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Sharon E Kim, Edy Soffer Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA Abstract: Patients with gastroesophageal reflux disease (GERD) who are not satisfied with acid suppression therapy can benefit primarily from fundoplication, a surgical intervention. Fundoplication has been the standard surgical procedure for GERD. It is effective but is associated with adverse effects, resulting in a declining number of interventions, creating a need for alternative interventions that are effective, yet have a better adverse effect profile. One such alternative involves the application of electrical stimulation to the lower esophageal sphincter. A number of animal studies showed that such stimulation can increase resting lower esophageal sphincter pressure. An acute human study confirmed this effect, and was followed by two open-label studies, with a follow-up of up to 3 years. Results thus far show that the therapy is associated with a significant improvement in symptoms, a significant reduction in esophageal acid exposure, and a very good safety profile. This review will describe the evolution of electrical stimulation therapy for GERD, as well as the safety and efficacy of this intervention. Keywords: gastroesophageal reflux disease, lower esophageal sphincter, health-related quality of life

Background: Interstitial cells of Cajal (ICC] are required for normal intestinal motility. ICC are found throughout the human colon and are decreased in the sigmoid colon of patients with slow [...]

Under normal physiological conditions, gastric acid production is controlled by a negative feedback mechanism. Proton pump inhibitors, such as pantoprazole, inhibit gastric acid secretion by irreversibly binding and inactivating luminally active hydrogen potassium ATPase. Recovery of acid production after treatment with a proton pump inhibitor is driven by new pump synthesis, activation of existing cytoplasmic pumps, or reversal of proton pump inhibition. The authors measured the time course of the inhibition and recovery of acid secretion in healthy volunteers following intravenous administration of pantoprazole to determine the rate of proton pump activation under maximally stimulated conditions. Gastric acid production was measured in 27 Helicobacter pylori negative healthy volunteers (mean age = 31 +/- 7 years; 17 men, 10 women) who received single doses of intravenous pantoprazole (20, 40, 80, or 120 mg) in the presence of a continuous intravenous infusion of 1 ug/kg/h of pentagastrin. From the time profile of acid secretion, the authors described the rate of change of acid output using an irreversible pharmacodynamic response model represented by the equation dR/dt = -k x R x Cpanto + Ln2/PPR x (Ro-R) and correlated the parameter values with demographic factors and gastric acid measurements. Mean stimulated acid output secretion was 21.6 +/- 18.4 mEq/h (range: 1.6-90.5) prior to the administration of pantoprazole and remained steady for 25 hours after placebo administration. Intravenous pantoprazole inhibited acid output in a dose-response fashion, with maximal inhibition (99.9%) occurring after an 80 mg dose. Mean proton pump recovery time was 37.1 +/- 21.0 hours (range: 6.7-75), and recovery was independent of the dose of pantoprazole. There was no association noted between proton pump recovery time and gender, age, race, body weight, or pantoprazole dose. However, there was an inverse correlation between acid output during baseline stimulation and recovery of acid secretion. Mean proton pump recovery time in stimulated normal human volunteers was 37.1 +/- 21.0 hours, with a range of 6.7 to 75 hours. The authors hypothesize that there may be a normal homeostatic mechanism that maintains acid secretory capability within a normal range by altering the rate of proton pump activation dependent on the individual's parietal cell mass. Abnormalities of this process may be responsible for the development of acid peptic disease in susceptible individuals. [ABSTRACT FROM AUTHOR]

Growth factors, such as epidermal growth factor (EGF), are known to protect upper gut mucosa against irritants and to enhance healing of ulcerative lesions in animal models. A number of salivary growth factors are found in human saliva. The aim of this study was to determine if salivary growth factors and cytokines are deficient in patients with esophagitis or with Barrett's metaplasia. Fifteen healthy subjects, eight patients with esophagitis, and 13 patients with Barrett's metaplasia were included. Salivary concentration of EGF, FGF, IL-1, and IL-6 were measured during esophageal saline and hydrochloric acid perfusion and in the postprandial state. There was no statistically significant difference in the concentration of EGF or cytokines among the three study groups in each experimental condition or among the three experimental conditions in each group. FGF basic could not be detected in saliva. In conclusion, these findings do not support the hypothesis that a deficiency in salivary growth factors or cytokines plays a significant role in the development of mild to moderate reflux esophagitis or Barrett's metaplasia. [ABSTRACT FROM AUTHOR]