921 been continued, together with phenobarbitone, while he has been receiving folic-acid therapy. Blood values The direct Coombs were virtually normal...

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921 been continued, together with phenobarbitone, while he has been receiving folic-acid therapy. Blood values The direct Coombs were virtually normal in 6 weeks. test was negative two weeks after folic-acid therapy The alkaline-phosphatase level is now was started. 17 K.-A. units.

epileptic patient, a woman aged 47, in whom megaloblastic ansemia also developed while she was taking phenytoin, has more recently been investigated. She, however, had histamine-fast achlorhydria and minor neurological signs, and showed a prompt hsematological response following 100 u.g. of vitamin Bl2 given intramuscularly. While we feel she is more likely to be an example of true addisonian (pernicious) ansemia occurring in an epileptic receiving drug therapy, we are keeping an open mind on this matter and further studies of both patients are being made. While we would, at present, hesitate to draw any conclusions as to the cause of these ansemias, the published Another








that careful

investigation of any anaemia developing in patients receiving anticonvulsant drugs-perforce before any hasmatinics are given-is necessary so that any connection between such therapy and megaloblastic anaemia may be brought to light. St. George’s Hospital Medical School, London, S.W.1.



SIR,-The article by Dr. Hawkins and Dr. in your issue of Oct. 9, prompts us to record the

Meynell, following


In February, 1952, a 19-year-old mentally defective girl admitted to hospital in status epilepticus. She had been treated at home with phenobarbitone for years and phenytoin sodium (gr. 11/2 b.d.) for three months. There was no clinical evidence of ansemia. Her fits were controlled by intramuscular injections of soluble phenobarbitone and paraldehyde, and phenytoin sodium was increased to gr. 11/2 t.d.s. along with


phenobarbitone. Six months later, whilst still


this treatment, she


to have vague abdominal pains and vomiting. She became pale and complained of a sore throat. There was no history of

She was nutritional deficiency, diarrhoea, or dyspepsia. readmitted to hospital in September, 1952. A severe megalocytic anaemia with megaloblasts in the peripheral blood and a megaloblastic bone-marrow were found. Laboratory investigations showed : test-meal, HCI 35/25 after histamine ; serum-bilirubin 0-1 mg., calcium 11-3 mg., inorganic phosphorus 4’9 mg., alkaline phosphatase 8-5 K.-A.

units per 100 ml. ; fat-balance test (one 3-day period only, therefore unreliable) 58% absorption with normal split-unsplit fat ratio. X-ray examination of the skeleton showed no signs of osteoporosis. Vitamin-Bl2 level in serum was 135 f.Lf.Lg. per ml. (estimated by courtesy of Dr. Ross). The patient received 1 pint of packed cells the day after admission. She gave only a weak reticulocyte response to 10 daily doses of 100 f.Lg. of ’Cytamen’ and the nucleated red cells in the peripheral blood remained megaloblastic. There was a very good response to 40 mg. of folic acid intramuscularly daily, the peripheral nucleated red cells becoming normoblasts on the third day and the reticulocyte peak reaching 27-6% on the sixth day of treatment. The patient made a very good recovery. She is still on small maintenance doses (5 mg. bi-weekly) of folic acid and continues taking phenytoin sodium and phenobarbitone. The main hsematological data are shown in the accompanying table.

It is possible that the folic-acid deficiency in this case due to an interference by phenytoin sodium with the folic-acid metabolism as Dr. Hawkins and Dr. Meynell suggest. As we were able to have only one 3-day fatbalance test, our original conclusion that this was a case of steatorrhcea might have been erroneous. There were no other laboratory findings or clinical symptoms to support this diagnosis. At about the same time another girl, aged 16, with megaloblastic anaemia due to folicacid deficiency came under our observation with no detectable cause whatsoever. Statistical evidence of a relationship between phenytoin sodium and megabloblastic erythropoiesis remains to be established. The importance, therefore, of recording all similar cases is obvious. A closer study of the erythropoiesis and fat-balance during phenytoin therapy is indicated. E. G. RHIND City General Hospital, Sheffield. S. VARADI. was


SiR,-May I thank Dr. Tredgold (Oct. 9) for his criticism of my article, even if he does seem a little harsh. " bedside manner " is the means by which Surely, " rapport" is established. I have no doubt that Dr. Tredgold, as any other good physician, forms rapport intuitively. My article is merely an attempt to elucidate some of the mechanisms involved in this process. I know that Dr. Tredgold cannot make a diagnosis before the initial hand-shake, but I am quite sure that he is aware of the degree to which the patient is inhibited, and so intuitively makes the appropriate greeting, which is good bedside manner," and so helps him establish " rapport." AINSLIE MEARES. "



SiR,—May I join the large number of readers who must be protesting against a most dangerous misuse of figures in your annotation of Oct. 16 ? In 1950, it is stated, 44% of all those killed (on the roads) were pedestrians : only 7%, 5%, and 2% were killed in motor-cars, goods-transport vehicles, and buses respectively. " Thus," it is deduced, " those who ride inside vehicles are far safer than those who walk.... " Far fewer test pilots were killed in 1950 than farmers. Are we to deduce that being a test pilot is one of the safer occupations in this country ? In this example, at least, it should be obvious that fewer test pilots were killed because there were fewer of them. It is reasonable to assume that the larger number of pedestrians than motorists in the country in some way accounts for the difference in the number of deaths. This is no matter of advanced statistical methodology. If we find it difficult to combine common sense with the figures we use, then please, may we stick to the common sense, and leave the figures alone ? Or shall we all buy motor-cars to save our lives ?‘ D. J. NEWELL. University of Durham.