ORAL PANCREATIC SUPPLEMENTS TO CORRECT PANCREATIC MALABSORPTION The goals of therapy in treating pancreatic exocrine insufficiency with oral supplements vary. They may be simple reversal of weight loss and growth impairment or control of unpleasant diarrhea or sore rectum symptoms or restoration of fat excretion to normal. Each of these goals requires different replacement programs and indeed few have obtained normalization of fat excretion without addition of supplements in massive quantities each hour. Two recent papers addressed the practical problems of supplying sufficient enzyme to the duodenum where it is needed. DiMagno and co-workers’ previously demonstrated that substantial increases in either fat or nitrogen in the stool did not occur until disease reduced the maximal stimulated output of the remaining pancreatic fragment to less than 10 percent of normal. This was the level of supplementation that they chose in a new study2 to use in replacement. They measured enzyme levels and pH in the duodenum of patients under treatment. Patients were intubated so that frequent samples could be obtained from the level of the ligament of Treitz and infusions of nonabsorbable marker ( 14C polyethylene glycol) were made. A meal of ground beef was ingested in the acute studies. The study design permitted the calculation of the total amount of enzyme recovered from the ligament of Treitz in active form. Whereas the total enzyme recovered without supplements in six patients with pancreatic insufficiency was 0.2 percent of normal these were increased in both trypsin and lipase to five times this level with any schedule of supplements. Eight 250 mg tablets (Viokase) with meals or two given each hour produced a significant rise in enzyme activity, but this was approximately 1/100 of the normal output and well below the amount aimed for of one-tenth of normal. Gastric pH was quite comparable after a meal in the normals and the pancreatic insufficiency patients, but duodenal pH was consistently lower in insufficiency than in normals, remaining usually under 4 for the 190

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entire interval of study from 0 to 210 minutes after a meal. In balance studies the stool fat fell from a mean of 65 g per 24 hours to 30 g. The stool nitrogen fell from a mean of 8 g to 3 g or slightly less. There were only modest differences between the use of the supplements with meals or given hourly for four hours. On either regimen it was estimated that only 22 percent of the trypsin and 8 percent of the lipase activity ingested was delivered to the ligament of Treitz. A paper by Graham3 assayed available pancreatic extracts and tested them in six different subjects with pancreatic insufficiency. Lipase activity varied from a low of 10 to 3600 U per tablet and 11 preparations contained significantly less than 600 U per dose. Lipase activity in vitro correlated with the potency in vivo. Enteric coated tablets are significantly less effective (20 2 13 percent reduction). The longer the gastric pH remained over 4 and the higher the average duodenal pH, the more marked the reduction in steatorrhea obtained by administration of the preparation. Exact data on various commercial -preparations available are given. It is apparent that control of pH of the stomach and duodenum through alkali and the initial enzyme potency of the preparation of supplement used are both important in obtaining objective improvement in pancreatic insufficiency. The minute levels of enzyme activity recorded with supplements at the level of the ligament of Treitz are not exactly reflective of the beneficial effects of these supplements. Clearly a better supplementation can be achieved. These two papers should indicate the need for more work on this common problem. 0

1. E.P. DiMagno, V.L.W. Go and W.H. Summerskill:

Relations Between Pancreatic Enzyme Outputs and Malabsorption in Severe Pancreatic Insufficiency. New Engl. J. Med. 288: 813-815, 1973 2. E.P. DiMagno, J.R. Malagelada, V.L.W. Go and C.G. Moertel: Fate of Orally Ingested Enzymes

in Pancreatic Insufficiency. Comparison of Two Dosage Schedules. New Engl. J. Med. 296: 1318- 1322, 1977 3. D.Y. Graham: Enzyme Replacement Therapy of

Exocrine Pancreatic Insufficiency in Man. Relation Between In Vitro Enzyme Activities and In Vivo Potency in Commercial Pancreatic Extracts. New Engl. J . Med. 296: 1314-1317, 1977

ALCOHOL CONSUMPTION AND BLOOD PRESSURE

The massive number of interviews conducted as a part of health checkup examinations between July, 1964, and August, 1968, in the Kaiser-Permanente Medical Care Program were used to relate alcohol consumption to blood pressure.’ Of 105,578 individuals who completed multiphasic screening, sufficient data on self-admitted alcohol consumption was available in 83,947 men and women from the ages of 15 to 79. Drinking history in the past year indicated (a) nondrinkers, (b) those taking zero to two drinks each day, (c) three to five drinks or (d) more than six drinks each day of an alcoholic beverage. Because of the large number of subjects, age, sex, race, cigarette and coffee use, education level and adiposity could be evaluated in relation to drinking. When compared with nondrinkers, those taking six or more portions each day had strikingly significant elevation of the systolic blood pressure (mean 10.9 mm Hg higher), and diastolic blood pressure (mean 4.5 mm Hg higher) in all groups. If significant hypertension is defined as blood pressure in excess of 160/95 in either level, then in comparing drinkers with nondrinkers, the percent-

ages of persons with both systolic and diastolic “hypertension” were as follows: in white men 11.21 versus 4.7 percent is found, white women 11.3 versus 6.3 percent, black men 15.1 versus 10.2 percent and black women 24.2 versus 14.7 percent. The effect did not become significant in all of the sex and racial groups until more than two drinks were taken each day, suggesting that there may be a threshold effect. The effect was independent of age, sex, race, cigarette smoking, drinking of more than six cups of coffee per day or educational attainment. The authors reviewed this experience in terms of three other epidemiological studies and found the conclusions similar. In contrast to other studies, however, the significance of the elevation seemed greater. Therefore this larger study supports heavy intake of alcohol as being of importance in clinically meaningful hypertension. 0 1. A.L. Klatsky, G.D. Friedman, A.B. Siegelaub and M.J. Gerard: Alcohol Consumption and Blood Pressure. New Engl. J. Med. 296: 1194-1200, 1977

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