DINITROPHENOL COMPOUNDS IN OBESITY
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746 and this would introduce a bias to the series. Such points make it difficult to exclude completely environmental and selective factors, but in general this interesting study adds to the cumulatively convincing evidence in support of hereditary factors in the duration of life. We still lack an adequate measure of the strength of these factors and evidence as to the mechanism of such inheritance. DINITROPHENOL COMPOUNDS IN OBESITY DURING the last two years drugs of the nitro- phenol group have been widely used in the treat- ment of obesity, and it may now be opportune to take stock of the experience gained on both sides of the Atlantic. It is clear that the nitrated phenols are powerful and hence potentially dangerous agents, their principal effect being a substantial acceleration of the basal metabolic rate. Three deaths have so far been recorded, for which dinitrophenol was responsible in two and dinitro- cresol in the third. The first fatality followed an enormous overdose taken, it seems, intentionally (J. C. GEIGER 1) ; the second occurred in a negress who received rather large daily doses of nitrophenol over a period of two weeks 2 ; while the third, which formed the subject of a recent coroner’s inquest in London, can also be attributed to over- dosage for which the patient was responsible. Apart from these deaths there is ample evidence that more or less serious toxic symptoms are not uncommon. Some of this evidence has already been mentioned in these columns,3 and further instances have more recently been described by J. H. MASSERMAN and H. GOLDSMITH,2 who observed unpleasant reactions, notably a fall in blood pressure, tachycardia, acidosis, and stupor in 4 out of 18 psychotic patients treated with dinitro- phenol. Such drawbacks, however strongly they may argue in favour of caution and rigid control of the sale of the drugs, do not necessarily provide reason for discarding them, for, as I. M. RABINO- wITCx and A. F. FOWLER 4 point out, some of the most useful drugs in the pharmacopoeia, 1 Jour. Amer. Med. Assoc., 1933, ci., 1333. 2 Ibid., Feb. 17th, 1934, p. 523. 3 THE LANCET, 1933, ii., 1098, 1218. 4 Canad. Med. Assoc. Jour., February, 1934, p. 128. such as morphia and strychnine, are equally open to abuse. But this argument can be pushed too far. The first care of the physician is to do no harm to his patient. He does not prescribe morphia when aspirin will answer his purpose; neither should he use dinitrophenol until he is satisfied that safer remedies are not available. This elementary principle of therapeutics seems in danger of being overlooked. It might be expected, with reason, that a drug which stimulates metabolism would be valuable mainly in treating conditions in which metabolism is depressed. The clearest example of such an abnormality is myxoedema, but myxoedema is more than a simple expression of slowed meta- bolism (DODDS and ROBERTSON,5 D. M. DUNLOF 6), and incidentally is not generally associated with conspicuous adiposity; so that nitrophenol is useless as a substitute for thyroxine. In the vast majority of cases of obesity the basal metabolic rate lies within normal limits and the excess fat must in theory, and can in practice, be readily dispersed by simple restriction of diet and increased physical activity. It is true that nitrophenol by raising the basal metabolism will increase the total output of heat from the body and will so permit the self-indulgent to eat their cakes while preserving their figures. But this entails habitual use of the drug ; and he would be a bold man who, mindful of what was learnt about nitrated aromatic com- pounds during the war, would ignore the possibility of ultimate damage to the liver. To revert to more immediate dangers, two facts may be emphasised: the first that, short of periodic measurements of basal metabolism, which are rarely practicable, there is no way of recognising intoxication from overdosage or idiosyncrasy in good time ; and the second that, once the meta- bolic fire has got out of control, the physician is helpless, for as yet he has nothing with which to quench the flames. The question may be fairly stated thus : is it justifiable, in dealing with a condition which almost always responds readily to a little wholesome discipline, to employ instead a drug of unquestioned potency but uncertain toxicity ? 1 5 THE LANCET, 1933, ii., 1197. 6 Brit. Med. Jour., March 24th, 1934, p. 523. ANNOTATIONS COMPULSORY CONSULTATIONS THE March number of St. Bartholomew’s Hospital Journal contains a rumour that the medical consul- tations held at the hospital are to be abolished. Let them pass, the surgeon might say, for they are only things of yesterday, mere mushroom growths. The old-time physicians rarely saw the patient; they prescribed for him sitting in a coffee house, upon the report of symptoms told them by the apothecary. They were far too individualistic to consult with anyone, least of all with a fellow physician, unless a great nobleman had the gout or a royal personage was about to die. It was far otherwise with the surgeons. From the earliest times of which there is any record in London the surgeons were the guardians of the public health and were held responsible for the cure of the sick and maimed. They were on duty at the city gates to see that no grossly diseased person was admitted ; and as early as Feb. 2nd, 1369, the chief f officers of their gild were sworn to take charge of the hurt and wounded and to give true information to the officers of the city about such persons " whether they be in danger of death or not." A few years later when the barbers had become a company they ordained, in what would now be called their standing orders, that " no barber practising the surgical faculty within the liberty of the city should presume to take under his charge any sick person in actual danger of death or of permanent disability from injury without showing him to the master and wardens." Should
Transcript of DINITROPHENOL COMPOUNDS IN OBESITY
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and this would introduce a bias to the series.Such points make it difficult to exclude completelyenvironmental and selective factors, but in generalthis interesting study adds to the cumulativelyconvincing evidence in support of hereditary factorsin the duration of life. We still lack an adequatemeasure of the strength of these factors andevidence as to the mechanism of such inheritance.
DINITROPHENOL COMPOUNDS IN OBESITY
DURING the last two years drugs of the nitro-phenol group have been widely used in the treat-ment of obesity, and it may now be opportune totake stock of the experience gained on both sidesof the Atlantic. It is clear that the nitrated
phenols are powerful and hence potentiallydangerous agents, their principal effect being asubstantial acceleration of the basal metabolic rate.Three deaths have so far been recorded, for whichdinitrophenol was responsible in two and dinitro-cresol in the third. The first fatality followed anenormous overdose taken, it seems, intentionally(J. C. GEIGER 1) ; the second occurred in a negresswho received rather large daily doses of nitrophenolover a period of two weeks 2 ; while the third,which formed the subject of a recent coroner’s
inquest in London, can also be attributed to over-dosage for which the patient was responsible.Apart from these deaths there is ample evidencethat more or less serious toxic symptoms are notuncommon. Some of this evidence has alreadybeen mentioned in these columns,3 and furtherinstances have more recently been described byJ. H. MASSERMAN and H. GOLDSMITH,2 who observedunpleasant reactions, notably a fall in blood
pressure, tachycardia, acidosis, and stupor in 4out of 18 psychotic patients treated with dinitro-phenol. Such drawbacks, however strongly theymay argue in favour of caution and rigid controlof the sale of the drugs, do not necessarily providereason for discarding them, for, as I. M. RABINO-wITCx and A. F. FOWLER 4 point out, some ofthe most useful drugs in the pharmacopoeia,
1 Jour. Amer. Med. Assoc., 1933, ci., 1333.2 Ibid., Feb. 17th, 1934, p. 523.
3 THE LANCET, 1933, ii., 1098, 1218.4 Canad. Med. Assoc. Jour., February, 1934, p. 128.
such as morphia and strychnine, are equallyopen to abuse. But this argument can be pushedtoo far. The first care of the physician is to dono harm to his patient. He does not prescribemorphia when aspirin will answer his purpose;neither should he use dinitrophenol until he issatisfied that safer remedies are not available.This elementary principle of therapeutics seems
in danger of being overlooked.It might be expected, with reason, that a drug
which stimulates metabolism would be valuable
mainly in treating conditions in which metabolismis depressed. The clearest example of such an
abnormality is myxoedema, but myxoedema ismore than a simple expression of slowed meta-bolism (DODDS and ROBERTSON,5 D. M. DUNLOF 6),and incidentally is not generally associated withconspicuous adiposity; so that nitrophenol isuseless as a substitute for thyroxine. In the vast
majority of cases of obesity the basal metabolicrate lies within normal limits and the excess fatmust in theory, and can in practice, be readilydispersed by simple restriction of diet and increasedphysical activity. It is true that nitrophenol byraising the basal metabolism will increase the totaloutput of heat from the body and will so permitthe self-indulgent to eat their cakes while preservingtheir figures. But this entails habitual use of thedrug ; and he would be a bold man who, mindfulof what was learnt about nitrated aromatic com-
pounds during the war, would ignore the possibilityof ultimate damage to the liver.To revert to more immediate dangers, two facts
may be emphasised: the first that, short of
periodic measurements of basal metabolism, whichare rarely practicable, there is no way of recognisingintoxication from overdosage or idiosyncrasy ingood time ; and the second that, once the meta-bolic fire has got out of control, the physician ishelpless, for as yet he has nothing with which toquench the flames. The question may be fairlystated thus : is it justifiable, in dealing with acondition which almost always responds readilyto a little wholesome discipline, to employ insteada drug of unquestioned potency but uncertain
toxicity ? 1 ---
5 THE LANCET, 1933, ii., 1197.6 Brit. Med. Jour., March 24th, 1934, p. 523.
ANNOTATIONS
COMPULSORY CONSULTATIONS
THE March number of St. Bartholomew’s HospitalJournal contains a rumour that the medical consul-tations held at the hospital are to be abolished. Letthem pass, the surgeon might say, for they are onlythings of yesterday, mere mushroom growths. Theold-time physicians rarely saw the patient; theyprescribed for him sitting in a coffee house, upon thereport of symptoms told them by the apothecary.They were far too individualistic to consult withanyone, least of all with a fellow physician, unless agreat nobleman had the gout or a royal personagewas about to die. It was far otherwise with thesurgeons.From the earliest times of which there is any record
in London the surgeons were the guardians of thepublic health and were held responsible for the cureof the sick and maimed. They were on duty at thecity gates to see that no grossly diseased person wasadmitted ; and as early as Feb. 2nd, 1369, the chief
f
officers of their gild were sworn to take charge of thehurt and wounded and to give true information tothe officers of the city about such persons " whetherthey be in danger of death or not." A few years laterwhen the barbers had become a company theyordained, in what would now be called their standingorders, that " no barber practising the surgical facultywithin the liberty of the city should presume to takeunder his charge any sick person in actual danger ofdeath or of permanent disability from injury withoutshowing him to the master and wardens." Should
