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  • 51.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Obesity research in adolescence: moving object-hard to target2013Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 98, nr 5, s. 1147-1148Artikkel i tidsskrift (Annet vitenskapelig)
  • 52.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Al-Saffar, Ahmad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Gastroparesis: pharmacotherapy and cardiac risk2018Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, nr 5, s. 513-518Artikkel, forskningsoversikt (Fagfellevurdert)
    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.

  • 53.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Al-Saffar, Anas K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Tartera Diaz, Hetzel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Gannavarapu, Venkata Ram
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Intestinal fatty acid binding protein parallels temporal changes in Harvey-Bradshaw Index and TNF alpha in response to infliximab in Crohn’s disease2017Inngår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, nr suppl 1, s. S389-S389Artikkel i tidsskrift (Fagfellevurdert)
  • 54.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Diaz, Hetzel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Lönnkvist, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Befrits, R.
    Fecal calprotectin and serum C-reactive protein predict outcome of infliximab induction therapy in inflammatory bowel disease2015Inngår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 9, nr S1, s. S287-S288Artikkel i tidsskrift (Annet vitenskapelig)
  • 55.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Uppsala University.
    Halim, Md Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Uppsala University.
    Tryggve, Ljung
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala University.
    Holst, Mikael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Karolinska Institutet.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi. Uppsala University.
    Luminal Nitric Oxide and Plasma Nitrite/Nitrate As Predictors of Colectomy in Corticosteroid-Treated Acute Colitis2015Inngår i: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 148, nr 4, suppl. 1, artikkel-id Sul 231Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Nitric oxide (NO) is known to be up-regulated by the induction of induciblenitric oxide synthase (iNOS) in inflammatory conditions. NO gas can be used as a markerof inflammatory activity in hollow organs. In parallel, plasma nitrite + nitrate (NOx) canreflect the ongoing inflammatory activity. We analyzed rectal NO before and after threedays, as well as plasma NOx in patients on glucocorticosteroid (GC) therapy in hospitalizedpatients. The aim of the study was to evaluate the relationship of rectal luminal NO andcirculating plasma NOx in acute fulminant colitis to the outcome as therapeutic responseor colectomy.

    Methods: 50 patients with median age 41 (range 20-78) years were hospitalizeddue to acute fulminant colitis and received treatment with high-dose GCs. Luminal nitricoxide was analyzed with chemiluminescence before therapy onset of therapy with GC andon day 3 of treatment. NOx was measured by nitrite/nitrate colorimetric assay. NO levelsand plasma NOx were compared to clinical disease activity index and C-reactive protein(CRP).

    Results: 32 responded to GC treatment and 18 did not, resulting in colectomy.The responders had higher luminal NO than non-responders (day 1: 12525±2600, day 3:15590±4157 ppb) vs non-responders (day 1: 2874±1283, day 3: 1137±297 ppb) (p<0.0114).Using an optimal cut-off NO level of 2250 ppb, sensitivity and specificity was 86% and81% for colectomy (p<0.0001). The area under the curve was 0.88 and likelihood ratio4.8. Similarly, plasma NOx was higher in responders vs non-responders (day 1: 6.2±0.3 vs3.9±0.4 umol/L) (p<0.0001). Using plasma NOx, we found a corresponding cut-off at 5umol/L with sensitivity 87% and specificity 87%. The area under the curve was 0.88 andlikelihood ratio 6.7. Luminal NO was also correlated to plasma NOx (r=0.33, p=0.0205).In the responder group, CRP levels decreased (day 1: 22.31±2.95, day 3: 15.69±3.57mg/L), whereas among non-responders CRP levels increased (day 1: 45.83±11.10, day 3:76.35±16.96 mg/L) (p<0.0167). Kaplan-Meier analysis showed that patients with baselineNO levels lower than 2250 ppb were at a significantly higher risk of colectomy within onemonth from onset of GCS treatment (p<0.0001). Twelve out of 18 (67%) in patients withday 1 NO <2250 ppb were colectomized, the corresponding number of patients with NO>2250 ppb was 3 out of 32 (9%). In a similar manner, using plasma NOx <5 uml/L foranalysis, we found 13 (72%) to be colectomized, and with >5 umol/L only two (6%).

    Conclusion: NO and its oxidation product NOx are markers of inflammatory activity in thegut. However, with more intense inflammation and mucosal damage, the less NO is produced.Luminal NO as well as plasma NOx can be used as a sensitive biomarker to predict colectomyin the outcome of acute fulminant colitis

  • 56. Hellström, Per M.
    et al.
    Hein, J
    Bytzer, P
    Björnsson, E
    Kristensen, J
    Schambye, H
    Clinical trial:  The glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome2009Inngår i: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 29, nr 2, s. 198-206Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype.

    AIMS:

    To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study.

    METHODS:

    Eligible patients (n = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 microg, 300 microg and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment.

    RESULTS:

    Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24%P = 0.011, 23%P = 0.005, and 12% after 300 microg, 100 microg and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients (P < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used.

    CONCLUSION:

    ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients.

  • 57.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hendolin, Panu
    Biohit Oyj, Clin Sci, Helsinki, Finland..
    Kaihovaara, Pertti
    Biohit Oyj, Clin Sci, Helsinki, Finland.;Univ Helsinki, Res Unit Acetaldehyde & Canc, Helsinki, Finland..
    Kronberg, Leif
    Abo Akad Univ, Johan Gadolin Proc Chem Ctr, Lab Organ Chem, Turku, Finland..
    Meierjohann, Axel
    Abo Akad Univ, Johan Gadolin Proc Chem Ctr, Lab Organ Chem, Turku, Finland..
    Millerhovf, Anders
    Univ Uppsala Hosp, Clin Trial Consultants, Uppsala, Sweden..
    Paloheimo, Lea
    Biohit Oyj, Clin Sci, Helsinki, Finland..
    Sundelin, Heidi
    Abo Akad Univ, Johan Gadolin Proc Chem Ctr, Lab Organ Chem, Turku, Finland..
    Syrjanen, Kari
    Biohit Oyj, Clin Sci, Helsinki, Finland..
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Salaspuro, Mikko
    Univ Helsinki, Res Unit Acetaldehyde & Canc, Helsinki, Finland..
    Slow-release L-cysteine capsule prevents gastric mucosa exposure to carcinogenic acetaldehyde: results of a randomised single-blinded, cross-over study of Helicobacter-associated atrophic gastritis2017Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, nr 2, s. 230-237Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Methods: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Results: Administration of L-cysteine increased MTCA (p < .0004) and decreased gastric acetaldehyde concentrations by 68% (p < .0001). The peak L-cysteine level was 7552 +/- 2687 mu mol/L at 40 min and peak MTCA level 196 +/- 98 mu mol/L at 80 min after intake. Gastric L-cysteine and MTCA concentrations were maintained for 3 h. The AUC for MTCA was 11-fold higher than acetaldehyde, indicating gastric first-pass metabolism of ethanol. With placebo, acetaldehyde remained elevated also at low ethanol concentrations representing 'non-alcoholic' beverages and food items. Conclusions: After gastric ethanol instillation, slow-release L-cysteine eliminates acetaldehyde to form inactive MTCA, which remains in gastric juice for up to 3 h. High acetaldehyde levels indicate a marked gastric first-pass metabolism of ethanol resulting in gastric accumulation of carcinogenic acetaldehyde. Local exposure of the gastric mucosa to acetaldehyde can be mitigated by slow-release L-cysteine capsules.

  • 58.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Lonnkvist, M.
    Karolinska Inst, Med, Stockholm, Sweden..
    Tartera, Hetzel O. Diaz
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Befrits, R.
    Karolinska Inst, Med, Stockholm, Sweden..
    Holst, M.
    Karolinska Inst, Womens & Childrens Hlth, Stockholm, Sweden..
    Faecal calprotectin predicts sustained treatment response of infliximab induction therapy superior to C-reactive protein and clinical activity scores in inflammatory bowel disease2018Inngår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 12, s. S310-S311Artikkel i tidsskrift (Annet vitenskapelig)
  • 59.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Saito, Yuri A.
    Bytzer, Peter
    Tack, Jan
    Mueller-Lissner, Stefan
    Chang, Lin
    Characteristics of Acute Pain Attacks in Patients With Irritable Bowel Syndrome Meeting Rome III Criteria2011Inngår i: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 106, nr 7, s. 1299-1307Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES:

    An international multicenter, prospective, non-interventional, 2-month study characterized acute pain attacks in patients with irritable bowel syndrome (IBS).

    METHODS:

    Adult patients meeting the Rome III IBS diagnostic criteria with a history of >= 3 pain attacks per month participated in a survey that captured daily and episodic information regarding IBS symptoms and pain attacks for 2 months. Acute pain attacks were defined as a sudden onset or increase in the intensity of IBS abdominal pain with a minimum intensity of 4 (0-10 scale).

    RESULTS:

    The majority (84%) of the 158 patients taking the survey were women with a mean age of 41 years and time since IBS diagnosis of 5 years. The median pain attack frequency was 5.4 attacks per month and was significantly higher in the IBS with diarrhea (IBS-D, 6.4 per month) group vs. the IBS with constipation (4.4 per month) and the IBS with mixed pattern (5.5 per month) groups (P = 0.019). The median pain attack duration was 2.8 h and the median intensity score was 7. The majority of pain attacks resulted in defecation (78%), and occurred more often in IBS-D patients than in other subgroups. The majority of pain attacks (63%) interfered with work and/or daily activities. Medication to manage pain attacks was used by 44% of patients during 29% of attacks. Although used by less than half of all patients, medication helped 66% of attacks treated.

    CONCLUSIONS:

    The frequency of severe pain attacks was 1.4 per week and the majority affected daily activities. However, most of the pain attacks were untreated in IBS patients. Pain attack management is an unmet need of IBS treatment.

  • 60.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Samuelsson, Bodil
    Danderyd Hosp, Div Orthoped, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.;Sophiahemmet Univ Coll, Stockholm, Sweden..
    Al-Ani, Amer N.
    Karolinska Univ Hosp, Dept Clin Sci & Technol Clintec, Div Orthoped, Karolinska Inst, Huddinge, Sweden..
    Hedström, Margareta
    Karolinska Univ Hosp, Dept Clin Sci & Technol Clintec, Div Orthoped, Karolinska Inst, Huddinge, Sweden..
    Normal gastric emptying time of a carbohydrate-rich drink in elderly patients with acute hip fracture: a pilot study2017Inngår i: BMC Anesthesiology, ISSN 1471-2253, E-ISSN 1471-2253, Vol. 17, artikkel-id 23Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Guidelines for fasting in elderly patients with acute hip fracture are the same as for other trauma patients, and longer than for elective patients. The reason is assumed stress-induced delayed gastric emptying with possible risk of pulmonary aspiration. Prolonged fasting in elderly patients may have serious negative metabolic consequences. The aim of our study was to investigate whether the preoperative gastric emptying was delayed in elderly women scheduled for surgery due to acute hip fracture. Methods: In a prospective study gastric emptying of 400 ml 12.6% carbohydrate rich drink was investigated in nine elderly women, age 77-97, with acute hip fracture. The emptying time was assessed by the paracetamol absorption technique, and lag phase and gastric half-emptying time was compared with two gender-matched reference groups: ten elective hip replacement patients, age 45-71 and ten healthy volunteers, age 28-55. Results: The mean gastric half-emptying time in the elderly study group was 53 +/- 5 (39-82) minutes with an expected gastric emptying profile. The reference groups had a mean half-emptying time of 58 +/- 4 (41-106) and 59 +/- 5 (33-72) minutes, indicating normal gastric emptying time in elderly with hip fracture. Conclusion: This pilot study in women with an acute hip fracture shows no evidence of delayed gastric emptying after an orally taken carbohydrate-rich beverage during the pre-operative fasting period. This implies no increased risk of pulmonary aspiration in these patients. Therefore, we advocate oral pre-operative management with carbohydrate-rich beverage in order to mitigate fasting-induced additive stress in the elderly with hip fracture.

  • 61.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Smithson, A.
    Stowell, G.
    Greene, S.
    Kenny, E.
    Damico, C.
    Leone-Bay, A.
    Baughman, R.
    Grant, M.
    Richardson, P.
    Receptor-mediated inhibition of small bowel migrating complex by GLP-1 analog ROSE-010 delivered via pulmonary and systemic routes in the conscious rat2012Inngår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 179, nr 1-3, s. 71-76Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: ROSE-010, a Glucagon-Like Peptide-1 (GLP-1) analog, reduces gastrointestinal motility and relieves acute pain in patients with irritable bowel syndrome (IBS). The rat small bowel migrating myoelectric complex (MMC) is a reliable model of pharmacological effects on gastrointestinal motility. Accordingly, we investigated whether ROSE-010 works through GLP-1 receptors in gut musculature and its effectiveness when administered by pulmonary inhalation. Materials and methods: Rats were implanted with bipolar electrodes at 5, 15 and 25 cm distal to pylorus and myoelectric activity was recorded. First, intravenous or subcutaneous injections of ROSE-010 or GLP-1 (1, 10, 100 mu g/kg) with or without the GLP-1 receptor blocker exendin(9-39)amide (300 mu g/kg.h), were studied. Second, ROSE-010 (100, 200 mu g/kg) Technosphere (R) powder was studied by inhalation. Results: The baseline MMC cycle length was 17.5 +/- 0.8 min. GLP-1 and ROSE-010. administered intravenously or subcutaneously, significantly inhibited myoelectric activity and prolonged MMC cycling; 100 mu g/kg completely inhibited spiking activity for 49.1 +/- 4.2 and 73.3 +/- 7.7 min, while the MMC cycle length increased to 131.1 +/- 11.4 and 149.3 +/- 15.5 min, respectively. Effects of both drugs were inhibited by exendin(9-39) amide. Insufflation of ROSE-010 (100, 200 mu g/kg) powder formulation totally inhibited myoelectric spiking for 52.6 +/- 5.8 and 70.1 +/- 5.4 min, and increased MMC cycle length to 102.6 +/- 18.3 and 105.9 +/- 9.5 min, respectively. Conclusions: Pulmonary delivery of ROSE-010 inhibits gut motility through the GLP-1R similar to natural GLP-1. ROSE-010 causes receptor-mediated inhibition of MMC comparable to that of intravenous or subcutaneous administration. This suggests that ROSE-010 administered as a Technosphere (R) inhalation powder has potential in IBS pain management and treatment.

  • 62.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Stålhammar, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och preventivmedicin.
    Beydogan, H.
    QuintilesIMS, Real World Evidence Solut & HEOR, Solna, Sweden..
    Huetson, P.
    QuintilesIMS, Real World Evidence Solut & HEOR, Solna, Sweden..
    Skup, M.
    AbbVie Inc, N Chicago, IL USA..
    Agreus, L.
    Karolinska Institute.
    Indirect burden of patients with moderate inflammatory bowel disease in Uppsala County Council, Sweden: a retrospective study using real-world data2017Inngår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 11, s. S457-S457Artikkel i tidsskrift (Annet vitenskapelig)
  • 63.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Tack, Jan
    Univ Leuven, Louvain, Belgium..
    Johnson, Lakshmi Vasist
    GlaxoSmithKline, Res Triangle Pk, NC USA..
    Hacquoil, Kimberley
    GlaxoSmithKline, Stevenage, Herts, England..
    Barton, Matthew E.
    GlaxoSmithKline, Res Triangle Pk, NC USA..
    Richards, Duncan B.
    GlaxoSmithKline, Stevenage, Herts, England..
    Alpers, David H.
    Washington Univ, Sch Med, St Louis, MO USA..
    Sanger, Gareth J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, London, England..
    Dukes, George E.
    GlaxoSmithKline, Res Triangle Pk, NC USA..
    The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying2016Inngår i: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 173, nr 11, s. 1768-1777Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND PURPOSE Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis. EXPERIMENTAL APPROACH In a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying (C-13-octanoic acid breath test), pharmacokinetics and safety were primary outcomes. KEY RESULTS Nine of the 10 patients enrolled completed the study. Gastric half-emptying time decreased by -95 min (95% CI: -156.8, -34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half-emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure-response relationship was demonstrated across all doses. The effects of camicinal on gastric half-emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose-proportional pharmacokinetic characteristics and a clear exposure-response relationship with gastric emptying. CONCLUSIONS AND IMPLICATIONS Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.

  • 64.
    Hellström, Per M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Irritable Bowel syndrome: Principles and novel treatment options2011Inngår i: Drugs of the future, ISSN 0377-8282, E-ISSN 2013-0368, Vol. 36, nr 9, s. 669-675Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    There is growing interest in the area of irritable bowel syndrome (IBS) in developing tools to separate various subgroups of this disease in order to identify potentially different pathogenetic mechanisms. From such work, the ultimate goal is tailored treatment for the various subtypes of the disease. Among major achievements in this research, the finding of increased gut permeability is of great interest and suggests a luminal factor as a cause of disease, which would be able to maintain low-grade inflammation. There are various treatment options and significant activity in developing drugs that have the capability to inhibit gut motility and increase luminal secretion. The development of analogues to gut peptide hormones, such as glucagon-like peptide 1, is of primary interest, as these drugs rarely give rise to inconvenient adverse reactions at therapeutic doses. Some of these drugs even exert their action directly on the luminal membranes, such as linaclotide, which means that oral administration is favored to diminish the risk of systemic reactions. The concept of IBS is anticipated to evolve into different disease mechanisms that will serve as the basis for customized treatments.

  • 65. Hopkins, M.
    et al.
    Gibbons, C.
    Caudwel, P.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Naslund, E.
    King, N. A.
    Finlayson, G.
    Blundell, J. E.
    The adaptive metabolic response to exercise-induced weight loss influences both energy expenditure and energy intake2014Inngår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 68, nr 5, s. 581-586Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND/OBJECTIVES: A decline in resting energy expenditure (SEE) beyond that predicted from changes in body composition has been noted following dietary-induced weight loss. However, it is unknown whether a compensatory downregulation in REE also accompanies exercise (EX)-induced weight loss, or whether this adaptive metabolic response influences energy intake (El). SUBJECTS/METHODS: Thirty overweight and obese women (body mass index (BMI) =30.6 +/- 3.6 kg/m(2)) completed 12 weeks of supervised aerobic EX. Body composition, metabolism, El and metabolic-related hormones were measured at baseline, week 6 and post intervention. The metabolic adaptation (MA), that is, difference between predicted and measured SEE was also calculated post intervention (MA(post)), with SEE predicted using a regression equation generated in an independent sample of 66 overweight and obese women (BMI =31.0 +/- 3.9 kg/m(2)). RESULTS: Although mean predicted and measured SEE did not differ post intervention, 43% of participants experienced a greater-than-expected decline in SEE ( 102.9 +/- 77.5 kcal per day). MA(post) was associated with the change in leptin (r= 0.47; P=0.04), and the change in resting fat (r= 0.52; P=0.01) and carbohydrate oxidation (r= 0.44;P= 0.02). Furthermore, MApost was also associated with the change in El following EX (r= 0.44; P=0.01). CONCLUSIONS: Marked variability existed in the adaptive metabolic response to EX. Importantly, those who experienced a downregulation in SEE also experienced an upregulation in El, indicating that the adaptive metabolic response to EX influences both physiological and behavioural components of energy balance.

  • 66. Hopkins, Mark
    et al.
    Gibbons, Catherine
    Caudwell, Phillipa
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Naslund, Erik
    Blundell, John E.
    Finlayson, Graham
    Fasting Leptin Is a Metabolic Determinant of Food Reward in Overweight and Obese Individuals during Chronic Aerobic Exercise Training2014Inngår i: International Journal of Endocrinology, ISSN 1687-8337, E-ISSN 1687-8345, s. 323728-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Changes in food reward have been implicated in exercise-induced compensatory eating behaviour. However, the underlying mechanisms of food reward, and the physiological correlates of exercise-induced changes in food reward, are unknown. Methods. Forty-six overweight and obese individuals completed 12 weeks of aerobic exercise. Body composition, food intake, and fasting metabolic-related hormones were measured at baseline, week six, and postintervention. On separate days, the reward value of high-and-low-fat food (explicit liking and implicit wanting) was also assessed at baseline, week six, and postintervention. Results. Following the intervention, FM, FFM, and VO2peak improved significantly, while fasting leptin decreased. However, food intake or reward did not change significantly. Cross-sectional analyses indicated that FM (P = 0.022) and FFM (P = 0.046) were associated with explicit liking for high-fat food, but implicit wanting was associated with FM only (P = 0.005). Fasting leptin was associated with liking (P = 0.023) and wanting (P = 0.021) for high-fat food. Furthermore, a greater exercise-induced decline in fasting leptin was associated with increased liking (P = 0.018). Conclusion. These data indicate that food reward has a number of physiological correlates. In particular, fasting leptin appears to play an active role in mediating food reward during exercise-induced weight loss.

  • 67. Høyerup, P.
    et al.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Schmidt, P. T.
    Brandt, C. F.
    Askov-Hansen, C.
    Mortensen, P. B.
    Jeppesen, P. B.
    Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser Doppler flowmetry in end-jejunostomy short bowel syndrome patients2013Inngår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 180, nr 1, s. 12-16Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunostomy short bowel syndrome (SBS) patients. Methods: In five SBS patients with end-jejunostomy a specially designed laser Doppler probe was inserted into the stoma nipple, and blood flow measured directly on the jejunal mucosa for 105. min in relation to no treatment, systemic saline infusion, topical adrenaline application and a subcutaneous injection of 800μg native GLP-2. Results: The GLP-2 injection increased jejunal mucosal blood flow by 79 ± 37% compared to conditions, where no treatment was given (p < 0.001). The significant effect was present at least 105. min. Systemic saline infusion and topical, mucosal adrenaline application did not affect mucosal microcirculation. Conclusions: GLP-2 raises jejunal microcirculation in SBS patients with end-jejunostomy. This may explain the redness and increase in the end-jejunostomy nipple size imminently after commencing GLP-2 injections. The potential beneficial effects of this GLP-2-mediated increase of blood flow in the mesenteric bed should be investigated in clinical conditions other than the short bowel syndrome.

  • 68.
    Karimian, N.
    et al.
    McGill Univ, Expt Surg, Montreal, PQ, Canada.
    Moustafa, M.
    McGill Univ, Dept Anesthesia, Montreal, PQ, Canada.
    Mata, J.
    McGill Univ, Dept Surg, Montreal, PQ, Canada.
    Al-Saffar, Anas K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Feldman, L. S.
    McGill Univ, Dept Surg, Montreal, PQ, Canada.
    Carli, F.
    McGill Univ, Dept Anesthesia, Montreal, PQ, Canada.
    The effects of added whey protein to a pre-operative carbohydrate drink on glucose and insulin response2018Inngår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 62, nr 5, s. 620-627Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 69. Karling, Pontus
    et al.
    Abrahamsson, Hasse
    Dolk, Anders
    Hallböök, Olof
    Hellström, Per M.
    Knowles, Charles H
    Kjellström, Lars
    Lindberg, Greger
    Lindfors, Per-Johan
    Nyhlin, Henry
    Ohlsson, Bodil
    Schmidt, Peter T
    Sjölund, Kristina
    Sjövall, Henrik
    Walter, Susanne
    Function and dysfunction of the colon and anorectum in adults: Working team report of the Swedish Motility Group (SMoG)2009Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 44, nr 6, s. 646-660Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 70.
    Keller, Jutta
    et al.
    Acad Hosp Univ Hamburg, Israelit Hosp, Orchideenstieg 14, D-22297 Hamburg, Germany.
    Bassotti, Gabrio
    Univ Perugia, Piazza Univ 1, I-06121 Perugia, Italy.
    Clarke, John
    Stanford Univ, 900 Blake Wilbur Dr, Palo Alto, CA 94304 USA.
    Dinning, Phil
    Flinders Med Ctr, GPO Box 2100, Adelaide, SA 5001, Australia.
    Fox, Mark
    Univ Hosp Zurich, Ramistr 100, CH-8091 Zurich, Switzerland;St Clara Hosp, Kleinriehenstr 30, CH-4058 Basel, Switzerland.
    Grover, Madhusudan
    Mayo Clin, 200 First St SW, Rochester, MN 55902 USA.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Ke, Meiyun
    Beijing Union Med Coll Hosp, 1 Shuaifuyuan Wangfujing Dongcheng Dist, Beijing 100730, Peoples R China.
    Layer, Peter
    Acad Hosp Univ Hamburg, Israelit Hosp, Orchideenstieg 14, D-22297 Hamburg, Germany.
    Malagelada, Carolina
    Univ Barcelona, Passeig Vall dHebron 119-129, Barcelona 08035, Spain.
    Parkman, Henry P.
    Temple Univ Hosp & Med Sch, 3401 N Broad St, Philadelphia, PA 19140 USA.
    Scott, S. Mark
    Queen Mary Univ London, Wingate Inst, 26 Ashfield St, London E1 2AJ, England.
    Tack, Jan
    Univ Leuven, Univ Hosp Gasthuisberg, Herestr 49, B-3000 Leuven, Belgium.
    Simren, Magnus
    Univ Gothenburg, Sahlgrenska Acad, Bla Straket 5, S-41345 Gothenburg, Sweden.
    Tornblom, Hans
    Univ Gothenburg, Sahlgrenska Acad, Bla Straket 5, S-41345 Gothenburg, Sweden.
    Camilleri, Michael
    Mayo Clin, 200 First St SW, Rochester, MN 55902 USA.
    Advances in the diagnosis and classification of gastric and intestinal motility disorders2018Inngår i: Nature Reviews. Gastroenterology & Hepatology, ISSN 1759-5045, E-ISSN 1759-5053, Vol. 15, nr 5, s. 291-308Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 71. Kharaziha, Pedram
    et al.
    Hellström, Per M.
    Noorinayer, Babak
    Farzaneh, Farivar
    Aghajani, Katayoun
    Jafari, Fereshteh
    Telkabadi, Mohammad
    Atashi, Amir
    Honardoost, Maryam
    Zali, Mohammad Reza
    Soleimani, Masoud
    Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial2009Inngår i: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 21, nr 10, s. 1199-1205Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    End-stage liver disease is a medical problem with high morbidity and mortality. We have investigated the feasibility, safety, and efficacy of using autologous mesenchymal stem cells (MSCs) as a treatment.

    METHODS:

    Eight patients (four hepatitis B, one hepatitis C, one alcoholic, and two cryptogenic) with end-stage liver disease having Model for End-Stage Liver Disease score > or =10 were included. Autologous MSCs were taken from iliac crest. Approximately, 30-50 million MSCs were proliferated and injected into peripheral or the portal vein. Liver function and clinical features were evaluated at baseline and 1, 2, 4, 8, and 24 weeks after injection.

    RESULTS:

    Treatment was well tolerated by all patients. Liver function improved as verified by the Model for End-Stage Liver Disease score, which decreased from 17.9±5.6 to 10.7±6.3 (P<0.05) and prothrombin complex from international normalized ratio 1.9±0.4 to 1.4±0.5 (P<0.05). Serum creatinine decreased from 114±35 to 80±18 µmol/l (P<0.05). Serum albumin changed from 30±5 to 33±5 g/l and bilirubin from 46±29 to 41±31 µmol/l. No adverse effects were noted.

    CONCLUSION:

    Our data show that MSCs injection can be used for the treatment of end-stage liver disease with satisfactory tolerability. Furthermore, this treatment may improve clinical indices of liver function in end-stage liver disease.

  • 72.
    Koubaa, Saloua
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Hallstrom, Tore
    Karolinska Inst, Div Psychiat, Dept Clin Neurosci, Stockholm, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Div Psychiat & Neurochem, Dept Neurosci & Physiol, Gothenburg, Sweden..
    Brismar, Kerstin
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hirschberg, Angelica Linden
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, SE-17176 Uppsala, Sweden..
    Biomarkers of nutrition and stress in pregnant women with a history of eating disorders in relation to head circumference and neurocognitive function of the offspring2015Inngår i: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 15, artikkel-id 318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Eating disorders during pregnancy can affect fetal growth and the child's early development, but the underlying mechanisms have not been elucidated. The aim of the present study was to investigate serum biomarkers of nutrition and stress in pregnant women with previous eating disorders compared to controls and in relation to head circumference and early neurocognitive development of the offspring. Methods: In a longitudinal cohort study, pregnant nulliparous non-smoking women with a history of anorexia nervosa (n = 20), bulimia nervosa (n = 17) and controls (n = 59) were followed during pregnancy and their children's growth and neurocognitive development were followed up to five years of age. We investigated maternal serum biomarkers of nutrition and stress (ferritin, cortisol, thyroid-stimulating hormone, free thyroxine, insulin, insulin-like growth factor I (IGF-I) and IGF binding protein 1) in blood samples collected during early pregnancy and compared between groups (ANOVA, LSD post-hoc test). The results were related to previous data on head circumference at birth and neurocognitive development at five years of age of the offspring (Spearman rank correlation or Pearson correlation test). Results: Serum levels of ferritin in the women with previous anorexia nervosa, but not in those with a history of bulimia nervosa, were significantly lower than in the controls (p < 0.01), and correlated strongly to impaired memory function in their children (rs = -0.70, p < 0.001). Maternal serum levels of free thyroxine were similar between groups but correlated positively to reduced head circumference at birth of the children in the bulimia nervosa group (r = 0.48, p < 0.05), and with the same tendency in the anorexia nervosa group (r = 0.42, p = 0.07), but not in the controls (r = 0.006). There were no significant differences in cortisol or the other biomarkers between groups. Conclusions: Low maternal serum ferritin in women with previous anorexia nervosa may be of importance for impaired memory capacity in the offspring at five years of age. Our results also indicate that thyroxin levels in pregnant women with previous eating disorders are positively associated with fetal head growth.

  • 73.
    Lee, Isabella
    et al.
    Swedish Univ Agr Sci, Dept Food Sci, POB 7051, SE-75007 Uppsala, Sweden..
    Shi, Lin
    Swedish Univ Agr Sci, Dept Food Sci, POB 7051, SE-75007 Uppsala, Sweden.;Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Risérus, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Landberg, Rikard
    Swedish Univ Agr Sci, Dept Food Sci, POB 7051, SE-75007 Uppsala, Sweden.;Karolinska Inst, Unit Nutr Epidemiol, Inst Environm Med, POB 210, SE-17177 Stockholm, Sweden.;Chalmers, Dept Biol & Biol Engn Food & Nutr Sci, SE-41296 Gothenburg, Sweden.;Chalmers, Dept Biol & Biol Engn, Gothenburg, Sweden..
    Effects of whole-grain rye porridge with added inulin and wheat gluten on appetite, gut fermentation and postprandial glucose metabolism: a randomised, cross-over, breakfast study2016Inngår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 116, nr 12, s. 2139-2149Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Whole-grain rye foods reduce appetite, insulin and sometimes glucose responses. Increased gut fermentation and plant protein may mediate the effect. The aims of the present study were to investigate whether the appetite-suppressing effects of whole-grain rye porridge could be enhanced by replacing part of the rye with fermented dietary fibre and plant protein, and to explore the role of gut fermentation on appetite and metabolic responses over 8 h. We conducted a randomised, cross-over study using two rye porridges (40 and 55 g), three 40-g rye porridges with addition of inulin: gluten (9:3; 6:6; 3:9 g) and a refined wheat bread control (55 g), served as part of complete breakfasts. A standardised lunch and an ad libitum dinner were served 4 and 8 h later, respectively. Appetite, breath hydrogen and methane, glucose, insulin and glucagon-like peptide-1 (GLP-1) responses were measured over 8 h. Twenty-one healthy men and women, aged 23-60 years, with BMI of 21-33 kg/m(2) participated in this study. Before lunch, the 55-g rye porridges lowered hunger by 20% and desire to eat by 22% and increased fullness by 29% compared with wheat bread (P < 0.05). Breath hydrogen increased proportionally to dietary fibre content (P < 0.05). Plasma glucose after lunch was 6% lower after the 55-g rye porridges compared with wheat bread (P< 0.05) and correlated to breath hydrogen (P < 0.001). No differences were observed in ad libitum food intake, insulin or GLP-1. We conclude that no further increase in satiety was observed when replacing part of the rye with inulin and gluten compared with plain rye porridges.

  • 74. Lind, Goran
    et al.
    Winter, Jaleh
    Linderoth, Bengt
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Therapeutic value of spinal cord stimulation in irritable bowel syndrome: a randomized crossover pilot study2015Inngår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 308, nr 10, s. R887-R894Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Irritable bowel syndrome (IBS) is characterized by abdominal pain and changed bowel habits. Spinal cord stimulation (SCS) has been used for treatment of chronic pain syndromes. Animal studies have shown SCS to reduce the reaction to colonic balloon distension, known to be increased in IBS patients. To elucidate the potential for SCS as treatment for IBS, a pilot study was performed. Ten IBS patients (age 26-56 yr) were recruited. A SCS system with a four-polar electrode was implanted at the T5-T8 level. After a 2-wk run-in, a randomized, crossover design SCS during 6 wk was compared with no stimulation, with an ensuing stimulation period for 12 wk; total study period 28 wk. Patients recorded pain level, pain attacks, diarrheas, and global quality of life in a diary. At end of the study patients could choose to retain their SCS system or have it removed. Nine patients completed the whole trial. During stimulation periods the median pain scores were significantly reduced from visual analogue scale (VAS) 7 (4-8) to 3 (2.5-7) and to 4 (2-6) during early and late stimulation periods, respectively (P < 0.03-0.04). Pain attacks were numerically reduced. A few patients reported reduced number of diarrheas. After study termination, six patients chose to retain their SCS system. To conclude, SCS is a minimally invasive treatment option for pain in IBS. With SCS the pain level was reduced though with merely a trend for number of attacks and diarrheas. The efficacy of SCS in IBS pain indicates a possible usefulness in other painful bowel disorders.

  • 75. Lönnkvist, Maria H
    et al.
    Befrits, Ragnar
    Lundberg, Jon O
    Lundahl, Joachim
    Fagerberg, Ulrika L
    Hjortswang, Henrik
    van Hage, Marianne
    Hellström, Per M.
    Infliximab in clinical routine: Experience with Crohn's disease and biomarkers of inflammation over 5 years2009Inngår i: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 21, nr 10, s. 1168-1176Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction:

    Infliximab was launched for the treatment of Crohn's disease (CD) in 1999. We set up a follow-up protocol to meticulously study disease development with repeated infusions of infliximab. 

    Aim:

    To follow the effects of infliximab treatment on disease activity, blood chemistry, quality of life, plasma nitrite, and titers of Saccharomyces cerevisiae antibodies (ASCA).

    Methods:

    During 1999–2008, CD patients were monitored for disease activity by Harvey–Bradshaw index, blood chemistry with hemoglobin, albumin, C-reactive protein, platelet count, leukocyte count and creatinine, quality of life by the Short Health Scale, and plasma nitrite. During the first year of treatment, follow-up was done repeatedly before and 1 week after each infusion and thereafter every year before the last infusion for 5 years. ASCA was analyzed by flow cytometry with fluorescein isothiocyanate-labelled antibodies.

    Results:

    A total of 1061 infusions were given to 103 patients; 92 responders and 11 nonresponders. Responders were further monitored and Harvey–Bradshaw index decreased with infusions during the first year of treatment (P<0.0001), whereas hemoglobin (P<0.01) and albumin (P<0.001) increased, C-reactive protein (P<0.01) decreased, platelets (P<0.001) increased, and leukocytes (P<0.01) decreased. Creatinine was not affected. Short Health Scale (questions analyzed separately) decreased (P<0.0001), and nitrite (P<0.001) increased. During the next 4 years the improved values remained stable. Adverse effects were noted among 32% of the patients; local circulatory reactions being most common. No correlation between ASCA titers and inflammatory activity or infliximab treatment was found.

    Conclusion:

    Infliximab treatment is highly effective in responders and maintains symptomatic improvement and low inflammatory activity over years in CD patients.

  • 76. Lönnkvist, Maria H.
    et al.
    Theodorsson, Elvar
    Holst, Mikael
    Ljung, Tryggve
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Blood chemistry markers for evaluation of inflammatory activity in Crohn's disease during infliximab therapy2011Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, nr 4, s. 420-427Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective.

    There is a discrepancy between clinical activity and biomarkers in inflammatory bowel disease. The Harvey--Bradshaw index (HBi) is steadfast to evaluate disease activity. A set of biological markers (high sensitive C-reactive protein [hs-CRP], calprotectin, total nitrite, soluble urokinase Plasminogen Activator Receptor [suPAR], ghrelin and endothelin) are investigated to study inflammatory activity and correlation with HBi during infliximab therapy.

    Material and methods.

    Patients with Crohn'sdisease (n == 22) were assessed and blood samples drawn before and 1 week after infliximab infusion (5 mg/kg) and repeated after 6 months, and compared to healthy volunteers. Hs-CRP, calprotectin, suPAR, ghrelin and endothelin were analyzed with immunoassays, and total nitrite with Griess-reaction. Results were analyzed with Wilcoxon matched-pairs test, Mann--Whitney test and Spearman correlations.

    Results.

    After the first infusion visit, HBi and calprotectin values decreased while nitrite increased (p < 0.05). At the 6-month visit, pre-infusion index and biomarkers had returned to baseline levels. Post-infusion, again the values of HBi, hs-CRP and calprotectin decreased (p < 0.05). The suPAR levels did not change between pre- and post-infusion periods at either visit. Calprotectin, nitrite and suPAR differed from healthy controls throughout the study (p < 0.05). Endothelin decreased with each treatment but was, like ghrelin, not different from controls. We found HBi to correlate with hs-CRP (Spearman r == 0.32, p < 0.05), but calprotectin did not, neither did nitrate nor suPAR.

    Conclusions.

    Although infliximab ameliorates Crohn'sdisease symptoms, inflammatory markers are not persistently normalized, indicating a chronic inflammatory condition that may require continued infliximab therapy.

  • 77. Marrinan, Sarah L
    et al.
    Otiker, Tal
    Vasist, Lakshmi S
    Gibson, Rachel A
    Sarai, Bhopinder K
    Barton, Matthew E
    Richards, Duncan B
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Nyholm, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurologi.
    Dukes, George E
    Burn, David J
    A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.2018Inngår i: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, nr 2, s. 329-332Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 78. Mikami, T
    et al.
    Ito, K
    Diaz, Hetzel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Mochiki, E
    Takemi, S
    Tanaka, T
    Tsuda, S
    Jogahara, T
    Sakata, I
    Sakai, T
    Study of termination of postprandial gastric contractions in humans, dogs and Suncus murinus: role of motilin- and ghrelin-induced strong contraction.2018Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, nr 2, artikkel-id e12933Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 79.
    Munch, Andreas
    et al.
    Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Div Gastroenterol & Hepatol, S-58185 Linkoping, Sweden..
    Bohr, Johan
    Univ Orebro, Orebro Univ Hosp, Dept Gastroenterol, SE-70182 Orebro, Sweden.;Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Miehlke, Stephan
    Ctr Digest Dis, Hamburg, Germany..
    Benoni, Cecilia
    Univ Hosp, Dept Gastroenterol, Malmo, Sweden..
    Olesen, Martin
    Univ Hosp, Dept Pathol, Malmo, Sweden..
    Ost, Ake
    Aleris Medilab, Dept Pathol & Cytol, Taby, Sweden..
    Strandberg, Lars
    Reg Hosp, Falun, Sweden..
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hertervig, Erik
    Univ Lund Hosp, Dept Gastroenterol, S-22185 Lund, Sweden..
    Armerding, Peter
    Stehlik, Jiri
    Reg Hosp, Dept Gastroenterol, Usti Nad Labem, Czech Republic..
    Lindberg, Greger
    Karolinska Univ Hosp Huddinge, Ctr Digest Dis, Stockholm, Sweden..
    Bjork, Jan
    Karolinska Univ Hosp Solna, Ctr Digest Dis, Stockholm, Sweden..
    Lapidus, Annika
    Ersta Hosp, Dept Gastroenterol, Stockholm, Sweden..
    Lofberg, Robert
    Sophiahemmet, Dept Gastroenterol, IBD Unit, Stockholm, Sweden..
    Bonderup, Ole
    Reg Hosp, Dept Gastroenterol, Silkeborg, Denmark..
    Avnstrom, Soren
    Amager Hosp, Dept Gastroenterol, Copenhagen, Denmark..
    Rossle, Martin
    Dilger, Karin
    Dr Falk Pharma GmbH, Freiburg, Germany..
    Mueller, Ralph
    Dr Falk Pharma GmbH, Freiburg, Germany..
    Greinwald, Roland
    Dr Falk Pharma GmbH, Freiburg, Germany..
    Tysk, Curt
    Univ Orebro, Orebro Univ Hosp, Dept Gastroenterol, SE-70182 Orebro, Sweden.;Univ Orebro, Sch Hlth & Med Sci, SE-70182 Orebro, Sweden..
    Strom, Magnus
    Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Div Gastroenterol & Hepatol, S-58185 Linkoping, Sweden..
    Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial2016Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, nr 1, s. 47-56Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis. Design A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase. Results Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious. Conclusions Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.

  • 80. Naessen, Sabine
    et al.
    Carlström, Kjell
    Holst, Jens J.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hirschberg, Angelica L.
    Women with bulimia nervosa exhibit attenuated secretion of glucagon-like peptide 1, pancreatic polypeptide, and insulin in response to a meal2011Inngår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 94, nr 4, s. 967-972Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background:

    The eating disorder bulimia nervosa (BN) is characterized by frequent episodes of binge eating, followed regularly by inappropriate compensatory behavior, such as self-induced vomiting.

    Objective:

    The current investigation was designed to examine possible alterations in the secretion of the gastrointestinal satiety peptides glucagon-like peptide 1 (GLP-1) and pancreatic polypeptide (PP) in women with BN.

    Design:

    Twenty-one women with BN and 17 healthy control subjects of comparable age and BMI were recruited. After fasting overnight, the subjects provided blood samples during ingestion of a standardized meal and self-rated their appetite on a visual analog scale. Fasting and meal-related secretion of the incretin GLP-1 and the meal-related feedback signal PP and insulin and glucose as indicators of the metabolic homeostasis were analyzed.

    Results:

    Women with BN had significantly lower fasting and postprandial serum concentrations of GLP-1 (P < 0.01) and PP (P < 0.05) than did the control subjects. Furthermore, both the basal (P < 0.001) and peak (P < 0.05) concentrations of insulin were significantly attenuated in the bulimic subjects, whereas glucose concentrations were normal. As a consequence, the bulimic homeostasis model assessment of insulin index values were also lower (P < 0.001).

    Conclusions:

    Women with BN secrete abnormally low amounts of GLP-1 and PP, possibly because of the adaption to large meals in the form of enlarged gastric capacity and reduced muscle tone in the gastric wall. Attenuated secretion of these gastrointestinal satiety peptides may play a role in the maintenance of bulimic behavior.

  • 81. Naslund, Erik
    et al.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Elucidating the Mechanisms Behind the Restoration of Euglycemia After Gastric Bypass Surgery2013Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 62, nr 4, s. 1012-1013Artikkel i tidsskrift (Annet vitenskapelig)
  • 82. Nybacka, Asa
    et al.
    Carlstrom, Kjell
    Fabri, Fredrika
    Hellström, Per Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hirschberg, Angelica Linden
    Serum antimullerian hormone in response to dietary management and/or physical exercise in overweight/obese women with polycystic ovary syndrome: secondary analysis of a randomized controlled trial2013Inngår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 100, nr 4, s. 1096-1102Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate whether randomized diet and/or physical exercise influence serum levels of antimullerian hormone (AMH) in obese women with polycystic ovary syndrome (PCOS). Design: Randomized, 4-month trial with three interventions. Setting: Women's health clinical research unit at a university hospital. Patient(s): Fifty-seven overweight/obese women with PCOS. Intervention(s): Diet, physical exercise, or both, using programs individually adapted and supervised by a dietician and/or a physiotherapist. Main Outcome Measure(s): Serum AMH levels before and after the interventions and correlations to reproductive function, body composition, and endocrine and metabolic variables. Result(s): After intervention, serum levels of AMH were significantly decreased only in the diet group, and the levels were significantly lower than in the exercise group. The strongest predictor of decreased AMH was a decrease in free T, whereas weight loss had no significant influence. Normalized levels of AMH were associated with improvements in menstrual cyclicity and hyperandrogenism but not in metabolic variables. Conclusion(s): This randomized study supports that diet reduces serum AMH in association with decreased androgen levels in obese women with PCOS. Increased serum AMH may be used as a marker of ovulatory dysfunction and hyperandrogenism but not as a marker of insulin resistance.

  • 83. Nybacka, Asa
    et al.
    Carlstrom, Kjell
    Stahle, Agneta
    Nyren, Sven
    Hellström, Per Martin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hirschberg, Angelica Linden
    Randomized comparison of the influence of dietary management and/or physical exercise on ovarian function and metabolic parameters in overweight women with polycystic ovary syndrome2011Inngår i: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 96, nr 6, s. 1508-1513Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective:

    To compare the influence of dietary management and/or physical exercise on ovarian function and metabolic variables in women with polycystic ovary syndrome (PCOS).

    Design:

    Randomized 4-month trial with three interventions and a long-term follow-up.

    Setting:

    Women's health clinical research unit at a university hospital.

    Patient(s):

    Fifty-seven overweight/obese women with PCOS.

    Intervention(s):

    Dietary management, physical exercise, or both, using programs individually adapted and supervised by a dietician and/or a physical therapist. Main

    Outcome Measure(s):

    Ovarian function, endocrinologic, and metabolic status and body composition.

    Result(s):

    On average, body mass index was reduced 6% by the dietary management, 3% by the exercise, and 5% by the combined interventions. Lower body fat and lean body mass were significantly decreased in the dietary groups, whereas upper body fat was lowered and lean body mass maintained by exercise alone. The menstrual pattern was significantly improved in 69% and ovulation confirmed in 34% of the patients, with no differences among the groups. The strongest predictor of resumed ovulation was a high serum level of insulin-like growth factor-binding protein 1 after the intervention. Follow-up of one-half of the patients for a median of 2.8 years revealed sustained weight reduction and improvement in menstrual pattern.

    Conclusion(s):

    Dietary management and exercise, alone or in combination, are equally effective in improving reproductive function in overweight/obese women with PCOS. The underlying mechanisms appear to involve enhanced insulin sensitivity. Supportive individualized programs for lifestyle change could exert long-term beneficial effects.

  • 84.
    Nybacka, Åsa
    et al.
    Karolinska Inst, Div Obstet & Gynecol, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Clin Nutr & Dietet, Stockholm, Sweden..
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hirschberg, Angelica L.
    Karolinska Inst, Div Obstet & Gynecol, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, Stockholm, Sweden..
    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 control2017Inngår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, nr 6, s. 680-688Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 85. Resendez, Angel
    et al.
    Halim, Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Landhage, Caroline M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Singaram, Bakthan
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Rapid small intestinal permeability assay based on riboflavin and lactulose detected by bis-boronic acid appended benzyl viologens2015Inngår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 439, s. 115-121Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Although organoboronic acids are efficient high-throughput sugar sensors, they have not been pursued for gut permeability studies. A modification of the lactulose/mannitol assay is described by which small intestinal permeability is assessed at the time of urine collection using a lactulose/riboflavin ratio.

    METHODS: Volunteers ingested 50mg riboflavin and either 5g mannitol or 10g lactulose. Urine was collected for 6hrs. Riboflavin was assayed by autofluorescence. Riboflavin was removed by C18 solid phase extraction. Lactulose and mannitol were then assayed using 1,1'-bis(2-boronobenzyl)-4,4'-bipyridinium (4,4'oBBV) coupled to the fluorophore HPTS.

    RESULTS: The temporal profile over 6hrs for riboflavin paralleled mannitol. Riboflavin recovery in urine was 11.1±1.9 % (mean±SEM, n=7), similar to mannitol. There was selective binding of 4,4'oBBV to lactulose, likely involving cooperativity between the fructose and galactose moieties. Lower limits of detection and quantification were 90 and 364μM. The lactulose assay was insensitive to other permeability probes (e.g., sucrose, sucralose) while tolerating glucose or lactose. This assay can be adapted to automated systems. Stability of 4,4'oBBV exceeds 4years.

    CONCLUSIONS: Riboflavin measured by autofluorescence combined with lactulose measured with 4,4'oBBV represents a useful new chemistry for rapid measurement of intestinal permeability with excellent stability, cost and throughput benefits.

  • 86. Rudholm, T
    et al.
    Wallin, B
    Theodorsson, E
    Näslund, E
    Hellström, Per M.
    Release of regulatory gut peptides somatostatin, neurotensin and vasoactive intestinal peptide by acid and hyperosmolal solutions in the intestine in conscious rats2009Inngår i: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 152, nr 1-3, s. 8-12Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The impact of exposure of the intestinal mucosa to acid and hyperosmolal solutions on the release of the inhibitory gut peptides somatostatin (SOM), neurotensin (NT) and vasoactive intestinal peptide (VIP) was studied in conscious rats during pentagastrin-stimulated gastric acid secretion. The animals were equipped with a chronic gastric fistula to measure acid secretion and a jejunal Thiry–Vella loop for intestinal challenge with saline, hydrochloric acid (HCl, 200 mmol L− 1) or hyperosmolal polyethylene glycol (PEG, 1200 mOsm kg− 1). Gut peptide concentrations were measured in intestinal perfusates, and in plasma samples collected during stimulated acid secretion, and at the end of experiments with luminal challenge of the loops.

    After pentagastrin-stimulation acid secretion was dose-dependently inhibited by intravenous administration of the gastrin receptor antagonist gastrazole, as well as ranitidine and esomeprazole by maximally 73 ± 10%; 95 ± 3%; 90 ± 10%, respectively.

    Acid perfusion of the Thiry–Vella loop caused a prominent release of SOM both to the lumen (from 7.2 ± 5.0 to 1279 ± 580 pmol L− 1) and to the circulation (from 18 ± 5.2 to 51 ± 9.0 pmol L− 1) simultaneously with an inhibition of gastric acid secretion. The release of NT and VIP was not affected to the same extent. PEG perfusion of the loop caused a release of SOM as well as NT and VIP, but less. Simultaneously acid secretion was slightly decreased.

    In conclusion, intestinal perfusion with acid or hyperosmolal solutions mainly releases SOM, which seems to exert a major inhibitory action in the gut, as shown by inhibition of acid secretion. The other peptides NT and VIP also participate in this action but to a much lesser degree. The operative pathways of these gut peptides hence involve both endocrine (SOM) and paracrine actions (SOM, NT, VIP) in order to exert inhibitory functions on the stomach. The inhibitory action of gastrazole, was in a similar range as that of SOM implying that physiological acid-induced inhibition of gastric acid may primarily be exerted through inhibition of gastrin endocrine secretion.

  • 87. Rudholm, Tobias
    et al.
    Hellstrom, Per M.
    Medicin K2, Karolinska Institutet.
    Theodorsson, Elvar
    Campbell, Colin-Allan
    McLean, Peter-Geoffrey
    Naslund, Erik
    Bravo capsule system optimizes intragastric pH monitoring over prolonged time: effects of ghrelin on gastric acid and hormone secretion in the rat.2008Inngår i: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, nr 40, s. 6180-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    AIM: To evaluate measurements of intragastric pH with the Bravo capsule system over a prolonged time.

    METHODS: A Bravo capsule was placed inside the rat gastric body and pH was studied for periods up to five consecutive days. For comparison, a gastric fistula model was used. Effects of ghrelin and esomeprazole, with or without pentagastrin, on gastric pH were studied. In addition, effects of esomeprazole on plasma ghrelin, gastrin and somatostatin were analyzed.

    RESULTS: All rats recovered after surgery. The average 24-h pH during free feeding was 2.3 +/- 0.1 (n = 20) with a variation of 18% +/- 6% over 5 d. Ghrelin, 2400 pmol/kg, t.i.d. increased pH from 1.7 +/- 0.1 to 3.1 +/- 0.3 (P < 0.01) as recorded with the Bravo system. After esomeprazole (1 mg/kg, 3 mg/kg and 5 mg/kg) there was a dose-dependent pH increase of maximally 3.4 +/- 0.1, with day-to-day variation over the entire period of 8% +/- 3%. The fistula and pH studies generated similar results. Acid inhibition with esomeprazole increased plasma ghrelin from 10 +/- 2 pmol/L to 65 +/- 26 pmol/L (P < 0.001), and somatostatin from 10 +/- 2 pmol/L to 67 +/- 18 pmol/L (P < 0.001).

    CONCLUSION: pH measurements with the Bravo capsule are reliable, and comparable to those of the gastric fistula model. The Bravo system optimizes accurate intragastric pH monitoring over prolonged periods and allows both short- and long-term evaluation of effects of drugs and hormones.

  • 88. Sanger, G J
    et al.
    Westaway, S M
    Barnes, A A
    Macpherson, D T
    Muir, A I
    Jarvie, E M
    Bolton, V N
    Cellek, S
    Näslund, E
    Hellström, Per M.
    Borman, R A
    Unsworth, W P
    Matthews, K L
    Lee, K
    GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility2009Inngår i: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 21, nr 6, s. 657-664, e30-31Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 89. Sanger, Gareth J
    et al.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Näslund, Erik
    The hungry stomach: Physiology, disease, and drug development opportunities2010Inngår i: Frontiers in pharmacology, ISSN 1663-9812, Vol. 1, s. 145-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    During hunger, a series of high-amplitude contractions of the stomach and small intestine (phase III), which form part of a cycle of quiescence and contractions (known as the migrating motor complex, MMC), play a "housekeeping" role prior to the next meal, and may contribute toward the development of hunger. Several gastrointestinal (GI) hormones are associated with phase III MMC activity, but currently the most prominent is motilin, thought to at least partly mediate phase III contractions of the gastric MMC. Additional GI endocrine and neuronal systems play even more powerful roles in the development of hunger. In particular, the ghrelin-precursor gene is proving to have a complex physiology, giving rise to three different products: ghrelin itself, which is formed from a post-translational modification of des-acyl-ghrelin, and obestatin. The receptors acted on by des-acyl-ghrelin and by obestatin are currently unknown but both these peptides seem able to exert actions which oppose that of ghrelin, either indirectly or directly. An increased understanding of the actions of these peptides is helping to unravel a number of different eating disorders and providing opportunities for the discovery of new drugs to regulate dysfunctional gastric behaviors and appetite. To date, ghrelin and motilin receptor agonists and antagonists have been described. The most advanced are compounds which activate the ghrelin and motilin receptors which are being progressed for disorders associated with gastric hypomotility.

  • 90.
    Saudi, Wan Salman Wan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Halim, Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Gillberg, A. L.
    Feldreich, T. Rudholm
    Sundbom, M.
    Karlbom, U.
    Naslund, E.
    Sommansson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sjöblom, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Neuropeptide S reduce small intestinal motility in rats and humans2014Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, nr S696, s. 94-94, artikkel-id P61Artikkel i tidsskrift (Annet vitenskapelig)
  • 91.
    Saudi, Wan Salman Wan
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Halim, Abdul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sjöblom, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysiologi.
    Neuropeptide S Reduces Gut Motility in Rats and Humans2015Inngår i: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 29, nr S1Artikkel i tidsskrift (Annet vitenskapelig)
  • 92.
    Sima, Eduardo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Non-Responders After Gastric Bypass: Hormone Response And Glucose Homeostasis During An Oral Glucose Tolerance Test2017Inngår i: IFSO 2017 22nd World Congress, Springer, 2017, Vol. 27, s. 208-208Konferansepaper (Annet vitenskapelig)
  • 93.
    Sima, Eduardo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Non-Responders after Gastric Bypass Surgery for Morbid Obesity: Peptide Hormones and Glucose Homeostasis2017Konferansepaper (Annet vitenskapelig)
  • 94.
    Sima, Eduardo
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Webb, Dominic-Luc
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Sundbom, Magnus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Gastrointestinalkirurgi.
    Non-responders After Gastric Bypass Surgery for Morbid Obesity: Peptide Hormones and Glucose Homeostasis2019Inngår i: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, nr 12, s. 4008-4017Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    INTRODUCTION: About 20% of patients operated with Roux-en-Y gastric bypass (RYGBP) experience poor long-term weight result. This study compared levels of leptin and gut hormones in long-term weight responders with non-responders after RYGBP. In a subgroup analysis, hormone levels were assessed in T2DM (type 2 diabetes mellitus) and normoglycemic participants.

    METHODS: Insulin, glucose, leptin, acyl-ghrelin, total PYY, active GLP-1, and GIP were measured during an oral glucose tolerance test (OGTT) in post-RYGBP subjects: 22 non-responders (BMI 40.6 ± 6.0 kg/m2 after an excess BMI loss [EBMIL] of 26.0 ± 15.9%) and 18 responders (BMI 29.5 ± 3.5 kg/m2 after an EBMIL of 74.9 ± 18.2%). Subjects were matched for preoperative age, BMI, and years of follow-up. Measures of glucose homeostasis were calculated, and body composition was measured.

    RESULTS: Fat mass-adjusted fasting leptin correlated negatively with %EBMIL (r = - 0.57, p < 0.01). Non-responders presented higher levels of leptin during the OGTT. Leptin decreased and ghrelin returned to baseline levels earlier in non-responders. Despite having higher insulin resistance than responders, non-responders demonstrated similar OGTT responses of GLP-1, GIP, and PYY. T2DM participants demonstrated lower GLP-1 levels than normoglycemic participants of similar weight.

    CONCLUSION: Fasting leptin is associated with weight result after RYGBP, and hormonal responses to a glucose oral load might work towards promoting obesity in long-term non-responders after RYGBP. Poor long-term weight result and glycemic status after RYGBP are each associated with differences in peptide hormone levels.

  • 95. Sjöberg, Mats
    et al.
    Walch, Andrea
    Meshkat, Mina
    Gustavsson, Anders
    Järnerot, Gunnar
    Vogelsang, Harald
    Hertervig, Erik
    Novacek, Gottfried
    Friis-Liby, Ingalill
    Blomquist, Lars
    Angelberger, Sieglinde
    Karlen, Per
    Grännö, Christer
    Vilien, Mogens
    Ström, Magnus
    Verbaan, Hans
    Hellström, Per M.
    Dejaco, Clemens
    Magnuson, Anders
    Halfvarson, Jonas
    Reinisch, Walter
    Tysk, Curt
    Infliximab or cyclosporine as rescue therapy in hospitalized patients with steroid-refractory ulcerative colitis: a retrospective observational study2012Inngår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 18, nr 2, s. 212-218Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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.

  • 96.
    Söderquist, Fanny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Cunningham, Janet L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Human Gastroenteropancreatic Expression of Melatonin and Its Receptors MT1 and MT22015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 3, artikkel-id e0120195Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and Aim The largest source of melatonin, according to animal studies, is the gastrointestinal (GI) tract but this is not yet thoroughly characterized in humans. This study aims to map the expression of melatonin and its two receptors in human GI tract and pancreas using microarray analysis and immunohistochemistry. Method Gene expression data from normal intestine and pancreas and inflamed colon tissue due to ulcerative colitis were analyzed for expression of enzymes relevant for serotonin and melatonin production and their receptors. Sections from paraffin-embedded normal tissue from 42 individuals, representing the different parts of the GI tract (n= 39) and pancreas (n= 3) were studied with immunohistochemistry using antibodies with specificity for melatonin, MT1 and MT2 receptors and serotonin. Results Enzymes needed for production of melatonin are expressed in both GI tract and pancreas tissue. Strong melatonin immunoreactivity (IR) was seen in enterochromaffin (EC) cells partially co-localized with serotonin IR. Melatonin IR was also seen in pancreas islets. MT1 and MT2 IR were both found in the intestinal epithelium, in the submucosal and myenteric plexus, and in vessels in the GI tract as well as in pancreatic islets. MT1 and MT2 IR was strongest in the epithelium of the large intestine. In the other cell types, both MT2 gene expression and IR were generally elevated compared to MT1. Strong MT2, IR was noted in EC cells but not MT1 IR. Changes in gene expression that may result in reduced levels of melatonin were seen in relation to inflammation. Conclusion Widespread gastroenteropancreatic expression of melatonin and its receptors in the GI tract and pancreas is in agreement with the multiple roles ascribed to melatonin, which include regulation of gastrointestinal motility, epithelial permeability as well as enteropancreatic cross-talk with plausible impact on metabolic control.

  • 97.
    Söderquist, Fanny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Sundberg, Isak
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Ramklint, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Widerström, Rebecka
    Uppsala Univ, Uppsala, Sweden..
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Daytime Salivary Melatonin Related to Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care2018Inngår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, nr 9, s. S185-S186Artikkel i tidsskrift (Annet vitenskapelig)
  • 98.
    Söderquist, Fanny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Sundberg, Isak
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Ramklint, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Widerström, Rebecka
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Psykiatri, Akademiska sjukhuset.
    The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care2019Inngår i: Psychosomatic Medicine, ISSN 0033-3174, E-ISSN 1534-7796, Vol. 81, nr 1, s. 51-56Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gutmotility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients.

    Methods: Ninety-six patients (86% women), aged 18-25 years (M (SD) = 21 (2)), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from the Gastrointestinal Symptoms Rating Scale -IBS were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11: 00 hours and 30 minutes after lunch) during the waking hours of 1 day.

    Results: After adjustment for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total Gastrointestinal Symptoms Rating Scale -IBS score after correction for multiple testing (B = 0.016, SE = 0.006, p =.015, q = 0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association.

    Conclusions: In young adult psychiatric patients, salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.

  • 99.
    Söderquist, Fanny
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.
    Syk, Mikaela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.
    Just, David
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.
    Novicic, Zorana Kurbalija
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.
    Jacobson, Annica
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk farmakogenomik och osteoporos.
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Gastroenterologi/hepatologi.
    Ramklint, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Barn- och ungdomspsykiatri. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.
    Cunningham, Janet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Ekselius: Psykiatri.
    Gastrointestinal symptoms, depression and trait anxiety in young adults seeking psychiatric careManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background and aim: Patients with functional gastrointestinal (GI) disorders have a high psychiatric co-morbidity, especially for mood and anxiety disorders. This study aimed to investigate and characterise GI symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult outpatients seeking psychiatric care.

    Material and methods: Patients, aged 18-25 years from the Uppsala Psychiatric Patient Samples (UPP) cohort seeking psychiatric care for primarily mood and anxiety disorders (n=491) were compared with healthy controls (n=85) for GI symptoms (measured using the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome, GSRS-IBS and depressive symptoms (measured using the Montgomery-Åsberg Depression Rating Scale – Self-Assessment, MADRS-S. Personality traits were assessed using the Swedish Universities Scales of Personality (SSP), in which three anxiety-related personality traits (stress susceptibility, psychic trait anxiety somatic trait anxiety) were assessed.

    Results: Patients, both on psychotropic medication and those not currently on psychotropic medication reported more GI symptoms than controls (median 30 vs. 22, p<0.001). GI symptom burden was higher in women than men (median 32 vs. 28, p<0.001). A principal component analysis produced a six-factor structure explaining 63% of the total variance in the data set. A cluster analysis was performed that allowed the identification of six cluster groups, characterised by the varying levels of these factors. The total GSRS-IBS score significantly correlated with depressive symptom severity (r=0.391, p<0.001), a relationship that remained after adjusting for possible confounders (sex, body mass index, bulimia). The total GSRS-IBS score correlated with the three SSP subscales: somatic trait anxiety (r=0.313, p<0.001), psychic trait anxiety (r=0.147, p=0.001) and stress susceptibility (r=0.233, p<0.001).

    Conclusion: GI symptoms are highly prevalent in young adult psychiatric outpatients compared with controls, regardless of whether the patient is currently on psychotropic medication or not. Depressive symptom severity and degree of trait anxiety are independently related to the total IBS symptoms score.

  • 100.
    Torkzad, Michael R
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för radiologi.
    Ullberg, Ulla
    Nyström, Niklas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Pediatrik.
    Blomqvist, Lennart
    Hellström, Per M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Fagerberg, Ulrika L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Manifestations of small bowel disease in pediatric Crohn's disease on magnetic resonance enterography2012Inngår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 18, nr 3, s. 520-528Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    We report the manifestations of Crohn's disease (CD) observed on magnetic resonance enterography (MRE) in a pediatric population at the time of CD diagnosis.

    METHODS:

    MRE of 95 consecutive pediatric patients with inflammatory bowel disease (IBD) examined in 2006-2009 were retrospectively analyzed, with documentation of findings based on type and location of the small bowel (SB) disease.

    RESULTS:

    In all, 51 were boys and 44 girls. 54 had CD, 31 non-CD IBD, and 10 no IBD. The most common site of SB involvement in CD was the terminal ileum seen in 29 (53.7%) patients, followed by ileum in 10 (18.5%) and jejunum in 9 (16.7%) patients. Solitary jejunal inflammation (3.7%), SB stenoses (1.9%), fistula formation (0.95%), and abscess (0.95%) were much less common. Perienteric lymphadenopathy was seen in 30 (55.6%) patients and fatty proliferation in 9 (16.7%). The most common manifestation of SB inflammation was increased contrast enhancement of bowel wall (93.5%), thickening of the bowel wall (90.3%), and derangement of bowel shape with saccular formations (25.8%).

    CONCLUSIONS:

    MRE in the pediatric population often demonstrates increased contrast uptake, bowel wall thickening, and perienteral lymphadenopathy in CD. More chronic small bowel changes seen commonly in adults and solitary jejunal involvements are less commonly seen.

123 51 - 100 of 112
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