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Hellström, Per M.
Alternative names
Publications (10 of 99) 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
Söderquist, F., Sundberg, I., Ramklint, M., Widerström, R., Hellström, P. M. & Cunningham, J. (2018). Daytime Salivary Melatonin Related to Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care. Paper presented at 73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), 2018, New York, NY. Biological Psychiatry, 83(9), S185-S186
Open this publication in new window or tab >>Daytime Salivary Melatonin Related to Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 9, p. S185-S186Article in journal, Meeting abstract (Other academic) Published
Keywords
Melatonin, Irritable Bowel Syndrome, Depression
National Category
Psychiatry Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-361431 (URN)000432466300462 ()
Conference
73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), 2018, New York, NY
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-12Bibliographically 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
Hellström, P. M. & Al-Saffar, A. (2018). Gastroparesis: pharmacotherapy and cardiac risk. Scandinavian Journal of Gastroenterology, 53(5), 513-518
Open this publication in new window or tab >>Gastroparesis: pharmacotherapy and cardiac risk
2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 5, p. 513-518Article, review/survey (Refereed) Published
Abstract [en]

Background: Gastroparesis is characterized by abnormal gastric motility and delayed emptying with symptoms of early satiety, postprandial fullness, bloating, nausea, vomiting and abdominal pain. Pharmacological discovery has been lagging because potential drugs often are associated with abnormalities of electrical conduction of the myocardium due to interaction with cardiac ion channels leading to limited pharmaceutical options for development of new drugs.

Objective: Addresses the safety of drugs for gastroparesis in terms of cardiotoxicity related to the clinical use of prokinetics and antiemetics.

Methods: Survey of QT drugs List and review of current literature.

Results: Many prokinetic drugs are associated with cardiac adverse events and manifest as prolongation of ventricular repolarization, i.e., QT-interval prolongation of the electrocardiogram. This disturbance may develop into a potentially fatal polymorphic ventricular tachyarrhythmia; Torsade de Pointes. Co-administration of prokinetics with other drugs affecting the repolarization process, pharmacokinetic interactions leading to increased blood levels, or the presence of clinical risk factors could further increase the risk for cardiac arrhythmias.

Conclusions: It is important that clinicians managing gastroparesis are aware of the arrhythmogenic potential of drugs used clinically and risk factors that contribute to QT prolongation to safeguard patients at risk for drug-induced cardiac arrhythmia.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
Torsade de pointes, QT interval prolongation, gastroparesis, gastroprokinetic, prokinetic, adverse drug reactions
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-365882 (URN)10.1080/00365521.2017.1401117 (DOI)000435599700002 ()29157021 (PubMedID)
Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2018-11-20Bibliographically 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
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