Detailed Biography:

My laboratory has been involved with elucidating gastric defense mechanisms in an in vivo animal model. Methods have been developed for the simultaneous measurement in vivo of intracellular pH (pHi), and viability of gastric surface cells, along with the concurrent measurement of mucus gel thickness, mucosal blood flow, and acid secretory rate. We have modified an in vivo microscopy technique so as to measure phi with fluorescein dyes and blood flow with laser-Doppler flowmetry. Thus far, we have shown that gastric surface cells transiently acidify in response to acid, with spontaneous recovery of pHi when luminal pH is 3 or more. We have found that, in the presence of i.v. pentagastrin, or oral isoproterenol or prostaglandins, that a hyperemic response to luminal acid is present. This hyperemic response is of interest in that it is the first time such an acid-related change in gastric mucosal blood flow has been observed in the absence of barrier disruption. It i likely that this hyperemic response is due to the direct stimulation of CGRP-containing primary afferent nerves by acid. It was found that inducing acid secretion with pentagastrin increased mucosal defenses, suggesting that the defensive 'readiness' of the gastric mucosa is matched to the acid secretory state of the stomach. We are currently elucidating the signals which signal these changes in the stomach's defenses. For example, we are currently testing the hypothesis that pentagastrin-related defensive enhancements may result at least partially from histamine release rather than from pentagastrin itself. Histamine in turn may have direct effects on blood flow, mucus secretion as well as its known effect on acid secretion. These physiological changes could then act in concert to improve the ability of the surface cells to resist luminal acid, which could translate into the clinical finding of increased resistance to ulcer disease. Most recently, we have evaluated the effect of bismuth compounds on gastric mucosal defenses, and are engaged at preliminary studies of esophageal defense mechanisms. It is hoped that these studies will eventually lead to an improved understanding of the integration of gastric defenses, which in turn may serve as a basis for the design of interventions which would enhance intrinsic gastric defenses to acid. My clinical activities consist of attending on the medical and GI consult services at the VA.