Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging.

BACKGROUND: In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS: Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS: 7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES: MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.

The effects of loperamide, or loperamide plus simethicone, on the distribution of gut water as assessed by MRI in a mannitol model of secretory diarrhoea.

BACKGROUND: Loperamide (LOP) is an anti-diarrhoeal agent which is thought to act largely by slowing transit with an uncertain effect on the fluid content of the small and large bowel in humans. Adding simethicone (SIM) to LOP improves its efficacy, but the mechanism of interaction is unclear. Novel MRI techniques to assess small bowel water content (SBWC) have shown that mannitol solutions markedly increase SBWC and can be used as a model of diarrhoea. AIM: We aimed to use quantitative MRI techniques to compare the actions in the gut of LOP and LOP + SIM in a model of secretory diarrhoea using mannitol. METHODS: A total of 18 healthy volunteers ingested capsules containing placebo (PLA) or 12 mg LOP or 12 mg LOP + 125 mg SIM. After 100 min they were given a drink containing 5% mannitol in 350 mL of water. They underwent baseline fasting and postprandial serial MRI scans at 45 min intervals for 4.5 h after ingesting the drink. A range of MRI sequences was acquired to image the gut. RESULTS: LOP and LOP + SIM significantly accelerated gastric emptying (P < 0.03) and reduced SBWC during the late phase (135-270 min after mannitol ingestion), P < 0.009, while delaying arrival of fluid in the ascending colon (AC). The relaxation time T2 of the contents of the AC was reduced by both drugs (P < 0.0001). CONCLUSIONS: LOP and LOP + SIM accelerate gastric emptying, but reduce small bowel water content which may contribute to the delay in oral-caecal transit and overall anti-diarrhoeal effect.

Effects of a 5-HT(3) antagonist, ondansetron, on fasting and postprandial small bowel water content assessed by magnetic resonance imaging.

BACKGROUND: 5-HT(3) antagonists have been shown to be effective in relieving the symptoms of irritable bowel syndrome with diarrhoea (IBS-D). Using a recently validated magnetic resonance imaging (MRI) method, we have demonstrated reduced fasting small bowel water content (SBWC) in IBS-D associated with accelerated small bowel transit. We hypothesized that slowing of transit with ondansetron would lead to an increase in SBWC by inhibiting fasting motility. AIM: To assess the effects of ondansetron compared with placebo in healthy volunteers on SBWC and motility in two different groups of subjects, one studied using MRI and another using manometry. METHODS: Healthy volunteers were given either a placebo or ondansetron on the day prior to and on the study day. Sixteen volunteers underwent baseline fasting and postprandial MRI scans for 270 min. In a second study, a separate group of n = 18 volunteers were intubated and overnight migrating motor complex (MMC) recorded. Baseline MRI scans were carried out after the tube was removed. RESULTS: Fasting SBWC was markedly increased by ondansetron (P < 0.0007). Ondansetron reduced the overall antroduodenal Motility Index (P < 0.04). The subjects who were intubated had significantly lower fasting SBWC (P < 0.0002) compared with the group of subjects who were not intubated. CONCLUSIONS: The 5-HT(3) receptor antagonism increased fasting small bowel water. This was associated with reduced fasting antroduodenal Motility Index which may explain the clinical benefit of such drugs.

Psychological and colonic factors in painful diverticulosis.

BACKGROUND: The importance of psychological factors in symptom expression in diverticulosis is unknown. This follow-up study assessed the relative importance of colonic and psychological factors in symptom expression. METHODS: Patients with barium enema-proven diverticula were sent a bowel symptom questionnaire in 1999 and again in 2006 with additional psychological questionnaires included. RESULTS: Some 170 of 261 initial responders were eligible for follow-up and 124 (72.9 per cent) provided complete replies. Forty-two (33.9 per cent) of 124 respondents experienced recurrent abdominal pain a median of 3.5 (interquartile range (i.q.r.) 2.00-9.25) days per month, with a median duration of 1 (i.q.r. 0.7-2) h. Multivariable analysis identified a history of acute diverticulitis (odds ratio 3.98; P = 0.010) and a raised score on the Hospital Anxiety and Depression Scale (odds ratio 2.53; P = 0.030) as the best predictors of recurrent pain. CONCLUSION: Psychological and colonic factors are important in symptom expression in diverticulosis.

Nutritional issues in irritable bowel syndrome.

Food products have variously been reported as causing, perpetuating or treating irritable bowel syndrome. The evidence for this is reviewed with regard to recent studies investigating symptom reporting, mono- and disaccharide malabsorption and probiotics. The development of objective measures remains an urgent priority because of the high placebo response to any dietary intervention in irritable bowel syndrome.

Moderation of lactulose-induced diarrhea by psyllium: effects on motility and fermentation.

Psyllium has been reported to inhibit lactulose-induced colonic mass movements and to benefit patients with irritable bowel syndrome, improving both constipation and diarrhea. Our aim was to define how psyllium modified the whole-gut transit of a radiolabeled lactulose-containing test meal by using gamma scintigraphy. Eight subjects participated in a randomized crossover study comparing gastric emptying and small bowel and colonic transit after consumption of 20 mL lactulose three times daily with or without 3.5 g psyllium three times daily. Psyllium significantly delayed gastric emptying: the time to 50% emptying increased from a control value of 69 +/- 9 to 87 +/- 11 min (mean +/- SEM; P < 0.05, n = 8). Small bowel transit was unaltered. However, progression through the colon was delayed with an increase in the percentage of the dose at 24 h in the ascending (control group: 2 +/- 3%, psyllium group: 11 +/- 8%; P < 0.02) and transverse colon (control group: 5 +/- 12%, psyllium group: 21 +/- 14%) with correspondingly less in the descending colon. Although the time for 50% of the isotope to reach the colon was not significantly different with psyllium, psyllium significantly delayed the rise in breath-hydrogen concentrations, which reached 50% of their peak at 217 +/- 34 min compared with control values of 155 +/- 27 min (P < 0.05). Psyllium delays gastric emptying, probably by increasing meal viscosity, and reduces the acceleration of colon transit, possibly by delaying the production of gaseous fermentation products.

Effect of bran, ispaghula, and inert plastic particles on gastric emptying and small bowel transit in humans: the role of physical factors.

BACKGROUND: Coarse bran is known to accelerate transit through the whole gut and to increase stool weight. This effect is much reduced by grinding the bran, suggesting that particle size influences gut motor patterns. AIMS: To compare the effect of 15 g coarse bran with 15 g inert plastic particles and 7 g of ispaghula on the gastric emptying and small bowel transit of a rice pudding test meal. SUBJECTS: 13 healthy volunteers. METHODS: Transit of 99mTc labelled rice studied by gamma-scintigraphy measuring gastric emptying and colonic arrival over 10 hours. Small bowel transit was estimated from the difference between time to 50% gastric emptying and 50% colonic arrival. RESULTS: Bran delayed gastric emptying by 22 (SEM 8) minutes compared with control values of 88 (SEM 6) minutes p < 0.05. Ispaghula and plastic particles had no significant effect. Small bowel transit was accelerated compared with control values of 322 (SEM 29) minutes, decreasing by 95 (29) minutes and 62 (22) minutes after bran and plastic particles respectively. Ispaghula again showed no significant effect. CONCLUSION: Coarse bran delays gastric emptying and accelerates small bowel transit. The marked acceleration of small bowel transit also seen with inert plastic particles may be due to increased upper gut secretions after stimulation of enteric nerves.

Impact of polyunsaturated fatty acids on human colonic bacterial metabolism: an in vitro and in vivo study.

Dietary polyunsaturated fatty acids (PUFA) reduce colonic proliferation and exert a mild laxative effect. We have studied the effect of the highly unsaturated eicosapentaenoic acid ethyl ester (EPA-EE) on the growth and metabolism of colonic bacteria in vitro, and in vivo. For the in vitro study, growth was assessed by viable counts. Bacteroides thetaiotaomicron was significantly inhibited in anaerobic media containing EPA-EE at concentrations > 7 milligrams. Escherichia coli was apparently resistant even at 100 milligrams. For the in vivo study, ten healthy volunteers ingested 18 g EPA-EE/d for 7 d. Stool frequency, 24 h stool weight and whole-gut transit time were assessed together with breath H2 and 14CO2 excretion following oral ingestion of 15 g lactitol labelled with 0.18 MBq [14C]lactitol. The area under the breath-H2-time curve was significantly reduced by EPA-EE, from a control value of 690.3 (SE 94.2) ppm.h to 449.5 (SE 91.7) ppm.h. Percentage dose of 14CO2 excreted, total stool weight and whole-gut transit time were unaltered, being respectively 24 (SE 2)%, 281 (SE 66) g and 45 (SE 4) h with EPA-EE v. control values of 27 (SE 1)%, 300 (SE 89) g and 42 (SE 5) h. It is concluded that dietary supplementation with EPA-EE reduces breath H2 excretion without apparently impairing overall colonic carbohydrate fermentation. The observed reduction may reflect utilization of H2 to hydrogenate the five double bonds of EPA-EE.

Frictional resistances using Teflon-coated ligatures with various bracket-archwire combinations.

Static frictional resistances were compared between Teflon-coated stainless steel and clear elastomeric ligatures used with various combinations of brackets and archwires. Stainless steel metal, polycrystalline ceramic and single crystal ceramic 0.022-inch slot brackets were used in combination with stainless steel and nickel titanium archwires, 0.018 inch and 0.016 x 0.022 inch. Friction was measured in the dry state at bracket-archwire angulations of 0, 5, 10, and 15 degrees. Moments induced by engagement of the archwires into the brackets were measured for each archwire type and bracket-archwire angulation. Teflon-coated ligatures produced less friction than elastomers for all bracket-archwire combinations. The ceramic brackets generally elicited greater frictional resistances than stainless steel brackets. Regarding both friction and control of tooth movement, these data suggest that sliding mechanics are best executed with stainless steel brackets and stainless steel archwires. Moreover, these data reveal the usefulness of Teflon-coated ligatures in minimizing the high friction of ceramic brackets when an esthetic appliance is imperative.

Inhibitory effect of polyunsaturated fatty acids on the growth of Helicobacter pylori: a possible explanation of the effect of diet on peptic ulceration.

Diets high in polyunsaturated fatty acids may protect against duodenal ulcer, possibly through inhibiting the growth of Helicobacter pylori. This hypothesis was tested in vitro by incubating H pylori microaerophilically with a range of polyunsaturated fatty acids. omega-3 Linolenic acid significantly, but reversibly, inhibited growth at 1.8, 2.5, and 5 x 10(-4) M (p < 0.01), while concentrations of 10(-3) M killed virtually all organisms, with cell lysis observed by electron microscopy. Similar inhibitory effects were seen with other polyunsaturated fatty acids, at concentrations of 2.5 x 10(-4) M the relative inhibitory potencies were oleic (C18:1) < linoleic (C18:2) < arachidonic (C20:4) < omega-3 linolenic (C18:3) = omega-6 linolenic (C18:3) = eicosapentanoic (C20:5) acid. Cell fractionation studies with 14C labelled linolenic acid showed that the linolenic acid was associated with the membrane fraction. Commonly ingested dietary polyunsaturated fatty acids inhibit the growth of H pylori in vitro, an effect which deserves further in vivo study.

Recurrent gastrointestinal bleeding of obscure origin: report of 17 cases and a guide to logical management.

Seventeen patients with chronic obscure gastrointestinal bleeding presenting over a 5-year period are described. While representing only 6 per cent of the total number of admissions due to gastrointestinal haemorrhage they required a disproportionate amount of medical attention, including 67 admissions, 73 radiological and 56 endoscopic procedures and transfusion of a total of 198 units of blood. The diagnoses included 5 cases of recurrent acute upper gastrointestinal erosions, 7 small bowel abnormalities and 4 colonic lesions, with 1 patient undiagnosed. Eight arteriovenous malformations (AVM) were demonstrated angiographically and one Meckel's diverticulum identified by a 99Tcm pertechnetate scan. There were 5 cases in which laparotomy yielded the final diagnosis and in one of these peroperative endoscopy of the small bowel was required. On the basis of our experience and a review of other series, a logical plan of investigation is described for such difficult cases.