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202. Reduction in Symptoms During Provocative Meal Testing with Insulin Pump Therapy Plus Continuous Glucose Monitoring in Patients with Gastroparesis due to Poorly Controlled Diabetes: Relation to Gastric Myoelectrical Activity

Author

Koch, Kenneth L., primary, Hasler, William L., additional, Calles-Escandon, Jorge, additional, Van Natta, Mark L., additional, Snape, William J., additional, Pasricha, Pankaj J., additional, Nguyen, Linda Anh B., additional, Parkman, Henry P., additional, McCallum, Richard W., additional, Sarosiek, Irene, additional, Abell, Thomas, additional, Farrugia, Gianrico, additional, Grover, Madhusudan, additional, Hamilton, Frank A., additional, Tonascia, James, additional, and Lee, Linda A., additional

Published
2017
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205. Aprepitant for Symptoms of Gastroparesis and Related Disorders: The APRON Randomized Clinical Trial

Author

Pasricha, Pankaj Jay, primary, Yates, Katherine, additional, Sarosiek, Irene, additional, McCallum, Richard, additional, Clarke, John, additional, Nguyen, Linda, additional, Dhalla, Sameer, additional, Stein, Ellen, additional, Koch, Kenneth, additional, Abell, Thomas, additional, Hasler, William, additional, Snape, William, additional, Lee, Linda, additional, Grover, Madhusudan, additional, Miriel, Laura, additional, Van Natta, Mark, additional, Farrugia, Gianrico, additional, Tonascia, James, additional, Hamilton, Frank, additional, and Parkman, Henry, additional

Published
2016
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206. Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces

Author

Wang, Fan, primary, Knutson, Kaitlyn, additional, Alcaino, Constanza, additional, Linden, David R., additional, Gibbons, Simon J., additional, Kashyap, Purna, additional, Grover, Madhusudan, additional, Oeckler, Richard, additional, Gottlieb, Philip A., additional, Li, Hui Joyce, additional, Leiter, Andrew B., additional, Farrugia, Gianrico, additional, and Beyder, Arthur, additional

Published
2016
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207. Improving the detection of environmental enteric dysfunction: a lactulose, rhamnose assay of intestinal permeability in children aged under 5 years exposed to poor sanitation and hygiene

Author

Faubion, W A, primary, Camilleri, M, additional, Murray, J A, additional, Kelly, P, additional, Amadi, B, additional, Kosek, M N, additional, Enders, F, additional, Larson, J, additional, Grover, Madhusudan, additional, Boe, G, additional, Dyer, R, additional, and Singh, R, additional

Published
2016
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208. 179 Mechanosensitive Ion Channel Piezo2 in Mouse Enterochromaffin Cells Is Important for Pressure-Induced Secretion From Small Bowel Mucosa

Author

Wang, Fan, primary, Ayala, Constanza A. Alcaino, additional, Knutson, Kaitlyn R., additional, Grover, Madhusudan, additional, Bernard, Cheryl, additional, Linden, David R., additional, Kashyap, Purna C., additional, Li, Hui Joyce, additional, Leiter, Andrew B., additional, Farrugia, Gianrico, additional, and Beyder, Arthur, additional

Published
2016
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210. 1082 Gastroparesis and Functional Dyspepsia of Postprandial Discomfort Phenotype Have Similar Clinical, Pathophysiological and Histopathological Features

Author

Pasricha, Pankaj J., primary, Grover, Madhusudan, additional, Yates, Katherine P., additional, Bernard, Cheryl, additional, Miriel, Laura A., additional, Clarke, John O., additional, Stein, Ellen M., additional, Dhalla, Sameer, additional, Koch, Kenneth L., additional, Hasler, William L., additional, McCallum, Richard W., additional, Sarosiek, Irene, additional, Snape, William J., additional, Nguyen, Linda Anh B., additional, Tonascia, James, additional, Hamilton, Frank A., additional, Parkman, Henry P., additional, Abell, Thomas L., additional, and Farrugia, Gianrico, additional

Published
2016
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213. Intragastric Meal Distribution During Gastric Emptying Scintigraphy for Assessment of Fundic Accommodation: Correlation with Symptoms of Gastroparesis.

Author

Orthey, Perry, Yu, Daohai, Van Natta, Mark L., Ramsey, Frederick V., Diaz, Jesus R., Bennett, Paige A., Iagaru, Andrei H., Fragomeni, Roberto Salas, McCallum, Richard W., Sarosiek, Irene, Hasler, William L., Farrugia, Gianrico, Grover, Madhusudan, Koch, Kenneth L., Nguyen, Linda, Snape, William J., Abell, Thomas L., Pasricha, Pankaj J., Tonascia, James, and Hamilton, Frank

Published
2018
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215. Platelet-derived growth factor receptor α (PDGFRα)-expressing 'fibroblast-like cells' in diabetic and idiopathic gastroparesis of humans

Author

Grover, Madhusudan, Bernard, Cheryl E., Pasricha, Pankaj J., Parkman, Henry P., Abell, Thomas L., Nguyen, Linda A., Snape, William, Shen, K. Robert, Sarr, Michael, Swain, James, Kendrick, Michael, Gibbons, Simon, Ordog, Tamas, and Farrugia, Gianrico

Subjects
Adult, Male, Gastroparesis, Receptor, Platelet-Derived Growth Factor alpha, Small-Conductance Calcium-Activated Potassium Channels, Stomach, Myenteric Plexus, Muscle, Smooth, Immunohistochemistry, Article, Diabetes Complications, Gastric Emptying, Gastric Mucosa, Case-Control Studies, Humans, Female
Abstract

Emerging evidence suggests that "fibroblast-like cells" (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca(2+) -activated K(+) channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFRα) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFRα-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced.Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFRα staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified.Intramuscular PDGFRα-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFRα-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients.In conclusion, PDGFRα identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function.

Published
2012

216. What Are the Important Subsets of Gastroparesis?

Author

Camilleri, Michael, Grover, Madhusudan, and Farrugia, Gianrico

Subjects
Gastroparesis, Humans, Article
Abstract

Gastroparesis is often divided into subsets based on etiology and pathophysiology; however, the utility of these subsets in the diagnosis and treatment of gastroparesis is not well defined. The objectives are to consider the subsets of gastroparesis from the perspectives of etiology and pathogenesis, pathophysiology, histopathology, and clinical associations, with particular focus on similarities and differences between diabetic and idiopathic gastroparesis and consideration of the potential subset of painful gastroparesis. We conclude that idiopathic and diabetic gastroparesis have similar initial presentations and manifestations, except that idiopathic gastroparesis tends to be associated more frequently with pain. Myopathic disorders are uncommon. Extrinsic denervation was considered the most common etiology; however, with the decline in surgery for peptic ulceration and in depth study of full thickness gastric biopsies, the most common intrinsic defects are being recognized in the interstitial cells of Cajal (ICC-opathy) and with immune infiltration and neuronal changes (intrinsic neuropathic gastroparesis). Histomorphological differences at the microscopic level between diabetic and idiopathic gastroparesis are still of unclear significance. Two gastroparesis subsets worthy of special mention, because they are potentially reversible with identification of the cause, are post-viral gastroparesis, which has a generally good prognosis, and iatrogenic gastroparesis, especially in patients with non-surgical gastroparesis, such as diabetics exposed to incretins such as pramlintide and exanetide.

Published
2012

219. 299 Diabetic and Idiopathic Gastroparesis Is Associated With Loss of Antral Interstitial Cells of Cajal and CD206 Positive Macrophages

Author

Bernard, Cheryl E., primary, Grover, Madhusudan, additional, Gibbons, Simon J., additional, Parkman, Henry P., additional, Abell, Thomas L., additional, Snape, William J., additional, Pasricha, Pankaj J., additional, Hasler, William L., additional, Lee, Linda A., additional, McCallum, Richard W., additional, Sarosiek, Irene, additional, Nguyen, Linda Anh B., additional, Koch, Kenneth L., additional, Tonascia, James, additional, Hamilton, Frank A., additional, Kendrick, Michael L., additional, Shen, K. Robert, additional, Kellogg, Todd A., additional, McKenzie, Travis J., additional, Lombardo, KMarie Reid, additional, Farrugia, Gianrico, additional, and Consortium, GpCRC, additional

Published
2015
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220. 678 Transcriptomic Changes in Colonic Mucosa in Patients With Campylobacter jejuni Post Infectious Irritable Bowel Syndrome

Author

Bisbee, Molly, primary, Nair, Asha, additional, Carlson, Paula, additional, Kolbert, Christopher, additional, Eckloff, Bruce, additional, Rakhshan, Fariborz, additional, Bernard, Cheryl E., additional, Kashyap, Purna C., additional, Farrugia, Gianrico, additional, Camilleri, Michael, additional, and Grover, Madhusudan, additional

Published
2015
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229. Sa1997 - Vitamin D Deficiency in Gastroparesis and Chronic Unexplained Nausea and Vomiting: Relationship with Gastric Emptying and Symptoms

Author

Pasricha, Pankaj J., Van Natta, Mark L., McCallum, Richard W., Nguyen, Linda Anh B., Sarosiek, Irene, Tonascia, James, Abell, Thomas, Hasler, William L., Stein, Ellen M., Clarke, John O., Grover, Madhusudan, Farrugia, Gianrico, Snape, William J., Koch, Kenneth L., Hamilton, Frank A., and Parkman, Henry P.

Published
2017
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230. Sa1789 - Prophylactic Fecal Microbial Transplant Restores Clostridium Difficile Colonization Resistance in a Dysbiotic Subset of Diarrhea Associated Human Microbial Communities Modeled in Germ Free Mice

Author

Battaglioli, Eric, Hale, Vanessa, Chen, Jun, Jeraldo, Patricio, Rekdal, Vayu Maini, Huq, Lutfi, Smits, Samuel A., Smyrk, Thomas, Khanna, Sahil, Pardi, Darrell S., Grover, Madhusudan, Patel, Robin, Nelson, Heidi, Chia, Nicholas, Sonnenburg, Justin, Farrugia, Gianrico, and Kashyap, Purna

Published
2017
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231. 526 - Reduction in Symptoms During Provocative Meal Testing with Insulin Pump Therapy Plus Continuous Glucose Monitoring in Patients with Gastroparesis due to Poorly Controlled Diabetes: Relation to Gastric Myoelectrical Activity

Author

Koch, Kenneth L., Hasler, William L., Calles-Escandon, Jorge, Van Natta, Mark L., Snape, William J., Pasricha, Pankaj J., Nguyen, Linda Anh B., Parkman, Henry P., McCallum, Richard W., Sarosiek, Irene, Abell, Thomas, Farrugia, Gianrico, Grover, Madhusudan, Hamilton, Frank A., Tonascia, James, and Lee, Linda A.

Published
2017
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234. Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production.

Author

Bhattarai, Yogesh, Schmidt, Bradley A., Linden, David R., Larson, Eric D., Grover, Madhusudan, Beyder, Arthur, Farrugia, Gianrico, and Kashyap, Purna C.

Subjects
SEROTONIN receptors, NEUROTRANSMITTERS, GASTROINTESTINAL system, INTESTINAL secretion, TETRODOTOXIN, DIAGNOSIS
Abstract

Serotonin [5-hydroxytryptamine (5- HT)], an important neurotransmitter and a paracrine messenger in the gastrointestinal tract, regulates intestinal secretion by its action primarily on 5-HT3 and 5-HT4 receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (Δsc) in GF compared with HM mice. Additionally, 5-HT3 receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT3 receptor antagonist, inhibited 5-HT-evoked Δsc in GF mice but not in HM mice. Furthermore, a 5-HT3 receptor-selective agonist, 2-methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher Δsc in GF compared with HM mice. Immunohistochemistry in 5-HT3A-green fluorescent protein mice localized 5-HT3 receptor expression to enterochromaffin cells in addition to nerve fibers. The significant difference in 5-HT-evoked Δsc between GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was lost after ondansetron application in the presence of TTX. Application of acetate (10 mM) significantly lowered 5-HT3 receptor mRNA in GF mouse colonoids. We conclude that host secretory response to 5-HT may be modulated by gut microbiota regulation of 5-HT3 receptor expression via acetate production. Epithelial 5-HT3 receptor may function as a mediator of gut microbiota-driven change in intestinal secretion. NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)-evoked intestinal secretion in a 5-HT3 receptordependent mechanism and gut microbiota metabolite acetate alters 5-HT3 receptor expression in colonoids. [ABSTRACT FROM AUTHOR]

Published
2017
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235. Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces.

Author

Wang, Fan, Knutson, Kaitlyn, Alcaino, Constanza, Linden, David R., Gibbons, Simon J., Kashyap, Purna, Grover, Madhusudan, Oeckler, Richard, Gottlieb, Philip A., Li, Hui Joyce, Leiter, Andrew B., Farrugia, Gianrico, and Beyder, Arthur

Subjects
GASTROINTESTINAL hormones, SEROTONIN, MECHANOTRANSDUCTION (Cytology), NEUROTRANSMITTERS, EPITHELIUM
Abstract

Key points The gastrointestinal epithelial enterochromaffin (EC) cell synthesizes the vast majority of the body's serotonin. As a specialized mechanosensor, the EC cell releases this serotonin in response to mechanical forces. However, the molecular mechanism of EC cell mechanotransduction is unknown., In the present study, we show, for the first time, that the mechanosensitive ion channel Piezo2 is specifically expressed by the human and mouse EC cells., Activation of Piezo2 by mechanical forces results in a characteristic ionic current, the release of serotonin and stimulation of gastrointestinal secretion., Piezo2 inhibition by drugs or molecular knockdown decreases mechanosensitive currents, serotonin release and downstream physiological effects., The results of the present study suggest that the mechanosensitive ion channel Piezo2 is specifically expressed by the EC cells of the human and mouse small bowel and that it is important for EC cell mechanotransduction., Abstract The enterochromaffin (EC) cell in the gastrointestinal (GI) epithelium is the source of nearly all systemic serotonin (5-hydroxytryptamine; 5-HT), which is an important neurotransmitter and endocrine, autocrine and paracrine hormone. The EC cell is a specialized mechanosensor, and it is well known that it releases 5-HT in response to mechanical forces. However, the EC cell mechanotransduction mechanism is unknown. The present study aimed to determine whether Piezo2 is involved in EC cell mechanosensation. Piezo2 mRNA was expressed in human jejunum and mouse mucosa from all segments of the small bowel. Piezo2 immunoreactivity localized specifically within EC cells of human and mouse small bowel epithelium. The EC cell model released 5-HT in response to stretch, and had Piezo2 mRNA and protein, as well as a mechanically-sensitive inward non-selective cation current characteristic of Piezo2. Both inward currents and 5-HT release were inhibited by Piezo2 small interfering RNA and antagonists (Gd3+ and D-GsMTx4). Jejunum mucosal pressure increased 5-HT release and short-circuit current via submucosal 5-HT3 and 5-HT4 receptors. Pressure-induced secretion was inhibited by the mechanosensitive ion channel antagonists gadolinium, ruthenium red and D-GsMTx4. We conclude that the EC cells in the human and mouse small bowel GI epithelium selectively express the mechanosensitive ion channel Piezo2, and also that activation of Piezo2 by force leads to inward currents, 5-HT release and an increase in mucosal secretion. Therefore, Piezo2 is critical to EC cell mechanosensitivity and downstream physiological effects. [ABSTRACT FROM AUTHOR]

Published
2017
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240. 389 Chronic Diarrhea in Subset of Patients With IBD and IBS is Associated With Altered Microbiota

Author

Rekdal, Vayu Maini, primary, Alnahhas, Mhd Firas, additional, Rainey, John F., additional, Reigstad, Christopher S., additional, Khanna, Sahil, additional, Grover, Madhusudan, additional, Devine, M Donna Felmlee, additional, Chia, Nicholas, additional, Loftus, Edward V., additional, Boardman, Lisa A., additional, Ahlquist, David A., additional, Pardi, Darrell S., additional, Farrugia, Gianrico, additional, and Kashyap, Purna C., additional

Published
2014
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242. Su2082 Colonic Barrier Function Is Impaired in Post-Campylobacter jejuni Irritable Bowel Syndrome

Author

Grover, Madhusudan, primary, Farrugia, Gianrico, additional, Linden, David R., additional, MacNaughton, Wallace K., additional, Kashyap, Purna C., additional, Smith, Kirk, additional, Griffith, Jayne, additional, Sharma, Anamay N., additional, Carlson, Paula, additional, Szurszewski, Joseph H., additional, Bernard, Cheryl E., additional, Burton, Duane D., additional, Busciglio, Irene A., additional, and Camilleri, Michael, additional

Published
2014
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244. Progress in Gastroparesis - A Narrative Review of the Work of the Gastroparesis Clinical Research Consortium.

Author

Pasricha, Pankaj J., Grover, Madhusudan, Yates, Katherine P., Abell, Thomas L., Koch, Kenneth L., McCallum, Richard W., Sarosiek, Irene, Bernard, Cheryl E., Kuo, Braden, Bulat, Robert, Shulman, Robert J., Chumpitazi, Bruno P., Tonascia, James, Miriel, Laura A., Wilson, Laura A., Van Natta, Mark L., Mitchell, Emily, Hamilton, Frank, Farrugia, Gianrico, and Parkman, Henry P.

Abstract

The Gastroparesis Clinical Research Consortium is a multicenter coalition created and funded by the National Institutes of Diabetes and Digestive and Kidney Disorders, with a mission to advance understanding of the pathophysiology of gastroparesis and develop an effective treatment for patients with symptomatic gastroparesis. In this review, we summarize the results of the published Gastroparesis Clinical Research Consortium studies as a ready and convenient resource for gastroenterologists and others to provide a clear understanding of the consortium's experience and perspective on gastroparesis and related disorders. [ABSTRACT FROM AUTHOR]

Published
2022
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247. Outcomes of Ultrasound-Guided Trigger Point Injection for Abdominal Wall Pain.

Author

Alnahhas, Mhd, Oxentenko, Shawn, Locke, G., Hansel, Stephanie, Schleck, Cathy, Zinsmeister, Alan, Farrugia, Gianrico, Grover, Madhusudan, Alnahhas, Mhd Firas, Oxentenko, Shawn C, Locke, G Richard 3rd, Schleck, Cathy D, and Zinsmeister, Alan R

Subjects
ABDOMINAL wall, ULTRASONIC imaging, ABDOMINAL pain, HEALTH outcome assessment, INJECTIONS, DISEASES, ABDOMEN, HUMAN body, LIDOCAINE, STEROIDS, RETROSPECTIVE studies, METHYLPREDNISOLONE, BUPIVACAINE, PHARMACODYNAMICS
Abstract

Background: Abdominal wall pain (AWP) is an important cause of chronic abdominal pain. History and physical examination are critical to the diagnosis of AWP. Trigger point injection (TPI) using either a steroid or a local anesthetic or a combination of both is often used to treat AWP.Aim: To determine the efficacy of ultrasound-guided TPI and to determine the predictors of a successful response.Methods: Patients who received ultrasound-guided TPI between July 2010 and June 2011 were surveyed. The primary outcome was determined using the Treatment Efficacy Questionnaire (TEQ). Electronic medical records were reviewed to determine patient, pain and TPI characteristics. Linear regression was used to determine the predictors of a successful response on the TEQ.Results: Right upper quadrant was the most common site of AWP, and the median pain duration was 12 months. Pain was rated as >8 (1-10 scale) by 57 % and 30 % described it as an ache. Narcotic use was reported in 38 %, and 73 % had a history of at least one abdominal surgery. Forty-four of the 120 (37 %) patients met the criteria for responder on the TEQ. Compared to before treatment, 36 % reported being "significantly better" and 22 % "slightly better." Multiple linear regression analysis showed that higher somatization negatively predicted response. None of the other historical, examination or TPI characteristics were associated with response to the TPI.Conclusion: TPI can provide significant, long-term symptom relief in a third of patients with chronic abdominal pain attributed to AWP. Somatization was inversely related to the treatment success. [ABSTRACT FROM AUTHOR]

Published
2016
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249. Endoscopic full-thickness biopsy of the gastric wall with defect closure by using an endoscopic suturing device: survival porcine study

Author

Rajan, Elizabeth, primary, Gostout, Christopher J., additional, Aimore Bonin, Eduardo, additional, Moran, Erica A., additional, Locke, Richard G., additional, Szarka, Lawrence A., additional, Talley, Nicholas J., additional, Deters, Jodie L., additional, Miller, Charles A., additional, Knipschield, Mary A., additional, Lurken, Matthew S., additional, Stoltz, Gary J., additional, Bernard, Cheryl E., additional, Grover, Madhusudan, additional, and Farrugia, Gianrico, additional

Published
2012
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