Review article: acid suppression in non-variceal acute upper gastrointestinal bleeding.

Despite a decreased incidence of ulcer disease and improvements in the management of acute upper gastrointestinal (GI) bleeding, mortality remains at about 6-7%. Although endoscopic haemostatic therapy has been demonstrated to be the mainstay of management, the search continues for less invasive medical modalities that might also improve patient outcome. In vitro data have indicated the important role of acid in impairing haemostasis and causing clot digestion. Therefore, theoretically, maintenance of a high intragastric pH (above 6.0) during management of upper GI bleeding is warranted. Until recently, available agents did not permit such a sustained elevation in gastric pH. Early studies with H2-receptor antagonists have not demonstrated significant improvements in important patient outcomes, such as rebleeding, surgery or mortality. With the availability of intravenous formulations of proton pump inhibitors, it is now possible to aim at maintaining gastric pH above 6.0 for 24 h per day. Recent clinical trial data would appear to support the use of proton pump inhibitors to decrease the rate of rebleeding and the need for surgery. This paper provides a review of non-variceal acute GI bleeding, with special reference to the role of proton pump inhibitors in this clinical setting.

One-week triple therapy with esomeprazole provides effective eradication of Helicobacter pylori in duodenal ulcer disease.

BACKGROUND: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases. METHODS: Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication. RESULTS: Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%). Between-group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy. CONCLUSIONS: Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease.

The Second Canadian Consensus Conference on the Management of Patients with Gastroesophageal Reflux Disease (GERD) was organized by the Canadian Association of Gastroenterology to address major advances in the understanding of the pathophysiology of GERD, to review the new methods of investigation and therapy introduced since the first conference in 1992 and to examine the issue of relevant health economics. The changes that have taken place over the past four years have been sufficiently dramatic to necessitate reassessment of the recommendations made following the first conference. The second conference dealt with the investigation and treatment of uncomplicated GERD and the complex issues of esophageal and extraesophageal complications such as chest pain, Barrett's esophagus, and reflux-related pulmonary and laryngeal disorders. The role of laparoscopic surgery was also discussed. A decision tree for investigation and treatment of patients with GERD was developed. The 38 participants represented a broad spectrum of experience, location of practice and special interests. The distribution of participants conformed to the recommendations of the Canadian Medical Association guidelines for consensus documents in that there should be input from all possible interested parties. A list of the state-of-the-art lectures presented during the conference, the small group sessions, the session chairpersons and participants are appended to this document. CONCLUSIONS. UNCOMPLICATED GERD: GERD with alarm symptoms must be investigated immediately. There was no consensus about when to investigate uncomplicated GERD, ie, whether to perform endoscopy immediately or after initial therapy fails. There was controversy regarding 'step up' (H2 receptor antagonist [H2RA] or prokinetic [PK] first therapy) versus 'step down' therapy (proton pump inhibitor [PPI] first therapy). The majority decision was for short term 'step up' therapy and investigation if symptoms do not improve or recur. Maintenance therapy should be carried out with the initial therapy that was effective. H2RAs and PKs may suffice for maintenance therapy in milder GERD; however, for severe esophagitis, PPIs should be used. SURGERY: Indications for laparoscopic surgery should be the same as for conventional antireflux operations. NONCARDIAC ANGINA-LIKE CHEST PAIN: After exclusion of nonesophageal causes, the majority decided that eight weeks of therapy with a PPI should be performed, while some suggested work-up before a therapeutic test. In the absence of response or recurrence, esophagogastroduodenoscopy (EGD) and, depending on the circumstances, 24 h ambulatory pH/motility may be indicated. BARRETT'S ESOPHAGUS: Only patients who, in case of future discovery of cancer or dysplasia, are able or willing to undergo therapy should have surveillance. In the absence of dysplasia EGD should be performed every two years, and in the presence of mild dysplasia every three to six months. All agreed that for severe dysplasia, esophagectomy or poor risk patients, esophageal mucosal ablation is indicated. ESTRAESOPHAGEAL COMPLICATONS (EECs): Asthma, chronic cough and posterior laryngitis were considered EECs. Although PPIs may decrease symptoms, improvement alone is not diagnostic of the presence of EEC. Ambulatory pH studies with two pH probes or ambulatory pH/motility may be useful in establishing causation. HEALTH ECONOMICS: There are limited data for an economic comparison among the different drugs or between medical and surgical therapy.

The echogenic echinococcal cyst. A diagnostic trap.

Two patients with echogenic solid echinococcal cysts of the liver are reported. The literature of this unusual form of echinococcal liver disease is reviewed.

Changes in body temperature produced by prostaglandins and pyrogens in the chicken.

Bacterial pyrogen from S. abortus equi (SAE) was injected into the wing veins of chickens. Following injection of 0.05-0.5 mug SAE, body temperatures did not change significantly, whereas 2.0 or 10 mug of pyrogen caused falls in body temperature of 0.56 +/- 0.10degrees C and 1.1 +/- 0.21degrees C (mean +/- SE, n=5). The temperature falls were accompanied by a flushing of the comb and an increase in respiratory rate and were not antagonized by 1.0 g of acetylsalicylic acid (ASA) given orally. The injection of SAE (0.1 mug in 1 mul) into the anterior hypothalamus produced fevers averaging 1.24 +/- 0.07 degrees C (n=9) which were antagonized by oral ASA. Injections of SAE at other brainstem loci produced no temperatur changes. Seven chickens were also injected with 0.1 mug PGE in 1.0 mul into the anterior hypothalamus, and they developed fevers averaging 0.90 +/- 0.16 degrees C. The results support the concept that prostaglandins may be involved in fever in chickens but suggest that the action of pyrogen injected intravenously may be different from that following its injection directly into the hypothalamus.

Adding once-daily omeprazole 20 mg to metronidazole/amoxicillin treatment for Helicobacter pylori gastritis: a randomized, double-blind trial showing the importance of metronidazole resistance.

OBJECTIVE: We compared the Helicobacter pylori eradication rate after a 14-day treatment with amoxicillin 500 mg t.i.d. and metronidazole 500 mg t.i.d. with or without omeprazole 20 mg once daily. METHODS: This was a randomized, controlled trial in which omeprazole was given in double-blind fashion. Patients with H. pylori-associated gastritis were enrolled in four centers in Canada from July 1991 to January 1994. Eradication of H. pylori was assessed by histological evaluation and culture of endoscopic biopsies obtained from the antrum and corpus of the stomach. RESULTS: The H. pylori eradication rate was 73% (33 of 45) in the omeprazole-amoxicillin-metronidazole group, compared with 66% (31 of 47) in the amoxicillin-metronidazole group. This 7% difference was not statistically significant (p = 0.43, 95% confidence interval for difference -11% to 26%). Metronidazole primary resistance in the prestudy cultures was found more frequently in the omeprazole-amoxicillin-metronidazole group than in the amoxicillin-metronidazole group. Resistance to metronidazole was an important predictor of treatment failure. The H. pylori eradication rate was 61% (19 of 31) for patients infected with metronidazole-resistant H. pylori strains, compared with 91% (30 of 33) eradication for those infected with metronidazole-sensitive strains (p < 0.01). Vaginal candidiasis was reported in four patients. CONCLUSIONS: The H. pylori eradication rate was higher (73%) for omeprazole-amoxicillin-metronidazole than for the dual antibiotic therapy given without omeprazole (66%); however, this difference was not statistically significant. Metronidazole resistance significantly reduces H. pylori eradication rates.