Impact of dietary fiber on absorption from the small intestine.
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Editorial↗
Biomedical subjects
R C Spiller
Publications and source records attributed to R C Spiller.
Upper gut dysmotility in slow-transit constipation: is it evidence for a pan-enteric neurological deficit in severe slow transit constipation?
Although constipation is common only a small fraction meet the criteria of slow transit constipation. Those that do are resistant to treatment and present a significant clinical problem to the physician and surgeon. Evidence has been accumulating over many years that the impaired colonic motility is part of a generalized motility defect. There are several reports of oesophageal dysmotility, delayed gastric emptying and slow small bowel transit. These abnormalities are not secondary to a distended colon since they are still seen after colonic cleansing and even after colectomy. The manometric abnormalities of small bowel motility are hard to assess unless done over a prolonged period (24 h) because of the great variability observed. The clinical picture of slow transit constipation is quite different from chronic intestinal pseudo-obstruction and the manometric abnormalities are much less obvious. The possibility of an underlying autonomic disturbance warrants further study.
Colon↗
Is there any difference in Helicobacter pylori eradication rates in patients with active peptic ulcer, inactive peptic ulcer and functional dyspepsia?
Omeprazole triple therapy has been shown to produce Helicobacter pylori eradication rates of up to 96% in patients with current or recent peptic ulceration. Such therapy is also now being used without endoscopy in H. pylori-positive patients who may have an inactive ulcer or dyspepsia, and in whom their effectiveness has been less well documented. Compliance is an important variable affecting H. pylori eradication; with 1-week omeprazole triple therapy, however, compliance is uniformly high, and this allows more detailed analysis of other causes of treatment failure. The strains of H. pylori in patients with functional dyspepsia may be associated with a lower degree of inflammation. Two new, large studies (DU-MACH and GU-MACH) have therefore looked at the impact of inflammation on H. pylori eradication. Polymorph infiltration in the antrum of patients with inflammation of grades 2/3 was associated with a significantly higher eradication rate when compared with inflammation of grades 0/1. Inflammation may be important for a number of reasons, including degradation of the mucus and epithelial layers (which may allow better penetration of charged antibiotics from the gastric lumen) and altered vascular and epithelial permeability (which may allow better systemic delivery of drugs). Alternatively, inflammation may be a marker for more aggressive H. pylori subtypes, which are also more vulnerable to antibiotic therapy.
Amoxicillin↗
Night-time quiescence and morning activation in the human colon: effect on transit of dispersed and large single unit formulations.
OBJECTIVES: Controlling the delivery of drugs to different regions of the colon remains an elusive goal. The aim of this study was to define the diurnal variation in colonic transit and show how this influences the colonic distribution and residence time of different formulations given either in the morning or evening. METHODS: Colonic transit of small particulates and a large capsule was measured during nocturnal sleep and daytime wakefulness. Eighteen healthy volunteers participated in a randomised crossover study. 111In-labelled resin (150-300 microm) and a large 99mTc-labelled non-disintegrating capsule (22 x 8 mm) were swallowed at either 0800h or 1700h. MAIN OUTCOME MEASURES: The geometric centre of isotope (range 1-9) was calculated from serial scintiscans allowing comparison of overnight and daytime transit. RESULTS: Transit of resin was delayed in the overnight compared to daytime 8 h periods (change in geometric centres (GCs), mean +/- SEM, 0.59 +/- 0.14 vs 1.46 +/- 0.39 respectively, P < 0.02). Maximal resin movement occurred immediately after awakening, prior to breakfast, in 9/18 studies (P < 0.05). The capsule was more distal than the resin at the end of the study 15 h after dosing (P < 0.001). There was marked inter-individual variability in distribution of both resin and capsule at 15 h, the range of GCs being 2.8-9 and 2.2-9, respectively. CONCLUSION: Sleep delays colonic transit and large capsules travel faster than dispersed small particles. However, substantial inter-individual variability in transit makes targeting specific regions of the human colon unreliable with either dispersed or single unit formulations.
Administration, Rectal↗
Echo-planar imaging relaxometry to measure the viscosity of a model meal.
A method for measuring noninvasively the viscosity of a polysaccharide model meal using the known relationship between relaxation times and polysaccharide concentration in solution in vitro is presented. The aim is to develop a method for monitoring digesta viscosity in vivo, using EPI to capture the motion of the gastrointestinal lumen. The transverse relaxation rate T-12 of locust bean gum solutions was calibrated against the zero-shear viscosity at 37 degreesC. Differences in viscosity were distinguished significantly using T-12 measurements. T-12 and viscosity were insensitive to exposure to gastric juice and changes in pH, and the model meal was well received by volunteers and provided good contrast in vivo in EPI images. Therefore it would be possible to use this method to monitor the changes in meal viscosity within the gastric lumen in vivo.
Echo-Planar Imaging↗
Mebeverine decreases mass movements and stool frequency in lactulose-induced diarrhoea.
BACKGROUND: In spite of its frequent use in the treatment of irritable bowel disease little is known about mebeverine's mode of action in man. AIM: To examine mebeverine's effect on transit though the gut during lactulose-induced diarrhoea. METHODS: Nine healthy volunteers undertook a two-way randomized crossover study. Diarrhoea was induced using lactulose pre-treatment (20 m t.d.s., 4 days) and subjects received either mebeverine (135 mg t.d.s.) or no treatment. Transit of two enteric-coated capsules containing radiolabelled 8.4 mm tablets and 180-250 microM ion exchange resin were followed using gamma scintigraphy. Stool frequency and symptoms were assessed by diary cards. RESULTS: Mebeverine reduced mean daily stool frequency associated with lactulose ingestion from a median of 2.25 (interquartile range (IQR) 1.75-2.75) to 1.5 (IQR 1.25-2.25) movements. Mebeverine significantly reduced the number of mass movements observed in the colon during the 11 h of the study from 2 (2-2) to 1 (1-2), and the number of retrograde movements from 1 (0-2) to 0 (0-0) (P < 0.05). Mebeverine did not significantly alter the gastric emptying rate of the intact capsule (2.9 (1.9-3.2) to 2.8 (2.6-4.0) h) however it induced a small but significant acceleration in small intestinal transit of the capsule (1.6 (0.8-2.0) h to 1.0 (0.52-1.32) h, P=0.02). CONCLUSION: Mebeverine reduces the diarrhoeal effect of lactulose by decreasing the mass movements induced in the ascending colon. This effect may contribute to its clinical effect in irritable bowel syndrome.
Adolescent↗
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.
Adult↗
The effect of protein binding and lipophilicity of penicillins on their in-vitro flux across gastric mucosa.
Delivery of amoxycillin across the human gastric mucosa to Helicobacter pylori is poor compared with that of metronidazole and clarithromycin, limiting the clinical effectiveness of this penicillin. To investigate the physicochemical properties of penicillins that influence their flux across gastric mucosa, the fluxes of metronidazole and eight penicillins were measured in vitro across rat gastric mucosa. The lipophilicity of these drugs was also measured using potentiometric titration. The mean fluxes of monobasic penicillins (range 0.66-0.89 nmol/cm2/h) were significantly lower than those of the aminopenicillins (range 1.94-2.80 nmol/cm2/h) (P < 0.005). Penicillin flux was not significantly correlated with lipophilicity as measured, but was significantly correlated with published protein binding data (rs = 0.9048, P < 0.002). Metronidazole flux was significantly higher than that of any penicillin at 22.6 (+/-0.9) nmol/cm2/h (P < 0.001). Therefore, the in-vitro gastric delivery of penicillins can be predicted from protein binding which may in turn predict activity against H. pylori in vivo.
Animals↗
Dissecting intramural haematoma of the oesophagus.
The largest series of patients (n = 10) with dissecting intramural haematoma of the oesophagus is described. The typical features, chest pain with odynophagia or dysphagia and minor haematemesis are usually present but not always elicited at presentation. If elicited, these symptoms should suggest the diagnosis and avoid mistaken attribution to a cardiac origin for the pain. Precipitating factors such as a forced Valsalva manoeuvre cannot be identified in at least half the cases. Early endoscopy is safe, and confirms the diagnosis when an haematoma within the oesophageal wall or the later appearances of a longitudinal ulcer are seen. Dissecting intramural haematoma of the oesophagus has an excellent prognosis when managed conservatively.
Adult↗
Small bowel transit of a bran meal residue in humans: sieving of solids from liquids and response to feeding.
BACKGROUND: Ileal motor patterns are adapted to the propulsion of viscous meal residue, such as bran, which accumulates in the distal ileum postprandially. AIMS: To examine the effects of a second liquid/solid meal on ileal emptying. SUBJECTS AND METHODS: Eleven healthy fasting subjects consumed a 1.47 MJ pancake containing 15 g bran and 5 MBq Technetium-99m labelled amberlite resin (meal A). Gastric emptying and transit through the left upper quadrant (proximal) and right lower quadrant (distal) small bowel regions and colon were assessed scintigraphically. Transit was compared with and without a second Indium-111 liquid/solid DTPA labelled 2.28 MJ meal (B) given three hours after the first meal. RESULTS: Gastric emptying of meal A was slower than meal B (the time for 50% of the activity to leave the stomach (T50) being 113 (11) minutes versus 48 (3) minutes respectively, p < 0.01, n = 11). Both meals passed rapidly through the proximal small bowel (T50 meal A = 57 (14) minutes versus T50 meal B = 42 (11) minutes). Transit of meal A through the distal small bowel was much slower (T50 more than 390 minutes versus 176 (29) minutes for meal B, p < 0.01), resulting in meal B overtaking meal A and entering the colon earlier. Ingestion of the second meal (B) resulted in significantly less meal A marker entering the colon (5 (3)%) at 11 hours than when meal A was taken alone (18 (4)%) (p < 0.05, n = 8). CONCLUSIONS: The distal small bowel selectively retains bran, allowing liquid phase markers through to the colon. Consuming a second liquid/solid meal does not stimulate ileal transit of bran which seems to be propelled quicker by fasting motor patterns.
Adult↗
How can we improve on the efficacy of Helicobacter pylori treatment?
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Anti-Bacterial Agents↗
Healing of duodenal ulcer after eradication of Helicobacter heilmannii.
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Bacterial Infections↗
The effect of omeprazole on the pharmacokinetics of metronidazole and hydroxymetronidazole in human plasma, saliva and gastric juice.
AIMS: To evaluate the effect of omeprazole on the pharmacokinetics of metronidazole and hydroxymetronidazole in plasma, gastric juice and saliva following intravenous infusion or oral dosing of metronidazole. METHODS: Eight volunteers received single doses of metronidazole (400 mg) intravenously and orally, whilst taking placebo or omeprazole (40 mg, twice daily for 5 days) in a randomized 4-way crossover study. Metronidazole and hydroxymetronidazole concentrations in plasma, saliva and gastric juice samples were determined by h.p.l.c. Pharmacokinetic parameters for metronidazole and hydroxymetronidazole were calculated, and the significance of the mean differences in parameters between omeprazole and placebo co-administration was assessed using a two-tailed, paired t-test. RESULTS: There were no significant differences (P < 0.05) in any of the plasma or saliva pharmacokinetic parameter values for metronidazole between volunteers receiving omeprazole or placebo when metronidazole was administered either as an intravenous infusion or orally. Following intravenous administration of metronidazole to the placebo group and omeprazole treated group respectively, the gastric transfer of metronidazole was significantly reduced from 15.5 +/- 10.4% to 2.6 +/- 1.0% of the dose (P = 0.007; 95% CI of difference 4.8 to 21.0) with concomitant changes in the metronidazole AUC (from 77.5 +/- 18.0 mumol l-1 h to 352.6 +/- 182.1 mumol l-1 h; P = 0.0003; 95% CI of difference 127.6 to 422.7), Cmax (from 61.4 +/- 26.5 mumol l-1 to 271.8 +/- 104.3 mumol l-1; p = 0.0001; 95% CI of difference 118.6 to 302.1). Similarly, the gastric juice AUC of hydroxymetronidazole was significantly reduced from 3.2 +/- 1.9 mumol l-1 h to 1.5 +/- 0.8 mumol l-1 h of the dose (P = 0.0043; 95% CI of difference 0.4 to 3.0) with a concomitant change in Cmax (from 5.0 +/- 2.5 mumol l-1 to 3.0 +/- 1.2 mumol l-1; P = 0.0007; 95% CI of difference 0.7 to 3.4). CONCLUSIONS: Omeprazole had little effect on the plasma and salivary pharmacokinetics of metronidazole (or its hydroxymetabolite) after intravenous or oral administration, but it did have a substantial effect on the pharmacokinetics of metronidazole and hydroxymetronidazole in gastric juice.
Adult↗
Use of echo planar imaging to demonstrate the effect of posture on the intragastric distribution and emptying of an oil/water meal.
Intragastric distribution of solids and liquids is far from uniform but until recently technical limitations have prevented detailed study. Echo planar imaging (EPI), which can provide high-quality images of intragastric contents, has been used in this study to assess the intragastric distribution of oil and water and gastric emptying in subjects lying on either their left or right side. Eight healthy volunteers underwent four gastric emptying studies after consuming either an aqueous meal (400 mL beef consomme soup + 100 mL water) or a fat/aqueous meal (400 mL soup + 100 mL olive oil) lying on either their left or right side. Using a water suppressed imaging mode the lipid phase was clearly seen layering above the aqueous phase with little evidence of mixing. Gastric emptying of the aqueous meal (A) was not significantly different when lying on the left compared to the right side. However, gastric emptying of the aqueous phase of the fat/aqueous meal (B) was considerably slower when lying on the left compared to the right side, gastric volumes actually increasing over the 90 min of the study P < or = 0.05. When lying on the right side the aqueous phase of meal B emptied significantly slower than meal A. Oil was clearly observed to layer above the water and fill the duodenal cap when subjects lay on their left and the fundus when they lay on their right side. EPI clearly demonstrates the intragastric layering of oil which causes posture to strongly influence gastric emptying. EPI is a tool with great potential to describe the intragastric events following ingestion of complex multiphase meals.
Adult↗
Clarification of the link between polyunsaturated fatty acids and Helicobacter pylori-associated duodenal ulcer disease: a dietary intervention study.
Epidemiological evidence has suggested that the declining prevalence of duodenal ulcer disease may be attributable to rising consumption of polyunsaturated fatty acids, a hypothesis supported by in vitro evidence of toxicity of such substances to Helicobacter pylori. The objective of the present study was to establish whether this association is causal. Forty patients with proven infection with H. pylori and endoscopic evidence of past or present duodenal ulcer disease were randomized to receive either polyunsaturated fatty acids (PUFA group), in the form of capsules and margarine, or a placebo (control). Both groups received concurrent H2 antagonist therapy. Efficacy of therapy was determined endoscopically by assessment of ulcer healing while H. pylori status was determined by antral biopsy, urease (EC 3.5.1.5) culture and histological assessment of the severity of H. pylori infection. Antral levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were quantified. Compliance was monitored. Before treatment, both groups were comparable for severity of H. pylori infection, smoking status and levels of LTB4 and PGE2. Despite a significant difference in consumption of linoleic acid (19.9 (SE 1.6) g for PUFA group v. 6.7 (SE 0.8) g for controls (P < 0.01) and linolenic acid (2.6 (SE 0.2) g v. 0.6 (SE 0.03) g (P < 0.01) there was no significant change in either the severity of H. pylori infection or prostaglandin levels in either group at 6 weeks. Consumption of a considerable amount of PUFA does not inhibit the colonization of the stomach by H. pylori nor does this alter the inflammatory changes characteristic of H. pylori gastritis. We conclude that the association between duodenal ulceration and a low level of dietary PUFA is likely to be spurious, probably reflecting the effect of confounding factors such as affluence, social class or smoking.
Combined Modality Therapy↗
The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment of Helicobacter pylori infection.
Although omeprazole is an important component in anti-Helicobacter pylori therapeutic regimes using clarithromycin, amoxycillin and metronidazole, the mechanism by which it enhances antimicrobial action is unknown. One potential explanation for this effect is increased antibiotic chemical stability resulting from gastric pH changes induced by co-administration of omeprazole. The chemical stability of clarithromycin, amoxycillin and metronidazole was investigated in aqueous solutions and in human gastric juice collected before and after a 7-day course of omeprazole. Amoxycillin, clarithromycin and metronidazole were prepared in buffered aqueous solutions of pH 1.0 to 8.0 and in gastric juice of pH 2.0 and 7.0. The gastric juice samples were obtained from fasted H. pylori-negative volunteers before and after they had received a 7-day course of omeprazole. All the samples were incubated at 37 degrees C and analysed at intervals by HPLC. Amoxycillin, clarithromycin and metronidazole were stable in aqueous solutions of pH 4.0-7.0, pH 5.0-8.0 and pH 2.0-7.0, respectively. At pH 2.0, the degradation half-lives were 19.0 +/- 0.2 h, 1.3 +/- 0.05 h and 2200 +/- 1100 h, respectively. In gastric juice samples of pH 2.0, the degradation half-lives were 15.2 +/- 0.3 h, 1.0 +/- 0.04 h and > or = 800 h, respectively. The half-lives of the drugs in the gastric juice samples of pH 7.0 were all > 68 h. The co-administration of omeprazole with amoxycillin or clarithromycin is likely to increase the chemical stability of amoxycillin and clarithromycin in gastric juice. Clarithromycin degrades rapidly at normal gastric pH (1.0-2.0) but amoxycillin and metronidazole are sufficiently stable at this pH to maintain an antibacterial concentration in the stomach.
Amoxicillin↗
In vitro assessment of gastric mucosal transfer of anti-Helicobacter therapeutic agents.
A novel animal model for studying antibiotic transfer across gastric mucosa was developed by using adult rats. Gastric corpus mucosa was mounted in an Ussing chamber system and bathed in oxygenated Krebs solution. Metronidazole flux from serosa to mucosa (J(S-->M)) was measured over 60 min under basal conditions and compared with mucosa-to-serosa flux (J(M-->S)). The effects of varying the chamber cross-sectional diameter and of stimulation by histamine and carbachol were assessed. Metronidazole J(M-->S) was measured with the mucosal pH at 2.2, 2.7, 3.2, and 7.4. Amoxicillin J(S-->M) under basal conditions was also measured and compared with metronidazole J(S-->M). Metronidazole J(S-->M) was proportional to serosal concentration (P < 0.001) under basal conditions, being 3.98 nmol x h(-1) x cm(-2) with a serosal concentration of 0.2 mmol/liter. Amoxicillin J(S-->M) was significantly lower under similar conditions at 0.50 nmol x h(-1) x cm(-2) (P < 0.01). Metronidazole J(S-->M) was not significantly different from J(M-->S), between chambers of different sizes, or following stimulation. When the mucosal pH was changed, J(M-->S) was proportional to the un-ionized concentration on the mucosal side (P < 0.001). Therefore, this model shows properties analogous to those of human gastric mucosa in vivo, with partitioning of metronidazole on the mucosal side according to pH, diffusion of metronidazole across the mucosa in both directions, and selectivity for different antibiotics, and it will be useful for the study of other therapeutic agents in the treatment of Helicobacter pylori.
Amoxicillin↗
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.
Aged↗