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Hellström, Per M.
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Publications (10 of 91) 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.

Keyword
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
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
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.

Keyword
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
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.

Keyword
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
Frigstad, S. O., Hammarlund, P., Bonderup, O., Rannem, T., Haaber, A., Fallingborg, J., . . . Hellström, P. M. (2017). Anaemia and iron deficiency in gastroenterology: a Scandinavian prospective, observational study of iron isomaltoside in clinical practice. Journal of Crohn's & Colitis, 11, S351-S351
Open this publication in new window or tab >>Anaemia and iron deficiency in gastroenterology: a Scandinavian prospective, observational study of iron isomaltoside in clinical practice
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2017 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, p. S351-S351Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-328843 (URN)000398606901067 ()28172956 (PubMedID)
Available from: 2017-09-04 Created: 2017-09-04 Last updated: 2017-09-04Bibliographically approved
Webb, D.-L., Abrahamsson, N., Sundbom, M. & Hellström, P. M. (2017). Bariatric surgery - time to replace with GLP-1?. Scandinavian Journal of Gastroenterology, 52(6-7), 635-640
Open this publication in new window or tab >>Bariatric surgery - time to replace with GLP-1?
2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 635-640Article, review/survey (Refereed) Published
Abstract [en]

Obesity with a body mass index (BMI) over 30kg/m(2) represents a significant risk for increased morbidity and mortality, with reduced life expectancy of about 10 years. Until now, surgical treatment has been the only effective longterm intervention. The currently standardized method of bariatric surgery, gastric bypass, means that many gastrointestinal peptide hormones are activated, yielding net reductions in appetite and food intake. Among the most important gut peptide hormones in this perspective is glucagon-like peptide-1 (GLP-1), which rises sharply after gastric bypass. Consistent with outcomes of this surgery, GLP-1 suppresses appetite and reduces food intake. This implies that GLP-1 has the potential to achieve a similar therapeutic outcome as gastric bypass. GLP-1 analogs, which are used for the treatment of type 2 diabetes mellitus, also lead to significant weight loss. Altered hormonal profiles after gastric bypass therefore indicate a logical connection between gut peptide hormone levels, weight loss and glucose homeostasis. Furthermore, combinations of GLP-1 with other gut hormones such as peptide YY (PYY) and cholecystokinin (CCK) may be able to reinforce GLP-1 driven reduction in appetite and food intake. Pharmacological intenvention in obesity by use of GLP-1 analogs (exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, taspoglutide) and inhibitors of dipeptidyl peptidase-IV (DPP-IV) degradation that inactivate GLP-1 (sitagliptin, vildagliptin), leading to reduced appetite and weight with positive effects on metabolic control, are realistically achievable. This may be regarded as a low-risk therapeutic alternative to surgery for reducing obesity-related risk factors in the obese with lower BMIs.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2017
Keyword
Gastric bypass, gastric emptying, glucagon-like peptides, glucose homeostasis, weight loss
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-328850 (URN)10.1080/00365521.2017.1293154 (DOI)000399808100004 ()28276830 (PubMedID)
Available from: 2017-09-01 Created: 2017-09-01 Last updated: 2017-09-01Bibliographically approved
Zamaratskaia, G., Johansson, D. P., Junqueira, M. A., Deissler, L., Langton, M., Hellström, P. M. & Landberg, R. (2017). Impact of sourdough fermentation on appetite and postprandial metabolic responses - a randomised cross-over trial with whole grain rye crispbread. British Journal of Nutrition, 118(9), 686-697
Open this publication in new window or tab >>Impact of sourdough fermentation on appetite and postprandial metabolic responses - a randomised cross-over trial with whole grain rye crispbread
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2017 (English)In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 118, no 9, p. 686-697Article in journal (Refereed) Published
Abstract [en]

Sourdough fermentation is considered to have beneficial effects on postprandial satiety and metabolic responses, but studies demonstrating effects at physiological conditions are lacking. The aim of this acute breakfast intervention study was to determine the effect of consumption of sourdough-fermented and unfermented rye crispbread on self-rated appetite, postprandial glucose and insulin response in healthy subjects. In all, twenty-four Swedish adults were included in a single-blinded, randomised cross-over trial. Three crispbreads (sourdough-fermented and unfermented whole grain rye and yeast-fermented refined wheat as control) were consumed as part of a standardised breakfast. Subjective appetite score, assessed using visual analogue scale, and plasma glucose and insulin concentrations were measured at baseline and postprandially until 360 and 240 min, respectively. Structural changes and viscosity during mastication and gastric digestion were investigated using in vitro methods. Hunger and desire to eat were lower (P<005) based on AUC measurements after intake of sourdough-fermented rye crispbread compared with after intake of yeast-fermented refined wheat crispbread. On the basis of AUC (0-230 min), insulin response was lowest after intake of unfermented rye crispbread compared with sourdough-fermented rye and yeast-fermented refined wheat crispbread. Degradation of viscous fibres and faster bolus disintegration for the sourdough-fermented bread may partly explain the less favourable metabolic responses compared with unfermented bread. Our results showed that food processing affects the composition and structural characteristics of rye bread, which has implications for appetite and metabolic responses.

Place, publisher, year, edition, pages
CAMBRIDGE UNIV PRESS, 2017
Keyword
Sourdough rye crispbread, Structures, Self-rated appetite, Postprandial glucose, Postprandial insulin
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-344321 (URN)10.1017/S000711451700263X (DOI)000417210100005 ()
Available from: 2018-03-08 Created: 2018-03-08 Last updated: 2018-03-08Bibliographically approved
Nybacka, Å., Hellström, P. M. & Hirschberg, A. L. (2017). Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement in overweight polycystic ovary syndromeSubstudy of randomized trial between diet, exercise and diet plus exercise for weight control. Clinical Endocrinology, 87(6), 680-688
Open this publication in new window or tab >>Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement in overweight polycystic ovary syndromeSubstudy of randomized trial between diet, exercise and diet plus exercise for weight control
2017 (English)In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, no 6, p. 680-688Article in journal (Refereed) Published
Abstract [en]

 Objective: Polycystic ovary syndrome (PCOS) is commonly affected by obesity. PCOS phenotypes are prone to increased waist/hip ratio, insulin resistance and dyslipidaemia. This substudy was undertaken to evaluate the effects of lifestyle interventions on metabolic biomarkers in overweight/obese PCOS women and the interventional effects of dietary components related to metabolic outcomes.

Design: Randomized three-arm parallel study.

Patients: Fifty-seven PCOS women body mass index (BMI >27kg/m(2), age 18-40) were randomly assigned to diet (D, n=19), exercise (E, n=19) or diet plus exercise (DE, n=19) in three-arm fashion over 16weeks. The D group received nutritional counselling by a dietician to reduce their energy intake by at least 600kcal/d. The E group received an ambulatory exercise regimen from a physiotherapist. The DE group had both interventions.

Measurements: Self-reported food intake over 4days, exercise pedometers, BMI, waist/hip ratio, blood pressure, body composition and oral glucose tolerance test were performed before and at the end of intervention.

Results: BMI, waist circumference and total cholesterol were significantly reduced in the D and DE groups, as well as low-density lipoprotein and Homeostasis Model of Assessment index in the D group. In the E group, exercise was increased along with a decrease in BMI and waist circumference. The strongest predictor of reduced BMI was increased fibre intake (-0.44, P=.03), while a decrease in trans fatty acid intake predicted reduced insulinogenic index (0.44, P<.01).

Conclusions: Nutritional counselling with dieting is clearly effective to improve metabolic disturbances in overweight/obese women with PCOS. Increased fibre and reduced trans fatty acid intake are primary predictors of metabolic improvement and weight control.

Place, publisher, year, edition, pages
WILEY, 2017
Keyword
body composition, insulin resistance, lifestyle intervention, obesity
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-343560 (URN)10.1111/cen.13427 (DOI)000415895800007 ()28727165 (PubMedID)
Funder
Stockholm County Council
Note

De 2 sista författarna delar sistaförfattarskapet.

Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2018-03-02Bibliographically approved
Hellström, P. M., Stålhammar, J., Beydogan, H., Huetson, P., Skup, M. & Agreus, L. (2017). Indirect burden of patients with moderate inflammatory bowel disease in Uppsala County Council, Sweden: a retrospective study using real-world data. Journal of Crohn's & Colitis, 11, S457-S457
Open this publication in new window or tab >>Indirect burden of patients with moderate inflammatory bowel disease in Uppsala County Council, Sweden: a retrospective study using real-world data
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2017 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, p. S457-S457Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-328844 (URN)000398606901268 ()
Available from: 2017-09-04 Created: 2017-09-04 Last updated: 2017-09-04Bibliographically approved
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