Publications by authors named "Carolyn Costigan"

11 Publications

  • Page 1 of 1

Increased fasting small-bowel water content in untreated coeliac disease and scleroderma as assessed by magnetic resonance imaging.

United European Gastroenterol J 2019 12 21;7(10):1353-1360. Epub 2019 Jun 21.

Nottingham Digestive Diseases Centre, University of Nottingham and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK.

Background And Aims: The regular overnight migrating motor complex (MMC) ensures that the normal fasting small-bowel water content (SBWC) is minimised. We have applied our recently validated non-invasive magnetic resonance technique to assess SBWC in newly diagnosed coeliac disease (CD), scleroderma (SCD) and irritable bowel syndrome (IBS), conditions possibly associated with small intestinal bacterial overgrowth (SIBO).

Methods: A total of 20 CD and 15 SCD patients with gastrointestinal symptoms were compared to 20 healthy volunteers (HV) and 26 IBS with diarrhoea (IBS-D) patients, as previously reported. All underwent a fasting magnetic resonance imaging (MRI) scan on a 1.5 T Philips Achieva MRI scanner to assess fasting SBWC and colonic volumes. Stool and symptom diaries were completed for one week.

Results: Compared to HV, all patients had significantly increased stool frequency and Bristol stool form score. SBWC was significantly increased in CD (median 109 mL; interquartile range (IQR) 53-224 mL) compared to HV (median 53 mL; IQR 31-98 mL;  < 0.01) and IBS-D (median 42 mL; IQR 28-67 mL;  < 0.01). A variable increase in SBWC was also found in SCD (median 77 mL; IQR 39-158 mL), but this was not significant ( = 0.2). Colonic volumes were similar for all groups, being a median of 547 mL (IQR 442-786 mL) for CD, 511 mL (453-789 mL) for SCD, 612 mL (445-746 mL) for HV and 521 mL (428-757 mL) for IBS-D. When CD patients were subdivided according to the Marsh classification, the higher grades had larger colonic volumes.

Conclusion: Fasting SBWC as assessed by MRI is significantly increased in newly diagnosed CD and SCD but decreased in IBS-D. Future studies should test whether increased resting fluid predisposes to SIBO.
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December 2019

Gastric motor and sensory function in health assessed by magnetic resonance imaging: Establishment of reference intervals for the Nottingham test meal in healthy subjects.

Neurogastroenterol Motil 2018 12 14;30(12):e13463. Epub 2018 Sep 14.

NIHR Nottingham BRC, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.

Background: Current investigations of gastric emptying rarely identify the cause of symptoms or provide a definitive diagnosis in patients with dyspepsia. This study assessed gastric function by magnetic resonance imaging (MRI) using the modular "Nottingham test meal" (NTM) in healthy volunteers (HVs).

Methods: The NTM comprises (a) 400 mL liquid nutrient (0.75 kcal/mL) labeled with Gadolinium-DOTA and (b) an optional solid component (12 agar-beads [0 kcal]). Filling sensations were documented. MRI measurements of gastric volume, emptying, contraction wave frequency, and secretion were obtained using validated methods.

Key Results: Gastric function was measured in a population of 73 HVs stratified for age and sex. NTM induced moderate satiety and fullness. Labeled fluid was observed in the small bowel in all subjects after meal ingestion ("early-phase" GE). Secretion was rapid such that postprandial gastric content volume was often greater than meal volume (GCV0 > 400 mL), and there was increasing dilution of the meal during the study (P < 0.001). Gastric half-time was median 66-minutes (95% reference interval 35 to 161-minutes ["late-phase" GE]). The number of intact agar beads in the stomach was 7/12 (58%) at 60-minutes and 1/12 (8%) at 120-minutes. Age, bodyweight and sex had measurable effects on gastric function; however, these were small compared to inter-individual variation for most metrics.

Conclusions And Inferences: Reference intervals are presented for MRI measurements of gastric function assessed for the mixed liquid/solid NTM. Studies in patients will determine which metrics are of clinical value and also whether the reference intervals presented here offer optimal diagnostic sensitivity and specificity.
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December 2018

Response to Uno.

Am J Gastroenterol 2017 07;112(7):1167

NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.

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July 2017

Endotoxemia in Peritoneal Dialysis Patients: A Pilot Study to Examine the Role of Intestinal Perfusion and Congestion.

Perit Dial Int 2017 1-2;37(1):111-115

University of Western Ontario, Kidney Clinical Research Unit, London, ON, Canada

Endotoxemia is common in advanced chronic kidney disease and is particularly severe in those receiving dialysis. In hemodialysis patients, translocation from the bowel occurs as a consequence of recurrent circulatory stress leading to a reduction in circulating splanchnic volume and increased intestinal permeability. Peritoneal dialysis (PD) patients are often volume expanded and have continuous direct immersion of bowel in fluid; these may also be important factors in endotoxin translocation and would suggest different therapeutic strategies to improve it. The mechanisms leading to endotoxemia have never been specifically studied in PD. In this study, 17 subjects (8 PD patients, 9 healthy controls) underwent detailed gastrointestinal and cardiac magnetic resonance imaging during fasted and fed states. Gross splanchnic perfusion was assessed by quantification of superior mesenteric artery flow. Magnetic resonance imaging findings were correlated to endotoxemia, markers of hydration status and cardiac structure and function.
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December 2017

Distinct Abnormalities of Small Bowel and Regional Colonic Volumes in Subtypes of Irritable Bowel Syndrome Revealed by MRI.

Am J Gastroenterol 2017 02 13;112(2):346-355. Epub 2016 Dec 13.

NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust and the University of Nottingham, Nottingham, UK.

Objectives: Non-invasive biomarkers which identify different mechanisms of disease in subgroups of irritable bowel syndrome (IBS) could be valuable. Our aim was to seek useful magnetic resonance imaging (MRI) parameters that could distinguish each IBS subtypes.

Methods: 34 healthy volunteers (HV), 30 IBS with diarrhea (IBS-D), 16 IBS with constipation (IBS-C), and 11 IBS with mixed bowel habit (IBS-M) underwent whole-gut transit and small and large bowel volumes assessment with MRI scans from t=0 to t=360 min. Since the bowel frequency for IBS-M were similar to IBS-D, IBS-M and IBS-D were grouped together and labeled as IBS non-constipation group (IBS-nonC).

Results: Median (interquartile range): fasting small bowel water content in IBS-nonC was 21 (10-42), significantly less than HV at 44 ml (15-70), P<0.01 as was the postprandial area under the curve (AUC) P<0.01. The fasting transverse colon volumes in IBS-C were significantly larger at 253 (200-329) compared with HV, IBS-nonC whose values were 165 (117-255) and 198 (106-270) ml, respectively, P=0.02. Whole-gut transit time for IBS-C was prolonged at 69 (51-111), compared with HV at 34 (4-63) and IBS-D at 34 (17-78) h, P=0.03. Bloating score (VAS 0-10 cm) correlated with transverse colon volume at t=405 min, Spearman r=0.21, P=0.04.

Conclusions: The constricted small bowel in IBS-nonC and the dilated transverse colon in IBS-C point to significant differences in underlying mechanisms of disease.
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February 2017

Corticotropin-releasing factor increases ascending colon volume after a fructose test meal in healthy humans: a randomized controlled trial.

Am J Clin Nutr 2016 May 20;103(5):1318-26. Epub 2016 Apr 20.

Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals, and Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom

Background: Poorly absorbed fermentable carbohydrates can provoke irritable bowel syndrome (IBS) symptoms by escaping absorption in the small bowel and being rapidly fermented in the colon in some susceptible subjects. IBS patients often are anxious and stressed, and stress accelerates small bowel transit, which may exacerbate malabsorption.

Objective: In this study we investigated the effect of an intravenous injection of corticotropin-releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel.

Design: We performed a randomized, placebo-controlled crossover study of CRF compared with saline injection in 11 male and 10 female healthy subjects, examining the effect on the malabsorption of a 40-g fructose test meal and its transit through the gut, which was assessed by serial MRI and breath hydrogen measurement. Orocecal transit was assessed with the use of the lactose [(13)C]ureide breath test and the adrenal response to CRF was assessed by serial salivary cortisol measurements.

Results: CRF injection caused a significant increase in salivary cortisol, which lasted for 135 min. Small bowel water content (SBWC) rose from baseline, peaking at 45 min after fructose ingestion, whereas breath hydrogen peaked later, at 75 min. The area under the curve for SBWC from -15 min to 135 min was significantly lower after CRF compared with saline [mean difference: 5911 mL · min (95% CI: 18.4, 11,803 mL · min), P = 0.049]. Considering all subjects, the percentage change in ascending colon volume rose significantly after CRF. This increase was significant for male (P = 0.026), but not female, volunteers.

Conclusions: CRF constricts the small bowel and increases fructose malabsorption, as shown by increased ascending colon volumes. This mechanism may help to explain the increased sensitivity of some stressed individuals to fructose malabsorption. This trial was registered at as NCT01763281.
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May 2016

Fat emulsion intragastric stability and droplet size modulate gastrointestinal responses and subsequent food intake in young adults.

J Nutr 2015 Jun 29;145(6):1170-7. Epub 2015 Apr 29.

Nottingham Digestive Diseases Centre and National Institute for Health Research Biomedical Research Unit, Nottingham University Hospitals, University of Nottingham, Nottingham, United Kingdom;

Background: Intragastric creaming and droplet size of fat emulsions may affect intragastric behavior and gastrointestinal and satiety responses.

Objectives: We tested the hypotheses that gastrointestinal physiologic responses and satiety will be increased by an increase in intragastric stability and by a decrease in fat droplet size of a fat emulsion.

Methods: This was a double-blind, randomized crossover study in 11 healthy persons [8 men and 3 women, aged 24 ± 1 y; body mass index (in kg/m(2)): 24.4 ± 0.9] who consumed meals containing 300-g 20% oil and water emulsion (2220 kJ) with 1) larger, 6-μm mean droplet size (Coarse treatment) expected to cream in the stomach; 2) larger, 6-μm mean droplet size with 0.5% locust bean gum (LBG; Coarse+LBG treatment) to prevent creaming; or 3) smaller, 0.4-μm mean droplet size with LBG (Fine+LBG treatment). The participants were imaged hourly by using MRI and food intake was assessed by using a meal that participants consumed ad libitum.

Results: The Coarse+LBG treatment (preventing creaming in the stomach) slowed gastric emptying, resulting in 12% higher gastric volume over time (P < 0.001), increased small bowel water content (SBWC) by 11% (P < 0.01), slowed appearance of the (13)C label in the breath by 17% (P < 0.01), and reduced food intake by 9% (P < 0.05) compared with the Coarse treatment. The Fine+LBG treatment (smaller droplet size) slowed gastric emptying, resulting in 18% higher gastric volume (P < 0.001), increased SBWC content by 15% (P < 0.01), and significantly reduced food intake by 11% (P < 0.05, equivalent to an average of 411 kJ less energy consumed) compared with the Coarse+LBG treatment. These high-fat meals stimulated substantial increases in SBWC, which increased to a peak at 4 h at 568 mL (range: 150-854 mL; P < 0.01) for the Fine+LBG treatment.

Conclusion: Manipulating intragastric stability and fat emulsion droplet size can influence human gastrointestinal physiology and food intake.
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June 2015

A study of T₁ relaxation time as a measure of liver fibrosis and the influence of confounding histological factors.

NMR Biomed 2015 Jun 24;28(6):706-14. Epub 2015 Apr 24.

NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.

Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non-invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the liver. Here, we extend this work to measure T1 of the whole liver and investigate the effects of additional histological factors such as steatosis, inflammation and iron accumulation on the relationship between liver T1 and fibrosis. We prospectively enrolled patients who had previously undergone liver biopsy to have MR scans. A non-breath-holding, fast scanning protocol was used to acquire MR relaxation time data (T1 and T2*), and blood serum was used to determine the enhanced liver fibrosis (ELF) score. Areas under the receiver operator curves (AUROCs) for T1 to detect advanced fibrosis and cirrhosis were derived in a training cohort and then validated in a second cohort. Combining the cohorts, the influence of various histology factors on liver T1 relaxation time was investigated. The AUROCs (95% confidence interval (CI)) for detecting advanced fibrosis (F ≥ 3) and cirrhosis (F = 4) for the training cohort were 0.81 (0.65-0.96) and 0.92 (0.81-1.0) respectively (p < 0.01). Inflammation and iron accumulation were shown to significantly alter T1 in opposing directions in the absence of advanced fibrosis; inflammation increasing T1 and iron decreasing T1. A decision tree model was developed to allow the assessment of early liver disease based on relaxation times and ELF, and to screen for the need for biopsy. T1 relaxation time increases with advanced fibrosis in liver patients, but is also influenced by iron accumulation and inflammation. Together with ELF, relaxation time measures provide a marker to stratify patients with suspected liver disease for biopsy.
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June 2015

Effects of Bolus and Continuous Nasogastric Feeding on Gastric Emptying, Small Bowel Water Content, Superior Mesenteric Artery Blood Flow, and Plasma Hormone Concentrations in Healthy Adults: A Randomized Crossover Study.

Ann Surg 2016 Mar;263(3):450-7

*Nottingham Digestive Diseases Centre, National Institute for Health Research, Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, UK †Sir Peter Mansfield Magnetic Resonance Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, UK ‡Metabolic Physiology Group, University of Nottingham, Nottingham, UK §Department of Gastroenterology, Nottingham University Hospitals NHS Trust, Nottingham, UK.

Objective: We aimed to demonstrate the effect of continuous or bolus nasogastric feeding on gastric emptying, small bowel water content, and splanchnic blood flow measured by magnetic resonance imaging (MRI) in the context of changes in plasma gastrointestinal hormone secretion.

Background: Nasogastric/nasoenteral tube feeding is often complicated by diarrhea but the contribution of feeding strategy to the etiology is unclear.

Methods: Twelve healthy adult male participants who underwent nasogastric intubation before a baseline MRI scan, received 400  mL of Resource Energy (Nestle) as a bolus over 5 minutes or continuously over 4  hours via pump in this randomized crossover study. Changes in gastric volume, small bowel water content, and superior mesenteric artery blood flow and velocity were measured over 4  hours using MRI and blood glucose and plasma concentrations of insulin, peptide YY, and ghrelin were assayed every 30 minutes.

Results: Bolus nasogastric feeding led to significant elevations in gastric volume (P < 0.0001), superior mesenteric artery blood flow (P < 0.0001), and velocity (P = 0.0011) compared with continuous feeding. Both types of feeding reduced small bowel water content, although there was an increase in small bowel water content with bolus feeding after 90 minutes (P < 0.0068). Similarly, both types of feeding led to a fall in plasma ghrelin concentration although this fall was greater with bolus feeding (P < 0.0001). Bolus feeding also led to an increase in concentrations of insulin (P = 0.0024) and peptide YY (P < 0.0001), not seen with continuous feeding.

Conclusion: Continuous nasogastric feeding does not increase small bowel water content, thus fluid flux within the small bowel is not a major contributor to the etiology of tube feeding-related diarrhea.
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March 2016

Differential effects of FODMAPs (fermentable oligo-, di-, mono-saccharides and polyols) on small and large intestinal contents in healthy subjects shown by MRI.

Am J Gastroenterol 2014 Jan 19;109(1):110-9. Epub 2013 Nov 19.

Nottingham Digestive Diseases Biomedical Research Unit and Nottingham Digestive Diseases Centre, Nottingham University Hospitals, University of Nottingham, Nottingham, UK.

Objectives: The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the origin of these symptoms by magnetic resonance imaging (MRI) of the gut.

Methods: A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H2) was measured and symptoms recorded after each scan.

Results: Data are reported as mean (s.d.) (95% CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0-5 h of SBWC to 71 (23) l/min, significantly greater than for glucose at 36 (11-132) l/min (P<0.001), whereas AUC SBWC after inulin, 33 (17-106) l/min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l/min (P=0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l/min, significantly greater than glucose and glucose+fructose (both P<0.05). Breath H2 rose more with inulin than with fructose. Glucose when combined with fructose significantly reduced breath H2 by 7,700 (3,121-12,300) p.p.m./min relative to fructose alone (P<0.01, n=13).

Conclusions: Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers.
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January 2014

Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study.

PLoS One 2013 3;8(7):e67223. Epub 2013 Jul 3.

Sir Peter Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom.

Objective: To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta.

Design: A case-control study, with operators performing the image analysis blinded.

Setting: Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom.

Participants: A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy.

Methods: Each fetus was scanned with MRI at 22-27 weeks and 33-38 weeks gestational age (GA).

Main Outcome Measures: Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes.

Results: Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume.

Conclusion: Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.
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February 2014