N. W. Read

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.

Effects of loperamide on anal sphincter function in patients complaining of chronic diarrhea with fecal incontinence and urgency

We have investigated the effect of loperamide (4 mg tds) on the continence to a standard volume of rectally infused saline and anorectal manometry in 26 patients complaing of chronic diarrhea complicated by fecal incontinence and severe urgency. Each patient was treated for one week with loperamide (4 mg tds) and for one week with an identical placebo in a double-blind cross-over trial. Our results showed that as well as its established effects of improving stool consistency and reducing stool weight, frequency and episodes of incontinence and severe urgency, loperamide also significantly improved continence to a standard volume of rectally infused saline. This action was associated with an increase in the maximum basal sphincter pressure, an increase in the rectal volume required to abolish recovery of the rectoanal inhibitory reflex, and a reduction in rectal compliance. These results suggest that loperamide may have a specific action on the anal sphincter, which may aid continence in patients who complain of diarrhea and fecal incontinence.

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.

Effect of ileal and intravenous infusions of fat emulsions on feeding and satiety in human volunteers

The effect of ileal infusion of a lipid emulsion, containing 50% corn oil and 3% albumen, on food intake and satiety was measured in paired experiments carried out in 6 healthy volunteers. Subjects ate for shorter periods of time during ileal infusions of fat emulsion compared with control infusions of albumen and saline (25 +/- 1 vs. 32 +/- 3 min, mean +/- SEM) and consumed a smaller amount of food (670 +/- 23 g vs. 884 +/- 89 g) and energy (1016 +/- 79 kcal vs. 1591 +/- 228 kcal). The quantity of liquid drunk and the rates of eating and drinking were not significantly affected by the infusion of fat emulsion. In a further series of experiments carried out in 5 normal volunteers, ileal infusion of corn oil emulsions delayed gastric emptying compared with ileal infusion of albumen and saline (t1/2 = 203 +/- 48 vs. 68 +/- 12 min, p less than 0.02). The possibility that the observed reductions in food intake were related to the effect of absorbed fat was investigated in 6 healthy volunteers during intravenous infusion of either fat emulsion or isosmotic saline. Food intake was not affected by intravenous infusion of lipid. Our results suggest that lipid may interact with ileal receptors to induce early satiety and reduce the amount of food consumed. The earlier inhibition of food intake during lipid infusion is perhaps best explained by early gastric distention caused by delayed gastric emptying, though the data would not exclude the release of an ileal mechanism, which has a direct action on the satiety centers.

Relationship of the motor activity of the antrum, pylorus, and duodenum to gastric emptying of a solid-liquid mixed meal

The postprandial motor activity of the antrum, pylorus, and duodenum in 15 healthy volunteers was compared with the profiles of emptying of the solid and liquid components of a meal. The liquid component of the meal emptied rapidly in an exponential manner, whereas the solid remained in the fundus of the stomach until approximately 80% of the liquid had emptied and then emptied in a linear manner. The onset of solid emptying was associated with an increase in the rate of occurrence of antral pressure waves (p less than 0.05), and the half-time for solid emptying (t1/2 - lag period) was inversely correlated (p less than 0.05) with the rate of coordinated contractions involving the antrum. The substitution of 25% dextrose in normal saline as the liquid component of the meal increased the half-time for liquid emptying from a median of 8 to 40 min (p less than 0.01), increased the lag period for solid emptying from 40 to 87 min (p less than 0.01), and increased the rate of occurrence of isolated pyloric pressure waves during the solid lag phase from 7 to 58/h (p less than 0.05), but did not affect the slope of solid emptying or the rate of coordinated contractions involving the antrum during the solid emptying period.

Reduction of rectal sensitivity and post-prandial motility by granisetron, a 5-HT3-receptor antagonist, in patients with irritable bowel syndrome

The effect of granisetron, a specific 5‐hydroxytryptamine 3‐receptor antagonist, on the anorectal responses to rectal distension and a 1000‐calorie meal was assessed in 12 patients with irritable bowel syndrome. Each patient was studied on three occasions, receiving intravenously either 40 mcg/kg granisetron, 160 mcg/kg granisetron or normal saline. Granisetron caused a dose‐dependent reduction in rectal sensitivity, manifested by an increase in the threshold volumes at which the sensations of gas, desire to defecate, urgency and discomfort were perceived. This reached significance for all sensations at the higher dose level (P < 0.01). No significant changes in anal pressures, rectal compliance or distension‐induced motor activity occurred following drug administration. A dose‐dependent reduction in post‐prandial motility was observed following intravenous granisetron and this was highly significant at 160 mcg/kg (P= 0.005). These results suggest that the 5 hydroxytryptamine receptor antagonists may have a therapeutic role in patients with irritable bowel syndrome.

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.

Gastrointestinal adaptation to diets of differing fat composition in human volunteers.

The effect of a low fat diet (9 MJ) v a high fat diet (19.26 MJ), each consumed separately for four and 14 days, on gastric emptying and mouth to caecum transit time of a high fat test meal and body weight and satiety were examined in groups of 10 and six normal male volunteers. The half time for gastric emptying (t1/2) and the mouth to caecum transit time of a high fat test meal was significantly faster after the high fat diet than the low fat diet when consumed for 14 days (t1/2=98 (80-116) v 147 (88-206) minutes (median (range)), p less than 0.05; mouth to caecum transit time 240 (130-350) v 360 (200-520) minutes, p less than 0.05), but not when consumed for only four days. The mean (SEM) body weight of all subjects significantly increased during the 14 day high fat diet (74.7 (1.3) v 72.7 (1.6) kg, p less than 0.05) but was not influenced during the consumption of the low fat diet. When subjects were given an appetising meal to consume on the day that they had consumed the transit test meal, they ate similar amounts irrespective of their recent dietary history, though the eating rate was significantly slower after the high fat diet (mean (SEM)) 46.7 (1.9) v 71.3 (14.8)/min, p less than 0.05). Maintaining normal subjects on a high or low fat diet for two weeks resulted in a desensitisation or sensitisation respectively of the mechanisms by which nutrients regulate gastrointestinal transit. These findings emphasise the importance of the recent dietary history in the interpretation of gastric emptying and small bowel transit time data.

Effect of aging on anorectal function.

Measurements of anorectal function were conducted on 37 elderly (66-87 years) and 48 young (19-55 years) normal subjects. Elderly subjects had decreased anal pressures compared with younger subjects, required lower rectal volumes to inhibit anal sphincter tone and had increased rectal pressures upon balloon distension. The rectal volume required to cause the desire to defecate and the maximum tolerated volume were lower in the elderly, but the corresponding rectal pressures were similar, indicating the sensations were mediated by tension, or pressure receptors. Rectal contractions were generated at similar degrees of rectal distension. A lower proportion of elderly, compared with young subjects could defecate a sphere 18 mm in diameter within 20 seconds. The degree of perineal descent was greater in the elderly female subjects compared with the young women, although there was no difference in this measurement between men. The anorectal angle was similar in young and old. The changes in anorectal function in the elderly would tend to make them more susceptible to faecal incontinence.

Differences in Anal Sphincter Function and Clinical Presentation in Patients With Pelvic Floor Descent

Perineal descent is found in patients with idiopathic fecal incontinence and patients with the descending perineum syndrome, who have little or no incontinence but present with a symptom pattern that suggests obstructed defecation. To investigate why patients with perineal descent present in different ways, manometric, radiologic, and neurophysiologic studies were performed in 53 patients with radiologically proven perineal descent and 34 control subjects. Thirty-two patients exhibited incontinence to rectally infused saline, while 21 patients presented with obstructed defecation but exhibited no incontinence. Both patient groups exhibited similar degrees of perineal descent on straining and increases in the motor unit potential duration of the external anal sphincter, indicative of neuropathic damage. Both groups had an abnormal rectoanal inhibitory reflex and an abnormal anorectal angle, though the latter was more obtuse in idiopathic fecal incontinence. However, although patients with incontinence had lower maximum basal and maximum squeeze sphincter pressures than normal, these values were normal in patients with obstructed defecation. Our findings suggest that perineal descent and neuropathy are not necessarily associated with incontinence as long as sphincter pressures remain normal.