SUMMARY Suppositories of sulphapyridine, 5-aminosalicylic acid, and placebo were used in 45 patients with idiopathic proctitis to determine the active part of sulphasalazine. Each patient used one of the suppositories twice daily for four weeks in a double-blind controlled trial. Complete clinical remission with normal rectal mucosa on sigmoidoscopy occurred in 60% of patients given 5-aminosalicylic acid, but in only 13% and 27% of those given sulphapyridine and placebo respectively. Twelve patients were included twice. tn eight of these patients 5-aminosalicylic acid was given one time and sulphapyridine (two patients) or placebo (six patients) another time. Clinical remission occurred in each patient with 5-aminosalicylic acid, but in only one patient during other therapy. The results suggest that 5-aminosalicylic acid is the active therapeutic moiety of sulphasalazine.Salicylazosulphapyridine (Salazopyrin, sulphasalazine, SASP) is widely used in the treatment of ulcerative colitis and Crohn's disease. Several controlled trials have established its value in mild and moderately active colitis ' and in maintenance therapy to prevent recurrence of the disease3 4. Its value in Crohn's disease has not yet been established. SASP is composed of sulphapyridine (SP) in azo linkage with 5-aminosalicylic acid (5-ASA). After an oral dose of SASP in man, only a small fraction is absorbed in the small bowel. Most of the drug reaches the colon and is almost completely split at the diazo bond by bacterial azo-reductases into SP and 5-ASA.5 6 SP is then mostly absorbed and partially metabolised in the liver (acetylation and glucuronidation) before excretion in the urine. Most of the 5-ASA moiety can be recovered in the faeces and only a small portion is found in the urine as the acetylated form.7The mode of action of SASP remains unknown.As SASP is particularly effective in the treatment of *Address for reprint requests: P A M van

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The response of active Crohn's disease to sulphasalazine (4-6 g per day) has been studied in a placebo-controlled trial. The study was carried out at two hospitals. From August 1977 to August 1979 all patients with established Crohn's disease were examined for their eligibility for the trial. A nine-item index of inflammatory activity was used as the primary measure of response. The variables in this index were serum albumin, ESR, body weight related to height, abdominal mass, temperature, stool consistency, bowel resection, and extraintestinal symptoms related to Crohn's disease. A favourable response to therapy was defined as a decrease of the activity index with 25 0 or more at the end of the trial period, compared with the initial value. Twenty-six patients (13 in each treatment group) have been followed up for six months. The response of active Crohn's disease to sulphasalazine was significantly better than to placebo. Sulphasalazine (SASP) is widely used in the medical treatment of active Crohn's disease but so far only two controlled trials have been published, the results of which are not unequivocal.'2 We therefore undertook a controlled double-blind study to evaluate the efficacy of SASP in the treatment of patients with active Crohn's disease. When the trial was planned there was no evidence that any medical treatment was effective in Crohn's disease, so the effect of SASP was compared with a placebo. Methods CASE SELECTION AND DIAGNOSTIC CRITERIA FOR CROHN'S DISEASE The study was carried out at two hospitals. From August 1977 to August 1979 all patients with established Crohn's disease who were seen at or referred to these hospitals and the patients who were

SUMMARY To evaluate the usefulness of provocation tests in the diagnosis of the Zollinger-Ellison (ZE) syndrome stimulation tests with calcium, 15 mg/kg.3 h, and secretin GIH, 1 U/kg.30 s, were performed in 15 patients with histologically proven or suspected ZE syndrome. Nine of these 15 patients were without previous gastric surgery and in them meal stimulated serum gastrin levels were measured as well. These tests were also performed in normal subjects and in patients with duodenal ulcer, antrectomy, total gastrectomy, and achlorhydria. All tests were considered to be positive if a more than a 50 % increase in serum gastrin was found. The results indicate that secretin stimulation is the provocation test of first choice in the diagnosis of this syndrome. This test is most valuable for the following reasons: (1) there were few (two out of 15) false-negative test results in ZE patients; (2) there were no false-positive tests in 69 patients without gastrinoma; (3) it was easy and quick to perform; and (4) there were no adverse reactions. The two ZE patientswithnegativesecretinstimulation tests had negative calcium provocation tests as well, in spite of histologically proven gastrinoma. In 11 patients with suspected or proven ZE syndrome and basal serum gastrin levels of less than 1000 pg/ml a rather good correlation (r = 0-841; p < 0 01) was found between the percental increase in serum gastrin after stimulation by calcium and secretin. Meal stimulated serum gastrin levels are helpful only in patients without previous gastric surgery.

The disposition of mesalazine from the azo compounds sulphasalazine and olsalazine (Dipentum) and from the slow-release mesalazine drugs Pentasa, Asacol, and Salofalk was studied in 20 patients with inflammatory bowel disease. Ten of them had diarrhoea, and 10 had normal stools. On the last 2 days of a 7-day maintenance treatment with each of the study drugs urine and faeces were collected for determination of mesalazine, acetyl-mesalazine, and unsplit azo compound. In patients with and without diarrhoea the urinary and the faecal excretion of acetyl-mesalazine was lowest during treatment with olsalazine. The proportion of acetyl-mesalazine in faeces was highest during treatment with Pentasa in both groups. The presence of diarrhoea was associated with a decrease in the proportion of acetyl-mesalazine in faeces during treatment with all drugs, not significant only for Pentasa. The proportion of unsplit azo compound in faeces increased in the case of diarrhoea to almost 50%. It is concluded that in patients with inflammatory bowel disease diarrhoea substantially influences the disposition from all these drugs except Pentasa.