Stephen J. Sontag

Most asthmatics have gastroesophageal reflux with or without bronchodilator therapy.

The relationship between gastroesophageal reflux and asthma has not been clearly defined. We measured the lower esophageal sphincter pressures and studied gastroesophageal reflux patterns over 24 hours using an ambulatory Gastroreflux Recorder (Del Mar Avionics, Irvine, CA) in 44 controls and 104 consecutive adult asthmatics. The presence or absence of reflux symptoms was not used as a selection criterion for asthmatics. All asthmatics had discrete episodes of diffuse wheezing and documented reversible airway obstruction of at least 20%. Patients underwent reflux testing while receiving, if any, their usual asthmatic medications: 71.2% required chronic bronchodilators and 28.8% required no bronchodilators. Compared with controls, asthmatics had significantly decreased lower esophageal sphincter pressures, greater esophageal acid exposure times, more frequent reflux episodes, and longer clearance times in both the upright and supine positions (P less than 0.0001 for all parameters tested). There were no differences in any of the measured reflux parameters between asthmatics who required bronchodilators and those who did not. Thus, the decreased lower esophageal sphincter pressures and increased levels of acid reflux in asthmatics were not entirely caused by the effects of bronchodilator therapy. Receiver-operating characteristic analysis generated reflux values that discriminated asthmatics from controls. More than 80% of adult asthmatics have abnormal gastroesophageal reflux. We conclude that most adult asthmatics, regardless of the use of bronchodilator therapy, have abnormal gastroesophageal reflux manifested by increased reflux frequency, delayed acid clearance during the day and night, and diminished lower esophageal sphincter pressures.

Adenocarcinomas arising in tongues or short segments of Barrett's esophagus.

SummaryThe diagnosis of Barretts esophagus is established when the esophageal mucosa is lined by 2–3 cm of columnar epithelium or when specialized (intestinal type) columnar epithelium of any length is present. Emphasis is frequently placed on long segments of Barretts because these patients reportedly are at higher risk of developing adenocarcinoma than patients with shorter segments. We present four cases of adenocarcinoma that arose in tongues or short segments (less than 2 cm) of specialized columnar epithelium near the gastroesophageal junction. We emphasize the need for biopsy of minimal appearing abnormalities in this area, and we suggest that histologic subtype, rather than length of involvement, be the major criterion for establishment of Barretts esophagus.

Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: The U.S. multicenter study

Two hundred thirty patients with reflux symptoms and endoscopically proven erosive esophagitis were enrolled from 15 U.S. centers into a randomized, double-blind, dose-ranging study comparing placebo with omeprazole, 20 or 40 mg given once daily in the morning. Esophagitis grade 2 was present in 44% of patients, grade 3 in 37% of patients, and grade 4 in 19% of patients. Endpoints, defined as complete relief of heartburn and complete esophageal mucosal healing, were assessed after 4 and 8 weeks of treatment. Both omeprazole doses were significantly superior to placebo in complete endoscopic healing. After 8 weeks of treatment, 73.5% of patients in the 20-mg omeprazole group and 74.7% in the 40-mg omeprazole group, compared with 14.0% in the placebo group, had complete healing of the esophageal mucosa. At the end of the study, complete relief of daytime heartburn was obtained in 79.5% of patients in the 20-mg omeprazole group, 81.6% in the 40-mg omeprazole group, and 37.2% in the placebo group (P less than or equal to 0.05). Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05). The median time to complete relief of daytime and nighttime heartburn occurred earlier in the 40-mg group than in the 20-mg group (9 vs. 17 days and 9 vs. 20 days, respectively); however, these differences were not statistically significant. Relief of acid regurgitation and dysphagia also occurred earlier in the 40-mg group. Omeprazole was well tolerated in this group of patients. No unexpected adverse experiences occurred. The results of this study confirm those of six multicenter, international trials in which omeprazole in doses of 20-60 mg provided a degree of esophageal mucosal healing and complete relief of reflux symptoms superior to any other medical treatment.

Efficacy of misoprostol (twice daily dosage) in acute healing of duodenal ulcer. A multicenter double-blind controlled trial.

This study was undertaken to evaluate the efficacy of misoprostol taken twice daily for the healing of duodenal ulcer. Three hundred thirty patients with endoscopically proven duodenal ulcer participated in a multicenter, double-blind, controlled trial comparing placebo with misoprostol 200 μg and 400 μg twice daily for up to four weeks. Patient characteristics were similar in all three treatment groups. Ulcers were between 0.3 cm and 2.0 cm in length. Healing was determined by endoscopy at two weeks; if ulcers were not healed, endoscopy was repeated at four weeks. All patients were given Al(OH)3 antacid (up to 54 meq a day) to be used as needed for pain. Healing rates at four weeks for a total of 280 evaluable patients in the three treatment groups were as follows: misoprostol 400 μg bid, 65.4%; misoprostol 200 μg bid, 52.9%; and placebo, 42.2%. Misoprostol 400 μg bid was superior to placebo (P=0.002) in healing ulcers. However, the healing rate for misoprostol 200 μg bid did not differ significantly from placebo. The percentage of nonsmokers who healed at four weeks was higher than that of smokers in both misoprostoltreatment groups, although the difference was not analyzed for statistical significance. There were no differences in antacid consumption or pain relief among the three experimental groups during the study. Diarrhea was the most common side effect but was mild and self-limiting, occurring in 8.9%, 5.9%, and 1.8% of the misoprostol 400 μg, 200 μg, and placebo groups, respectively. These results indicate that misoprostol 400 μg, 200 μg, and for four weeks is effective and safe for the treatment of duodenal ulcers.

Prostaglandins in peptic ulcer disease: an overview of current status and future directions

SummaryNaturally occurring prostaglandins almost certainly play an important role in maintaining the integrity of the gastrointestinal mucosa. Clinical evidence available to date indicates that synthetic analogues of prostaglandins heal gastroduodenal ulcer only in doses that suppress gastric acid. However, non-antisecretory doses of prostaglandins may eventually have a role in the treatment of ulcer disease by maintaining ulcer healing and preventing recurrence. This possibility along with the potential of prostaglandins to prevent gastroduodenal mucosal injury caused by NSAIDs, alcohol, aspirin and stress, if supported by the results of ongoing clinical trials, may prove to be a major therapeutic advance for the treatment of acid peptic disease.

Large trial compares lansoprazole to omeprazole

Q LARGE TRIAL COMPARES LANSOPRAZOLE TO OMEPRAZOLE DO Castell, JE Richter, M Robinson, S Sontag. The Graduate Hospital, Philadelphia, PA; University of Alabama, Birmingham, AL; Oklahoma Foundation for Digestive Research, Oklahoma City, OK; Hines VA Hospital, Hines, IL. Lansoprazole (LAN) 30 mg and l5 mg QD were compared to omeprazole (OME) 20 mg QD and placebo (PBO) in patients with endoscopically proven erosive reflux esophagitis (RE) in a randomized, double-blind, multicenter clinical trial. Forty-four (44) investigators enrolled 1284 patients (836 males/448 females): LAN 30 rag: 422 patients, LAN 15 mg: 218 patients, OME 20 rag: 431 patients, PBO: 213 patients. Study medication was taken each day for eight weeks. Endoscopies were performed at baseline, weeks 2, 4 and 8 (and week 6 if not healed at week 2 and week 4). Results: LAN 30 mg was as effective as r~nt~ e of Ni hts with a e ~ m OME 20 mg and both were more effective ~w,,.~L ~,~,,,o~ (p 2% occurrence) were headache, diarrhea, and nausea. As expected, fasting serum gastrin levels increased significantly from baseline in all active-treatment groups; however, median fasting serum gastrin levels remained within normal limits for all treatment groups. Conclusion: LAN 30 mg QD provided faster heartburn reliefthan OME 20 mg QD and is as safe and effective as OME 20 mg QD in healing erosive RE. This research was funded by TAP Pharmaceuticals Inc., Deerfield, IL. • HP POSITIVE FUNCTIONAL DYSPEPSIA IN ELDERLY PATIENTS: COMPARISON OF TWO TREATMENTS. F. catalano, °R. Terranova, A. Brogna, G. Branciforte, R. Catanzaro, A. Liberti, C. Bentivegna, *S. Luca. Dept of Internal Medicine. Gastroenterology Unit. *Geriatric Dept. University of Catania. Italy.

Mineral-Zinc and Protein-Zinc Interactions in Man

Interaction of calcium with zinc leads to decreased zinc absorption in animals1 and parakeratosis2 due to excess dietary pytic acid3. Phosphorus intensified this effect4. In man, dairy products containing calcium and phosphorus, decrease zinc absorption5. However, in this Research Unit, a 10-fold increase in calcium intake did not decrease zinc absorption6,7. In the present study the effect of calcium, phosphorus and protein on zinc metabolism was investigated in man and the effect of zinc on the absorption of calcium and iron.

Changes in Zinc Metabolism During the Use of EDTA

Ethylenediaminetetraacetic acid, EDTA, a chelating agent with a high stability constant for lead, is commonly used for the diagnosis and treatment of pad poisoningl,2; but EDTA has also a very high stability constant for zinc and is therefore expected to bind and remove this essential trace element. In the present study the zinc loss during the use of conventional doses of EDTA for lead poisoning was determined.