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OVERDOSE OF CHLORDIAZEPOXIDE
826 themselves spontaneously, and annulus tears and nucleus protrusions need operation. Apart from the evidence of our investigation, I have the personal experience of a cricket accident before I started medicine at the age of 32, which in retrospect I recognise as a disc protrusion and which was cured by 10 days in bed without the intervention of a doctor. As a medical student I played football until qualified and afterwards up to the age of 45 and am still playing cricket, so are you saying that I ought to have been operated on at 32 ? And I am only one example of thousands who, so far from getting to the orthopaedic outpatient department, never even go to their own doctor, and their annulus tears and disc protrusions heal just the same. Is there any wonder therefore that in America-where the sell cost of treatment is high, where doctors feel the need to medicine to the American public ", and where conservative treatment would often end in the patient going elsewhereis there any wonder that operation is still advocated in the face of the success of conservative methods ? The one common factor in those cases which fail to reach the doctor at all and those which we treat either by physiotherapy or plaster casts is, in my opinion, the relief of muscle spasm. One pointer to the truth of this is the success of cold-spray treatment with ’ Skefron’ as advocated by Ellis at the Leeds
cure
"
General Infirmary.
Great Glea,
G. A. Leiccstershire.
STANTON.
OVERDOSE OF CHLORDIAZEPOXIDE SIR,-Iwas interested in the report of changes in the electroencephalogram (E.E.G.) described by Dr. Thompson and Dr. Glen (Sept. 23) as I have recently carried out a preliminary investigation into the effect of chlorodiazepoxide on the E.E.G., and found changes similar to those described by Kaim and Rosenstein.l Fast activity, as found by Dr. Thompson and Dr. Glen, was the commonest change, associated with normal doses of chlorodiazepoxide (15-45 mg. daily), and occurred in 24 of 41
cases.
There are other more dramatic and unusual changes, however, which can broadly be described as a tendency for the E.E.G. to become normal (see accompanying figure). Thus, in the 41 cases, 17 showed a reduction of paroxysmal discharges, 23 showed a reduction or disappearance of abnormal background slow activity (theta), and 18 showed an increase in normal alpha activity. Unfortunately, while there may be clinical improvement in association with E.E.G. improvement, this is not always so, and 1.
Kaim, S. C., Rosenstein,
I. N. Dis.
nerv.
Syst. 1960, 21, (suppl.) 46.
equally one change.
may get clinical
improvement
without much
E.E.G.
The effect of chlorodiazepoxide on the E.E.G. and its action anticonvulsant in major and minor epilepsy and in infantile spasms is most interesting and deserves further study. All Saints Hospital, P. M. JEAVONS. Birmingham.
as an
ANTICOAGULANTS IN ACUTE MYOCARDIAL INFARCTION SIR,—In his letter of Aug. 19 Dr. Poller objected to our study reported in your issue of Aug. 12 on the grounds that our series did not fulfil his requirements for objective Dr. Poller implied that the comparability assessment. between our treated and control group is highly questionable. If Dr. Poller carefully rereads our paper he will find that the two groups in our series will satisfy any statistical analysis for comparability in terms of size, age of patients, sex-distribution, associated diseases, recurrent infarction, period from onset and supportive therapy-all the requirements Dr. Poller mentions. We feel confident therefore that we have achieved a satisfactory random distribution of cases into treated and untreated groups. Dr. Poller suggests that our results would have been different if we had adopted a more "modern " therapeutic approach. First, he raises the question of the effectiveness of subcutaneous heparin therapy. It has been shown, however, that sub-
heparin (25,000 units twice daily) produces a sustained prolongation of the coagulation time (as opposed to the intermittent intravenous administration of heparin).1 Secondly, he implies that dicoumarol is an unsuitable drug to use. We are not aware of any convincing evidence of the superiority of the newer anticoagulants compared with dicoumarol. In a study like ours where the patients are covered by heparin until dicoumarol takes effect, the difference in the rapidity of the action of the different drugs is of no importance. Dr. Poller states that we have given our patients less than the optimum amount of dicoumarol, but since he is informed about the excellent results obtained elsewhere in Scandinavia with a regimen comparable to ours, he suggests that our testsystems are inadequate and that " faulty reagents or technique may be the cause of the poor results in the Danish hospitals ". In reply to the latter criticism, we would emphasise that Owren’s P. & P. test was closely standardised in the group of laboratories in the investigation, and that the tests were adequately controlled at regular intervals. That the treatment we gave was effective is demonstrated by the pronounced reduction in thromboembolic complications in the treated group. As the mortality was unchanged, however, this must mean that the prognosis in acute myocardial infarction is determined by factors not influenced by anticoagulant therapy. We are disappointed that, according to Dr. Poller, a short-term controlled trial of anticoagulant treatment in acute myocardial infarction-even if morally justifiable would be physically impossible in Britain. Wehope this attitude does not extend to other forms of treatment in common use today. Moreover, we do not feel that " the fact that the medical journals have been assuring us of the value of anticoagulants since the early 1940s can be taken as a proof of the efficacy of such a cutaneous
"
treatment.
We
pleased that the remarks of Dr. (Sept. 9) give us an opportunity to amplify our original report of Aug. 12. Mr. are
Deutsch
Deutsch asks whether the patients 1.
Refn, I., Raaschou, F.,
abk
to
L. 1st InterThrombosis and Embo.
Vestergaard,
on national Basel, 1954; p. 758. Basel, 1955.
Conference
were
cure
"
General Infirmary.
Great Glea,
G. A. Leiccstershire.
STANTON.
OVERDOSE OF CHLORDIAZEPOXIDE SIR,-Iwas interested in the report of changes in the electroencephalogram (E.E.G.) described by Dr. Thompson and Dr. Glen (Sept. 23) as I have recently carried out a preliminary investigation into the effect of chlorodiazepoxide on the E.E.G., and found changes similar to those described by Kaim and Rosenstein.l Fast activity, as found by Dr. Thompson and Dr. Glen, was the commonest change, associated with normal doses of chlorodiazepoxide (15-45 mg. daily), and occurred in 24 of 41
cases.
There are other more dramatic and unusual changes, however, which can broadly be described as a tendency for the E.E.G. to become normal (see accompanying figure). Thus, in the 41 cases, 17 showed a reduction of paroxysmal discharges, 23 showed a reduction or disappearance of abnormal background slow activity (theta), and 18 showed an increase in normal alpha activity. Unfortunately, while there may be clinical improvement in association with E.E.G. improvement, this is not always so, and 1.
Kaim, S. C., Rosenstein,
I. N. Dis.
nerv.
Syst. 1960, 21, (suppl.) 46.
equally one change.
may get clinical
improvement
without much
E.E.G.
The effect of chlorodiazepoxide on the E.E.G. and its action anticonvulsant in major and minor epilepsy and in infantile spasms is most interesting and deserves further study. All Saints Hospital, P. M. JEAVONS. Birmingham.
as an
ANTICOAGULANTS IN ACUTE MYOCARDIAL INFARCTION SIR,—In his letter of Aug. 19 Dr. Poller objected to our study reported in your issue of Aug. 12 on the grounds that our series did not fulfil his requirements for objective Dr. Poller implied that the comparability assessment. between our treated and control group is highly questionable. If Dr. Poller carefully rereads our paper he will find that the two groups in our series will satisfy any statistical analysis for comparability in terms of size, age of patients, sex-distribution, associated diseases, recurrent infarction, period from onset and supportive therapy-all the requirements Dr. Poller mentions. We feel confident therefore that we have achieved a satisfactory random distribution of cases into treated and untreated groups. Dr. Poller suggests that our results would have been different if we had adopted a more "modern " therapeutic approach. First, he raises the question of the effectiveness of subcutaneous heparin therapy. It has been shown, however, that sub-
heparin (25,000 units twice daily) produces a sustained prolongation of the coagulation time (as opposed to the intermittent intravenous administration of heparin).1 Secondly, he implies that dicoumarol is an unsuitable drug to use. We are not aware of any convincing evidence of the superiority of the newer anticoagulants compared with dicoumarol. In a study like ours where the patients are covered by heparin until dicoumarol takes effect, the difference in the rapidity of the action of the different drugs is of no importance. Dr. Poller states that we have given our patients less than the optimum amount of dicoumarol, but since he is informed about the excellent results obtained elsewhere in Scandinavia with a regimen comparable to ours, he suggests that our testsystems are inadequate and that " faulty reagents or technique may be the cause of the poor results in the Danish hospitals ". In reply to the latter criticism, we would emphasise that Owren’s P. & P. test was closely standardised in the group of laboratories in the investigation, and that the tests were adequately controlled at regular intervals. That the treatment we gave was effective is demonstrated by the pronounced reduction in thromboembolic complications in the treated group. As the mortality was unchanged, however, this must mean that the prognosis in acute myocardial infarction is determined by factors not influenced by anticoagulant therapy. We are disappointed that, according to Dr. Poller, a short-term controlled trial of anticoagulant treatment in acute myocardial infarction-even if morally justifiable would be physically impossible in Britain. Wehope this attitude does not extend to other forms of treatment in common use today. Moreover, we do not feel that " the fact that the medical journals have been assuring us of the value of anticoagulants since the early 1940s can be taken as a proof of the efficacy of such a cutaneous
"
treatment.
We
pleased that the remarks of Dr. (Sept. 9) give us an opportunity to amplify our original report of Aug. 12. Mr. are
Deutsch
Deutsch asks whether the patients 1.
Refn, I., Raaschou, F.,
abk
to
L. 1st InterThrombosis and Embo.
Vestergaard,
on national Basel, 1954; p. 758. Basel, 1955.
Conference
were