Publications
309 results found
Nolan JD, Johnston IM, Walters JRF, 2015, Physiology of malabsorption, Surgery (United Kingdom), Vol: 33, Pages: 193-199, ISSN: 0263-9319
Malabsorption occurs when the function of the gastrointestinal tract is suboptimal and nutrient absorption is reduced. Malnutrition, weight loss, diarrhoea, steatorrhoea, anaemia and other specific nutrient deficiencies can be produced. This article will review the principles of normal nutrient absorption and the pathophysiology in disorders which result in malabsorption. Normal absorption needs coordinated processes of motility, hormone release, digestive secretion from the salivary glands, stomach, pancreas, liver and intestine, and the expression of specific enzymes and transporter molecules. Gastric, pancreatic and intestinal disorders can all produce malabsorption. These can be complications of surgical procedures, or be due to inflammatory and autoimmune disorders such as coeliac disease, Crohn's disease, small intestinal bacterial overgrowth, chronic pancreatitis, or autoimmune gastritis. Understanding the mechanisms involved and how these are affected by surgical procedures and disease will enable malabsorption to be recognized, investigated and treated appropriately.
Walters JR, Appleby RN, 2015, A variant of FGF19 for treatment of disorders of cholestasis and bile acid metabolism., Annals of translational medicine, Vol: 3, Pages: S7-S7, ISSN: 2305-5847
Appleby RN, Nolan JD, Johnston IM, et al., 2015, Bile Acid Diarrhea Is Associated With Non-Alcoholic Fatty Liver Disease, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S68-S69, ISSN: 0016-5085
Nolan JD, Madhan GK, Appleby RN, et al., 2015, Stimulated Expression of Ileal Fibroblast Growth Factor 19 by Bile Acids Is Impaired in Patients With Primary Bile Acid Diarrhea, 46th Annual Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S329-S330, ISSN: 0016-5085
Walters JRF, Appleby RN, 2015, Editorial: colesevelam effects on faecal bile acids in IBS with diarrhoea, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 41, Pages: 696-697, ISSN: 0269-2813
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- Citations: 1
Walters JRF, Johnston IM, Nolan JD, et al., 2015, The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 41, Pages: 54-64, ISSN: 0269-2813
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- Citations: 120
Waters J, Walters JWJ, 2015, What's Up With Your Gut? Why You Bloat After Eating Bread and Pasta... and Other Gut Problems, ISBN: 9781781610688
Nolan JD, Johnston IM, Pattni SS, et al., 2014, Diarrhea in Crohn's Disease: investigating the role of the ileal hormone Fibroblast Growth Factor 19., Journal of Crohns & Colitis, Vol: 9, Pages: 125-131, ISSN: 1873-9946
Background: Bile acids (BA) are usually reabsorbed by the terminal ileum, but this is frequently abnormal in Crohn's disease (CD). BA malabsorption occurs and excess colonic BA cause secretory diarrhea. Furthermore, the hormone Fibroblast Growth Factor 19 (FGF19) is synthesized in the ileum in response to BA absorption and regulates BA synthesis. We hypothesized that reduced serum FGF19 levels will be associated with diarrheal symptoms and disease activity in both ileal-resected (IR-CD) and non-resected CD (NR-CD) patients. Methods: Fasting serum FGF19 levels were measured in 58 patients (23 IR-CD patients and 35 NR-CD patients). Disease activity was assessed using the Harvey Bradshaw Index and CRP. Stool frequency, Bristol stool form scale and length of previous ileal resection were recorded. FGF19 levels were also compared to healthy and diarrhea control patients. Results: FGF19 levels were inversely correlated with ileal resection length in IR-CD patients (r=-0.54, p=0.02). In NR-CD patients, median FGF19 levels were significantly lower in patients with active disease compared to inactive disease (103 vs 158 pg/ml, p=0.04) and in those with symptoms of diarrhea compared to those without (86 vs 145 pg/ml, p=0.035). FGF19 levels were inversely correlated (r =-0.52, P=0.02) with stool frequency, Bristol stool form and CRP in NR-CD patients with ileal disease. Conclusions: Reduced FGF19 levels are associated with diarrhea and disease activity. FGF19 may have utility as a biomarker for functioning ileum in CD. This study supports a potential role of FGF19 in guiding treatments for diarrhea in Crohn's disease.
Appleby RN, Walters JRF, 2014, The role of bile acids in functional GI disorders, NEUROGASTROENTEROLOGY AND MOTILITY, Vol: 26, Pages: 1057-1069, ISSN: 1350-1925
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- Citations: 45
Walters JRF, 2014, Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy, NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, Vol: 11, Pages: 426-434, ISSN: 1759-5045
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- Citations: 77
Nolan JD, Vassie C, Johnston IM, et al., 2014, A PRELIMINARY STUDY OF THE EFFECTS OF OBETICHOLIC ACID, A FARNESOID X RECEPTOR AGONIST, IN PATIENTS WITH CHRONIC DIARRHOEA SECONDARY TO CROHN'S ILEAL DISEASE, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A258-A258, ISSN: 0017-5749
Nolan J, Pattni S, Walters JR, et al., 2014, FGF19 LEVELS IN SUBJECTS WITH PRIMARY BILE ACID DIARRHOEA AND ELEVATED TRIGLYCERIDES, Annual Meeting of the British-Society-of-Gastroenterology (BSG), Publisher: BMJ PUBLISHING GROUP, Pages: A13-A14, ISSN: 0017-5749
Vassie C, Nolan JD, Johnston IM, et al., 2014, Obeticholic Acid, a Farnesoid X Receptor Agonist, Reduces Bile Acid Synthesis in Patients With Primary Bile Acid Diarrhea, 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S797-S797, ISSN: 0016-5085
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- Citations: 1
Nolan JD, Vassie C, Johnston IM, et al., 2014, The Effects of Obeticholic Acid, a Farnesoid X Receptor Agonist, in Patients With Chronic Diarrhea Secondary to Crohn's Ileal Disease, 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S797-S797, ISSN: 0016-5085
George DA, Hui LL, Rattehalli D, et al., 2014, The role of near-patient coeliac serology testing in the follow-up of patients with coeliac disease., Frontline Gastroenterol, Vol: 5, Pages: 20-25, ISSN: 2041-4137
OBJECTIVE: This pilot study was undertaken to assess the validity and effectiveness of near-patient coeliac immunological testing, compared to standard laboratory immunological techniques, used in the context of dietician-led coeliac disease follow-up clinics. DESIGN: The study was designed in two phases, each assessing the near-patient test and standard laboratory immunological techniques. Phase 1 analysed stored serum samples; Phase 2 analysed whole blood from patients attending the dietician-led coeliac disease clinics. SETTING: Patients were recruited from New Cross Hospital, Wolverhampton (n=50), and Imperial College London (n=30), between March 2010 and February 2011. PATIENTS: Those with a diagnosis of coeliac disease for greater than 12 months attending dietician-led coeliac disease clinics. INTERVENTIONS: In addition to whole blood taken for routine analysis, patients required a capillary finger-prick blood sample. MAIN OUTCOME MEASURE: To determine if the whole blood and serum near-patient test results were in correlation with outcomes of standard laboratory evaluation. RESULTS: Phase 1 demonstrated that the near-patient serum test had a sensitivity of 93.5% (95% CI 0.79% to 0.98%), specificity of 94.9% (0.83% to 0.99%), when compared to standard laboratory ELISA. Phase 2, involving patients whole blood, had a sensitivity of 77.8% (0.45% to 0.93%), and specificity of 100% (0.94% to 1%). CONCLUSIONS: This pilot study has demonstrated that there appears to be a role for near-patient testing in coeliac disease, but further studies are recommended.
Peters AM, Walters JRF, 2013, Recycling rate of bile acids in the enterohepatic recirculation as a major determinant of whole body <SUP>75</SUP>SeHCAT retention, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 40, Pages: 1618-1621, ISSN: 1619-7070
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- Citations: 9
Pattni SS, Brydon WG, Dew T, et al., 2013, Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention, ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Vol: 38, Pages: 967-976, ISSN: 0269-2813
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- Citations: 86
Johnston I, Nolan JD, Dew T, et al., 2013, A NOVEL, RATIONAL APPROACH TO TREATING PRIMARY BILE ACID DIARRHOEA: A PROOF OF CONCEPT STUDY OF THE FXR AGONIST OBETICHOLIC ACID, Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: BMJ PUBLISHING GROUP, Pages: A127-A128, ISSN: 0017-5749
Nolan JD, Johnston I, Dew T, et al., 2013, SERUM FGF19 LEVELS ARE RELATED TO DISEASE ACTIVITY IN ILEAL CROHN'S DISEASE, Annual General Meeting of the British-Society-of-Gastroenterology, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A130, ISSN: 0017-5749
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- Citations: 1
Kennie S, Nolan JD, Zhang JH, et al., 2013, Relative Potencies of Bile Acids in Inducing Fibroblast Growth Factor 19 in the Human Ileum, Digestive Disease Week / 28th Annual Residents and Fellows Research Conference of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S539-S539, ISSN: 0016-5085
Nolan JD, Pattni SS, Kennie S, et al., 2013, Ileal Bile Acid Transporter and FGF19 Transcript Expression Related to SEHCAT Retention in Patients With Chronic Diarrhea, Digestive Disease Week / 28th Annual Residents and Fellows Research Conference of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S667-S667, ISSN: 0016-5085
Johnston IM, Nolan JD, Dew T, et al., 2013, A New Therapy for Chronic Diarrhea? A Proof of Concept Study of the FXR Agonist Obeticholic Acid in Patients With Primary Bile Acid Diarrhea, Digestive Disease Week / 28th Annual Residents and Fellows Research Conference of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S60-S60, ISSN: 0016-5085
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- Citations: 7
Zhang JH, Nolan JD, Kennie SL, et al., 2013, Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids, AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, Vol: 304, Pages: G940-G948, ISSN: 0193-1857
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- Citations: 74
Nolan JD, Johnston IM, Walters JRF, 2013, Altered enterohepatic circulation of bile acids in Crohn's disease and their clinical significance: a new perspective, EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, Vol: 7, Pages: 49-56, ISSN: 1747-4124
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- Citations: 19
Pournaras DJ, Glicksman C, Vincent RP, et al., 2012, The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control, ENDOCRINOLOGY, Vol: 153, Pages: 3613-3619, ISSN: 0013-7227
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- Citations: 284
Pattni SS, Brydon WG, Dew T, et al., 2012, Fibroblast Growth Factor 19 and 7α-Hydroxy-4-Cholesten-3-one in the Diagnosis of Patients With Possible Bile Acid Diarrhea, Clinical and Translational Gastroenterology, Vol: 3, ISSN: 2155-384X
OBJECTIVES: Increased colonic bile acids can cause chronic diarrhea. Bile acid diarrhea (BAD) is treatable by sequestrants, and may be secondary to ileal disease or primary BAD. It is underdiagnosed, partly because the selenium-75-homocholic acid taurine (SeHCAT) retention test is not available in many countries, and is underutilized in others. Serum 7α-hydroxy-4-cholesten-3-one (C4), a measure of bile acid synthesis, is available for diagnosis in specialist centers. Recently, deficiency of the ileal hormone fibroblast growth factor 19 (FGF19) has been shown in BAD. Our aim is to evaluate the diagnostic value of FGF19 in a large and prospective group of patients with chronic diarrhea, previously investigated with C4.METHODS: Patients undergoing routine investigation provided fasting blood samples. C4 was determined by high-performance liquid chromatography, and used to stratify two groups: group 1 (n=119), consisting of patients with normal C4 (≤ 28 ng/ml), and group 2 (n=139), consisting of patients with high C4 (>28 ng/ml), including any of the possible causes of BAD. Serum FGF19 was measured in stored samples by enzyme-linked immunosorbent assay.RESULTS: FGF19 and C4 were significantly inversely related (rs=−0.64, P<0.001). Patients with raised C4 had significantly lower median FGF19 values. Both of these were more marked when secondary to ileal disease, in particular ileal resection, than in primary BAD. The sensitivity and specificity of FGF19 at 145 pg/ml for detecting a C4 level >28 ng/ml were 58% and 79%, respectively. For C4 >60 ng/ml, these were 74% and 72%; on receiver-operating characteristic analysis, the area under the curve was 0.80 (95% confidence interval 0.74–0.87).CONCLUSIONS: Serum FGF19 could be developed as a simple blood test to increase the diagnostic rates of BAD.
Nolan JD, Johnston I, Dew T, et al., 2012, REDUCED CIRCULATING FGF19 LEVELS ARE ASSOCIATED WITH SYMPTOMS OF DIARRHOEA IN CROHN'S DISEASE, GUT, Vol: 61, Pages: A34-A35, ISSN: 0017-5749
Nolan JD, Zhang JH, Johnston I, et al., 2012, FGF19 EXPRESSION IS HIGHLY RESPONSIVE TO BILE ACIDS COMPARED TO OTHER BILE ACID REGULATORY GENES WITHIN THE HUMAN ILEUM, GUT, Vol: 61, Pages: A34-A34, ISSN: 0017-5749
Johnston I, Pattni SS, Nolan JD, et al., 2012, A PROSPECTIVE STUDY OF SERUM VITAMIN A AND D LEVELS IN PRIMARY BILE ACID DIARRHOEA, Publisher: B M J PUBLISHING GROUP, Pages: A249-A250, ISSN: 0017-5749
Johnston I, Pattni SS, Lin J, et al., 2012, GENETIC POLYMORPHISMS AND PATTERNS OF FGF19 RESPONSE TO MEALS IN PRIMARY BILE ACID DIARRHOEA, GUT, Vol: 61, Pages: A35-A35, ISSN: 0017-5749
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