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Detecting the effects of a standardized meal challenge on small bowel motility with MRI in prepared and unprepared bowel.
de Jonge, CS, Menys, A, van Rijn, KL, Bredenoord, AJ, Nederveen, AJ, Stoker, J
Neurogastroenterology and motility. 2019;(2):e13506
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Abstract
OBJECTIVE MRI is increasingly used to evaluate small bowel contractility. The objective of this study was to validate a clinically practical stimulation test (300-kcal meal) for small bowel motility. METHODS Thirty-one healthy subjects underwent dynamic MRI to capture global small bowel motility after ±10h fasting, of which 15 underwent bowel preparation consisting of 1 L 2.5% mannitol solution and 16 did not. Each subject underwent (1) a baseline motility scan (2) a food challenge (3) a post-challenge scan, and (4) second post-challenge scan (after ±20 minutes). This protocol was repeated within 2 weeks. Motility was quantified using a validated motility assessment technique. KEY RESULTS Motility in prepared subjects at baseline was significantly higher than motility in unprepared subjects (0.36 AU vs 0.18 AU, P < 0.001). In the prepared group, the food challenge produced an 8% increase in motility (P = 0.33) while in the unprepared subjects a significant increase of 30% was observed (P < 0.001). Responses to food remained insignificant (P = 0.21) and significant (P = 0.003), for the prepared and unprepared subjects, respectively, ±20 minutes post food challenge. These results were confirmed in the repeated scan session. CONCLUSION & INFERENCES A significant response to a 300-kcal meal was measured within 10 minutes in unprepared bowel, supporting the clinical use of this challenge to provoke and assess motility changes. A caloric challenge did not produce an observable increase in motility in mannitol prepared subjects.
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Cine MRI assessment of motility in the unprepared small bowel in the fasting and fed state: Beyond the breath-hold.
Khalaf, A, Nowak, A, Menys, A, Marciani, L, Taylor, SA, Spiller, RC, Gowland, PA, Moran, GW, Hoad, CL
Neurogastroenterology and motility. 2019;(1):e13466
Abstract
BACKGROUND The symptoms of functional bowel disorders are common in postprandial but investigations are generally undertaken in the fasted state using invasive procedures. MRI provides a noninvasive tool to study the gastrointestinal tract in an unperturbed, fed state. The aim of this study was to develop a technique to assess small bowel motility from cine MRI data in the unprepared bowel in fasting and fed states. METHODS Fifteen healthy volunteers underwent a baseline MRI scan after which they consumed a 400 g soup. Subjects then underwent a postprandial scan followed by further scans at regular intervals. Small bowel motility was assessed using single-slice bTFE cine MRI. An optimized processing technique was used to generate motility data based on power spectrum analysis of voxel-signal changes with time. Interobserver variability (n = 15) and intra-observer (n = 6) variability were assessed. Changes in the motility index were compared between fasted and immediate postprandial state. KEY RESULTS Excellent agreement between observers was seen across the range of motility measurements acquired, with intraclass correlation coefficient (ICC) of 0.979 (P < 0.0001) and Bland-Altman limits of agreement 95% CI: -28.9 to 45.9 au. Intra-observer variability was low with ICC of 0.992 and 0.960 (2 observers, P < 0.0001). Changes from the fasted to immediately postprandial state showed an average increase of 122.4% ± 98.7% (n = 15). CONCLUSIONS & INFERENCES This optimized technique showed excellent inter and intra observer agreement. It was sensitive to changes in motility induced feeding. This technique will be useful to study contractile activity and regional patterns along the gastrointestinal tract under physiological conditions.
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Bangladesh Environmental Enteric Dysfunction (BEED) study: protocol for a community-based intervention study to validate non-invasive biomarkers of environmental enteric dysfunction.
Mahfuz, M, Das, S, Mazumder, RN, Masudur Rahman, M, Haque, R, Bhuiyan, MMR, Akhter, H, Sarker, MSA, Mondal, D, Muaz, SSA, et al
BMJ open. 2017;(8):e017768
Abstract
INTRODUCTION Environmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting. METHODS AND ANALYSIS The BEED study is a community-based intervention where participants are recruited from three cohorts: stunted children aged 12-18 months (length for age Z-score (LAZ) <-2), at risk of stunting children aged 12-18 months (LAZ <-1 to -2) and malnourished adults aged 18-45 years (body mass index <18.5 kg/m2). After screening, participants eligible for study provide faecal, urine and plasma specimens to quantify the levels of candidate EED biomarkers before and after receiving a nutritional intervention. Participants who fail to respond to nutritional therapy are considered as the candidates for upper gastrointestinal endoscopy with biopsy. Histopathological scoring for EED will be performed on biopsies obtained from several locations within the proximal small intestine. Candidate EED biomarkers will be correlated with nutritional status, the results of histochemical and immunohistochemical analyses of epithelial and lamina propria cell populations, plus assessments of microbial community structure. ETHICS AND DISSEMINATION Ethics approval was obtained in all participating institutes. Results of this study will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER ClinicalTrials.gov ID: NCT02812615. Registered on 21 June 2016.
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Evaluation of Patient Tolerance and Small-Bowel Distention With a New Small-Bowel Distending Agent for Enterography.
Kolbe, AB, Fletcher, JG, Froemming, AT, Sheedy, SP, Koo, CW, Pundi, K, Bruining, DH, Tung, J, Harmsen, WS, Barlow, JM, et al
AJR. American journal of roentgenology. 2016;(5):994-1002
Abstract
OBJECTIVE The objective of our study was to compare a flavored beverage containing a thickening agent for enterography with a low-Hounsfield-value barium suspension for side effects, taste, subjects' willingness to repeat the drinking protocol, and small-bowel distention. SUBJECTS AND METHODS The following five drinking protocols were administered to 10 volunteers: 1000 mL of flavored beverage followed by 350 mL of water, 1500 mL of flavored beverage, 900 mL of low-Hounsfield-value barium suspension followed by 450 mL of water, 1350 mL of low-Hounsfield-value barium suspension followed by 150 mL of water, and 1500 mL of water. MR images were obtained 50 and 60 minutes after initiation of drinking. Subjects completed a questionnaire evaluating the side effects, the taste of the drink, and their willingness to repeat the drinking protocol. Reviewers assigned scores evaluating small-bowel distention and ranked the examinations in order of preference. RESULTS There was no significant difference in nausea or vomiting among the protocols (p = 0.20 and 0.42, respectively), but larger volumes of flavored beverage and low-Hounsfield-value barium suspension resulted in more cramping and diarrhea (p = 0.001 and 0.002, respectively). The taste of the low-Hounsfield-value barium suspension was rated the worst (p < 0.0001). The subjects' willingness to repeat the drinking protocol was highest for the 1000 mL of flavored beverage or water alone (p < 0.05). There were no significant differences in subjective small-bowel distention except that water was rated the worst by two of the three readers (p < 0.02). There was no significant difference in the diameter of the most dis-tended small bowel for any segment or reader (p > 0.23). CONCLUSION A flavored beverage containing a thickening agent has a similar side effect profile and results in equivalent small-bowel distention compared with a low-Hounsfield-value barium suspension, but subjects rate taste and their willingness to repeat the drinking protocol higher for this new agent.
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Vitamin D and vitamin B12 deficiencies are common in patients with midgut carcinoid (SI-NET).
Lind, A, Wängberg, B, Ellegård, L
European journal of clinical nutrition. 2016;(9):990-4
Abstract
BACKGROUND/OBJECTIVES Patients with small intestinal neuroendocrine tumours (SI-NET) often have diarrhoea from hormonal overproduction, surgery and medical treatment, leading to malabsorption of bile salts, fats, vitamin B12 and fat-souble vitamins. This could lead to malnutrition. SUBJECTS/METHODS We assessed nutritional status in 50 consecutive out patients with disseminated SI-NET, 25 patients in each cohort. The first cohort was descriptive and the second cohort supplemented with vitamin D, B12 and calcium. Vitamin D deficiency was defined as <50 nmol/l. All patients were assessed by clinical chemistry and dual-energy X-ray absorptiometry (DXA) and interviewed about weight changes, appetite, gastrointestinal disorders, sunhabits and the use of supplements. RESULTS In the first cohort, 29% of the patients were severely and 17% moderately vitamin D deficient. In patients without prior substitution, 32% had subnormal vitamin B12 levels. Seventy-six percent had low bone density. In the second cohort with vitamin and mineral supplementation, none had severe vitamin D deficiency, but 28% had moderate deficiency. No patient had subnormal vitamin B12 levels. Sixty percent had low bone density. The serum levels of vitamin D and B12 were higher and parathyroid hormone (PTH) lower in the second cohort compared with the first cohort (P⩽0,022). Vitamin D and PTH were negatively correlated, r=-30, P=⩽0.036. CONCLUSIONS Low serum levels of vitamin D and vitamin B12, and low bone density are common in patients with disseminated SI-NET. Supplementation of vitamin D, B12 and calcium resulted in higher serum levels of vitamins, lower PTH levels and diminished severe vitamin D deficiency and is thus recommended as standard care.
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Supersaturation and Precipitation of Posaconazole Upon Entry in the Upper Small Intestine in Humans.
Hens, B, Brouwers, J, Corsetti, M, Augustijns, P
Journal of pharmaceutical sciences. 2016;(9):2677-2684
Abstract
The purpose of this study was to explore gastrointestinal dissolution, supersaturation and precipitation of the weakly basic drug posaconazole in humans, and to assess the impact of formulation pH and type on these processes. In a cross-over study, two posaconazole suspensions (40 mg dispersed in 240 mL water at pH 1.6 and pH 7.1, respectively) were intragastrically administered; subsequently, gastric and duodenal fluids were aspirated. In parallel, blood samples were collected. Additionally, posaconazole was intragastrically administered as a solution (20 mg in 240 mL water, pH 1.6). When posaconazole was administered as an acidified suspension, supersaturated duodenal concentrations of posaconazole were observed for approximately 45 min. However, extensive intestinal precipitation was observed. Administration of the neutral suspension resulted in subsaturated concentrations with a mean duodenal AUC0-120 min and Cmax being approximately twofold lower than for the acidified suspension. The mean plasma AUC0-8 h of posaconazole was also twofold higher following administration of the acidified suspension. Similar to the acidified suspension, significant intestinal precipitation (up to 92%) was observed following intragastric administration of the posaconazole solution. This study demonstrated for the first time the gastrointestinal behavior of a weakly basic drug administered in different conditions, and its impact on systemic exposure.
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Management of malignant bowel obstruction with decompression tubes.
Hu, LJ, Yu, SY
European review for medical and pharmacological sciences. 2014;(19):2798-802
Abstract
OBJECTIVE To build a quantitative assessment system for normative cancer pain management. PATIENTS AND METHODS Two groups of 60 patients with malignant lower bowel obstruction were formed: the study group (n=30) patients receiving routine small intestinal decompression and enteral nutrition, and the control group (n=30) patients receiving nasogastric decompression and parenteral nutrition. The weight, protein indicators and occurrence of complications in the two groups were compared during the treatment. RESULTS The weight gain, increase of albumin and prealbumin, and complication rate were (1.9667 ± 1.38298) kg, (2.9133 ± 1.38258) g/L, (18.5333 ± 10.92840) mg/L and 26.67% in the study group compared with (0.6667±0.87428) kg, (1.5500 ± 0.72099) g/L, (12.9333 ± 8.47688) mg/L and 86.67% in the control group. There were statistically significant differences (t = -4,352,-4.789, -2.218; χ2 = 21.9910; p < 0.05 or p < 0.01) between the two groups. CONCLUSIONS The application of small bowel decompression tubes can improve the nutritional status, physical fitness, reduce complications in patients with malignant lower intestinal obstruction.
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Characteristic hydrolyzing of megalosaccharide by human salivary α-amylase and small intestinal enzymes, and its bioavailability in healthy subjects.
Nakamura, S, Takami, M, Tanabe, K, Oku, T
International journal of food sciences and nutrition. 2014;(6):754-60
Abstract
The digestibility of Megalosaccharide® (newly developed carbohydrate comprising α-1,4-glucosaccharide) was investigated in vitro and in vivo. Isomaltosyl-megalosaccharide® (IMS) and nigerosyl-megalosaccharide® (NMS) contain 20% and 50% of the megalosaccharide fraction (degree of polymerization (DP) 10-35), respectively. IMS was hydrolyzed readily by α-amylase to oligosaccharides (DP ≤ 7), and a small amount of glucose was produced from oligosaccharides by small intestinal enzymes (SIEs). NMS was partially hydrolyzed by α-amylase to oligosaccharides, and a small amount of glucose produced by SIEs. When IMS and NMS were treated by SIEs after treatment with human saliva α-amylase for a few minutes, IMS and NMS were hydrolyzed readily to glucose. Plasma levels of glucose and insulin upon ingestion of 50 g of IMS or NMS were elevated the same as those for 50 g of glucose, and breath hydrogen was not excreted. These results suggest that IMS and NMS are digestible carbohydrates.
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Teduglutide enhances structural adaptation of the small intestinal mucosa in patients with short bowel syndrome.
Tappenden, KA, Edelman, J, Joelsson, B
Journal of clinical gastroenterology. 2013;(7):602-7
Abstract
BACKGROUND Intestinotrophic therapies, such as glucagon-like peptide-2 (GLP-2) analogs, may enhance intestinal adaptation and reduce dependence on parenteral nutrition (PN) in patients with intestinal failure associated with short bowel syndrome (SBS-IF). However, because GLP-2 enhances cellular growth, there is concern that GLP-2 analogs may also encourage growth of malignant cells. AIMS To histologically examine the effects of teduglutide, a recombinant human GLP-2 analog, on the mucosa of the small and large intestine for indications of dysplastic transformation. METHODS In a multicenter, prospective, randomized, placebo-controlled study, 83 PN-dependent patients with SBS-IF were monitored for several weeks to ensure optimal and stable PN. Patients were then randomized to receive 24 weeks of placebo (n=16), teduglutide (0.5 mg/kg/d; n=35), or teduglutide (0.10 mg/kg/d; n=32). RESULTS Biopsies were obtained from 77 patients to yield 390 individual histologic interpretations. After 6 months of treatment, no features of dysplasia were found in any biopsy from the large or small intestine of patients receiving placebo or either dose of teduglutide. New secondary diagnoses, such as eosinophilic colitis or Crohn's disease, were found at a low frequency overall: teduglutide (0.05 mg/kg/d; range, 3.1% to 6.3%); teduglutide (0.10 mg/kg/d, 3.3%); placebo (range, 6.7% to 13.3%). CONCLUSIONS Although this histologic substudy of biopsy samples was not powered to detect differences in occurrence of dysplasia between teduglutide-treated patients and those randomized to placebo, it demonstrated that no dysplasia or other pathologic processes were evident within the intestinal mucosa in the placebo group or the 2 teduglutide groups after 6 months of treatment.
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First clinical trial of a newly developed capsule endoscope with panoramic side view for small bowel: a pilot study.
Friedrich, K, Gehrke, S, Stremmel, W, Sieg, A
Journal of gastroenterology and hepatology. 2013;(9):1496-501
Abstract
BACKGROUND AND STUDY AIMS Capsule endoscopy is the first-line diagnostic technique for the small bowel. However, the inability to visualize the duodenal papilla is an inherent limitation of this method. In the present study, we evaluated feasibility of a newly developed CapsoCam SV1 capsule. PATIENTS AND METHODS This is a prospective dual center study of a newly developed video capsule CapsoCam SV1 from Capsovision, CA, providing panoramic 360° imaging. A high frequency of 20 frames occurs per second for the first 2 h and thereafter 12 frames/s, with a battery life of 15 h. We evaluated feasibility and completeness of small bowel examination together with secondary endpoints of duodenal papilla detection in 33 patients. Patients swallowed the capsules following colonoscopy or were prepared with 2 L of polyethylene glycol solution prior to the examination. All patients swallowed 20 mg of metoclopramide and 160 mg of simethicone 30 min before ingestion of the capsule. RESULTS Thirty-one of the 33 patients' data could be evaluated. Small bowel examination was complete in all procedures. Mean time to pass the small bowel was 258 ± 136 min. Average small bowel cleanliness was 3.3 ± 0.5. In 71% of the patients, we identified the duodenal papilla. No adverse reaction in relation to the capsule examination was observed. CONCLUSIONS CapsoCam SV1 is a safe and efficient tool in small bowel examination. The duodenal papilla as the only landmark in small bowel is detected in more than 70% of the patients.