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Biomedical subjects

R C Spiller

Publications and source records attributed to R C Spiller.

At least 19 recordsLinked to original sources
PubMed1995

Echo-planar magnetic resonance imaging to assess water volume in the distal small bowel.

PURPOSE: Assessment of fluid volumes and flow through the small intestine has in the past only been possible by means of invasive intubation studies on human volunteers. Intubation very likely disturbs gut motility and stimulates secretion. METHODS: The aim of this study was to utilise the new technique of echo-planar magnetic resonance imaging in order to non-invasively visualise the changing volume of water in the small intestinal lumen. 200 mls of test solution was ingested and water volume assessed using a multi-slice scanning technique on 3 separate days. The solutions were pure water, pure water plus 2.264 or 10 g of mannitol. These were taken on separate days by 8 healthy male volunteers. Regions of interest were constructed in the area of the lower pelvis excluding retroperitoneal structure. RESULTS: The water content of the lower small intestine did not change significantly over the 4 hours after the control solution. By contrast after both mannitol solutions there was an increase in the amount of water in the distal intestine as assessed by the area under the curve of the volume time profile (Control 51 ml.h (SD +/- 47); mannitol 2.264 g/200 ml 72 ml.h (SD +/- 57); 10 g/200 ml mannitol 115 ml.h (SD +/- 56)). Page's L Trend test showed that the trend for the volume to increase with increasing mannitol concentration to be statistically significant at the 1% level (L = 108). CONCLUSIONS: The study highlights the potential of echo-planar magnetic resonance imaging to visualise changes in gastrointestinal physiology in a noninvasive manner.

Adult↗
PubMed1995

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.

Adult↗
PubMed1995

Effect of a test meal on the intragastric distribution of urea in the 13C-urea breath test for Helicobacter pylori.

Test meals are invariably used in the 13C-urea breath test (UBT) but their effect on the intragastric distribution and gastric residence time of urea given in the test is unknown. The site of Helicobacter pylori urease measured in the test is unknown and whether the test measures total or regional gastric urease is uncertain. This study reports the results of paired UBTs with simultaneous gastric distribution studies, one with and one without a fatty test meal, two weeks apart on seven H pylori infected subjects. The test meal did not affect UBT results at 10 minutes, but increased values at 30 minutes and thereafter. The amount of scintigraphic label in the antrum at 10 minutes was also unaffected by the meal but increased at 30 minutes and thereafter, whereas the amount in the body/fundus was greatly increased both at 10 minutes and throughout the test. There was considerable variation in intragastric distribution of urea between subjects, both with and without the test meal. This study shows that a test meal profoundly affects intragastric distribution of urea solution in the UBT, and increases UBT values at 30 minutes and later. Variability between subjects, however, means that accurate measurement of total or regional gastric urease is probably unrealistic.

Adult↗
PubMed1995

Detection of the intragastric sites at which Helicobacter pylori evades treatment with amoxycillin and cimetidine.

Treatment of Helicobacter pylori infection with amoxycillin is known to reduce the bacterial load to undetectable levels, while not eradicating the infection. It seems, therefore, that bacteria escape treatment at a 'sanctuary site'. This study examined whether such a site existed in the gastric antrum, body, or fundus. Twenty two patients with H pylori infection and duodenal ulcer disease were treated for one week with amoxycillin (500 mg three times a day) and cimetidine (800 mg at night). Before treatment, H pylori was detected throughout all stomachs, and 13C-urea breath testing at least 28 days after treatment confirmed that eradication of H pylori had occurred in no patients. While under treatment, H pylori was sought by conventional methods and by polymerase chain reaction assay and was found in the gastric fundus in 13 of 22 subjects, in the body in 10 of 22, and the antrum in three of 22: the difference between fundus and antrum was significant (p < 0.01). The continued antral infection in three subjects may have resulted from generalised treatment failure as two of three had H pylori detected throughout the stomach, and these two had compiled relatively poorly with treatment. This study suggests that amoxycillin and cimetidine are relatively effective at clearing H pylori from the gastric antrum, but that escape from treatment may occur in the gastric body, and especially the fundus.

Adult↗
PubMed1995

Effect of bran particle size on gastric emptying and small bowel transit in humans: a scintigraphic study.

Bran is an effective treatment for constipation but its use is often limited by heartburn and bloating. This study examined the effect of fine and coarse bran (15 g) on the gastric emptying and small bowel transit of a 325 kcal rice test meal. Twelve healthy volunteers underwent a three way cross over study, ingesting the technetium-99m labelled rice meal with or without 15 g of indium-111m labelled fine or coarse bran, in random order. Serial scintigraphic images were obtained to define gastric emptying and colonic arrival of label. Compared with control values (99 (9) minutes) (mean (SEM)), the time to 50% gastric emptying was significantly delayed by coarse but not fine bran, being 121 (6) and 104 (9) minutes respectively, p < 0.05, n = 12. Fundal emptying was unchanged but both brans seemed to increase the proportion of isotope in the antrum at 90 minutes. Small bowel transit was slightly faster with both bran types but in this study the difference was not significant. Both the bran and rice labels moved down the gut without significant separation. Fine bran causes less disturbance of gastric physiology than coarse bran.

Adult↗
PubMed1994

Pharmacology of dietary fibre.

"Dietary fibre" includes a range of relatively poorly digested food substances mainly composed of non-starch polysaccharides. Pectins and gums are multi-branched hydrophilic substances, forming viscous solutions that delay gastric emptying and nutrient absorption from the small bowel. They are used to delay gastric emptying and improve glycemic control in diabetes, as well as to alleviate constipation. Other fibres, including cellulose and lignins, are insoluble and have little effect on gastric emptying and small bowel transit. They markedly accelerate colonic transit and are frequently used as laxatives. Other important, less well-characterised effects of fibre include lowering of blood cholesterol, increase in satiety and possibly reduction in colon neoplasia.

Animals↗
PubMed1994

Scintigraphic assessment of the intragastric distribution and gastric emptying of an encapsulated drug: the effect of feeding and of a proton pump inhibitor.

BACKGROUND: Local delivery of therapeutic agents to the stomach may be a useful strategy in the treatment of Helicobacter pylori infection. We aimed to see whether the intragastric distribution and gastric retention of a therapeutic agent could be improved, either by giving omeprazole or by dosing after a meal. METHODS: Twelve healthy volunteers took part in this double-blind placebo-controlled crossover study comparing the effects of omeprazole 20 mg twice daily for 5 days with placebo, and the fasted with the fed state, on the gastric emptying and intragastric distribution of a soluble scintigrapic marker contained in a drug capsule. RESULTS: Dosing after food profoundly prolonged gastric residence of the drug label, prolonging mean time to 50% emptying (T50) from 0.5 +/- 0.1 h in the fasted state to 2.0 +/- 0.2 h when given after food. Food also improved intragastric distribution by increasing delivery to the body and fundus. Omeprazole enhanced the effect of food, prolonging T50 to 2.9 +/- 0.3 h, but had no effect in fasted subjects. CONCLUSIONS: Dosing after food markedly improves the aspects of local drug delivery to the stomach investigated in this study, and omeprazole enhances this effect. Post-prandial dosing may, therefore, be useful for improving delivery of some anti-Helicobacter agents.

Adult↗
PubMed1994

Amoxycillin capsules with omeprazole for the eradication of Helicobacter pylori. Assessment of the importance of antibiotic dose timing in relation to meals.

BACKGROUND: Giving antibiotics after meals prolongs their gastric residence time and improves their intragastric distribution. We aimed to see whether this would result in improved eradication of Helicobacter pylori. METHODS: Eighty patients with H. pylori infection were treated with 40 mg omeprazole in the morning for 28 days and amoxycillin 500 mg q.d.s. for days 15-28. Amoxycillin dosing was randomised to either 1 h before or 10 min after food. Good compliance was pre-defined as missing less than four doses of amoxycillin or two of omeprazole. RESULTS: Amoxycillin dosing after meals was shown not to affect H. pylori eradication rate either when results were analysed on an intention-to-treat basis [amoxycillin before meals successful in 63% (25/40), after in 65% 26/40)] or for good compliers only [before meals 81% (17/21), after 71% (20/28)]. This excludes, with 95% confidence, a benefit of greater than 18% from dosing before, or 23% from dosing after meals. Good compliance, however, was shown to be important, with H. pylori eradication in 76% (37/49) of good compliers compared with 48% (11/23) of others completing the protocol (P < 0.05). CONCLUSIONS: The timing of antibiotic administration in relation to meals is not important in the treatment of H. pylori infection with this regimen of amoxycillin capsules and omeprazole. Good compliance, is however, an important determinant of treatment success.

Adolescent↗
PubMed1994

Impaired oesophageal transit of capsule versus tablet formulations in the elderly.

Drug induced oesophageal injury is an important and preventable cause of iatrogenic injury. In most cases the injury is considered to be due to mucosal contact from formulations lodged in the oesophagus. A scintigraphic study was performed comparing the oesophageal transit of enteric coated tablets with similar sized and shaped gelatin capsules, using a population of elderly healthy volunteers similar in age (50-79 years) to the population most likely to be receiving regular treatment. Twenty three volunteers injected the radiolabelled tablet or capsule with 50 ml of water while sitting on two separate occasions according to a randomisation schedule. Oesophageal transit was assessed by gamma scintigraphy. Gastric residence was also assessed in 11 of 23 subjects. While the tablet was readily cleared from the oesophagus, mean transit time 4.3 seconds (range 1.0-14.0), the capsule often showed a comparatively prolonged holdup, mean transit time 20.9 seconds (range 1.5-174.5). Ten of 11 tablets emptied from the stomach intact, while all 11 capsules broke up in the stomach. Gelatin capsules showed a clear tendency to remain within the oesophagus of healthy elderly volunteers, while similar sized enteric coated tablets did not. These studies show the importance of assessing oesophageal transit when designing the formulation of drugs with a potential for oesophageal injury.

Administration, Oral↗
PubMed1994

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.

Diet↗
PubMed1994

Intestinal absorptive function.

The normal gut is adapted to intermittent feeding with complex macromolecular substrates of low sodium content. The high permeability of the upper small intestine to sodium, together with sodium rich saliva and pancreaticobiliary secretions results in large sodium fluxes into the lumen. These substantial sodium influxes are matched by equally large effluxes from the ileum and proximal colon, which are comparatively impermeable to sodium and capable of active sodium absorption. Resection of these distal, sodium absorbing regions of the intestine, lead to problems with sodium depletion. Controlled transit of chyme is essential to permit time for optimum digestion and absorption and a range of feedback control mechanisms exist. Partially digested nutrients, both in the duodenum and ileum, exert inhibitory feedback to delay delivery of further nutrients and here again surgery may compromise these reflexes. Brush border hydrolase values are strongly influenced by luminal nutrient concentrations, being impaired by malnutrition and total parenteral nutrition, but restored by enteral feeding. Viscous fibre slows absorption and may delay transit through mechanisms that are as yet uncertain. Whether and how novel substrates activate normal control mechanisms will be important factors determining their effectiveness and patient acceptability.

Digestion↗