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Name of journal: World Journal of GastroenterologyManuscript NO: 32407Manuscript?Type: ORIGINAL ARTICLEBasic StudyEnhanced electrogastrography: a realistic way to salvage a promise that was never kept?Poscente MD et al. Enhanced electrogastrographyMichael D Poscente, Martin P MintchevMichael D Poscente, Martin P Mintchev, Department of Electrical and Computer Engineering, University of Calgary, Calgary, Alberta T2N1N4, CanadaAuthor contributions: Poscente MD participated in the entire research and development process, assisted with the surgical experiments, and wrote the initial version of the manuscript; Mintchev MP proposed the original idea, supervised the entire research and development process, designed the surgical experiments and performed the surgeries, structured the manuscript and edited it.Institutional animal care and use committee statement: The experimental work was approved by the Veterinary Sciences Animal Care Committee, University of Calgary, Calgary, Alberta, Canada T2N1N4, Protocol No. SHC11R-03.Conflict-of-interest statement: The authors declare no conflict of interest.Data sharing statement: The data have been collected, processed, stored and utilized solely by the authors.Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: source: Invited manuscriptCorrespondence to: Martin P Mintchev, Professor, Department of Electrical and Computer Engineering, University of Calgary, Calgary, Alberta T2N1N4, Canada. mintchev@ucalgary.caTelephone: +1-403-2205309Fax: +1-403-2826855Received: January 6, 2017Peer-review started: January 9, 2017First decision: April 14, 2017Revised: April 29, 2017Accepted: June 9, 2017Article in press:Published online:AbstractAIMTo ehance the clinical utility of electrogastrography (EGG), which has been recorded since 1922, but is clinically unutilized.METHODSAn innovative method to salvage the promise of EGG is proposed by introducing a preliminary procedure, while maintaining the electrodes, standardized equipment, and signal processing utilized in the well-established EGG testing of today. The proposed enhanced EGG (EEGG) protocol involves swallowing an ingestible capsule containing miniature electronic oscillator embedded in an expandable, self-disintegratable, biocompatible pseudobesoar residing in the stomach for the duration of the test. The benefits of the proposed approach are outlined, tested and discussed in details. RESULTSExperiments were performed on eight mongrel dogs (6F, 4M, 23.8 ± 3.3 kg). Four were administered an active EEGG capsule, while the rest were given a deactivated (battery removed) capsule. Pharmacologically facilitated gastric motility revealed a significant (p < 0.01) Pearson correlation between gastric motility indices obtained by force transducers implanted directly on the stomach, and the motility indices obtained by EEGG. A particular emphasis was made on preserving standard EGG-related hardware and software in order to facilitate the introduction of the proposed EEGG in environments which already utilize standard EGG testing. The expanded intragastric pseudobezoar containing the miniature electronic oscillator was retained during the tests, and could be disintegrated on demand. CONCLUSIONEnhancing standard EGG by an ingestible, self-expanding and self-disintegrating pseudobesoar containing a miniature electronic oscillator can be an important avenue for clinical applicability of this test.Key words: Electrogastrography; Functional dyspepsia; Gastroparesis; Ingestible oscillator; Pseudobesoar? The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.Core tip: Intrinsic gastric electrical activity is of specific nature that restricts the clinical applicability of its non-invasive measurements known as electrogastrography (EGG). This study proposes the utilization of an ingestible, self-expanding and self-disintegrating pseudobesoar containing a miniature electrical oscillator to enhance the clinical utility of EGG in diagnosing functional dyspepsia and gastroparesis.Poscente MD, Mintchev MP. Enhanced Electrogastrography: a realistic way to salvage a promise that was never kept? World J Gastroenterol 2017; In pressINTRODUCTIONCutaneous recordings of gastric electrical activity (GEA), known as electrogastrography (EGG), have been recorded since 1922 ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2mcg77bevn","properties":{"formattedCitation":"[1]","plainCitation":"[1]"},"citationItems":[{"id":8,"uris":[""],"uri":[""],"itemData":{"id":8,"type":"article-journal","title":"The electrogastrogram and what it shows","container-title":"Journal of the American Medical Association","page":"1116-1119","volume":"78","issue":"15","DOI":"10.1001/jama.1922.02640680020008","ISSN":"0002-9955","author":[{"literal":"W Alvarez"}],"issued":{"date-parts":[["1922",4,15]]}}}],"schema":""} [1] and has been groomed to become a single, non-invasive test for the early diagnosis of functional gastric dyspepsia and gastroparesis. However, to this day remain clinically unutilized, although two distinct Current Procedural Terminology (CPT) codes associated with EGG have been introduced in the USA for diagnostic purposes ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"faeu4v9H","properties":{"formattedCitation":"[2]","plainCitation":"[2]"},"citationItems":[{"id":10,"uris":[""],"uri":[""],"itemData":{"id":10,"type":"article-journal","title":"The Gastrointestinal Motility Laboratory","container-title":"Gastroenterology Clinics of North America","collection-title":"Gastrointestinal Motility Disorders","page":"515-529","volume":"36","issue":"3","source":"ScienceDirect","abstract":"Abnormalities of gastrointestinal (GI) motor function contribute directly or indirectly to a number of common clinical problems and account for significant health care–related expenditure. Proper evaluation of patients who have suspected GI motility disorders is important to ensure a correct diagnosis and to embark on an appropriate plan of treatment. The GI motility laboratory serves as an important area for patient evaluation in gastroenterology and is an essential element in any comprehensive digestive disease program. This article addresses important concepts in setting up and running an efficient and practical GI motility laboratory.","DOI":"10.1016/j.gtc.2007.07.010","ISSN":"0889-8553","author":[{"family":"Parkman","given":"Henry P."},{"family":"Orr","given":"William C."}],"issued":{"date-parts":[["2007",9]]}}}],"schema":""} [2]. Despite numerous unsubstantiated claims regarding the clinical utility of EGG, the prevailing attitude addressing the limitations of EGG for clinical decision-making is that they have overwhelmingly cast their shadow over this tempting non-invasive test which was promoted as a primary clinical tool for diagnosing functional dyspepsia ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"9xIfCm3L","properties":{"formattedCitation":"{\\rtf [2]\\uc0\\u8211{}[4]}","plainCitation":"[2]–[4]"},"citationItems":[{"id":10,"uris":[""],"uri":[""],"itemData":{"id":10,"type":"article-journal","title":"The Gastrointestinal Motility Laboratory","container-title":"Gastroenterology Clinics of North America","collection-title":"Gastrointestinal Motility Disorders","page":"515-529","volume":"36","issue":"3","source":"ScienceDirect","abstract":"Abnormalities of gastrointestinal (GI) motor function contribute directly or indirectly to a number of common clinical problems and account for significant health care–related expenditure. Proper evaluation of patients who have suspected GI motility disorders is important to ensure a correct diagnosis and to embark on an appropriate plan of treatment. The GI motility laboratory serves as an important area for patient evaluation in gastroenterology and is an essential element in any comprehensive digestive disease program. This article addresses important concepts in setting up and running an efficient and practical GI motility laboratory.","DOI":"10.1016/j.gtc.2007.07.010","ISSN":"0889-8553","author":[{"family":"Parkman","given":"Henry P."},{"family":"Orr","given":"William C."}],"issued":{"date-parts":[["2007",9]]}}},{"id":13,"uris":[""],"uri":[""],"itemData":{"id":13,"type":"article-journal","title":"Gastric myoelectrical activity and gastric emptying in patients with functional dyspepsia","container-title":"The American Journal of Gastroenterology","page":"2384-2389","volume":"94","issue":"9","source":"","abstract":"OBJECTIVES: The aims of this study were to investigate gastric myoelectrical activity and gastric emptying (GE) and their relationship in patients with functional dyspepsia.\nMETHODS: The study was conducted in 15 healthy volunteers (six women, nine men, mean age: 42 yr) and 15 patients (13 women, two men, mean age: 43 yr) with functional dyspepsia. Gastric myoelectrical activity was recorded using cutaneous electrogastrography (EGG) for 30 min in the fasting state and for 120 min simultaneously with GE monitoring after an isotope-labeled solid meal. The anterior/posterior images of the stomach were taken using a technetium scanner immediately after eating, and then at 1, 2, and 4 h to determine the percentage of gastric retention. The dominant frequency of the EGG, the change of the postprandial EGG peak power (P), and the percentage of normal 2–4 cycles/min (cpm) slow waves during each recording session were calculated and compared between the patients and healthy subjects.\nRESULTS: The patients had a significantly lower mean percentage of 2–4 cpm slow waves, both in the fed state and in the fasting state, than did healthy subjects. Compared to the EGG in the fasting state, a significant increase of the EGG dominant frequency in the fed state was observed in healthy subjects but not in the patients. The mean postprandial EGG power increase in the patients was substantially less than in the healthy subjects during the first postprandial hour but similar during the second postprandial hour. The mean percentage of gastric retention in patients is substantially higher than in the healthy subjects, both at 2 h after eating and at 4 h after eating. Of 15 patients, nine (60%) had delayed GE (gastric retention at 2 h >50%) and 10 (66%) had abnormal EGGs (percentage of 2–4 cpm <70% and/or P < 0). Eight of these 10 patients (80%) with abnormal EGGs had delayed GE.\nCONCLUSIONS: A high proportion of adult patients (60%) with functional dyspepsia have abnormally slow GE and abnormalities in gastric myoelectrical activity.","DOI":"10.1111/j.1572-0241.1999.01362.x","ISSN":"0002-9270","language":"en","author":[{"family":"Lin","given":"Zhiyue"},{"family":"Eaker","given":"Ervin Y."},{"family":"Sarosiek","given":"Irene"},{"family":"McCallum","given":"Richard W."}],"issued":{"date-parts":[["1999",9]]}}},{"id":16,"uris":[""],"uri":[""],"itemData":{"id":16,"type":"article-journal","title":"Electrogastrography as a diagnostic tool for delayed gastric emptying in functional dyspepsia and irritable bowel syndrome","container-title":"Neurogastroenterology & Motility","page":"467-473","volume":"15","issue":"5","source":"Wiley Online Library","abstract":"Several pathophysiological mechanisms have been proposed in functional gastrointestinal (GI) disorders, e.g. altered GI motility and sensitivity. The aim of this study was to investigate gastric electrical activity (GEA) in patients with functional dyspepsia (FD) or irritable bowel syndrome (IBS) compared with healthy controls (HC), and to assess if abdominal symptoms and delayed gastric emptying are associated with alterations in GEA, as determined by electrogastrography (EGG). Forty patients with FD, IBS or both were compared with 22 HC. EGG was performed before and after a standard meal. Frequencies and amplitudes pre- and post-prandially were analysed. Furthermore, gastric emptying and symptom scores were assessed. Eight of 40 patients (20%; three FD, three IBS, two FD and IBS) had delayed gastric emptying. Disturbed gastric emptying and lack of a postprandial increase in the EGG amplitude were significantly correlated (r?=?0.8; P?<?0.005). No differences between controls and patients were observed in the distribution of EGG frequencies. Treatment with the prokinetically active macrolide erythromycin improved gastric emptying, GEA and symptoms (n?=?4). The data suggest that EGG could be useful as a diagnostic tool in patients with FD and IBS to identify a subgroup of patients with delayed gastric emptying.","DOI":"10.1046/j.1365-2982.2003.00433.x","ISSN":"1365-2982","language":"en","author":[{"family":"Van Der Voort","given":"I. R."},{"family":"Osmanoglou","given":"E."},{"family":"Seybold","given":"M."},{"family":"Heymann-M?nnikes","given":"I."},{"family":"Tebbe","given":"J."},{"family":"Wiedenmann","given":"B."},{"family":"Klapp","given":"B. F."},{"family":"M?nnikes","given":"H."}],"issued":{"date-parts":[["2003",10,1]]}}}],"schema":""} [2-4]. In this study we discuss an innovative method to salvage the promise of EGG, by introducing a preliminary procedure to the patient preparation, while maintaining the electrodes, standardized equipment, and signal processing utilized in the standard EGG testing of today, with the hope that this technique can revive the promise of EGG as a clinical diagnostic test for functional dyspepsia and gastroparesis.Functional dyspepsia as a disorder of gastric motilityFunctional dyspepsia is a multifaceted disorder of the upper gastrointestinal tract that affects between 5 and 11% of the world population ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1ps1js8vvq","properties":{"formattedCitation":"[5]","plainCitation":"[5]"},"citationItems":[{"id":23,"uris":[""],"uri":[""],"itemData":{"id":23,"type":"article-journal","title":"Review article: current treatment options and management of functional dyspepsia","container-title":"Alimentary Pharmacology & Therapeutics","page":"3-15","volume":"36","issue":"1","source":"onlinelibrary.","DOI":"10.1111/j.1365-2036.2012.05128.x","ISSN":"1365-2036","shortTitle":"Review article","language":"en","author":[{"family":"Lacy","given":"B. E."},{"family":"Talley","given":"N. J."},{"family":"Locke","given":"G. R."},{"family":"Bouras","given":"E. P."},{"family":"DiBaise","given":"J. K."},{"family":"El‐Serag","given":"H. B."},{"family":"Abraham","given":"B. P."},{"family":"Howden","given":"C. W."},{"family":"Moayyedi","given":"P."},{"family":"Prather","given":"C."}],"issued":{"date-parts":[["2012",7,1]]}}}],"schema":""} [5], and is defined by the so called Rome IV criteria, which include: (1) sensation of pain and/or burning in the epigastrium; (2) early satiety (inability to finish a normal-sized meal); (3) distinct feeling of fullness during and immediately after meal; and (4) combination of these symptoms in a repetitive manner ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"99told9cp","properties":{"formattedCitation":"[6]","plainCitation":"[6]"},"citationItems":[{"id":26,"uris":[""],"uri":[""],"itemData":{"id":26,"type":"article-journal","title":"Development and Validation of the Rome IV Diagnostic Questionnaire for Adults","container-title":"Gastroenterology","collection-title":"Rome IV - Functional GI Disorders: Disorders of Gut-Brain Interaction","page":"1481-1491","volume":"150","issue":"6","source":"ScienceDirect","abstract":"The Rome IV Diagnostic Questionnaires were developed to screen for functional gastrointestinal disorders, serve as inclusion criteria in clinical trials, and support epidemiologic surveys. Separate questionnaires were developed for adults, children and adolescents, and infants and toddlers. For the adult questionnaire, we first surveyed 1162 adults without gastrointestinal disorders, and recommended the 90th percentile symptom frequency as the threshold for defining what is abnormal. Diagnostic questions were formulated and verified with clinical experts using a recursive process. The diagnostic sensitivity of the questionnaire was tested in 843 patients from 9 gastroenterology clinics, with a focus on clinical diagnoses of irritable bowel syndrome (IBS), functional constipation (FC), and functional dyspepsia (FD). Sensitivity was 62.7% for IBS, 54.7% for FD, and 32.2% for FC. Specificity, assessed in a population sample of 5931 adults, was 97.1% for IBS, 93.3% for FD, and 93.6% for FC. Excess overlap among IBS, FC, and FD was a major contributor to reduced diagnostic sensitivity, and when overlap of IBS with FC was permitted, sensitivity for FC diagnosis increased to 73.2%. All questions were understandable to at least 90% of individuals, and Rome IV diagnoses were reproducible in three-fourths of patients after 1 month. Validation of the pediatric questionnaires is ongoing.","DOI":"10.1053/j.gastro.2016.02.014","ISSN":"0016-5085","author":[{"family":"Palsson","given":"Olafur S."},{"family":"Whitehead","given":"William E."},{"family":"Tilburg","given":"Miranda A. L.","non-dropping-particle":"van"},{"family":"Chang","given":"Lin"},{"family":"Chey","given":"William"},{"family":"Crowell","given":"Michael D."},{"family":"Keefer","given":"Laurie"},{"family":"Lembo","given":"Anthony J."},{"family":"Parkman","given":"Henry P."},{"family":"Rao","given":"Satish S. C."},{"family":"Sperber","given":"Ami"},{"family":"Spiegel","given":"Brennan"},{"family":"Tack","given":"Jan"},{"family":"Vanner","given":"Stephen"},{"family":"Walker","given":"Lynn S."},{"family":"Whorwell","given":"Peter"},{"family":"Yang","given":"Yunsheng"}],"issued":{"date-parts":[["2016",5]]}}}],"schema":""} [6]. Gastric motility abnormalities such as delayed emptying, impaired initial distribution of a meal within the stomach, impaired accommodation to a meal, antral hypomotility, gastric electrical dysrhythmias (tachygastrias, bradygastrias, and mixed dysrhythmias), and delayed gastric emptying have all been identified in patients with functional dyspepsia ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"it7o5ul37","properties":{"formattedCitation":"[7]","plainCitation":"[7]"},"citationItems":[{"id":29,"uris":[""],"uri":[""],"itemData":{"id":29,"type":"article-journal","title":"Gastric emptying of liquids and solids: roles of proximal and distal stomach","container-title":"American Journal of Physiology - Gastrointestinal and Liver Physiology","page":"G71-G76","volume":"239","issue":"2","source":"ajpgi.","abstract":"The objective was to explore the hypothesis that the proximal stomach has a major role in gastric emptying of liquids and the distal stomach a major role in gastric emptying of solids. The results of experiments on the intact stomach and on the stomach after selective resections, denervations, and during hormonal infusions are, in general, consistent with the hypothesis.","ISSN":"0193-1857, 1522-1547","note":"PMID: 6996495","shortTitle":"Gastric emptying of liquids and solids","language":"en","author":[{"family":"Kelly","given":"K. A."}],"issued":{"date-parts":[["1980",8,1]]},"PMID":"6996495"}}],"schema":""} [7]. The portfolio of dyspeptic symptoms strongly suggests an impaired gastric motility association with the disorder. However, although antral hypomotility and delayed gastric emptying are frequent in patients with functional dyspepsia ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2d7rj612ig","properties":{"formattedCitation":"[6]","plainCitation":"[6]"},"citationItems":[{"id":26,"uris":[""],"uri":[""],"itemData":{"id":26,"type":"article-journal","title":"Development and Validation of the Rome IV Diagnostic Questionnaire for Adults","container-title":"Gastroenterology","collection-title":"Rome IV - Functional GI Disorders: Disorders of Gut-Brain Interaction","page":"1481-1491","volume":"150","issue":"6","source":"ScienceDirect","abstract":"The Rome IV Diagnostic Questionnaires were developed to screen for functional gastrointestinal disorders, serve as inclusion criteria in clinical trials, and support epidemiologic surveys. Separate questionnaires were developed for adults, children and adolescents, and infants and toddlers. For the adult questionnaire, we first surveyed 1162 adults without gastrointestinal disorders, and recommended the 90th percentile symptom frequency as the threshold for defining what is abnormal. Diagnostic questions were formulated and verified with clinical experts using a recursive process. The diagnostic sensitivity of the questionnaire was tested in 843 patients from 9 gastroenterology clinics, with a focus on clinical diagnoses of irritable bowel syndrome (IBS), functional constipation (FC), and functional dyspepsia (FD). Sensitivity was 62.7% for IBS, 54.7% for FD, and 32.2% for FC. Specificity, assessed in a population sample of 5931 adults, was 97.1% for IBS, 93.3% for FD, and 93.6% for FC. Excess overlap among IBS, FC, and FD was a major contributor to reduced diagnostic sensitivity, and when overlap of IBS with FC was permitted, sensitivity for FC diagnosis increased to 73.2%. All questions were understandable to at least 90% of individuals, and Rome IV diagnoses were reproducible in three-fourths of patients after 1 month. Validation of the pediatric questionnaires is ongoing.","DOI":"10.1053/j.gastro.2016.02.014","ISSN":"0016-5085","author":[{"family":"Palsson","given":"Olafur S."},{"family":"Whitehead","given":"William E."},{"family":"Tilburg","given":"Miranda A. L.","non-dropping-particle":"van"},{"family":"Chang","given":"Lin"},{"family":"Chey","given":"William"},{"family":"Crowell","given":"Michael D."},{"family":"Keefer","given":"Laurie"},{"family":"Lembo","given":"Anthony J."},{"family":"Parkman","given":"Henry P."},{"family":"Rao","given":"Satish S. C."},{"family":"Sperber","given":"Ami"},{"family":"Spiegel","given":"Brennan"},{"family":"Tack","given":"Jan"},{"family":"Vanner","given":"Stephen"},{"family":"Walker","given":"Lynn S."},{"family":"Whorwell","given":"Peter"},{"family":"Yang","given":"Yunsheng"}],"issued":{"date-parts":[["2016",5]]}}}],"schema":""} [6], the clinical importance of these findings remains uncertain, mainly for two reasons: (1) they do not always correlate with symptoms; and (2) the link to impaired gastric motility has not been demonstrated ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2gpq90vgs9","properties":{"formattedCitation":"[8]","plainCitation":"[8]"},"citationItems":[{"id":33,"uris":[""],"uri":[""],"itemData":{"id":33,"type":"article-journal","title":"Symptoms Associated With Impaired Gastric Emptying of Solids and Liquids in Functional Dyspepsia","container-title":"The American Journal of Gastroenterology","page":"783-788","volume":"98","issue":"4","source":"","abstract":"OBJECTIVES: The relationship between functional dyspepsia and delayed gastric emptying of solids or liquids is still unclear. The aim of the present study was to investigate in dyspeptic patients the prevalence of delayed gastric emptying for solids or for liquids and to investigate the relationship to the dyspepsia symptom pattern.\nMETHODS: In 392 and 330 patients with functional dyspepsia, the solid and liquid gastric emptying, respectively, was measured using breath tests, and the severity of eight dyspeptic symptoms was scored.\nRESULTS: Gastric emptying of solids and liquids were delayed in 23% and 35% of the patients. Multivariate analysis showed that the presence of vomiting and postprandial fullness was associated with delayed solid emptying (OR 2.65, 95% CI = 1.62–4.35 and OR 3.08, 95% CI = 1.28–9.16, respectively). Postprandial fullness was also associated with the risk of delayed liquid emptying when symptom was present (OR 3.5, 95% CI = 1.57–8.68), relevant or severe (OR 2.504, 95% CI = 1.41–4.65), and severe (OR 2.214, 95% CI = 1.34–3.67). Severe early satiety was associated with the risk of delayed liquid emptying (OR 1.902, 95% CI = 1.90–3.30).\nCONCLUSIONS: A subset of dyspeptic patients has delayed gastric emptying of solids or of liquids. Delayed gastric emptying of solids was constantly associated with postprandial fullness and with vomiting. Delayed emptying for liquids was also associated with postprandial fullness and with severe early satiety.","DOI":"10.1111/j.1572-0241.2003.07389.x","ISSN":"0002-9270","language":"en","author":[{"family":"Sarnelli","given":"Giovanni"},{"family":"Caenepeel","given":"Philip"},{"family":"Geypens","given":"Benny"},{"family":"Janssens","given":"Jozef"},{"family":"Tack","given":"Jan"}],"issued":{"date-parts":[["2003",4]]}}}],"schema":""} [8] due to the lack of a single, reliable, 24-hour (or longer) ambulatory test for assessing gastric motility in settings not different than the normal daily routine of the patient, as is presently investigated in the evaluation of esophageal reflux ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"pqujq213k","properties":{"formattedCitation":"[9]","plainCitation":"[9]"},"citationItems":[{"id":36,"uris":[""],"uri":[""],"itemData":{"id":36,"type":"article-journal","title":"Technology Review: Esophageal Impedance Monitoring","container-title":"The American Journal of Gastroenterology","page":"187-194","volume":"102","issue":"1","source":"","abstract":"Intraluminal impedance monitoring is a new technique that can be used to detect the flow of liquids and gas through hollow viscera. In combination with manometry, it is used for esophageal function testing and while manometry provides information on contractile activity, impedance provides information on esophageal bolus transit. This is especially useful in patients with nonobstructive dysphagia. However, impedance monitoring appears to be less suitable for the evaluation of patients with achalasia. When used in combination with esophageal pH monitoring, impedance monitoring makes gastroesophageal reflux monitoring more complete because it allows recognition of both acidic and weakly acidic reflux episodes. The results of several studies suggest that impedance–pH monitoring is useful in the evaluation of patients with PPI-resistant typical reflux symptoms, chronic unexplained cough, excessive belching, and rumination.","DOI":"10.1111/j.1572-0241.2006.00966.x","ISSN":"0002-9270","shortTitle":"Technology Review","language":"en","author":[{"family":"Bredenoord","given":"Albert J."},{"family":"Tutuian","given":"Radu"},{"family":"Smout","given":"André JPM"},{"family":"Castell","given":"Donald O."}],"issued":{"date-parts":[["2007",1]]}}}],"schema":""} [9].In this situation, the availability of a reliable long-term, ambulatory gastric motility test could possibly correlate the presence of dyspeptic symptoms to gastric motor function abnormalities, or, alternatively, to dispel such relationship altogether. This testing deficiency prompted researchers to search for alternative causes and reasons that could possibly be associated with functional dyspepsia ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2hrec44euq","properties":{"formattedCitation":"[10]","plainCitation":"[10]"},"citationItems":[{"id":48,"uris":[""],"uri":[""],"itemData":{"id":48,"type":"article-journal","title":"Functional Dyspepsia","container-title":"New England Journal of Medicine","page":"1853-1863","volume":"373","issue":"19","source":"Taylor and Francis+NEJM","abstract":"Dyspepsia is a constellation of symptoms referable to the gastroduodenal region of the upper gastrointestinal tract. Functional dyspepsia, a relapsing and remitting disorder, is the most common cause of these symptoms. The current standard for the diagnosis of functional dyspepsia is the Rome III criteria, developed by the Rome III Committees, a multinational group of experts in the field, first convened in 1990, that meets regularly to review and revise the diagnostic criteria for all functional gastrointestinal disorders. The Rome III criteria for functional dyspepsia consist of a sensation of pain or burning in the epigastrium, early satiety (inability to . . .","DOI":"10.1056/NEJMra1501505","ISSN":"0028-4793","note":"PMID: 26535514","author":[{"family":"Talley","given":"Nicholas J."},{"family":"Ford","given":"Alexander C."}],"issued":{"date-parts":[["2015",11,5]]},"PMID":"26535514"}}],"schema":""} [10]. Thus, presently, the diagnosis of functional dyspepsia is predominantly symptom-based, with the support of several tests, including most typically antral manometry and gastric emptying, but in what could be classified as a scientific curiosity associated with mild desperation, researchers are actively seeking other valid reasons for the dyspeptic symptoms to manifest themselves ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2nikp0banv","properties":{"formattedCitation":"[10], [11]","plainCitation":"[10], [11]"},"citationItems":[{"id":48,"uris":[""],"uri":[""],"itemData":{"id":48,"type":"article-journal","title":"Functional Dyspepsia","container-title":"New England Journal of Medicine","page":"1853-1863","volume":"373","issue":"19","source":"Taylor and Francis+NEJM","abstract":"Dyspepsia is a constellation of symptoms referable to the gastroduodenal region of the upper gastrointestinal tract. Functional dyspepsia, a relapsing and remitting disorder, is the most common cause of these symptoms. The current standard for the diagnosis of functional dyspepsia is the Rome III criteria, developed by the Rome III Committees, a multinational group of experts in the field, first convened in 1990, that meets regularly to review and revise the diagnostic criteria for all functional gastrointestinal disorders. The Rome III criteria for functional dyspepsia consist of a sensation of pain or burning in the epigastrium, early satiety (inability to . . .","DOI":"10.1056/NEJMra1501505","ISSN":"0028-4793","note":"PMID: 26535514","author":[{"family":"Talley","given":"Nicholas J."},{"family":"Ford","given":"Alexander C."}],"issued":{"date-parts":[["2015",11,5]]},"PMID":"26535514"}},{"id":51,"uris":[""],"uri":[""],"itemData":{"id":51,"type":"article-journal","title":"Functional Dyspepsia in Review: Pathophysiology and Challenges in the Diagnosis and Management due to Coexisting Gastroesophageal Reflux Disease and Irritable Bowel Syndrome","container-title":"Gastroenterology Research and Practice","page":"e351086","volume":"2013","source":"","abstract":"Functional dyspepsia is a common disorder which imposes significant diagnostic and treatment challenges for patients and physicians. The most recent update of the diagnostic criteria subdivides functional dyspepsia into two subcategories based on the main symptom of epigastric pain or postmeal fullness. As we discuss in this review, several studies have shown significant overlap in symptoms and pathophysiology between functional dyspepsia, irritable bowel syndrome, and the spectrum of reflux disorders. This overlap in symptoms can be informative in helping us to understand the underlying pathophysiology, diagnostic approaches, and treatment strategies. The addition of diagnostic testing such as pH impedance manometry of the distal esophagus to the current common diagnostic tests might be helpful in distinguishing between functional dyspepsia and reflux disease. Importantly, various treatment modalities may be more effective than others if the main symptom is burning rather than pain or postmeal fullness rather than early satiation.","DOI":"10.1155/2013/351086","ISSN":"1687-6121","note":"PMID: 23762034","shortTitle":"Functional Dyspepsia in Review","language":"en","author":[{"family":"Yarandi","given":"Shadi S."},{"family":"Christie","given":"Jennifer"}],"issued":{"date-parts":[["2013",5,16]]},"PMID":"23762034"}}],"schema":""} [10,11].Electrogastrography and its limitationsElectrogastrography (EGG), the cutaneous, non-invasive recordings of gastric electrical activity, seemed to be perfectly suited to offer the missing link between gastric motility abnormalities and dyspeptic symptoms, as it was supposed to be a true representation of the intrinsic, omnipresent gastric electrical activity, which in turn controls gastric motility ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2g7akh9vrc","properties":{"formattedCitation":"[12]","plainCitation":"[12]"},"citationItems":[{"id":55,"uris":[""],"uri":[""],"itemData":{"id":55,"type":"article-journal","title":"What is measured in electrogastrography?","container-title":"Digestive Diseases and Sciences","page":"179-187","volume":"25","issue":"3","source":"link.","abstract":"The object of this study was to elucidate what is actually measured in electrogastrography. Comparison of gastric signals simultaneously recorded from serosal and cutaneous electrodes in the conscious dog led to the following findings: 1. In the absence of phasic contractile activity and electrical response activity (ERA), the cutaneous recordings contained a frequency corresponding to the fundamental frequency of the electrical control activity (ECA) of the stomach (about 0.08 Hz). 2. Tachygastrias gave rise to cutaneous signals containing the tachygastric frequency (about 0.25 Hz). 3. The amplitude of the electrogastrogram increased when ERA occurred. It is concluded that both ECA and ERA are reflected in the electrogastrogram. A model is proposed that describes the electrogastrogram as the result of field potentials generated by depolarization and repolarization dipoles.","DOI":"10.1007/BF01308136","ISSN":"0163-2116, 1573-2568","language":"en","author":[{"family":"Smout","given":"A. J. P. M."},{"family":"Schee","given":"E. J. Van Der"},{"family":"Grashuis","given":"J. L."}],"issued":{"date-parts":[["1980",3,1]]}}}],"schema":""} [12]. Not quite, unfortunately. Although arguments pro ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"IaH06KmQ","properties":{"formattedCitation":"[13]","plainCitation":"[13]"},"citationItems":[{"id":147,"uris":[""],"uri":[""],"itemData":{"id":147,"type":"article-journal","title":"Utilizing Electrogastrography in the Evaluation of Idiopathic Dyspepsia","container-title":"Journal of Medical Diagnostic Methods","volume":"2014","source":"Google Scholar","URL":"","author":[{"family":"Randall","given":"Charles W."},{"family":"Zaga-Galante","given":"Jonathan"},{"family":"Vergara-Suarez","given":"Adriana"},{"family":"Taboada","given":"Carlo M."}],"issued":{"date-parts":[["2014"]]},"accessed":{"date-parts":[["2016",11,29]]}}}],"schema":""} [13] and con ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"lbm2kq6am","properties":{"formattedCitation":"[14]","plainCitation":"[14]"},"citationItems":[{"id":61,"uris":[""],"uri":[""],"itemData":{"id":61,"type":"article-journal","title":"Electrogastrography: Methodology, Validation and Applications","container-title":"Journal of Neurogastroenterology and Motility","page":"5-17","volume":"19","issue":"1","source":"e-","abstract":"Title: Electrogastrography: Methodology, Validation and Applications, Journal title: Journal of Neurogastroenterology and Motility","DOI":"10.5056/jnm.2013.19.1.5","ISSN":"2093-0879, 2093-0887","shortTitle":"Electrogastrography","language":"English","author":[{"family":"Yin","given":"Jieyun"},{"family":"Chen","given":"Jiande D. Z."}],"issued":{"date-parts":[["2013",1,8]]}}}],"schema":""} [14] have been circulating in the research community for the last 30 years, the prevalent objective scientific opinion outlines the following 4 major limitations associated with plain EGG:(1) EGG cannot reliably represent gastric contractions or their shape, pattern, frequency, coupling and strength ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"16cgqdvr2v","properties":{"formattedCitation":"[15]","plainCitation":"[15]"},"citationItems":[{"id":91,"uris":[""],"uri":[""],"itemData":{"id":91,"type":"article-journal","title":"Correlations Among Electrogastrogram, Gastric Dysmotility, and Duodenal Dysmotility in Patients With Functional Dyspepsia:","container-title":"Journal of Clinical Gastroenterology","page":"716-722","volume":"43","issue":"8","source":"CrossRef","DOI":"10.1097/MCG.0b013e31818b8ed9","ISSN":"0192-0790","shortTitle":"Correlations Among Electrogastrogram, Gastric Dysmotility, and Duodenal Dysmotility in Patients With Functional Dyspepsia","language":"en","author":[{"family":"Sha","given":"Weihong"},{"family":"Pasricha","given":"Pankaj J."},{"family":"Chen","given":"Jiande D.Z."}],"issued":{"date-parts":[["2009",9]]}}}],"schema":""} [15]; (2) Although EGG seems to represent a heavily integrated picture of the intrinsic gastric electrical rhythm, it fails where its reliability is needed most – in truthfully representing objectively existing internal gastric electrical abnormalities -- dysrhythmias, tachygastrias and bradygastrias ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1h2nkv3s5n","properties":{"formattedCitation":"[16]","plainCitation":"[16]"},"citationItems":[{"id":39,"uris":[""],"uri":[""],"itemData":{"id":39,"type":"article-journal","title":"Pitfalls in the analysis of electrogastrographic recordings","container-title":"Gastroenterology","page":"453-460","volume":"117","issue":"2","source":"ScienceDirect","abstract":"Electrogastrography (EGG) is a noninvasive method to study gastric myoelectrical activity in humans. Because frequency characteristics are the most reliable parameters and visual analysis of the EGG recordings is notoriously difficult, automated frequency analysis, especially running spectrum analysis, is often used. However, EGG frequency spectra can be misinterpreted easily. Movement artifacts and noise from various sources can result in abnormal frequency spectra with significant power in the low-frequency and high-frequency range, or even make the EGG completely uninterpretable. Signals that differ from a sinusoid waveform have harmonics in the high-frequency range of the spectrum and may be interpreted as abnormal. Visual inspection of raw signals and frequency spectra remains essential in the analysis of EGG signals. The value of computerized analysis should not be overrated. EGG is an important research tool, but a clinical role still needs to be established.","DOI":"10.1053/gast.1999.0029900453","ISSN":"0016-5085","author":[{"family":"Verhagen","given":"Marc A. M. T."},{"family":"Van Schelven","given":"Leonard J."},{"family":"Samsom","given":"Melvin"},{"family":"Smout","given":"André J. P. M."}],"issued":{"date-parts":[["1999",8]]}}}],"schema":""} [16]; (3) Although postprandial EGG somewhat differs from fasting EGG, these differences have not led to any reliable clinical association with abnormal gastric motility, even if a standardized meal is administered ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1oliqu8227","properties":{"formattedCitation":"[17]","plainCitation":"[17]"},"citationItems":[{"id":69,"uris":[""],"uri":[""],"itemData":{"id":69,"type":"article-journal","title":"Model to simulate the gastric electrical control and response activity on the stomach wall and on the abdominal surface","container-title":"Medical and Biological Engineering and Computing","page":"157-163","volume":"24","issue":"2","source":"link.","abstract":"A new physical model to simulate the gastric electrical activity (ECA and ERA) as picked up at points on the stomach wall and on the abdominal surface is proposed. In this model the part of the stomach where the electrical activity originates and propagates is represented by a truncated cone of finite length; the electrical potential representing the electrical activity of the cell is generated by a distal movement of an annular band polarised by electric dipoles which are oriented perpendicularly to the surface of the cone. The model reproduces not only the spatial and temporal organisation of the gastric electrical activity (ECA and ERA) but also its morphological characteristics (waveform, amplitude, frequency, phase lag) as obtained by experimentsin vivo. This model also reproduces the morphological characteristics of the signal as picked up, by experimentsin vivo on the abdominal surface in man.","DOI":"10.1007/BF02443929","ISSN":"0140-0118, 1741-0444","language":"en","author":[{"family":"Mirizzi","given":"N."},{"family":"Stella","given":"R."},{"family":"Scafoglieri","given":"U."}],"issued":{"date-parts":[["1986",3,1]]}}}],"schema":""} [17]; and (4) The intrinsic electrical activity of the stomach is a complex, multi-component phenomenon, and the omnipresent rhythmic electrical component (also known as Electrical Control Activity, or ECA) is a necessary, but not sufficient condition for gastric contractions to occur. Because of the different physiological nature of the gastric pump compared to the cardiac pump, the electrical fields of the stomach and of the heart differ substantially, with the stomach resembling functionally an “asynchronous pump”, irregularly exhibiting intermittent contractions during the presence of which the underlying electrical activity controlling it grows in complexity by the superposition over ECA of the so-called Electrical Response Activity (ERA), which in turn is of two types, plateau and spikes ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"156c0s48ed","properties":{"formattedCitation":"[18]","plainCitation":"[18]"},"citationItems":[{"id":72,"uris":[""],"uri":[""],"itemData":{"id":72,"type":"article-journal","title":"Electrical activity of the normal human stomach","container-title":"The American Journal of Digestive Diseases","page":"969-976","volume":"17","issue":"11","source":"link.","abstract":"Using monopolar electrodes, the gastric electrical activity was recorded in waking human beings from both the mucosal and the serosal sides of the gastric wall. For each electrode location in a given subject, a mean curve of the regular fluctuations in potential (pacesetter potential) was obtained by an iteration process allowing measurement of characteristic amplitudes. A detailed study of the variations of the electrical period within and between subjects was undertaken. The frequency variations of the normal human gastric pacemaker appear in a slow and gradual fashion rather than in irregularities in the period; rhythm disorders rarely occur. Since frequent shifts of the baseline prevent the routine use of DC recordings, the use of a time constant of 4 seconds allows correct reproduction of the second component of the pacesetter potential. The morphology of the pacesetter potential is dependent on the gastric area and on the recording source—ie, mucosal or serosal. The amplitude and slope of the first component are greater in the antrum than in the corpus; the relative amplitudes of the first and the second component are dependent on the recording source.","DOI":"10.1007/BF02239136","ISSN":"0002-9211, 1573-2568","language":"en","author":[{"family":"Couturier","given":"D."},{"family":"Rozé","given":"C."},{"family":"Paolaggi","given":"J."},{"family":"Debray","given":"C."}],"issued":{"date-parts":[["1972",11,1]]}}}],"schema":""} [18]. Only the presence of the latter has been associated with meaningfully strong contractions. However, unfortunately, although often of high amplitude, spikes are of very short duration, which results in relatively low electrical power that dissipates before it can influence the cutaneous EGG recordings in any reliable and meaningful manner. In contrast, the heart can be regarded as a “synchronous” pump, with its electrical and mechanical activity corresponding quite intimately and with mutually reflected changes ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1cn1sqil8v","properties":{"formattedCitation":"[19]","plainCitation":"[19]"},"citationItems":[{"id":162,"uris":[""],"uri":[""],"itemData":{"id":162,"type":"article-journal","title":"The relationship between electrical and mechanical events in the cardiac cycle of man","container-title":"British heart journal","page":"1","volume":"11","issue":"1","source":"Google Scholar","author":[{"family":"Coblentz","given":"B."},{"family":"Harvey","given":"R. M."},{"family":"Ferrer","given":"M. I."},{"family":"Cournand","given":"A."},{"family":"Richards Jr","given":"D. W."}],"issued":{"date-parts":[["1949"]]}}}],"schema":""} [19].Unfortunately, the tempting promise of EGG as a non-invasive test for assessing gastric motor function similarly to the way its overwhelmingly successful sister, electrocardiography (ECG) can assess the motor function of the heart, continue to overshadow the above limitations, which in our opinion are objectively prohibitive. Although the arguments pro- and con-EGG can continue forever, the facts are clear: one after another, the assessment panels of state insurance companies in the United States label EGG as an investigative, but not as a diagnostic test, and refuse to offer any reimbursement for it, despite that two distinct Current Procedural Terminology (CPT) codes associated with EGG have been introduced long time ago ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2dpbp5ke3i","properties":{"formattedCitation":"[20]","plainCitation":"[20]"},"citationItems":[{"id":166,"uris":[""],"uri":[""],"itemData":{"id":166,"type":"article-journal","title":"Motility and GI Function Studies Billing and Coding Guidelines: A Position Paper of the American Motility Society","container-title":"The American Journal of Gastroenterology","page":"1228-1236","volume":"98","issue":"6","source":"","abstract":"Tests that measure gastrointestinal function, such as esophageal motility testing, ambulatory twenty-four hour pH, electrogastrography, gastroduodenal, sphincter of Oddi, and anorectal manometry, as well as hydrogen breath testing are now an essential part in the evaluation of patients with functional gastrointestinal disorders. They are widely performed in a variety of clinical settings. In this paper we outline the position of the American Motility Society on billing and coding for these studies, and review the issues for these studies under the current United States Relative Value Scale system. We have also provided an outline for standardization of reports for these procedures, and propose changes and modifications of current medical necessity diagnoses.","DOI":"10.1111/j.1572-0241.2003.t01-1-07493.x","ISSN":"0002-9270","shortTitle":"Motility and GI Function Studies Billing and Coding Guidelines","journalAbbreviation":"Am J Gastroenterol","language":"en","author":[{"family":"Botoman","given":"V. Alin"},{"family":"Rao","given":"Satish"},{"family":"Dunlap","given":"Polly"},{"family":"Abell","given":"Tom"},{"family":"Falk","given":"Gary W."}],"issued":{"date-parts":[["2003",6]]}}}],"schema":""} [20]. It is our opinion, therefore, that unless a major change in the EGG paradigm is proposed, the test will slowly decay and die its natural death. Thus, in our view, the standard EGG testing of today can be regarded not as a promise, only partially kept ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1tjdo6m5qh","properties":{"formattedCitation":"[21]","plainCitation":"[21]"},"citationItems":[{"id":78,"uris":[""],"uri":[""],"itemData":{"id":78,"type":"article-journal","title":"Electrogastrography: A Seductive Promise, Only Partially Kept","container-title":"The American Journal of Gastroenterology","page":"1791-1794","volume":"93","issue":"10","source":"","abstract":"The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professional support for clinicians dealing with the gastroenterological disorders seen most often in patients. Published with practicing clinicians in mind, the journal aims to be easily accessible, organizing its content by topic, both online and in print. , *2007 Journal Citation Report (Thomson Reuters, 2008)","DOI":"10.1111/j.1572-0241.1998.01791.x","ISSN":"0002-9270","shortTitle":"Electrogastrography","language":"en","author":[{"family":"Bortolotti","given":"M."}],"issued":{"date-parts":[["1998",10]]}}}],"schema":""} [21], but as a promise not kept at all, at least in the context of objectively assessing gastric motility. The “SmartPill” alternativeRecently, and with much fanfare, the so-called “SmartPill” has been introduces as a possible gastric motility test, at least as a minimally invasive tool to measure gastric emptying ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"25uiferkps","properties":{"formattedCitation":"[22]","plainCitation":"[22]"},"citationItems":[{"id":83,"uris":[""],"uri":[""],"itemData":{"id":83,"type":"article-journal","title":"Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule","container-title":"Neurogastroenterology & Motility","page":"527-e117","volume":"22","issue":"5","source":"Wiley Online Library","abstract":"Background? The wireless motility capsule (WMC) measures intraluminal pH and pressure, and records transit time and contractile activity throughout the gastrointestinal tract. Our hypothesis is that WMC can differentiate antroduodenal pressure profiles between healthy people and patients with upper gut motility dysfunctions. This study aims to analyze differences in the phasic pressure profiles of the stomach and small intestine in healthy and gastroparetic subjects. Methods? Data from 71 healthy and 42 gastroparetic subjects were analyzed. The number of contractions (Ct), area under the pressure curve and motility index (MI?=?Ln (Ct *sum amplitudes +1)) were analyzed for 60?min before gastric emptying of the capsule (GET), (gastric window) and after GET (small bowel window) and results between groups were compared with the Wilcoxon rank sum test. Key Results? Significant differences were observed between healthy and gastroparetic subjects for Ct and MI (P?<?0.05). Median values of the motility parameters in gastric window were Ct?=?72, MI?=?11.83 for healthy and Ct?=?47, MI?=?11.12 for gastroparetics. In the small bowel, median values were Ct?=?144.5, MI?=?12.78 for healthy and Ct?=?93, MI?=?12.12 for gastroparetics. Diabetic subjects with gastroparesis showed significantly lower Ct and MI compared with healthy subjects in both gastric and small bowel windows while idiopathic gastroparetic subjects did not show significant differences. Conclusions & Inferences? The WMC is able to differentiate between healthy and gastroparetic subjects based on gastric and small bowel motility profiles.","DOI":"10.1111/j.1365-2982.2010.01468.x","ISSN":"1365-2982","language":"en","author":[{"family":"Kloetzer","given":"L."},{"family":"Chey","given":"W. D."},{"family":"Mccallum","given":"R. W."},{"family":"Koch","given":"K. L."},{"family":"Wo","given":"J. M."},{"family":"Sitrin","given":"M."},{"family":"Katz","given":"L. A."},{"family":"Lackner","given":"J. M."},{"family":"Parkman","given":"H. P."},{"family":"Wilding","given":"G. E."},{"family":"Semler","given":"J. R."},{"family":"Hasler","given":"W. L."},{"family":"Kuo","given":"B."}],"issued":{"date-parts":[["2010",5,1]]}}}],"schema":""} [22]. Although this could represent a welcome replacement of traditional scintigraphy for measuring gastric emptying, it has been already discussed that gastric emptying test alone could not be the long searched single diagnostic test for dyspepsia, and by itself is not a direct gastric motility test ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2cogefsleh","properties":{"formattedCitation":"[23], [24]","plainCitation":"[23], [24]"},"citationItems":[{"id":172,"uris":[""],"uri":[""],"itemData":{"id":172,"type":"article-journal","title":"Methods for measurement of gastric motility","container-title":"American Journal of Physiology-Gastrointestinal and Liver Physiology","page":"G461–G475","volume":"296","issue":"3","source":"Google Scholar","author":[{"family":"Szarka","given":"Lawrence A."},{"family":"Camilleri","given":"Michael"}],"issued":{"date-parts":[["2009"]]}}},{"id":169,"uris":[""],"uri":[""],"itemData":{"id":169,"type":"article-journal","title":"Variability of gastrointestinal transit in healthy women and men.","container-title":"Gut","page":"299–305","volume":"39","issue":"2","source":"Google Scholar","author":[{"family":"Degen","given":"L. P."},{"family":"Phillips","given":"S. F."}],"issued":{"date-parts":[["1996"]]}}}],"schema":""} [23,24]. The need for gastric retentionOur present opinion is that in order to reliably assess gastric motility, particularly in ambulatory settings closely resembling the daily routine of the patient, three necessary conditions need to be met: (1) A “smart” capsule needs to be ingested by the patient; (2) The capsule should be retained in the stomach for the duration of the test, but should has the capability to disintegrate and safely exit the gut naturally after the testing is completed; and (3) Existing testing equipment and established procedures need to be used in order to optimise the path to clinical utilization of the technique, and respectively, to its reimbursement by insurance companies as a legitimate diagnostic test.Pseudobezoar-based gastric retentive oscillatorRecently, we have been exploring the utilization of passive, temporary, controllable pseudobezars as ingestible implements for the treatment of obesity ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"hlsflmov8","properties":{"formattedCitation":"[25]","plainCitation":"[25]"},"citationItems":[{"id":95,"uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Utilization of Temporary Controllable Intragastric Pseudobezoars for the Treatment of Obesity","container-title":"Current Obesity Reports","page":"68-74","volume":"1","issue":"2","source":"link.","abstract":"The growing worldwide obesity epidemic has prompted the development of two main treatment streams: 1) conservative approaches and 2) invasive techniques. However, only invasive surgical methods have delivered significant and sustainable benefits. Therefore, contemporary research exploration has focused on the development of gastric volume reduction methods having noninvasive administration and termination, while featuring a safe but reliable and long-term sustainable weight loss effect similar to the one delivered by bariatric surgeries. This antiobesity approach is based on placing external devices in the stomach ranging from intragastric balloons to temporary pseudobezoars for a predetermined amount of time. The present review examines the evolution of these techniques from invasively positionable and removable units to completely noninvasive patient-controllable implements. Comparative discussion over the available pilot and clinical studies related to temporary controllable pseudobezoars outlines this new concept as an alternative gastric volume reduction antiobesity strategy. Available short-term studies reported an average weight loss of 6 % for a 1-month period. The beneficial features of this method include patient-specific design, performance flexibility, full controllability, and particularly low level or lack of side effects. More multicenter, placebo-controlled, long-term studies on a significant number of patients and further technological improvements of the design of the pseudobezoars are required before the technique can be considered a reliable alternative to present-day bariatric surgeries.","DOI":"10.1007/s13679-012-0015-x","ISSN":"2162-4968","language":"en","author":[{"family":"Deneva","given":"Marlena G."},{"family":"Yadid-Pecht","given":"Orly"},{"family":"Fattouche","given":"Michel"},{"family":"Mintchev","given":"Martin P."}],"issued":{"date-parts":[["2012",6,1]]}}}],"schema":""} [25]. The safety of these implements has been established in various tests on animals and humans ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"onjend3e3","properties":{"formattedCitation":"[25]","plainCitation":"[25]"},"citationItems":[{"id":95,"uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Utilization of Temporary Controllable Intragastric Pseudobezoars for the Treatment of Obesity","container-title":"Current Obesity Reports","page":"68-74","volume":"1","issue":"2","source":"link.","abstract":"The growing worldwide obesity epidemic has prompted the development of two main treatment streams: 1) conservative approaches and 2) invasive techniques. However, only invasive surgical methods have delivered significant and sustainable benefits. Therefore, contemporary research exploration has focused on the development of gastric volume reduction methods having noninvasive administration and termination, while featuring a safe but reliable and long-term sustainable weight loss effect similar to the one delivered by bariatric surgeries. This antiobesity approach is based on placing external devices in the stomach ranging from intragastric balloons to temporary pseudobezoars for a predetermined amount of time. The present review examines the evolution of these techniques from invasively positionable and removable units to completely noninvasive patient-controllable implements. Comparative discussion over the available pilot and clinical studies related to temporary controllable pseudobezoars outlines this new concept as an alternative gastric volume reduction antiobesity strategy. Available short-term studies reported an average weight loss of 6 % for a 1-month period. The beneficial features of this method include patient-specific design, performance flexibility, full controllability, and particularly low level or lack of side effects. More multicenter, placebo-controlled, long-term studies on a significant number of patients and further technological improvements of the design of the pseudobezoars are required before the technique can be considered a reliable alternative to present-day bariatric surgeries.","DOI":"10.1007/s13679-012-0015-x","ISSN":"2162-4968","language":"en","author":[{"family":"Deneva","given":"Marlena G."},{"family":"Yadid-Pecht","given":"Orly"},{"family":"Fattouche","given":"Michel"},{"family":"Mintchev","given":"Martin P."}],"issued":{"date-parts":[["2012",6,1]]}}}],"schema":""} [25]. It has been already discussed that the intrinsic gastric electrical oscillator is a complex, multicomponent and dynamic phenomenon, whose relationship with actual gastric motility is so multifaceted that plain EGG cannot reliably assess it. Thus, we recently proposed to enhance an ingestible pill containing a temporary, controllable pseudobezoar with a miniature electronic oscillator of known and strong enough emitting frequency, optimized for good transluminal transmission ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2L5bsosh","properties":{"formattedCitation":"{\\rtf [26]\\uc0\\u8211{}[28]}","plainCitation":"[26]–[28]"},"citationItems":[{"id":98,"uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Design, implementation and testing of an implantable impedance-based feedback-controlled neural gastric stimulator","container-title":"Physiological Measurement","page":"1103","volume":"32","issue":"8","source":"Institute of Physics","abstract":"Functional neural gastrointestinal electrical stimulation (NGES) is a methodology of gastric electrical stimulation that can be applied as a possible treatment for disorders such as obesity and gastroparesis. NGES is capable of generating strong lumen-occluding local contractions that can produce retrograde or antegrade movement of gastric content. A feedback-controlled implantable NGES system has been designed, implemented and tested both in laboratory conditions and in an acute animal setting. The feedback system, based on gastric tissue impedance change, is aimed at reducing battery energy requirements and managing the phenomenon of gastric tissue accommodation. Acute animal testing was undertaken in four mongrel dogs (2 M, 2 F, weight 25.53 ± 7.3 kg) that underwent subserosal two-channel electrode implantation. Three force transducers sutured serosally along the gastric axis and a wireless signal acquisition system were utilized to record stimulation-generated contractions and tissue impedance variations respectively. Mechanically induced contractions in the stomach were utilized to indirectly generate a tissue impedance change that was detected by the feedback system. Results showed that increasing or decreasing impedance changes were detected by the implantable stimulator and that therapy can be triggered as a result. The implantable feedback system brings NGES one step closer to long term treatment of burdening gastric motility disorders in humans.","DOI":"10.1088/0967-3334/32/8/007","ISSN":"0967-3334","language":"en","author":[{"family":"Arriagada","given":"A. J."},{"family":"Jurkov","given":"A. S."},{"family":"Neshev","given":"E."},{"family":"Muench","given":"G."},{"family":"Andrews","given":"C. N."},{"family":"Mintchev","given":"M. P."}],"issued":{"date-parts":[["2011"]]}}},{"id":100,"uris":[""],"uri":[""],"itemData":{"id":100,"type":"article-journal","title":"Characterization of drug disposition and dosing using bioelectrical impedance.","container-title":"Medical progress through technology","page":"193-198","volume":"19","issue":"4","source":"","abstract":"Abstract: Bioelectrical impedance analysis (BIA) yields accurate, safe and non-invasive estimates of body composition in humans. Pharmacokinetic...","ISSN":"0047-6552","note":"PMID: 8052175","language":"eng","author":[{"family":"Bj","given":"Zarowitz"},{"family":"El","given":"Peterson"},{"family":"S","given":"Robert"}],"issued":{"date-parts":[["1992"]],"season":"1993"},"PMID":"8052175"}},{"id":160,"uris":[""],"uri":[""],"itemData":{"id":160,"type":"patent","title":"Device and method for monitoring internal organs","abstract":"The present invention provides a method and an apparatus for minimally-invasive diagnosis of conditions within the body of an animal. In one particular embodiment, the present invention provides a method and an apparatus for utilizing intraluminally-generated signals to diagnose disorders or monitor the function of internal organ of an animal by assessing the signal transcutaneously. The signals can be electrical, magnetic, electromagnetic, acoustic, ultrasonic, optical, etc.","URL":"","note":"International Classification A61B5/00; Cooperative Classification A61B5/4244, A61B5/6861, A61B5/6852, A61B5/0028, A61B5/0031, A61B5/4255, A61B5/4233, A61B5/4238, A61B5/0538","number":"US20160206200 A1","author":[{"family":"Poscente","given":"Michael D."},{"family":"Yadid-Pecht","given":"Orly"},{"family":"Andrews","given":"Christopher N."},{"family":"Mintchev","given":"Martin P."}],"issued":{"date-parts":[["2016",7,21]]},"accessed":{"date-parts":[["2016",11,29]]},"submitted":{"date-parts":[["2014",8,22]]}}}],"schema":""} [26-28]. This is a way to essentially enhance the intrinsic gastric electrical oscillator with a strong, simple, single-frequency source, which could be easily detected cutaneously by traditional EGG equipment and can be consequently processed by the same signal processing tools that plain EGG testing of today employs. Thus, not only long-term gastric retention could be achieved, but also the internal manipulation of the oscillator-containing pseudobezoar by gastric motility would be able to manifest itself cutaneously in a far more reliable fashion. Thus, our proposition is: (1) Convert an ingestible, passive, temporary, controllable pseudobezoar capsule into an active oscillator source, while preserving its gastric retentive capability; and (2) Utilize routine EGG testing equipment, electrode arrangement and signal processing tools to record the electric power dynamics of the ingested gastric-retentive oscillator, with the hope that it would reliably reflect gastric motility. Materials and methods Design of the EEGG ingestible capsuleOscillator: Previous literature demonstrated that 50 kHz is an optimal frequency for luminal electrical impedance measurements to minimize interference with regular muscle, nerve, and organ functions, while enabling effective transmission through the body ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"ackoqphu4","properties":{"formattedCitation":"[26], [27]","plainCitation":"[26], [27]"},"citationItems":[{"id":98,"uris":[""],"uri":[""],"itemData":{"id":98,"type":"article-journal","title":"Design, implementation and testing of an implantable impedance-based feedback-controlled neural gastric stimulator","container-title":"Physiological Measurement","page":"1103","volume":"32","issue":"8","source":"Institute of Physics","abstract":"Functional neural gastrointestinal electrical stimulation (NGES) is a methodology of gastric electrical stimulation that can be applied as a possible treatment for disorders such as obesity and gastroparesis. NGES is capable of generating strong lumen-occluding local contractions that can produce retrograde or antegrade movement of gastric content. A feedback-controlled implantable NGES system has been designed, implemented and tested both in laboratory conditions and in an acute animal setting. The feedback system, based on gastric tissue impedance change, is aimed at reducing battery energy requirements and managing the phenomenon of gastric tissue accommodation. Acute animal testing was undertaken in four mongrel dogs (2 M, 2 F, weight 25.53 ± 7.3 kg) that underwent subserosal two-channel electrode implantation. Three force transducers sutured serosally along the gastric axis and a wireless signal acquisition system were utilized to record stimulation-generated contractions and tissue impedance variations respectively. Mechanically induced contractions in the stomach were utilized to indirectly generate a tissue impedance change that was detected by the feedback system. Results showed that increasing or decreasing impedance changes were detected by the implantable stimulator and that therapy can be triggered as a result. The implantable feedback system brings NGES one step closer to long term treatment of burdening gastric motility disorders in humans.","DOI":"10.1088/0967-3334/32/8/007","ISSN":"0967-3334","language":"en","author":[{"family":"Arriagada","given":"A. J."},{"family":"Jurkov","given":"A. S."},{"family":"Neshev","given":"E."},{"family":"Muench","given":"G."},{"family":"Andrews","given":"C. N."},{"family":"Mintchev","given":"M. P."}],"issued":{"date-parts":[["2011"]]}}},{"id":100,"uris":[""],"uri":[""],"itemData":{"id":100,"type":"article-journal","title":"Characterization of drug disposition and dosing using bioelectrical impedance.","container-title":"Medical progress through technology","page":"193-198","volume":"19","issue":"4","source":"","abstract":"Abstract: Bioelectrical impedance analysis (BIA) yields accurate, safe and non-invasive estimates of body composition in humans. Pharmacokinetic...","ISSN":"0047-6552","note":"PMID: 8052175","language":"eng","author":[{"family":"Bj","given":"Zarowitz"},{"family":"El","given":"Peterson"},{"family":"S","given":"Robert"}],"issued":{"date-parts":[["1992"]],"season":"1993"},"PMID":"8052175"}}],"schema":""} [26,27]. Body conduction of small low frequency signals has been clinically proven to be safe, and has found application in other GI related technologies ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"8apf94g6k","properties":{"formattedCitation":"[29]","plainCitation":"[29]"},"citationItems":[{"id":103,"uris":[""],"uri":[""],"itemData":{"id":103,"type":"patent","title":"Endoscope and a method for finding its location","abstract":"An endoscope and method for determining a position of an endoscope body within the human body are disclosed. The endoscope (100) includes at least one first electrode (200) provided in an endoscope body and adapted to generate and transmit an electric signal, at least one second electrode adapted to receive the electric signal transmitted from the first electrode (200), a database for storing electric potential values depending on positions of the endoscope body, and a controller for determining the position of the endoscope body by comparing the electric signal with the electric potential values. The endoscope can recognize the position of the endoscope within the internal organs of the human body with the use of the electric signal induction arrangement and thus, can recognize accurate positions of illness symptoms of the internal organs.","URL":"","note":"U.S. Classification 600/117; International Classification A61B1/00; Cooperative Classification A61B1/00016, A61B5/065, A61B5/06, A61B5/073, A61B1/041; European Classification A61B1/04C, A61B5/06E, A61B1/00C2D, A61B5/07B, A61B5/06","number":"US20100168517 A1","author":[{"family":"Shim","given":"Han Bo"},{"family":"Hwang","given":"Jung Jin"},{"family":"Kim","given":"Kwang Seop"},{"family":"Seo","given":"Young Dae"},{"family":"KIM","given":"Byung Hyuk"},{"family":"Lee","given":"Yong Woo"},{"family":"Cha","given":"Chul"},{"family":"Baek","given":"Bong Ki"}],"issued":{"date-parts":[["2010",7,1]]},"accessed":{"date-parts":[["2016",11,29]]},"submitted":{"date-parts":[["2006",9,28]]}}}],"schema":""} [29]. Size and power consumption were taken into account when it was decided to utilize the TS3001 (Silicon Labs, Austin, TX, United States) programmable oscillator integrated circuit that offers a frequency range from 9 to 300 kHz and uses a maximum of 5.4 ?A of supply current to maintain operation. The complete design including a battery, the selected oscillator chip, resistor and capacitor fitted onto a 10-mm by 6-mm two sided printed circuit board that was custom manufactured. enhanced EGG capsule body: In order to protect the circuitry, the custom-designed electronics were held in a custom capsule that was made for the prototype models. The capsule consisted of a cylindrical body with two cap electrodes on either end, with an outer dimension of 10 mm in diameter and 19 mm in length, (Figure 1). The hollow cylindrical body was made of a machined biocompatible chemically resistant medical grade polyetherimide (PEI) resin (Ultem 2300; Ritter GmbH, Schwabmunchen, Germany). This material was selected for its corrosion resistance, dielectric insulation, and high strength to weight ratio ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2b8ltkfnkk","properties":{"formattedCitation":"[30]","plainCitation":"[30]"},"citationItems":[{"id":105,"uris":[""],"uri":[""],"itemData":{"id":105,"type":"article-journal","title":"Polyetherimide as biomaterial: preliminary in vitro and in vivo biocompatibility testing","container-title":"Journal of Materials Science: Materials in Medicine","page":"738-742","volume":"5","issue":"9-10","source":"link.","abstract":"During the last few years, on the basis of their physico-chemical characteristics, thermoplastic materials, already used in several advanced industries, have become very attractive candidates for biomedical applications as matrix for composite femoral stems and bone plates. In the present study, the biocompatibility of a thermoplastic material, polyetherimide (PEI), was investigated both in vivo, and in vitro. Our results show that PEI did not elicit any toxic response in cell culture testing. It was possible to grow on PEI surfaces not only 3T3 fibroblasts but also human endothelial cells (HEC) from human umbelical cord, with no apparent deleterious effects on the cell viability. The attachment, spreading, and growth of cells on PEI material was followed with respect to time. Both the number of adhering HEC, and the spreading area of individual cells, increased as a function of time. The hydrogen peroxide-sensitive dye DCFH-DA was used to examine the functional activity of cells adherent to PEI or control material implants. PEI material did not induce significant DCFH oxidation until day 14, when levels of DCFH oxidation were significantly higher than observed with PDMS negative control, but lower than those observed on Pellethane positive control.","DOI":"10.1007/BF00120367","ISSN":"0957-4530, 1573-4838","shortTitle":"Polyetherimide as biomaterial","language":"en","author":[{"family":"Peluso","given":"G."},{"family":"Petillo","given":"O."},{"family":"Ambrosio","given":"L."},{"family":"Nicolais","given":"L."}],"issued":{"date-parts":[["1994",9,1]]}}}],"schema":""} [30]. The inner diameter of the cylindrical body was 8.36 mm, allowing the custom electronics to fit. On either end of the body the last 2.5 mm had recessed threading to allow custom-made caps to be tightly screwed into place. The main constraint on the size of the capsule was the presence of embedded electronics, as well as the need for gastric retentive polymers surrounding the capsule but within a dissolvable pill body. The custom caps were made of machined copper that was threaded to closely fit the body in order to be able to seal the contents of the pill. The inside surface of the copper caps was soldered to thin wires connected to output vias on the circuit board before being screwed together. Particular care was taken to ensure that body fluids did not enter the capsule; the two caps were screwed onto the shell with a layer of ultra-thin polytetrafluoroethylene (PTFE) film in order to provide high quality waterproof seal between threads. Figure 1 shows the full design of the internal circuitry and body of the enhanced EGG (EEGG) capsule.Gastric retention: In order to provide long term gastric motility measurements and prevent the expulsion of the EEGG pill into the duodenum, a gastric retentive enclosure was incorporated into the prototype. The oscillating EEGG capsule was embedded in 0.15g of dry, non-toxic, hydrophilic, crosslinked polyacrylate polymer granules contained inside a nonwoven, high permeability 20-gsm polyvinyl alcohol (PVA) mesh. The polymer granules are able to immediately absorb and retain hundreds of times their weight in water, and swell to 30-50 times their dry size in gastric liquids if accompanied by the concurrent intake of strong antacid. Once the polymers have swelled they are unable to dissolve due to the three dimensional crosslinked structure ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"fu2l8n8sa","properties":{"formattedCitation":"[35]","plainCitation":"[35]"},"citationItems":[{"id":120,"uris":[""],"uri":[""],"itemData":{"id":120,"type":"article-journal","title":"Preparation and swelling properties of crosslinked sodium polyacrylate","container-title":"Journal of applied polymer science","page":"1515–1520","volume":"82","issue":"6","source":"Google Scholar","author":[{"family":"Liu","given":"Mingzhu"},{"family":"Guo","given":"Tianhua"}],"issued":{"date-parts":[["2001"]]}}}],"schema":""} [30], making them an ideal choice for gastric retention when held in place by a permeable mesh structure. The PVA mesh was designed to ensure that upon expansion the whole structure would exceed 1.5 cm in any direction, but not be larger than 4 cm in any direction, with a fully expanded volume between 20 to 30 ml, which is well below the threshold of perception ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1e9o6dojtb","properties":{"formattedCitation":"[36]","plainCitation":"[36]"},"citationItems":[{"id":122,"uris":[""],"uri":[""],"itemData":{"id":122,"type":"article-journal","title":"Role of impaired gastric accommodation to a meal in functional dyspepsia","container-title":"Gastroenterology","page":"1346–1352","volume":"115","issue":"6","source":"Google Scholar","author":[{"family":"Tack","given":"Jan"},{"family":"Piessevaux","given":"Hubert"},{"family":"Coulie","given":"Bernard"},{"family":"Caenepeel","given":"Philip"},{"family":"Janssens","given":"Jozef"}],"issued":{"date-parts":[["1998"]]}}}],"schema":""} [31]. When pressure is applied the polymer granules linearly retain less water, allowing a certain degree of compliance of the structure to the mechanical activity of the stomach. The mesh was also chosen due to its permeability to fluids, which enable the polymer granules to make adequate contact with the gastric juices. The 40-degree PVA mesh is biodegradable, and will disintegrate within 2-3 days in order to avoid obstruction, and similar gastric retentive technologies have been demonstrated to withstand digestive antral pressures, and produce no adverse mucosal impact or evacuation obstruction issues ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2ir6o07qio","properties":{"formattedCitation":"[25]","plainCitation":"[25]"},"citationItems":[{"id":95,"uris":[""],"uri":[""],"itemData":{"id":95,"type":"article-journal","title":"Utilization of Temporary Controllable Intragastric Pseudobezoars for the Treatment of Obesity","container-title":"Current Obesity Reports","page":"68-74","volume":"1","issue":"2","source":"link.","abstract":"The growing worldwide obesity epidemic has prompted the development of two main treatment streams: 1) conservative approaches and 2) invasive techniques. However, only invasive surgical methods have delivered significant and sustainable benefits. Therefore, contemporary research exploration has focused on the development of gastric volume reduction methods having noninvasive administration and termination, while featuring a safe but reliable and long-term sustainable weight loss effect similar to the one delivered by bariatric surgeries. This antiobesity approach is based on placing external devices in the stomach ranging from intragastric balloons to temporary pseudobezoars for a predetermined amount of time. The present review examines the evolution of these techniques from invasively positionable and removable units to completely noninvasive patient-controllable implements. Comparative discussion over the available pilot and clinical studies related to temporary controllable pseudobezoars outlines this new concept as an alternative gastric volume reduction antiobesity strategy. Available short-term studies reported an average weight loss of 6 % for a 1-month period. The beneficial features of this method include patient-specific design, performance flexibility, full controllability, and particularly low level or lack of side effects. More multicenter, placebo-controlled, long-term studies on a significant number of patients and further technological improvements of the design of the pseudobezoars are required before the technique can be considered a reliable alternative to present-day bariatric surgeries.","DOI":"10.1007/s13679-012-0015-x","ISSN":"2162-4968","language":"en","author":[{"family":"Deneva","given":"Marlena G."},{"family":"Yadid-Pecht","given":"Orly"},{"family":"Fattouche","given":"Michel"},{"family":"Mintchev","given":"Martin P."}],"issued":{"date-parts":[["2012",6,1]]}}}],"schema":""} [25]. The PVA mesh can be immediately disintegrated on demand via the consumption of a glass of hot (> 40 oC) water. Obviously, in human testing, the patients should be advised not to drink hot (> 36 oC) beverages for the duration of the test, unless they need to terminate it. Encapsulation: In order to orally deliver the EEGG capsule and gastric retentive enclosure to the stomach the prototype models were encased in a split hard gelatin shell capsule (AAA DB capsule, Capsugel, Greenwood, SC, USA). The size of the gelatin capsule directly affected how much expanding polymer could be integrated into the design, as the size of the inner EEGG capsule was determined from the internal electronics. For the present feasibility study the emphasis was on demonstrating the effectiveness of the electronics. Figure 2 presents an exploded image of the pill, as well as the order of assembly. Testing EEGG in a canine studyExperiments were performed on eight mongrel dogs (6F, 4M, 23.8 ± 3.3 kg). Four were administered an active EEGG capsule, while the rest were given a deactivated (battery removed) capsule. The dogs were vaccinated and dewormed as per the Canadian Veterinary Medical Association’s recommended yearly protocol regime. Vaccines included Canine distemper/adenovirus, Type 2 parvovirus/bordetella/rabies. Drontal Plus (Bayer HealthCare LLC, Shawnee Mission, KS, United States) was used as an oral dewormer. Each animal underwent a physical examination by a board-certified veterinarian and was found to be in good condition. After 24 h of fasting and 12 h of water deprivation, each animal transorally ingested a single capsule as described above with 500 cc of room temperature water (21.0 oC). The pill swelled to its maximum size in the stomach within 15 minutes after ingestion to dimensions exceeding 1.5 cm in any direction, and subsequently was unable to pass the pyloric sphincter even when subjected to pharmacologically induced propulsive peristalsis. Each animal underwent an induction with an intravenous injection of thiopental (Thiotal 15 mg/kg IV, Vetoquinol Canada, Lavaltrie, QC, Canada) and was subsequently maintained on inhalant isoflurane and oxygen (Halocarbon Laboratories, River Edge, NJ, United States) with a vaporizer setting of 1%-3%. The anesthesia was chosen because it did not influence gastric neurotransmitters, and as such would not affect gastric contractions ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"16edi2q7nq","properties":{"formattedCitation":"[37]","plainCitation":"[37]"},"citationItems":[{"id":125,"uris":[""],"uri":[""],"itemData":{"id":125,"type":"article-journal","title":"Gastric myoelectric and motor activity in dogs after isoflurane anesthesia","container-title":"Veterinary Surgery","page":"456–463","volume":"24","issue":"5","source":"Google Scholar","author":[{"family":"Hall","given":"Jean A"},{"family":"Dunlop","given":"Colin"},{"family":"Solie","given":"Thomas N"},{"family":"Hodgson","given":"David S"},{"family":"Twedt","given":"David C"}],"issued":{"date-parts":[["1995"]]}}}],"schema":""} [32]. Individually, the animals were then positioned supine, their abdomens shaved, cleaned, and sterilized with alcohol before performing laparotomy via a median incision vertically along the linea alba to gain access to the stomach.After the incision the location of the ingested pill in the stomach was verified endoscopically using an EPK-700 veterinary endoscope (Pentax, Tokyo, Japan), and the voltage developed on the serosa of the stomach was measured using an oscilloscope (Tektronix, Beaverton, OR, United States) to confirm the presence of an activated or deactivated pill. After this verification, two 90W24 force transducers (RB Products, Stillwater, MN, United States) were surgically sutured to the serosal side of the antral stomach along the gastric axis ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1vbjviabuk","properties":{"formattedCitation":"[38]","plainCitation":"[38]"},"citationItems":[{"id":128,"uris":[""],"uri":[""],"itemData":{"id":128,"type":"article-journal","title":"Patterns of dog gastrointestinal contractile activity monitored in vivo with extraluminal force transducers","container-title":"Digestive Diseases and Sciences","page":"113–141","volume":"12","issue":"2","source":"Google Scholar","author":[{"family":"Reinke","given":"David A."},{"family":"Rosenbaum","given":"Alan H."},{"family":"Bennett","given":"Donald R."}],"issued":{"date-parts":[["1967"]]}}}],"schema":""} [33]. The first force transducer was positioned 1-2 cm from the pylorus, and the second was affixed proximally 5-6 cm from the pylorus, along the gastric axis. The mesenteric innervation and the blood supply of the stomach were carefully preserved. The internal position of the EEGG oscillator and the serosal position of the force transducers is shown in Figure 3. The signals from the force transducers were amplified using a custom-designed multichannel bridge amplifier, and digitized using a PCMCIA DAQ Card-AL-16XE-50 (National Instruments, Austin, TX, United States). The force transducer signals were monitored and analyzed with custom-designed signal processing and visualization software (GAS-6.2, Biomedical Instrumentation Laboratory, University of Calgary, Calgary, Alberta, Canada). Once the force transducers were in place, their functionality was verified mechanically by manual palpation of variable strength, and the offsets and gains were calibrated accordingly for maximal sensitivity. The intragastric position of the pill was then verified mechanically by palpating it to ensure that it had not been compromised during surgery. Following the FT implantations, the abdomen was closed, and after appropriate skin cleaning and preparation, three pediatric ECG electrodes (Conmed, Utica, NY, United States) were placed cutaneously over the stomach along the abdominal projection of the gastric axis, with a ground electrode positioned close to the left hip of the animal ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"11glq14ev5","properties":{"formattedCitation":"[39]","plainCitation":"[39]"},"citationItems":[{"id":133,"uris":[""],"uri":[""],"itemData":{"id":133,"type":"article-journal","title":"Transcutaneous Intraluminal Impedance Measurement for Minimally Invasive Monitoring of Gastric Motility: Validation in Acute Canine Models","container-title":"Gastroenterology research and practice","volume":"2014","source":"Google Scholar","URL":"","shortTitle":"Transcutaneous Intraluminal Impedance Measurement for Minimally Invasive Monitoring of Gastric Motility","author":[{"family":"Poscente","given":"Michael D."},{"family":"Wang","given":"Gang"},{"family":"Filip","given":"Dobromir"},{"family":"Ninova","given":"Polya"},{"family":"Muench","given":"Gregory"},{"family":"Yadid-Pecht","given":"Orly"},{"family":"Mintchev","given":"Martin P."},{"family":"Andrews","given":"Christopher N."}],"issued":{"date-parts":[["2014"]]},"accessed":{"date-parts":[["2016",11,29]]}}}],"schema":""} [34]. The position of the electrodes was similar to the one associated with impedance epigastrography, since previous studies have suggested optimal electrode placement ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2dvtocge78","properties":{"formattedCitation":"[40]","plainCitation":"[40]"},"citationItems":[{"id":136,"uris":[""],"uri":[""],"itemData":{"id":136,"type":"article-journal","title":"Optimal placement of impedance epigastrography electrodes","container-title":"Annals of biomedical engineering","page":"328–332","volume":"24","issue":"2","source":"Google Scholar","author":[{"family":"Kee","given":"Wing C."},{"family":"Kingma","given":"Y. Jack"},{"family":"Mintchev","given":"Martin P."},{"family":"Bowes","given":"Kenneth L."}],"issued":{"date-parts":[["1996"]]}}}],"schema":""} [35]. The EEGG signals were measured with a custom-designed 16-channel electrogastrograph. The amplification of the electrogastrograph was set to 1000X, in order to utilize the range of the analog to digital converter. The cut-off frequencies of the bandpass filter of the custom electrogastrograph were set to the commonly used 0.03-0.1 Hz following the hypothesis that gastric motility signals in the animals will not exceed 6 cycles-per-minute (cpm) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"10pdsfb4g4","properties":{"formattedCitation":"[41]","plainCitation":"[41]"},"citationItems":[{"id":138,"uris":[""],"uri":[""],"itemData":{"id":138,"type":"article-journal","title":"Patterns of canine gastric electrical activity","container-title":"American Journal of Physiology–Legacy Content","page":"461–470","volume":"217","issue":"2","source":"Google Scholar","author":[{"family":"Kelly","given":"K. A."},{"family":"Code","given":"CHARLES F."},{"family":"Elveback","given":"LILA R."}],"issued":{"date-parts":[["1969"]]}}}],"schema":""} [36] and will amplitude-modulate the intraluminal oscillator frequency of 50 kHz, the latter acting only as their carrier. The 0.1-Hz low pass filter would thus act as a demodulator for this transcutaneous signal transmission, and would prevent higher frequency electrophysiological and mechanical processes (e.g. electrocardiographic activity and respiration) from interfering with the signal originating from within the stomach. The signals were then digitized using the same PCMCIA card DAQ Card-AL-16XE-50 (National Instruments, Austin, TX, United States) simultaneously with the force transducer signals, and were subsequently monitored and stored for further analysis using the same custom software. The overall setup of this experiment is shown in Figure 4.Immediately after the experimental setup was completed, a baseline recording was performed with no pharmacological stimulant for 30 minutes. Following this recording, bolus neostigmine (0.04 mg kg-1, APP Pharmaceuticals, Schaumburg, IL, United States) was administered intravenously as a smooth muscle stimulant to invoke contractions ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"12sq6jk77p","properties":{"formattedCitation":"[38]","plainCitation":"[38]"},"citationItems":[{"id":128,"uris":[""],"uri":[""],"itemData":{"id":128,"type":"article-journal","title":"Patterns of dog gastrointestinal contractile activity monitored in vivo with extraluminal force transducers","container-title":"Digestive Diseases and Sciences","page":"113–141","volume":"12","issue":"2","source":"Google Scholar","author":[{"family":"Reinke","given":"David A."},{"family":"Rosenbaum","given":"Alan H."},{"family":"Bennett","given":"Donald R."}],"issued":{"date-parts":[["1967"]]}}}],"schema":""} [34]. Thirty minutes of post-neostigmine recordings were subsequently obtained. The total recorded time from each animal was 60 min; 30 min in the basal state, and 30 min in the post-neostigmine state, with a one-minute time interval between them for the intravenous (IV) administration of the bolus neostigmine. At the end of the experiments the animals were sacrificed by an IV injection of Euthanyl, 480 mg/4.5 kg (Bimeda-MTC Animal Health Inc., Cambridge, ON, Canada). Subsequent retrieval of the expanded pill was performed in order to verify its retention within the stomach, and to confirm the presence of the signal in the active EEGG pills or the lack thereof in the inactive sham pills using an oscilloscope. The post-administration volume of each gastric-retentive pill was measured to quantify expansion dimensions. The study was approved by the Veterinary Sciences Animal Care Committee, University of Calgary, Calgary, Alberta, Canada.Signal acquisition, conditioning, digitization, processing, and data loggingSignal acquisition: The cutaneous biovoltage evoked from the induced EEGG signal was measured via disposable Ag/AgCl ECG electrodes (Cleartrode, Conmed, Utica, NY, United States). Two EEGG channels were bipolarly recorded as the potential differences between two active electrodes measured relative to a common ground electrode placed away from the stomach on the shaved inner thigh of the animal. These bipolar signals were processed to reflect the dynamics of their electrical power, which was hypothesized to correlate highly with contractile activity. Electrodes were placed in a similar configuration to that used in standard EGG recordings (Figure 4) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"12licnd1n9","properties":{"formattedCitation":"[42]","plainCitation":"[42]"},"citationItems":[{"id":140,"uris":[""],"uri":[""],"itemData":{"id":140,"type":"article-journal","title":"Electrogastrography in healthy subjects","container-title":"Digestive diseases and sciences","page":"1445–1450","volume":"40","issue":"7","source":"Google Scholar","author":[{"family":"Pfaffenbach","given":"Boris"},{"family":"Adamek","given":"Romuald Joachim"},{"family":"Kuhn","given":"Klaus"},{"family":"Wegener","given":"Martin"}],"issued":{"date-parts":[["1995"]]}}}],"schema":""} [37]. Signal conditioning: The raw analog signals from the ECG electrodes were amplified and filtered using a custom-designed multichannel electrogastrograph (EGG, James Long Company, Caroga Lake, NY, United States), which measured the voltages relative to the ground electrode using analog gain of 10000. The high pass filtering cut-off frequency was set at 0.03 Hz, while the low pass filtering cut-off frequency was 0.1 Hz.Signal digitization: After being amplified and filtered, the EEGG signal was digitized using a PCMCIA DAQ Card-AL-16XE-50 (National Instruments, Austin, TX, United States). This analog to digital converter can record 16 bit voltages between 0 and 5 volts at a maximum rate of 200 kS/s. Since the low-pass cut-off frequency of the amplifier was set at 0.1 Hz, a sampling frequency of 10 Hz was chosen for simplicity and to avoid aliasing effects. The resolution of this analog-to-digital converter was found to be 0.076 mV ± 0.038 mV.Signal processing: The signals were viewed using custom signal processing and visualization software (GAS-6.2, Biomedical Instrumentation Laboratory, University of Calgary, Calgary, Alberta, Canada). This software was designed with electrogastrography in mind, and can visualize up to 16 channels simultaneously in real time. Signals are monitored and stored for further analysis. After the signals were acquired they were further processed using a custom program developed using Matlab (MathWorks, Natick, MA, USA) that normalized each signal before calculating one-minute motility indices, and computing Pearson correlation coefficients between the input signals. Normalization is done because of the inhomogeneity of the tissues between the EEGG transducer capsule and whichever electrode recorded the signal. As a result, EEGG signals are presented in terms of relative units, where the highest value is represented by a 1 and the lowest by a 0. Normalization was performed according to equation (1.1).DNorm=DO-DMinDMax-DMin(1.1)where, DNorm is the new normalized data point, [dimensionless]; DO is the original point to be normalized, [dimensionless]; DMin is the minimum data point in the entire set, [dimensionless]; and DMax is the maximum data point in the entire set, [dimensionless].One-minute motility indices ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"apt0lti9s","properties":{"formattedCitation":"[43]","plainCitation":"[43]"},"citationItems":[{"id":142,"uris":[""],"uri":[""],"itemData":{"id":142,"type":"article-journal","title":"Gastric emptying and its relationship to antral contractile activity.","container-title":"Gastroenterology","page":"649–653","volume":"69","issue":"3","source":"Google Scholar","author":[{"family":"Stemper","given":"T. J."}],"issued":{"date-parts":[["1975"]]}}}],"schema":""} [38] effectively low-pass filter the signals, reducing the effect of erroneous outlying data and presenting the general trend of gastric motility. Motility indices are a convenient way to interpret the impedance dynamics of the tissue because they represent the power of the signal ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1fn1ticrc0","properties":{"formattedCitation":"[44]","plainCitation":"[44]"},"citationItems":[{"id":144,"uris":[""],"uri":[""],"itemData":{"id":144,"type":"article-journal","title":"Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients: a double-blind, randomized, placebo-controlled study.","container-title":"Critical care medicine","page":"1356–1362","volume":"23","issue":"8","source":"Google Scholar","shortTitle":"Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients","author":[{"family":"Dive","given":"Alain"},{"family":"Miesse","given":"Christian"},{"family":"Galanti","given":"Laurence"},{"family":"Jamart","given":"Jacques"},{"family":"Evrard","given":"Patrick"},{"family":"Gonzalez","given":"Manuel"},{"family":"Installé","given":"Etienne"}],"issued":{"date-parts":[["1995"]]}}}],"schema":""} [39], which is independent of pill polarity. This is important because the pill is effectively floating within the stomach, and its orientation cannot be predicted so by measuring the power of the signal we can negate this effect. One-minute motility indices are further advantageous because signals from force transducers and EEGG may be out of phase due to the spatial difference in ECG electrodes. In this case if could appear that little to no correlation in activity was present. Motility indices are calculated by taking the sum of squared data points over the course of a minute. In one minute there were 600 samples, as the sampling frequency was 10 Hz. After motility indices were calculated using equation (1.2) they were again normalized according to equation (3.1). This normalization is indicative of the average power, and can be compared across samples even with varying sample rates. Mi=j=600*i+1600*(i+1)Dj2 (1.2)where Mi is the motility index M calculated for minute i, [dimensionless]; and Dj is the normalized data at point j, [dimensionless];Once the general trends of gastric motility are established by the motility indices, Pearson correlation coefficients can be computed in order to compare the different signals, and provide a metric for validation. Pearson correlation coefficients were chosen for statistical validation because they indicate a measure of linearity between two signals. Pearson correlation coefficients with p<0.05 were considered to be significant ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2jledtr2cc","properties":{"formattedCitation":"[45]","plainCitation":"[45]"},"citationItems":[{"id":146,"uris":[""],"uri":[""],"itemData":{"id":146,"type":"book","title":"Pages 258–380 in: Statistical Methods","publisher":"The Iowa State University Press, Ames, IA","source":"Google Scholar","shortTitle":"Pages 258–380 in","author":[{"family":"Snedecor","given":"G. W."},{"family":"Cochran","given":"W. G."}],"issued":{"date-parts":[["1967"]]}}}],"schema":""} [40].Further processing of the signals was done to assess the contractions per minute visible in each respective channel. Dominant peaks of the frequency for each measuring modality (basal and post-neostigmine) were subjected to a comprehensive statistical analysis using the paired Student’s t-test ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"WEeYHHiK","properties":{"formattedCitation":"[44]","plainCitation":"[44]"},"citationItems":[{"id":144,"uris":[""],"uri":[""],"itemData":{"id":144,"type":"article-journal","title":"Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients: a double-blind, randomized, placebo-controlled study.","container-title":"Critical care medicine","page":"1356–1362","volume":"23","issue":"8","source":"Google Scholar","shortTitle":"Effect of erythromycin on gastric motility in mechanically ventilated critically ill patients","author":[{"family":"Dive","given":"Alain"},{"family":"Miesse","given":"Christian"},{"family":"Galanti","given":"Laurence"},{"family":"Jamart","given":"Jacques"},{"family":"Evrard","given":"Patrick"},{"family":"Gonzalez","given":"Manuel"},{"family":"Installé","given":"Etienne"}],"issued":{"date-parts":[["1995"]]}}}],"schema":""} [40] to evaluate the relationship between the frequency dynamics of EEGG, sham and force transducer measurements. Frequency analysis was done using the Fast Fourier Transform, implemented in the custom visualization and analysis GAS-6.2 software used previously. RESULTSGastric retentionBefore the implantation of the force transducers an oscilloscope was used to detect the 50 kHz signal, or lack thereof being emitted by the ingested EEGG capsule. Oscilloscope leads were placed in electrical contact with the serosa of the stomach over the pill, the position of which was approximately determined by manual palpation. A sample oscilloscope recording for an active pill is shown in Figure 5a, while Figure 5B shows a recording of an inactive pill. The expanded pill was retrieved from each animal after experimentation, in order to verify the pill’s activity using the same oscilloscope used previously, as well as to assess the expansion dimensions and structural integrity of the gastric retentive enclosure during testing. Each experiment revealed that all the EEGG pills remained either active during testing, and did not fail as a result of liquid exposure or battery failure. Conversely, the sham pills remained inactive, as expected. The average post-retrieval volume of the pills was 12.1 ± 0.4 ml, and had dimensions exceeding 1.5 cm in all directions. The presence of the intact pill within the stomach at the conclusion of the experiments indicated that the pharmacologically induced contractions were unable to propel the expanded gastric retentive enclosure into the small intestine, nor were the pressures within the stomach high enough to rupture the gastric retentive enclosure itself. Motility indices, Pearson correlation coefficients, and contractions per minute (cpm)The testing was divided into two sections, baseline and post-neostigmine, and results were recorded and labelled accordingly. During the baseline tests there was sporadic presence of spontaneous contractile activity as measured by the force transducers, and evidenced in the visual comparisons of Figure 6A and B. Following the introduction of neostigmine several gastric motility factors dramatically increased, notably the frequency, regularity, and amplitudes of contractile activity. A typical simultaneous force transducer and EEGG recording for an active capsule is shown in Figure 6A, along with the post processed one-minute motility indices in parallel. Thirty minutes of baseline activity and thirty minutes of post-neostigmine activity was recorded and normalized together, in order to put each recording into perspective with respect to the maximum and minimum of both states combined. In both states there were statistically significant (p < 0.01) correlations demonstrated between the one-minute motility indices of EEGG and force transducer signals. The more distal or proximal cutaneous electrode combinations were compared to their corresponding force transducer. In the case of the battery removed sham pill the results showed no significant correlations between respective motility indices. Another typical simultaneous recording is shown in Figure 6B, for the case of the sham pill. REF _Ref450552104 \h \* MERGEFORMAT Table 1 summarizes the Pearson correlation coefficients of the one-minute gastric motility indices, divided into baseline or post-neostigmine, and active or sham capsule.Frequency spectral analysis was performed in order to assess the contractions per minute of each signal. As in the case of Pearson correlation coefficients distal and proximal EEGG recordings were compared to the corresponding force transducer. The dominant frequency peaks revealed statistically significant relationships between EEGG and force transducer recordings. The sham study revealed substantial dissociation between the dominant frequency peaks, particularly during the baseline period in which the limited spontaneous gastric activity was sporadic and irregular. Accordingly, there was no significant relationship between the sham study (which can be effectively be considered a standard EGG study) and the force transducers. The averaged values of the dominant peaks in the frequency spectra (0.03-0.1 Hz) are presented in REF _Ref450552113 \h \* MERGEFORMAT Table 2. Comparative statistical evaluation of the frequency dynamics of the dominant spectral peaks is presented in Table 3. DISCUSSIONThe history of cutaneous recordings of human gastric electrical activity spans almost one full century ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"14mton2iok","properties":{"formattedCitation":"[1]","plainCitation":"[1]"},"citationItems":[{"id":8,"uris":[""],"uri":[""],"itemData":{"id":8,"type":"article-journal","title":"The electrogastrogram and what it shows","container-title":"Journal of the American Medical Association","page":"1116-1119","volume":"78","issue":"15","DOI":"10.1001/jama.1922.02640680020008","ISSN":"0002-9955","author":[{"literal":"W Alvarez"}],"issued":{"date-parts":[["1922",4,15]]}}}],"schema":""} [1]. However, in contrast to its extremely successful twin sister, electrocardiography (ECG) ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"2bdrpjc9d5","properties":{"formattedCitation":"[19]","plainCitation":"[19]"},"citationItems":[{"id":162,"uris":[""],"uri":[""],"itemData":{"id":162,"type":"article-journal","title":"The relationship between electrical and mechanical events in the cardiac cycle of man","container-title":"British heart journal","page":"1","volume":"11","issue":"1","source":"Google Scholar","author":[{"family":"Coblentz","given":"B."},{"family":"Harvey","given":"R. M."},{"family":"Ferrer","given":"M. I."},{"family":"Cournand","given":"A."},{"family":"Richards Jr","given":"D. W."}],"issued":{"date-parts":[["1949"]]}}}],"schema":""} [19], which became a pivotal clinical tool that immensely enhanced the frontiers of cardiology, EGG, by any objective account, is a failure. The explanation of this failure can easily be sought in various different directions, ranging from the lack of critical, life-saving diagnostic importance, to the lack of scientific consensus in identifying dyspepsia and gastroparesis as clear-cut gastric motility disorders, to the lack of attention of brilliant enough academics and scholars, to a bad luck due to numerous misrepresenting and over-exaggerated EGG-related claims, etc. In our opinion, all these reasons cannot be regarded as serious. In our view, the deep reason for the lack of any clinical utility in the present-day EGG testing is rooted in the nature of the gastric electromagnetic field[17, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1834gou0hc","properties":{"formattedCitation":"[46], [47]","plainCitation":"[46], [47]"},"citationItems":[{"id":116,"uris":[""],"uri":[""],"itemData":{"id":116,"type":"article-journal","title":"Multiscale modelling of human gastric electric activity: can the electrogastrogram detect functional electrical uncoupling?","container-title":"Experimental physiology","page":"383–390","volume":"91","issue":"2","source":"Google Scholar","shortTitle":"Multiscale modelling of human gastric electric activity","author":[{"family":"Buist","given":"M. L."},{"family":"Cheng","given":"L. K."},{"family":"Sanders","given":"K. M."},{"family":"Pullan","given":"A. J."}],"issued":{"date-parts":[["2006"]]}}},{"id":118,"uris":[""],"uri":[""],"itemData":{"id":118,"type":"article-journal","title":"Electrophysiology of the gastric musculature","container-title":"Handbook of Physiology. The Gastrointestinal System. Motility and Circulation","page":"187–216","source":"Google Scholar","author":[{"family":"Sanders","given":"Kenton M."},{"family":"Publicover","given":"NELSON G."}],"issued":{"date-parts":[["1989"]]}}}],"schema":""} 41,42]. In contrast to the electromagnetic field of the heart ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"1rbg0k6fd1","properties":{"formattedCitation":"[48]","plainCitation":"[48]"},"citationItems":[{"id":113,"uris":[""],"uri":[""],"itemData":{"id":113,"type":"article-journal","title":"The pacemaker current: from basics to the clinics","container-title":"Journal of cardiovascular electrophysiology","page":"342–347","volume":"18","issue":"3","source":"Google Scholar","shortTitle":"The pacemaker current","author":[{"family":"Barbuti","given":"Andrea"},{"family":"Baruscotti","given":"Mirko"},{"family":"DiFrancesco","given":"Dario"}],"issued":{"date-parts":[["2007"]]}}}],"schema":""} [43], its gastric counterpart can be modeled with a dynamically moving annular cylindrical band of electrical dipoles pointing to the center, towards the gastric axis[17, ADDIN ZOTERO_ITEM CSL_CITATION {"citationID":"si9oigr6i","properties":{"formattedCitation":"[47]","plainCitation":"[47]"},"citationItems":[{"id":118,"uris":[""],"uri":[""],"itemData":{"id":118,"type":"article-journal","title":"Electrophysiology of the gastric musculature","container-title":"Handbook of Physiology. The Gastrointestinal System. Motility and Circulation","page":"187–216","source":"Google Scholar","author":[{"family":"Sanders","given":"Kenton M."},{"family":"Publicover","given":"NELSON G."}],"issued":{"date-parts":[["1989"]]}}}],"schema":""} 42]. This is a special type of electromagnetic field that presents a highly integrated signature when its electrical potentials are recorded in its outer vicinity. Add to that the humble amplitude range of these biopotentials, their infralow frequency nature, and their secondary integration over the surface area of the recording cutaneous electrodes, and what emerges is the hypothesis that it is the very nature of the gastric electromagnetic field that objectively limits traditional present-day electrogastrography. So, what can we do to revive EGG testing and breathe a new life in its promise as a single diagnostic test for dyspepsia and/or gastroparesis?Our proposal is simple – if the nature of the gastric electromagnetic field is prohibitive to any meaningful cutaneous, non-invasive EGG testing of gastric motility, we create our own electromagnetic field inside the stomach, which can do the job in a far more meaningful and reliable way. In the present article we present one such possibility – an ingestible, temporary, controllable pseudobezoar containing a point source of a 50-kHz electromagnetic field. Upon swallowing, the structure would swell in the stomach to a size prohibiting its expulsion through the pylorus for at least 48 h. Supplied by a powerful enough battery, this pseudobezoar-based, gastric-retentive electromagnetic oscillator overshadows the spontaneously existing gastric electrical activity in a powerful, yet meaningful fashion. In fact, canine testing revealed that the cutaneous recordings of this new electromagnetic field reflect gastric contractions in a very reliable fashion. Subsequently, when the battery supplying the electronic oscillator in the pseudobezoar exhausts itself, the structure disintegrates into its constituent fibers (with the encapsulated electronic oscillator and its supplying battery being only several millimeters in diameter), which leave the gastrointestinal system in a natural way. An additional safety feature can be also integrated within the pseudobezoar, allowing its disintegration at any time prior to its self-disintegration, based on ingesting strong antacids, or drinking hot (> 45 degrees C) liquids. As with any innovative idea, a lot more needs to be done before this radically new approach in the non-invasive ambulatory assessment of gastric motility becomes a reliable clinical tool for diagnosing gastric dyspepsia and/or gastroparesis. First and foremost, the clinical community should clearly defend and loudly support the need for such a single, non-invasive and inexpensive test. Second, controlled clinical trials on humans should take place in order to explicitly show the real diagnostic value of such testing, including its sensitivity and specificity. Third, the existing EGG insurance codes should be revisited so that the routine EGG is replaced by EEGG and it enters the clinical mainstream, rather than remain forever “a research tool” of little consequence, administered free of charge only now and again and here and there by curious investigators.In conclusion, EEGG is a new modality to record reliably and non-invasively gastric motility utilizing the same recording setup used in present-day plain EGG. Its clinical utilization promises to revive a non-invasive gastric testing that is fading in MENTSBackgroundCutaneous recordings of gastric electrical activity, known as electrogastrography (EGG) could not find any reliable clinical applicability for almost a century.Research frontiersAlthough a promising non-invasive test to possibly diagnose gastric dyspepsia and/or gastroparesis, EGG is still a research tool with no clinical utilization.Innovations and breakthroughIn this study, it is proposed to preserve the overall EGG test protocol and standard equipment but provide enhanced patient preparation by swallowing a self-expandable, self-disintegratable pseudobesoar capsule containing a miniature electronic oscillator. ApplicationsThe proposed Enhanced Electrogastrography method can be utilized for the early diagnosis of functional dyspepsia and/or gastroparesis.Peer-review ECG is so limited in diagnosing for its lack of clinical utility. The innovative method for EGG recording introduced in this paper, which leave the gastrointestinal system in a natural way, is non-invasive, reliable and long-hour ambulatory for gastric motility monitoring. It would become a promising clinical tool for diagnosing gastric motility disorder.References1 Alvarez W. The electrogastrogram and what it shows. JAMA 1922 78: 1116-1119 [DOI: 10.1001/jama.1922.02640680020008]2?Parkman HP, Orr WC. The gastrointestinal motility laboratory.?Gastroenterol Clin North Am?2007;?36: 515-529, vii-viii [PMID: 17950436 DOI: 10.1016/j.gtc.2007.07.010]3?Lin Z, Eaker EY, Sarosiek I, McCallum RW. Gastric myoelectrical activity and gastric emptying in patients with functional dyspepsia.?Am J Gastroenterol 1999;?94: 2384-2389 [PMID: 10483996 DOI: 10.1111/j.1572-0241.1999.01362.x]4?van der Voort IR, Osmanoglou E, Seybold M, Heymann-M?nnikes I, Tebbe J, Wiedenmann B, Klapp BF, M?nnikes H. 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The pacemaker current: from basics to the clinics.?J Cardiovasc Electrophysiol?2007;?18: 342-347 [PMID: 17284289 DOI: 10.1111/j.1540-8167.2006.00736.x]P-Reviewer: Arya V, Liu MJ, Nicodeme F S-Editor: Gong ZML-Editor: E-Editor:Specialty type: Gastroenterology and hepatologyCountry of origin: CanadaPeer-review report classificationGrade A (Excellent): AGrade B (Very good): B, BGrade C (Good): 0Grade D (Fair): 0Grade E (Poor): 0Figure 1 The oscillator circuit, printed circuit board layout, and enhanced electrogastrography capsule body. Dimensions of the circuit board were 10mm x 6mm, which allowed it to fit inside the capsule body that had dimensions 19mm x 10mm. Size of the board was constrained by component choice, as well as the need for swelling polymers surrounding the capsule body.Figure 2 Breakdown of the enhanced electrogastrography gastric retentive pill. The oscillator circuit was first sealed into the assembled capsule, and added to superabsorbent granules held in a liquid-permeable mesh. This was inserted into a dissolvable pill, which completely disintegrated in the stomach after 10 min, allowing the granules to swell. A mm scale is provided on the left of the image. 1: Oscillator circuit; 2: Capsule body; 3: Assembled capsule; 4; Superabsorbent granules; 5: Capsule and granules inside a liquid-permeable mesh; 6: Dissolvable pill containing the mesh enclosed capsule; 7: EEGG gastric retentive pill; 8: Pill expanded in water; 9: Test dish.Figure 3 The serosal view of the stomach showing the placement of the force transducers (A), and the internal view of the stomach showing the position of the EEGG capsule and gastric retentive mesh (B). EEGG: enhanced electrogastrography.Figure 4 Overall gastric retentive pill-based experimental setup. 1: Stomach; 2: Gastric retentive mesh; 3: EEGG capsule; 4: Implanted force transducers; 5: Connecting wire from force transducers; 6: Custom bridge amplifier; 7: Cutaneous electrodes; 8: Receiving wires from ECG electrodes; 9: Isolated bioelectric amplifier; 10: Analog-to-digital converter; 11: Real-time data acquisition software. EEGG: enhanced electrogastrography.Figure 5 An oscilloscope reading from the gastric serosa prior to the force transducer implantation verified the presence of an activated enhanced electrogastrography pill inside the stomach (A). The sham pills did not demonstrate any signal (B).Figure 6 Combined plot of the raw signals and the one-minute motility indices for an active pill (A) and an inactive pill (B) in the baseline state (0-1800) and post-neostigmine administration (1800-3600). A vertical line denotes the administration of neostigmine. Measurements are normalized and displayed in relative units (RU). Table SEQ Table \* ARABIC \s 1 1 Averaged pearson correlation coefficients of the one-minute gastric motility indices per state per capsule typeModalityStatePCCs proximal FT-proximalp valuePCCs distalFT-distalp valueCutaneous GMIsCutaneous GMIsEEGG capsuleBaseline0.763 ± 0.2< 0.010.674 ± 0.47< 0.01After neostigmine0.731 ± 0.12< 0.010.734 ± 0.14< 0.01Sham capsuleBaseline0.160 ± 0.03> 0.100.071 ± 0.02> 0.10After neostigmine0.113 ± 0.09> 0.100.051 ± 0.03> 0.10PCCs: Pearson correlation coefficients; GMIs: gastric motility indices.Table SEQ Table \* ARABIC \s 1 2 Averaged cycles per minute of the dominant spectral peaks of the raw force transducer and cutaneous recordings per state per capsule typeModalityStateChannelcpmEEGG capsuleBaselineFT2.38 ± 1.2EEGG2.42 ± 1.27After neostigmineFT3.55 ± 0.94EEGG3.58 ± 0.95Sham capsuleBaselineFT2.65 ± 1.15Sham3.94 ± 1.67After neostigmineFT3.84 ± 0.91Sham4.12 ± 1.56FT: force transducer; EEGG: enhanced electrogastrography; cpm: cycles per minute.Table SEQ Table \* ARABIC \s 1 3 Statistical comparison between the dominant spectral peaks of the force transducer and enhanced electrogastrography/Sham recordings using the paired student t-testModalityStateP valueEEGG capsuleBaseline (FT EEGG)0.048aAfter neostigmine (FT EEGG)0.049aSham capsuleBaseline (FT EGG)0.92After neostigmine (FT EGG)0.33ap < 0.05. FT: force transducer; EEGG: enhanced electrogastrography. ................
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