significantly greater effect that 5 mg. delivered by a conventional hospital type aerosol " and also that " its (medihaler) duration of action has been estimated at between one and twelve hours, and that this duration is probably not a function of the dilating effect of the drug but of the strength of the constrictor stimuli opposing it ". Dr. Brown and Dr. Chalmers claim the converse. Surely this difference in results must be due to the variable selection of patients, and not in this instance to the method of administration of isoprenaline. I believe that
methods of administering isoeffective than others, but I am not prenaline convinced that this trial has shown which might be the best. In my experience, a patient with uncomplicated bronchial asthma will respond maximally to approximately the predicted normal after one or two inhalations of an isoprenaline aerosol, if the constrictor stimuli are not too strong, in which case one must resort to abolishing the allergic reaction by other means. On the other hand, the response of a bronchitic is too unreliable and should not be used to estimate the efficacy of a method of administration of a bronchodilator drug. some
The Hospital, Middleton-in-Wharfedale, near Ilkley, Yorkshire.
R. A. BRUCE.
MECLOZINE AND CONGENITAL MALFORMATIONS SIR,-I have read with interest Dr. Folke Pettersson’s letter (March 21), and I wonder if he may not be comparing two unlike sets of figures. Dr. Pettersson reports an incidence of congenital malformation of " about 2-6% in his first series of 11,200 babies. This figure agrees closely with the average incidence of babies born with severe congenital malformations in Europe. Unless there are special features applying to the University Hospital, Uppsala, one can assume that this figure excludes minor malformations such as vascular nsevus, pigmented naevus, talipes, and undescended testicles. All these, however, are reported by Dr. Pettersson in his second series of 585 babies. McIntosh et al.l have shown that, if all minor malformations are included, the congenital-abnormality rate can be expected to be around "
should perhaps be taken of the possibility that the metabolic upset of nausea and vomiting may itself cause foetal malformations. P. L. C. DIGGORY. London, W.8. note
SIR,-I gratified by your review (March 14, of and welcomed your punctilious Medindex p. 621) was
know that two of the three general criticisms already the subject of revisions which will appear in the next edition. These went to the printer some weeks before your review comments.
You will be reassured
appeared. Your third and perhaps most important criticism is of the summary of the cardiotonic glycosides. In.this field, in which the mechanism of action is still somewhat obscure, it is evident that a short summary of digitalis leaves little room for discussion. But I am informed that we cannot hope to avoid controversy. The production of an error-free periodical is a perfection seldom attained as you, Sir, and the compositor of your review (vide line 7) will I am sure appreciate. Each new edition offers the opportunity of improvement, resulting not only from the kind of criticisms made in your review, but also from the helpful and detailed suggestions contributed by the many physicians and other professional readers who have written to us welcoming Medindex and who will, I trust, continue to let us have the benefit of their views. We do indeed recognise that Medindex can be improved and are expanding this work of reference in a variety of " wavs to serve the needs of the busv nhvsician ". MICHAEL GAVIN Managing Editor, Medindex.
We need hardly say that Mr. Gavin’s friendly response to our comments includes a direct hit on line 7.
- end. L.
7-3%. When a drug is given for the first time after the 12th to 14th week of pregnancy, a teratogenic effect is not to be expected. Excluding such cases, Dr. Pettersson records 412 women who took meclozine during the first 12 weeks of pregnancy and gave birth to a total of 399 children, 21 of whom showed malformations. The total incidence of congenital malformations in this group is therefore somewhat less than the average figure to be expected according to McIntosh. When a drug has a teratogenic effect, the malformations encountered may be expected to show some pattern such as occurred in the thalidomide disaster. The wide spread of malformations in Dr. Pettersson’s series is some evidence against meclozine being the cause. In my experience it is extremely difficult to obtain retrospec-
tively reliable information about drugs taken by women during pregnancy, and I have found that it is impossible to be certain that any one drug was not received by the woman unless she is questioned about this during the relevant pregnancy. For the relief of nausea and vomiting, women are liable to take drugs obtained from their obstetricians, their general practitioners, their local chemists (meclozine has been obtainable without prescription in this country and was so in Sweden until the end of 1962), from doctors in holiday areas, and from their female friends and relations. Thus it would be of great interest to know at what date and at what stage of pregnancy Dr. Pettersson questioned his 11,200 patients to be sure that none of them received any meclozine.
In considering the possible teratogenic effects of drugs taken for the relief of nausea and vomiting in pregnancy, 1.
McIntosh, R., Richards, M. R., Samuels, M. H., Bellows, M.T. Pediatrics, 1954, 14, 505.
HUMAN DIELDRIN POISONING
SIR,-During Independence celebrations, a schoolmaster, thinking to give three of his senior boys a treat, invited them
his house for
He had found a tin of cocoa, a drink that neither he nor the ever had before, and he made up four cups according to the directions on the label, putting a heaped teaspoonful of£ powder in each cup and adding hot water, milk, and sugar. Unfortunately the tin contained dieldrin 50% wettable powder. The schoolmaster and one of the boys sipped their drink but did not care for the taste. The other two, presumably after the manner of boys drinking their first glass of beer, swallowed it without comment. After an interval said to have been about thirty minutes they complained of dizziness, began to vomit profusely, and rapidly passed into coma with continuous convulsions. When admitted to hospital about four hours afterwards they were deeply unconscious and having repeated convulsions, The vomit smelled of dieldrin. Physical examination showed no other abnormality except subnormal temperature. The fits were controlled with intramuscular paraldehyde, and penicillin was given prophylactically. Both boys began to recover consciousness about twenty-four hours after poisoning, and this was accompanied by a return to normal temperature. One bey rapidly became mentally normal, but the other had disordered sleep rhythm and was manic and irrational for about seven days. Both boys complained of palpitations and epigastric pain for several weeks afterwards, but they were well when seen
twelve mnnttn laterWest Cameroons, W. Africa.
DAVID R. FRY.