PubMed Health⌕ Search

Biomedical subjects

Robin C Spiller

Publications and source records attributed to Robin C Spiller.

At least 19 recordsLinked to original sources

Improved methods for fMRI studies of combined taste and aroma stimuli.

Previous neuroimaging studies of the cortical representation of gustatory and olfactory stimuli have often delivered tastants to the mouth in very small quantities or stimulated olfaction orthonasally. In studies of retro-nasal olfaction, swallowing was generally delayed to reduce head motion artefacts. The present fMRI study aims to improve upon such methodological limitations to allow investigation of the cortical representation of flavour (taste and aroma combination) as it typically occurs during the consumption of liquid foods. For this purpose we used (1) a novel, automated, sprayed stimulus delivery system and a larger volume of liquid sample (containing sweet tastants and banana/pear aroma volatiles) to achieve more extensive stimulation of the oral cavity taste receptors, (2) a pseudo-natural delivery paradigm that included prompt swallowing after each sample delivery to obtain physiological retro-nasal olfactory stimulation, (3) fMRI acquisition with wide brain coverage and double-echo EPI to improve sensitivity. We validated our paradigm for the delivery of volatiles using atmospheric pressure chemical ionisation mass spectrometry. This showed that the main retro-nasal delivery of volatiles in the paradigm occurs immediately after the swallow. Several brain areas were found to be activated, including the insula, frontal operculum, rolandic operculum/parietal lobe, piriform, dorsolateral prefrontal cortex, anterior cingulate cortex, ventro-medial thalamus, hippocampus and medial orbitofrontal cortex.

Adult↗

Abnormalities of serotonin metabolism and their relation to symptoms in untreated celiac disease.

BACKGROUND AND AIMS: Serotonin (5-hydroxytryptamine [5-HT]) is a key modulator of gut function that in excess causes nausea, vomiting, and diarrhea. We recently showed that patients with post-infective irritable bowel syndrome have increased postprandial release of 5-HT associated with low-grade T-cell mediated inflammation. Celiac disease is another common disease in which a T-cell enteropathy is associated with increased mucosal 5-HT levels. Our aim was to determine how this inflammatory lesion influenced 5-HT bioavailability and how changes in 5-HT related to the symptoms of nausea, vomiting, and diarrhea seen in untreated celiac patients. METHODS: Fasting plasma and platelet 5-HT and postprandial plasma 5-HT levels were measured after a high-carbohydrate meal in celiac patients (n = 18) and healthy controls (n = 18) using high-pressure liquid chromatography. Dyspepsia was assessed during the postprandial period using a questionnaire. Finally, we compared the histology and mucosal 5-HT levels in duodenal biopsy specimens from celiac patients and controls. RESULTS: Celiac patients had increased 5-HT-containing enterochromaffin cell numbers and significantly higher peak plasma 5-HT levels (P = .0002), postprandial area under the curve (P = .0006), and platelet 5-HT stores (P = .031) than controls. Peak 5-HT levels correlated significantly with postprandial dyspepsia scores (P = .005). Celiac patients had higher duodenal 5-HT levels (P = .007) than controls. CONCLUSIONS: Celiac disease is associated with increased mucosal 5-HT content and enhanced 5-HT release from the upper small bowel, which correlates with postprandial dyspepsia. Serotonin excess may mediate dyspeptic symptoms in untreated celiac disease.

Adolescent↗

Esophageal transit of the weekly film-coated risedronate (Actonel) placebo tablet in subjects with Kyphosis.

Risedronate sodium is a pyridinyl bisphosphonate of proven effectiveness for the treatment and prevention of osteoporosis and Paget's disease of the bone. The aim of this study was to compare the esophageal transit and gastric emptying of the placebo film-coated risedronate tablet when taken with 50 or 120 mL of water in subjects with Kyphosis. A total of 23 patients with radiologically documented osteoporosis participated in a single-center, open-label, crossover gamma scintigraphy study. The mean esophageal transit times were 15.6 s (50 mL) and 12.0 s (120 mL) and the mean gastric emptying half-times were 20.5 min (50 mL) and 14.3 min (120 mL). There was no relationship between the degree of Kyphosis measured from lateral standing radiographs and the esophageal transit time. This study demonstrated that even when taken with a minimal volume of water the esophageal transit and gastric emptying of the film-coated 35 mg weekly risedronate placebo tablet was similar in kyphotic subjects to previously obtained results from healthy control subjects.

Administration, Oral↗

Functional bowel disorders.

Employing a consensus approach, our working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations. Diagnosis of a functional bowel disorder (FBD) requires characteristic symptoms during the last 3 months and onset > or =6 months ago. Alarm symptoms suggest the possibility of structural disease, but do not necessarily negate a diagnosis of an FBD. Irritable bowel syndrome (IBS), functional bloating, functional constipation, and functional diarrhea are best identified by symptom-based approaches. Subtyping of IBS is controversial, and we suggest it be based on stool form, which can be aided by use of the Bristol Stool Form Scale. Diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. Treatment of FBDs is based on an individualized evaluation, explanation, and reassurance. Alterations in diet, drug treatment aimed at predominant symptoms, and psychotherapy may be beneficial.

Constipation↗

Magnetic resonance imaging of the behaviour of oil-in-water emulsions in the gastric lumen of man.

Pre-processed foods often contain a high percentage of lipid, present as emulsions stabilised with various surface-active agents. The acidic gastric environment can affect the behaviour of such emulsions, modifying the lipid spatial distribution and, in turn, the rate of gastric emptying and nutrient delivery to the gut. The aim of the present study was to use echo-planar magnetic resonance imaging (EPI) to determine the behaviour of model olive oil emulsions during gastric processing. Six healthy male volunteers were intubated nasogastrically on two separate occasions and fed 500 ml 15 % (w/w) olive oil-in-water, surfactant-stabilised emulsions designed to have identical droplet size distribution and which were either stable or unstable under gastric acid conditions. EPI was used to assess the oil fraction of the intragastric emulsions, gastric emptying and to visualise the spatial distribution of the oil at 10, 30 and 50 min postprandially. The in vivo imaging measurements of the oil volume fraction of the emulsions correlated well (r 0.66, acid-stable; r 0.52, acid-unstable) with that assayed in the gastric aspirates. Compared with the acid-stable emulsion, the acid-unstable emulsion in the gastric lumen rapidly separated into lipid-depleted 'aqueous' and lipid layers. Phase separation in the acid-unstable meal allowed the oil-depleted component to empty first and more rapidly than the stable emulsion as determined by the gastric emptying curves. These pilot data suggest that gastric processing and emptying of high-fat foods could be manipulated by careful choice of emulsifier.

Adult↗

Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes.

OBJECTIVES: Irritable bowel syndrome (IBS) is a heterogeneous condition and defined according to symptoms. Low-grade inflammation has been associated with IBS, particularly that following infection, but whether altered intestinal permeability profiles relate to irritable bowel subtype or onset is uncertain. Our aim was to compare small and large intestinal permeability in various subtypes of IBS to healthy controls. METHODS: Intestinal permeability was measured using 1.8 MBq of 51Cr-EDTA and collecting urine over 24 h; Study 1: patients with diarrhea-predominant postinfectious IBS (N=15), constipation-predominant IBS (N=15), and healthy controls (N=15); Study 2: two groups of diarrhea-predominant IBS (D-IBS), one with a history of onset after acute gastroenteritis (postinfectious) (N=15) and the other without such a history (nonpostinfectious) (N=15) both compared with healthy controls (N=12). RESULTS: Permeability expressed as percentage of total dose excreted in urine (median [inter-quartile range]). Study 1: Proximal small intestinal permeability was increased in postinfectious IBS (0.19 [0.12-0.23]) in contrast to constipated IBS (0.085 [0.043-0.13]) and controls (0.07 [0.035-0.19]) (p=0.02). IBS patients with eczema, asthma, or hayfever had increased proximal small intestinal permeability compared with IBS patients without atopy (p=0.02). Study 2: Small intestinal permeability was greater in nonpostinfectious diarrhea-predominant IBS (0.84 [0.69-1.49]) compared with postinfectious IBS (0.43 [0.29-0.63], p=0.028) or controls (0.27 [0.2-0.39]), p=0.001). CONCLUSIONS: Small intestinal permeability is frequently abnormal in diarrhea-predominant IBS. Those without a history of infectious onset appear to have a more severe defect.

Adolescent↗

Irritable bowel syndrome.

Irritable bowel syndrome (IBS) is one of the most common 'functional' gastrointestinal disorders accounting for 3% of all primary care consultations, with a strong female predominance. Although most of the literature comes from Western industrialized societies, when it has been looked for, this disorder appears to be equally common in the Third World. It is characterized by chronic abdominal pain or discomfort associated with disordered bowel habit and visceral hypersensitivity. Anxiety and somatization are more common in IBS than in the general population and may encourage consultation; however, they correlate poorly with symptoms. Bacterial gastroenteritis may be followed by the development of IBS in 5-10% of patients, depending on the severity of initial illness and prior anxiety or depression. The Rome criteria allow reliable diagnosis provided that there are no 'alarm' features which mandate further investigation. Microscopic colitis and bile salt malabsorption can easily be mistaken for IBS, as can chronic infestations or infections which should be considered, while recognizing that these are extremely uncommon in westernized societies. Some patients respond to exclusion diets as lactose and wheat intolerance are common. Others with prominent anxiety and/or depression respond to psychotherapy or antidepressants. Diarrhoeal symptoms respond to loperamide and 5HT3 receptor antagonists, while constipation responds to 5HT4 agonists. Antispasmodics may have limited benefit in treating pain. Low-dose tricyclic antidepressants are also helpful in alleviating pain and anxiety, even in those without obvious psychiatric disorders. If diagnostic criteria are met, then once diagnosed, new diagnoses rarely appear.

Diagnosis, Differential↗

Monitoring of gallbladder and gastric coordination by EPI.

PURPOSE: To assess for the first time the potential of echo-planar magnetic resonance imaging (EPI) for measuring simultaneously both gallbladder and gastric emptying. MATERIALS AND METHODS: Eight healthy subjects ingested 500 mL of an acid-stable liquid test meal containing 15% olive oil and flavoring. Every 20 minutes for three hours thereafter, a rapid EPI multislice set was acquired across the whole abdomen, using a dedicated whole-body 0.5-T EPI scanner. RESULTS: The bile in the gallbladder and the test meal in the stomach appeared bright in the EPI images, aiding localization and region of interest analysis. We measured the gallbladder emptying curve and fitted the data to a simple analytical model. The mean fasted gallbladder volume was 25 +/- 4 mL, comparable to previously published MRI and ultrasound values. Gastric emptying data fitted well to a linear model linear (R2 = 0.99), and we observed an exponential (R2 = 0.98) relationship between gallbladder and gastric volumes for the first 90 minutes. CONCLUSION: This study shows the potential of EPI to monitor simultaneously and noninvasively the emptying of the gallbladder and of the gastric lumen. No contrast enhancing agents are needed. This method could overcome the limitations of previous gamma scintigraphy and ultrasound techniques.

Echo-Planar Imaging↗

Gallbladder contraction, gastric emptying and antral motility: single visit assessment of upper GI function in untreated celiac disease using echo-planar MRI.

PURPOSE: To assess gallbladder contraction, gastric emptying, and antral motility in untreated celiac patients and healthy controls using a single MRI examination. MATERIALS AND METHODS: Gallbladder emptying, gastric emptying, and antral motility were measured in 15 celiac patients and 15 age/sex-matched healthy controls following a 323-kcal test meal using EPI techniques. Postprandial dyspepsia scores were recorded on a questionnaire. RESULTS: Fasting gallbladder volume (P=0.01) and the volume of bile ejected postprandially (P=0.014) were increased in celiacs. Gastric emptying tended to be slower in celiacs (P=0.142). Three celiac patients with severe postprandial dyspepsia and total villous atrophy had pathologically delayed gastric emptying and increased fasting gallbladder volume. Antral contractions were absent in five out of 14 patients (36%) five minutes after the meal, but in none of 10 volunteers in whom the antrum could be visualized (P=0.128). CONCLUSION: This study shows that using MRI, multiple parameters related to upper gastrointestinal function in celiac disease can be measured in a single noninvasive study, whereas previously three separate visits would have been required. Celiacs have increased fasting gallbladder volumes and tend to have slower gastric emptying.

Adolescent↗

Potential future therapies for irritable bowel syndrome: will disease modifying therapy as opposed to symptomatic control become a reality?

Irritable bowel syndrome can remit spontaneously, implying cure is possible. Predictors of good prognosis include a short history, acute onset(possibly postinfective origin), absence of psychological disorders, and resolution of chronic life stressors. Possible-disease modifying treatments with long-lasting effects include diet and anti-inflammatory and psychological treatments. Dietary modifications, which often involve excluding dairy and wheat products, are successful in some patients. Anti-inflammatory treatments have been subjected to one RCT in postinfective IBS without benefit. Probiotics may have benefit in altering bacterial flora and as anti-inflammatory agents, but further trials are needed before they can be recommended. Psychological treatments may produce long-lasting responses. Relaxation therapy appears to have a nonspecific benefit. Psychotherapy has been shown to have long-term benefit and is particularly acceptable to, and effective for, those with overt psychological distress. Hypnotherapy has been shown to be effective in randomized placebo controlled trials and has a sustained effect.

Antidepressive Agents↗

Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.

BACKGROUND & AIMS: 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists improve symptoms in patients with diarrhea-predominant irritable bowel syndrome (D-IBS), 5-HT 4 agonists help those with constipation-predominant IBS (C-IBS). These data suggest excess or deficiency in 5-HT in D-IBS or C-IBS, respectively. Mucosal 5-HT-containing enterochromaffin cells (EC) are increased in postinfectious IBS (PI-IBS). Our aim was to define the postprandial release of 5-HT in PI-IBS and C-IBS patients and to relate this to mucosal 5-HT turnover. METHODS: Fifteen PI-IBS patients with diarrhea-predominant symptoms, 15 C-IBS patients, and 15 healthy controls underwent serial (platelet-poor) plasma 5-HT measurement for 3 hours after a standard 520-kcal meal. Rectal biopsy specimens were assayed for 5-HT and its metabolite 5-hydroxindoleacetic acid (5-HIAA). Colonic transit was measured using radio-opaque markers. RESULTS: Colonic transit was prolonged in C-IBS patients (mean +/- SEM) (49.4 +/- 3.8 h) compared with PI-IBS (26.7 +/- 4.5) and control patients (34.1 +/- 4.5) ( P < .02). Release of 5-HT assessed by area under the curve (AUC) of platelet-poor plasma 5-HT from 0 to 180 minutes postprandially was significantly lower in C-IBS patients (2593 +/- 309 mmol/L . min) compared with P-IBS (5623 +/- 721) and control patients (4822 +/- 598) ( P < .001). PI-IBS patients showed significantly higher peak postprandial plasma 5-HT values (median, range) (71.7, 43.4-125.3) ng/L compared with C-IBS patients (31.2, 15.2-40.5) and control patients (43.6, 26.7-50.1) ( P < .01). Mucosal 5-HT turnover as assessed by mucosal 5-HIAA/5-HT ratio was decreased in both C-IBS and PI-IBS patients, .14 (.01-.6) and .21 (.02-2.5), respectively, compared with control patients 1.12 (.17-3.1) ( P < .002). CONCLUSIONS: C-IBS patients show impaired postprandial 5-HT release whereas PI-IBS patients have higher peak levels, abnormalities that may be related to their different symptoms.

Adult↗

Information assimilation and distribution challenges and goals for real and virtual journals.

The distribution of biomedical information was transfigured over three centuries ago with the introduction of scientific journals. This enabled the widespread dissemination of data to global audiences and greatly facilitated not only the advance of science but amplified the interaction between investigators despite their different locations. This process continued to expand in a linear fashion prior to the emergence of the Internet. The latter system has prompted a phenomenal augmentation of information accessibility, and its ever-expanding use has resulted in an exponential increase in the demand for digital technology and online resources. This technology has achieved unprecedented acceptance in the scientific domain and enabled publishers to expeditiously produce and distribute journal contents online. Such unparalleled access to information has sparked incendiary debate within the scientific community and among journal publishers in regard to numerous issues. It is thus much debated as to who has the right to "own" or control intellectual property, whether information should be made freely available to the online global community, how to gauge the legitimacy and authenticity of published research, and the need to reexamine the feasibility and profitability of paper journals in consideration of the digital, online formats that continue to gain popularity. To assess the current status of the situation, a meeting of journal editors, research scientists, and publishing executives was held in Constance, Germany, on June 26, 2004, to discuss these issues and formulate strategies and recommendations for the future of biomedical publishing. Herewith we provide a summation (manifesto) of the meeting's proceedings and provide a consensus opinion with the aim of illuminating the subject and also proposing some putative solutions for the major challenges that currently confront the scientific and publishing community.

Forecasting↗

In vivo imaging of intragastric gelation and its effect on satiety in humans.

Previous studies indicated that physical characteristics of food influence satiety, but the relative importance of the oral, gastric, and intestinal behaviors of the food is unclear. The aim of this study was to investigate the satiating effects of 2 types of alginates, which gel weakly or strongly on exposure to acid, compared with guar gum whose viscosity is unaffected by acid. Subjects (n = 12; 3 men, 9 women) ingested a 325-mL sweetened, milk-based meal replacer beverage on 4 separate occasions, either alone as a control or including 1% by weight alginate or guar gum. Intragastric gelling, gastric emptying, and meal dilution were assessed by serial MRI while satiety was recorded for 4 h. MR images showed that all of the meals became heterogeneous in the stomach except for guar, which remained homogeneous. The alginate meals formed lumps in the stomach, with the strong-gelling alginate producing the largest volume. Although gastric emptying was similar for all 4 meals, the sense of fullness at the same gastric volume was significantly greater for all 3 viscous meals than for the control. Compared with the control meal, the strong-gelling alginate (P = 0.031) and guar (P = 0.041) meals increased fullness at 115 min, and the strong-gelling alginate decreased hunger by the 115-min (P = 0.041) and 240-min (P = 0.041) time points. Agents that gel on contact with acid may be useful additions to weight-reducing diets. We hypothesize that this effect is due to distension in the gastric antrum and/or altered transport of nutrients to the small intestine in the lumps.

Adult↗

Age-related decline in rectal mucosal lymphocytes and mast cells.

BACKGROUND: Previous studies have shown that irritable bowel syndrome declines with age and is more common in women. Recent reports suggest that some diarrhoea predominant irritable bowel syndrome patients have low-grade inflammation with increased numbers of mucosal T lymphocytes, 5-hydroxytryptamine (5-HT) containing enteroendocrine cells and mast cells. OBJECTIVE: To determine whether there are age or gender-related changes in mucosal T lymphocytes, mast cells or enteroendocrine cells which might explain these findings. METHODS: Forty healthy volunteers (20 subjects below 55 years of age and 20 above 55 years) free from gastro-intestinal symptoms or disease answered detailed bowel symptom questionnaires and underwent sigmoidoscopy, rectal biopsy and colonic transit measurement. Biopsies were immunostained and quantified for lamina propria and intra-epithelial T lymphocytes, mast cells and 5-HT and peptide YY enteroendocrine cells. RESULTS: There was a reduction in lamina propria T lymphocyte counts (P = 0.018), crypt intra-epithelial T lymphocytes (P = 0.014) and mast cells (P = 0.02) in the > 55 year group. Enteroendocrine cell numbers did not decline with age and were not related to colonic transit. There were no gender differences between any of the cells quantified. CONCLUSIONS: Lymphocyte and mast cell numbers decline with age in normal large bowel mucosa. Reduced numbers of mucosal inflammatory cells may influence the low-grade inflammatory response to luminal antigens and contribute to the reduction of irritable bowel syndrome observed in older subjects.

Adult↗

Postinfectious irritable bowel syndrome.

A small but significant subgroup of patients with irritable bowel syndrome (IBS) report a sudden onset of their IBS symptoms after a bout of gastroenteritis. Population-based surveys show that although a history of neurotic and psychologic disorders, pain-related diseases, and gastroenteritis are all risk factors for developing IBS, gastroenteritis is the most potent. More toxigenic organisms increase the risk 11-fold, as does an initial illness lasting more than 3 weeks. Hypochondriasis and adverse life events double the risk for postinfective (PI)-IBS and may account for the increased proportion of women who develop this syndrome. PI-IBS is associated with modest increases in mucosal T lymphocytes and serotonin-containing enteroendocrine cells. Animal models and some preliminary human data suggest this leads to excessive serotonin release from the mucosa. Both the histologic changes and symptoms in humans may last for many years with only 40% recovering over a 6-year follow-up. Celiac disease, microscopic colitis, lactose intolerance, early stage Crohn's disease, and bile salt malabsorption should be excluded, as should colon cancer in those over the age of 45 years or in those with a positive family history. Treatment with Loperamide, low-fiber diets, and bile salt- binding therapy may help some patients. Serotonin antagonists are logical treatments but have yet to be evaluated.

Bacterial Infections↗

Gastric juice, gastric tissue and blood antibiotic concentrations following omeprazole, amoxicillin and clarithromycin triple therapy.

BACKGROUND: Amoxicillin and clarithromycin are key antibiotics in proton pump inhibitor-based Helicobacter pylori eradication therapies. AIMS: To study gastric mucus and tissue concentrations and collect basic data about optimal antibacterial doses. METHODS: Plasma, gastric mucosa and gastric juice antibiotic concentrations were measured following either low- or high-dose amoxicillin (750 or 1000 mg b.i.d.) and clarithromycin (400 or 500 mg b.i.d.) given in combination with omeprazole 20 mg bid to 12 male volunteers in an open crossover design. Gastric juice and mucosal biopsy collection was performed either 2 (n=6) or 6 hours (n=6) after dosing. RESULTS: Amoxicillin concentrations 2 hours after high dosage were gastric juice > gastric body > antral mucosa > plasma. At 6 hours, plasma and gastric juice concentrations were still above the MIC for amoxicillin-susceptible bacteria but no antibiotic was detectable in mucosa samples. Clarithromycin concentrations after high dosage were gastric juice > mucosa > serum; all above the MIC for clarithromycin-susceptible bacteria at both 2 and 6 hours. CONCLUSIONS: Both dosage regimens provided effective antibiotic concentrations in gastric juice at 2 hours. After dosing, both antibiotics demonstrated high gastric tissue concentrations via local diffusion while clarithromycin also provided sustained delivery (6 hours) via gastric mucosa penetration.

Adult↗