Assessment of gastric electrical activity and autonomic function among diabetic and nondiabetic patients with symptoms of gastroesophageal reflux.

Gastroesophageal reflux disease (GERD) may present differently in patients with diabetes mellitus (DM) than in nondiabetics (NDM). We compared three tests in two patient groups with GERD symptoms: a DM group (n = 10) and a NDM group (n = 13). The tests were 24-hr esophageal pH, autonomic function testing (AFT), and electrogastrography (EGG). Analysis of the 23 patients revealed the DM group had normal 24-hr pH values (9 of 10 patients, mean pH 3.1 +/- 1.7), while NDM displayed abnormal pH values (9 of 13 patients, mean pH 21.2 +/- 5.9). AFT results were abnormal in DM (demonstrating cholinergic/ adrenergic dysfunction), but normal in NDM. EGG values were abnormal in both groups (mean 3.31 +/- 0.1 in each). We conclude that in GERD-symptomatic patients, those with DM frequently have normal 24-hr pH, but abnormal autonomic functioning, in contrast to NDM, who have abnormal 24-hr pH but normal autonomic function. Both groups had identically abnormal mean EGG values.

Sequential group trial to determine gastrointestinal site of absorption and systemic exposure of azathioprine.

Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different dosages of AZA into the cecum. In phase I, six healthy male volunteers received three 50 mg sequential doses of AZA via an oral tube directly placed into the stomach, jejunum, and cecum, respectively. In phase II, six healthy male volunteers received three different dosages (50, 300, 600 mg of AZA) into the cecum. Plasma concentrations of AZA and 6-MP at various times were quantified and area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were determined. No significant differences in the AUC of AZA were seen at the different sites. The AUC of 6-MP following administration of AZA into the jejunum (67.0 +/- 30.1 ng x hr/ml) was higher compared to the stomach (39.9 +/- 38.1 ng/hr/ml) and cecum (29.2 +/- 10.9 ng x hr/ml). Jejunal absorption was 68% higher than absorption from the stomach and 129% higher than that of the cecum. Gastric absorption was 27% higher than that of the cecum. Increased dosages given into the cecum resulted in increased AUCs of AZA and 6-MP. The AUCs of AZA following 50, 300, and 600 mg dosages were 16.9 +/- 7.4, 52.3 +/- 67.2, and 132 +/- 151 ng x hr/ml, respectively, and the AUCs of 6-MP were 22.2 +/- 14.9, 63.4 +/- 50.6, and 104 +/- 115 ng x hr/ml, respectively. Systemic exposure to 6-MP is reduced following administration of AZA into the cecum, most likely secondary to reduced absorption of 6-MP from the colon. Higher dosages of AZA presented to the cecum do result in increased systemic absorption, but may still allow more drug to be administered with less toxicity than the same dose received orally.

A fistula from the portal vein to the bile duct: an unusual complication of transjugular intrahepatic portosystemic shunt.

We describe a case of a portal vein bile duct fistula as a complication of transjugular intrahepatic portosystemic shunt (TIPS) placement. The patient's course was complicated by endocarditis, hemobilia, recurrent episodes of fever, and bacteremia, followed by liver transplant. The findings of fever, bacteremia (especially with Gram-negative organisms), and a decreased hematocrit after shunt placement should raise the suspicion of an infected shunt with a possible fistula.

Biliary, pancreatic, and sphincter of Oddi electrical and mechanical signals recorded during ERCP.

Measurements of biliary tract motility have focused on radiologic and pressure measurements to quantify biliary motility rather than measurements of electrical activity of the biliary tract. We previously reported the recording of biliary electrical signals during ERCP and now report on the continued development and validation of a system to measure biliary tract electrical activity as well as biliary mechanical activity. In 26 patients presenting with a variety of clinical indications, we recorded measurements of electrical activity from the common bile duct sphincter (16 patients), pancreatic duct sphincter (eight patients), and/or sphincter of Oddi (eight patients). Electrical recordings were performed with a specially modified ERCP catheter, using two circular electrodes as well as a custom catheter that measured both electrical and mechanical activity. Electrical activity of the biliary tract was successfully recorded in 25 of 26 patients (96%), including the common bile duct sphincter (16 patients, 62%), pancreatic duct sphincter (eight patients, 31%) and sphincter of Oddi (eight patients, 31%). Along with the electrical recordings, common bile duct sphincter mechanical activity was recorded in 12 patients (67%), pancreatic duct sphincter mechanical activity in six patients (33%), and sphincter of Oddi mechanical activity in six patients (33%). Frequency analysis of electrical signals revealed a mean frequency (cycles/min) of 4.7 +/- 0.5 in the common bile duct sphincter, 4.1 +/- 0.6 in the pancreatic duct sphincter, and 4.9 +/- 0.7 in the sphincter of Oddi. Phasic mechanical frequency in cycles per minute was recorded at a frequency of 4.8 +/- 0.5 in common bile duct sphincter, 4.0 +/- 0.6 in pancreatic duct sphincter, and 5.3 +/- 0.9 in sphincter of Oddi. Tonic pressure (averaged 12.1 +/- 1.5 mm Hg) in common bile duct sphincter, 12.4 +/- 1.4 mm Hg in pancreatic duct sphincter, and 15.0 +/- 5.1 mm Hg in sphincter of Oddi. Analysis of wave form propagations (noted as percentage antegrade, retrograde, or indeterminant) revealed 50% antegrade, 23% retrograde, and 27% indeterminant). One patient was recorded on two occasions via ERCP; the same patient had an intraoperative recording. All three recordings showed similarities. We conclude that measurements of biliary, pancreatic, and sphincter of Oddi electrical and mechanical activity are feasible and can be done as part of ERCP. There was good correlation between biliary tract electrical and mechanical events and different wave form characteristics were noted for different parts of the biliary tree. Further studies are warranted to evaluate the potential usefulness of measurement of biliary tract electrical activity, and to confirm its correlation with mechanical events in the pancreato-biliary tree.

Gastrointestinal motility disorders.

A careful history can localize gastrointestinal motility disorders and suggest appropriate diagnostic tests. Dysphagia, odynophagia, heartburn and reflux have esophageal origins. The same symptoms occur in achalasia, a classic motor disorder of the lower esophageal sphincter, which can be diagnosed by barium swallow, endoscopy and esophageal motility studies. Nausea, vomiting, anorexia, bloating and abdominal pain are symptoms of motor disorders of the stomach and small intestine. When these symptoms are accompanied by unexplained right upper quadrant pain, elevated liver enzyme levels and unexplained recurrent pancreatitis, the diagnosis of impaired biliary motility is suggested. Colorectal motility disorders may present as abdominal pain, diarrhea, constipation and/or fecal incontinence. If symptoms do not resolve with dietary changes and appropriate medications and the anatomy is normal on lower gastrointestinal studies, colorectal motility studies may be indicated.

Biochemical changes in the intestine associated with anoxia and reoxygenation: in vivo and in vitro studies.

In ischemia/reperfusion injury, it is hypothesized that superoxide is responsible for the component of injury due to reperfusion. The superoxide is hypothesized to result from the aerobic oxidation of purines produced by the ischemia-mediated breakdown of high-energy phosphates. This oxidation is catalyzed by xanthine oxidase proposed to be rapidly formed as a result of ischemia-mediated protease conversion from xanthine dehydrogenase. In vivo experiments with the intestine of either rats or guinea pigs were unable to confirm the rapid conversion of xanthine dehydrogenase to xanthine oxidase as a result of ischemia. In vitro experiments with isolated guinea pig enterocytes did show a significant increase in xanthine oxidase activity after these cells were first placed in an anaerobic environment for 60 min and then reoxygenated; however, the magnitude of the increase is such that the biological importance of this finding remains uncertain. Using a variety of techniques, including spin trapping, hydroxylamine oxidation, and vanadate NADPH oxidation, we explored the possibility that superoxide was produced as a result of anoxia followed by reoxygenation in the in vitro enterocyte system. From these experiments, we determined that superoxide is generated as a result of anoxia/reoxygenation. However, from xanthine oxidase inhibition experiments using pterinaldehyde, only a small percentage of the total superoxide produced comes from the action of this enzyme on purines.