RECTAL METHYLPENTYNOL IN LABOUR

743 1200 calories of the total 3000, or 40%, in both diets, and, in our terms, we have values of s==20 and p 20 with the first diet and S=0, p=O with the second. The iodine value will be identical in the two cases (=86) and, according to Ahrens et al., there will be no change in serum-cholesterol. But the equation based on our experimental results predicts a serum-cholesterol change:

A Chol.-2-74(0-20) 1’31(0-20) = - 29, average, the serum-cholesterol concentration will fall by 29 mg. per 100 ml. on the second diet. Finally, we may consider a third diet which differs from the first only in that the total fat is only 67 g. (20% of total calories). The

i.e., on the

iodine value is still 86 in both diets. Ahrens

et al. apparently predict change, or at least they provide no clue as to what may happen. But our equation predicts: A Chol.=274(10-20)---131(10-20)= -14, i.e., changing from the first to the third diet will, on the average, no

produce

a

fall of 14 mg. per 100 ml.

In view of the fact that the great current interest on these points seems to be matched by an equal degree of confusion in many quarters, we should point out that the prediction equation refers to the average changes in serum-cholesterol to be expected in men without a high serum-cholesterol within two to four weeks after a dietary change. Larger responses may be expected in hypercholosterolxmia and also, perhaps, with dietary differences maintained for very long periods of time. And, of course, there is no place here for speculations about " essential-

fatty-acid deficiency." Laboratory of Phsyiological Hygiene, University of Minnesota, Minneapolis.

ANCEL KEYS ANDERSON FRANCISCO GRANDE.

JOSEPH T.

REDUCTION OF CIRCULATING LIPIDS SIR,-With reference to the article by Dr. Oliver and Dr. Boydyour readers may be interested to hear of our

results in a similar butyric acid amide.*

therapeutic trial with 2-phenyl-n-

Of 15 men with considerable hypercholesterolaemia, 12 had had a myocardial infarction between six weeks and a year previously, but had no signs at present of cardiac failure or of angina: 1 had essential hypertension, another had essential hypercholesterolxmia without clinical manifestations, and 1 had hypercholesterolaemia with xanthoma tuberosum on the fingers and elbows. The ages of the patients varied from 36 to 63

(average 50-6). dosage of 2-phenyl-n-butyric acid amide was 1 g. every eight hours. All patients were carrying on their usual occupations; no special diet was given, but they were asked to be careful not to put on weight. 1 patient received the treatment for four weeks, 3 for two months, and the others for from three to five months. In 10 of the 15 patients, plasma-cholesterol level was reduced by 20 mg. or more per 100 ml. The initial mean total plasma-cholesterol in the 10 patients who reacted favourably was 346 mg. per 100 ml.; this dropped to 310 mg. after giving the drug. The mean initial absolute level of P-cholesterol was 310 mg. per 100 ml., dropping to 258 mg. after treatment (the B-cholesterol level was determined by analytical chemical methods after elution of the fraction from The

the paper after electrophoresis). The average total plasma-cholesterol among healthy men of European Jewish origin in Israel in the age-group 40-60 is 220 mg. per 100 ml., and of 3-cholesterol 180 mg. ; taking these levels as 100%, our results for the 10 patients were a drop in total cholesterol from 157% to 131% and a drop in P-cholesterol from 162% to 143%. The effect of 2-phenyl-n-butyric acid amide seems to be greater in patients with a high initial level of plasma cholesterol ; 4 of the 5 patients who did not react to the treatment (and only 1 of the 10 who did) had an initial plasma-cholesterol less than 300 mg. per 100 ml. *Marketed as ’Nivonorm’ by Teva, Jerusalem. Oliver, M. F., Boyd, G. S. Lancet, 1957, ii, 829. Brunner, D., Loebl, W., Schindel, L. E. (in the press).

1. 2.

Like Dr. Oliver and Dr. Boyd, we found hardly any change in the ratio between oc and P cholesterol, even where there was a significant fall in total cholesterol. We have noted this in other therapeutic trials for lowering the lipid levels, and it seems that the ratio of (x to cholesterol is one of the most stable factors of the lipid patterns. In none of the 15 patients did the lipid levels rise. We infer that 2-phenyl-n-butyric acid amide has a genuine, though not great, cholesterol-depressing effect. Our results are not so favourable as those of the French and Italian clinical workers,3-6 but we believe that n-phenyln-butyric acid amide does have some effect, especially when the Dlasma-cholesterol is verv high. DANIEL BRUNNER K. LOEBL. L. E. SCHINDEL. CORONARY-ARTERY DISEASE SiR,łIn your leading article of March 22 you quote the statement that " in the healthy organism fibrinolysis is in a dynamic equilibrium with the fibrin-depositing

coagulation process ", the implication being that so much has been established. This is rather misleading, since what is quoted is an intelligent speculation first put forward to my knowledge by Nolf in 1908, and adopted as a working hypothesis by many workers, including Astrup. However attractive the concept may seem it should be made clear that it is unsupported by direct evidence. It will be a pity if the observations of various workers on fibrinolysis in vitro, including the effect of fat, be pressed into speculative dynamic hypotheses, subsequently to be quoted as if proven. Such a tendency is likely to retard and not to advance knowledge. G. R. FEARNLEY. RECTAL METHYLPENTYNOL IN LABOUR

SIR,-The place of methylpentynol in labour is now well recognised, but rectal administration receives no mention. This route has been found effective in over 5000 women admitted to the Birmingham Maternity Hospital in the past three years. This method was first tried when it was noted that the who most often vomited the oral capsule was the nervous primigravida-the patient whose apprehension it was hoped to relieve, not increase. Bournereported that 8% of patients vomit the capsule, but a second dose is usually retained. By use of the rectal route, increase of nervous tension from this vomiting can be avoided without loss of the drug’s

patient

efficiency. Methylpentynol is given half an hour after an enema to a patient in early established labour. The usual dose is 750 mg. (i.e., 3 capsules), inserted with the finger as far. as possible beyond the anal margin. Occasionally in a very nervous primigravida 1 g. of methylpentynol is given; and, again uncommonly, the dose may be repeated in not less than three hours. When the patient’s anxiety is associated with painful contractions it is our practice to give 100 mg. of pethidine hydrochloride intramuscularly with the initial dose, for methylpentynol does not relieve pain. The drug is as efficient when given rectally as it is by mouth. The clinical impression is that labour is shortened and the incidence of postpartum haemorrhage is not increased. 3.

4. 5. 6. 7.

Cottet, J., Vignalou, J., Redel, J., Colas-Belcour. Bull. méd. hôp. Paris. 1953, 69, 903. Mathivat, A., Cottet, J. ibid. p. 1030. Cottet, J., Mathivat, A., Redel, J. Pr. méd. 1954, 62, 939. Rossi, B., Rulli, V. Amer. Heart J. 1957, 53, 277. Bourne, G. Lancet, 1954, ii, 522.

mem.

Soc.

744 If it is given late in the first stage, pressure of the head during the second stage will at times expel a proportion of the dissolved capsule and drug from the anus. As it is a brilliant green it is easily distinguishable from meconium. No ill effects have been seen, either generally or locally in the rectum. The infant appears unaffected. This method has been of value in general practice,

where not

constant

supervision

in the

early stage of labour is

alwavs nossihle.

University

of

W. L. WHITEHOUSE.

Birmingham.

AUTOMATIC SIGNAL FOR URINE-COLLECTING BOTTLES

SIR,-It is sometimes hard for nurses, especially during busy night-watches, to cope with the rapidly filling urinecollecting bottles of polyuric patients with indwelling catheters. An automatic device for calling the nurses’ attention to a full bottle would therefore be of value, and the following signal system was constructed. Two electrodes, connected to the

regular

patient-

bell system (working under 24 volts) are put into the upper part of the urine - collecting bottle (see accompanying figure); as soon as the urine reaches the electrodes, the electric circuit is closed (by electrolysis of the urine), and the bell rings-incessantly, of course, thereby differentiating this call from the normal one-ring call by patients.

Our

nurses

are now more

I

am

grateful

appreciate this device. Urine collections accurate, and ward hygiene has improved. to

Mr.

J. Fraenkel,

the

hospital electrician,

for his

advice. Shaarei Zedek General Hospital,

Jerusalem.

J. LEURER.

NO PEACE FOR THE PATIENT

SIR,-" Ex-Patient " (March 22) lists forty separate calls on her attention during the hospital day, but does not describe how sleep is murdered at night too. A recent extended visit to hospital (when I had every reason to be grateful for the excellent care which I received) opened my eyes, both figuratively and in fact. The main causes of the disturbance seem to be the

clanging and squeaky trolleys (which are apparently indispensable to nurses in the course of their duty), and the constant shouting of the senile and demented. Could not the hospital trolleys be oiled, and the senile all be placed together in one ward ? In order to fill a ward, medical and surgical patients might have to go together, but, after all, this is supposed to be an age where barriers are breaking down. While the vast majority of patients do not suffer physically at all under these nocturnal disturbances, the effect on children (and there is usually one in every ward in a large general hospital) must surely be bad. The Medical School, Manchester.

VALERIE FRAZER.

P.A.S. AND THE PATIENT

SIR,-We should like

to join the discussion which has article on outpatient P.A.S. therapy.1-6 Our main aim was to indicate the size of the problem presented by the failure of patients to consume their prescribed P.A.s. Whether the default-rate is 50% (as found by us in the 151 members of a complete outpatient population), or whether it is 25%7 or 22%5 (as found in more selected groups), the conclusion must be the same: patients who fail to take P.A.S. form a very substantial proportion of those so treated. We cannot believe that patients vary so much from district to district that any physician could afford to disregard this fact when deciding to use oral medication. The difficulties of providing an alternative to long-term streptomycin and isoniazid 25

followed

our

freely admitted, but they must be weighed carefully against the possible failure to take P.A.S. The toxic effects of streptomycin, in our experience, can partly be avoided by giving equal parts of streptomycin and dihydrostreptomycin, and this is our practice in patients over 50 If oral therapy is chosen, then every years of age. and encouragement explanation must be given to the on frequent and unexpected and urine tested patients, are

occasions. Our second aim was to draw attention to a modification of the ferric-chloride test which is simple enough to use as a routine in outpatient departments and is, when performed exactly as described, sensitive enough to detect P.A.S. taken in full dosage whilst minimising confusion with the usual doses of aspirin. A test that is too sensitive would react strongly with the urine of patients who have taken aspirin or salicylate; inadequate doses of P.A.S. would also give positive results. At the same time we consider that the problem of occasional false results is of little importance compared with the default-rate revealed. The detection of calcium B-P.A.S. in the urine is affected by the dosage schedule and dose/test time intervals as indicated by Dr. Lauener and Dr. Friedrich. During the period of our trial the daily prescriptions were 14 g. of calcium B-P.A.S. or 10 g. of P.A.S. We have felt these to be the minimum desirable doses. At this dosage of calcium B-P.A.S. the proposed increase in sensitivityis unnecessary and in fact undesirable: in its present form the test may well be negative if patients are taking very low doses of calcium B-P.A.s., but we feel this to be an advantage. We always prescribe oral P.A.S. in two equal daily doses at twelve-hour intervals, as you recommend,2and therefore our single dose of calcium B-P.A.S. was always twice that mentioned by your correspondents.During our trial calcium In 21 (49%) a positive B-P.A.S. was prescribed in 43 cases. urine test was found and in 9 cases the test was still positive at ten to twelve hours after ingestion. It thus seems clear that a 7 g. dose of calcium B-P.A.S. is capable of giving a positive reaction to our ferric-chloride test, which should be of sufficient sensitivity to be of practical value to those physicians who continue to prescribe this drug. We ourselves are not convinced that calcium B-P.A.S. is as effective in preventing isoniazid resistance as is P.A.s., and for this and other reasons we no longer use it. ’

However, to return to the main argument, even if we assumed that all our negative tests with calcium B-P.A.S. were false (which we do not believe), the proportion of defaulters among our patients is lowered only from 50% to 36%. It is evident that all published work on this subject has revealed a high default-rate in taking P.A.S. 1. Dixon, W. M., Stradling, P., Wootton, I. D. P. 2. ibid. p. 881. 3. ap. Simon, D. J. ibid. p. 947. 4. Edwards, J. H. ibid. p. 1171. 5. Leggat, P. C. ibid. p. 1283. 6. Lauener, H., Friedrich, T. ibid. March 15, 1958, 7. Simpson, J. McD. Tubercle, 1956, 37, 333.

Lancet, 1957, ii,

p. 592

871.