Esophageal Acid Clearance During Random Swallowing Is Faster in Patients with Barrett`s Esophagus Than in Healthy Controls

( Christian Lottrup ),( Anne L Krarup ),( Hans Gregersen ),( Per Ejstrud ),( Asbjorn M Drewes ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.4

Background/Aims Impaired esophageal acid clearance may be a contributing factor in the pathogenesis of Barrett’s esophagus. However, few studies have measured acid clearance as such in these patients. In this explorative, cross-sectional study, we aimed to compare esophageal acid clearance and swallowing rate in patients with Barrett’s esophagus to that in healthy controls. Methods A total of 26 patients with histology-confirmed Barrett’s esophagus and 12 healthy controls underwent (1) upper endoscopy, (2) an acid clearance test using a pH-impedance probe under controlled conditions including controlled and random swallowing, and (3) an ambulatory pH-impedance measurement. Results Compared with controls and when swallowing randomly, patients cleared acid 46% faster (P = 0.008). Furthermore, patients swallowed 60% more frequently (mean swallows/minute: 1.90 ± 0.74 vs 1.19 ± 0.58; P = 0.005), and acid clearance time decreased with greater random swallowing rate (P < 0.001). Swallowing rate increased with lower distal esophageal baseline impedance (P = 0.014). Ambulatory acid exposure was greater in patients (P = 0.033), but clearance times assessed from the ambulatory pHmeasurement and acid clearance test were not correlated (all P > 0.3). Conclusions More frequent swallowing and thus faster acid clearance in Barrett’s esophagus may constitute a protective reflex due to impaired mucosal integrity and possibly acid hypersensitivity. Despite these reinforced mechanisms, acid clearance ability seems to be overthrown by repeated, retrograde acid reflux, thus resulting in increased esophageal acid exposure and consequently mucosal changes.

Rectal Mechano-sensory Function in Patients with Carcinoid Diarrhea

( Tine Gregersen ),( Christina Brock ),( Anne Mette Haase ),( Søren Laurberg ),( Asbjørn M Drewes ),( Henning Grønbæk ),( Klaus Krogh ) 대한소화기기능성질환·운동학회 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.2

Background/Aims In patients with neuroendocrine tumors, excessive production of serotonin and other amines may cause the carcinoid syndrome, which is mainly characterized by diarrhea and flushing. Little is known about the pathophysiology of carcinoid diarrhea. In several other groups of patients, diarrhea may be associated with rectal hypersensitivity and increased rectal tone. Therefore, the aim of the present study was to compare rectal sensitivity and compliance in patients with carcinoid diarrhea and in healthy subjects. Methods Twelve patients (6 males, aged 54-78 years, median 65 years), with carcinoid diarrhea and 19 healthy subjects (7 males, aged 50-78 years, median 61 years) were included. Rectal mechanical and heat stimulation was used for assessment of rectal mechano-sensory properties. Results Overall, 5.3% higher temperatures were needed to elicit sensory responses in patients with carcinoid diarrhea than in healthy subjects (P = 0.015). Posthoc analyses revealed that the sensory threshold to heat was 48.1 ± 3.1oC in patients vs 44.7 ± 4.7oC in healthy subjects (P = 0.041). In contrast, patients and healthy subjects showed no overall differences in rectal sensory response to mechanical distension (P = 0.731) or rectal compliance (P = 0.990). Conclusions Patients with carcinoid diarrhea have higher sensory thresholds to heat stimulation in comparison to healthy subjects, but normal rectal sensation to mechanical distension and normal compliance. Therefore, treatment of carcinoid diarrhea should aim at prolonging gastrointestinal transit and decreasing secretion, rather than modifying rectal mechano-sensory function. (J Neurogastroenterol Motil 2016;22:264-271)

Probing leptogenesis

Chun, E. J.,Cvetič,, G.,Dev, P. S. B.,Drewes, M.,Fong, C. S.,Garbrecht, B.,Hambye, T.,Harz, J.,Herná,ndez, P.,Kim, C. S.,Molinaro, E.,Nardi, E.,Racker, J.,Rius, N.,Zamora-Saa, J. World Scientific Publishing Company 2018 International journal of modern physics. A, Partic Vol.33 No.6

<P>The focus of this paper lies on the possible experimental tests of leptogenesis scenarios. We consider both leptogenesis generated from oscillations, as well as leptogenesis from out-of-equilibrium decays. As the Akhmedov-Rubakov-Smirnov (ARS) mechanism allows for heavy neutrinos in the GeV range, this opens up a plethora of possible experimental tests, e.g. at neutrino oscillation experiments, neutrinoless double beta decay, and direct searches for neutral heavy leptons at future facilities. In contrast, testing leptogenesis from out-of-equilibrium decays is a quite difficult task. We comment on the necessary conditions for having successful leptogenesis at the TeV-scale. We further discuss possible realizations and their model specific testability in extended seesaw models, models with extended gauge sectors, and supersymmetric leptogenesis. Not being able to test high-scale leptogenesis directly, we present a way to falsify such scenarios by focusing on their washout processes. This is discussed specifically for the left-right symmetric model and the observation of a heavy <TEX>$ W_{R}$</TEX>, as well as model independently when measuring <TEX>$ \Updelta L = 2$</TEX> washout processes at the LHC or neutrinoless double beta decay.</P>

Colorectal Transit and Volume During Treatment With Prolonged-release Oxycodone/Naloxone Versus Oxycodone Plus Macrogol 3350

( Jakob L Poulsen ),( Esben B Mark ),( Christina Brock ),( Jens B Frøkjær ),( Klaus Krogh ),( Asbjørn M Drewes ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.1

Background/Aims Opioid-induced constipation (OIC) is the most common gastrointestinal (GI) side effect to opioid treatment. Opioid receptor antagonists against OIC have been introduced, but their efficacy has not been directly compared to conventional laxatives. Our aim was to compare symptoms and objective parameters of gut function in an experimental model of OIC during treatment with the opioid antagonist naloxone and oxycodone in prolonged-release (PR) formulation versus oxycodone plus macrogol 3350. Methods In this randomized, double-blind, crossover trial 20 healthy men received a 5-day treatment of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Regional GI transit times and segmental colorectal transit were assessed with the Motilis 3D-Transit electromagnetic capsule system. Colorectal volumes were determined by MRI. OIC symptoms were assessed with validated questionnaires, along with stool frequency and consistency. Results Total colorectal volume did not change after 5 days’ treatment with PR oxycodone/naloxone (941 vs 1036 mL; P = 0.091), but increased significantly after PR oxycodone plus macrogol treatment (912 vs 1123 mL; P < 0.001). Neither regional GI transit times nor segmental colorectal transit differed between the treatments (all P > 0.05). The Patient Assessment of Constipation Symptom Questionnaire abdominal symptoms score was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (0.2 vs 3.2; P = 0.002). Stool frequency was lower during PR oxycodone/naloxone compared to PR oxycodone plus macrogol (4.2 vs 5.4; P = 0.035). Conclusions PR oxycodone plus macrogol increases colorectal volume, but does not improve GI transit compared to PR oxycodone/naloxone. However, PR oxycodone/naloxone results in a lower abdominal symptom burden, despite higher stool frequency during macrogol treatment. (J Neurogastroenterol Motil 2018;24:119-127)

Effects of Naloxegol on Gastrointestinal Transit and Colonic Fecal Volume in Healthy Participants Receiving Oxycodone

Anne E Olesen,Debbie Grønlund,Esben B Mark,Klaus Krogh,Jens B Frøkjær,Asbjørn M Drewes 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.4

Background/Aims Opioids cause gastrointestinal (GI) dysmotility, decrease gut secretion, and affect gut sphincters. Symptoms of opioid-induced bowel dysfunction may be alleviated by peripherally acting opioid antagonists like naloxegol, but detailed knowledge on GI effects of this drug is lacking. We hypothesized that naloxegol, compared to placebo, would reduce GI transit time and colonic fecal volume in opioid-treated healthy participants. Methods We conducted a randomized, double-blinded, single-center, 2-way cross-over study in 24 healthy males, randomized to a 6 day treatment period of oxycodone (15 mg twice a day) co-administered with either naloxegol (25 mg once a day) or matching placebo. Participants swallowed an electromagnetic capsule which determined GI transit times. Colonic fecal volume was quantified with magnetic resonance imaging both pre-treatment and post-treatment. Results Naloxegol reduced total GI transit time by 21% (56 hours vs 71 hours, P = 0.02) and colonic transit time by 23% (45 hours vs 59 hours, P < 0.01), compared to placebo. However, no difference in colonic fecal volume was found (818 mL vs 884 mL, P = 0.20). Conclusions Short-term administration of naloxegol in healthy participants reverses the retardation of total GI and colonic transit induced by oxycodone. This supports the use of naloxegol in the treatment of GI side effects to opioid treatment, and add knowledge to the current understanding of mechanisms behind peripherally-acting opioid antagonists.

The Impact of Opioid Treatment on Regional Gastrointestinal Transit

( Jakob L Poulsen ),( Matias Nilsson ),( Christina Brock ),( Thomas H Sandberg ),( Klaus Krogh ),( Asbjørn M Drewes ) 대한소화기기능성질환·운동학회 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.2

Background/Aims To employ an experimental model of opioid-induced bowel dysfunction in healthy human volunteers, and evaluate the impact of opioid treatment compared to placebo on gastrointestinal (GI) symptoms and motility assessed by questionnaires and regional GI transit times using the 3-dimensional (3D)-Transit system. Methods Twenty-five healthy males were randomly assigned to oxycodone or placebo for 5 days in a double blind, crossover design. Adverse GI effects were measured with the bowel function index, gastrointestinal symptom rating scale, patient assessment of constipation symptom questionnaire, and Bristol stool form scale. Regional GI transit times were determined using the 3D-Transit system, and segmental transit times in the colon were determined using a custom Matlab® graphical user interface. Results GI symptom scores increased significantly across all applied GI questionnaires during opioid treatment. Oxycodone increased median total GI transit time from 22.2 to 43.9 hours (P < 0.001), segmental transit times in the cecum and ascending colon from 5.7 to 9.9 hours (P = 0.012), rectosigmoid colon transit from 2.7 to 9.0 hours (P = 0.044), and colorectal transit time from 18.6 to 38.6 hours (P = 0.001). No associations between questionnaire scores and segmental transit times were detected. Conclusions Self-assessed GI adverse effects and increased GI transit times in different segments were induced during oxycodone treatment. This detailed information about segmental changes in motility has great potential for future interventional head-to-head trials of different laxative regimes for prevention and treatment of constipation. (J Neurogastroenterol Motil 2016;22:282-291)

Axial Movements and Length Changes of the Human Lower Esophageal Sphincter During Respiration and Distension-induced Secondary Peristalsis Using Functional Luminal Imaging Probe

( Donghua Liao ),( Christian Lottrup ),( Lotte Fynne ),( Barry P Mcmahon ),( Klaus Krogh ),( Asbjørn M Drewes ),( Jingbo Zhao ),( Hans Gregersen ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2018 Journal of Neurogastroenterology and Motility (JNM Vol.24 No.2

Background/Aims Efficient transport through the esophago-gastric junction (EGJ) requires synchronized circular and longitudinal muscle contraction of the esophagus including relaxation of the lower esophageal sphincter (LES). However, there is a scarcity of technology for measuring esophagus movements in the longitudinal (axial) direction. The aim of this study is to develop new analytical tools for dynamic evaluation of the length change and axial movement of the human LES based on the functional luminal imaging probe (FLIP) technology and to present normal signatures for the selected parameters. Methods Six healthy volunteers without hiatal hernia were included. Data were analyzed from stepwise LES distensions at 20, 30, and 40 mL bag volumes. The bag pressure and the diameter change were used for motion analysis in the LES. The cyclic bag pressure frequency was used to distinguish dynamic changes of the LES induced by respiration and secondary peristalsis. Results Cyclic fluctuations of the LES were evoked by respiration and isovolumetric distension, with phasic changes of bag pressure, diameter, length, and axial movement of the LES narrow zone. Compared to the respiration-induced LES fluctuations, peristaltic contractions increased the contraction pressure amplitude (P < 0.001), shortening (P < 0.001), axial movement (P < 0.001), and diameter change (P < 0.01) of the narrow zone. The length of the narrow zone shortened as function of the pressure increase. Conclusions FLIP can be used for evaluation of dynamic length changes and axial movement of the human LES. The method may shed light on abnormal longitudinal muscle activity in esophageal disorders. (J Neurogastroenterol Motil 2018;24:255-267)

Gastric Emptying Time and Volume of the Small Intestine as Objective Markers in Patients With Symptoms of Diabetic Enteropathy

( Mette W Klinge ),( Nanna Sutter ),( Esben B Mark ),( Anne-mette Haase ),( Per Borghammer ),( Vincent Schlageter ),( Sten Lund ),( Jesper Fleischer ),( Karoline Knudsen ),( Asbjørn M Drewes ),( Klaus 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.3

Background/Aims Patients with diabetes mellitus (DM) often suffer from gastrointestinal (GI) symptoms, but these correlate poorly to established objective GI motility measures. Our aim is to perform a detailed evaluation of potential measures of gastric and small intestinal motility in patients with DM type 1 and severe GI symptoms. Methods Twenty patients with DM and 20 healthy controls (HCs) were included. GI motility was examined with a 3-dimensional-Transit capsule, while organ volumes were determined by CT scans. Results Patients with DM and HCs did not differ with regard to median gastric contraction frequency (DM: 3.0 contractions/minute [interquartile range {IQR}, 2.9-3.0]; HCs: 2.9 [IQR, 2.8-3.1]; P = 0.725), amplitude of gastric contractions (DM: 9 mm [IQR, 8-11]; HCs: 11 mm (IQR, 9-12); P = 0.151) or fasting volume of the stomach wall (DM: 149 ㎤ [IQR, 112-187]; HCs: 132 ㎤ [IQR, 107-154]; P = 0.121). Median gastric emptying time was prolonged in patients (DM: 3.3 hours [IQR, 2.6-4.6]; HCs: 2.4 hours [IQR, 1.8-2.7]; P = 0.002). No difference was found in small intestinal transit time (DM: 5 hours [IQR, 3.7-5.6]; HCs: 4.8 hours [IQR, 3.9-6.0]; P = 0.883). However, patients with DM had significantly larger volume of the small intestinal wall (DM: 623 ㎤ [IQR, 487-766]; HCs: 478 ㎤ [IQR, 393-589]; P = 0.003). Among patients, 13 (68%) had small intestinal wall volume and 9 (50%) had gastric emptying time above the upper 95% percentile of HCs. Conclusion In our study, gastric emptying time and volume of the small intestinal wall appeared to be the best objective measures in patients with DM type 1 and symptoms and gastroenteropathy. (J Neurogastroenterol Motil 2021;27:390-399)

Cloud-Based Synchronization for Interface Settings for Older Adults

Drew Williams,Sheikh Iqbal Ahamed,William Cheng-Chung Chu,Mong-Te Wang,Chih-Hung Chang 보안공학연구지원센터 2014 International Journal of Hybrid Information Techno Vol.7 No.4

Comparison of two techniques for transpharyngeal endoscopic auditory tube diverticulotomy in the horse

Drew W. Koch,Jeremiah T. Easley,Brad B. Nelson,Jeremy J. Delcambre,Erin G. McCready,Eileen S. Hackett 대한수의학회 2018 Journal of Veterinary Science Vol.19 No.6

Auditory tube diverticula, also known as guttural pouches, are naturally occurring dilations of the auditory tube in horses that communicate with the nasopharynx through a small ostium. Infection and select other conditions can result in inflammation and narrowing of the nasopharyngeal ostium, which prevents drainage of fluid or egress of air and can lead to persistent infection or guttural pouch tympany. Auditory tube diverticulotomy allows continuous egress from the auditory tube diverticula and is a feature of disease treatment in horses, in which medical treatment alone is not successful. Transpharyngeal endoscopic auditory tube diverticulotomy was performed using a diode laser either at a single dorsal pharyngeal recess location or bilaterally caudal to the nasopharyngeal ostium in 10 horse head specimens. Both methods resulted in clear communication between the nasopharynx and auditory tube diverticula. Diverticulotomy performed in the dorsal pharyngeal recess required less laser energy and activation time and had a shorter surgical duration than diverticulotomy performed caudal to the nasopharyngeal ostium. Further study related to the clinical application of both techniques is warranted.