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Experimental and Clinical Observations on Poldine In APRIL 15, 1961 MYOCARDIAL INFARCTION MBRrM 1071 Prognosis.-Our first patient is of interest because of the long survival period. A significant feature of septal EXPERIMENTAL AND CLINICAL perforation is that death does not occur immediately: OBSERVATIONS ON POLDINE IN Edmondson and Hoxie (1942) found an average period of survival of 7.4 days. In the series of Sanders et al. TREATMENT OF DUODENAL ULCER (1956) 13% (12 patients) lived from two months to BY several years. J. E. LENNARDiJONES, M.A., M.B., M.R.C.P. general principles of treatment are Treatment.-The Member, Medical Research Council Department of Clinical based on the knowledge that the efficiency of the heart Research, University College Hospital Medical School; in which septal perforation has occurred has already been Late Registrar, Department of Gastroenterology, Central impaired by coronary atherosclerosis followed by Middlesex Hospital, London myocardial infarction. The left-to-right shunt, with increased blood-flow and raised pressure in the The gastric secretion of acid by a patient with duodenal pulmonary circulation, throws an extra strain on the ulcer in response to a glucose test meal is about halved ventricles, and leads to heart failure. In our first two if an effective dose of poldine methosulphate (" nacton ") cases the administration of digitalis was of benefit, and is taken beforehand (Douthwaite and Hunt, 1958). The diuretics were of considerable help. In Case 1, after a drug also reduces gastric secretion of acid in response few weeks, there was a loss of response to mercurial to a large dose of histamine (R. Seidelin, 1960, personal diuretics: chlorothiazide with potassium supplements communication). These observations, made under had an immediate beneficial effect. strictly controlled experimental conditions, suggest that the drug might be useful in the treatment of duodenal Summary ulcer. To investigate this possibility, the effect of the Three cases of ventricular septal perforation are drug on the acidity of gastric contents has been investi- described. The diagnosis should be considered when a gated under the conditions of clinical use, and the drug patient with an acute myocardial infarction suddenly has been subjected to a small controlled therapeutic trial. deteriorates and develops a loud blowing pansystolic murmur between the left sternal edge and apex in the Experimental Observations fourth and fifth left intercostal spaces. Dye-dilution Observations are reported on 16 patients with an curves in two cases showed the presence of a left-to-right uncomplicated radiologically proved duodenal ulcer. All shunt. were admitted to hospital, they were allowed up, and We thank Professor J. McMichael for his advice and drugs other than poldine and sedatives were withheld encouragement, Dr. D. Emslie-Smith for the phonocardio- unless stated otherwise. The individual dose of poldine grams, and Miss E. Mason for the photographs. for each patient was found by giving increasing doses until side-effects appeared. The initial dose given was REFRENCES 7.5 mg. daily, divided into three doses, or 12.5 mg., Briggs, J. F., and Holt, J. (1954). Amer. Heart J., 47, 926. divided into five doses, and the total dose was increased Cooley, D. A., Belmonte, B. A., Zeis, L. B., and Schnur, S. (1957). by 7.5 or 12.5 mg. each day. If the first side-effects to Surgery, 41, 930. Diaz-Rivera, R. S., and Miller, A. J. (1948). Amer. Heart J., 35, appear were trivial the dose was further increased until 126. definite side-effects developed. The dose just below that Edmondson, H. A., and Hoxie, H. J. (1942). Ibid., 24, 719. producing uncomfortable side-effects was defined as the Gottsegen, G., Szdm, I., Romoda, T., and Matheides, P. (1957). " Acta med. scand., 158, 157. "optimum dose. Latham, P. M. (1846). Lectures on Clinical Medicine, Comprising On the days of the test, samples of gastric contents Diseases of the Heart, 2nd ed., 2, 168. Longman, London. were withdrawn every hour, on the hour, for 24 hours Maher, J. F., Mallory, G. K., and Laurenazi, G. A. (1956). New Engi. J. Med., 255, 1. through a fine naso-gastric tube placed radiologically Muller, O., Humerfelt, S., Rasmussen, H., and Storstein, 0. so that the aspiration holes lay in the likely position of (1950). Acta cardiol. (Brux.), 5, 633. the gastric antrum. The pH of the samples was Oakley, C., Taylor, S., Wilcken, D., Hollman, A., Goodwin, J. F., and Shillingford, J. (1960). Brit. Heart J., 22, 533. measured with a sealed glass electrode. Doses of the Oblath, R. W., Levinson, D. C., and Griffith, G. C. (1952). J. drug, food, and drinks were given immediately after a Amer. med. Ass., 149, 1276. sample was withdrawn. Romanoff, H., and Cooley, D. A. (1960). Israel med. J., 19, 103. Sanders, R. J., Kern, W. H., and Blount, S. G. (1956). Amer. Gastric Addity of Patients Taking Gastric-type Diet Heart J., 51, 736. effect different doses of was studied Schlappi, J. C., and Landale, D. G. (1954). Ibid., 47, 432. The of poldine Shickman, M. D., Fields, J., Pearce, M..L. (1959). Arch. int. under these conditions in 16 patients. Observations Med., 103, 140. made on a control day without poldine were compared Swan, H. J. C., and Wood, E. H. (1957). Proc. Mayo Clin., 32, made on days when the drug was 486. with observations Wood, F. C., and Livezey, M. M. (1942). Amer. Heart J., 24, given. The control observations were made first in 807. 13 patients and last in three patients. Four patients were Zucker, R., Leibowitz, S., Brody, H., and Sussman, R. M. (1952). studied while the dose of poldine was being increased Arch. intern. Med., 89, 899. and at a time when they were experiencing no side-effects from the drug; two patients were studied on one day at daily doses of 30 and 40 mg. respectively, the other two About one child in every 600 born in this country is a patients were studied on two days at daily doses of 30 mongol, and the National Association for Mental Health 60 30 90 mg., Of 10 patients has published a booklet, A Letter to Parents of a Mongol and mg., and respectively. Baby, prepared by a children's specialist, which will be of taking the drug in the optimum dose, nine received five help to those concerned with what, how, and when to tell daily doses and the other patient three daily doses. Four the parents that their child suffers from this condition. of these patients had received the drug continuously in (N.A.M.H., 39 Queen Anne Street, London W.l1, price the optimum dose for periods of 1, 4, 9, and 12 days is. 3d.) respectively before the test. The results in these four BRMTISH 1072 APRIL 15, 1961 POLDINE METHOSULPHATE MEDICAL JouINAL patients did not differ from those in patients who began patients taking a ward gastric-type diet, poldine did not the optimum dose (found by previous trial) on the day affect the acidity of the gastric contents whether given of the test. Three patients were studied at a time when in a dose insufficient to produce side-effects, in the they were experiencing severe side-effects from the optimum dose, or in a dose producing side-effects too drug. The results from all the patients are combined severe to be tolerated as a maintenance treatment. in-Figs. 1 and 2. Each section of the histogram in Fig. 1 Gastric Acidity Under Special Dietary Conditions shows the total number of samples in a particular pH to range on the control day and on the day when the drug Some other antisecretory drugs have been shown as by the sampling was given. Fig. 2 shows the mean acidity on an arith- lower gastric acidity, measured metic scale at each hour of the day. It is clear that in technique, when patients take hourly drinks of a milk- cream mixture without other food. The effect of poldine SIDE-EFFECTS under these conditions has been compared with the effect when the same patients took a standard diet. Four NONE SLIGHT SEVERE DIET patients were each studied during four 24-hour periods: CONTROL 96 SAMPLES 228 SAMPLES 70 SAMPLES hourly milk-cream drinks, with and without poldine; 232 SAMPLES -~7 1 SAMPLES and on the diet, with and without poldine. The order of these 24-hour periods was varied from patient to patient in a latin-square pattern. Details of the method employed and the standard diet used are described elsewhere (Bingle and Lennard-Jones, 1960). Poldine was given in the optimum dose, five times daily. The MILK- CREAM DIET CONTROL - 9S SAMPLES CONTROL 91 SAMPLES + POLDINE - 95 SAMPLES POLDINE - 89 SAMPLES L) w L____- 0. pH <I-S 2-0 3-0 >3-5 <I-S 2-0 30 >3-5 <I1S 2-0 3-0 >3 5 Ii X2.5S- n=5 P->O I X2.07 n-4 P->O9 0 z Fia. 1.-Number of samples in different pH ranges on the day when poldine was given compared to the control day. No differ- ence between the two days is apparent even when poldine was given in a dose large enough to produce severe side-effects. Differences between the distribution of the samples have been pH <IS 20 3-0 >3-S <15 2-0 3-0 >33S x' in the series with no assessed by the test except side-effects, 4 nos P->O I where two observations at different doses of poldine were made X2.28 n-4 P-<0OOI X2-4 unless the number of in two of the four patients (n=5, samples FIG. 3.-Distribution of samples in different pH ranges when in any range was small, when two adjacent ranges were combined).
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