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26 P Medical Research Society 93 A RANWMISED CONROLLED TRIAL OF ELEMENTAL DIET VERSUS PREDNISOLONE IN TREA'IME OF NEW AND RECURRENT CROHN'S DISEASE do .*- do JB m," JJ PAYNE-JAMES;' KR PALMEX,"PJ KW;' .I_ ML CLARK, IUG FARTHING, JJ MISIEWIW and DBA SILK (;:' introduced) Departments of Gastroenterology, St Bartholomew's Hospital, London, Central Middlesex Hospital, London and Western General Infirmary,Minburgh Traditional medical treatment of Crohn's disease (CD) consists of corticosteroid therapy. Elemental diet (ED) has been shown to be equally effective as corticosteroids for inducing remission in new presentations of CD. This may be due to improved nutritional intake with ED. The efficacy of ED in relapses of CD has not been tested. We have randomised 30 adults (18 new (N), 12 recurrent disease (R)) according to nutritional and disease status to receive ED (Vivonex TEN) 2 l/day for 28 days, n=16) or prednisolone (P, 0.75 mg/kg/day for 2 weeks with subsequent dose reduction, n=14) to assess (i) practicality of ED as primary treatment (ii) the efficacy of ED in N and R CD and (iii) any differences in protein energy intake with ED or P. -isease activity index (DAI), ESR, albumin (Alb) and Hb were assessed at entry and weekly for 4 weeks. Inspite of hospitalisation 7 patients (3 N, 4 R) were unable to tolerate ED. 'Ihey were excluded from further analysis. Results: -EN) Elemental diet (n=9) Prednisolone (n=14) 0 Weeks 4 Weeks 0 Weeks 4 Weeks 4.9 1.1 ) 2.2 (0.6b: 5.5 (0.6) 1.8(0.7 );:' DAI E R 52(i4) ' 22(11);*:' 48(ii) ' ig(ti);? ' 34.9( 1.6) 38.5( 1.O) Alb 34.7( 1.5) 38.3(0.8) ll.Z(O.5) 12.4(0.4) Hb 12.3(0.6) 12.6(0.5) :2' 0 vs 4 weeks p<O.O5 When tolerated, ED and P produced similar improvements in DAI and ESR at 4 weeks. Nutritional intake was the same in both groups. These results confirm ED to be equal to P for treatment of Crohn's disease and suggest (i) the effect is not due to difference in nutritional intake, (ii) ED is a viable alternative to prednisolone in s m e patients with Crohn's disease. 94 HUMAN PEPSINS: PARTIAL AMINO-ACID COMPOSITION AND N-TERMINAL AMINO-ACID SEQUENCES J.N. KEEN,*+ J.B.C. FINDLAY*+ K. PEEK,+ N.B. ROBERTS AND W.H. TAYLOR Departments of Biochemistry, University of Leeds,* LS2 gJT, and Chemical Pathology, Royal Liverpool Hospital, Liverpool L7 ~ X W (+introduced The amino-acid composition and sequence o f human pepsins A and C,(named also pepsins 3 and 5, from their position on electrophoresis of gastric juice), are known. The amino-acid structure of pepsin 1 , the ulcerassociated pepsin, is not known, nor is that of pepsins 3A and 3C, which are components of pepsin 3. After acid hydrolysis,thepartial amino-acid compositions of pepsins 1 , 3 and 5 have been determined and can be conveniently expressed as percentages by mass of determined glycine. The known data from pepsins A and C can be expressed similarly. The ratios for the individual amino-acids of pepsin 1:pepsin 3 ranged from 0.84 to 1.08, for pepsin 1: pepsin A from 0.84 to 1.17 (except cystine 0.60), for pepsin 1: pepsin 5 from 0.34 to 2.22 and f o r pepsin 1: pepsin C 0.52 to 1.66. The amino-acid composition of pepsin 1 is thus more similar to that of pepsin 3 than to pepsin 5. The N-terminal sequences of pepsins 1 , 3A, 3, 3C and 5 have been determined by automated solid phase Edman degradation on the "Leedsffapparatus (Findlay, J.B.C., Pappin, D.J.C. and Keen, J.N. in press). Our HPIEC preparations of pepsin 3 and pepsin 5 have the same Nterminal sequence as pepsins A and C respectively, f o r the first 24 and 30 residues respectively, except that residue 1 has not been identified in both. For pepsins 1 , 3A and 3C, the first 30 residues are identical with pepsin A, except that residue 28 in pepsin 1, and 22 in 3A have not been identified. The protein component of pepsin 1 is thus similar to pepsin 3 in amino-acid composition and N-terminal sequence, raising the possibility that pepsin 1 , containing about 50% carbohydrate by weight, may be a carbohydrate/pepsin3 complex. How such a hypothesis might account f o r the unusual collagenolytic and mucolytic properties of pepsin 1 requires further investigation. 95 ANALYSIS OF DUODENAL BILE CONFIRMS HEIGHTENED FREE PADICAL ACTIVITY IN PRIMARY BILIARY CIRRHOSIS (PBC) Pi4 KAY, Pi.1 GUYAN, H KLASS, TW WARNES and JM BRAGANZA Department of Gastroenterology, Royal Infirmary, danchester, M13 9WL, England In PBC the brunt of the early attack is borne by epithelial cells lining medium sized bile ducts, suggesting that a toxic biliary constituent(s) initiates tne trouble. Free radical oxidation products are a plausible candidate for this role, since some are known to alter the structure, and thereby, the immunogenicity of globulin, whilst others interfere with membrane fluidity and could thii.: lead to intrahepatic cholestasis. We examined the hypothesis in the first instance by analysing serum for the % "molar ratio" of the free radical oxidation isomer (9,11 LA') to linoleic acid (9,12 LA) in 11 PBC patients and 20 controls: the levels in the patients were significantly higher (mean SE 6.63 0.62% v 2.14 L 0.18%, ~(0.001). Confirmation that the liver was the source of heightened free radical activity was obtained by analysing duodenal bile collected in the first 10 min after an intravenous injection of secretin. In 7 controls this fraction contained 34 L 5.75 unol of 9,12 LA and 1.62 + 0.31 unol of 9,11 LA', giving a % molar ratio of 4.75 '-0.74%. In 8 ratients with LudJi: grade 1-111 PBC the corresponding values were elevated - 104 + 27 umol (p<0.05), 6.59 + 2.12 umol (p t O . 0 5 ) and 6.9g L 1.80% (NS). CholestasTs in patients with grade IV disease resulted in very low lipid outputs (8.00 + 3.21 umol of 9.12 LA; 0.76 + 0.17 unol of 9.11 LA) but-the molar ratio was very hi&, 12.0 There was no overall correlation + 3.09% (p<O.O>). between molar ratio in bile/serum and histology grade but patients with grade I disease tended to have lower ratios Thus increased hepatic free radical activity is a feature of PBC, including the pre-cirrhotic stages. 96 PLACEBO-CONTROLLED DOUBLE-BLIND TRIAL OF ANTIOXIDANT SUPPLEMENTS IN PATIENTS WITH RECURRENT PANCREATITIS S UDEN, C MAIN, LP HUNT, L NATHAN and JM BRAGANZA Departments of Gastroenterolozy, Computation and Pharmacy, r?oyal Infirmary, Manchester, ill3 9WL; and Department of Psychology, Hope Hospital, Salford, M6 8ND, England Oxidant stress seems to play a pivotal role in the pathogenesis of pancreatitis: hence antioxidant supplements could be beneficial in patients with (non-gallstone) recurrent pancreatitis. We tested this notion in a doseseeking study, spanning five years, in 20 patients and then examined the successful combination in a 20-week double-blind placebo-controlled switchover trial in a further 20 patients with frequent attacks (acute five, chronic 1 5 ) . The combination, which was chosen on the basis of published dietary (European Journal of Clinical Nutrition 1988; 42: 561) and biochemical studies (Trace Elements in Medicine 1988; 5: 79), provdided daily doses of 600 pg organic selenium. 9000 IU !-carotene, 0.54 g vitamin C, 270 IU vitamin E and 2 g methionine. Patients kept diaries to gauge overall pain on a 10 cm visual analogue scale (VAS). Before entry, at crossover and at the end of the trial, they completed VAS pain descriptor