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| |  DG DISPATCH - DDW: Cutting Reflux At The Source By Andrew Bowser Special to DG News ORLANDO, FL -- May 18, 1999 -- Gastroesophageal reflux sufferers may have a new ally in the form of baclofen, a gamma-amino butyric acid (GABA)B agonist approved in the United States for the treatment of spasticity. Researchers with Royal Adelaide Hospital in Adelaide, Australia have tested the drug in 20 healthy volunteers given either 40 mg of baclofen orally or placebo on two separate days at least one week apart. The findings were presented at Digestive Diseases Week (DDW) in Orlando, FL. The drugs were taken approximately 90 minutes before a meal and the patients sat upright for three hours. The number of reflux episodes decreased by 70 percent, from 1.0 to 0.3 per hour over the course of three hours, but no reduction was observed on esophageal acid pressure or acid clearance time. Additionally, baclofen decreased the rate of transient lower esophageal sphincter (LES) relaxations -- the major mechanism of gastroesophageal reflux for most patients. The exact mechanism of action remains to be elucidated, but researchers at DDW said it seems plausible that GABAB receptor agonists inhibit transient LES relaxations. Even if baclofen became an accepted treatment for gastroesophageal reflux, a small proportion of patients would not benefit: those who reflux predominantly due to absent basal lower esophageal sphincter pressure. Male Sex Hormones May Protect Against Irritable Bowel Syndrome Observations over the past few years have led researchers to suggest female sex hormones play a role in irritable bowel syndrome (IBS). Now there is some evidence that male sex hormones may also be important. A research project described as a shot in the dark yielded the finding that male patients with IBS had significantly lower plasma levels of luteinizing hormone (LH) compared to healthy volunteer control subjects. Somewhat paradoxically, the level of testosterone and free testosterone in male IBS patients was negatively correlated with the patients' rectal discomfort threshold to balloon distension. The research was presented at DDW by Dr. Lesley Houghton, associate professor with the University Hospital of South Manchester. The finding that more normalised testosterone correlated with increased visceral sensitivity couldn't be explained, the researcher said, but was reproducible. The researcher also stopped short of recommending follow-up clinical studies of hormonal injections for male IBS patients with low testosterone, saying the two related but somewhat divergent findings illustrated the need for further investigation. "We need to firm up these data and see where we go from there," she said. Fewer Ulcers With Rofecoxib More evidence that selective cyclooxygenase (COX)-2 inhibitors may cause less negative sequelae than traditional non-selective non-steroidal anti-inflammatory agents (NSAIDs): gastroduodenal ulcer incidence in osteoarthritis patient groups treated with the COX-2 inhibitor rofecoxib was up five times less than in patients treated with ibuprofen, according to research presented yesterday at DDW. Dr. Loren Laine of the University of Southern California School of Medicine, Los Angeles, CA. reported on two identical six-month double blind, randomised trials, both comparing incidence of gastroduodenal ulcers in 1,516 osteoarthritis patients treated with placebo, ibuprofen or rofecoxib in 25 mg or 50 mg doses. At 12 weeks, the cumulative incidence of ulcers at least 3 mm in size was 28.5 percent for patients taking ibuprofen, compared with 8.1 percent for patients taking the high dose of rofecoxib and 4.7 percent for patients taking the low dose. Patients on placebo had an incidence of 7.3 percent, considered comparable to rofecoxib. At 24 weeks, ulcer incidence was 46.4 percent for the ibuprofen group, compared to 9.7 percent for high-dose rofecoxib and 13.5 percent for low-dose rofecoxib. A significantly greater number of erosions-of minimal clinical significance but yet another marker of gross gastrointestinal injury-were seen in the ibuprofen group as compared to the rofecoxib-treated group. Rofecoxib is currently under study to see how it impacts clinically-important ulcers -- the ones which bring people to the doctor's office. The results should be available in one to two years.
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