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URÆMIA IN ACUTE RENAL FAILURE
172 As
one of the earliest, next to I. M. Orr, to use vagotomy in Britain, I beg to advocate the view that only gross demonstrable hypersecretion should be considered to justify this operation.
H. DAINTREE JOHNSON. PREVENTION OF MEGALOBLASTIC ANÆMIA IN PREGNANCY BY FOLIC ACID
SIR,-Dr. Buttafuoco (Jan. 5) has ignored the main trial.1
The efficacy of the drug was assessed by comparing the incidence of megaloblastic anaemia in treated and control patients, and the beneficial effect was shown in table I (Dr. C. W. Dunnett, Lederle Laboratories, has calculated X2 to be 32-3 and p < 0.00001 on these data). The purpose of table IV was merely to illustrate that a rise in haemoglobin also occurred, even with a small total dose of folic acid. Despite all the variables listed by Dr. Buttafuoco, this rise may be considered to be of significance. D. W. DAWSON Department of Pathology, J. R. S. MORE Crumpsall Hospital, D. C. AIRD. Manchester.
findings
of
our
URÆMIA IN ACUTE RENAL FAILURE
SIR,-Since the article of Aug. 18 on acute renal failure, by Professor Finckh, a controversy has developed between Mr. Sophian ( Sept. 15 and Dec. 22) and himself (Nov. 10) on the part that the " shunt " which is often associated with my name may play in the causation of renal failure without severe tubular damage. While remaining faithful to my decision to leave the field of renal function and pathology for as long as I am the holder of the chair of orthopaedic surgery at Oxford, I should like to correct a mistake frequently made in referring to two of our findings as given in the book on renal studies we published in 1947.2 The first is to attribute to us the assertion that the " shunt " of the blood away from the cortex at the juxta" medullary area is an all or nothing " mechanism which when operating would result in ischsemia of the cortical renal tubules. What we stated in that book was thus: " We found ample evidence that the circulation through the cortex could be either diminished and even in some circumstances totally arrested, while the circulation continued through the medulla " (p. 113). Evidently, only when these circumstances present themselves, damage to the tubules-and even to the glomeruli-would be caused. The other frequent assertion is that we have postulated that the juxtamedullary pathway when fully functioning would carry as much blood as the whole kidney in resting conditions. This is contrary to our findings as reported in the book, where we insisted that the reduction of blood flowing through the cortex is accompanied by a contraction of the renal artery which of necessity must cause a reduction of the total blood-flow. I want to thank Mr. Sophian for his unfailing support and Professor Finckh for the quality of his work which brings nearer the acceptance of the views I had the privilege to expound in your journal in 1945. I quote from that letter 3 : " Since 1936 I have been collecting data about renal failures consequent upon traumata, and have attributed them to interference with the blood-supply-i.e., to renal anoxia. Because of my previous work on the splanchnics (Rev. Med. Barcelona, 1935, 24, 412; Giorn. Ital. Anest. Anal. 1935, 1, 476), I have ascribed the interference with the blood-supply to persistence of the arterial spasm which accompanies the very early stages of shock. That the renal (and other) 1. Dawson, D. W., More, J. R. S., Aird, D. C. Lancet, 2. Studies of the Renal Circulation. Oxford, 1947. 3. Lancet, 1945, ii, 415.
1962, ii, 1015.
arteries
can be overstimulated reflexly or centrally, in unduly susceptible persons, is suggested, for example, by the development of anuria through the irritation of the ureter, or by the findings in hysterical anuria (Osler and McCrea, Modern Medicine, vol. v, 489)." That this contraction of the cortical arterioles would cause the opening of the juxtamedullary circulation was, of course, unsuspected by me even when the letter was written.
Nuffield Orthopædic Centre, Oxford.
J. TRUETA.
EVALUATION OF ANTICOAGULANT THERAPY FOR MYOCARDIAL INFARCTION
SIR,-We hope Dr. Irving Wright will be pleased to the optimistic attitude in which Professor Holten (Dec. 29) perseveres. Wright himself was much more pessimistic 1: "No perfect studies have yet been conducted, nor are any likely to be developed for evaluating this form of therapy in man." see
"
Holten writes that it is quite Dr. Jacobs2 did, the public-ward
unjustified "
to pick out, as of the 8 hospitals contributing only public-ward cases from the material of Wright et al.3 Holten, however, does not give any arguments why he feels so. On the contrary we are convinced that Jacobs is perfectly right in doing so, since hospitals with only one type of patients give a more uniform and suitable material for controlled clinical trials. Holten mentions that when all public-ward cases in Wright et al.’s material are included there are 624 patients, of whom 281 were controlled, with a mortality-rate of 23-8%, and 343 treated patients with a mortality-rate of 19%. Holten says that the procedure of Jacobs gives an incomplete picture of the truth." Even if the inclusion of all public-ward cases would give the truth, it has to be emphasised that there is no statistically significant difference between the above-mentioned groups of treated and non-treated public-ward cases (p 0-17). Holten criticises us because in our reply4 to Dr. Wright we refer only to the total mortality (52%) of the study of Griffith et al.5 We did not go into details of this study of Griffith et al. for obvious reasons, of which we only want to mention a few. In this paper no information is given why only 256 patients from the original material of 1078 patients were selected for the clinical trial. Of these 250 patients, 68 were not treated, but no criteria are mentioned for the selection of the treated and non-treated groups. In a matter of such importance, we are disappointed to see that Holten feels obliged to refer to papers about groups which are quite incomparable and therefore useless in this discussion. Holten again discusses the incidence of bleeding in our material. Since we last answered him, the number of bleedings has remained the same. We have discussed the bleedings in detail 6and they have also been discussed by Jacobs 2, who compared the number of our bleedings with those found by Wright et al. and concluded that they did not differ greatly. The main point is that the incidence of bleeding and especially of severe bleeding does not in any way invalidate our conclusion-that anticoagulants are not indicated in the treatment of acute myocardial infarction. Holten has so far written nine letters on this topic to various medical journals during the past eighteen months, and everybody must be impressed by his eagerness and indefatigability. It is, however, evident that he has not succeeded in giving any new arguments during this long time; and several papers and letters from various parts of the world have disclosed a feeling of uncertainty and scepticism about his viewpoint. In a recent symposium on thrombosis and anticoagulation the literature 1. Wright, I. S. Lancet, 1962, ii, 654. cases
"
=
Jacobs, A. L. Brit. med. J. 1962, i, 1831. Wright, I. S., Marple, C. D., Beck, D. F. Myocardial Infarction. New York, 1954. 4. Hilden, T., Inversen, K., Raaschou, F., Schwartz, M. Lancet, 1962, ii, 1056. 5. Griffith, G. C., Leak, D., Hegde, B. Ann. intern. Med. 1962, 57, 254. 6. Hilden, T., Iversen, K., Raaschou, F., Schwartz, M. Lancet, 1962, i, 694. 7. Hilden, T., Iversen, K., Raaschou, F., Schwartz, M. ibid. p. 1411.
2. 3.
one of the earliest, next to I. M. Orr, to use vagotomy in Britain, I beg to advocate the view that only gross demonstrable hypersecretion should be considered to justify this operation.
H. DAINTREE JOHNSON. PREVENTION OF MEGALOBLASTIC ANÆMIA IN PREGNANCY BY FOLIC ACID
SIR,-Dr. Buttafuoco (Jan. 5) has ignored the main trial.1
The efficacy of the drug was assessed by comparing the incidence of megaloblastic anaemia in treated and control patients, and the beneficial effect was shown in table I (Dr. C. W. Dunnett, Lederle Laboratories, has calculated X2 to be 32-3 and p < 0.00001 on these data). The purpose of table IV was merely to illustrate that a rise in haemoglobin also occurred, even with a small total dose of folic acid. Despite all the variables listed by Dr. Buttafuoco, this rise may be considered to be of significance. D. W. DAWSON Department of Pathology, J. R. S. MORE Crumpsall Hospital, D. C. AIRD. Manchester.
findings
of
our
URÆMIA IN ACUTE RENAL FAILURE
SIR,-Since the article of Aug. 18 on acute renal failure, by Professor Finckh, a controversy has developed between Mr. Sophian ( Sept. 15 and Dec. 22) and himself (Nov. 10) on the part that the " shunt " which is often associated with my name may play in the causation of renal failure without severe tubular damage. While remaining faithful to my decision to leave the field of renal function and pathology for as long as I am the holder of the chair of orthopaedic surgery at Oxford, I should like to correct a mistake frequently made in referring to two of our findings as given in the book on renal studies we published in 1947.2 The first is to attribute to us the assertion that the " shunt " of the blood away from the cortex at the juxta" medullary area is an all or nothing " mechanism which when operating would result in ischsemia of the cortical renal tubules. What we stated in that book was thus: " We found ample evidence that the circulation through the cortex could be either diminished and even in some circumstances totally arrested, while the circulation continued through the medulla " (p. 113). Evidently, only when these circumstances present themselves, damage to the tubules-and even to the glomeruli-would be caused. The other frequent assertion is that we have postulated that the juxtamedullary pathway when fully functioning would carry as much blood as the whole kidney in resting conditions. This is contrary to our findings as reported in the book, where we insisted that the reduction of blood flowing through the cortex is accompanied by a contraction of the renal artery which of necessity must cause a reduction of the total blood-flow. I want to thank Mr. Sophian for his unfailing support and Professor Finckh for the quality of his work which brings nearer the acceptance of the views I had the privilege to expound in your journal in 1945. I quote from that letter 3 : " Since 1936 I have been collecting data about renal failures consequent upon traumata, and have attributed them to interference with the blood-supply-i.e., to renal anoxia. Because of my previous work on the splanchnics (Rev. Med. Barcelona, 1935, 24, 412; Giorn. Ital. Anest. Anal. 1935, 1, 476), I have ascribed the interference with the blood-supply to persistence of the arterial spasm which accompanies the very early stages of shock. That the renal (and other) 1. Dawson, D. W., More, J. R. S., Aird, D. C. Lancet, 2. Studies of the Renal Circulation. Oxford, 1947. 3. Lancet, 1945, ii, 415.
1962, ii, 1015.
arteries
can be overstimulated reflexly or centrally, in unduly susceptible persons, is suggested, for example, by the development of anuria through the irritation of the ureter, or by the findings in hysterical anuria (Osler and McCrea, Modern Medicine, vol. v, 489)." That this contraction of the cortical arterioles would cause the opening of the juxtamedullary circulation was, of course, unsuspected by me even when the letter was written.
Nuffield Orthopædic Centre, Oxford.
J. TRUETA.
EVALUATION OF ANTICOAGULANT THERAPY FOR MYOCARDIAL INFARCTION
SIR,-We hope Dr. Irving Wright will be pleased to the optimistic attitude in which Professor Holten (Dec. 29) perseveres. Wright himself was much more pessimistic 1: "No perfect studies have yet been conducted, nor are any likely to be developed for evaluating this form of therapy in man." see
"
Holten writes that it is quite Dr. Jacobs2 did, the public-ward
unjustified "
to pick out, as of the 8 hospitals contributing only public-ward cases from the material of Wright et al.3 Holten, however, does not give any arguments why he feels so. On the contrary we are convinced that Jacobs is perfectly right in doing so, since hospitals with only one type of patients give a more uniform and suitable material for controlled clinical trials. Holten mentions that when all public-ward cases in Wright et al.’s material are included there are 624 patients, of whom 281 were controlled, with a mortality-rate of 23-8%, and 343 treated patients with a mortality-rate of 19%. Holten says that the procedure of Jacobs gives an incomplete picture of the truth." Even if the inclusion of all public-ward cases would give the truth, it has to be emphasised that there is no statistically significant difference between the above-mentioned groups of treated and non-treated public-ward cases (p 0-17). Holten criticises us because in our reply4 to Dr. Wright we refer only to the total mortality (52%) of the study of Griffith et al.5 We did not go into details of this study of Griffith et al. for obvious reasons, of which we only want to mention a few. In this paper no information is given why only 256 patients from the original material of 1078 patients were selected for the clinical trial. Of these 250 patients, 68 were not treated, but no criteria are mentioned for the selection of the treated and non-treated groups. In a matter of such importance, we are disappointed to see that Holten feels obliged to refer to papers about groups which are quite incomparable and therefore useless in this discussion. Holten again discusses the incidence of bleeding in our material. Since we last answered him, the number of bleedings has remained the same. We have discussed the bleedings in detail 6and they have also been discussed by Jacobs 2, who compared the number of our bleedings with those found by Wright et al. and concluded that they did not differ greatly. The main point is that the incidence of bleeding and especially of severe bleeding does not in any way invalidate our conclusion-that anticoagulants are not indicated in the treatment of acute myocardial infarction. Holten has so far written nine letters on this topic to various medical journals during the past eighteen months, and everybody must be impressed by his eagerness and indefatigability. It is, however, evident that he has not succeeded in giving any new arguments during this long time; and several papers and letters from various parts of the world have disclosed a feeling of uncertainty and scepticism about his viewpoint. In a recent symposium on thrombosis and anticoagulation the literature 1. Wright, I. S. Lancet, 1962, ii, 654. cases
"
=
Jacobs, A. L. Brit. med. J. 1962, i, 1831. Wright, I. S., Marple, C. D., Beck, D. F. Myocardial Infarction. New York, 1954. 4. Hilden, T., Inversen, K., Raaschou, F., Schwartz, M. Lancet, 1962, ii, 1056. 5. Griffith, G. C., Leak, D., Hegde, B. Ann. intern. Med. 1962, 57, 254. 6. Hilden, T., Iversen, K., Raaschou, F., Schwartz, M. Lancet, 1962, i, 694. 7. Hilden, T., Iversen, K., Raaschou, F., Schwartz, M. ibid. p. 1411.
2. 3.