[Show abstract][Hide abstract] ABSTRACT: Gastroparesis (GP), defined as delayed gastric emptying in the absence of any mechanical obstruction, is a challenging clinical condition, mainly because of limited treatment options. Studies in animal models of delayed gastric emptying as well as patients with gastroparesis revealed depletion or ultrastructural changes of interstitial cells of Cajal (ICC) in the gastric tissue, recently termed ICC-opathy. ICC are the pacemakers of the gastrointestinal tract and are involved in the transmission of the neuronal signaling to the smooth muscles. Therefore, lack of ICC could be one explanation of delayed gastric emptying in gastroparetic patients. How frequently ICC changes are observed in gastroparesis is not yet clear. In this review, the data on gastric ICC counts and morphology in animal models and patients with gastroparesis are discussed.
Journal of neurogastroenterology and motility 10/2015; 21(4):486-93. DOI:10.5056/jnm15075 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastric surgery has long been known to be a cause of dumping syndrome (DS). However, the increasing incidence of gastric bypass surgery, as well as reports of DS unrelated to previous gastric surgeries, has increased the importance of understanding DS in recent years. DS is due to the gastrointestinal response to voluminous and hyperosmolar chyme that is rapidly expelled from the stomach into the small intestine. This response involves neural and hormonal mechanisms. This review encompasses the symptoms, diagnosis, and treatment approaches of DS and also focuses on the current research status of the pathophysiology of DS.
Digestive Diseases and Sciences 09/2015; DOI:10.1007/s10620-015-3839-x · 2.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of chronic nausea and vomiting on quality of life and economic burden are substantial. New findings show that interstitial cells of Cajal are depleted or have ultrastructural changes in patients with chronic nausea and vomiting who have normal gastric emptying. Abnormalities of the gastric slow waves were also observed.
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Domperidone is a dopamine receptor antagonist with peripheral prokinetic and central antiemetic properties. Prolongation of the QTc interval with chronic use of oral domperidone in standard doses has been reported in the literature. Our goal was to investigate cardiac toxicity in patients receiving 2-fold greater doses than in previous reports.
A retrospective chart review was conducted of patients with nausea (N) and vomiting (V) receiving domperidone from 2009 to 2013 under an Investigational New Drug (IND) protocol. Patient demographics, indications for therapy, clinical outcomes, cardiac symptoms and electrocardiogram tracings were reviewed. Prolonged QTc was verified if >470 milliseconds in females (F) and >450 milliseconds in males (M).
A total of 64 patients, 44 female (37% Hispanic, 60% white, 3% African American), were taking domperidone for diabetic gastroparesis 45%; idiopathic gastroparesis 36%; chronic N&V 8%; dumping syndrome 5%; cyclic vomiting 5% and conditioned vomiting 1%. Mean duration of therapy was 8 months (range, 3 months to 4 years). Doses ranged from 40 to 120 mg/d with 90% receiving 80 to 120 mg compared with the standard dose of 40 mg. Of note, 73% of subjects benefited from treatment with reduced nausea and vomiting. Thirty-seven patients had follow-up electrocardiograms available, and they showed that the mean QTc at baseline was 424 milliseconds ± 28.4 (SD) compared with 435 milliseconds ± 27.2 (SD) at follow-up (not significant). Ten of these patients had prolonged QTc at F/U ranging from 453 to 509 milliseconds, without any cardiovascular complaints. There was no relationship between prolonged QTc and daily dose of domperidone, body mass index or age.
Our data indicate that at very high dosing, the prokinetic/antiemetic agent domperidone has a low risk of adverse cardiovascular events while exhibiting good clinical efficacy.
The American Journal of the Medical Sciences 03/2015; 146(5). DOI:10.1097/MAJ.0000000000000439 · 1.39 Impact Factor