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CEREBRAL METABOLISM AFTER PORTACAVAL SHUNT
626 ASPARAGINASE AND LEUKÆMIA SiR,ňYour annotationstated that guineapigs rarely have cancer. Later Homburger 2 criticised the view that guineapig L-asparaginase may prevent tumours in guineapigs, by pointing out that cancer is not uncommon in certain strains of guineapigs over the age of 3 years. But there are data which suggest that guineapig L-asparaginase may be a factor in the low incidence of spontaneous tumours in young animals. Firstly, spontaneous tumours in guineapigs are almost nonexistent before the age of 3 years 34 it is difficult to induce tumours in guineapigs by X rays,4 and methylcholanthrene induces tumours in young guineapigs with great ease.3 Secondly, the anti-tumour activity of guineapig serum (G.P.s.) in mouse leukxmias varies with the mode of mouse-tumour induction.5 Of 109 murine leukxmias treated with G.p.s., tumour inhibition was demonstrated in 5 of 19 spontaneous tumours, 21 of 48 X-ray-induced tumours, none of 12 D.M.B.A. (9, 10-dimethyl-1,2-benzanthracene) induced tumours, 2 of 14 urethane-induced tumours, and none of 16 tumours induced by a variety of viruses. Thus, G.P.S. inhibition of murine leuksmias is primarily restricted to spontaneous and X-ray-induced tumours. The final point concerns the relative tumour-inhibitory effect of G.P.S. taken from animals at different ages. Although no data are available on the levels of L-asparaginase in very aged guineapigs, the tumourinhibitory effectiveness of G.P.S. from aged guineapigs has been shown to be greatly reduced.s One can therefore postulate that L-asparaginase in guineapigs and related rodents may confer a selective advantage through inhibition of spontaneous tumours, and that with advanced age and loss of this selective advantage the rodent becomes more susceptible to spontaneous tumour formation.
conservative procedure, for at 150 days, by deleting, n is reduced to 9 and U to 3 and p is then only 0-020. Similarly, at 10 days, n is reduced to 7 and U becomes 26; p is again reduced, to 0-046. All probabilities were calculated on the basis of two-sided alternatives (i.e., that either the tape-closed or the sutureclosed wound might be the stronger). Thus the tabled p values 27-5 (the equality are double those given by Owen.1 When U > when the p value used. At 150 days for 55-U was n=10) point the p values for U=5and U=6were added to obtain a " fair"" two sided p value for U==5-5. Department of Surgery, University of Dundee, and California State Department JAMES C. FORRESTER of Public Health, HANS K. URY. California. Berkeley,
CORTICOTROPHIN AND LINEAR GROWTH SIR,-We agree with Dr. Friedman and Professor Strang (March 8, p. 527) that further data showing failure of a growth response to corticotrophin would have been helpful in our paper (Feb. 8, p. 287). Pressure on space prevented us from giving all our illustrations. The accompanying figure is a
Solid Tumor Service,
Medicine Branch, National Cancer Institute, Bethesda, Maryland 20014.
C. M. HASKELL G. P. CANELLOS Typical growth on
THE SIGNED-RANK (WILCOXON) TEST SIR,-We have read with interest the letters from Mr. Miller (Feb. 15, p. 371), Dr. Saracci (Feb. 22, p. 416), and Dr. West (March 8, p. 526) on our paper (Feb. 1, p. 239), and thank them for their help in bringing the test to wider notice. As so often happens, the need for brevity can lead to slight confusion. We emphasise that in our study the rats were killed before taking tensile-strength measurements. The observations are therefore independent and there is no tendency to " capitalise on chance " as claimed by Mr. Miller. We agree that ideal analysis (which we were not discussing) may
require
more
complex techniques. Thus, although
we
readily
established the significance of our data with the Wilcoxon test we later carried out a factorial analysis. All tests have their limitations, and as Dr. Saracci points out, confidence limits are usually more easily obtained with classical procedures. However, not every investigator requires these, and the fact remains that, in the right circumstances, the Wilcoxon test accurately and easily indicates information trends without access to computers or other sophisticated aids. We are grateful to Dr. West for underlining this and outlining the two-sample variant. For the sake of clarity we should like to add two points which were in our original manuscript. In the test we incorporated zero differences into the calculation. Some statisticians delete these and carry out the test on the reduced value of n. This is simply a matter of preference. In our example their inclusion was the more 1. 2. 3. 4. 5. 6.
Lancet, 1968, i, 1075. Homburger, F. ibid. p. 1313. Blumenthal, H. T., Rogers, J. B. in Progress in Experimental Tumour Research; vol. IX, p. 183. Basle, 1967. Congdon, C. C., Lorenz, E. Am. J. Path. 1954, 30, 337. Adamson, R. H., Fabro, S. Cancer Chemother. Rep. 1968, 52, 617. Herbut, P. A., Kraemer, W. H., McKeon, F. A., Taylor, R. C. Am. J. Path. 1961, 38, 387.
curves
of
steroid-dependent adolescent asthmatic.
corticotrophin (9 months)..........on prednisone.
typical example of the growth curves of our cases. It will be noted that there was a gain in weight but no growth acceleration on corticotrophin. This figure also answers their comment that 6 months is too short a period to assess the effects of corticotrophin
on
linear growth.
The Hospital for Sick Children, Great Ormond Street, London W.C.1.
A. P. NORMAN STUART SANDERS.
CEREBRAL METABOLISM AFTER PORTACAVAL SHUNT SIR,-The figures reported in the tables in our letter (Jan. 18, p. 153) and those calculated by Dr. Walshe (Feb. 22," " p. 424) differ not because of mathematical discrepancies but simply because they have been obtained by different procedures. Dr. Walshe has calculated the mean cerebral glucose/oxygen quotient (c.G./OQ.) from the mean values of cerebral metabolic rates of glucose and oxygen given in our tables. On the other hand we obtained the mean c.G./OQ. by calculating the mean of various r-.G.IOQ.s derived from each single case. The individual values were given in detail in the reference2 cited in our letter. In any event, the results obtained by the two procedures differ but slightly, and the conclusions which can be drawn are not affected. In fact Dr. Walshe’s figures largely fall into the s.E. range of the figures given in our tables. Istituto di
Patologia medica e Metodologia Clinica, University of Milan, Italy.
E. POLLI G. BIANCHI PORRO A. T. MAIOLO.
Owen, D. B. Handbook of Statistical Tables; p. 326. Reading, Massachusetts, 1962. 2. Polli, E., Bianchi Porro, G., Della Porta, P., Maiolo, A. T. Proceedings of the 68th Congress of the Italian Society of Internal Medicine (edited by L. Pozzi). Rome, 1967. 1.
conservative procedure, for at 150 days, by deleting, n is reduced to 9 and U to 3 and p is then only 0-020. Similarly, at 10 days, n is reduced to 7 and U becomes 26; p is again reduced, to 0-046. All probabilities were calculated on the basis of two-sided alternatives (i.e., that either the tape-closed or the sutureclosed wound might be the stronger). Thus the tabled p values 27-5 (the equality are double those given by Owen.1 When U > when the p value used. At 150 days for 55-U was n=10) point the p values for U=5and U=6were added to obtain a " fair"" two sided p value for U==5-5. Department of Surgery, University of Dundee, and California State Department JAMES C. FORRESTER of Public Health, HANS K. URY. California. Berkeley,
CORTICOTROPHIN AND LINEAR GROWTH SIR,-We agree with Dr. Friedman and Professor Strang (March 8, p. 527) that further data showing failure of a growth response to corticotrophin would have been helpful in our paper (Feb. 8, p. 287). Pressure on space prevented us from giving all our illustrations. The accompanying figure is a
Solid Tumor Service,
Medicine Branch, National Cancer Institute, Bethesda, Maryland 20014.
C. M. HASKELL G. P. CANELLOS Typical growth on
THE SIGNED-RANK (WILCOXON) TEST SIR,-We have read with interest the letters from Mr. Miller (Feb. 15, p. 371), Dr. Saracci (Feb. 22, p. 416), and Dr. West (March 8, p. 526) on our paper (Feb. 1, p. 239), and thank them for their help in bringing the test to wider notice. As so often happens, the need for brevity can lead to slight confusion. We emphasise that in our study the rats were killed before taking tensile-strength measurements. The observations are therefore independent and there is no tendency to " capitalise on chance " as claimed by Mr. Miller. We agree that ideal analysis (which we were not discussing) may
require
more
complex techniques. Thus, although
we
readily
established the significance of our data with the Wilcoxon test we later carried out a factorial analysis. All tests have their limitations, and as Dr. Saracci points out, confidence limits are usually more easily obtained with classical procedures. However, not every investigator requires these, and the fact remains that, in the right circumstances, the Wilcoxon test accurately and easily indicates information trends without access to computers or other sophisticated aids. We are grateful to Dr. West for underlining this and outlining the two-sample variant. For the sake of clarity we should like to add two points which were in our original manuscript. In the test we incorporated zero differences into the calculation. Some statisticians delete these and carry out the test on the reduced value of n. This is simply a matter of preference. In our example their inclusion was the more 1. 2. 3. 4. 5. 6.
Lancet, 1968, i, 1075. Homburger, F. ibid. p. 1313. Blumenthal, H. T., Rogers, J. B. in Progress in Experimental Tumour Research; vol. IX, p. 183. Basle, 1967. Congdon, C. C., Lorenz, E. Am. J. Path. 1954, 30, 337. Adamson, R. H., Fabro, S. Cancer Chemother. Rep. 1968, 52, 617. Herbut, P. A., Kraemer, W. H., McKeon, F. A., Taylor, R. C. Am. J. Path. 1961, 38, 387.
curves
of
steroid-dependent adolescent asthmatic.
corticotrophin (9 months)..........on prednisone.
typical example of the growth curves of our cases. It will be noted that there was a gain in weight but no growth acceleration on corticotrophin. This figure also answers their comment that 6 months is too short a period to assess the effects of corticotrophin
on
linear growth.
The Hospital for Sick Children, Great Ormond Street, London W.C.1.
A. P. NORMAN STUART SANDERS.
CEREBRAL METABOLISM AFTER PORTACAVAL SHUNT SIR,-The figures reported in the tables in our letter (Jan. 18, p. 153) and those calculated by Dr. Walshe (Feb. 22," " p. 424) differ not because of mathematical discrepancies but simply because they have been obtained by different procedures. Dr. Walshe has calculated the mean cerebral glucose/oxygen quotient (c.G./OQ.) from the mean values of cerebral metabolic rates of glucose and oxygen given in our tables. On the other hand we obtained the mean c.G./OQ. by calculating the mean of various r-.G.IOQ.s derived from each single case. The individual values were given in detail in the reference2 cited in our letter. In any event, the results obtained by the two procedures differ but slightly, and the conclusions which can be drawn are not affected. In fact Dr. Walshe’s figures largely fall into the s.E. range of the figures given in our tables. Istituto di
Patologia medica e Metodologia Clinica, University of Milan, Italy.
E. POLLI G. BIANCHI PORRO A. T. MAIOLO.
Owen, D. B. Handbook of Statistical Tables; p. 326. Reading, Massachusetts, 1962. 2. Polli, E., Bianchi Porro, G., Della Porta, P., Maiolo, A. T. Proceedings of the 68th Congress of the Italian Society of Internal Medicine (edited by L. Pozzi). Rome, 1967. 1.