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Biomedical subjects

R C Spiller

Publications and source records attributed to R C Spiller.

At least 91 records · Page 5Linked to original sources
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↗
PubMed1993

Quantitative, noninvasive assessment of antidiarrheal actions of codeine using an experimental model of diarrhea in man.

Enteric coating of a capsule has been used to deliver a bolus of radioisotope to the ileocecal region. This has allowed quantitative assessment of regional colonic transit in a group of healthy subjects whose proximal colonic transit was accelerated by lactulose 20 ml thrice daily. In this experimental model of diarrhea, codeine delayed transit from mouth to terminal ileum and also delayed transit through the ascending colon from 5.3 +/- 2.5 hr to 7.4 +/- 2.5 hr, N = 11, P < 0.05. Furthermore, codeine delayed whole colon transit, as assessed by geometric center analysis, which showed the delay to be most marked in the right colon with little effect noted in the left colon. In addition, codeine significantly reduced the number of retrograde movements observed and reduced the colonic response to eating. The antidiarrheal effect of codeine appears to be due to a combination of delayed mouth-cecum transit plus an additional delay in the ascending colon. This colonic delay may be partially explained by a reduction in postprandial propulsive movements that were seen in this model of diarrhea.

Adult↗
PubMed1993

Proximal colonic response and gastrointestinal transit after high and low fat meals.

The fat component of meals has been thought to make a major contribution to the colonic response to feeding. We have combined gamma scintigraphy and radiotelemetry to noninvasively study the response of the normally inaccessible proximal colon after ingestion of either a high or low fat meal. Separate studies were performed to measure the rate of passage of the same meals through the whole gut. Gastric emptying and small bowel transit of the two meals to the colon was similar, 50% of meal marker reaching the ascending colon 4.8 +/- 0.2 and 4.5 +/- 0.3 hr after the high and low fat meals respectively (N = 8, difference not significant). The low fat meal caused a consistent increase in motility index, which rose from a basal value of 1.0 +/- 0.3 to 2.6 +/- 0.7 mm Hg in the 2 hr after the meal (N = 8, P < 0.01). Response to the high fat meal was less consistent, motility index increasing from 1.6 +/- 0.6 basally to 2.3 +/- 0.7 mm Hg postprandially (N = 8, P = 0.21). Despite these increases in motor activity there was no net caudal propulsion of colonic contents after either meal. The geometric center was comparable, being 3.2 +/- 0.4 and 3.7 +/- 0.4 before the high and low fat meals. This did not change significantly after either meal, being then 3.5 +/- 0.4 and 3.6 +/- 0.4 2 hr after the high and low fat meals, respectively. We conclude that in normal subjects equicaloric high and low fat meals transit the whole gut at a similar rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Scintigraphic demonstration of lactulose-induced accelerated proximal colon transit.

Although lactulose, a widely used cathartic, is known to increase stool frequency, details of its site of action in the colon are obscure. In the present study a noninvasive scintigraphic technique was used to closely follow the movements of proximal colonic contents. Lactulose, 10-20 mL three times daily, significantly accelerated mean transit through the ascending colon from 12.9 +/- 3.7 to 7.0 +/- 2.5 hours (n = 11; P less than 0.01). This was associated with the occurrence of mass movements, with six such events seen during lactulose treatment whereas only one was seen during the control study (P less than 0.05). Lactulose also accelerated movement through the rest of the colon so that at 24 hours after dosing the geometric center of the isotope bolus was distal to that seen during the control study (6.6 +/- 1.2 vs. 4.7 +/- 1.3; n = 11, P less than 0.001). This model of diarrhea in otherwise normal subjects was subsequently used to study the effects of viscous gels in diarrhea. The viscous and relatively poorly fermented gel ispaghula, 3.5 g three times daily, abolished mass movements and was associated with a small but significant increase in proximal colonic transit time, which increased from 6.1 +/- 2.1 to 7.7 +/- 1.5 hours (n = 8; P less than 0.05). By contrast, the viscous but readily fermentable gelling agent guar gum, 5 g three times daily, further accelerated the cathartic effect of lactulose, with the mean transit time decreasing from 6.4 +/- 2.3 to 4.7 +/- 1.7 hours (n = 8; P less than 0.05). The acceleration of proximal colonic transit by lactulose may be a useful model to study diarrhea and its modification by therapy.

Adolescent↗
PubMed1991

Megaduodenum due to hollow visceral myopathy successfully managed by duodenoplasty and feeding jejunostomy.

A 29 year old man with a history of childhood polymyositis developed insulin dependent diabetes and was found coincidentally to have chronic intestinal pseudo-obstruction due to visceral myopathy. Multiple full thickness biopsy specimens showed severe disease in the duodenum and the proximal jejunum only, with less involvement distally. Total parenteral nutrition has been avoided for more than a year by enteral feeding through a fine bore jejunostomy catheter positioned with its tip in the distal jejunum.

Adult↗
PubMed1989

Effect of ileal infusion of glycochenodeoxycholic acid on segmental transit, motility, and flow in the human jejunum and ileum.

The hypothesis that the presence of glycochenodeoxycholic acid (GCDC) in the human Ileal bile acid concentrations showed a 54.0 (9.3)% absorption of glycochenodeoxycholic acid by the been tested in healthy volunteers. Mean transit times, flow rates and intraluminal pressures in a 40 cm jejunal segment proximal (n = 6) and a 40 cm ileal segment distal (n = 6) to a GCDC infusion port were measured. During GCDC infusion (60 mumol/min) jejunal and ileal transit were markedly (p less than 0.05) delayed (31.6 (7.7), mean (SEM) v 14.5 (3.8) min and 37.0 (5.7) v 21.0 (3.5) min, respectively), segment volumes increased (141.1 (30.2) v 59.2 (9.9) ml and 173.2 (26.3) v 83.9 (9.5) ml; p less than 0.05), while flow rates did not change significantly (4.6 (0.6) v 4.5 (0.6) ml/min and 4.8 (0.5) v 4.2 (0.3) ml/min, respectively). Ileal pressures (distal to the GCDC infusion port) decreased (p less than 0.05) promptly (1.0 (0.1) min) after the start of GCDC infusion. Inhibition of jejunal motility was more gradual and reached significance (p less than 0.05) only 30 min after beginning of the infusion. Ileal bile acid concentrations showed a 54.0 (9.3)% absorption of glycochenodeoxycholic acid by the 40 cm ileal segment. These observations suggest the existence of an intestinal control mechanism in healthy man, whereby presence of glycochenodeoxycholic acid in the ileum inhibits motility and delays transit in the jejunum and ileum.

Adult↗
PubMed1988

Effect of cholecystectomy on mouth-to-cecum transit of a liquid meal.

Mouth-to-cecum transit and serum bile acid profile after ingestion of a lactulose-labeled liquid meal (440 kcal) were measured in eight patients with gallstones and a radiologically functioning gallbladder before and three to five months after cholecystectomy and in 15 controls. In the patients mouth-to-cecum transit was longer after the operation, 87.5 +/- 18.5 (mean +/- SEM) min vs 57.5 +/- 9.7 min (P less than 0.05). Mouth-to-cecum transit times before and after the operation were not different from controls (58.0 +/- 6.7 min). Serum bile acid AUCs were similar (P = NS) in patients and controls, while total bile acid and cholylglycine fasting concentrations were higher after cholecystectomy (P less than 0.05 and P less than 0.01 respectively). Cholecystectomy prolongs mouth-to-cecum transit of a liquid meal.

Adult↗
PubMed1988

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions.

Adult↗
PubMed1988

Adult acquired cytomegalovirus infection with gastric and duodenal ulceration.

Recent reports of cytomegalovirus associated colonic and oesophageal ulceration in immunosuppressed patients infected with the human immunodeficiency virus, have focused attention on the possibility that viral infections may in some cases be the initial insult which leads in susceptible subjects to gastrointestinal ulceration. In this case report we describe how systemic primary infection with the cytomegalovirus was associated with the development of multiple gastric and duodenal erosions.

Adult↗
PubMed1987

Emptying of the terminal ileum in intact humans. Influence of meal residue and ileal motility.

Emptying of the terminal ileum was assessed in 15 healthy humans by injecting technetium 99m-diethyltriaminopentaacetic acid into the bowel through a multilumen orocolonic tube. The subsequent arrival of isotope in the colon was quantified by gamma-scintigraphy and colonic filling curves were obtained. Studies were performed during fasting (n = 5) cnd 2.5 h after either a low residue meal (n = 5) or a meal made high in residue (n = 5) by adding 4 g of guar. The time for 50% of the isotope to reach the colon (T50) was significantly accelerated after both meals, being 72 +/- 15 min for the high residue meal and 62 +/- 8 min for the low residue meal, compared with 183 +/- 37 min (p less than 0.01) in the 5 fasting subjects. Although the addition of guar did not alter T50 significantly, it did cause a significant fall in the rate of colonic filling, implying increased isotope dilution. Delay at the ileocolonic junction, as shown by plateaus in the middle of the colonic filling curves, was uncommon. Hold-up was significant in only 2 of 10 postprandial and 2 of 5 fasting studies. Rates of ileocolonic transit could not be related to either a mean ileal motility index or the occurrence of specific ileal motor patterns immediately proximal to the ileocolonic junction. Fasting ileocolonic transit was characteristically erratic but could not be related to interdigestive migrating motor complexes, which were rarely observed in the last 60 cm of ileum. We conclude that ileocolonic transit in humans is related to the rate at which material accumulates in the ileum, being rapid postprandially (when ileal flow is high) and slow and erratic during fasting. This method yields consistent results and could be used to define further factors that influence ileocolonic inflow.

Adult↗
PubMed1987

Delayed postprandial plasma bile acid response in coeliac patients with slow mouth-caecum transit.

Coeliac patients are known to have an expanded bile salt pool which recirculates slowly due, at least in part, to impaired gall bladder contractility. We have investigated the possibility that delayed small bowel transit of chyme and bile may also contribute to this sluggish recycling. Plasma cholylglycine, total bile acids and cholecystokinin concentrations were measured after a lactulose-labelled test meal whose mouth-caecum transit time (M-C TT) was assessed by the breath hydrogen technique. Overall there were no significant differences in plasma bile acid profiles between seven healthy controls and a group of 25 coeliac patients. However, when subjects were divided according to their M-C TT, the 10 with the slowest transit were found to have significant elevation of fasting levels when compared with the 10 with the fastest transit, fasting total bile acids being 3.4 +/- 1.3 versus 0.7 +/- 0.6 mumol/l (P less than 0.02) and fasting cholylglycine being 0.43 +/- 0.17 versus 0.06 +/- 0.04 mumol/l (P less than 0.05) respectively. Peak bile acid levels did not differ significantly between subjects with fast or slow transit. However, subjects with slow transit were found to have a delay in the return of plasma bile acid levels to fasting levels so that the 4 h postprandial levels were significantly elevated when compared with those observed in the subjects with fast transit (total bile acids 3.6 +/- 1.2 versus 0.19 +/- 0.1 mumol/l and cholylglycine 0.70 +/- 0.13 versus 0.24 +/- 0.07 mumol/l respectively, both P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗