Mechanisms underlying the laxative effect of lactulose: A randomized placebo-controlled trial showing increased small bowel water and motility unaltered by the 5-HT3 receptor antagonist, ondansetron.

BACKGROUND: Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti-diarrheal actions of ondansetron. METHODS: A double-blind, randomized, placebo-controlled crossover study of the effect of ondansetron 8 mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6 h after a meal. Participants then received lactulose 13.6 g twice daily and study drug for a further 36 h. On Day 3, they had further serial MRI scans for 4 h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content. KEY RESULTS: Lactulose increased area under the curve (AUC) of SBWC from 0 to 240 min, mean difference 14.2 L · min (95% CI 4.1, 24.3), p = 0.009, and substantially increased small bowel motility after 4 h (mean (95% CI) 523 (457-646) a.u. to 852 (771-1178) a.u., p = 0.007). There were no changes in T1AC after 36 h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose. CONCLUSION & INFERENCES: Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti-diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.

Demonstration of differences in colonic volumes, transit, chyme consistency, and response to psyllium between healthy and constipated subjects using magnetic resonance imaging.

BACKGROUND: In functional gastrointestinal disorders a lack of objective biomarkers limits evaluation of underlying mechanisms. We aimed to demonstrate the utility of magnetic resonance imaging for this task using psyllium, an effective constipation treatment, in patients and controls. METHODS: Two crossover studies: (i) adults without constipation (controls, n = 9) took three treatments in randomized order for 6 days - maltodextrin (placebo), psyllium 3.5 g t.d.s and 7 g t.d.s., (ii) adults with chronic constipation (patients, n = 20) took placebo and psyllium 7 g t.d.s. for 6 days. MRI was performed fasting and postprandially on day 6. Measurements included small bowel and ascending colon water content, colonic volume, transit time, and MR relaxometry (T1, T2) to assess colonic chyme. Stool water percentage was measured. RESULTS: 7 g psyllium t.d.s. increased fasting colonic volumes in controls from median 372 mL (IQR 284-601) to 578 mL (IQR 510-882), and in patients from median 831 mL (IQR 745-934) to 1104 mL (847-1316), P < .05. Mean postprandial small bowel water was higher in controls and patients after 7 g psyllium t.d.s. vs placebo. Whole gut transit was slower in patients than controls (P < .05). T1 of the descending colon chyme (fasting) was lower in patients (213 ms, 176-420) than controls (440 ms, 352-884, P < .05) on placebo, but increased by 7 g psyllium t.d.s. (590 ms, 446-1338), P < .001. Descending colon T1 correlated with baseline stool water content and stool frequency on treatment. CONCLUSIONS AND INFERENCES: MRI measurements can objectively demonstrate the mode of action of therapy targeting intestinal fluid content in constipation.

Cortical differences in diverticular disease and correlation with symptom reports.

BACKGROUND: Recent studies have shown that the brain of patients with gastrointestinal disease differ both structurally and functionally from that of controls. Highly somatizing diverticular disease (HSDD) patients were also shown to differ from low somatizing (LSDD) patients functionally. This study aimed to investigate how they differed structurally. METHODS: Four diseases subgroups were studied in a cross-sectional design: 20 patients with asymptomatic diverticular disease (ADD), 18 LSDD, 16 HSDD, and 18 with irritable bowel syndrome. We divided DD patients into LSDD and HSDD using a cutoff of 6 on the Patient Health Questionnaire 12 Somatic Symptom (PHQ12-SS) scale. All patients underwent a 1-mm isotropic structural brain MRI scan and were assessed for somatization, hospital anxiety, depression, and pain catastrophizing. Whole brain volumetry, cortical thickness analysis and voxel-based morphometry were carried out using Freesurfer and SPM. KEY RESULTS: We observed decreases in gray matter density in the left and right dorsolateral prefrontal cortex (dlPFC), and in the mid-cingulate and motor cortex, and increases in the left (19, 20) and right (19, 38) Brodmann Areas. The average cortical thickness differed overall across groups (P = .002) and regionally: HSDD > ADD in the posterior cingulate cortex (P = .03), HSDD > LSDD in the dlPFC (P = .03) and in the ventrolateral PFC (P < .001). The thickness of the anterior cingulate cortex and of the mid-prefrontal cortex were also found to correlate with Pain Catastrophizing (Spearman's ρ = 0.24, P = .043 uncorrected and Spearman's ρ = 0.25, P = .03 uncorrected). CONCLUSION & INFERENCES: This is the first study of structural gray matter abnormalities in diverticular disease patients. The data show brain differences in the pain network.

MRI assessment of the postprandial gastrointestinal motility and peptide response in healthy humans.

BACKGROUND: Feeding triggers inter-related gastrointestinal (GI) motor, peptide and appetite responses. These are rarely studied together due to methodological limitations. Recent MRI advances allow pan-intestinal, non-invasive assessment of motility in the undisturbed gut. This study aimed to develop a methodology to assess pan-intestinal motility and transit in a single session using MRI and compare imaging findings to GI peptide responses to a test meal and symptoms in a healthy volunteer cohort. METHODS: Fifteen healthy volunteers (29.3±2.7 years and BMI 20.1±1.2 kg m-2 ) underwent baseline and postprandial MRI scans, symptom questionnaires, and blood sampling (for subsequent GI peptide analysis, Glucagon-like peptide-1 [GLP-1], Polypeptide YY [PYY], Cholecystokinin [CCK]) at intervals for 270 minutes following a 400 g soup meal (204 kcal, Heinz, UK). Gastric volume, gall bladder volume, small bowel water content, small bowel motility, and whole gut transit were measured from the MRI scans. KEY RESULTS: (mean±SEM) Small bowel motility index increased from fasting 39±3 arbitrary units (a.u.) to a maximum of 87±7 a.u. immediately after feeding. PYY increased from fasting 98±10 pg mL-1 to 149±14 pg mL-1 at 30 minutes and GLP-1 from fasting 15±3 µg mL-1 to 22±4 µg mL-1 . CCK increased from fasting 0.40±0.06 pmol mL-1 to 0.94±0.1 pmol mL-1 . Gastric volumes declined with a T1/2 of 46±5 minute and the gallbladder contracted from a fasting volume of 19±2 mL-1 to 12±2 mL-1 . Small bowel water content increased from 39±2 mL-1 to 51±2 mL-1 postprandial. Fullness VAS score increased from 9±5 mm to 41±6 mm at 30 minutes postprandial. CONCLUSIONS AND INFERENCES: The test meal challenge was effective in inducing a change in MRI motility end-points which will improve understanding of the pathophysiological postprandial GI response.

Randomised clinical trial: mesalazine versus placebo in the prevention of diverticulitis recurrence.

BACKGROUND: Previous studies have reached conflicting conclusions regarding the efficacy of mesalazine in the prevention of recurrent diverticulitis. AIM: To investigate the efficacy and safety of mesalazine granules in the prevention of recurrence of diverticulitis after acute uncomplicated diverticulitis. METHODS: Two phase 3, randomised, placebo-controlled, double-blind multicentre trials (SAG-37 and SAG-51) investigated mesalazine granules in patients with prior episodes (<6 months) of uncomplicated left-sided diverticulitis. Patients were randomised to receive either 3 g mesalazine once daily or placebo (SAG-37, n=345) or to receive either 1.5 g mesalazine once daily, 3 g once daily or placebo for 96 weeks (SAG-51, n=330). The primary endpoint was the proportion of recurrence-free patients during 48 weeks (SAG-37 and SAG-51) or 96 weeks (SAG-51) of treatment. RESULTS: Mesalazine did not increase the proportion of recurrence-free patients over 48 or 96 weeks compared to placebo. In SAG-37, the proportion of recurrence-free patients during 48 weeks was 67.9% with mesalazine and 74.4% with placebo (P=.226). In SAG-51, the proportion of recurrence-free patients over 48 weeks was 46.0% with 1.5 g mesalazine, 52.0% with 3 g mesalazine and 58.0% with placebo (P=.860 for 3 g mesalazine vs placebo) and over 96 weeks 6.9%, 9.8% and 23.1% respectively (P=.980 for 3 g mesalazine vs placebo). Patients with only one diverticulitis episode in the year prior to study entry had a lower recurrence risk compared to >1 episode. Safety data revealed no new adverse events. CONCLUSION: Mesalazine was not superior to placebo in preventing recurrence of diverticulitis.

Assessment of motion of colonic contents in the human colon using MRI tagging.

BACKGROUND: We have previously reported a non-invasive, semi-automated technique to assess motility of the wall of the ascending colon (AC) using Magnetic Resonance Imaging. This study investigated the feasibility of using a tagged MRI technique to visualize and assess the degree of flow within the human ascending colon in healthy subjects and those suffering from constipation. METHODS: An open-labeled study of 11 subjects with constipation and 11 subjects without bowel disorders was performed. MRI scans were acquired fasted, then 60 and 120 minutes after ingestion of a 500 mL macrogol preparation. The amount of free fluid in the small and large bowel was assessed using a heavily T2-weighted MRI sequence. The internal movement of the contents of the AC was visualized using a cine tagged MRI sequence and assessed by a novel analysis technique. Comparisons were made between fasting and postprandial scans within individuals, and between the constipation and control groups. KEY RESULTS: Macrogol significantly increased the mobile, MR visible water content of the ascending colon at 60 minutes postingestion compared to fasted data (controls P=.001, constipated group P=.0039). The contents of the AC showed increased motion in healthy subjects but not in the constipated group with significant differences between groups at 60 minutes (P<.002) and 120 minutes (P<.003). CONCLUSIONS AND INFERENCES: This study successfully demonstrated the use of a novel MRI tagging technique to visualize and assess the motion of ascending colon contents following a 500 mL macrogol challenge. Significant differences were demonstrated between healthy and constipated subjects.

Anticipation of thermal pain in diverticular disease.

BACKGROUND: The relative importance of peripheral nerve injury or central pain processing in painful diverticular disease (DD) is unclear. Functional magnetic resonance imaging (fMRI) has demonstrated that dysfunctional central pain processing predominates in irritable bowel syndrome (IBS). This study aims to identify anticipatory changes in symptomatic DD (SDD) compared to asymptomatic DD (ADD) and IBS patients. METHODS: Gastrointestinal symptoms and somatization were evaluated via the Patient Health Question-12 Somatic Symptom and the SDD group divided into low (≤6 [LSDD]) and high (≥7 [HSDD]) somatization. Cued painful cutaneous thermal stimuli were delivered to the left hand and foot during fMRI. Fixed effect group analysis of the 'cued' anticipatory phase was performed. KEY RESULTS: Within the right posterior insula, greater deactivation was found in the ADD compared to other groups. In emotion processing centers, anterior and middle insula, greater activation was identified in all patient compared to the ADD group, and in LSDD compared to IBS and HSDD groups. In comparison, amygdala deactivation was greater in ADD than the IBS and HSDD groups, and in LSDD vs HSDD groups. Descending nociceptive control centers, such as the superior medial frontal and orbitofrontal cortex, also showed greater deactivation in the ADD and LSDD compared to the HSDD and IBS groups. CONCLUSIONS & INFERENCES: The HSDD group have altered anticipatory responses to thermal pain, similar to IBS group. The LSDD are similar to ADD group. This suggests underlying differences in pain pathophysiology, and the need for individualized treatment strategies to target the cause of their chronic pain.

Colonic response to laxative ingestion as assessed by MRI differs in constipated irritable bowel syndrome compared to functional constipation.

BACKGROUND: Functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) share many symptoms but underlying mechanisms may be different. We have developed a magnetic resonance imaging (MRI) technique to measure intestinal volumes, transit, and motility in response to a laxative, Moviprep(®) . We aim to use these biomarkers to study the pathophysiology in IBS-C and FC. METHODS: Twenty-four FC and 24 IBS-C were studied. Transit was assessed using the weighted average position score (WAPS) of five MRI marker pills, taken 24 h before MRI scanning. Following baseline scan, participants ingested 1 L of Moviprep(®) followed by hourly scans. Magnetic resonance imaging parameters and bowel symptoms were scored from 0 to 4 h. KEY RESULTS: Weighted average position score for FC was 3.6 (2.5-4.2), significantly greater than IBS-C at 2.0 (1.5-3.2), p = 0.01, indicating slower transit for FC. Functional constipation showed greater fasting small bowel water content, 83 (63-142) mL vs 39 (15-70) mL in IBS-C, p < 0.01 and greater ascending colon volume (AC), 314 (101) mL vs 226 (71) mL in IBS-C, p < 0.01. FC motility index was lower at 0.055 (0.044) compared to IBS-C, 0.107 (0.070), p < 0.01. Time to first bowel movement following ingestion of Moviprep(®) was greater for FC, being 295 (116-526) min, compared to IBS-C at 84 (49-111) min, p < 0.01, and correlated with AC volume 2 h after Moviprep(®) , r = 0.44, p < 0.01. Using a cut-off >230 min distinguishes FC from IBS-C with low sensitivity of 55% but high specificity of 95%. CONCLUSION & INFERENCES: Our objective MRI biomarkers allow a distinction between FC and IBS-C.

Colon wall motility: comparison of novel quantitative semi-automatic measurements using cine MRI.

BACKGROUND: Recently, cine magnetic resonance imaging (MRI) has shown promise for visualizing movement of the colonic wall, although assessment of data has been subjective and observer dependent. This study aimed to develop an objective and semi-automatic imaging metric of ascending colonic wall movement, using image registration techniques. METHODS: Cine balanced turbo field echo MRI images of ascending colonic motility were acquired over 2 min from 23 healthy volunteers (HVs) at baseline and following two different macrogol stimulus drinks (11 HVs drank 1 L and 12 HVs drank 2 L). Motility metrics derived from large scale geometric and small scale pixel movement parameters following image registration were developed using the post ingestion data and compared to observer grading of wall motion. Inter and intra-observer variability in the highest correlating metric was assessed using Bland-Altman analysis calculated from two separate observations on a subset of data. KEY RESULTS: All the metrics tested showed significant correlation with the observer rating scores. Line analysis (LA) produced the highest correlation coefficient of 0.74 (95% CI: 0.55-0.86), p < 0.001 (Spearman Rho). Bland-Altman analysis of the inter- and intra-observer variability for the LA metric, showed almost zero bias and small limits of agreement between observations (-0.039 to 0.052 intra-observer and -0.051 to 0.054 inter-observer, range of measurement 0-0.353). CONCLUSIONS & INFERENCES: The LA index of colonic motility derived from cine MRI registered data provides a quick, accurate and non-invasive method to detect wall motion within the ascending colon following a colonic stimulus in the form of a macrogol drink.

Magnetic resonance imaging to evaluate gastrointestinal function.

Magnetic resonance imaging of gastrointestinal (GI) function has advanced substantially in the last few years. The ability to obtain high resolution images of the undisturbed bowel with tunable tissue contrast and using no ionizing radiation are clear advantages, particularly for children and women of reproductive age. Barriers to diffusion in clinical practice so far include the need to demonstrate clinical value and the burden of data processing. Both difficulties are being addressed and the technique is providing novel insights into both upper and lower GI disorders of function at an ever increasing rate.

A meta-analysis of immunogenetic Case-Control Association Studies in irritable bowel syndrome.

BACKGROUND: To date, genetic-association studies of single nucleotide polymorphisms (SNP) in selected candidate genes with the symptom phenotype of irritable bowel syndrome (IBS) have typically involved hundreds to 2000 patients. SNPs in immune-related genes, such as cytokine and cytokine receptor encoding genes, have been reported to associate with IBS risk. METHODS: We conducted two independent case-control studies on 16 SNPs in IL1R1, IL4, IL6, IL8, IL10, IL23R, TNFA, and TNFSF15, one from the UK (194 patients and 92 healthy volunteers) and one from the USA (137 patients and 96 healthy volunteers). The main aim was to examine the relationship between inherited immunological diversity and IBS risk in a meta-analysis which included 12 additional, earlier studies. The meta-analysis comprised a total of 2894 patients (839 IBS-C, 1073 IBS-D, 502 IBS-M), and 3138 healthy volunteers with self-reported Caucasian ancestry. KEY RESULTS: The association of SNP rs4263839 (TNFSF15) was investigated in four studies and confirmed in the meta-analysis: IBS (OR 1.19, 95% CI 1.08-1.31), and IBS-C (OR 1.24, 95% CI 1.08-1.42). No additional SNPs residing in immunogenes associated with IBS symptom phenotypes. CONCLUSIONS & INFERENCES: Our meta-analysis could not confirm a major role of most investigated SNPs, but a moderate association between rs4263839 TNFSF15 and IBS, in particular IBS-C. The analysis emphasizes the importance of definition and phenotype homogeneity, adequate study size and representativeness of the patient and control collective.

Changing views on diverticular disease: impact of aging, obesity, diet, and microbiota.

The development of colonic diverticulosis is a common aging change in industrialized nations. While most patients have asymptomatic diverticulosis, around one in five develops symptomatic diverticular disease. This is characterized by recurrent abdominal pain and disturbed bowel habit. Some of the pain episodes are prolonged and are due to acute diverticulitis, which itself may be complicated by abscess, perforation, fistulation, or stricture formation. Risk factors favouring the development of symptomatic diverticular disease include obesity, smoking and diets low in fiber but high in red meat and animal fat. What determines the transition from asymptomatic diverticulosis to symptomatic diverticular disease is unclear but neuromuscular changes following acute diverticulitis may be responsible in some cases. The severity of symptoms generated depends on cerebral pain processing which is influenced by psychosocial factors. These are important considerations in deciding optimal patient management. Prior theories of the cause of diverticulosis suggested that constipation was an important cause, but new data challenge this and has provoked new ideas. Underlying mechanisms causing diverticulosis include weakening of the colonic wall and/or degenerative changes in the enteric nerves. Dietary induced changes in microbiota and the host inflammatory response may underlie the subsequent development of acute/chronic diverticulitis and its sequela.

Effect of experimental stress on the small bowel and colon in healthy humans.

BACKGROUND: Symptoms of irritable bowel syndrome (IBS) are frequently reported to be exacerbated by stress. Animal studies suggest that corticotrophin releasing hormone (CRH) mediates the effect of stress on the bowel. We have shown that stressed IBS patients with diarrhea have constricted small bowels. We hypothesized that we could mimic this effect by applying experimental stress in the form of either hand immersion in ice water or CRH injection in healthy volunteers (HV). METHODS: The postprandial effect of the cold pressor test (repeated hand immersion in ice cold water) and injection of CRH, were assessed vs control in two groups of 18 HVs. KEY RESULTS: CRH produced a significant rise from baseline salivary cortisol levels (p = 0.004) not seen with the cold pressor test. Small bowel water content (SBWC) fell postprandially on all four treatments. SBWC was significantly reduced by both stressors but CRH caused a greater effect (anova, p < 0.003 vs p = 0.02). Ascending colon (AC) volume was greater after CRH injection compared with saline (p = 0.002) but no differences were seen with the cold pressor test vs warm water. Postprandial increase in colon volume was also reduced by CRH which also increased the sensations of distension and bloating. CONCLUSIONS & INFERENCES: Two experimental stressors were shown to constrict the small bowel, mimicking the effect previously seen in IBS-D patients. CRH increased the volume of the AC. We speculate that stress accelerates transfer of water from the small bowel to the AC.

Measurement of gastric meal and secretion volumes using magnetic resonance imaging.

MRI can assess multiple gastric functions without ionizing radiation. However, time consuming image acquisition and analysis of gastric volume data, plus confounding of gastric emptying measurements by gastric secretions mixed with the test meal have limited its use to research centres. This study presents an MRI acquisition protocol and analysis algorithm suitable for the clinical measurement of gastric volume and secretion volume. Reproducibility of gastric volume measurements was assessed using data from 10 healthy volunteers following a liquid test meal with rapid MRI acquisition within one breath-hold and semi-automated analysis. Dilution of the ingested meal with gastric secretion was estimated using a respiratory-triggered T1 mapping protocol. Accuracy of the secretion volume measurements was assessed using data from 24 healthy volunteers following a mixed (liquid/solid) test meal with MRI meal volumes compared to data acquired using gamma scintigraphy (GS) on the same subjects studied on a separate study day. The mean ± SD coefficient of variance between 3 observers for both total gastric contents (including meal, secretions and air) and just the gastric contents (meal and secretion only) was 3 ± 2% at large gastric volumes (>200 ml). Mean ± SD secretion volumes post meal ingestion were 64 ± 51 ml and 110 ± 40 ml at 15 and 75 min, respectively. Comparison with GS meal volumes, showed that MRI meal only volume (after correction for secretion volume) were similar to GS, with a linear regression gradient ± std err of 1.06 ± 0.10 and intercept -11 ± 24 ml. In conclusion, (i) rapid volume acquisition and respiratory triggered T1 mapping removed the requirement to image during prolonged breath-holds (ii) semi-automatic analysis greatly reduced the time required to derive measurements and (iii) correction for secretion volumes provided accurate assessment of gastric meal volumes and emptying. Together these features provide the scientific basis of a protocol which would be suitable in clinical practice.

Additive effects of gastric volumes and macronutrient composition on the sensation of postprandial fullness in humans.

BACKGROUND/OBJECTIVES: Intake of food or fluid distends the stomach and triggers mechanoreceptors and vagal afferents. Wall stretch and tension produces a feeling of fullness. Duodenal infusion studies assessing gastric sensitivity by barostat have shown that the products of fat digestion have a greater effect on the sensation of fullness and also dyspeptic symptoms than carbohydrates. We tested here the hypothesis that fat and carbohydrate have different effects on gastric sensation under physiological conditions using non-invasive magnetic resonance imaging (MRI) to measure gastric volumes. SUBJECTS/METHODS: Thirteen healthy subjects received a rice pudding test meal with added fat or added carbohydrate on two separate occasions and underwent serial postprandial MRI scans for 4.5 h. Fullness was assessed on a 100-mm visual analogue scale. RESULTS: Gastric half emptying time was significantly slower for the high-carbohydrate meal than for the high-fat meal, P=0.0327. Fullness significantly correlated with gastric volumes for both meals; however, the change from baseline in fullness scores was higher for the high-fat meal for any given change in stomach volume (P=0.0147), despite the lower energy content and faster gastric emptying of the high-fat meal. CONCLUSIONS: Total gastric volume correlates positively and linearly with postprandial fullness and ingestion of a high-fat meal increases this sensation compared with high-carbohydrate meal. These findings can be of clinical interest in patients presenting with postprandial dyspepsia whereby manipulating gastric sensitivity by dietary intervention may help to control digestive sensations.

Stimulation of colonic motility by oral PEG electrolyte bowel preparation assessed by MRI: comparison of split vs single dose.

BACKGROUND: Most methods of assessing colonic motility are poorly acceptable to patients. Magnetic resonance imaging (MRI) can monitor gastrointestinal motility and fluid distributions. We predicted that a dose of oral polyethylene glycol (PEG) and electrolyte solution would increase ileo-colonic inflow and stimulate colonic motility. We aimed to investigate the colonic response to distension by oral PEG electrolyte in healthy volunteers (HVs) and to evaluate the effect of single 2 L vs split (2 × 1 L) dosing. METHODS: Twelve HVs received a split dose (1 L the evening before and 1 L on the study day) and another 12 HVs a single dose (2 L on the main study day) of PEG electrolyte. They underwent MRI scans, completed symptom questionnaires, and provided stool samples. Outcomes included small bowel water content, ascending colon motility index, and regional colonic volumes. KEY RESULTS: Small bowel water content increased fourfold from baseline after ingesting both split (p = 0.0010) and single dose (p = 0.0005). The total colonic volume increase from baseline was smaller for the split dose at 35 ± 8% than for the single dose at 102 ± 27%, p = 0.0332. The ascending colon motility index after treatment was twofold higher for the single dose group (p = 0.0103). CONCLUSIONS & INFERENCES: Ingestion of 1 and 2 L PEG electrolyte solution caused a rapid increase in the small bowel and colonic volumes and a robust rise in colonic motility. The increase in both volumes and motility was dose dependent. Such a challenge, being well-tolerated, could be a useful way of assessing colonic motility in future studies.

A low calorie morning meal prevents the decline of hepatic glycogen stores: a pilot in vivo (13)C magnetic resonance study.

Previous studies have reported a meal-induced rise in hepatic glycogen stores from baseline levels following a fast and it is generally assumed that glycogen levels rise steadily following meals throughout the day. However, measurements are normally taken in conditions that are not typical of the Western breakfast, which is relatively carbohydrate rich with a lower calorific content than most experimental test meals. As such, little is known about the normal metabolic response to a realistic, low calorie morning meal. Therefore, the aim of this pilot study was to evaluate the effects of a low dose oral glucose intake on hepatic glycogen levels following an overnight fast in healthy subjects. Glycogen levels were monitored in vivo using (13)C Magnetic Resonance Spectroscopy at baseline and hourly for 4 hours following either a 50 g glucose drink (773 kJ) or a control drink (0 kJ) given over two different visits. During the control visit hepatic glycogen levels decreased throughout the experiment with statistically significant decreases from baseline at 190 minutes (P < 0.05) and 250 minutes (P < 0.05). By contrast, the low dose glucose intake maintained glycogen concentrations with no significant decrease from baseline over 4 hours. A comparison between visits revealed that mean glycogen concentrations were significantly greater during the glucose visit (control visit, AUC = 218 ± 39 mol L(-1) min(-1); glucose visit, AUC = 305 ± 49 mol L(-1) min(-1); P < 0.05). Liver volume decreased significantly from baseline at 180 minutes (P < 0.05) post consumption in both groups, with no significant difference found between visits. Gastric content volumes were significantly higher for the glucose visit immediately following consumption (P < 0.001) and at 60 minutes (P = 0.007) indicating slower gastric emptying for the glucose compared with the control. In conclusion, following an overnight fast, a low dose oral glucose challenge prevents a reduction in hepatic glycogen content but does not increase it above fasted levels.

Review article: The pathogenesis and management of acute colonic diverticulitis.

BACKGROUND: Acute diverticulitis, defined as acute inflammation associated with a colonic diverticulum, is a common emergency presentation managed by both surgeons and physicians. There have been advances in both the medical and the surgical treatments offered to patients in recent years. AIM: To review the current understanding of the aetiology and treatment of acute diverticulitis. METHODS: A search of PubMed and Medline databases was performed to identify articles relevant to the aetiology, pathogenesis and management of acute diverticulitis. RESULTS: There are 75 hospital admissions per year for acute diverticulitis per 100,000 of the population in the United States. Recent reports suggest a 26% increase in admissions over a 7-year period. Factors predisposing to the development of acute diverticulitis include obesity, smoking, diet, lack of physical activity and medication use such as aspirin and nonsteroidal anti-inflammatory drugs. The condition is associated with a low mortality of about 1% following medical therapy, rising to 4% in-hospital mortality in those requiring surgery. There is limited evidence on the efficacy of individual antibiotic regimens, and antibiotic treatment may not be required in all patients. The rates of recurrence reported for patients with acute diverticulitis following medical management vary from 13% to 36%. The surgical management of those patients who fail medical treatment has moved towards a laparoscopic nonresectional approach; however, the evidence supporting this is limited. CONCLUSIONS: Further high-quality randomised controlled trials are required of both medical and surgical treatments in patients with acute diverticulitis, if management is to be evidence-based.

Novel MRI tests of orocecal transit time and whole gut transit time: studies in normal subjects.

BACKGROUND: Colonic transit tests are used to manage patients with Functional Gastrointestinal Disorders. Some tests used expose patients to ionizing radiation. The aim of this study was to compare novel magnetic resonance imaging (MRI) tests for measuring orocecal transit time (OCTT) and whole gut transit time (WGT), which also provide data on colonic volumes. METHODS: 21 healthy volunteers participated. Study 1: OCTT was determined from the arrival of the head of a meal into the cecum using MRI and the Lactose Ureide breath test (LUBT), performed concurrently. Study 2: WGT was assessed using novel MRI marker capsules and radio-opaque markers (ROMs), taken on the same morning. Studies were repeated 1 week later. KEY RESULTS: OCTT measured using MRI and LUBT was 225 min (IQR 180-270) and 225 min (IQR 165-278), respectively, correlation r(s) = 0.28 (ns). WGT measured using MRI marker capsules and ROMs was 28 h (IQR 4-50) and 31 h ± 3 (SEM), respectively, correlation r(s) = 0.85 (p < 0.0001). Repeatability assessed using the intraclass correlation coefficient (ICC) was 0.45 (p = 0.017) and 0.35 (p = 0.058) for MRI and LUBT OCTT tests. Better repeatability was observed for the WGT tests, ICC being 0.61 for the MRI marker capsules (p = 0.001) and 0.69 for the ROM method (p < 0.001) respectively. CONCLUSIONS & INFERENCES: The MRI WGT method is simple, convenient, does not use X-ray and compares well with the widely used ROM method. Both OCTT measurements showed modest reproducibility and the MRI method showed modest inter-observer agreement.