- Email: [email protected]
SERUM-VITAMIN-B12 AND CHLORPROMAZINE
713 from mid-year values published by the U.S. Bureau of Census Annual incidence-rates of hepatitis (per million population were calculated from cases in the 4th quarter of one year anc the lst 3 quarters of the next (October to September inclusive) Annual leukaemia death-rates (per million population) were computed by single year of age for all children under 5 years by the method of Slocumb and MacMahon 4; but we arranged the rates by year of birth (cohorts of births from July of on year to June of the next, both months inclusive) rather than b3 year of death. The leukaemia deaths and population estimates were then combined to obtain rates for deaths under 2 years and 2-4 years inclusive, and for all deaths under 5 years of age In the accompanying fig., the data are aligned so thai hepatitis incidence can be compared with leukaemia-rates for children born 9 months later. For example, leukaemia deaths used in calculating rates for 1954 occurred among children whose births centred around Jan. 1, 1954, and hepatitis-rates were obtained from cases and population estimate! centring around April 1, 1953 (9 months earlier). The fluctuations in hepatitis incidence among the general population sinc 1952 are shown in the figure to be unrelated to the smalle] variations in birth-cohort rates for leukaemia. There is nc evidence that epidemic peaks of hepatitis which occurred ir 1954 and 1961 in the U.S.5 were followed by any increase ir the births of children fated to develop leukaemia early in life. It appears that the association noted between viral hepatiti and Down’s syndrome does not have implications extending t( childhood leukaemia. Epidemiology Branch, National Cancer Institute, JOSEPH F. FRAUMENI, Jr. National Institutes of Health, FRANK E. LUNDIN, Jr. Bethesda 14, Maryland, U.S.A.
CERVICAL-SMEAR PROBLEMS SIR,-It may interest Dr. Nettell (March 12) that in this Association’s leaflet Calling all Women the following statement is made in connection with the cervical-smear test: " Now if the woman is told that the scales [cells] are normal that will be a great relief, but she must not. think that this means nothing else can ever go wrong with the womb. She may some day have ’fibroid lumps’ in the womb or’polypi’.Most of these other things show themselves by irregular bleeding from the womb-i.e., bleeding between the normal periods, or floodings, or irregular bleeding during the change of life. If such bleeding occurs the woman must go to the doctor at once. This is urgent. She must not wait until the bleeding has stopped, and if it has stopped hope that it will not occur again." Cancer Information Association, MALCOLM DONALDSON. 6, Queen Street, Oxford.
RESPONSE TO PHYTOHÆMAGGLUTININ SIR,-A bean extract, phytohaemagglutinin (P.H.A.), when added to blood-lymphocytes in serum causes a proportion of them to transform to large pyroninophilic cells which divide.g Studies on lymphocyte transformation, using a quantitative ribonucleic-acid assay, show that the P.H.A. concentration required for an optimal response is linearly related to the serum-concentration.7 This is in keeping with reports of precipitation of P.H.A. with serum-factors.8 Many investigators have examined the responsiveness to P.H.A. of cells taken from patients with different disorders. Since the levels of some serum-constituents are known to vary in disease, it is likely that the level of P.H.A.-binding factors will also vary. Thus if cells are stimulated in autologous serum the P.H.A. requirement will alter. Failure to adjust the P.H.A. concentration mav be a Dossible source of error. Department of Biochemistry, D. FORSDYKE. University of Cambridge. 4. Slocumb, J. C., MacMahon, B. New Engl. J. Med. 1963, 268, 922. 5. McCollum, R. W. Am. J. Med. 1962, 32, 657. 6. Nowell, P. C. Cancer Res. 1960, 20, 462. 7. Forsdyke, D., Korner, A. Unpublished. 8. Holland, N., Holland, P. Nature, Lond. 1965, 207, 1307.
SERUM-VITAMIN-B12 AND CHLORPROMAZINE SIR,-I cannot understand how Dr. Forshaw and Miss Harwood (March 12) conclude that the cost of radioisotope dilution assay of serum-vitamin-B121 is "B40 for the first serum-assay in each batch, and E20 for each other serum-assay " when using a 5’Co-vitamin-Blz solution of high specific activity, and E4 and E2 respectively when using 5’Co-vitaminB12 of low specific activity. Do they in fact use this technique ? And if so how do they arrive at these figures ? The technique in question is under trial use in this laboratory, and the approximate costs are as follows (where n=number of sera to be assayed): 1. Using 57 Co-vitamin-B12 of high specific activity (60 jjf.C per g.), (6+6n) shillings. 2. Using 5’Co-vitamin-Blz of low specific activity (-t: 1 {j!.C per g.), (1 +n) pence. 3. Using 57Co-vitamin-B12 of recommended specific activity (about 10 u.C
per
tLg.), (1 +n) shillings.
Attic Laboratory, Children’s Department, Royal Victoria Infirmary, Newcastle upon Tyne.
M. LANDON.
HYPERSENSITIVITY AND THE LUNG SIR,-Your leading article (Feb. 26) provides an excellent review of recent developments in this field. But you dismiss somewhat cursorily the study of allergy in your sentence "... and ’allergology ’, concerned with the study of asthma and other hypersensitivity diseases in man, usually by only qualitative and sometimes almost subjective techniques ..." Whilst this might well be a valid criticism of many studies of asthma and hay-fever in the past, allergy (or should it be the more cumbersome " allergology " ?) is any acknowledged specialty in many parts of the world, and any allergic (allergologic ?) patient, particularly if his complaint is seasonal, has no doubts whatever about the relation between the allergen and his symptoms. There is no doubt that immunological techniques have made a very significant contribution to the elucidation of hypersensitivity disease associated with precipitating antibodies, but this is far from the case in the very much greater number of patients who have immediate-type allergic hypersensitivity to grass-pollen, moulds, and other allergens. Such cases are very much more frequent than bird fancier’s lung, farmer’s lung, and the other rarer hypersensitivity diseases mentioned in your leader. The major difference appears to be that, in the rare conditions mentioned, immunological evidence is easily demonstrated, whereas in reaginic-type sensitisation it is not yet possible to send serum to the laboratory and receive the answer by return post. My personal belief is that the study of allergic states will remain the object of criticism and scepticism until these studies are placed on a suitably objective basis by means of provocation tests. In this way objective proof of the effectiveness of hyposensitisation procedures can be demonstrated by repeating the test after treatment, so that results no longer depend on whatever statement the patient decides to make. Your issue of March 12 features a preliminary communication by Professor Herxheimer and his colleagues, regarding asthma caused by fungal spores, which is an excellent example of objective allergy research, and which, in relation to sporobolomyces, fully confirms my findings with the nasal provocation test. This type of provocation test is widely applicable because it can be carried out on an outpatient basis. Any new immunological tests would have to show results confirming the provocation tests, and demonstrating significant changes after successful treatment. It is unfortunate that your leader, by the dismissal of " allergology " in a sentence, could lead to the precedence of the esoteric over the commonplace. Perhaps it epitomises the 1.
Lau, K.-S., Gottlieb, C., Wasserman, L. R., Herbert, V. Blood, 1965, 26, 202.
CERVICAL-SMEAR PROBLEMS SIR,-It may interest Dr. Nettell (March 12) that in this Association’s leaflet Calling all Women the following statement is made in connection with the cervical-smear test: " Now if the woman is told that the scales [cells] are normal that will be a great relief, but she must not. think that this means nothing else can ever go wrong with the womb. She may some day have ’fibroid lumps’ in the womb or’polypi’.Most of these other things show themselves by irregular bleeding from the womb-i.e., bleeding between the normal periods, or floodings, or irregular bleeding during the change of life. If such bleeding occurs the woman must go to the doctor at once. This is urgent. She must not wait until the bleeding has stopped, and if it has stopped hope that it will not occur again." Cancer Information Association, MALCOLM DONALDSON. 6, Queen Street, Oxford.
RESPONSE TO PHYTOHÆMAGGLUTININ SIR,-A bean extract, phytohaemagglutinin (P.H.A.), when added to blood-lymphocytes in serum causes a proportion of them to transform to large pyroninophilic cells which divide.g Studies on lymphocyte transformation, using a quantitative ribonucleic-acid assay, show that the P.H.A. concentration required for an optimal response is linearly related to the serum-concentration.7 This is in keeping with reports of precipitation of P.H.A. with serum-factors.8 Many investigators have examined the responsiveness to P.H.A. of cells taken from patients with different disorders. Since the levels of some serum-constituents are known to vary in disease, it is likely that the level of P.H.A.-binding factors will also vary. Thus if cells are stimulated in autologous serum the P.H.A. requirement will alter. Failure to adjust the P.H.A. concentration mav be a Dossible source of error. Department of Biochemistry, D. FORSDYKE. University of Cambridge. 4. Slocumb, J. C., MacMahon, B. New Engl. J. Med. 1963, 268, 922. 5. McCollum, R. W. Am. J. Med. 1962, 32, 657. 6. Nowell, P. C. Cancer Res. 1960, 20, 462. 7. Forsdyke, D., Korner, A. Unpublished. 8. Holland, N., Holland, P. Nature, Lond. 1965, 207, 1307.
SERUM-VITAMIN-B12 AND CHLORPROMAZINE SIR,-I cannot understand how Dr. Forshaw and Miss Harwood (March 12) conclude that the cost of radioisotope dilution assay of serum-vitamin-B121 is "B40 for the first serum-assay in each batch, and E20 for each other serum-assay " when using a 5’Co-vitamin-Blz solution of high specific activity, and E4 and E2 respectively when using 5’Co-vitaminB12 of low specific activity. Do they in fact use this technique ? And if so how do they arrive at these figures ? The technique in question is under trial use in this laboratory, and the approximate costs are as follows (where n=number of sera to be assayed): 1. Using 57 Co-vitamin-B12 of high specific activity (60 jjf.C per g.), (6+6n) shillings. 2. Using 5’Co-vitamin-Blz of low specific activity (-t: 1 {j!.C per g.), (1 +n) pence. 3. Using 57Co-vitamin-B12 of recommended specific activity (about 10 u.C
per
tLg.), (1 +n) shillings.
Attic Laboratory, Children’s Department, Royal Victoria Infirmary, Newcastle upon Tyne.
M. LANDON.
HYPERSENSITIVITY AND THE LUNG SIR,-Your leading article (Feb. 26) provides an excellent review of recent developments in this field. But you dismiss somewhat cursorily the study of allergy in your sentence "... and ’allergology ’, concerned with the study of asthma and other hypersensitivity diseases in man, usually by only qualitative and sometimes almost subjective techniques ..." Whilst this might well be a valid criticism of many studies of asthma and hay-fever in the past, allergy (or should it be the more cumbersome " allergology " ?) is any acknowledged specialty in many parts of the world, and any allergic (allergologic ?) patient, particularly if his complaint is seasonal, has no doubts whatever about the relation between the allergen and his symptoms. There is no doubt that immunological techniques have made a very significant contribution to the elucidation of hypersensitivity disease associated with precipitating antibodies, but this is far from the case in the very much greater number of patients who have immediate-type allergic hypersensitivity to grass-pollen, moulds, and other allergens. Such cases are very much more frequent than bird fancier’s lung, farmer’s lung, and the other rarer hypersensitivity diseases mentioned in your leader. The major difference appears to be that, in the rare conditions mentioned, immunological evidence is easily demonstrated, whereas in reaginic-type sensitisation it is not yet possible to send serum to the laboratory and receive the answer by return post. My personal belief is that the study of allergic states will remain the object of criticism and scepticism until these studies are placed on a suitably objective basis by means of provocation tests. In this way objective proof of the effectiveness of hyposensitisation procedures can be demonstrated by repeating the test after treatment, so that results no longer depend on whatever statement the patient decides to make. Your issue of March 12 features a preliminary communication by Professor Herxheimer and his colleagues, regarding asthma caused by fungal spores, which is an excellent example of objective allergy research, and which, in relation to sporobolomyces, fully confirms my findings with the nasal provocation test. This type of provocation test is widely applicable because it can be carried out on an outpatient basis. Any new immunological tests would have to show results confirming the provocation tests, and demonstrating significant changes after successful treatment. It is unfortunate that your leader, by the dismissal of " allergology " in a sentence, could lead to the precedence of the esoteric over the commonplace. Perhaps it epitomises the 1.
Lau, K.-S., Gottlieb, C., Wasserman, L. R., Herbert, V. Blood, 1965, 26, 202.