266 duce fever. Our data on cimetidine’s behavioural and electrocortical effects4 may also explain the mental confusion observed in some patients on this drug. We thank Smith Kline &
French Laboratories
Ltd, for supplying
dimaprit.
G. NISTICÒ D. ROTIROTI
Institute of Pharmacology,
A. DE SARRO F. NACCARI
University of Messina, 98100 Messina, Italy
CIMETIDINE AND PANCREATITIS: LESSONS FROM ANIMAL EXPERIMENTS
SiR,—Jane and Lee1 described acute, hsemorrhagic, and necrotising pancreatitis in rats given cimetidine and gastric secretagogues (pentagastrin and carbachol). Cimetidine did not prevent duodenal ulcers. Clinical reports on the possible association of cimetidine and acute pancreatitis have been con-
troversial.2-4 We describe here studies of cimetidine in the cysteamine-induced duodenal-ulcer model. 5-7 Female Sprague-Dawley derived Charles River rats with an initial body-weight of 200 g were given cimetidine (20, 10, 5, or 1 mg per 100 g) by stomach tube or no cimetidine 30 min
cysteamine (28 mg/100 g by mouthx 3, at 4 h intervals). Surviving animals were killed on the third or the seventh day. Duodenal ulcers were rated 0 (no ulcer), 1 (mucosal erosion), 2 (deep mural ulcer), or 3 (perforated and/or penetrated ulcer). before
creatitis seemed to correlate with the frequency of duodenal ulcer, and cimetidine did not affect these changes. These results are not in line with the observations of Jaffe and Lee’ and favour those clinical reports which dissociate acute pancreatitis and treatment with cimetidine. The dose range of cimetidine was similar in the two animal experiments; The severe pancreatitis described by Jaffe and Lee might have been due to interaction between cimetidine and the very large doses of pentagastrin and carbachol given or to the non-specific stress of irritation by the 24 h subcutaneous infusion of the secretagogues. Also, since duodenal ulcers in that study were not prevented by cimetidine, sustained ulceration with attendant peritonitis8 and vascular ischmmia,9 might have been responsible for the pancreatic necrosis. Our results indicate that cimetidine significantly decreases the incidence and severity of cysteamine-induced duodenal ulcer and does not aggravate the peripancreatitis and/or interstitial pancreatitis frequently seen in association with duodenal ulcer. The mild inflammation around the pancreas and in pancreatic septa seems to be a consequence of local peritonitis accompanying duodenal ulcer. Departments of Pathology, Peter Bent Brigham Hospital and Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115, U.S.A.
SANDOR SZABO HARVEY GOLDMAN
CHENODEOXYCHOLIC ACID AND DIARRHÆA MODULATION BY CIMETIDINE OF DUODENAL ULCERS PRODUCED BY CYSTEAMINE
SIR Therapeutic administration of chenodeoxycholic acid (C.D.C.A.) for dissolution of cholesterol gallstones has been associated with increased frequency and/or looseness of stools. 1-4 This side-effect seems to be dose-related.2 We have compared the effect of C.D.C.A. and placebo on bowel frequency, total gastrointestinal transit-time, and segmental colonic transittimes. Six females and
Statistical analysis by Fisher-Yates exact and Student’s t-test (intensity): * P
French Laboratories
Ltd, for supplying
dimaprit.
G. NISTICÒ D. ROTIROTI
Institute of Pharmacology,
A. DE SARRO F. NACCARI
University of Messina, 98100 Messina, Italy
CIMETIDINE AND PANCREATITIS: LESSONS FROM ANIMAL EXPERIMENTS
SiR,—Jane and Lee1 described acute, hsemorrhagic, and necrotising pancreatitis in rats given cimetidine and gastric secretagogues (pentagastrin and carbachol). Cimetidine did not prevent duodenal ulcers. Clinical reports on the possible association of cimetidine and acute pancreatitis have been con-
troversial.2-4 We describe here studies of cimetidine in the cysteamine-induced duodenal-ulcer model. 5-7 Female Sprague-Dawley derived Charles River rats with an initial body-weight of 200 g were given cimetidine (20, 10, 5, or 1 mg per 100 g) by stomach tube or no cimetidine 30 min
cysteamine (28 mg/100 g by mouthx 3, at 4 h intervals). Surviving animals were killed on the third or the seventh day. Duodenal ulcers were rated 0 (no ulcer), 1 (mucosal erosion), 2 (deep mural ulcer), or 3 (perforated and/or penetrated ulcer). before
creatitis seemed to correlate with the frequency of duodenal ulcer, and cimetidine did not affect these changes. These results are not in line with the observations of Jaffe and Lee’ and favour those clinical reports which dissociate acute pancreatitis and treatment with cimetidine. The dose range of cimetidine was similar in the two animal experiments; The severe pancreatitis described by Jaffe and Lee might have been due to interaction between cimetidine and the very large doses of pentagastrin and carbachol given or to the non-specific stress of irritation by the 24 h subcutaneous infusion of the secretagogues. Also, since duodenal ulcers in that study were not prevented by cimetidine, sustained ulceration with attendant peritonitis8 and vascular ischmmia,9 might have been responsible for the pancreatic necrosis. Our results indicate that cimetidine significantly decreases the incidence and severity of cysteamine-induced duodenal ulcer and does not aggravate the peripancreatitis and/or interstitial pancreatitis frequently seen in association with duodenal ulcer. The mild inflammation around the pancreas and in pancreatic septa seems to be a consequence of local peritonitis accompanying duodenal ulcer. Departments of Pathology, Peter Bent Brigham Hospital and Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02115, U.S.A.
SANDOR SZABO HARVEY GOLDMAN
CHENODEOXYCHOLIC ACID AND DIARRHÆA MODULATION BY CIMETIDINE OF DUODENAL ULCERS PRODUCED BY CYSTEAMINE
SIR Therapeutic administration of chenodeoxycholic acid (C.D.C.A.) for dissolution of cholesterol gallstones has been associated with increased frequency and/or looseness of stools. 1-4 This side-effect seems to be dose-related.2 We have compared the effect of C.D.C.A. and placebo on bowel frequency, total gastrointestinal transit-time, and segmental colonic transittimes. Six females and
Statistical analysis by Fisher-Yates exact and Student’s t-test (intensity): * P
