluntary hospital and local-authority hospital lay not in accountancy techniques, budgetary controls, and other tools of administration. The distinction was rather in responsibility. On the one hand this responsibility was carried entirely by the hospital board and its administration, and was immediately affected by public reactions to its policies. On the other hand there was an administration responsible in an auditing sense to a financial authority outside the hospital, elected for other than hospital tasks, and having no special sanction or experience in the field of economy consistent with the requirements of the sick. Dr. MacWilliam’s analysis demonstrates some important 1. Nocr, B.
Dansk. Tidsskr. Farm. 1949,
23,
111.