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The objective of this study was to endoscopically assess in healthy subjects the gastrointestinal effects of over-the-counter (OTC) doses of ketoprofen. Ketoprofen is a potent nonsteroidal antiinflammatory agent (NSAID) recently approved for OTC use as an analgesic/antipyretic at doses of 75 mg versus the usual dose ofor = 300 mg daily. In epidemiological studies, ketoprofen at prescription doses has consistently been in the higher relative risk group of NSAIDs in the occurrence of gastrointestinal complications of therapy. The gastrointestinal effects of the OTC (US) dose of ketoprofen have not been reported.In a randomized, double blind, three way crossover study, 24 healthy subjects received 7 days of therapy with ketoprofen 75 mg/day, acetaminophen 4000 mg/day, and placebo. Gastroduodenal endoscopy was performed before and at the end of each treatment period. The condition of the mucosa was graded compositely for the gastric antrum, fundus, body, and duodenum.Significantly more frequent and severe gastric mucosal injury was observed after dosing with ketoprofen compared with acetaminophen (p = 0.0001). The acetaminophen group showed no difference from placebo (p = 0.8783). Two subjects developed frank gastric ulcers with ketoprofen therapy. Marginally more frequent (p = 0.0703) and significantly more severe (p = 0.0117) duodenal mucosal injury was seen. No significant differences were observed between treatment groups with respect to subjective symptoms of gastric discomfort or adverse events.These results indicate that even at lower (OTC) doses (75 mg/day) ketoprofen is associated with significant gastrointestinal irritation.

Thirty-five healthy adults were randomized to receive either: (1) ibuprofen 800 mg tablets; (2) ibuprofen 800 mg aqueous suspension; (3) ibuprofen 800 mg orange juice suspension; or (3) 325 mg aspirin tablets. All treatments were tid for 7 days. Pharmacokinetic sampling was conducted on days 1, 4 and 8. Gastroduodenoscopy was performed on days 1 and 8. Side effects and safety laboratory tests were monitored throughout the study. On day 8 the aspirin group showed significantly more gastric irritation than all of the ibuprofen groups (P less than .005). Both ibuprofen suspension groups showed more gastric irritation than the ibuprofen tablet group (P less than .1). The duodenal scores did not differ among the treatment groups. The aspirin group experienced a higher rate of tinnitus and abdominal pain. The rate and extent of absorption of the ibuprofen suspensions were significantly less than that of the tablets. These data suggest that the taking of ibuprofen as an extemporaneous suspension is therapeutically inferior to ibuprofen tablets and therefore should be discouraged.

Bisphosphonates are effective treatments for osteoporosis. Since some primary amino bisphosphonates are associated with oesophageal injury, we conducted a study of the upper gastrointestinal effects of risedronate, a pyridinyl bisphosphonate.Healthy, postmenopausal women received risedronate 5 mg (n=26), aspirin 2600 mg (n=27), or placebo (n=27) daily for 14 days and underwent endoscopy at baseline, Day 8 and Day 15.Oesophageal erosions were noted in one subject in the aspirin group, two in the placebo group, and none in the risedronate group, and an ulcer in one aspirin-treated subject. Gastric erosions and ulcers were observed most frequently in the aspirin group. Gastric ulcers were noted in eight subjects in the aspirin group, one in the placebo group, and none in the risedronate group (P=0.010, placebo vs. aspirin; P=0.002, risedronate vs. aspirin). Duodenal erosions and ulcers were observed in the aspirin group only. Gastroduodenal erosion scores of three or more occurred more frequently in the aspirin than in the risedronate and placebo groups (P0.001).Risedronate 5 mg was not associated with oesophageal or gastroduodenal ulcers in healthy, postmenopausal women, a population representative of patients who will receive risedronate in the clinical setting.

Compared with currently available NSAIDs (which inhibit COX-1 and COX-2 isoforms of cyclooxygenase), MK-0966 (a specific COX-2 inhibitor) is expected to cause less gastrointestinal toxicity.To compare the effect on the upper gastrointestinal mucosae of a high dose of MK-0966 with that of conventional doses of ibuprofen and aspirin.Healthy subjects (n = 170; age range 18-54 years) with endoscopically normal gastric and duodenal mucosa were randomized to either MK-0966 250 mg q.d. (n = 51), ibuprofen 800 mg t.d.s. (n = 51), aspirin 650 mg q.d.s. (n = 17), or placebo (n = 51) in this 7-day, double-blind, parallel-group study. The mucosae were evaluated by endoscopy using a predefined scale; scores could range from 0 to 4. The primary end-point was the percentage of subjects who developed a mucosal score/= 2 (i.e. the development of one or more erosions). To evaluate COX-1 activity, serum thromboxane B2 levels were determined in a subset of the population.The percentage of subjects who developed a mucosal score/= 2 in the MK-0966 group (12%) was significantly lower (P0.001) than that in the ibuprofen (71%) and aspirin (94%) groups, and was similar to that in the placebo group (8%). Only ibuprofen and aspirin significantly (P0.0001) reduced baseline thromboxane B2 levels. All treatments were generally well tolerated.In this acute short-term endoscopic study, MK-0966 250 mg q.d. (a dose at least 10 times higher than that demonstrated to reduce the signs and symptoms of osteoarthritis) produced significantly less gastrointestinal mucosal damage than either ibuprofen 800 mg t.d.s. or aspirin 650 mg q.d.s. and was comparable to placebo in this regard.

To investigate the efficacy and safety of SC-58635 (celecoxib), an antiinflammatory and analgesic agent that acts by selective cyclooxygenase 2 (COX-2) inhibition and is not expected to cause the typical gastrointestinal (GI), renal, and platelet-related side effects associated with inhibition of the COX-1 enzyme.Four phase II trials were performed: a 2-week osteoarthritis efficacy trial, a 4-week rheumatoid arthritis efficacy trial, a 1-week endoscopic study of GI mucosal effects, and a 1-week study of effects on platelet function.The 2 arthritis trials identified SC-58635 dosage levels that were consistently effective in treating the signs and symptoms of arthritis and were distinguished from placebo on standard arthritis scales. In the upper GI endoscopy study, 19% of subjects receiving naproxen (6 of 32) developed gastric ulcers, whereas no ulcers occurred in subjects receiving SC-58635 or placebo. The study of platelet effects revealed no meaningful effect of SC-58635 on platelet aggregation or thromboxane B2 levels, whereas aspirin caused significant decreases in 2 of 3 platelet aggregation measures and thromboxane B2 levels. In all 4 trials, SC-58635 was well tolerated, with a safety profile similar to that of placebo.SC-58635 achieves analgesic and antiinflammatory efficacy in arthritis through selective COX-2 inhibition, without showing any evidence of 2 of the toxic effects of COX-1 inhibition associated with nonsteroidal antiinflammatory drugs.

The American College of Gastroenterology (ACG) Institute for Clinical Research and Education conducted a survey study to assess demographics, management strategies, and outcome for patients with gastrointestinal bleeding. This pilot project was intended to determine the feasibility of surveying the ACG membership about common clinical issues.Color-coded survey forms were sent to all ACG members and Fellows, with instructions to supply information about demographics, presenting symptoms, management, and outcome for bleeding patients and procedure-matched controls. Forms returned between June 1 and August 31, 1995, were tabulated and analyzed for differences between the bleeding group and procedure-matched controls.A total of 1235 forms were returned by respondents, 60% of whom were in private practice. Patient demographics indicated that bleeding patients were significantly older, more likely to be male, and more likely to use alcohol, tobacco, and prescription or over-the-counter aspirin or nonsteroidal anti-inflammatory drugs and anticoagulants than were controls. Upper GI bleeding accounted for 76% of bleeding events, with duodenal and gastric ulcers being the source in more than 50% of the upper GI bleeders. Diverticula was the most common bleeding source identified in lower GI bleeders. In the bleeding group, 78.8% were anemic, with 60.9% having hemoglobin of10 g/dl; 31% presented with orthostatic changes in blood pressure or shock. Most bleeding subjects, regardless of source, were hospitalized, 58.2% received blood transfusions, and 45.5% received endoscopic therapy. Rebleeding (11.2%), need for surgery (7.1%), and fatalities (2.1%) were uncommon. Over-the-counter aspirin and nonsteroidal anti-inflammatory drugs were used significantly more often in the bleeding population (47.6%) than in controls (19.4%).The success of the GI Bleeding Registry supports the feasibility of surveying ACG members about common clinical problems. Data suggest that ACG members manage sick patients with severe gastrointestinal bleeding who require hospitalization, transfusions, and endoscopic treatment. These preliminary results will serve as an impetus to conduct further survey studies of gastrointestinal bleeding and other common digestive disease conditions.

The linkage between gastroduodenal mucosal injury and nonsteroidal anti-inflammatory drugs (NSAIDs) is now well established. Fifteen percent to 20% of patients taking these agents develop gastric or duodenal ulcer, and about 3% of this group goes on to experience hemorrhage or perforation. Gastrointestinal (GI) complications occur primarily in certain high risk groups, notably elderly female patients and patients with a prior history of peptic ulcer or GI bleeding. Recently, two new NSAIDs, nabumetone and etodolac, which are reportedly safer because they selectively inhibit prostaglandin synthesis in target tissues but spare that in the stomach, have been introduced in the United States. Further, data from clinical trials of oxaprozin, an NSAID not yet available in the United States, indicate that this agent may have a better safety profile than older NSAIDs. A review of the literature concerning the mucosal toxicity of these three agents reveals that the overall ulceration and major complication rate is low. However, a direct comparison with older NSAIDS in a large group of patients in a dose with similar efficacy is lacking.

Numerous studies have shown that higher doses of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with increased levels of mucosal injury and ulceration in both normal volunteers and patients. The present dose-ranging study was designed to determine whether escalating doses of a commonly prescribed NSAID, flurbiprofen, when expressed as mg/kg dosages, were associated with increased mucosal injury and ulceration. Subjects received either the recommended dose of 300 mg/day of flurbiprofen (N = 10), or the higher than recommended doses of 400 mg/day (N = 20) and 500 mg/day (N = 10), for a period of 7 days. Endoscopic examination was performed on day 0 and day 7, and the stomach was evaluated on day 7 for mucosal injury on a 0-4 scale, and for the presence or absence of ulcer. One gastric ulcer was seen in each of the 300- and 400-mg groups. However, in the 500 mg/day group, four gastric ulcers were seen (40%) (p = 0.04). Three of the six subjects developing gastric ulcer were of a fairly low body weight (two women, one man), and when the data were analyzed on a mg/kg basis, all six ulcers occurred in 19 of the 40 subjects receiving5.95 mg/kg, whereas no gastric ulcers were seen in the 21 subjects receiving dosages below that level (p0.01). These data suggest that, at least for this agent, a threshold level may exist above which gastric ulcers are much more likely to occur. This may in part explain why elderly debilitated, low-body-weight female patients are more prone to NSAID-related gastric ulcer.

This multicenter randomized, double-blind, 4-wk study compared the new H2-receptor antagonistic roxatidine (R) to placebo (P) for treatment of endoscopically diagnosed active duodenal ulcer disease. Subjects were evaluated after 2 and 4 wk of treatment. Those whose ulcer was unhealed at 2 wk received 2 more weeks of treatment before final evaluation. Ulcer healing (endoscopically determined) with roxatidine was more effective than placebo at both wk 0-2 (R = 33.9%, P = 21.9%, p = 0.018) and wk 2-4 (R = 68.2%, P = 29.7%, p less than 0.001), with an overall 4-wk effectiveness of 78.9% compared to 44.8% (p less than 0.001). At the end of treatment, average maximum ulcer diameter diminished 83% in R and 50% in P (p less than 0.001). Roxatidine was also more effective than placebo in decreasing abdominal pain (p less than 0.001), decreasing the number of antacid tablets taken for pain relief (p less than 0.001), improving dyspeptic symptoms (p less than 0.001), and permitting return to a normal routine for subjects with previous illness-imposed restrictions on work and/or other daily activities. The profile of laboratory values and adverse experiences demonstrated roxatidine to be safe and well-tolerated. The efficacy of roxatidine as evaluated by the healing rate of duodenal ulcer and reduction in abdominal pain emphasize its value as an addition to the family of H2-receptor antagonists.

Ninety-one normal, healthy volunteers participated in a single-center, double-blind, placebo-controlled, randomized, parallel group study: 1) to compare the prostaglandin E1 analog, misoprostol, given at a dose of 200 micrograms bid, with the recommended dose of 200 micrograms qid in protecting the gastroduodenal mucosa against injury due to anti-inflammatory doses of aspirin (3900 mg/day); and 2) to determine whether the reduced dose was associated with a lesser incidence of gastrointestinal (GI) side effects, particularly diarrhea. All subjects received 975 mg of aspirin qid with meals and at bedtime. They were concurrently administered either misoprostol 200 micrograms qid, misoprostol 200 micrograms bid and placebo bid, or placebo qid. All subjects were endoscopically normal at the onset of the study and were re-endoscoped on the morning of the 7th day of therapy, 2 h after the morning dose of medications. Gastric and duodenal mucosa were assessed separately on a 0-7 scale which gave a greater weight to erosions than to hemorrhages. GI symptoms, especially bowel habits, were assessed by means of diary cards. Subjects in both misoprostol groups had significantly less gastric and duodenal mucosal injury than subjects who received placebo (p less than 0.007 for each pairwise comparison). There was no statistically significant difference between the two misoprostol groups (p less than 0.093). Subjects in the misoprostol 200 micrograms qid group had significantly more loose and watery bowel movements than the subjects in the misoprostol 200 micrograms bid group (p less than 0.013), whereas there were no significant differences in bowel habits between the misoprostol 200 micrograms bid and placebo groups (p less than 0.122). More subjects in the misoprostol 200 micrograms qid group reported abdominal pain, loose stools, watery stools, flatulence, dyspepsia, and nausea than in the misoprostol 200 micrograms bid and placebo groups. In conclusion, the adverse events in the misoprostol 200 micrograms bid group were not significantly different from those in the placebo group, and were significantly better than in the misoprostol 200 micrograms qid group. The lower dose retained mucosal protective activity that was statistically indistinguishable from that of misoprostol 200 micrograms qid.

This study asked whether Helicobactor pylori infection accentuated the severity of NSAID-induced mucosal injury of the stomach or duodenum. We evaluated the severity of acute mucosal injury and H. pylori status in 61 normal volunteers (ages 22-43 yr) receiving naproxen (1000 mg, n = 30) or aspirin (3900 mg, n = 31) daily for 7 days. NSAID-induced gastric and duodenal mucosa each were endoscopically graded separately for hemorrhages and erosions-ulcers on a scale of 0 to 4. H. pylori infection was identified by a sensitive and specific ELISA. Nine of the 30 subjects in the naproxen group and 12 of the 31 subjects in the aspirin group were H. pylori positive (p = NS). There was no statistically significant difference between the frequency of mucosal hemorrhage in those with and those without H. pylori infection (44% compared with 33% for those receiving naproxen and 90% of those receiving ASA, p = NS for each). There were also no differences in the frequency or severity of erosive mucosal injury seen, e.g., acute ulcers were found in 16.5% and 17.5% of infected and uninfected subjects, respectively. We conclude that the presence of H. pylori infection does not influence the degree or type of mucosal damage associated with the acute administration of naproxen or aspirin.

This 7-day, single blind, randomized endoscopic tolerance study compared daily doses of 100, 150 and 200 mg flurbiprofen with 2600 mg aspirin. After seven days the flurbiprofen 100 and 150 mg groups had significantly less gastric irritation than the flurbiprofen 200 mg and aspirin groups. Flurbiprofen showed a linear dose-response relationship with respect to gastric injury and serum drug levels. Four subjects each on aspirin and flurbiprofen with the most severe injuries continued on their medications plus cimetidine and antacids for four more weeks. Both drug groups showed clinical improvement in the gastroduodenal area. In conclusion, flurbiprofen and aspirin therapy can be tolerated in the presence of gastroduodenal irritation by concomitantly administering cimetidine and antacids.

All gastric ulcers diagnosed during the period November, 1969-May, 1974, were prospectively evaluated by roentgenography, fiberoptic gastroscopy, directed biopsy, and brush cytology. Gastroscopy was performed routinely in patients with radiologic diagnosis of gastric ulcer or questionable findings, and in symptomatic individuals with negative roentgenograms. A total of 123/142 ulcers, 109 benign, 14 malignant, were available for complete follow-up. Gastroscopy was correct in 106 of 109 benign ulcers visualized. Roentgenoscopy demonstrated 91 of 109, of which 7 were incorrectly called carcinoma. Gross diagnosis was correct by gastroscopy in 11 of 14 malignant ulcers. Radiology visualized 6 of 14; gross diagnosis was correct in 1 of 6 (5 called benign). Directed gastroscopic biopsy was negative for malignant changes in all 109 benign and 3 of 14 malignant ulcers. Total complete gastroscopic diagnostic failures were 4 of 123, for an overall accuracy of 96.7%. Overall roentgenographic accuracy was 70.8%.

Acetaminophen has been proposed as an agent which protects the gastric mucosa against damage induced by aspirin and other non-steroidal anti-inflammatory agents. In order to evaluate this proposal further, 45 normal human volunteers were divided into three groups (n = 15); group one received ibuprofen 2400 mg daily (600 mg qid); group two received acetaminophen 3900 mg daily (975 mg qid) and group three received both drugs at the same dosages. There was no significant difference in the mucosal injury scores noted at endoscopy between the ibuprofen and the ibuprofen-acetaminophen group. The acetaminophen group had virtually no observed mucosal injury and this was statistically significant in comparison with the other groups (p less than 0.01). We conclude that contrary to previously reported studies using single doses of aspirin, acetaminophen failed to decrease the mucosal injury seen with ibuprofen when given for a period of seven days in combination with acetaminophen.

The effect on the gastroduodenal mucosa of alcohol combined either with aspirin or ibuprofen was studied in 60 normal volunteers. The volunteers were divided into six groups comprised of 10 subjects receiving ibuprofen, placebo, or aspirin with or without alcohol. Medications consisted of 1) three 325-mg aspirin tablets, or three identical placebo tablets, 2) one 600-mg ibuprofen tablet, and 3), three ounces of 100 proof vodka diluted in 6 ounces of orange juice, or alcohol placebo made by diluting 3 ounces of water in orange juice. All subjects received 4 doses over a 24-hr period and underwent endoscopic examination the following morning. The gastroduodenal mucosa was graded according to a 0 to 4 + scale. Aspirin caused considerably greater duodenal and gastric damage than did either ibuprofen or placebo. The addition of alcohol to all drugs increased the damage seen in the stomach but not to a significant degree; this effect was slightly more pronounced with ibuprofen than with placebo or aspirin and approached significance (0.1 greater than p greater than 0.05). These results are compatible with alcohol being a mild damaging agent or a potentiating agent for damage from other drugs.

Forty-five normal volunteers were divided into 3 equal groups, each receiving indomethacin or placebo once daily in he evening as a capsule or suppository for 10 days. The dose of indomethacin was 50 mg for the first 5 days and 100 mg for the second 5 days. Endoscopic evaluation of the gastric mucosa was carried out on days 1, 6 and 11. It was found that indomethacin capsules caused significantly more gastric irritation than indomethacin suppositories (p less than .01) or placebo (p less than .0001). No significant difference was found in the incidence of gastric injury observed in the indomethacin suppository and placebo groups.

Seventy-three upper gastrointestinal endoscopic polypectomies were performed in 63 patients over a period of five years. Thiry-eight patients (52%) had adenomatous polyps, two of which contained carcinoma in situ and 26 (36%) were inflammatory in nature. Four lesions were removed from the duodenum. Hemodynamically significant hemorrhage occurred in five cases and persistent symptomatic ulcer in three cases. All complications occurred early in the series and responded to conservative measures. There was no mortality or need for surgical intervention in any case. It was concluded that: 1. upper gastrointestinal tract endoscopic polypectomy is a safe and relatively simple procedure; 2. postprocedural complications can be markedly reduced by prophylactic conservative antiulcer therapy and 3. especially in the area of adenomatous polyps, excision of the entire lesion is superior to biopsy in the detection of early malignancy.

Unlike the clinical trials of the previous decade, those conducted during the past 10 yr have had considerable impact on current therapeutic practices in the management of disorders of the upper gastrointestinal tract. This article reviews the clinical experience from 1975 to 1985 that pertains to the effectiveness of antacids compared to placebo and other anti-ulcer medications in the prevention and treatment of duodenal and gastric ulcers, stress ulceration and acute gastrointestinal bleeding, and gastroesophageal reflux disease.

Patients who have demonstrated a gastric mucosal sensitivity to aspirin often react to other nonsteroidal, anti-inflammatory drugs to a similar or lesser degree. In a single-blind crossover study, five healthy volunteers who had previously developed erosive gastritis secondary to one week of aspirin therapy were randomly assigned to seven-day courses of treatment with ibuprofen, tolmetin and placebo. Treatment schedules were separated by washout periods to eliminate residual drug effects. Ibuprofen produced less gastric mucosal injury than tolmetin and, over all, appeared to be better tolerated. It was also noted that clinical symptoms often do not reflect the severity of gastroscopic findings, which may explain silent hemorrhaging in patients treated with agents of this type.

Studies in normal volunteers from our laboratory and by other investigators have demonstrated that non-steroidal anti-inflammatory agents (NSAIDs) can significantly damage the gastroduodenal mucosa. This damage is maximal with plain and buffered aspirin products. The injury produced by non-aspirin NSAIDs in anti-inflammatory doses is less than with aspirin but depends primarily on the dosages used. Pro-drugs and enteric-coated aspirin tend to produce less injury. The incidence of gastric ulcer in 1064 normal volunteers studied in our laboratory over a period of 7 years is reviewed. Seventy-two (6.7%) normal subjects developed a gastric ulcer after 7 days of therapy with anti-inflammatory doses of these drugs. The largest number of ulcers were seen with plain and buffered aspirin, and the lowest number with the lower anti-inflammatory doses of the non-aspirin NSAIDs.

Sucralfate is a nonsystemic drug used in the therapy of peptic ulcer disease. It is an aluminum salt of a sulfated disaccharide which adheres to ulcerated sites and forms a cytoprotective barrier to acid peptic digestion. The purposes of this study were to determine whether sucralfate had antacid activity in humans and to test the validity of the in vitro antacid qualifying test by comparing its results for tableted products with those of in vivo studies. In the in vitro antacid qualifying test Maalox #1 (4 tablets) passes and sucralfate (1 gm.) failed. These findings were consistent with the results of in vivo tests utilizing a telemetric device, the Heidelberg capsule and tube aspirations. We conclude that sucralfate does not possess antacid properties and that the results of the standard in vitro antacid qualifying test correlated well with those of in vitro studies.

Although bougienage is widely used to treat benign esophageal stricture, the rate of stricture recurrence and the long-term effectiveness of bougienage are unknown. We studied the natural history of esophageal stricture in 154 patients in whom bougienage was used as primary therapy. Dilatations were considered successful in terms of relief or major improvement of dysphagia in 84.5% of 103 patients followed 6 mo or longer (median, 26 mo). The risk of requiring esophageal dilatation after the initial episode was greatest in the first year of follow-up; thereafter, a smaller fraction of patients required dilatation each year. Forty-three percent of patients required no further dilatations, and a life-table analysis showed that 36% of patients would require no further dilatation during a projected 4-yr follow-up. The median frequency of subsequent dilatation was less than once a year. We were unable to identify any significant factors, such as initial severity of stricture, cause of stricture, presence of active esophagitis, or initial caliber of dilatation, that could predict the need for subsequent dilatation. Our results suggest that patients with benign strictures fall into two groups. In one group, the natural history was to improve or become asymptomatic after an initial series of dilatations, and only a small proportion eventually developed recurrent symptoms. The second group (46% of patients) required further dilatations to treat dysphagia during the first year of follow-up. Two-thirds of these patients needed regular dilatations in subsequent years. We conclude that bougienage is effective treatment for benign esophageal strictures, and should be utilized as primary therapy for most strictures.

The effects of fenbufen (1,000 mg a day), indomethacin (150 mg a day), naproxen (750 mg a day), and placebo on gastric mucosa were determined by endoscopy and recorded photographically. One hundred normal subjects, randomly divided into equal, parallel-treatment groups, were given the drugs in divided daily doses for seven consecutive days. The results revealed that the effects of fenbufen on gastric mucosa were significantly (p less than or equal to 0.05) less than those of either naproxen or indomethacin and not statistically different from those observed with placebo.

Ninety patients with benign esophageal stricture were treated conservatively with bougienage, antireflux, and antacid therapy. There was improvement in 79% of these patients, only 14% were unchanged, and 7% became worse. Only three patients eventually were operated upon. Bougienage was accomplished in many cases using the fiberscope as a bougie, followed by progressive dilatations with soft mercury-filled dilators. Many patients had initial dilatation with a guidewire placed through the stricture into the stomach under direct vision through the fiberscope. All patients were treated with antireflux measures and antacid subsequent to their dilatations. These measures were found to be both safe and effective in most cases. Surgery was believed to be indicated only in patients who failed to respond to these measures.

A review of the literature is presented on the gastrointestinal effects of etodolac, a new nonsteroidal anti-inflammatory drug (NSAID), as evaluated in both microbleeding and endoscopic studies. In four microbleeding studies, gastrointestinal blood loss in healthy subjects was estimated by a 51Cr-erythrocyte labeling method before drug treatment, after 7 days of treatment with NSAIDs including etodolac, and 1 week after the last day of treatment. In these 7-day studies, the gastrointestinal blood loss seen with etodolac (600 to 1200 mg/day) was similar to that seen with placebo and significantly (p less than 0.05) less than that seen with aspirin (2600 mg/day), naproxen (750 mg/day), ibuprofen (2400 mg/day), or indomethacin (200 mg/day). Naproxen, ibuprofen, and indomethacin caused mean daily blood losses in excess of 1 ml/day over baseline values. The increase with aspirin was 4 to 5 ml/day. In contrast, the greatest mean daily increase in blood loss with etodolac therapy was 0.2 ml. In a 4-week study of etodolac (600 and 1000 mg/day) and piroxicam (20 mg/day) given to patients with osteoarthritis or rheumatoid arthritis, blood loss seen with etodolac was comparable to that seen with placebo and significantly less than that seen with piroxicam. Gastrointestinal irritation was also assessed by endoscopy after 1 week of NSAID or placebo treatment. Endoscopy scores after etodolac treatment (up to 1200 mg/day) were similar to scores at baseline and after placebo and were significantly lower than scores following treatment with aspirin (3900 mg/day), indomethacin (200 mg/day), ibuprofen (2400 mg/day), or naproxen (100 mg/day). The effects of etodolac (600 or 1000 mg/day) and diclofenac (150 mg/day) were not different from each other or from baseline. These data indicate that etodolac, in these studies, did not cause clinically significant gastrointestinal microbleeding or visible gastric injury. By the criteria used in these studies, etodolac is less irritating to the gastrointestinal tract than aspirin, indomethacin, ibuprofen, naproxen, or piroxicam, and compares favorably with diclofenac.

Ibuprofen, a commonly proscribed nonsteroidal anti-inflammatory drug that is also available in many countries, including the United States, without a prescription, is known to cause hemorrhage and erosion of the gastroduodenal mucosa. This study was conducted to compare the efficacy of 200, 100, and 50 micrograms of misoprostol and placebo administered qid for 6 days, with a final dose on the morning of the 7th day, in the prevention of gastric and duodenal lesions induced by the concurrent administration of 800 mg of ibuprofen qid. A total of 120 healthy subjects with endoscopically normal gastric and duodenal mucosae were enrolled in the study. The endoscopic examination was repeated 2 h after the final dose on day 7, and the mucosae were graded on a 0 to 4+ scale. In the stomach, all three misoprostol groups were significantly more protective than placebo and did not differ significantly from each other. In the duodenum, the endoscopic scores of the 200- and 100-micrograms misoprostol groups, but not the 50-micrograms group differed significantly from placebo. The 200- and 100-microgram groups did not differ significantly from each other, but both differed from the 50-micrograms group for duodenal mucosal injury. Subjective symptoms thought to be primarily attributable to the NSAID (e.g., pain, indigestion/heartburn and nausea) were recorded by each subject in a diary. Subjects in the 200-micrograms misoprostol group attained the greatest degree of mucosal protection and had a significantly higher incidence of indigestion/heartburn and abdominal pain than the placebo group. One can conclude that misoprostol in both antisecretory (200- and 100-micrograms) and non-antisecretory (50-micrograms) doses protects the gastric mucosa from injury from high anti-inflammatory doses of ibuprofen (3200 mg/day). Only the antisecretory doses (100 and 200 micrograms qid) were effective in the duodenum, suggesting that acid suppression is necessary for mucosal protection to occur in the duodenum.

A double-blind, placebo-controlled, randomized crossover study was made of 60 patients with chronic heartburn to test the efficacy of foaming antacid in promoting symptom relief. Heartburn was induced by a meal consisting of chili, black coffee, and a spicy tomato drink mix. Of the 60 patients, 40 (67%) had relief within 15 minutes after taking foaming antacid tablets as compared to only 17 (28%) after taking a placebo. The difference in response was significant (P less than .05). Foaming antacid appears to be an effective therapy for acute postprandial heartburn.

Twenty-five normal volunteers were randomized into five equal parallel groups. Groups I received ibuprofen (2,400 mg./day); group II received tolmetin (2,000 mg./day); group III received indomethacin (150 mg./day); group IV received naproxen (750 mg./day) and group V received placebo (four tablets daily). All drugs were given on a q.i.d. basis except naproxen which was given b.i.d. The doses selected represented the manufacturer's highest recommended dosage for the treatment of arthritic disorders. A single-blind technic was used in which the investigators were unaware of which drug each volunteer was taking. Upper gastrointestinal endoscopy and photography were carried out before and after seven days of administration of each medication. Gastric and duodenal mucosal injury was graded on a 0-4 + scale. Three of the four drugs studied produced essentially equal gastric and duodenal mucosal injury with tolmetin producing the most damage followed by naproxen and indomethacin. Ibuprofen produced gastric mucosal injury equivalent to that seen with naproxen and indomethacin but no duodenal mucosal injury was seen with this drug. Extremely poor correlation was found between subjective symptomatology and endoscopic findings.

Esophageal stricture is the most frequent serious complication of reflux esophagitis. Bougienage was used as the primary therapy of benign esophageal stricture in 92 patients, followed by institution of a medical antireflux program. Response to treatment was excellent, and 78% of patients required two or fewer subsequent dilations. Twenty patients were followed up for two years or longer, and 75% did not require more than one dilation annually. Primary therapy for most patients with peptic stenosis of the esophagus is recommended to be dilation; operative therapy should be reserved for those patients in whom a malignant neoplasm is suspected or those in whom frequent and rapid stricture recurrence makes medical therapy impractical.