GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist,slows colonic transit in healthy man

The newly recognized class of 5-hydroxytryptamine receptors (5HT₃) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT₃ receptors are present on enteric neurons, and 5HT₃ blockers may produce mild constipation; we thus hypothesized that 5HT₃ receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT₃ antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18–70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P<0.0005). Transit times through the left colon (P<0.0005) and rectosigmoid (P<0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P<0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug. We conclude that 5HT₃ receptors may be involved in the regulation of colonic transit in healthy man.Supported in part by a grant from Glaxo Group Research, Ltd., and the Mayo Digestive Disease Center (grant DK34988, National Institutes of Health, Bethesda, Maryland).Presented, in part, at the American Motility Socicty in October 1988, and published as an abstract inGastroenterology 95:891, 1988.     

Management of recurrent ventricular tachyarrhythmias associated with Q-T prolongation

Eleven patients with acquired prolongation of the Q-Tc interval and recurrent ventricular tachyarrhythmias were studied. Five patients required 5 to 44 direct current shocks to correct prolonged ventricular tachyarrhythmias, and five were given at least two antiarrhythmic agents in an attempt to control the arrhythmias. In 4 of the 11 patients, when thioridazine, diuretic drugs and antiarrhythmic agents were withdrawn and hypokalemia or hypocalcemia corrected, ventricular tachyarrhythmias did not recur. The Q-Tc interval normalized in 2 to 3 days. Ventricular tachyarrhythmias were recurrent in the remaining seven patients, despite withdrawal of the drugs that caused the Q-Tc prolongation, attempted correction of hypokalemia when present and the administration of antiarrhythmic agents to four of the seven. All antiarrhythmic agents were then withdrawn in this group.

Immediately on the establishment of overdrive ventricular or atrioventricular sequential pacing in these patients, ventricular tachyarrhythmias were abolished. No breakthrough ventricular tachyarrhythmias occurred during temporary pacing. Temporary pacing was required for an average of 10 days and the Q-Tc interval normalized an average of 5 days from the onset of pacing. Three patients required a permanent pacemaker, one because of chronic complete heart block, one because of the sick sinus syndrome, and one because of frequent ventricular ectopic complexes complicating ischemic heart disease. All 11 patients survived their period of hospitalization.     

Esophageal tamponade in the management of acute variceal hemorrhage

Over a seven-year period, 138 patients with portal hypertension presented on 223 occasions with endoscopically proven acute variceal hemorrhage. Hemorrhage ceased spontaneously on 92 occasions (41%). On 126 occasions (57%) passage of the four-lumen modification of the Sengstaken-Blakemore tube was required, and hemorrhage was successfully controlled in 98%. Intubation was refused on five occasions (2%). Hemorrhage recurred during these 223 admissions on 47 occasions (21%); on 11 occasions a second rebleed occurred and on two occasions, a third. Tamponade was required during all of these rebleeds and arrest of hemorrhage was achieved in 87%. Hemorrhage in patients with poorer modified Child's grade was less likely to cease with intubation. The overall rate of control in the 186 episodes of hemorrhage requiring tamponade was 94%. There were 28 complications attributed to the use of tamponade in 186 episodes of hemorrhage (15%). On 12 occasions these complications proved fatal (6.4%). In four further patients failure of tamponade to control hemorrhage was fatal.     

Discriminant analysis of data in ulcer and nonulcer populations

The purpose of this study was to assess whether consideration of age and body weight measurements improved discrimination between normal subjects and duodenal ulcer subjects using the maximal acid output test. Seventy-seven male volunteers were the normal group, and 155 patients with surgically proven duodenal ulcers were the ulcer group. We found that the ratio of maximal acid output to actual weight gave the best discrimination between the two groups. Using this ratio, there were 45 hypersecretors in the ulcer group, and only 1 false-positive among the normal subjects. A graphic method is described which employs the ratio of acid to weight and can correctly classify two-thirds of the ulcer group. The disadvantage of this method, however, is that one-third of the control group in our series were misclassified as hypersecretors; therefore, the clinician must consider history and barium meal findings as well as this evaluation of the subject.Deceased.     

Percutaneous treatment of a popliteal bifurcation—The value of coronary devices and strategies

In this case report, we describe the use of coronary techniques and devices in the treatment of a complex popliteal artery bifurcation. In particular, we demonstrate that the Venture? wire control catheter is a useful tool not only in coronary lesions but also in wiring angulated peripheral lesions. © 2008 Wiley‐Liss, Inc.