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VASODILATOR DRUGS IN OCCLUSIVE VASCULAR DISEASE OF THE LEGS
59
number of days taken to become symptom-free and signfree was greater when treatment was started early. We do not, therefore, see any inconsistencies in our results and believe that it would be wrong to use Dr. Doherty’s analysis of our scatter diagram to support the use of
penicillin in leptospirosis. (e) Now, as to leptospiral arrange
groups.
serotypes: it is not possible to equal distribution between control and treated Dr. Doherty feels that in a study of the efficacy of
The only condition under which conservative treatment is logical is where the inflammation has spread beyond the appendix and peritonitis is present, the decision then for operation against conservative treatment being a nice one to be made with every ounce of the surgeon’s lifetime’s experience. (2) Appendix abscess is now the most dangerous of all the situations resultant on appendicular inflammation.
W. SKYRME REES.
an
there should be a similar distribution of serotypes, as he believes the clinical severity varies with the infecting serotype. Trimblein an analysis of 236 cases in Malaya showed that there was absolutely no correlation between clinical severity and serotype. Analysis of our own resultsalso showed that the severity of the illness and the incidence of complications bore no relationship to any serotype or serogroup. This, combined with the knowledge that as far as we know, all serotypes are sensitive to penicillin,s makes it unnecessary, even though desirable, to ensure an equal distribution between treated and control groups. It does not support Dr. Doherty’s contention that the results of our clinical trial should be rejected because of this unequal distribution. We agree, however, that it invalidates one particular criticism previously made concerning the use of controls from another time period.9 Nevertheless we still feel that in a clinical trial of treatment in leptospirosis it is desirable that controls and treated patients should be selected in a random manner and compared at approximately the same time period by the same observers-even when, as in this instance, it results in an unequal distribution of serotypes. treatment
We do not think that there is anything " sweeping " or inaccurate in our statement4 that " penicillin and chloramphenicol play no useful part in the treatment of uncomplicated leptospirosis in British troops in Malaya ... " Our reasons are as follows: (1) Penicillin (or any other antibiotic) has never been shown to affect the mortality of the disease nor the incidence of the complications, jaundice, oliguria, or anuria .4 10 11 (2) In our controlled trial there was no significant effect of penicillin on total duration of pyrexia, symptoms, and signs as compared with the controls. The mean results show that the length of illness was slightly shorter in the penicillin group. The well-recognised variability of leptospirosis, common sense, and our statistical analysis suggest this a chance finding. If it was real and due to penicillin it was marginal and of doubtful value, especially when balanced against the discomfort of frequent intramuscular injections over several days and the other disadvantages of massive antibiotic therapy. Above all, it is in complete disagreement with the reported dramatic effects of penicillin elsewhere 12 and makes nonsense of any suggestion that controlled trials are unjustifiable in this instance. The
Maudsley Hospital, London, S.E.5. St. Thomas’s Hospital Medical School, London, S.E.1.
A. C. FAIRBURN. S.
J. G. SEMPLE.
THE ABNORMAL APPENDIX
SIR,-In his article of Dec. 26 Mr. Jewers referred to my work on this subject. His thoughtful paper confirms the two conclusions at which I arrived in 1952, namely: (1) There is no such thing as the " conservative treatment" of appendicitis. If one ever considers conservative treatment it is in relation to peritonitis and never to appendicitis, which is a different thing. The treatment of appendicitis, when the necessary facilities are available, is to remove the appendix. 7. Trimble, A. P. Proc. R. Soc. Med. 1957, 50, 125. 8. Schlipkoter, H. W., Beckers, M. Z. ImmunForsch. 1951, 9. Semple, S. J. G. Lancet, 1959, ii, 289. 10. Broom, J. C. Brit. med. J. 1951, ii, 689. 11. Ross-Russell, R. W. R. Lancet, 1958, ii, 1143. 12. Mackay-Dick, J., Robinson, J. F. J. R. Army med. Cps,
108,
301.
1957, 103, 186.
EVENING COLIC IN INFANTS SIR,-Professor Illingworth’s views on the management of screaming infants are of considerable importance to family doctors. In his report (Dec. 19) on the trial of dicyclomine hydrochloride in evening colic in infants he shows that, of the 15 babies who received active drug and inert substance, each for a week, 9 had higher scores with the drug, 3 had equal improvement with drug and control, and 3 improved more with the inert substance than with the drug. There were also four scores of +3 and two of +2 with the inert substance. Do these figures really justify his conclusion that the drug is of considerable value ? E. TUCKMAN. St. Mary Cray, Kent. VASODILATOR DRUGS IN OCCLUSIVE VASCULAR DISEASE OF THE LEGS SiR,—The conclusions arrived at by Mr. Gillespie1 cannot be allowed to go unchallenged. Mr. Gillespie measured the blood-flow in the foot and calf of patients with and without obliterative arterial disease after intravenous injections of four so-called vasodilator drugs. He concluded that, as the vasodilators he used did not increase the calf-muscle blood-flow and often decreased it, all prescribing of vasodilators for the treatment of intermittent claudication is The vasodilator drugs he used were tolazoline useless.
(’Priscol’), phenoxybenzamine (’Dibenyline’), chlorpromazine (’ Largactil ’), and promazine. I have found that tolazoline is the least active peripheral dilator used in my series, and I have abandoned the use of phenoxybenzamine in the treatment of obliterative arterial disease. Chlorpromazine and promazine are not claimed by the makers to have any benefit in the treatment of this disease. By contrast, I have repeatedly shownthat spasmocyclone (’ Cyclospasmol’), nicotinyl alcohol tartrate (’Ronicol’), and azapetine (’ Ilidar ’), used alone or in combination, are the drugs of choice in the treatment of peripheral vascular disease. It is ridiculous to condemn the action of satisfactory drugs on the basis of tests carried out with ineffective ones. In practice vasodilators are used either by mouth or by intra-arterial injection, and not intravenously. If Mr. Gillespie wished to disprove the action of vasodilators in the treatment of peripheral vascular disease, he should have used them in this way. The symptoms of occlusive arterial disease develop rapidly after the disease has been present for some years. A minor decrease in the blood-flow must finally precipitate the first symptoms. The effective vasodilators increase the blood-flow sufficiently to ameliorate these symptoms. The method used by Mr. Gillespie to measure the blood-flow is not sufficiently accurate to detect small increases in the blood-flow.
The long-term effect of drugs in the body cannot be assessed accurately by any method other than clinical trial. The vast number of publications describing the advantageous clinical action of the various vasodilators is evidence of their value in the treatment of peripheral arterial disease. Dudley Road Hospital, R. O. GILLHESPY. Birmingham, 18. 1. Gillespie, J. A. Lancet, 1959, ii, 995. 2. Gillhespy, R. O. Angiology, 1956, 7, 27; Brit. med. J. 1957, i, 207; ibid. 1957, ii, 1543; Brit. J. clin. Pract. 1959, 13, 608; Lancet, 1959, i, 1096.
number of days taken to become symptom-free and signfree was greater when treatment was started early. We do not, therefore, see any inconsistencies in our results and believe that it would be wrong to use Dr. Doherty’s analysis of our scatter diagram to support the use of
penicillin in leptospirosis. (e) Now, as to leptospiral arrange
groups.
serotypes: it is not possible to equal distribution between control and treated Dr. Doherty feels that in a study of the efficacy of
The only condition under which conservative treatment is logical is where the inflammation has spread beyond the appendix and peritonitis is present, the decision then for operation against conservative treatment being a nice one to be made with every ounce of the surgeon’s lifetime’s experience. (2) Appendix abscess is now the most dangerous of all the situations resultant on appendicular inflammation.
W. SKYRME REES.
an
there should be a similar distribution of serotypes, as he believes the clinical severity varies with the infecting serotype. Trimblein an analysis of 236 cases in Malaya showed that there was absolutely no correlation between clinical severity and serotype. Analysis of our own resultsalso showed that the severity of the illness and the incidence of complications bore no relationship to any serotype or serogroup. This, combined with the knowledge that as far as we know, all serotypes are sensitive to penicillin,s makes it unnecessary, even though desirable, to ensure an equal distribution between treated and control groups. It does not support Dr. Doherty’s contention that the results of our clinical trial should be rejected because of this unequal distribution. We agree, however, that it invalidates one particular criticism previously made concerning the use of controls from another time period.9 Nevertheless we still feel that in a clinical trial of treatment in leptospirosis it is desirable that controls and treated patients should be selected in a random manner and compared at approximately the same time period by the same observers-even when, as in this instance, it results in an unequal distribution of serotypes. treatment
We do not think that there is anything " sweeping " or inaccurate in our statement4 that " penicillin and chloramphenicol play no useful part in the treatment of uncomplicated leptospirosis in British troops in Malaya ... " Our reasons are as follows: (1) Penicillin (or any other antibiotic) has never been shown to affect the mortality of the disease nor the incidence of the complications, jaundice, oliguria, or anuria .4 10 11 (2) In our controlled trial there was no significant effect of penicillin on total duration of pyrexia, symptoms, and signs as compared with the controls. The mean results show that the length of illness was slightly shorter in the penicillin group. The well-recognised variability of leptospirosis, common sense, and our statistical analysis suggest this a chance finding. If it was real and due to penicillin it was marginal and of doubtful value, especially when balanced against the discomfort of frequent intramuscular injections over several days and the other disadvantages of massive antibiotic therapy. Above all, it is in complete disagreement with the reported dramatic effects of penicillin elsewhere 12 and makes nonsense of any suggestion that controlled trials are unjustifiable in this instance. The
Maudsley Hospital, London, S.E.5. St. Thomas’s Hospital Medical School, London, S.E.1.
A. C. FAIRBURN. S.
J. G. SEMPLE.
THE ABNORMAL APPENDIX
SIR,-In his article of Dec. 26 Mr. Jewers referred to my work on this subject. His thoughtful paper confirms the two conclusions at which I arrived in 1952, namely: (1) There is no such thing as the " conservative treatment" of appendicitis. If one ever considers conservative treatment it is in relation to peritonitis and never to appendicitis, which is a different thing. The treatment of appendicitis, when the necessary facilities are available, is to remove the appendix. 7. Trimble, A. P. Proc. R. Soc. Med. 1957, 50, 125. 8. Schlipkoter, H. W., Beckers, M. Z. ImmunForsch. 1951, 9. Semple, S. J. G. Lancet, 1959, ii, 289. 10. Broom, J. C. Brit. med. J. 1951, ii, 689. 11. Ross-Russell, R. W. R. Lancet, 1958, ii, 1143. 12. Mackay-Dick, J., Robinson, J. F. J. R. Army med. Cps,
108,
301.
1957, 103, 186.
EVENING COLIC IN INFANTS SIR,-Professor Illingworth’s views on the management of screaming infants are of considerable importance to family doctors. In his report (Dec. 19) on the trial of dicyclomine hydrochloride in evening colic in infants he shows that, of the 15 babies who received active drug and inert substance, each for a week, 9 had higher scores with the drug, 3 had equal improvement with drug and control, and 3 improved more with the inert substance than with the drug. There were also four scores of +3 and two of +2 with the inert substance. Do these figures really justify his conclusion that the drug is of considerable value ? E. TUCKMAN. St. Mary Cray, Kent. VASODILATOR DRUGS IN OCCLUSIVE VASCULAR DISEASE OF THE LEGS SiR,—The conclusions arrived at by Mr. Gillespie1 cannot be allowed to go unchallenged. Mr. Gillespie measured the blood-flow in the foot and calf of patients with and without obliterative arterial disease after intravenous injections of four so-called vasodilator drugs. He concluded that, as the vasodilators he used did not increase the calf-muscle blood-flow and often decreased it, all prescribing of vasodilators for the treatment of intermittent claudication is The vasodilator drugs he used were tolazoline useless.
(’Priscol’), phenoxybenzamine (’Dibenyline’), chlorpromazine (’ Largactil ’), and promazine. I have found that tolazoline is the least active peripheral dilator used in my series, and I have abandoned the use of phenoxybenzamine in the treatment of obliterative arterial disease. Chlorpromazine and promazine are not claimed by the makers to have any benefit in the treatment of this disease. By contrast, I have repeatedly shownthat spasmocyclone (’ Cyclospasmol’), nicotinyl alcohol tartrate (’Ronicol’), and azapetine (’ Ilidar ’), used alone or in combination, are the drugs of choice in the treatment of peripheral vascular disease. It is ridiculous to condemn the action of satisfactory drugs on the basis of tests carried out with ineffective ones. In practice vasodilators are used either by mouth or by intra-arterial injection, and not intravenously. If Mr. Gillespie wished to disprove the action of vasodilators in the treatment of peripheral vascular disease, he should have used them in this way. The symptoms of occlusive arterial disease develop rapidly after the disease has been present for some years. A minor decrease in the blood-flow must finally precipitate the first symptoms. The effective vasodilators increase the blood-flow sufficiently to ameliorate these symptoms. The method used by Mr. Gillespie to measure the blood-flow is not sufficiently accurate to detect small increases in the blood-flow.
The long-term effect of drugs in the body cannot be assessed accurately by any method other than clinical trial. The vast number of publications describing the advantageous clinical action of the various vasodilators is evidence of their value in the treatment of peripheral arterial disease. Dudley Road Hospital, R. O. GILLHESPY. Birmingham, 18. 1. Gillespie, J. A. Lancet, 1959, ii, 995. 2. Gillhespy, R. O. Angiology, 1956, 7, 27; Brit. med. J. 1957, i, 207; ibid. 1957, ii, 1543; Brit. J. clin. Pract. 1959, 13, 608; Lancet, 1959, i, 1096.