| 1. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 2. |
- Krarup, Anne L., et al.
(författare)
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Exploration of the effects of gender and mild esophagitis on esophageal pain thresholds in the normal and sensitized state of asymptomatic young volunteers
- 2013
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 25:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Clinical data suggest gender differences in gastrointestinal pain, but very little experimental data exist. Esophageal painful thresholds to mechanical, thermal, electric, and chemical stimuli can be measured with the esophageal multimodal pain model. The aim was to measure the effect of gender and mild esophagitis on esophageal pain perception. Methods Thirty-five healthy asymptomatic volunteers [19 men, median age 29 (22-56 years)] underwent upper GI endoscopy, 24 h pH/impedance measurement, and multimodal esophageal pain stimulation before and after sensitization with acid. Stimulus intensities at painful thresholds were recorded. Key Results Men had higher pain thresholds (PT) to mechanical stimulation (mean volume: men 20.9 +/- 10 mL vs women 15.2 +/- 6.8 mL, P = 0.02) and more men tolerated the maximum acid challenge (58% vs 20%, P = 0.03). There were no differences between genders for PT to 1 thermal stimulation [mean stimulation time (men, women): heat; 20 +/- 5 s vs 21 +/- 6 s or cold; 33.3 +/- 20.1 s vs 20.7 +/- 21.4 s, P > 0.2], 2 electrical current (mean current: men 17.6 +/- 9.2 mA vs women 12.9 +/- 3.7 mA, P = 0.11), or 3 acid volume [median volume: men 200 (20; 200) mL vs women 133 (40; 200) mL, P = 0.2]. Fifteen asymptomatic subjects had mild esophagitis (10 men, all Los Angeles A). There were no differences in esophageal PT between subjects with normal endoscopy or mild esophagitis (all P > 0.3). Conclusions & Inferences The effects of gender and mild esophagitis on esophageal multimodal pain perception have been measured in asymptomatic volunteers. The study suggests that gender, not mild esophagitis, tends to influence mechanical and chemical esophageal pain.
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| 3. |
- Krarup, Anne L., et al.
(författare)
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Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain.
- 2011
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Ingår i: Alimentary pharmacology & therapeutics. - : Wiley. - 1365-2036 .- 0269-2813. ; 33:10, s. 1113-22
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Tidskriftsartikel (refereegranskat)abstract
- Background Many patients with gastro-oesophageal reflux disease (GERD) are hypersensitive to heat and acid and may respond insufficiently to standard treatment. Antagonists of the heat and acid receptor ‘transient receptor potential vanilloid 1’(TRPV1) are a potential drug class for GERD treatment. Aim To investigate the effect of a TRPV1 antagonist (AZD1386) on experimentally induced oesophageal pain. Methods Twenty-two healthy men (20–31 years) participated in this randomised, placebo-controlled, double-blinded, crossover study examining the effects of a single-dose oral AZD1386 (30 and 95 mg). Subjects were block-randomised. On treatment days, participants were stimulated with painful heat, distension, electrical current and acid in the oesophagus. Heat and pressure pain on the forearm were somatic control stimuli. Data analysis: intention-to-treat. Results A total of 21 participants completed the protocol and 1 voluntarily discontinued. In the oesophagus, both 30 and 95 mg of AZD1386 increased pain thresholds to heat stimuli 23% [95% confidence interval (CI): 10–38%] and 28%, respectively (CI: 14–43%). The skin heat tolerance was increased 2.1 °C (CI: 1.1–3.2 °C) after 30 mg AZD1386 and 4.0 °C (CI: 3.0–5.0 °C) after 95 mg. Heat analgesia persisted for 2.5 h. Pain thresholds to the other stimuli were unaffected by AZD1386. 50% reported ‘feeling cold’ and body temperature increased in all subjects exposed to 30 and 95 mg AZD1386 (mean increase 0.4 ± 0.3 °C and 0.7 ± 0.3 °C, respectively, P < 0.05). Conclusions AZD1386 increased oesophageal and skin heat pain thresholds and had a safe adverse-event profile. This drug class may have a potential for treatment of GERD (ClinicalTrials.gov identifier: NCT00711048).
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| 4. |
- Krarup, Anne L., et al.
(författare)
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Randomized clinical trial: inhibition of the TRPV1 system in patients with nonerosive gastroesophageal reflux disease and a partial response to PPI treatment is not associated with analgesia to esophageal experimental pain.
- 2013
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Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 48:3, s. 274-84
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Many patients with nonerosive reflux disease (NERD) have insufficient relief on proton pump inhibitors (PPIs). Some patients have a hypersensitive esophagus and may respond to transient receptor potential vanilloid 1 (TRPV1) antagonists. Aim. To investigate the effect of the TRPV1 antagonist AZD1386 on experimental esophageal pain in NERD patients. Material and methods. Enrolled patients had NERD and a partial PPI response (moderate-to-severe heartburn or regurgitation ≥3 days/week before enrolment despite ≥6 weeks' PPI therapy). Fourteen patients (21-69 years, 9 women) were block-randomized into this placebo-controlled, double-blinded, crossover study examining efficacy of a single dose (95 mg) of AZD1386. On treatment days, each participant's esophagus was stimulated with heat, distension, and electrical current at teaching hospitals in Denmark and Sweden. Heat and pressure pain served as somatic control stimuli. Per protocol results were analyzed. Results. Of 14 randomized patients, 12 were treated with AZD1386. In the esophagus AZD1386 did not significantly change the moderate pain threshold for heat [-3%, 95% confidence interval (CI), -22;20%], distension (-11%, 95% CI, -28;10%), or electrical current (6%, 95% CI, -10;25%). Mean cutaneous heat tolerance increased by 4.9°C (95% CI, 3.7;6.2°C). AZD1386 increased the maximum body temperature by a mean of 0.59°C (95% CI, 0.40-0.79°C), normalizing within 4 h. Conclusions. AZD1386 had no analgesic effect on experimental esophageal pain in patients with NERD and a partial PPI response, whereas it increased cutaneous heat tolerance. TRPV1 does not play a major role in heat-, mechanically and electrically evoked esophageal pain in these patients. ClinicalTrials.gov identifier: D9127C00002.
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| 5. |
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| 6. |
- Krarup, Anne L., et al.
(författare)
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The Short Health Scale A Simple, Valid, Reliable, and Responsive Way of Measuring Subjective Health in Patients With Irritable Bowel Syndrome
- 2015
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Ingår i: Journal of Clinical Gastroenterology. - : Lippincott, Williams andamp; Wilkins: No Hybrid Open Access. - 0192-0790 .- 1539-2031. ; 49:7, s. 565-570
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Tidskriftsartikel (refereegranskat)abstract
- Goals:To evaluate validity, reliability, and responsiveness of the Short Health Scale (SHS) in irritable bowel syndrome (IBS) patients.Background:Subjective health assessment is central when treating patients with IBS. The Short Health Scale is a quick 4-item questionnaire covering most aspects of subjective health that has been validated for inflammatory bowel disease.Study:To test validity, 451 patients with IBS (mean age, 38 y; 81% females) completed the SHS and questionnaires assessing IBS symptom severity (IBS-SSS), gastrointestinal (GI)-specific anxiety (VSI), and quality of life (IBSQOL). To evaluate reliability and responsiveness to changes, the questionnaires were repeated after 2 weeks in 18 patients, and after 12 weeks in 212 patients who had completed a patient-education program.Results:Validity was documented with (1) gradually increasing mean scores for all 4 SHS items with increasing IBS-SSS (Pless than0.0001), and (2) correlations between the 4 SHS items and the corresponding items from the other subjective health assessment tools [item 1 (symptom burden): =0.67, item 2 (daily function): =-0.44 to -0.46, item 3 (disease-related worry): =-0.51 to 0.57, item 4 (general well-being): =-0.34 to -0.46, Pless than0.0001]. Reliability was confirmed (Spearman greater than0.7 and intraclass correlations greater than0.7). Responsiveness was good with responders to the patient-education program (IBS-SSS reduction 50 points) having significant reductions in 3 of the SHS items (Pless than0.05), and borderline change for the fourth SHS item (P=0.06).Conclusions:SHS is a health measure that shows promising evidence of validity, reliability, and responsiveness in IBS patients. It is quickly completed and evaluated, which supports its usefulness in the busy clinical practice.
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| 7. |
- Krarup Sørbye, Ingvil, et al.
(författare)
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Birthweight of Babies Born to Migrant Mothers - What Role Do Integration Policies Play?
- 2019
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Ingår i: SSM - Population Health. - : Elsevier BV. - 2352-8273. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Birthweights of babies born to migrant women are generally lower than those of babies born to native-born women. Favourable integration policies may improve migrants’ living conditions and contribute to higher birthweights. We aimed to explore associations between integration policies, captured by the Migrant Integration Policy Index (MIPEX), with offspring birthweight among migrants from various world regions. In this cross-country study we pooled 31 million term birth records between 1998 and 2014 from ten high-income countries: Australia, Belgium, Canada, Denmark, Finland, Japan, Norway, Spain, Sweden and United Kingdom (Scotland). Birthweight differences in grams (g) were analysed with regression analysis for aggregate data and random effects models.Proportion of births to migrant women varied from 2% in Japan to 28% in Australia. The MIPEX score was not associated with birthweight in most migrant groups, but was positively associated among native-born (mean birthweight difference associated with a 10-unit increase in MIPEX: 105 g; 95% CI: 24, 186). Birthweight among migrants was highest in the Nordic countries and lowest in Japan and Belgium. Migrants from a given origin had heavier newborns in countries where the mean birthweight of native-born was higher and vice versa. Mean birthweight differences between migrants from the same origin and the native-born varied substantially across destinations (70 g–285 g).Birthweight among migrants does not correlate with MIPEX scores. However, birthweight of migrant groups aligned better with that of the native-born in destination counties. Further studies may clarify which broader social policies support migrant women and have impacts on perinatal outcomes.
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