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1. The effect of beta-adrenoceptor agonists and antagonists on gastric emptying of a solid meal labelled with Indium113m was measured by a gamma camera in healthy volunteers or patients with hypertension. Each subject acted as his own control. 2 In ten subjects given isoprenaline (10 or 20 mg) sublingually 30 min before the meal, gastric emptying half-times were significantly prolonged (P less than 0.05). No effect was observed when isoprenaline was given immediately before the meal. 3 Salbutamol, 4 mg four times daily for 1 week also significantly prolonged gastric emptying in four subjects (P less than 0.05). 4 The effect of isoprenaline on gastric emptying was blocked by propranolol 40 mg four times daily for 1 week. 5 In ten subjects propranolol 40 mg four times daily alone for 1 week was found to significantly speed up gastric emptying (P less than 0.005), suggesting that emptying of the normal stomach is subject to some degree of adrenergic inhibition. [ABSTRACT FROM AUTHOR]

1 The effect of drugs acting on beta-adrenoceptors on the absorption and excretion of paracetamol was studied in 26 volunteers and nine patients with mild hypertension, each subject acting as his/her own control. 2 Isoprenaline given 30 min before paracetamol significantly slowed absorption, the effect being dose related, and blocked by prior administration of propranolol. 3 When isoprenaline was given immediately before the paracetamol, absorption was not altered, although a cardiovascular response was seen. 4 Oral salbutamol also delayed paracetamol absorption. 5 Propranolol given alone increased the rate of paracetamol absorption. 6 These results with the changes in the rate of gastric emptying produced by these agents. [ABSTRACT FROM AUTHOR]

Background: Sulfasalazine is accepted therapy for active ulcerative colitis, but side-effects and intolerance are common. Balsalazide is an azo-bonded pro-drug which also releases 5-aminosalicylic acid into the colon, but uses an inert carrier molecule., Aim: To compare the safety and efficacy of sul- fasalazine, 3 g, with balsalazide, 6.75 g, in the initial daily treatment of mild to moderate ulcerative colitis., Methods: A randomized, multicentre, double-blind, parallel group study was performed, with a treatment duration of 8 weeks. Patients on previous maintenance treatment were excluded. The trial medication was the sole treatment for the colitis. Efficacy was assessed by patient diaries, symptom assessment, sigmoidoscopic appearance and histology., Results: Fifty patients were recruited: 26 allocated to the balsalazide group and 24 to the sulfasalazine group. More patients withdrew due to adverse events in the sulfasalazine group (nine patients vs. one patient in the balsalazide group, P=0.004). Improvement occurred in both groups, with a tendency to a faster response with balsalazide. Of the patients taking balsalazide, 61% achieved clinical and sigmoidoscopic remission., Conclusions: Balsalazide, 6.75 g, is effective as the sole treatment for patients with mild to moderately active ulcerative colitis, with significantly fewer withdrawals due to side-effects than in a similar group of patients taking sulfasalazine, 3 g.

Background: Nutritional therapy plays an important role in the management of Crohn disease, particularly during the acute phase. Nutritional supplementation may also prevent relapses during the quiescent phase of Crohn disease, though this aspect has not been widely explored., Methods: Thirty-three patients with Crohn disease in remission were studied. All had steroid-dependent disease. Patients were randomized to receive either elemental diet (n = 19, EO28 Extra) or polymeric diet (Forticips, n = 14). The supplement was given orally in addition to normal food in an amount to provide 35%-50% of pre-trial total calorie intake. Prednisolone was withdrawn gradually. Patients were followed up for 12 months. Failure was defined as increase in CDAI by 100 points from baseline to >200, inability to withdraw chronic steroid therapy completely, need for surgery or steroid therapy., Results: The nutritional supplement was successful in 14 (43%) patients who remained in remission for 12 months with complete withdrawal of steroids. The response to elemental diet (42%) was similar to that of polymeric diet (43%). Nutrition supplement failed in 13 (39%). Six (18%) patients were intolerant to enteral feeding because of smell and taste problems. Per-protocol analysis of data indicated that the success rate of nutrition supplement in steroid-dependent patients was 52% (14 out of 27 patients). No disease or patient-related factors helped predict the response to nutrition supplement., Conclusion: Nutritional supplementation with either an elemental or polymeric diet may provide a safe and effective alternative to chronic steroid therapy in patients with steroid-dependent Crohn disease.

Background: Despite widespread use of aminosalicylates as maintenance treatment for ulcerative colitis (UC), patients still report troublesome symptoms, often nocturnally., Aim: To compare the efficacy and safety of balsalazide (Colazide) with mesalazine (Asacol) in maintaining UC remission., Methods: A randomized, double-blind comparison of balsalazide 3 g daily (1.04 g 5-ASA) and mesalazine 1.2 g daily for 12 months, in 99 (95 evaluable) patients in UC remission., Results: Balsalazide patients experienced more asymptomatic nights (90% vs. 77%, P=0.0011) and days (58% vs. 50%, N.S.) during the first 3 months. Balsalazide patients experienced more symptom-free nights per week (6.4+/-1.7 vs. 4.7+/-2.8; P=0.0006) and fewer nights per week with blood on their stools or on the toilet paper, mucus with their stools or with sleep disturbance resulting from symptoms or lavatory visits (each P < 0.05). Fewer balsalazide patients relapsed within 3 months (10% vs. 28%; P=0.0354). Remission at 12 months was 58%, in both groups. Similar proportions of patients reported adverse events (61% balsalazide vs. 65% mesalazine). There were five serious adverse events (two balsalazide, three mesalazine) and four withdrawals due to unacceptable adverse events (three balsalazide, one mesalazine), of which one in each group was also a serious adverse event., Conclusions: Balsalazide 3 g/day and mesalazine 1.2 g/ day effectively maintain UC remission and are equally well tolerated over 12 months. At this dose balsalazide prevents more relapses during the first 3 months of treatment and controls nocturnal symptoms more effectively.

Background & Aims: Aminosalicylates are widely used in the treatment of ulcerative colitis (UC). Balsalazide is a novel mesalamine prodrug, activated by colonic bacteria. The aim of this study was to compare the efficacy and safety of balsalazide with that of a pH-dependent formulation of mesalamine in active UC., Methods: A randomized, double-blind study was performed comparing balasalazide, 6.75 g daily, with mesalamine, 2.4 g daily, administered for 4, 8, or 12 weeks to 101 (99 evaluable) patients with symptomatic, sigmoidoscopically verified UC., Results: More patients treated with balsalazide achieved symptomatic remission after 2 (64% [balsalazide] vs. 43% [mesalamine]), 4 (70% vs. 51%), 8 (78% vs. 45%), and 12 weeks (88% vs. 57%) and complete remission (none/mild symptoms, sigmoidoscopy grade 0/1, no rectal steroid use within 4 days) after 4 (38% vs. 12%), 8 (54% vs. 22%), and 12 weeks (62% vs. 37%). Patients taking balsalazide experienced more asymptomatic days (4 weeks, 24% vs. 14%) and achieved the first asymptomatic day more rapidly (median, 10 vs. 25 days). Fewer patients in the balsalazide group reported adverse events (48% vs. 71%); four serious adverse events occurred in the mesalamine group., Conclusions: Balsalazide is more effective and better tolerated than mesalamine as treatment for acute UC.

The ideal imaging method in inflammatory bowel disease would reliably detect inflammation, identify the correct intestinal location, and assess the severity of the disease. The aim of this study was to compare scintigraphic methods of quantifying overall disease activity using both indium-111 (111In) and technetium-99M (99mTc) HMPAO labelled leucocyte scans. The four day faecal excretion of 111In was measured after 111In scintigraphy in 24 patients known to have inflammatory bowel disease. The same patients also underwent 99mTc HMPAO scanning. The scans were performed 10 days or less apart with no changes in treatment between scans. Bowel activity on the 99mTc HMPAO scans was assessed using a computer based method (scan score) and a visual grading method in a further 54 99mTc HMPAO. The results showed a close correlation between inflammatory activity defined by faecal 111In excretion and the scan score generated from the computer analysis of the 99mTc HMPAO image (Spearman rank correlation: rs = 0.78; p < 0.001). Accurate information to localise inflammatory activity could be obtained by simple visual assessment of both types of scan images, although image quality was superior with 99mTc HMPAO. Qualification of disease activity from 99mTc HMPAO images by visual grading was associated with a large variability, only 69% of scans had similar scores when graded by three observers. Computer generated image analysis was more reproducible. In conclusion, in inflammatory bowel disease 99mTc HMPAO scintigraphy and faecal 111In excretion correlated well. Either method can quantify and localise the inflammation. As 99mTc HMPAO scanning provides a quicker result, with a lower radiation dose, and avoids faecal collection, it may be the preferred method.

Elemental diets are effective in inducing remission in active Crohn's disease, but how they exert this therapeutic effect is unclear. In a previous study a whole protein containing diet proved less effective than one in which food antigens were excluded, suggesting that exclusion of food antigens from the gut was a possible mechanism. This study was designed to test whether an oligopeptide diet of hydrolysed proteins was as effective as an amino acid based diet. These diets were equally antigen free but with different nitrogen sources. Forty four patients with active Crohn's disease were randomised in a controlled trial of amino acid versus oligopeptide diet. The feeds were given by nasogastric tube in equicaloric quantities and were the sole form of nutrition. Treatment was continued for four weeks although failure to improve by day 10 resulted in withdrawal. Quantitative leucocyte scintigraphy was used to investigate the effect of diet treatment on gut inflammation. Clinical and nutritional responses to treatment were also measured. Sixteen patients entered remission (including withdrawal of corticosteroids), six patients could not tolerate the nasogastric tube, and 22 patients failed to respond. The two diets were equally effective. Patients who responded had a rapid drop in clinical index of disease activity and a major reduction in the bowel uptake of leucocytes on scintigraphy. The oligopeptide and amino acid based enteral feeds were equally effective at inducing remission in active Crohn's disease. With both diets clinical improvement was accompanied by a reduction in intestinal inflammation.

Background/aims: Ulcerative colitis and Crohn's disease have well-recognized familial tendencies, but the genetic basis of this clinical observation remains unknown. The cytokine interleukin-1 receptor antagonist is a potent anti-inflammatory protein that can prevent immune-mediated bowel inflammation in animals. We have previously characterized a polymorphism within the gene for this cytokine and others in the genes for the proinflammatory cytokines interleukin 1 alpha, interleukin 1 beta, and tumor necrosis factor alpha. The aim of this study was to determine whether inflammatory bowel disease was associated with particular alleles of these polymorphic cytokine genes., Methods: The allelic frequencies of these polymorphic cytokine genes were determined in patients with ulcerative colitis (n = 113), Crohn's disease (n = 78), and healthy controls (n = 261)., Results: Allele 2 of interleukin-1 receptor antagonist was significantly over-represented in the ulcerative colitis patients: 35% versus 24% in controls (P = 0.007). Carriage of at least one copy of this allele gave an odds ratio of 2.0 for ulcerative colitis compared with controls. This association with allele 2 of interleukin 1 receptor antagonist was greatest in patients with total colitis and was not seen in Crohn's disease. There were no associations between UC and any of the other cytokine genes examined., Conclusions: This observation provides evidence that interleukin-1 receptor antagonist may have a role in determining the genetic susceptibility to and pathogenesis of ulcerative colitis.

A computer-based technique for the quantification of abnormal bowel uptake in Crohn's disease has been developed and compared with pre-existing clinical, laboratory and scintigraphic methods of assessment. The standard technique for labelling leucocytes with 99mTc-HMPAO is applied. Images were obtained at 40, 120 and 240 min after the injection of radiolabelled leucocytes. The count in the bowel area after subtracting background activity corrected to the injected dose and image acquisition times is the 'scan score', an objective measure of disease activity. The scan score is significantly higher in patients with clinically active disease (mean 82.1 +/- SEM 13.6) than in those with quiescent disease (24.7 +/- 7.0) (p < or = 0.005). Optimum separation between active and quiescent disease is achieved with a threshold scan score of 20. The scan score was comparable in small bowel disease (73.3 +/- 16.2), large bowel (94.4 +/- 33) and disease at both locations (94.1 +/- 19.2). The scan score correlated favourably with Crohn's Disease Activity Index (rs = 52, p < or = 0.0001), Harvey & Bradshow Simple Index (rs = 0.4, p < or = 0.001), serum C-reactive protein (rs = 0.72, p < or = 0.001), serum alpha acid glycoprotein (rs 0.67, p < or = 0.001), haemoglobin (rs = 0.66, p < or = 0.001), platelet count (rs = 0.47, p < or = 0.006), albumin (rs = 0.61, p < or = 0.0001) and faecal 111Indium excretion (rs = 0.78, p < or = 0.001), but not with the ESR (rs = 0.22, p < or = 0.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Fluticasone propionate is a corticosteroid with the potential for topical treatment of ulcerative colitis because of low systemic bioavailability. The drug was compared with prednisolone in the management of active left sided or total ulcerative colitis. Two hundred and five patients were studied in the multicentre four week double blind study. Prednisolone was given in a dose of 40 mg daily orally, reducing over four weeks to 10 or 20 mg. Fluticasone propionate was given in an oral daily dose of 20 mg. The primary end point was the investigator's overall assessment of response. Patient's assessment, sigmoidoscopic appearance, and histology were also studied. Patients improved more rapidly with prednisolone. Differences between the two groups were significant at two weeks. At four weeks differences were not significant, but there was a trend in favour of prednisolone. Corticosteroid side effects were minimal in the fluticasone propionate group, and there was minimal suppression of the hypothalamic pituitary adrenal axis. Fluticasone propionate 20 mg daily is not as effective in the treatment of active ulcerative colitis as prednisolone tapering from 40 mg daily to 10 or 20 mg. The complete absence of suppression of the corticoadrenal axis by fluticasone propionate was encouraging, however, and a higher dosage schedule should be assessed.

The reliability and clinical applications of computerised image analysis measurement of bowel uptake of Tc-99m HMPAO labelled leucocytes has been examined as a measure of disease activity in Crohn's disease. In 54 studies carried out on 33 patients with established Crohn's disease, the mean 'scan score', a quantitative assessment of image intensity, was 82.1 SEM (13.6), in patients with clinically active disease compared to 24.7 (7.0) in those with quiescent disease, p < or = 0.0005. A significant correlation was found between the scan score and Crohn's Disease Activity Index (rs = 0.52, p < 0.0001), and Harvey and Bradshaw Simple Index (rs = 0.4, p < 0.004). A low scan score correctly identified seven patients whose raised Crohn's Disease Activity Index incorrectly indicated active disease because symptoms used in calculation of the index were not caused by active inflammation. Of the laboratory measurements, the scan score correlated with the haemoglobin (rs = 0.66, p < 0.0001), albumin level (rs = -0.6, p < 0.0001), C-reactive protein (rs = 0.7, p < 0.0001), alpha-acid glycoprotein (rs = 0.57, p < 0.001), and platelet count (rs = 0.47, p < or = 0.006), but not with the erythrocyte sedimentation rate (rs = 0.2, p < or = 0.25). The scan score was raised in all patients who had clinically active disease but normal laboratory tests. The results of this study indicate that the scan score provides an objective indicator of disease activity in Crohn's disease which may be superior to clinical indices, and also to laboratory tests which although objective are often normal in the presence of active disease.

The efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double-blind multicentre trial. Sixty-five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3-monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P less than 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well-tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.

Saccharomyces cerevisiae (baker's yeast) may play an important part in the pathogenesis of Crohn's disease. Because of this the levels of IgG and IgA antibodies against three S cerevisiae strains (NCYC 77, NCYC 79, and NCYC 1108) were assayed in 49 patients with Crohn's disease, 43 with ulcerative colitis, 14 with coeliac disease, and 21 healthy controls. Coded serum samples were tested by ELISA. Similar antibody patterns to all three strains were found. IgG and IgA antibody levels were significantly raised in patients with Crohn's disease compared with healthy controls (p < 0.001 and p < 0.0001 respectively) and with ulcerative colitis patients (p < 0.0001 and p < 0.0006 respectively). Raised IgA, but not IgG, yeast antibody levels were found in two patients with Crohn's disease who were intolerant to yeast, but these values were similar to those in other patients without yeast intolerance. In ulcerative colitis, both IgG and IgA levels were similar to normal controls. Patients with small bowel Crohn's disease had significantly higher IgG antibody levels than those with colonic disease (p < 0.01). High levels of IgG, but not IgA, antibody were present in patients with coeliac disease, the antibody responses being indistinguishable from those found in Crohn's disease. It is concluded that the presence of IgG antibody to S cerevisiae is characteristic but not specific to Crohn's disease. Although raised IgA antibody levels are more frequently found in Crohn's disease, their pathogenic importance remains to be established.

Escherichia coli strains cultured from 74 patients with inflammatory bowel disease at different stages of disease activity (Crohn's disease (40), ulcerative colitis (34)) and 18 healthy controls were studied in relation to haemolysin and verotoxin production and enteroadherence. Disease activity was assessed by standard clinical and laboratory tests. Haemolytic E coli were isolated from 18% of patients with Crohn's disease, 24% with ulcerative colitis, and 11% of healthy controls. None of these differences was significant. No verotoxin producing strains were detected among the 216 E coli isolates examined but the extract from five strains (Crohn's (4), ulcerative colitis (1) produced a distinctive cytopathic effort on Vero cell monolayers which was later shown not to be due to verotoxin. The adhesion indices of E coli isolates cultured were: mean (SEM) 42.2 (6.4) for Crohn's disease, 43.3 (6.2) for ulcerative colitis, and 11.3 (2.0) for normal controls (p less than or equal to 0.0001). Adhesive E coli were isolated from 62% of patients with Crohn's disease and 68% with ulcerative colitis but from only 6% of normal controls (p less than or equal to 0.0002). Neither haemolysin production nor enteroadherence was dependent upon disease activity, disease location, sulphasalazine treatment, or previous intestinal resection. These results indicate that only enteroadherent E coli were frequently associated with inflammatory bowel disease; their relation to the pathogenesis of these conditions, however, remains uncertain.

A new technique for the quantitative analysis of labelled leucocyte images from patients with inflammatory bowel disease is described. The method involves the computer generation of a 'background' image which, after appropriate registration, is subtracted from the patient's image to leave a residue which represents abnormal uptake in the bowel. Quantification of the residual activity yields a scan score which can be related to the level of disease activity in patients with Crohn's disease. In 54 investigations on 33 patients the scan scores correctly agreed with a clinical assessment of disease activity in 16 of 20 cases with inactive disease and 32 out of 34 cases with active disease. Most of the discrepancies reflected inaccuracies in the clinical assessment of activity rather than shortcomings of the imaging technique.

The clinical tolerance to three 5-aminosalicylic acid (5-ASA) releasing preparations (mesalazine, olsalazine and balsalazide) was assessed in a consecutive series of 43 patients with inflammatory bowel disease who were intolerant to sulphasalazine. The relative contributions to the side-effects of sulphasalazine made by its two components, 5-ASA and sulphapyridine, were also assessed in these patients. Thirty-nine (91%) patients were able to tolerate at least one of the three 5-ASA preparations. Only four (9%) patients were intolerant to all preparations, having adverse reactions previously experienced with sulphasalazine and presumably related to 5-ASA rather than sulphapyridine. The clinical tolerance to mesalazine (63%), olsalazine (70%) and balsalazide (70%) was similar, and tolerance to one drug only was found in nine (18%) patients. The commonest adverse reactions associated with 5-ASA preparations were gastrointestinal. Diarrhoea was a problem in five patients during treatment with olsalazine and three each while on mesalazine and balsalazide. Allergic reactions from 5-ASA preparations were uncommon; of ten patients with rash following sulphasalazine only one developed a rash with mesalazine. The results of this study indicate that the vast majority of patients with inflammatory bowel disease can be managed with at least one of these four 5-ASA containing preparations and that the side-effects of sulphasalazine are multifactorial in aetiology, some being due to the parent molecule, and some to one of its two metabolites, 5-ASA and sulphapyridine.

Sixteen patients with Crohn's disease who had symptoms uncontrolled by high-dose steroids (n = 11) or symptoms invariably appearing on reduction or withdrawal of immunosuppressive therapy (n = 5) were treated with elemental diet. After 4 wk of dietary treatment, 10 patients were in remission and off all medication. Seven continued to be well without treatment for a minimum of 6 months, and four for at least 1 yr. No patient who subsequently relapsed had further steroid-refractory symptoms. Of the six patients failing to respond to elemental diet, four with steroid-refractory disease required early resective surgery for symptom relief, and two continued with steroid therapy, one in much reduced dosage. Elemental diet can bring about a sustained remission in many patients with Crohn's disease dependent on or refractory to corticosteroids, and reduce the need for surgical intervention.

A semi-quantitative bacteriological method was used to study faecal flora in 42 patients with Crohn's disease, 37 with ulcerative colitis and 21 healthy controls. Faecal homogenates were plated on primary isolation plates by a technique that allowed the growth of various microbial isolates to be assessed on a visual 1(+)-5+ score. This method was first calibrated against a standard quantitative bacteriological technique, which confirmed the reliability and reproducibility of the results obtained by the simpler method. Patients with clinically active Crohn's disease (22) had significantly higher total aerobe scores than patients with quiescent disease (20) (p less than or equal to 0.006) or ulcerative colitis (p less than or equal to 0.04) or normal controls (p less than or equal to 0.02). The scores of Escherichia coli were parallel to those of total aerobes. Lactobacillus and bifidobacteria scores were significantly reduced in patients with Crohn's disease compared to those with ulcerative colitis and controls. The anaerobic flora in both Crohn's disease and ulcerative colitis was indistinguishable from that of controls. Bacteroides vulgatus and B. fragilis were the predominant bacteroides in all groups. Patients with ulcerative colitis, regardless of disease activity, harboured faecal flora that did not differ from that of normal controls. The abnormal faecal flora in Crohn's disease did not correlate with established clinical and laboratory indicators of disease activity.

Previous studies have confirmed the therapeutic value of elemental diets in promoting remission in active Crohn's disease, but their long-term benefit has not been established. Twenty-seven patients with established Crohn's disease who attained clinical remission after four weeks of enteral feeding were followed prospectively for up to 36 months. Twenty of these were willing to be tested for specific food intolerance using a pre-defined dietary elimination protocol; the others continued on a normal unrestricted diet. Eighteen patients (67%) have since relapsed; 89% of the relapse occurred within the first 6 months. Of the 15 patients with colonic involvement, 12 (80%) relapsed by 6 months. In contrast only 3 of 11 with isolated small bowel disease experienced early relapse. Of the 14 patients who completed the process of dietary testing, 5 could not identify any trigger foods; the remaining 9 were maintained on exclusion diets, 3 of whom relapsed early. Of the 11 taking a normal diet, 9 relapsed. Disease duration, previous intestinal resection or prior steroid therapy did not affect the relapse rate. Eight patients (31%) obtained a long-term remission, mean 23 months (range 12-36 months), without any medication. Long-lasting remissions can be obtained in about one-third of patients with Crohn's disease following treatment with a defined formula diet. Colonic involvement is associated with a high early relapse rate.

The presence or absence of nine autoantibodies were assessed in 44 patients with ulcerative colitis (17 with hyposplenism) and 22 patients with Crohn's disease (eight with hyposplenism). The purpose of the study was to determine whether hyposplenism in inflammatory bowel disease is associated with an increased tendency to autoimmunity, or whether autoimmunity is linked not to hyposplenism itself but to the underlying bowel disease. The results strongly suggest that the latter hypothesis is correct. There was a much higher frequency of autoantibodies in patients with ulcerative colitis than in those with Crohn's disease (P < or = 0.01), suggesting that autoimmune factors are more important in the pathogenesis of ulcerative colitis than in Crohn's disease.

30 patients with active Crohn's disease, mean Crohn's Disease Activity Index 301 (SE 32), who would otherwise have been treated with steroids, were randomised to receive for 4 weeks either an elemental diet ('Vivonex') (n = 16) or a polymeric diet ('Fortison') (n = 14). Assessment on days 10 and 28 showed that clinical remission occurred in 5 (36%) of the 14 patients on fortison compared with 12 (75%) of the 16 patients assigned to vivonex. The difference in remission rate was significant (p less than 0.03). Dietary treatment resulted in little change in the nutritional state and various laboratory indices of activity over a 4 week period despite clinical improvement. Polymeric diets do not seem to offer an effective therapeutic alternative to elemental diets in patients with acute exacerbations of Crohn's disease.

The effect of open treatment with coarse wheat bran was compared with response to placebo, given in the form of a double blind, cross over drug trial, in patients with irritable bowel syndrome. Both bran and placebo significantly reduced the severity of most of the symptoms. Constipation was the only symptom that improved significantly with bran, but not with placebo, and was the only symptom that predicted a successful outcome with bran. Diarrhoea did not improve with bran. In fact, stools became less formed in patients presenting with this symptom. The incidence of pain and urgency was significantly more frequent on bran compared with placebo. Compared with a baseline period, bran treatment resulted in an acceleration of whole gut transit time (p less than 0.05) increases in daily stool weight (p less than 0.01) and the proportion of unformed stools (p less than 0.01) but no change in stool frequency. Coarse wheat bran was no better than placebo for most symptoms in irritable bowel syndrome, although its efficacy in constipation was confirmed.

A case is reported in which granulomatous gingival hyperplasia was the presenting feature of generalised sarcoidosis. Treatment with oral prednisolone resulted in resolution of both the granulomatous lesion of the gums, and of proteinuria. It is pointed out that although on histological examination sarcoidosis in this site cannot be distinguished from Crohn's disease, the clinical appearance in this patient (and the only similar case in the literature) was quite different from that seen in oral Crohn's disease.

Patients with ulcerative colitis and coeliac disease who had been shown by impaired clearance of heat damaged red cells to have diminished splenic phagocytosis, were examined for evidence of more generalised reticuloendothelial malfunction by measuring their circulatory clearance of micro-aggregated albumin. Although in animals micro-aggregated albumin is largely removed by Kupffer cells, we found impaired clearance in otherwise normal subjects who had previously had surgical splenectomy. In patients with hyposplenism because of bowel disease there was no additional impairment of micro-aggregated albumin clearance, indicating that their hyposplenism is an isolated phenomenon and not part of a generalised reticuloendothelial atrophy. Patients with coeliac disease and normal splenic function had increased reticuloendothelial catabolic activity; this was not present in patients with coeliac disease and abnormal splenic function.

Culture for bacteria and assays for endotoxin were performed on specimens of mesenteric and peripheral venous blood from eight patients with ulcerative colitis who underwent surgery for severe uncontrolled disease. No significant bacteraemia occurred in either portal or systemic blood. Systemic endotoxaemia developed in three patients during surgery but occurred before bowel mobilisation only in the one patient whose colitis was complicated by hyposplenism. Mesenteric endotoxaemia occurred in only three patients before bowel mobilisation, but was detected during surgery in two of the three patients who developed systemic endotoxaemia. We conclude that, contrary to earlier reports, portal bacteraemia must be infrequent in ulcerative colitis. Systemic endotoxaemia does, however, occur in a significant proportion of cases during colectomy. Although in the patients studied this led to no clinical problems, it is likely to have been the precipitating factor for the syndrome of disseminated intravascular coagulation (DIC) that we have previously observed after colectomy in some of our patients with hyposplenism secondary to inflammatory bowel disease.

In order to determine whether failure of the colon to salvage carbohydrate could contribute to the diarrhoea of ulcerative colitis we investigated the effect of ingesting a drink containing 20 g lactulose on stool output and breath hydrogen production in 39 colitic patients subdivided according to their disease extent and activity and in 14 normal volunteers. Each subject took a standard diet for four days and stool output was monitored throughout this period. Administration of lactulose on day three significantly increased stool weight and frequency in patients with both active and quiescent total colitis (p less than 0.01), but not in patients with distal colitis or in the volunteers. The basal and peak breath hydrogen responses to ingested lactulose were similar to normal controls in all patient groups but the hydrogen concentration tended to be higher in colitics. The mouth to caecum transit of the lactulose meal was slower in all groups of colitics (p less than 0.02) when compared with controls. These results suggest that impaired colonic salvage of carbohydrate could contribute to the diarrhoea in patients with total colitis who are ingesting a diet rich in unabsorbed carbohydrate, or who are hypolactasic.

Using an electrical technique we estimated the thickness of the unstirred layer in the human jejunum during kinetic studies of electrogenic glucose absorption. The unstirred layer in seven healthy volunteers (632 +/- 24 mum: mean +/- SEM) was significantly thicker than in 10 patients with active coeliac disease (442 +/- 23 mum) but not significantly different in seven patients who had responded to treatment by gluten withdrawal (585 +/- 49 mum). There were similar differences in the values of ;Apparent Km' for electrogenic glucose absorption between healthy control subjects (36 +/- 6 mM) active coeliac patients (11 +/- 1 mM) and treated coeliac patients (31 +/- 5 mM). The changes in PDmax however, showed a different pattern. The PDmax in the active coeliac group (6.8 +/- 0.7 mV) was lower than in controls (7.6 +/- 0.6 mV) but not significantly so, while the PDmax in the treated coeliac group (10.6 +/- 0.9 mV) was significantly higher than in both the active coeliac and control groups. It should be noted that both operational kinetic parameters obtained in the present study are much lower than those obtained previously (Read et al., 1976b) because of the use of siphonage. Analysis of the results using a computer simulation indicates that the reduction in Apparent Km in active coeliac disease can be caused by the interaction of the decreased maximal absorption rate for glucose (Jmax) with the attenuated unstirred layer. In these circumstances it is not necessary to postulate any change in the affinity of the transport mechanism for glucose (;Real Km'). It is remarkable that the disease process produces an Apparent Km which is much closer to the Real Km than that found in health.

1. A large-volume scintillation counter was used to measure calcium absorption from the ratio of forearm uptake of 47Ca after oral 47CaCl2 (administered with milk) to forearm uptake after intravenously administered 47CaCl2. 2. In some subjects serial measurements of both forearm uptake of 47Ca and blood 47Ca radioactivity were also recorded, and by using deconvolution both total calcium absorption and calcium absorption rate were determined. 3. The forearm ratio determination of 47Ca absorption correlated well with that obtained by deconvolution of either serial blood 47Ca or forearm 47Ca measurements provided that the forearm radioactivity measurements were made at least 8 h after the administration of 47CaCL2. 4. Although the two deconvolution techniques gave similar estimates of total calcium absorption there were discrepancies between their measurements of calcium absorption rate. These discrepancies were reduced but not eliminated by the use of additional lead shielding around the Armac counter.

Thirty-four patients with ulcerative colitis completed a double-blind assessment comparing the efficacy of two weeks of treatment with nightly retention enemas containing 3 g sulphasalazine or placebo. Symptom grading, sigmoidoscopic appearance, rectal biopsy specimens, and diary records were used to assess benefit and side effects. The active drug conferred significant benefit compared with placebo as shown by several criteria, but this benefit was confined to patients not already taking sulphasalazine by mouth. Overall assessment showed improvement in 11 of the 16 patients (70%) given the active treatment but in only two of the 18 (11%) given placebo. No side effects attributable to the drug were observed, even in patients previously intolerant to oral preparations. The logical therapeutic role of sulphasalazine enemas in ulcerative colitis would appear to be in patients who experience side effects such as nausea, abdominal discomfort, or headaches when taking the drug by mouth.

Anorectal function in ulcerative colitis was assessed by measuring pressures at multiple sites in the anus and rectum under basal conditions and during balloon distention of the rectum in 29 patients with ulcerative colitis (12 active, 11 quiescent, and 6 during both phases) and in 12 normal controls. Resting and squeeze sphincter pressures were similar in the three groups. The lowest rectal volume that could be perceived, the volume required to induce a desire to defecate, and the maximum tolerable rectal volume were all lower in patients with active colitis than in patients with quiescent colitis (p less than 0.001) and controls (p less than 0.001). The rectal volume required to cause a sustained anal relaxation was lower in patients with active colitis (p less than 0.05) than in controls. Both peak and steady state rectal pressures in response to rectal distention were significantly higher in patients with active colitis than in patients with quiescent colitis (p less than 0.05) and controls (p less than 0.02). Paired studies showed that during remission of disease there was a decrease in rectal sensitivity (p less than 0.05) and an increase in rectal compliance (p less than 0.05). These results suggest that the frequent and urgent defecation, i.e., the predominant feature of active colitis, is related to a hypersensitive and poorly compliant rectum, which, upon distention, is more reactive and is more likely to induce prolonged sphincter relaxation.

As no adequate comparison of these widely used drugs has been made, we have performed a double-blind cross-over trial in 30 individuals with chronic diarrhea. Each underwent three randomized treatment periods of 4 wk duration. Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable. Stool frequency, consistency, urgency, and incontinence were then compared when a stable dose was reached. Though 2.3 capsules (4.6 mg) of loperamide, 2.3 capsules (103.5 mg) of codeine and 2.5 capsulses (12.5 mg) of diphenoxylate all reduced stool frequency to the same extent, diphenoxylate was significantly less effective in producing a solid stool. Before treatment 95% of patients experienced urgency, sometimes associated with fecal incontinence, often as their major diability. Loperamide and codeine were more effective in relieving this than was diphenoxylate. Side effects, particularly central nervous effects, were greatest with diphenoxylate and least with loperamide. Approximately equal numbers discontinued each preparation; poor control and central-nervous-system side effects were the usual reasons for stopping diphenoxylate and codeine, and abdominal pain and constipation for stopping loperamide. We conclude that both loperamide and codeine phosphate are superior to diphenoxylate in the symptomatic treatment of chronic diarrhea.

The prevalence of symptoms and stool patterns was assessed prospectively in 96 patients with ulcerative colitis subdivided according to the extent and activity of the disease. Increased frequency of defecation (83%), urgency (85%), a feeling of incomplete evacuation (78%) and tenesmus (63%) were the most frequent symptoms experienced by patients with active colitis. All were significantly more common (p less than 0.001) in patients with active than quiescent colitis and their prevalence was similar in those with total and distal colitis, indicating that these symptoms are related to an inflamed and irritable distal colon. Twenty seven per cent of patients with active colitis voided hard stools indicative of constipation, however, and this was more common in active, than quiescent colitis (p less than 0.05). This feature is probably secondary to faecal stasis in the proximal colon, and an apt description of the bowel disturbance in ulcerative colitis, irrespective of the extent of disease is that the colon suffers from proximal constipation and distal irritability.

We have reported previously the association between hyposplenism and inflammatory bowel disease. Our study has now been extended to a total of 65 patients with ulcerative colitis and 42 with Crohn's disease so that the incidence of hyposplenism could be more accurately determined. Hyposplenism rarely complicated distal ulcerative colitis, but was found in 15 of 37 patients with total colonic disease. Hyposplenism occurred in 11 out of 31 patients with Crohn's disease of the colon, but in none of 11 individuals with isolated ileal disease. In order to determine whether hyposplenism has any prognostic implications, the peri-operative course of 12 hyposplenic individuals who underwent colectomy was compared with that of 12 controls who required surgery and who had normal splenic function. Four of the hyposplenic subjects became severely shocked after operation and developed disseminated intravascular coagulation. In contrast, the post-operative course in the control patients was uneventful.

The effect of oral lidamidine hydrochloride and subcutaneous long acting somatostatin analogue, SMS 201-995, on stool output and salt and water transport in the small intestine was investigated in a patient with gross secretory diarrhoea caused by a vasoactive intestinal polypeptide (VIP) secreting tumour in the liver. Transport in the jejunum and ileum were assessed by steady state perfusion techniques. Under basal conditions, the patient was absorbing fluid and electrolytes from the jejunum and ileum, but at rates that were abnormally low. Lidamidine had no effect on either intestinal transport or stool frequency and output. SMS 201-995 increased intestinal absorption in the jejunum and ileum, reduced plasma VIP concentrations, daily stool frequency and weight, and enabled the patient to resume a normal diet without oral or intravenous fluid and electrolyte supplements. After two months of treatment, medical control was becoming increasingly difficult and stool output had risen again to 2 litres per day. Surgical resection, fortunately, was possible and led to resolution of symptoms and normal plasma VIP concentrations.

Using an electrical technique for measuring transjejunal potential differences (PDs) in conscious man, we have estimated the electrogenic absorption of the hexoses liberated by hydrolysis of lactose which was infused into the jejunum of one normal control and 21 patients with diarrhoea. The results were compared with jejunal lactase levels determined from biopsy specimens taken from the recording site immediately after infusion. The PD evoked by 100 mM lactose was very significantly lower in patients with lactase levels below 4 units (lactase deficient) compared with subjects with normal lactase levels. There was also a significant correlation (r = 0.87, P less than 0.005) between the magnitude of the lactose potential (expressed as the ratio of the maximum glucose transfer potential) and the mucosal lactase level in the hypolactasic subjects but not in patients with normal lactase levels. Thus, in the subjects with lactase deficiency, the electrogenic transfer of hexose is clearly limited by the rate of lactose hydrolysis. Unlike other assessments of functional lactase activity, the electrical test provides a specific index of jejunal function and, moreover, can be adapted to investigate the possible disorders of small intestinal motility and secretion associated with hypolactasia.

Olsalazine (2 g/day) and sulphasalazine (3 g/day) were compared in a double blind three centre trial in 37 patients presenting with first attack of distal colitis. Sigmoidoscopic appearances, rectal biopsies, and symptom and stool diary records were used to assess benefit and adverse effects. Both groups showed a similar decrease in stool frequency (p less than 0.001). The proportion of unformed stools was also decreased, but to a lesser extent (p less than 0.05) in those taking olsalazine (78% v 55%; p less than 0.001) compared with those taking sulphasalazine (72% v 28%; p less than 0.001). There was a diminution in the proportion of stools containing blood in both groups (olsalazine: 61% v 22%; p less than 0.001/sulphasalazine: 67% v 37%; p less than 0.001). Sigmoidoscopic and histological appearances and clinical activity improved significantly and to a similar extent in both groups. Intolerance was encountered in two patients on olsalazine and four on sulphasalazine; intolerance to sulphasalazine being even higher (five of seven patients) in a preliminary study using a dose of sulphasalazine releasing the same amount of 5-aminosalicylic acid as 2 g olsalazine. Olsalazine was at least as effective as sulphasalazine in the treatment of new patients with distal colitis, and in a dose releasing an equivalent amount of 5-aminosalicylic acid was better tolerated.

The effect of olsalazine on stool output and the transit of a solid radiolabelled meal through the stomach, small intestine and colon was studied in six patients with ulcerative colitis intolerant of sulphasalazine. Olsalazine 250 mg four times daily significantly accelerated gastric emptying (mean +/- SD; 45.3 +/- 24.2 min v 67.3 +/- 33.1 min, p less than 0.05), mouth to caecum transit time (242 +/- 41 min v 325 +/- 33 min, p less than 0.02) and whole gut transit time (60.5 +/- 26 h v 37.8 +/- 17.8 h, p less than 0.05). No significant changes were seen in mean daily stool weight (215 +/- 41 g v 162 +/- 62 g) and mean daily stool frequency (2.2 +/- 0.6 v 2.4 +/- 1.8). None of these patients developed diarrhoea, but acceleration of gastric and intestinal transit may be responsible for the diarrhoea reported in some patients taking this drug.