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Biomedical subjects

R C Spiller

Publications and source records attributed to R C Spiller.

At least 73 records · Page 4Linked to original sources
PubMed1996

Rapid and selective high-performance liquid chromatographic method for the determination of metronidazole and its active metabolite in human plasma, saliva and gastric juice.

A rapid and selective HPLC method has been developed for the separation and quantitation of metronidazole and its hydroxylated metabolite in human plasma, saliva and gastric juice. The assay requires a simple protein precipitation step prior to analysis and is selective, sensitive and reproducible. The limits of quantitation (0.5-ml sample) were at least 0.25 microgram/ml for metronidazole and 0.20 micrograms/ml for its hydroxy metabolite. A Hypersil ODS 5 micron (150 x 4.5 mm I.D.) column was used with a mobile phase of acetonitrile-aqueous 0.05 M potassium phosphate buffer (pH 7) containing 0.1 % triethylamine (10:90) delivered at a flow-rate of 1.0 ml/min.

Anti-Infective Agents↗
PubMed1996

Enhanced eradication of Helicobacter pylori by pre- versus post-prandial amoxycillin suspension with omeprazole: implications for antibiotic delivery.

BACKGROUND: Strategies to improve antibiotic treatment of Helicobacter pylori infection are hampered by lack of knowledge about the route of antibiotic delivery. Post-prandial dosing with antibiotics prolongs their gastric residence time and improves their intragastric distribution, leading to improved local delivery compared with pre-prandial dosing. We aimed to assess whether pre- or post-prandial dosing. with amoxycillin suspension was more effective for H. pylori eradication in an amoxycillin/omeprazole regimen. METHODS: Seventy-nine patients with H. pylori infection were treated with omeprazole 40 mg o.m. for 28 days and amoxycillin suspension 500 mg q.d.s. for days 15-28, the amoxycillin being randomized to either 1 h before or immediately after food. RESULTS: The H. pylori eradication rate, for those completing the trial, was 67% (22/33) when amoxycillin suspension was given pre-prandially, compared with 39% (15/38) when it was given post-prandially (P < 0.05). Good compliance was achieved, with H. pylori eradication in 59% (28/46) of good compliers compared with 36% (9/25) of others completing the protocol (P < 0.05). CONCLUSION: When given with omeprazole, pre-prandial dosing with amoxycillin suspension is more effective for H. pylori eradication than post-prandial dosing. This is consistent with the hypothesis that systemic rather than local delivery of amoxycillin is important for H. pylori eradication.

Adult↗
PubMed1996

Helicobacter pylori eradication in clinical practice: one-week low-dose triple therapy is preferable to classical bismuth based triple therapy.

BACKGROUND: Both classical 2-week bismuth based triple therapy and the newer 1-week low-dose omeprazole based triple therapies achieve high Helicobacter pylori eradication rates in controlled clinical trials and are in widespread use in routine clinical practice. However, their efficacy and acceptability in this setting is unproved. METHODS: Over a 1-year period, the notes for patients attending a dedicated H. pylori treatment clinic were audited. Assessments were made of patient demographics, diagnosis, smoking habits, use of H2-antagonists, regimen used, efficacy of treatment, compliance and side-effects experienced. RESULTS: 223 sets of notes were audited. 89 patients received bismuth, tetracycline and metronidazole for two weeks and 111 patients received omeprazole, clarithromycin and either metronidazole (63 patients) or tinidazole (48 patients) for 1 week. Successful eradication was achieved in 75/89 (84.3%), 56/63 (89%) and 42/48 (88%), respectively, (P = N.S.). Severe side-effects occurred in 11 (12%) of patients receiving bismuth based treatment compared to 1 (0.9%) patient receiving omeprazole based regimens (P < 0.02). Treatment failure in patients receiving omeprazole based treatment was associated with smoking (P < 0.05). CONCLUSIONS: Outside the context of clinical trials, both regimens achieved acceptable eradication rates. However, 1-week low-dose therapy is preferable due to the lower incidence of severe side-effects.

Antacids↗
PubMed1996

Effect of omeprazole on the distribution of metronidazole, amoxicillin, and clarithromycin in human gastric juice.

BACKGROUND & AIMS: The mechanism by which antimicrobial therapy against Helicobacter pylori is enhanced by acid suppression is unknown. The aim of this study was to investigate the effect of omeprazole on gastric juice, plasma, and saliva concentrations of metronidazole, amoxicillin, and clarithromycin. METHODS: Single doses of antibiotic were administered intravenously to 24 healthy men (each antibiotic to 8 subjects) while taking placebo or omeprazole. Antibiotic concentrations were measured in gastric juice, plasma, and saliva. The pharmacokinetic parameters gastric clearance and gastric transfer fraction were calculated for each antibiotic. RESULTS: In the omeprazole group compared with the placebo group, mean maximum antibiotic gastric juice concentrations (in milligram per liter) of metronidazole decreased from 33.6 to 8.3 (P = 0.0001), whereas those of clarithromycin were unchanged, and those of amoxicillin increased from 0.13 to 0.68 (P = 0.02). Omeprazole increased salivary concentrations of metronidazole (P = 0.02) but had no effect on clarithromycin concentrations (no amoxicillin was detectable in saliva). CONCLUSIONS: Omeprazole decreases the intragastric concentrations of metronidazole by reducing acid secretion and increases intragastric concentrations of amoxicillin partly by reducing gastric juice volume. Novel pharmacokinetic parameters have been described that provide an insight into the mechanisms underlying drug transfer across the blood-stomach barrier.

Adult↗
PubMed1996

The effect of omeprazole on gastric juice viscosity, pH and bacterial counts.

BACKGROUND: In vitro studies have shown that pH is an important determinant of mucus structure and function, but the relationship in vivo is unclear. Omeprazole increases intragastric pH and also allows bacterial overgrowth. In this study we have assessed the effect of omeprazole on gastric juice viscosity and examined the influence of pH and bacterial overgrowth on the resulting change. METHODS: Gastric juice specific viscosity, pH and total bacterial counts were measured in nine healthy male volunteers before and after omeprazole 20 mg twice daily for 1 week. The effect of incubation at pH 2 and 7 was also determined. Viscosity changes were compared with changes in pH and bacterial counts. RESULTS: Mean viscosity fell (P < 0.05) following treatment, though there was a wide range in viscosity both before and after treatment. The decrease was reproduced by incubation of pre-treatment juice at pH 7 but not pH 2. The fall in viscosity was correlated (P < 0.05) with change pH. CONCLUSION: Omeprazole decreases gastric juice, and hence gastric mucus, viscosity by increasing intragastric pH. This could be important if it allows improved penetration of antimicrobials to Helicobacter pylori within the mucus layer.

Adult↗
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↗