C. D. Holdsworth

Irritable bowel syndrome: relationship of disorders in the transit of a single solid meal to symptom patterns.

The time taken for a solid meal to pass through the stomach, small intestine, and colon was measured in 61 patients with irritable bowel syndrome, subdivided according to their presenting symptoms, and in 53 healthy volunteers. Small bowel transit times were significantly shorter in patients who complained predominantly of diarrhoea (3.3 +/- 0.3 vs 4.2 +/- 0.2 h; p = 0.01; n = 21) and significantly longer in patients who complained predominantly of constipation (5.4 +/- 0.3 vs 4.2 +/- 0.2 h; p less than 0.01; n = 23) or pain and distension (5.4 +/- 0.4 vs 4.2 +/- 0.2 h; p less than 0.01; n = 17) compared with controls. Whole gut transit times were shorter in patients who complained of diarrhoea (35 +/- 5 vs 53 +/- 4 h; p less than 0.01), and longer in patients with constipation (87 +/- 13 vs 53 +/- 4 h; p less than 0.05) compared with controls. No significant differences in gastric emptying rates were shown between any of the patient groups and normal controls. Thirty-four patients reported pain, particularly in the right iliac fossa, during the meal transit test, and in 25 of these (74%), the onset of the pain was associated with the arrival of residues of the test meal in the caecum. Our results indicate that irritable bowel syndrome should be considered a disease of the small intestine as well as the colon.

Role of loperamide and placebo in management of irritable bowel syndrome (IBS)

Symptom scores, stool data, and the transit of a standard, solid meal were measured in 28 patients with irritable bowel syndrome (IBS) during baseline conditions and after five weeks of treatment with placebo and loperamide, given as a flexible dosage regime in the form of a double-blind, cross-over trial. All patients had undergone a comprehensive series of diagnostic investigations and had failed to respond to dietary supplementation with coarse wheat bran (10–30 g daily). Loperamide treatment accelerated gastric emptying, compared with placebo (1.2±0.1 vs 1.5±0.1 hr; P<0.001) and delayed both small bowel (6.2±0.3 vs 4.3±0.3 hr P<0.001) and whole gut transit (56±5 vs 42±4 hr; P<0.01). Eighteen patients said they felt better taking loperamide compared with placebo and, at follow up, 15 of these patients remained satisfied with the effects of the drug. Most symptoms improved significantly on placebo compared with the baseline period, but three of these [diarrhea (P<0.01), urgency (P<0.01) and borborygmi (P<0.05)] showed a further significant improvement on loperamide. Improvement in diarrhea was not associated with any change in stool weight but was associated with reductions in stool frequency (P<0.001), passage of unformed stools (P<0.01), and incidence of urgency (P<0.001). Urgency was the only symptom that was significantly more common in the success group, compared with the group who did not feel better on loperamide.

Studies on the mechanism of bowel disturbance in ulcerative colitis

The transit of a radiolabeled meal through the gastrointestinal tract and stool output were measured in 62 patients with ulcerative colitis, subdivided according to the activity and extent of their disease. The results were compared with those from 20 sex-matched normal subjects. Mouth-to-cecum transit was significantly slower than normal in all patient groups although gastric emptying was normal. Whole gut transit was not accelerated in any group of patients. An abdominal x-ray taken 48 h after ingesting the meal showed that patients with active colitis had proximal colonic stasis, whereas transit through the rectosigmoid region was rapid. Stool weights and frequencies were higher in patients with active colitis than in patients with quiescent disease. Patients with active colitis also passed smaller amounts of stool during each bowel movement, suggesting that they experienced a desire to defecate at lower rectal volumes. These results indicate that (a) diarrhea in ulcerative colitis is associated with rectosigmoid irritability rather than rapid transit and (b) caution should be used when treating active colitis with antidiarrheal drugs that could further retard proximal colonic transit.

What is the benefit of coarse wheat bran in patients with irritable bowel syndrome

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.

Anorectal sensitivity and responses to rectal distention in patients with ulcerative colitis

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.

Symptoms and stool patterns in patients with ulcerative colitis.

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.

Clinical Experience of the Tolerance of Mesalazine and Olsalazine in Patients Intolerant of Sulphasalazine

We assessed the tolerance and safety of two new preparations designed to release 5-aminosalicylic acid in the colon in patients with ulcerative colitis who were intolerant of sulphasalazine. Twenty-eight of 37 patients (76%) given mesalazine and 18 of 21 patients (86%) given olsalazine tolerated the new preparations with no adverse effects. No haematologic or biochemical abnormalities were detected. Adverse reactions to the new preparations were usually but not always similar to those they had previously encountered with sulphasalazine, but a few patients experienced rash and diarrhoea. In some patients intolerant of one of the new preparations, their tolerance of the other was assessed. Three patients intolerant of mesalazine tolerated olsalazine. Similarly, three other patients intolerant of olsalazine tolerated mesalazine. We conclude that not all adverse effects of sulphasalazine are due to the sulphapyridine part of the molecule. Some are due to the released 5-aminosalicylic acid and some to the parent compound. Both drugs are likely to prove useful in the management of patients intolerant of sulphasalazine.

Anorectal contractility under basal conditions and during rectal infusion of saline in ulcerative colitis.

Pressure activity in the rectum and anal canal was measured with a multilumen probe in 29 patients with ulcerative colitis (12 active, 11 quiescent, six studied during both phases) and 18 normal controls under resting conditions and during rectal infusion of saline. Resting motor activity was significantly decreased in patients with active colitis compared with quiescent colitis (p less than 0.005) and normal controls (p less than 0.001). Forty per cent of active colitics showed a featureless record compared with only one patient with quiescent colitis and one normal subject. The volume of saline infused before leakage occurred, and the total volume retained were significantly lower (p less than 0.001) in patients with active and quiescent colitis compared with normal controls. Rectal infusion of saline provoked regular rectal contractions, of significantly higher (p less than 0.05) amplitude in patients with active colitis, than in quiescent colitis or controls. These rectal contractions were associated with simultaneous anal relaxations. During saline infusion, peak and pressures were lower in patients with ulcerative colitis than in normal subjects, but there were no significant differences in relaxation pressures. In normal subjects, the rectal pressures remained below the anal pressures throughout the saline infusion. Peak rectal pressures exceeded the anal relaxation pressures during the last five minutes of saline infusion in patients with ulcerative colitis and throughout the infusion in those patients who complained of incontinence. Results suggest that although the resting rectal motor activity is diminished in patients with ulcerative colitis, luminal distension causes the inflamed rectum to generate abnormally strong contractions that may threaten continence.

Olsalazine or sulphasalazine in first attacks of ulcerative colitis? A double blind study.

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.

Oral domperidone: double blind comparison with placebo in irritable bowel syndrome.

Symptom scores, stool data, and the transit of a standard, solid meal were measured in 25 patients with irritable bowel syndrome during baseline conditions and after four weeks treatment with placebo and domperidone in the form of a double-blind cross-over trial. All patients had previously undergone a comprehensive series of diagnostic investigations and had failed to respond to dietary supplementation with coarse wheat bran (10-30 g daily). Compared with placebo treatment, domperidone had no significant effect on gastric emptying, small bowel or whole gut transit times, stool weight, frequency, or consistency. Most symptoms improved significantly with both placebo and domperidone treatments, compared with the baseline period, but there was no significant difference between placebo and domperidone for any of the symptoms. Abdominal distension, however, was reported on more days per week during domperidone treatment (p = 0.02). The findings in this study do not support the use of domperidone in the management of irritable bowel syndrome.