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Hellström, Per M.
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Publications (10 of 97) Show all publications
Marrinan, S. L., Otiker, T., Vasist, L. S., Gibson, R. A., Sarai, B. K., Barton, M. E., . . . Burn, D. J. (2018). A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.. Movement Disorders, 33(2), 329-332
Open this publication in new window or tab >>A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.
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2018 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, no 2, p. 329-332Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD.

METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days.

RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l-dopa concentration was reduced, indicating more rapid absorption of l-dopa. Camicinal resulted in significant reduction in OFF time (-2.31 hours; 95% confidence interval: -3.71, -0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS-UPDRS score (-12.5; 95% confidence interval: -19.67, -5.29). Camicinal treatment was generally well tolerated.

CONCLUSIONS: PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l-dopa. This study provides evidence of an improvement of the motor response to l-dopa in people with PD treated with camicinal 50 mg once-daily compared with placebo, which will require further evaluation.

Keywords
Clinical trials Randomized controlled (CONSORT agreement), Parkinson's disease/parkinsonism
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-343107 (URN)10.1002/mds.27259 (DOI)000424815100022 ()29278279 (PubMedID)
Funder
GlaxoSmithKline (GSK)
Available from: 2018-02-25 Created: 2018-02-25 Last updated: 2018-03-26Bibliographically approved
Keller, J., Bassotti, G., Clarke, J., Dinning, P., Fox, M., Grover, M., . . . Camilleri, M. (2018). Advances in the diagnosis and classification of gastric and intestinal motility disorders. Nature Reviews. Gastroenterology & Hepatology, 15(5), 291-308
Open this publication in new window or tab >>Advances in the diagnosis and classification of gastric and intestinal motility disorders
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2018 (English)In: Nature Reviews. Gastroenterology & Hepatology, ISSN 1759-5045, E-ISSN 1759-5053, Vol. 15, no 5, p. 291-308Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-356201 (URN)10.1038/nrgastro.2018.7 (DOI)000430799600008 ()29622808 (PubMedID)
Available from: 2018-07-20 Created: 2018-07-20 Last updated: 2018-07-20Bibliographically approved
Hellström, P. M., Lonnkvist, M., Tartera, H. O. D., Befrits, R. & Holst, M. (2018). Faecal calprotectin predicts sustained treatment response of infliximab induction therapy superior to C-reactive protein and clinical activity scores in inflammatory bowel disease. Journal of Crohn's & Colitis, 12, S310-S311
Open this publication in new window or tab >>Faecal calprotectin predicts sustained treatment response of infliximab induction therapy superior to C-reactive protein and clinical activity scores in inflammatory bowel disease
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S310-S311Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-357064 (URN)000427318901184 ()
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Halim, A., Degerblad, M., Sundbom, M., Karlbom, U., Juul Holst, J., Webb, D.-L. & Hellström, P. M. (2018). Glucagon-like peptide-1 inhibits prandial gastrointestinal motility through myenteric neuronal mechanisms in humans. Journal of Clinical Endocrinology and Metabolism, 103(2), 575-585
Open this publication in new window or tab >>Glucagon-like peptide-1 inhibits prandial gastrointestinal motility through myenteric neuronal mechanisms in humans
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2018 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 2, p. 575-585Article in journal (Refereed) Published
Abstract [en]

Context: Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility.

Objective: Investigate whether physiological plasma concentrations of GLP-1 can inhibit human postprandial gastrointestinal motility; determine target mechanism of GLP-1 and analogue ROSE-010 action.

Design: Single-blind parallel study.

Setting: University research laboratory.

Participants: Healthy volunteers investigated with antroduodenojejunal manometry. Human gastric, intestinal and colonic muscle strips.

Interventions: Motility indices (MI) obtained before and during infusion of saline or GLP-1 were compared. Plasma GLP-1 and glucagon-like peptide-2 (GLP-2) measured by radioimmunoassay. Gastrointestinal muscle strips, pre-contracted with bethanechol/electric field stimulation (EFS), investigated for GLP-1- or ROSE-010-induced relaxation. GLP-1, GLP-2 and their receptors localized by immunohistochemistry. Action mechanisms studied employing exendin(9-39)amide, Lω-nitro-monomethylarginine (L-NMMA), 2´,5´-dideoxyadenosine (DDA), tetrodotoxin (TTX).

Main outcome measures: Hypothesize postprandial gastric relaxation induced by GLP-1, the mechanism of which intrinsic neuronally-mediated.

Results: Food intake increased MI to 6.4±0.3 (antrum), 5.7±0.4 (duodenum) and 5.9±0.2 (jejunum). GLP-1 administered intravenously raised plasma GLP-1, but not GLP-2. GLP-1 0.7 pmol/kg·min significantly suppressed MI to 4.6±0.2, 4.7±0.4 and 5.0±0.2, respectively, while 1.2 pmol/kg·min suppressed corresponding MI to 5.4±0.2, 4.4±0.3 and 5.4±0.3 (p<0.0001-0.005). GLP-1 and ROSE-010 prevented bethanechol- or EFS-induced muscle contractions (p <0.005-0.05). Inhibitory responses to GLP-1 and ROSE-10 were blocked by exendin(9-39)amide, L-NMMA, DDA or TTX (all p <0.005-0.05). GLP-1 and GLP-2 were localized to epithelial cells; GLP-1 also in myenteric neurons. GLP-1R and GLP-2R were localized at myenteric neurons but not muscle, GLP-1R also in epithelial cells.

Conclusions: GLP-1 inhibits postprandial motility through GLP-1R at myenteric neurons, involving nitrergic and cAMP-dependent mechanisms.

National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-334892 (URN)10.1210/jc.2017-02006 (DOI)000424937300025 ()29177486 (PubMedID)
Funder
Swedish Research Council, 7916The Karolinska Institutet's Research FoundationSwedish Society of MedicineSven Jerring Foundation
Available from: 2017-11-28 Created: 2017-11-28 Last updated: 2018-04-16Bibliographically approved
Wallner, B., Bjoer, O., Andreasson, A., Hellström, P. M., Forsberg, A. M., Talley, N. J. & Agreus, L. (2018). Identifying clinically relevant sliding hiatal hernias: a population-based endoscopy study. Scandinavian Journal of Gastroenterology, 53(6), 657-660
Open this publication in new window or tab >>Identifying clinically relevant sliding hiatal hernias: a population-based endoscopy study
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2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 6, p. 657-660Article in journal (Refereed) Published
Abstract [en]

Objectives: The clinical relevance of small to moderate sliding hiatal hernias is controversial. The aims of the present study were to (1) investigate which symptoms are associated with sliding hiatal hernias and (2) define the length of a sliding hiatal hernia at which gastrointestinal symptoms occur.Methods: A study population representative of the general Swedish population answered a questionnaire regarding gastrointestinal symptoms and was investigated with an upper endoscopy. The length of any sliding hiatal hernia was measured.Results: Only reflux-related symptoms were associated with length of the hiatal hernia (acid regurgitation OR 1.46, CI 1.19-1.79, heartburn OR 1.27, CI 1.05-1.54), and the association did not become significant until an axial hiatal hernia length of 2cm.Conclusions: Only reflux symptoms could be attributed to sliding hiatal hernias. Hiatal hernias less than 2cm should be considered clinically insignificant.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Endoscopy, sliding hiatal hernia, gastroesophageal reflux, gastroesophageal junction
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-360555 (URN)10.1080/00365521.2018.1458896 (DOI)000438146900004 ()29616831 (PubMedID)
Available from: 2018-09-14 Created: 2018-09-14 Last updated: 2018-09-14Bibliographically approved
Andersson, H., Hellström, P. M. & Frykholm, P. (2018). Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children. Pediatric Anaesthesia, 28(1), 46-52
Open this publication in new window or tab >>Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children
2018 (English)In: Pediatric Anaesthesia, ISSN 1155-5645, E-ISSN 1460-9592, Vol. 28, no 1, p. 46-52Article in journal (Refereed) Published
Abstract [en]

Background

Children often starve for longer than recommended by current preoperative fasting guidelines.

Aims

We studied the effects of implementing a more lenient fasting regimen on the duration of clear fluid fasting, as well as the incidence of extended fasting in children.

Methods

Preoperative duration of clear fluid fasting was recorded for patients scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This group was compared with a cohort in the same unit 1year after transitioning to a 6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting regimen has been implemented for over a decade was also studied for comparison.

Results

Patients fasting according to the 6-4-2 fasting regimen (n=66) had a median fasting time for clear fluids of 4.0h and a 33.3% incidence of fasting more than 6h. After transitioning to the 6-4-0 fasting regimen (n=64), median duration of fasting for clear fluids decreased to 1.0h, and the incidence of fasting more than 6h decreased to 6.3%. In the second unit (n=73), median fasting time was 2.2h and the proportion of patients fasting more than 6h was 21.9%.

Conclusion

The introduction and implementation of the 6-4-0 fasting regimen reduces median fluid fasting duration and the number of children subjected to extended fasting.

Keywords
anesthesia, children, fasting, fluids, preoperative
National Category
Anesthesiology and Intensive Care Pediatrics
Identifiers
urn:nbn:se:uu:diva-343890 (URN)10.1111/pan.13282 (DOI)000417604600008 ()29168341 (PubMedID)
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-03-08Bibliographically approved
Farmer, A. D., Wegeberg, A.-M. -., Brock, B., Hobson, A. R., Mohammed, S. D., Scott, S. M., . . . Brock, C. (2018). Regional gastrointestinal contractility parameters using the wireless motility capsule: inter-observer reproducibility and influence of age, gender and study country. Alimentary Pharmacology and Therapeutics, 47(3), 391-400
Open this publication in new window or tab >>Regional gastrointestinal contractility parameters using the wireless motility capsule: inter-observer reproducibility and influence of age, gender and study country
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2018 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 47, no 3, p. 391-400Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-341481 (URN)10.1111/apt.14438 (DOI)000419586100008 ()29210098 (PubMedID)
Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-02-28Bibliographically approved
Al-Saffar, A. K., Halim, M. A., Hall, G., Hellström, P. M. & Webb, D.-L. (2018). Small intestinal lactulose and sucralose hyper-permeability in inflammatory bowel disease. Journal of Crohn's & Colitis, 12, S124-S124
Open this publication in new window or tab >>Small intestinal lactulose and sucralose hyper-permeability in inflammatory bowel disease
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2018 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, p. S124-S124Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-357062 (URN)000427318900189 ()
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Mikami, T., Ito, K., Diaz, H., Hellström, P. M., Mochiki, E., Takemi, S., . . . Sakai, T. (2018). Study of termination of postprandial gastric contractions in humans, dogs and Suncus murinus: role of motilin- and ghrelin-induced strong contraction.. Acta Physiologica, 222(2), Article ID e12933.
Open this publication in new window or tab >>Study of termination of postprandial gastric contractions in humans, dogs and Suncus murinus: role of motilin- and ghrelin-induced strong contraction.
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2018 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, no 2, article id e12933Article in journal (Refereed) Published
Abstract [en]

AIM: Stomach contractions show two types of specific patterns in many species, that is migrating motor contraction (MMC) and postprandial contractions (PPCs), in the fasting and fed states respectively. We found gastric PPCs terminated with migrating strong contractions in humans, dogs and suncus. In this study, we reveal the detailed characteristics and physiological implications of these strong contractions of PPC.

METHODS: Human, suncus and canine gastric contractions were recorded with a motility-monitoring ingestible capsule and a strain-gauge force transducer. The response of motilin and ghrelin and its receptor antagonist on the contractions were studied by using free-moving suncus.

RESULTS: Strong gastric contractions were observed at the end of a PPC in human, dog and suncus models, and we tentatively designated this contraction to be a postprandial giant contraction (PPGC). In the suncus, the PPGC showed the same property as those of a phase III contraction of MMC (PIII-MMC) in the duration, motility index and response to motilin or ghrelin antagonist administration. Ghrelin antagonist administration in the latter half of the PPC (LH-PPC) attenuated gastric contraction prolonged the duration of occurrence of PPGC, as found in PII-MMC.

CONCLUSION: It is thought that the first half of the PPC changed to PII-MMC and then terminated with PIII-MMC, suggesting that PPC consists of a digestive phase (the first half of the PPC) and a discharge phase (LH-PPC) and that LH-PPC is coincident with MMC. In this study, we propose a new approach for the understanding of postprandial contractions.

Keywords
ghrelin, migrating motor contraction, motilin, postprandial contraction, suncus
National Category
Medical and Health Sciences
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-334233 (URN)10.1111/apha.12933 (DOI)000423367700012 ()28786555 (PubMedID)
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-03-07Bibliographically approved
Karimian, N., Moustafa, M., Mata, J., Al-Saffar, A. K., Hellström, P. M., Feldman, L. S. & Carli, F. (2018). The effects of added whey protein to a pre-operative carbohydrate drink on glucose and insulin response. Acta Anaesthesiologica Scandinavica, 62(5), 620-627
Open this publication in new window or tab >>The effects of added whey protein to a pre-operative carbohydrate drink on glucose and insulin response
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2018 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, no 5, p. 620-627Article in journal (Refereed) Published
Abstract [en]

Background

Pre-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.

Methods

Twelve 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).

Results

There 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.

Conclusion

The 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.

National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-354097 (URN)10.1111/aas.13069 (DOI)000429532400005 ()29377065 (PubMedID)
Available from: 2018-06-19 Created: 2018-06-19 Last updated: 2018-06-19Bibliographically approved
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