| 1. |
- Keller, J., et al.
(författare)
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Advances in the diagnosis and classification of gastric and intestinal motility disorders
- 2018
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Ingår i: Nature Reviews Gastroenterology & Hepatology. - : Springer Science and Business Media LLC. - 1759-5045 .- 1759-5053. ; 15:5, s. 291-308
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Tidskriftsartikel (refereegranskat)abstract
- Disturbances of gastric, intestinal and colonic motor and sensory functions affect a large proportion of the population worldwide, impair quality of life and cause considerable health-care costs. Assessment of gastrointestinal motility in these patients can serve to establish diagnosis and to guide therapy. Major advances in diagnostic techniques during the past 5-10 years have led to this update about indications for and selection and performance of currently available tests. As symptoms have poor concordance with gastrointestinal motor dysfunction, clinical motility testing is indicated in patients in whom there is no evidence of causative mucosal or structural diseases such as inflammatory or malignant disease. Transit tests using radiopaque markers, scintigraphy, breath tests and wireless motility capsules are noninvasive. Other tests of gastrointestinal contractility or sensation usually require intubation, typically represent second-line investigations limited to patients with severe symptoms and are performed at only specialized centres. This Consensus Statement details recommended tests as well as useful clinical alternatives for investigation of gastric, small bowel and colonic motility. The article provides recommendations on how to classify gastrointestinal motor disorders on the basis of test results and describes how test results guide treatment decisions.
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| 2. |
- Shrestha, Sarita, 1991-, et al.
(författare)
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The use of ICD codes to identify IBD subtypes and phenotypes of the Montreal classification in the Swedish National Patient Register
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:4, s. 430-435
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Whether data on International Classification of Diseases (ICD)-codes from the Swedish National Patient Register (NPR) correctly correspond to subtypes of inflammatory bowel disease (IBD) and phenotypes of the Montreal classification scheme among patients with prevalent disease is unknown. Materials and methods: We obtained information on IBD subtypes and phenotypes from the medical records of 1403 patients with known IBD who underwent biological treatment at ten Swedish hospitals and retrieved information on their IBD-associated diagnostic codes from the NPR. We used previously described algorithms to define IBD subtypes and phenotypes. Finally, we compared these register-generated subtypes and phenotypes with the corresponding information from the medical records and calculated positive predictive values (PPV) with 95% confidence intervals. Results: Among patients with clinically confirmed disease and diagnostic listings of IBD in the NPR (N = 1401), the PPV was 97 (96-99)% for Crohn's disease, 98 (97-100)% for ulcerative colitis, and 8 (4-11)% for IBD-unclassified. The overall accuracy for age at diagnosis was 95% (when defined as A1, A2, or A3). Examining the validity of codes representing disease phenotype, the PPV was 36 (32-40)% for colonic Crohn's disease (L2), 61 (56-65)% for non-stricturing/non-penetrating Crohn's disease behaviour (B1) and 83 (78-87)% for perianal disease. Correspondingly, the PPV was 80 (71-89)% for proctitis (E1)/left-sided colitis (E2) in ulcerative colitis. Conclusions: Among people with known IBD, the NPR is a reliable source of data to classify most subtypes of prevalent IBD, even though misclassification commonly occurred in Crohn's disease location and behaviour and also among IBD-unclassified patients.
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| 3. |
- Sjöberg, Mats, 1965-, et al.
(författare)
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Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis : a retrospective observational study
- 2012
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Ingår i: Inflammatory Bowel Diseases. - : John Wiley & Sons. - 1078-0998 .- 1536-4844. ; 18:2, s. 212-218
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cyclosporine (CsA) or infliximab (IFX) are used as rescue therapies in steroid-refractory, severe attacks of ulcerative colitis (UC). There are no data comparing the efficacy of these two alternatives. Methods: Outcome of rescue therapy was retrospectively studied in two cohorts of patients hospitalized due to steroid-refractory moderate to severe UC: 1) a Swedish-Danish cohort (n 49) treated with a single infusion of IFX; 2) an Austrian cohort (n 43) treated with intravenous CsA. After successful rescue therapy, maintenance immunomodulator treatment was given to 27/33 (82%) of IFX patients and to 31/40 (78%) of CsA patients. Endpoints were colectomy-free survival at 3 and 12 months. Kaplan-Meier and Cox regression models were used to evaluate the association between treatment groups and colectomy. Results: At 15 days, colectomy-free survival in the IFX cohort was 36/49 (73%) versus 41/43 (95%) in the CsA cohort (P = 0.005), at 3 months 33/49 (67%) versus 40/43 (93%) (P = 0.002), and at 12 months 28/49 (57%) versus 33/43 (77%) (P = 0.034). After adjusting for potential confounding factors, Cox regression analysis yielded adjusted hazard ratios for risk of colectomy in IFX-treated patients of 11.2 (95% confidence interval [CI] 2.4-53.1, P = 0.002) at 3 months and of 3.0 (95% CI 1.1-8.2, P = 0.030) at 12 months in comparison with CsA-treated patients. There were no opportunistic infections or mortality. Conclusions: Colectomy frequencies were significantly lower after rescue therapy with CsA than with a single infusion of IFX both at 3 and 12 months' follow-up. The superiority of CsA was seen principally during the first 15 days.
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| 4. |
- Farmer, A. D., et al.
(författare)
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Regional gastrointestinal contractility parameters using the wireless motility capsule : inter-observer reproducibility and influence of age, gender and study country
- 2018
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 47:3, s. 391-400
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Tidskriftsartikel (refereegranskat)abstract
- Background:The wireless motility capsule concurrently measures temperature, pH and pressure as it traverses the gastrointestinal tract. Aims: To describe normative values for motility/contractility parameters across age, gender and testing centres.Methods:Healthy participants underwent a standardised wireless motility capsule assessment following an overnight fast and consumption of a meal of known nutritional content. Traces were divided into regions of interest and analysed using 2 software packages (MotiliGI and GIMS Data Viewer). Inter-observer agreement was independently assessed by 2 investigators.Results:Normative data for motility/contractility parameters (maximum amplitude, mean peak amplitude, contraction frequency and motility index) are presented for 107 individuals (62 male, median age 40years, range 18-78). MotiliGI-Gastric, small bowel and colonic maximal contraction amplitude correlated with age (r = .24, P = .01; r = .22, P = .02; and r = .2, P = .04 respectively). Small bowel motility index was higher in females than males (150.412 vs 122 +/- 7.6, P = .04). Inter-observer agreement was excellent for transit times, pH and contractility/motility parameters. GIMS Data viewer-Gastric, small bowel and colonic log(e) motility index correlated with the respective area under the contraction curve, total contractions, sum of amplitudes and contraction frequency (all r>.35, P < .0003) but not with transit times.Conclusions: Our analysis provides normative data for motility/contractility parameters. Log motility index summarises a number of measures. In future, the measurement of contractile activity with the wireless motility capsule may potentially aid in the diagnosis of disease states such as visceral myopathic disorders.
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| 5. |
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| 6. |
- Karling, Pontus, et al.
(författare)
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Function and dysfunction of the colon and anorectum in adults: working team report of the Swedish Motility Group (SMoG).
- 2009
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 44:6, s. 646-60
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Forskningsöversikt (refereegranskat)abstract
- Symptoms of fecal incontinence and constipation are common in the general population. These can, however, be unreliably reported and are poorly discriminatory for underlying pathophysiology. Furthermore, both symptoms may coexist. In the elderly, fecal impaction always must be excluded. For patients with constipation, colon transit studies, anorectal manometry and defecography may help to identify patients with slow-transit constipation and/or pelvic floor dysfunction. The best documented medical treatments for constipation are the macrogols, lactulose and isphagula. Evolving drugs include lubiprostone, which enhances colonic secretion by activating chloride channels. Surgery is restricted for a highly selected group of patients with severe slow-transit constipation and for those with large rectoceles that demonstrably cause rectal evacuatory impairment. For patients with fecal incontinence that does not resolve on antidiarrheal treatment, functional and structural evaluation with anorectal manometry and endoanal ultrasound or magnetic resonance (MR) of the anal canal may help to guide management. Sacral nerve stimulation is a rapidly evolving alternative when other treatments such as biofeedback and direct sphincter repair have failed. Advances in understanding the pathophysiology as a guide to treatment of patients with constipation and fecal incontinence is a continuing important goal for translational research. The content of this article is a summary of presentations given by the authors at the Fourth Meeting of the Swedish Motility Group, held in Gothenburg in April 2007.
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| 7. |
- Sanger, G J, et al.
(författare)
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GSK962040 : a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility
- 2009
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:6, s. 657-664, e30-31
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent clinical need for a safe, efficacious stimulant of gastric emptying; current therapies include erythromycin (an antibiotic with additional properties which preclude chronic use) and metoclopramide (a 5-hydroxytryptamine type 4 receptor agonist and an antagonist at brain D2 receptors, associated with movement disorders). To move away from the complex motilide structure of erythromycin, a small molecule motilin receptor agonist, GSK962040, was identified and characterized. The compound was evaluated using recombinant human receptors, rabbit and human isolated stomach preparations known to respond to motilin and in vivo, by measuring its ability to increase defecation in conscious rabbits. At the human motilin receptor, the pEC50 (the negative logarithm to base 10 of the EC50 value, the concentration of agonist that produces 50% of the maximal response) values for GSK962040 and erythromycin as agonists were, respectively, 7.9 and 7.3; GSK962040 had no significant activity at a range of other receptors (including ghrelin), ion channels and enzymes. In rabbit gastric antrum, GSK962040 300 nmol L−1–10 μmol L−1 caused a prolonged facilitation of the amplitude of cholinergically mediated contractions, to a maximum of 248 ± 47% at 3 μmol L−1. In human-isolated stomach, GSK962040 10 μmol L−1, erythromycin 10 μmol L−1 and [Nle13]-motilin 100 nmol L−1, each caused muscle contraction of similar amplitude. In conscious rabbits, intravenous doses of 5 mg kg−1 GSK962040 or 10 mg kg−1 erythromycin significantly increased faecal output over a 2-h period. Together, these data show that GSK962040, a non-motilide structure, selectively activates the motilin receptor. Simplification of the structural requirements to activate this receptor greatly facilitates the design of potentially new medicines for gastroparesis.
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| 8. |
- Scarpellini, E., et al.
(författare)
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International consensus on the diagnosis and management of dumping syndrome
- 2020
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Ingår i: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 16:8, s. 448-466
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Tidskriftsartikel (refereegranskat)abstract
- Dumping syndrome is a common but underdiagnosed complication of gastric and oesophageal surgery. We initiated a Delphi consensus process with international multidisciplinary experts. We defined the scope, proposed statements and searched electronic databases to survey the literature. Eighteen experts participated in the literature summary and voting process evaluating 62 statements. We evaluated the quality of evidence using grading of recommendations assessment, development and evaluation (GRADE) criteria. Consensus (defined as >80% agreement) was reached for 33 of 62 statements, including the definition and symptom profile of dumping syndrome and its effect on quality of life. The panel agreed on the pathophysiological relevance of rapid passage of nutrients to the small bowel, on the role of decreased gastric volume capacity and release of glucagon-like peptide 1. Symptom recognition is crucial, and the modified oral glucose tolerance test, but not gastric emptying testing, is useful for diagnosis. An increase in haematocrit >3% or in pulse rate >10 bpm 30 min after the start of the glucose intake are diagnostic of early dumping syndrome, and a nadir hypoglycaemia level <50 mg/dl is diagnostic of late dumping syndrome. Dietary adjustment is the agreed first treatment step; acarbose is effective for late dumping syndrome symptoms and somatostatin analogues are preferred for patients who do not respond to diet adjustments and acarbose. Dumping syndrome is a frequent complication of oesophageal and gastric surgery, as well as bariatric surgery; however, guidance on how to manage patients with this condition is lacking. In this Evidence-based guideline, the authors use a Delphi consensus process to develop uniform guidance for the definition, diagnosis and management of dumping syndrome.
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| 9. |
- Ud-din, Moeen, et al.
(författare)
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DIgestive COmplications in DIabetes : the DICODI population study
- 2023
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 58:1, s. 3-6
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiabetes type 1 and type 2 may develop gastrointestinal complications e.g., gastroparesis and gastroenteropathy. Concomitant celiac disease and pancreatic exocrine insufficiency occur with high prevalence in diabetes and with symptomatic overlap. Consequently, it is a challenge to disentangle symptoms of these conditions and separate them from functional dyspepsia. We aim to develop a clinical decision-support tool to differentiate the underlying disease in a plethora of gastrointestinal symptoms.MethodsAn internet-based computerized survey will collect basic characteristics (diabetes type, age, gender, duration, HbA1c, treatment) and patient reported outcomes by validated questionnaires focusing on (1) gastroparesis using Gastroparesis Cardinal Symptom Index; (2) gastroenteropathy using Gastrointestinal Symptom Rating Scale; (3) celiac disease using Celiac Symptom Index and (4) pancreatic exocrine insufficiency with Pancreatic Exocrine Insufficiency Questionnaire. Logistic regression and multiple regression analyses will identify risk factors and gastrointestinal complications. Cluster analyses and machine learning will classify different symptoms and co-existing presentations, into a likely diagnosis. We seek biomarkers for autonomic neuropathy by characterizing development of retinopathy using the Visual Function Questionnaire-25 and peripheral neuropathy by the Michigan neuropathy questionnaire. Participants are re-examined yearly for disease progression over time.ResultsFrom focus group studies gastrointestinal symptoms are of major concern in diabetes. Potentially, estimates of symptom prevalence, risk factor identification and classifications of gastrointestinal complications can be unraveled for feedback to health care providers.ConclusionThe web-based DICODI project will open up possibilities to detect gastrointestinal complications of diabetes in a societal setting, benefitting people living with diabetes, health care professionals, and society.
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| 10. |
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| 11. |
- Andreasson, Anna, et al.
(författare)
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An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years : A Prospective Population-Based Study in Sweden
- 2021
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 116:1, s. 210-213
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing.METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21–79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22–80 years, rr = 87%), 1995 (n = 1,139, 20–85 years, rr = 76%), and 2011 (n = 1,175, 20–93 years, rr = 63%).RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60–4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42–1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50–2.73).DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.
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| 12. |
- Dahlgren, David, et al.
(författare)
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Fasted and fed state human duodenal fluids : Characterization, drug solubility, and comparison to simulated fluids and with human bioavailability
- 2021
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 163, s. 240-251
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Tidskriftsartikel (refereegranskat)abstract
- Accurate in vivo predictions of intestinal absorption of low solubility drugs require knowing their solubility in physiologically relevant dissolution media. Aspirated human intestinal fluids (HIF) are the gold standard, followed by simulated intestinal HIF in the fasted and fed state (FaSSIF/FeSSIF). However, current HIF characterization data vary, and there is also some controversy regarding the accuracy of FaSSIF and FeSSIF for predicting drug solubility in HIF. This study aimed at characterizing fasted and fed state duodenal HIF from 16 human volunteers with respect to pH, buffer capacity, osmolarity, surface tension, as well as protein, phospholipid, and bile salt content. The fasted and fed state HIF samples were further used to investigate the equilibrium solubility of 17 representative low-solubility small-molecule drugs, six of which were confidential industry compounds and 11 were known and characterized regarding chemical diversity. These solubility values were then compared to reported solubility values in fasted and fed state HIF, FaSSIF and FeSSIF, as well as with their human bioavailability for both states. The HIF compositions corresponded well to previously reported values and current FaSSIF and FeSSIF compositions. The drug solubility values in HIF (both fasted and fed states) were also well in line with reported solubility data for HIF, as well as simulated FaSSIF and FeSSIF. This indicates that the in vivo conditions in the proximal small intestine are well represented by simulated intestinal fluids in both composition and drug equilibrium solubility. However, increased drug solubility in the fed vs. fasted states in HIF did not correlate with the human bioavailability changes of the same drugs following oral administration in either state.
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| 13. |
- Diaz Tartera, Hetzel O., et al.
(författare)
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Validation of SmartPill® wireless motility capsule for gastrointestinaltransit time : Intra-subject variability, software accuracy and comparison with video capsule endoscopy
- 2017
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 29:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is interest in ultimately combining endoscopy and motility assessments. Gastric emptying (GET), small bowel (SBTT), colon (CTT) and whole gut transit (WGTT) times are conveniently obtained by SmartPill® wireless motility capsule (WMC) that records luminal pH, temperature and pressure. Reproducibility within same subjects and accuracy of software derived times (MotiliGI® ) were investigated for diagnostic application. GET and SBTT were separately measured using video capsule endoscopy (VCE). The aim of this investigation was to assess same subject reproducibility of WMC, accuracy of software derived transit times and relate to Pillcam® SB (small bowel) VCE motility data.METHODS: Seventy three healthy adults ingested a 260 kcal mixed meal followed by WMC tests. Food intake was permitted after 6 hours. Regional transit data was obtained for GET, SBTT and CTT, the sum yielding WGTT. Nineteen subjects repeated WMC tests 2 or 4 weeks later; a separate 70 underwent VCE while fasted.KEY RESULTS: Visually derived data from WMC yielded GET 3.46±0.27, SBTT 5.15±0.21, CTT 20.76±1.19 and WGTT 29.53±1.28 hours (mean±SEM). Pearson's correlation coefficients (r) against software derived results were: GET 0.78 (P<.0001), SBTT 0.28 (P<.05), CTT 0.96 (P<.0001), WGTT 0.99 (P<.0001). VCE yielded lower GET (0.71±0.08 hours) and SBTT (4.15±0.13 hours).CONCLUSIONS AND INFERENCES: GET, SBTT, CTT and WGTT obtained by WMC are commensurate with literature values, including by other methods. Visually and software derived transit times have strongest correlations for CTT and WGTT. WMC yields longer GET and SBTT than VCE, perhaps due to meal related effects on motility.
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| 14. |
- Edholm, T., et al.
(författare)
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Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis
- 2010
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 22:11, s. 1191-e315
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Tidskriftsartikel (refereegranskat)abstract
- Background Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are major incretins with important effects on glucoregulatory functions. The aim of this study was to investigate effects of GIP and GLP-1 on gastric emptying and appetite after a mixed meal, and effects on insulin secretion and glucose disposal in humans. Methods Randomized crossover single-blind study in 17 healthy volunteers receiving GIP (2 or 5 pmol kg−1 min−1, n = 8), GLP-1 (0.75 pmol kg−1 min−1, n = 9) or NaCl for 180 min with a radionuclide-labeled omelette and fruit punch (370 kcal). Outcome measures were gastric emptying rate, insulinogenic index, hunger, satiety, desire to eat, and prospective food consumption. Blood was analyzed for GIP, GLP-1, glucagon, C-peptide, peptide YY (PYY) and ghrelin. Key Results Glucose-dependent insulinotropic polypeptide 2 and 5 pmol kg−1 min−1 decreased gastric half-emptying time from 128.5 ± 34.0 min in controls to 93.3 ± 6.3 and 85.2 ± 11.0 min (P < 0.05). Glucose-dependent insulinotropic polypeptide 5 pmol kg−1 min−1 decreased postprandial glucose (P < 0.001) and insulin (P < 0.05) with increased insulinogenic index. Glucose-dependent insulinotropic polypeptide had no effects on hunger, desire to eat, satiety or prospective consumption. Glucagon-like peptide-1 0.75 pmol kg−1 min−1 increased half-emptying time from 76.6 ± 7.6 min to 329.4 ± 71.6 (P < 0.01). Glucagon-like peptide-1 decreased plasma glucose and insulin (both P < 0.05–0.001), and increased insulinogenic index markedly. Hunger, desire to eat and prospective consumption were decreased (P < 0.05), and satiety borderline increased (P < 0.06). Conclusion & Inferences The incretin effect of GIP and GLP-1 differs as GLP-1 exerts a strong glucoregulatory incretin through inhibition of gastric emptying, which GIP does not. Thus, GLP-1 as incretin mimetic may offer unique benefits in terms of weight loss in treatment of type 2 diabetes.
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| 15. |
- Edholm, T, et al.
(författare)
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The incretin hormones GIP and GLP-1 in diabetic rats : effects on insulin secretion and small bowel motility
- 2009
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 21:3, s. 313-321
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Tidskriftsartikel (refereegranskat)abstract
- Incretin hormones often display inhibitory actions on gut motility. The aim of this study was to investigate if altered responsiveness to glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) as regards insulin release and small bowel motility could bring further clarity to the pathophysiology of diabetes in the Goto-Kakizaki (GK) rat. The isolated perfused pancreas was studied in male GK and Wistar rats (controls) under euglycemic and hyperglycemic conditions. Glucose-dependent insulinotropic peptide (10 nmol L−1) or GLP-1 (10 nmol L−1) were added to the medium and perfusate was collected and analysed for insulin. Moreover, GK and Wistar rats were supplied with bipolar electrodes in the small bowel and myoelectric activity was recorded during intravenous administration of GIP (1–400 pmol kg−1 min−1) or GLP-1 (0.1–20 pmol kg−1 min−1). Finally, tissue was collected from GK and Wistar rats for RNA extraction. Under euglycemia, GIP and GLP-1 stimulated the initial insulin response by 10-fold in GK rats (P < 0.05). At later hyperglycemia, the insulin response to GIP and GLP-1 was blunted to about one-third compared with controls (P < 0.05). In the bowel GLP-1 was about 2.6–16.7 times more potent than GIP in abolishing the migrating myoelectric complex in the GK and control rats. Polymerase chain reaction (PCR) showed GIP and GLP-1 receptor gene expression in pancreatic islets and in small bowel. The initially high, but later low insulin responsiveness to stimulation with GIP and GLP-1 along with inhibition of small bowel motility in the GK rat indicates a preserved incretin response on motility in diabetes type 2.
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| 16. |
- Fadda, Hala M, et al.
(författare)
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Intra- and inter-subject variability in gastric pH following a low-fat, low-calorie meal
- 2022
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 625
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Tidskriftsartikel (refereegranskat)abstract
- Food can alter drug bioavailability through gastric pH changes. Time spent at gastric pH ranges is reported here, including variability data following ingestion of a light, mixed, 260 kcal meal. pH data was obtained for 20 healthy subjects undergoing SmartPill™ wireless motility capsule investigations on three separate visits. Gastric phase pH was sorted into pH < 2, 2-3, 3-4, 4-5 and > 5. All visits and all subjects were pooled to determine median time (25-75th percentiles) in minutes. Gastric emptying time was 176 (137-205) min with the majority of time, 111 (67 - 163), spent at pH < 2. Times spent at pH 2-3 and 3-4 were similar: 17 (5.7 - 35.6) and 18 (7.2-29.3). Time spent at pH 4-5 was 9 (1.3-20.6) and at pH > 5 was 0.7 (0-4.4). Intra-subject variability as determined by robust coefficient of variation (RCV)% was 30 % for pH < 2, 57 % for pH 2-3, 71 % for pH 3-4, 106 % for pH 4-5 and 144 % for pH > 5. Inter-subject variability RCV% was 49 % for pH < 2, 89 % for pH 2-3, 54 % for pH 3-4, 97 % for pH 4-5 and 148 % for pH > 5. Inter-subject variability can be up to approximately twofold higher than intra-subject variability at the lower pH ranges.
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| 17. |
- Frigstad, Svein Oskar, et al.
(författare)
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The NIMO Scandinavian Study : A Prospective Observational Study of Iron Isomaltoside Treatment in Patients with Iron Deficiency
- 2017
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Ingår i: Gastroenterology Research and Practice. - : Hindawi Limited. - 1687-6121 .- 1687-630X. ; 2017
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Tidskriftsartikel (refereegranskat)abstract
- Background. Intravenous iron allows for efficient and well-tolerated treatment in iron deficiency and is routinely used in diseases of the gastrointestinal tract. Objective. The aims of this study were to determine the probability of relapse of iron deficiency over time and to investigate treatment routine, effectiveness, and safety of iron isomaltoside. Methods. A total of 282 patients treated with iron isomaltoside were observed for two treatments or a minimum of one year. Results. Out of 282 patients, 82 had Crohn's disease and 67 had ulcerative colitis. Another 133 patients had chronic blood loss, malabsorption, or malignancy. Patients who received an iron isomaltoside dose above 1000 mg had a 65% lower probability of needing retreatment compared with those given 1000 mg. A clinically significant treatment response was shown, but in 71/191 (37%) of patients, anaemia was not corrected. The mean dose given was 1100 mg, lower than the calculated total iron need of 1481 mg. Adverse drug reactions were reported in 4% of patients. Conclusion. Iron isomaltoside is effective with a good safety profile, and high doses reduce the need for retreatment over time. Several patients were anaemic after treatment, indicating that doses were inadequate for full iron correction.
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| 18. |
- Graven-Nielsen, Christoffer S., et al.
(författare)
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Opioids in the Treatment of Chronic Idiopathic Diarrhea in Humans : A Systematic Review and Treatment Guideline
- 2023
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Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:7
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Forskningsöversikt (refereegranskat)abstract
- In patients with chronic idiopathic diarrhea resistant to standard treatment, opioids are often used as rescue therapy. This systematic review investigated opioid effects on gut function in chronic diarrhea. PubMed and Embase were searched regarding effects of opioid agonists on the gastrointestinal tract in humans with chronic or experimentally induced diarrhea. A total of 1472 relevant articles were identified and, after thorough evaluation, 11 clinical trials were included. Generally, studies reported a reduction in stool frequency and an increase in transit time during treatment with the opioid receptor agonists loperamide, asimadoline, casokefamide, and codeine compared with placebo. Loperamide and diphenoxylate significantly improved stool consistency compared with placebo, whereas asimadoline showed no such effects. Compared with placebo, loperamide treatment caused less abdominal pain and urgency. Asimadoline showed no significant subjective improvements, but fedotozine was superior to placebo in reducing abdominal pain and bloating in selected patients. Only two relevant studies were published within the last 20 years, and standardized endpoint measures are lacking. Most trials included few participants, and further evidence is needed from larger, prospective studies. Likewise, consensus is needed to standardize endpoints for stool frequency, transit time, and consistency to conduct future meta-analyses on opioids in management of chronic idiopathic diarrhea.
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| 19. |
- Grüttner, Jana, et al.
(författare)
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Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection
- 2023
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Giardia intestinalis is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to G. intestinalis trophozoites, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, “non-fit” or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, “fit” trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active G. intestinalis suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and G. intestinalis gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how G. intestinalis infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite.Author summaryDiarrhoeal infectious diseases are still a major problem worldwide, each year killing nearly 800,000 children. These infections are caused by a variety of pathogenic bacteria, viruses, fungi and protozoa. The protozoan parasite Giardia intestinalis is the most common eukaryotic intestinal pathogen found in humans. In contrast to most bacteria and viruses that cause diarrhoea, Giardia parasites elicit a highly variable clinical picture and often do not cause pronounced inflammation in the intestine of infected patients. Here we show, by using human intestinal epithelial cells derived from adult intestinal stem cells, that “fit” Giardia parasites can actively suppress epithelial inflammatory signalling, while their “non-fit” counterparts instead induce inflammatory responses. These two faces of the parasite are associated with specific gene expression programs and may explain the earlier observed high variability in outcome of a Giardia infection, and its modulatory effect on infection by other intestinal pathogens.
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| 20. |
- Gryback, Per, et al.
(författare)
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Gastroparesis versus dyspepsia by intragastric meal distribution : new diagnostics and definitions ahead
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:2, s. 251-255
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Tidskriftsartikel (refereegranskat)abstract
- Gastroparesis often presents a challenge to the practicing gastroenterologist. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also significant disruption of social activities that often center around food. The treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic and idiosyncratic nature of the illness, often with some common psychiatric co-morbidity, parallels other functional disorders of the gastrointestinal tract. These parallels have provided the rationale for studies investigating alternative diagnostic features of the gastric emptying test as employed in the clinical setting. Hence, not only the regular cut-offs of 60% or 10% gastric retention of a meal at 2 and 4 h, but also a new concept, the intragastric meal distribution at time 0 (IMD0) is now introduced as a plausible diagnostic feature that should be more aligned with the patients' symptoms as they appear in close connection with the meal. Impaired gastric accommodation with absence of fundic relaxation followed by dumping of the meal into antrum is suggested to be diagnostic for functional dyspepsia and gastroparesis. The diagnostic cut-off is considered when more than 57% of the meal is distributed to the distal part of the stomach immediately on food intake. This new diagnostic feature of the gastric emptying profile lend support to better understanding of the patients' symptoms and provides a new basis for pharmacological treatment options in gastroparesis that may provide an improved quality of life in affected individuals.
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| 21. |
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| 22. |
- Gustavsson, Anders, et al.
(författare)
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Clinical trial : colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study
- 2010
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 32:8, s. 984-989
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.
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| 23. |
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| 24. |
- Karimian, N., et al.
(författare)
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The effects of added whey protein to a pre-operative carbohydrate drink on glucose and insulin response
- 2018
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:5, s. 620-627
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPre-operative complex carbohydrate (CHO) drinks are recommended to attenuate post-operative insulin resistance. However, many institutions use simple CHO drinks, which while convenient, may have less metabolic effects. Whey protein may enhance insulin release when added to complex CHO. The aim of this study was to compare the insulin response to simple CHO vs. simple CHO supplemented with whey protein.MethodsTwelve healthy volunteers participated in this double-blinded, within subject, cross-over design study investigating insulin response to simple CHO drink vs. simple CHO+whey (CHO+W) drink. The primary outcome was the accumulated insulin response during 180min after ingestion of the drinks (Area under the curve, AUC). Secondary outcomes included plasma glucose and ghrelin levels, and gastric emptying rate estimated by acetaminophen absorption technique. Data presented as mean (SD).ResultsThere was no differences in accumulated insulin response after the CHO or CHO+W drinks [AUC: 15 (8) vs. 20 (14)nmol/l, P=0.27]. Insulin and glucose levels peaked between 30 and 60min and reached 215 (95)pmol/l and 7 (1)mmol/l after the CHO drink and to 264 (232)pmol/l and 6.5 (1)mmol/l after the CHO+W drink. There were no differences in glucose or ghrelin levels or gastric emptying with the addition of whey.ConclusionThe addition of whey protein to a simple CHO drink did not change the insulin response in healthy individuals. The peak insulin responses to simple CHO with or without whey protein were lower than that previously reported with complex CHO drinks. The impact of simple carbohydrate drinks with lower insulin response on peri-operative insulin sensitivity requires further study.
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| 25. |
- Lundquist, Patrik, et al.
(författare)
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Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
- 2022
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:9, s. 14210-14229
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Tidskriftsartikel (refereegranskat)abstract
- Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
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