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Biomedical subjects

R C Spiller

Publications and source records attributed to R C Spiller.

At least 37 records · Page 2Linked to original sources
PubMed2001

Inflammatory bowel disease, azathioprine and skin cancer: case report and literature review.

A 42-year-old blond Caucasian woman taking azathioprine for 8 years developed an intra-epidermal carcinoma of the shin. She regularly used a sun bed to maintain a tan. Although the increased risk of non-melanoma skin cancer in immunosuppressed transplant recipients is well recognized, patients with Crohn's disease are not currently warned of the risk of exposure to ultraviolet light. Individuals with inflammatory bowel disease who take azathioprine, especially those with a fair complexion, should be informed of the potential dangers of sun bathing and should be advised to limit sun exposure.

Adult↗
PubMed2001

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.

Colon↗
PubMed2001

Assessment of antral grinding of a model solid meal with echo-planar imaging.

Mathematical modeling of how physical factors alter gastric emptying is limited by lack of precise measures of the forces exerted on gastric contents. We have produced agar gel beads (diameter 1.27 cm) with a range of fracture strengths (0.15-0.90 N) and assessed their breakdown by measuring their half-residence time (RT(1/2)) using magnetic resonance imaging. Beads were ingested either with a high (HV)- or low (LV)-viscosity liquid nutrient meal. With the LV meal, RT(1/2) was similar for bead strengths ranging from 0.15 to 0.65 N but increased from 22 +/- 2 min (bead strength <0.65 N) to 65 +/- 12 min for bead strengths >0.65 N. With the HV meal, emptying of the harder beads was accelerated. The sense of fullness after ingesting the LV meal correlated linearly (correlation coefficient = 0.99) with gastric volume and was independently increased by the harder beads, which were associated with an increased antral diameter. We conclude that the maximum force exerted by the gastric antrum is close to 0.65 N and that gastric sieving is impaired by HV meals.

Adult↗
PubMed2001

Effect of meal viscosity and nutrients on satiety, intragastric dilution, and emptying assessed by MRI.

The relationship between the intragastric distribution, dilution, and emptying of meals and satiety was studied using noninvasive magnetic resonance imaging techniques in 12 healthy subjects with four polysaccharide test meals of varying viscosity and nutrient content as follows: 1) low-viscosity nonnutrient, 2) low-viscosity nutrient, 3) high-viscosity nonnutrient, and 4) high-viscosity nutrient. Increasing the nutrient content of the high-viscosity meal delayed gastric emptying from 46 +/- 9 to 76 +/- 6 min (P < 0.004), whereas increasing viscosity had a smaller effect. The volume of secretions within the stomach 60 min after ingestion was higher for the high-viscosity nutrient meal (P < 0.04). A simple model to calculate the total volume of secretion added to the test meal is presented. Color-coded dilution map images showed the heterogeneous process of progressive gastric dilution of high-viscosity meals, whereas low-viscosity meals were uniformly diluted. Fullness was found to be linearly related to total gastric volumes for the nutrient meals (R(2) = 0.98) and logarithmically related for the nonnutrient meals (R(2) = 0.96). Fullness was higher for high- compared with low-viscosity meals (P < 0.02), and with the nutrient meals this was associated with greater antral volumes (P < 0.05).

Adult↗
PubMed2000

Echoplanar imaging in GI clinical practice: assessment of gastric emptying and antral motility in four patients.

Gastric emptying, frequency of antral contractions, and speed of antral contraction propagation were assessed in four patients using echoplanar imaging techniques. The results obtained and their impact on the diagnosis and management of the patients are presented and discussed. This shows that echoplanar evaluation of gastric function is noninvasive, well-tolerated by patients, detects clinically relevant abnormalities, and has the potential of becoming a valuable examination in the clinical gastrointestinal practice.

Adult↗
PubMed2000

Limited exposure of the healthy distal colon to orally-dosed formulation is further exaggerated in active left-sided ulcerative colitis.

BACKGROUND: Active distal ulcerative colitis is often resistant to topically acting oral formulations. We speculated that the left side of the colon is underexposed to orally-dosed topical agents in patients with active distal colitis. METHODS: Twenty-two healthy volunteers (12 males, aged 22-47 years), and 10 patients (6 males, aged 33-73 years) with active left-sided ulcerative colitis ingested a Eudragit-coated gelatine capsule containing 111In-labelled amberlite resin on four successive days. Regional colonic distribution, transit times and percentage of daily dose resident were calculated from the average of four serial gamma camera images on the 4th day. RESULTS: (mean [95% CI]). When compared to controls, patients with colitis had significantly faster total colon transit (24.3 h [9.5-39.1] vs. 51.7 h [41.1-62.3]) as well as faster proximal colon transit (18.7 h [9.1-28.3] vs. 36.7 [28.5-44.9]), and distal colon transit (3.1 h [-0.5 to 6.8] vs. 15.0 h [10.5-19.5]), respectively (all P < 0.01). Material was asymmetrically distributed in health (proximal colon 69% [63-76] vs. distal colon 31% [24-37]). This asymmetry was more extreme in colitis, with corresponding values of 91% [85-96] vs. 9% [4-15]. As a result colitics had less material in the left-sided colon (9% [4-15] vs. 31% [24-37]), P < 0. 001. Colitics had a significantly lower percentage of the daily dose resident within the left side of the colon compared to controls (13% [-2 to 28] vs. 63% [44-81]), P < 0.01. CONCLUSIONS: Delayed release oral formulation is asymmetrically distributed within the colon in health. This asymmetry is exaggerated in active left-sided ulcerative colitis and, together with faster colonic transit, results in reduced exposure of the distal colon to orally-dosed topical agents.

Administration, Oral↗
PubMed2000

Gastric response to increased meal viscosity assessed by echo-planar magnetic resonance imaging in humans.

Normal meals are highly viscous, and viscosity is a key factor in influencing gastric emptying of food. However, the process of meal dilution and mixing is difficult to assess with the use of conventional methods. The aim of this study was to validate an in vivo, novel, noninvasive, echo-planar magnetic resonance imaging (EPI) technique, capable of monitoring the viscosity of a model meal, and to use this to investigate the effects of viscosity on gastric emptying, meal dilution and satiety. Healthy volunteers (n = 8) ingested 500 mL of locust bean gum (0.25, 0.5, 1.0 or 1.5 g/100 g), nonnutrient, liquid meals of varying viscosities, and labeled with a nonabsorbable marker, phenol red. Meal viscosity was calibrated against the water proton transverse relaxation rate (T(2)(-1)) in vitro before ingestion, thus viscosity was measured in vivo via EPI measurements of T(2)(-1). Viscosity and dilution were also measured directly using nasogastric aspirates. Gastric volumes as measured by EPI, fullness, appetite and hunger were also assessed serially. Before ingestion, the log of initial meal viscosity was linearly related to T(2)(-1) (n = 8, r(2) = 0.95). Similarly, T(2)(-1) measured in vivo was also linearly related to the viscosity of the aspirates (r(2) = 0.88). All meals underwent rapid dilution, leading to a reduction in viscosity, which was greatest for the most viscous meal (P < 0.01). Surprisingly, despite the fact that the initial meal viscosity varied 1000-fold, there was only a small delay in gastric emptying (P for trend < 0.05). The area under the curve for satiety increased with initial meal viscosity, whereas that for hunger decreased (P < 0.05). In conclusion, the viscosity of a meal in vivo can be measured noninvasively using EPI. The stomach responds to meal ingestion by rapid intragastric dilution, causing a reduction of meal viscosity, and gastric emptying is minimally delayed. However, increased viscosity is associated with more prolonged satiety.

Adult↗
PubMed2000

Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome.

BACKGROUND AND AIMS: Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. METHODS: Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. RESULTS: In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01). CONCLUSION: Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.

Acute Disease↗
PubMed1999

Problems and challenges in the design of irritable bowel syndrome clinical trials: experience from published trials.

The last two decades have seen many studies that are of inadequate design and power. This report focuses on what we have learned from the 25 randomized, controlled studies that included at least 30 patients during the period 1976-1998. The most important finding has been that the median placebo response was 47% (range, 0-84%), which is approximately three times the size of the difference between placebo and drug response, median 16% (range, -17-64%). This tells us the importance of reassurance and the powerful nonspecific therapeutic effects of entering patients into clinical trials in irritable bowel syndrome (IBS). Patients should be stratified according to the dominant symptoms that are relevant to the drug's intended effect. A randomized, double-blind, controlled, parallel group study appears the most robust design. Minimizing the placebo response reduces the numbers needed to detect a significant difference. The optimum length of trial is probably >3 months, because the placebo effect takes approximately 12 weeks to start to recede. Dose titration should maximize the chance of detecting a benefit.

Clinical Trials as Topic↗
PubMed1999

Esophageal transit of risedronate cellulose-coated tablet and gelatin capsule formulations.

Risedronate sodium is an orally active antiresorptive agent and a member of the pyridinyl class of bisphosphonates. It has been approved for the treatment of Paget's disease of the bone and is under development as a chronic therapy for the treatment and prevention of osteoporosis. A novel cellulose film-coated tablet formulation was developed to optimize esophageal transit of this bisphosphonate. The aim of the present study was to compare the esophageal transit of the film-coated tablet formulation of risedronate with its original gelatin capsule dose form. A total of 25 elderly, healthy volunteers (mean 66 years), who were dysphagia-free, participated in this randomized cross-over study. On separate occasions, volunteers swallowed radiolabeled placebo formulations with 50 ml water. Dynamic images with participants in a sitting position were recorded for 10 min using a gamma camera. Scintigraphic imaging showed a delay in esophageal transit (greater than 15 s) in 28% of patients in the capsule group but in none of the tablet group (P<0.05). The mean transit times of the capsules and tablets were 23.8 and 3.3 s, respectively. Esophageal transit of film-coated tablets was faster than gelatin capsules, suggesting that film-coated tablets would be the appropriate formulation for all pivotal trials with risedronate and for subsequent commercialization.

Aged↗
PubMed1999

Stool water content and colonic drug absorption: contrasting effects of lactulose and codeine.

PURPOSE: By varying stool water content using lactulose and codeine, we investigated the influence of luminal water content on the absorption of quinine, a transcellular probe, and 51Cr-EDTA, a paracellular probe, from the distal gut. METHODS: Sixteen volunteers entered a three-way cross-over trial in which absorption of probe markers from a timed-release delivery system was determined following treatment with lactulose 20 mls tds (increasing water content), or codeine 30 gms qds (decreasing water content), and compared with control untreated values. Stool water content was assessed by freeze drying stool samples. Site of release was determined by gamma scintigraphy, and absorption was measured by plasma levels and urinary recovery of the marker probes. RESULTS: Lactulose accelerated ascending colon transit (3.7 +/- 0.8 vs 4.5 +/- 1.4 hrs, p < 0.05), increased stool water content (75 +/- 2 vs 71 +/- 2%, p < 0.01), caused greater dispersion of released material (dispersion score 3.4 +/- 0.3 vs 1.8 +/- 0.2, p < 0.01), and enhanced absorption of the transcellular probe quinine (4.66 +/- 0.78 vs 3.02 +/- 0.63%, p < 0.05) compared to control. Conversely codeine slowed ascending colon transit (8.9 +/- 1.8 hrs), reduced stool water content (61 +/- 2 vs 71.2%, p < 0.05), and tended to diminish absorption (2.60 +/- 0.77 vs 3.02 +/- 0.63%, p = 0.20). Within the ascending colon specifically, there was a significant trend for treatments increasing luminal water content to enhance quinine absorption (medians: codeine = 1.2%, [n = 81 < control = 2.3%, [n = 5] < lactulose = 3.2%, [n = 71, p < 0.01). Delivery site also had an important influence on absorption, with more distal release resulting in less absorption in the control arm (medians: small intestine = 4.4% [n = 5] > ascending colon = 2.3% [n = 5] > transverse colon = 1.5% [n = 6], p < 0.005). CONCLUSIONS: Lactulose accelerates transit, increases stool water content, and enhances drug absorption from the distal gut whilst codeine slows transit, decreases stool water content, and tends to diminish absorption, compared to controls. We conclude that water content may be an important determinant in colonic drug absorption.

Adult↗
PubMed1999

Regional differences in quinine absorption from the undisturbed human colon assessed using a timed release delivery system.

PURPOSE: To investigate the regional absorption characteristics of the distal gut using two markers of permeability, quinine (a transcellular probe) and 51CrEDTA (a paracellular probe). METHODS: The permeability markers were delivered to the undisturbed gastrointestinal tract in 39 healthy volunteers using an oral timed-release delivery vehicle which allowed pulsed release within a particular site of the gut. Site of release was identified using gamma scintigraphy. Absorption of quinine and 51CrEDTA was assessed by measuring the percent excretion in the urine using HPLC and gamma counting respectively. Serial plasma samples allowed time-concentration curves for quinine to be plotted. RESULTS: There was a significant trend for diminished absorption with more distal delivery of the transcellular probe, quinine, which was: 6.26 +/- 0.87% (small intestine, n = 10); 4.65 +/- 0.93% (ascending colon, n = 16); and 2.59 +/- 0.52% (transverse colon, n = 10) of the ingested dose excreted respectively (p < 0.001). No such gradient was seen with the paracellular marker, 51CrEDTA. CONCLUSIONS: These results suggest that delayed release formulations should aim for release in the distal small bowel and proximal colon if absorption is to be maximised. Absorption by the transcellular route diminishes in the more distal colon, a fact which has implications for delayed or sustained release formulations.

Adult↗
PubMed1999

The DU-MACH study: eradication of Helicobacter pylori and ulcer healing in patients with acute duodenal ulcer using omeprazole based triple therapy.

AIM: To investigate the efficacy of two omeprazole triple therapies for the eradication of Helicobacter pylori, ulcer healing and ulcer relapse during a 6-month treatment-free period in patients with active duodenal ulcer. METHODS: This was a double-blind, randomized study in 15 centres across Canada. Patients (n = 149) were randomized to omeprazole 20 mg once daily (O) or one of two 1-week b. d. eradication regimens: omeprazole 20 mg, metronidazole 400 mg and clarithromycin 250 mg (OMC) or omeprazole 20 mg, amoxycillin 1000 mg and clarithromycin 500 mg (OAC). All patients were treated for three additional weeks with omeprazole 20 mg once daily. Ulcer healing was assessed by endoscopy after 4 weeks of study therapy. H. pylori eradication was determined by a 13C-urea breath test and histology, performed at pre-entry, at 4 weeks after the end of all therapy and at 6 months. RESULTS: The intention-to-treat (intention-to-treat) analysis contained 146 patients and the per protocol (per protocol) analysis, 114 patients. The eradication rates were (intention-to-treat/per protocol): OMC-85% and 92%, OAC-78% and 87% and O-0% (O). Ulcer healing (intention-to-treat) was greater than 90% in all groups. The differences in the eradication and relapse rates between O vs. OMC and O vs. OAC were statistically significant (all, P < 0.001). Treatment was well tolerated and compliance was high. CONCLUSION: The OMC and OAC 1-week treatment regimens are safe and effective for eradication, healing and the prevention of relapse in duodenal ulcer patients.

Acute Disease↗
PubMed1999

Randomized controlled comparison of nitroimidazoles for the eradication of Helicobacter pylori and relief of ulcer-associated and non-ulcer dyspepsia.

BACKGROUND: A combination of omeprazole, clarithromycin and either metronidazole or tinidazole is commonly used for Helicobacter pylori eradication. Metronidazole is considerably cheaper than tinidazole but the two have not previously been compared in a randomized trial. METHODS: One hundred and twenty dyspeptic H. pylori-positive patients with endoscopically defined peptic ulcer [DU (n = 65), GU (n = 12)] or non-ulcer dyspepsia (NUD, n = 43) were randomized to receive a 1-week course of twice daily omeprazole 20 mg, clarithromycin 250 mg and either metronidazole 400 mg (OCM) or tinidazole 500 mg (OCT) in a double-blind fashion. Eradication of H. pylori, safety and side-effects of treatment, dyspeptic symptom score and consumption of antisecretory drugs were assessed at 6 weeks and 1 year after treatment. RESULTS: H. pylori eradication was successfully achieved in 57/60 (95%, ITT analysis) of patients receiving OCT and 58/60 (97%, ITT analysis) receiving OCM. Both regimens had similar side-effect profiles, which accounted for only one patient withdrawal. All patients remained uninfected (as assessed by 14C-urea breath test) at 1-year follow-up, but major symptom improvements and decreased antisecretory drug use were only seen in patients with DU (P<0.0001). CONCLUSIONS: Treatment with OCM is as effective as the more expensive OCT at eradicating H. pylori. H. pylori eradication results in long-term relief of dyspeptic symptoms and reduced antisecretory consumption only in patients with DU, and not in those with NUD.

Adult↗
PubMed1999

The GU-MACH study: the effect of 1-week omeprazole triple therapy on Helicobacter pylori infection in patients with gastric ulcer.

AIMS: To study the efficacy of omeprazole triple therapy in the eradication of Helicobacter pylori in patients with active gastric ulcer, and to assess healing and relapse of gastric ulcer. METHODS: A double-blind, randomized study was carried out in 18 centres in Germany, Hungary and Poland. Patients (n = 160) with gastric ulcer and a positive H. pylori screening test were randomized to a 7-day twice daily treatment with omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1000 mg (OAC) or omeprazole 20 mg, clarithromycin 250 mg and metronidazole 400 mg (OMC), or with omeprazole 20 mg once daily (O). After completion of this 1-week treatment, patients were treated with omeprazole until healing (maximum 12 weeks), and followed for 6 months. H. pylori was assessed by urea breath test (UBT) and histology. RESULTS: Eradication rates ITT were OAC 79% (95% CI: 65-90%), OMC 86% (95% CI: 73-94%) and O 4% (95% CI: 0-14%). Eradication rates PP were OAC 83% (95% CI: 68-93%), OMC 93% (95% CI: 80-98%) and O 3% (95% CI: 0-13%). Gastric ulcer relapses occurred in 5, 0 and 11 patients in the groups, respectively. CONCLUSIONS: The results from the study demonstrate that OMC and OAC 1-week regimens are safe and effective for eradication of H. pylori in gastric ulcer patients, and that ulcer relapse is infrequent after successful eradication.

Adult↗
PubMed1999

Fat delays emptying but increases forward and backward antral flow as assessed by flow-sensitive magnetic resonance imaging.

Flow has been assessed in the gastric antrum using a velocity-sensitive version of the high-speed magnetic resonance imaging technique, echo planar imaging (EPI). Eight healthy volunteers attended fasted on three separate days and consumed 800 mL of either a 5% glucose (0.2 kcal mL-1), 10% glucose (0.4 kcal mL-1) or an isotonic mixed nutrient meal, Fresubin (1 kcal mL-1, 27.2 g fat). Gastric volumes were obtained at 10-min intervals for 1 h. Flow measurements were performed on a single slice through the antropyloric region 5 and 35 min after meal ingestion. Gastric volumes at 45 min were inversely proportional to the calorie density of the meal with (mean +/- SEM) 89 +/- 10%* of the Fresubin, 64 +/- 5%* of the 10% glucose and 41 +/- 5% of the 5% glucose remaining (*P < 0.005 vs 5% glucose). Substantial forward and backward antral flow was observed after all three meals in the initial 5-min imaging period. AT 35 min flow activity was significantly greater after both the high-calorie meals relative to the 5% meal (total number of flow events: Fresubin = 6.6 +/- 1.7,[symbol: see text] 10% glucose = 9.9 +/- 2.2, [symbol: see text] 5% glucose = 2.5 +/- 0.9,[symbol: see text] P < 0.03,[symbol: see text] P < 0.007 vs 5% glucose, n = 8). Peak forward velocities for the initial phase of emptying tended to be greater for the rapidly emptying 5% meal (5.9 +/- 0.8 cm-1) compared with the Fresubin (3.3 +/- 0.6 cm-1, P < 0.069, n = 8) and the 10% glucose (2.9 +/- 1.0 cm-1, P < 0.068, n = 8) meals. In spite of delayed gastric emptying, high-calorie meals were associated with substantial to and fro movements which may be important for meal tritruration and fat emulsification.

Adult↗
PubMed1999

Disturbances in large bowel motility.

Although there is a wide variability in symptoms, disorders of colonic motility are the most prominent features in irritable bowel syndrome (IBS). Stool weight is within the normal range but many patients appear to have abnormal rectal sensations. Straining even with soft stool is common. Dietary fibre stimulates ileocolonic flow and may induce more symptoms in IBS than normal. There is evidence of increased responsiveness of the IBS colon, both to the effect of eating and to stress. Defaecatory disorders are common and may reflect both increased or decreased rectal sensitivity. The normal colon is quiescent during sleep, but in IBS coma sleep is often abnormal, with more periods of arousal and the colon consequently more active. There is evidence of increased responsiveness to corticotrophin releasing factor, which mediates much of the effect of stress on the gut. Many patients show a sympathetic/vagal imbalance with relative excess of sympathetic influence in keeping with increased levels of psychological stress and anxiety. There is undoubtedly more than one cause of IBS and around 25% appear to develop symptoms after an infectious enteritis. This has effects on the entero-endocrine system which may take many years to subside.

Animals↗