192 RADIATION AND LEUKÆMIA SIR,-Court-Brown and Dollhave now published in extenso the data derived from a survey of ankylosing spondylitics treated by...

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192 RADIATION AND LEUKÆMIA SIR,-Court-Brown and Dollhave now published in extenso the data derived from a survey of ankylosing spondylitics treated by wide-field X irradiation. They were unable to decide for certain but thought it likely that there was no threshold dose for the induction of leukaemia and that the relation between dose and incidence of leukaemia was a simple linear one. Their report, the most substantial contribution to date " and probably for some time to come, is likely to be used by everyone interested in these problems, as for instance Lewis,2 and is certainly a model for others to emulate "




The only other set of human data, from the survivors of the atomic explosions at Hiroshima and Nagasaki, provides an uncertain basis for relating dose and incidence of leukaemia because the dose received was so uncertain. Thus the simple classification of dose by distance, used by Lewis,2 and others was discarded in favour of a much more detailed classification in the extensive genetic survey by Neel and Schull.3 Unfortunately a similar analysis of dose in relation to leukaemia incidence does not seem to have been made. Thus, the report of Court-Brown and Doll is at present the only source of human data on radiation-induced leukaemia where a tolerably accurate idea of the dose is available. There may therefore be some point in a further analysis of their data which suggests that susceptibility to leukaemia-induction by irradiation increases with age, the opposite of what would be expected from the findings of Stewart et awl.4 It is also noteworthy that in ankylosing spondylitics treated by irradiation aplastic anaemia occurred almost exclusively in the older half of the population at risk

From table 16 the mean man-years at risk per male patient 5-5 years. Dividing by 5-5 therefore gives the annual incidence per million per rontgen (see accompanying table. column 3). Multiplying these figures by 55 gives, on the linear hypothesis, the annual incidence per million expected to follow a dose of 55r (see table, column 4). The age-specific death-rates for leukaemia in England and Wales are given by Lea and Abbatt(data cited from Case and Pearson), and are also shown in the accompanying table. There is a surprising similarity between these national death. rates and the expected annual rate per 55 rontgen (columns 4 and 5), which suggests that the susceptibility to irradiation in absolute terms increases with age, whereas the doubling dose (over a 6-5 year observation period) is about 55r partial body irradiation at all ages.


This comparison may suggest a variety of speculations but proves nothing. Nevertheless, over the apparently linear portion of the curve relating dose and leukaemia-rate (Court-Brown and Doll’s fig. 1), the variation with age in leukaemia-rate--standardised for dose as far as the reported data allow (column 2)-is as great as the variation with dose in leukaemia-rate (standardised for age)-i.e., age is quantitatively almost as important as dose. Thus the straightforward method of assessing dose and years at risk used in the reportmay not be valid. Some weighting factor is needed to take into account the increase in susceptibility to radiation with ageing. and until this is provided the dose-response relations given in the report should perhaps be regarded as not to be relied upon. It is not possible to check this suggestion by more detailed analysis of the data provided by Court-Brown and Doll: their dosage data are given in the form suitable to the analysis which they chose to make.


Medical Research Council

,(table 6).1 Table 12 of the reportshows a fivefold in the standardised leukaemia-rate. This

Radiobiological Research Unit, was


The age-specific death-rates

are given for age-groups 5 years older than the rates for spondylitics where the grouping was according to the age of initial treatment.

by a standardisation procedure when estimating doseresponse relationships, but no consideration seems to have been given to the possibility that the difference in incidence with age might represent a real difference in susceptibility to leukaemogenesis by radiation. If such a difference exists, different conclusions might have been reached about simple proportionality between incidence of leukaemia and radiation dose. Court-Brown and Doll’s table 15 gives the mean spinal dose (for males only) for the same age-groups as the leukaemia-rates of table 12 (males and females together). By combining the two sets of data it is possible to derive the leukaemia-rate per 1000 patients per 1000r, as in the table above (column 2). On the hypothesis that there is a linear relation between dose and leukaemia-rate, these rates will be the same as the leukaemiarate per million per rontgen. account


Court-Brown, W. M., Doll, R. Leukæmia and Aplastic Anæmia in Patients Irradiated for Ankylosing Spondylitis. Spec. Rep. Ser. med. Res. Coun., Lond. 1957, no. 295. See Lancet, 1957, i, 1130.

2. Lewis, E. B. Science, 1957, 125, 965. 3. Neel, J. V., Schull, W. J. Effect of Exposure to the Atomic Bombs on Pregnancy Termination in Hiroshima and Nagasaki. National Academy of Sciences, Washington, publication no. 461, 1956. 4. Stewart, A., Webb, J., Giles, D., Hewitt, D. Lancet, 1956, ii, 447.


Harwell, Berks.

with age taken into


SiR,-The warm spell at the end of June brought spate of adder bites in the south of England. Accounts

of some of these accidents find their way into the popular press, with the result that the dangers from the bite of our only poisonous reptile become much exaggerated. It is doubtful whether adults ever succumb to viper (or adder) bites (Vipera berus) in this country, and the venom is dangerous only to small children. The question arises whether the heroic measures often employed are justifiable. It may well be that more damage is done by the treatment than by the vicious adder itself. The popular remedial measures are the tourniquet, incision, and laceration of the wound, together with suction. The latter two have now been discountenanced in countries, such as India and Brazil, where snakebite is a serious business. In most cases it is onlv necessary to put the victim to bed, to give a sedative, and feed him with glucose drinks till he recovers. Whether antivenin is always essential is a contentious matter; but certainly, on account of the danger of anaphylaxis. it should never be given, in this country, by the intravenous route. I should like to draw attention to the neutralising action of carbolic or’Lifebuoy’ soaps6 which are now used in India for Russell’s viper bite, with apparent success. This is a simple and harmless remedy, sanctified by long usage, and a 5% solution can be injected into the site of the bite and surrounding subcutaneous tissue. It delays absorption of the venom PHILIP MANSON-BAHR.

Sir,-Has have





inquestwe were told that for given serum to anyone bitten by


Ata doctor not to an adder would

anybody ? a

5. Lea, A. J., Abbatt, J. D. Ibid, 1957, i, 389. 6. Ahuja, M. L., Brooks, A. G. Ind. J. med. Res. 7. See Lancet, 1957, i, 1095.

1945, 36, 173.

193 have been criminal neglect. Yet that great naturalist W. H. Hudson observed (in his Hints to Adder-Seekers) that people greatly exaggerated the dangers of adderbites. Was he right?z? J. GIBSON. VITAMIN A AND THE CEREBROSPINAL FLUID SiR,-Your review1 of vitamin A and the spinal fluid, with regard to teratogenesis, was most stimulating. The reference on which the clinical warning was based, however, was in error because the article cited2 discussed the development of hydrocephalus following a deficiency of vitamin A in the infant’s diet rather than a deficiency in the maternal diet. The maternal dietary intake was noted as excellent, and the infant developed signs of hydrocephalus while being maintained on a hypoallergenic feeding relatively devoid of vitamin A. Consequently postnatal factors alone were held responsible for the

hydrocephalus. time it should be noted that animal excessive doses of vitamin A, as well as deficiencies of this compound, has resulted in teratogenesis.3 Consequently the possibility should be considered that either excessive or deficient intake of vitamin A might result in the development of fcetal At the


experimentation using

145 m.eq., K 5 m.eq., Mg 2 m.eq., P 2-5 m.eq., Ca 5 m.eq., 25 m.eq., Cl 129 m.eq. per litre). Measurement in a pH meter was necessary to avoid polarisation. The results were :


Vitallium/extracellular fluid/KCI/HgCI/Hg: Screw-point/electrode +90 to +110 mV. Screw-head/electrode +130 to +155 mV. Difference head/point -20-66 mV. Plate/electrode +145 mV.

It is possible that under these conditions the alloys will act as a series of solid solutions with different iron content and resulting potential differences. When Venable et al.introduced vitallium in surgery it was only to avoid the polarisation reactions of the metals used up till then. According to their description, vitallium should be an iron-free alloy of 65% cobalt, 30% chromium, and 5% molybdenum. It was also shown to be completely neutral electrically in the human

organism.7 Both the clinical picture and the chemical analysis in the case presented here agree with the fact that polarisation-reactions, which depend on electric activity, are also possible in vitallium. This is probably caused by the iron shown to be present. FINN ASKEVOLD ROLF ASKEVOLD.




Laboratories, Columbus, Ohio.

W. O. ROBERTSON Director, Research Conference Program.


SiE,—Dr. Bowden and his colleagues (May 25) suggested for corrosion in stainless steel used for internal fixation of fractures. Cater and Hicks4 have recommended that other corrosion-free metals, including ’Vitallium,’ be used instead. They made, however, a reservation with regard to vitallium, in saying that slight corrosion reactions had been seen. The following case shows that this is of practical importance. some reasons

was injured at work on Aug. 4, 1950. He was admitted to Ulleval Hospital the same day with a simple cross-fracture of his left femur, at the junction of the middle and distal thirds of the bone. He also had a fracture of the left tibia and fibula, which are not considered here. A radiograph showed shortening of 2 in., with the distal fragment dislocated dorsomedially. Tibial traction corrected the shortening, but not the dorsal dislocation. Because of this, the fracture was fixed internally on Aug. 10 with a 6-screw Lane plate of vitallium and bone-chips round the fracture line. Control radiographs on Sept. 5 and 20 showed unchanged conditions with satisfactory position of the

A married

SIR,-I thought that it would be of interest to your readers to know the results of the advertisement for a trainee appointment as administrative medical officer to this board, which was referred to in my letter in your issue of April 20. There was a very good response to the advertisement, the board receiving 25 applications from a wide field of applicants, including those now engaged in clinical hospital work, in public health, in general practice, and in other walks of life. The successful applicant is in fact now an orthopaedic registrar in a teaching hospital. He will be taking up his duties on Sept. 1, 1957. R. H. M. STEWART Newcastle Regional Hospital Board.

dock-hand, aged 46,

fragments. A radiograph on density around the

Nov. 1 showed a fine zone of decreased 2 distal screws. There was little callus formation, but this was not noticed till later, and on Nov. 13 the cast was removed and the patient got up on crutches. Two days later an axial bend of his thigh was observed, and a radiograph on Nov. 20 showed that the above-mentioned screws had lost their grip in both cortical layers of the bone. The Lane plate was removed on Nov. 20, and the patient was treated with adhesive tape traction until Dec. 28. He was discharged on Jan. 13, 1951, with the fracture consolidated, but with an axial bend of 160°. The plate and the screws were analysed chemically by Scott’s method.The iron content was found to be 1’0±0-1% in the screw-point, l’0z0’l% in the screw-head, and I’3:r0’l% in the plate. The potential differences against a calomel electrode were measured in a Phillip pH meter G.M.4491. A synthetic proteinfree fluid of extracellular type was used as electrolyte (Na 1. Lancet, 1957, i, 826. 2. Cornfeld, D., Cooke, R. E. Pediatrics, 1952, 10, 33. 3. Cohlan, S. Q. Amer. J. Dis. Child. 1953, 86, 438 ; Pediatrics, 1954, 13, 556. Gebauer. Pharmazie, 1954, 9, 684. 4. Cater, W. H., Hicks, J. H. Lancet, 1956, ii, 871. 5. Scott, W. W. Standard Methods of Chemical Analysis. New York, 1939.

Senior Administrative Medical Officer.


was very interested in Dr. Lomax’s correlabetween levels of serum-proteins and lesions of the

SIR,-I tion


hypothalamic region. In this connection, Dr. Lomax may be interested to hear that when I visited Professor Lauder’s 2nd Department of Medicine at the University of Vienna in the summer of 1950, work was in progress there which showed a definite lowering or disappearance of the specific dynamic action of proteins in subjects with hypothalamic lesions and in fact estimations of metabolic-rates before and after a protein load were used to localise cerebral lesions. I have no recent knowledge of this study, nor do I know references relating to this work. But it is very likely that the altered plasma-protein values which Dr. Lomax found in certain cerebral lesions are the expression of altered protein metabolism, which is also shown by the lowered or absent specific dynamic action of proteins, indicating, if impaired absorption has been ruled out, decreased tissue utilisation, the hypothalamus presumably exercising control over protein metabolism in a similar way to that in which it controls carbohydrate and fat metabolism, probably via the pituitary gland and a humoral factor. For example, we know that certain steroid hormones, notably androgens, have a marked influence on protein metabolism. 6.

Venable, C. S., Stuck, W. G., Beach, A. Ann. Surg. 1937, 105, 917. 7. Venable, C. S., Stuck, W. G. J. Amer. med. Ass. 1938. 111, 1349. 8. Lancet, 1957, i, 904