Scope and specificity of acarbose in slowing carbohydrate absorption in man.

Fifty-gram carbohydrate tolerance tests were performed on healthy volunteers to test the activity and specificity of an alpha-glucoside hydrolase inhibitor, acarbose (BAY g 5421). Two hundred milligrams acarbose reduced the area under the blood glucose response curve by 89% (P less than 0.001) after sucrose by 80% (P less than 0.002) after starch, by 19% (N.S.) after maltose, with no effect on glucose. Breath hydrogen measurements indicated an almost complete malabsorption of the sucrose. At 50 mg acarbose, some reduction in blood glucose and insulin response to sucrose was still seen, but no significant hydrogen production. It is suggested that at lower doses, acarbose may prolong the time course over which carbohydrate is absorbed as does dietary fiber; as with fiber, it may be a useful adjunct to diabetic therapy.

Effect of acarbose on the 24-hour blood glucose profile and pattern of carbohydrate absorption.

Acarbose (Bay g 5421) is a powerful alpha-glucoside hydrolase inhibitor of potential value in the treatment of diabetes and hypoglycemic dumping syndrome after gastric surgery. The extent of its use may be limited by symptoms produced by carbohydrate malabsorption. To minimize these, the action of low doses of acarbose on 24-h blood glucose profiles and hydrogen evolution have been studied on four ambulant volunteers on control diets, after exclusion of sucrose and also after addition of guar in an attempt to enhance the therapeutic effect. Replacement of dietary sucrose by starch abolished significant hydrogen evolution in the morning after low doses of acarbose but did not reduce its effectiveness in decreasing the mean three-meal blood glucose area by 41% (P less than 0.002). Addition of hydrated guar to this diet reduced the mean three-meal glucose area after acarbose further by 72% (P less than 0.001) but increased hydrogen evolution. The results suggest that acarbose will be both effective and acceptable given at low dose when the dietary carbohydrate is starch.

What is new in the epidemiology and pathogenesis of peptic ulcer?

The old dictum 'no acid--no ulcer' is no longer a sufficient explanation of the pathogenesis of ulcer disease. The real question is 'if acid--why ulcer?' Although acid remains predominant, some of the other factors influencing ulcerogenesis are nocturnal acid secretion, pepsin enzyme subspecies, the mucus layer, bicarbonate levels, prostaglandins, Campylobacter pylori infection, consumption of non-steroidal anti-inflammatory drugs, and smoking habits. Although the ulcer burden has been greatly reduced by the introduction of H2-receptor antagonists, complications such as bleeding and perforation remain a problem, especially in the elderly. Medical treatment, in the form of H2-receptor antagonists, is effective for many patients.

Is oropharyngeal anaesthesia with topical lignocaine useful in upper gastrointestinal endoscopy?

The aim of this study was to determine whether patients' tolerance of upper gastrointestinal endoscopy is related to the dose of lignocaine spray used for oropharyngeal anaesthesia and to measure plasma concentrations at these doses. Sixty consecutive patients undergoing routine upper gastrointestinal endoscopy with sedation were randomized to receive lignocaine spray 50 mg (Group A), 100 mg (Group B) or 200 mg (Group C). Patient, endoscopist and endoscopy nurse were unaware of the variation in dose used. Each patient's tolerance of the intubation and of the remainder of the gastroscopy was assessed independently by the patient, endoscopy nurse, and endoscopist using a visual analogue scale. Plasma lignocaine concentration was measured at 20, 40, 60 and 80 min after administration of the spray. Fifty (83%) patients were unable to recall either the intubation, or the procedure. On the endoscopy nurse's assessment, the patients in Group B tolerated the intubation better than those in Group A, and Groups B and C tolerated the remainder of the gastroscopy better than those in Group A. On the endoscopist's assessment, Groups B and C tolerated the remainder of the gastroscopy better than Group A. There were fewer gags per min in Groups B and C compared to Group A. Mean plasma lignocaine concentrations showed a dose-dependent absorption of the spray, but none exceeded the potentially toxic level of 5 mg/L.

Oral or intravenous erythromycin has no effect on human distal colonic motility.

Erythromycin is a prokinetic agent for the lower oesophageal sphincter, the stomach, the gallbladder and the small bowel, acting directly on motilin receptors. Its effect on pressure activity of the human colon has not been investigated. Eight healthy volunteers were studied on 2 occasions and given intravenous or oral erythromycin, or placebo in a single-blind, randomized crossover study. Sigmoid pressure activity was measured using a 4-lumen water perfused system placed sigmoidoscopically at 50, 45, 30 and 15 cm from the anal verge. The pressures were analysed for activity index (mmHg.min) for the 35 cm colonic study segment using dedicated software. No significant difference was found in the activity index following oral erythromycin (500 mg) or placebo, or following intravenous erythromycin 1.8 mg/kg or placebo. A further 8 subjects were studied in a single-blind crossover study to determine the effect of oral erythromycin (500 mg) b.d. on colonic transit, measured with radio-opaque markers and a single abdominal X-ray. Mean or segmental colonic transit times were not statistically significantly different (Student's paired t-test) in the subjects on placebo or erythromycin. This lack of effect of erythromycin on the distal large intestine may indicate the absence of receptors for motilin in that part of the gut.

Eradication of Helicobacter pylori and prevention of recurrence of duodenal ulcer: a randomized, double-blind, multi-centre trial of omeprazole with or without clarithromycin.

BACKGROUND: Antimicrobial treatment for Helicobacter pylori eradication is currently recommended for all patients with duodenal ulcer disease, but consensus on the best treatment is lacking. METHODS: Patients with active duodenal ulcer and H. pylori were enrolled in a double-blind, randomized, placebo-controlled multi-centre study. Patients received omeprazole 40 mg daily for 28 days and either clarithromycin 500 mg t.d.s. or placebo t.d.s. for the first 14 days. Patients underwent endoscopy before starting treatment, at 2 weeks, immediately after stopping treatment if unhealed at 2 weeks, and at 1, 6 and 12 months after the end of treatment, or at the recurrence of symptoms. Eradication of H. pylori, duodenal ulcer healing and ulcer recurrence were measured. RESULTS: One-hundred and fifty-four patients were recruited and randomized to omeprazole plus clarithromycin (n = 74) or to omeprazole plus placebo (n = 80). One month after treatment, H. pylori was eradicated in 57 of 69 (83%; 95% CI: 72-91%) patients receiving omeprazole plus clarithromycin, compared with 1 of 75 (1%; 95% CI: 0-7%) receiving omeprazole alone (P < 0.001). In patients receiving omeprazole plus clarithromycin the ulcer healed at 2 weeks in 83% (95% CI: 71-91%) and at 4 weeks in 100% (95% CI: 95-100%), compared with 77% (95% CI: 66-86%) and 97% (95% CI: 91-100%) in those given omeprazole plus placebo (N.S.). Ulcers recurred at 12 months in 6% (95% CI: 1-16%) of patients given omeprazole plus clarithromycin, compared with 76% (95% CI: 63-86%) of patients given omeprazole plus placebo (P < 0.001). The incidence of side-effects was similar in both treatment groups (38% with clarithromycin dual therapy and 29% with omeprazole plus placebo; P = 0.304). Ninety per cent of patients took at least 90% of their prescribed medication. CONCLUSIONS: Omeprazole plus clarithromycin dual therapy eradicated H. pylori in 83% of patients with duodenal ulcer and significantly decreased 12-month recurrence from 76% to 6%.

Eradication of Helicobacter pylori with lansoprazole and clarithromycin.

BACKGROUND: Helicobacter pylori eradication with omeprazole and clarithromycin varies between 40 and 80%. The dose, frequency and duration of treatment may account for these differences. Lansoprazole, a recently introduced proton pump inhibitor, is a more potent H. pylori bacteriostat in vitro than omeprazole. The aim of this open, comparative, randomized study was to investigate the efficacy and safety of lansoprazole 30 mg once or twice a day (and for 2 vs. 4 weeks) plus clarithromycin 500 mg t.d.s. for 2 weeks. in the eradication of H. pylori. METHODS: Sixty-six patients with H. pylori infection received clarithromycin 500 mg t.d.s. for 2 weeks and one of four lansoprazole regimens: 30 mg once a day for 2 (Group 1, n = 16) or 4 (Group 2, n = 16) weeks, or 30 mg b.d. for 2 (Group 3, n = 18) or 4 (Group 4, n = 16) weeks. H. pylori eradication was determined by the 13C-urea breath test 4 weeks after finishing treatment. RESULTS: Per protocol analysis (53 patients) shows that H. pylori was eradicated in 6/13 (46%) in Group 1, 7/13 (54%) in Group 2, 9/14 (64%) in Group 3 and 9/13 (69%) in Group 4. Thirty-one of 68 patients experienced side effects. Analysis on an intention-to-treat basis gave similar results. CONCLUSION: The dose of lansoprazole appears to be more important than the duration of therapy. Dual therapy with lansoprazole and clarithromycin should be investigated further as a possible treatment regimen for H. pylori infection.

Two-week eradication regimen for metronidazole-resistant Helicobacter pylori.

At present there is no generally accepted treatment regimen for eradicating metronidazole-resistant Helicobacter pylori. This study determines the eradication rate after treatment with 40 mg omeprazole o.m. and 500 mg amoxycillin q.d.s. for 14 days, with 120 mg tripotassium dicitrato bismuthate q.d.s. for the first week (Days 1-7) and 750 mg ciprofloxacin b.d. for the second week (Days 8-14). Thirty patients (16 male, mean age 45 years, range 16-80 years) with duodenal ulcers (n = 18) or non-ulcer dyspepsia (n = 2) and metronidazole-resistant H. pylori detected by histology, culture, in vitro sensitivity tests and a positive 13C-urea breath test entered the study. Follow-up was by 13C-urea breath test at the end of treatment and at 1, 3, 6, and 12 months. Eradication was defined as a negative 13C-urea breath test at least 1 month after finishing treatment. H. pylori was successfully eradicated in 21/30 (71%) patients (median follow-up 10.2 months, range 4-12 months). A pre-treatment ciprofloxacin-resistant strain was isolated in 1/9 patients in whom eradication failed. Of 30 patients 29 completed the 2-week regimen; one patient experienced dizziness after 3 days of treatment. The most common side-effect was increased stool frequency (n = 6). This 2-week treatment regimen for metronidazole-resistant H. pylori is well tolerated and achieves an eradication rate of 70%.

Lansoprazole, clarithromycin and metronidazole for seven days in Helicobacter pylori infection.

BACKGROUND: This study determines the efficacy and safety of a 1-week triple therapy regimen of lansoprazole, clarithromycin and metronidazole in an area with a high prevalence of pre-treatment metronidazole-resistant strains of Helicobacter pylori. METHODS: Seventy-five H. pylori positive patients with gastritis or duodenal ulcer were entered into an open study of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. H. pylori status was determined by CLOtest, histology, culture and by 13C-urea breath test (repeated > or = 28 days after treatment). RESULTS: Seventy-one patients completed the treatment and returned for follow-up. H. pylori was eradicated in 61 of 71 (86%) patients by per-protocol analysis, and in 61 of 75 (81%) patients by intention-to-treat analysis. H. pylori was eradicated in 12 of 16 (75%) patients with metronidazole-resistant strains compared with 22 of 24 (92%) in patients with metronidazole-sensitive strains of H. pylori (P = 0.14). Fourty-five patients reported at least one adverse event, and three patients stopped treatment due to them (two with headaches and one with diarrhoea). CONCLUSIONS: A 1-week course of lansoprazole 30 mg o.m., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. eradicates H. pylori in up to 86% of patients. It is of proven benefit in patients with pre-treatment metronidazole-resistant strains of H. pylori.

Recurrence of duodenal ulcer after Helicobacter pylori eradication is related to high acid output.

BACKGROUND: Helicobacter pylori eradication reduces the recurrence of duodenal ulcers. It is unclear why duodenal ulcers rarely recur in the absence of reinfection with H. pylori or NSAID treatment. METHODS: Basal, gastrin-releasing peptide- and pentagastrin-stimulated peak acid outputs in patients with ulcer relapse after H. pylori eradication were measured, and compared with patients without ulcer relapse after H. pylori eradication. RESULTS: Pentagastrin-stimulated peak acid output was significantly higher in H. pylori-positive patients with duodenal ulcers than in H. pylori-negative controls, and fell significantly after H. pylori eradication. In H. pylori-negative patients with recurrent duodenal ulcers, pentagastrin-stimulated peak acid output was significantly higher than in controls and similar to H. pylori-positive patients with duodenal ulcers. CONCLUSIONS: These findings suggest that duodenal ulcer relapse after eradication of H. pylori may be related to high pentagastrin-stimulated peak acid output. In this subset of patients with duodenal ulcers, maintenance anti-secretory treatment may be necessary to prevent relapse.

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori. The Lansoprazole Helicobacter Study Group.

BACKGROUND: A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens. AIM: To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease. METHODS: Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a 13C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment. RESULTS: Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n = 262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P = 0.85, chi-squared test) with regard to the healing of duodenal ulcer disease. CONCLUSIONS: The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

Antral hypertrophic gastritis: a rare cause of iron deficiency.

A case of an unusual hypertrophic gastropathy confined to the gastric antrum which presented with chronic anaemia is described. The clinical and pathological features are contrasted with Menetrier's disease and hypersecretory hypertrophic gastropathy, and a possible relation to solitary hyperplastic (regenerative) polyps is discussed.

Parietal cells in the duodenal bulb and their relation to Helicobacter pylori infection.

AIM: To investigate the prevalence, and relation to Helicobacter pylori, of parietal cells in the duodenal bulb using a monoclonal antibody directed against H+,K(+)-ATPase (HK12.18). METHODS: Twenty six patients with duodenal ulcer disease and 16 healthy controls were studied. H pylori status was determined by gastric histology and culture and by the 13C-urea breath test. Four biopsy specimens were taken from the duodenal bulb and stained with HK12.18. The presence/absence and number of parietal cells in the duodenal bulb were assessed blindly by a histopathologist. RESULTS: The overall prevalence of parietal cells in the duodenal bulb was 31% (13/42) and was similar in patients with duodenal ulcer and in controls, and in H pylori positive and negative subjects. The median (range) number of parietal cells in the duodenal bulb was 7.5 (4-20) parietal cells/subject, and was similar in all four groups. CONCLUSIONS: The prevalence of parietal cells in the duodenal bulb (31%) is notably higher than previously reported in endoscopic studies, and is in keeping with reports from studies on necropsy/operative specimens. There was no difference in the prevalence or number of parietal cells in the duodenal bulb between patients with duodenal ulcer and controls, regardless of H pylori status. These findings suggest that parietal cells in the duodenal bulb do not contribute to the pathogenesis of duodenal ulcer.

Management of Helicobacter pylori-related disorders.

The discovery of Helicobacter pylori has opened new opportunities in the management of gastrointestinal disorders, with the cure of chronic ulcer disease now being possible for the first time. The 1994 United States National Institutes of Health Consensus Conference recommended that patients with duodenal or gastric ulcers unrelated to the use of non-steroidal anti-inflammatory drugs (NSAID) should be given eradication therapy. These guidelines were refined at a conference held recently in Maastricht. The updated guidelines strongly recommend treatment in patients with duodenal or gastric ulcer disease, low-grade mucosa-associated lymphoid tissue (MALT) gastric lymphoma, gastritis with severe macro- or microscopic changes and after resection of early gastric cancer. Despite a lack of hard scientific evidence, the guidelines also suggest that eradication treatment is advisable in patients with unequivocally diagnosed functional dyspepsia, a family history of gastric cancer, long-term treatment with proton-pump inhibitors for gastro-oesophageal reflux disease (GORD), planned or existing NSAID treatment, after gastric surgery for ulcer or cancer, or if the patient wants to be treated. Many different therapeutic regimens have been used previously, but at present the best treatment is proton-pump inhibitor-based triple therapy, comprising a proton-pump inhibitor plus two drugs out of clarithromycin, a nitroimidazole and amoxycillin. One-week low-dose triple therapy cures 85-95% of infected patients.

Motility of Helicobacter pylori in a viscous environment.

BACKGROUND: Patients with gastroduodenal disease produce gastric mucus of higher viscosity, and mucins that are of a smaller size, than normal. We have modelled these changes to the mucus layer in solutions of methylcellulose, and measured bacterial motility in biopsied mucus, to assess how they might influence the movements of Helicobacter pylori. METHODS: Motilities of Helicobacter pylori were measured in solutions of methylcellulose with molecular mass of 14 and 41 kDa, and in biopsied mucus with a Hobson BacTracker. Four parameters of bacterial motility were quantified: curvilinear velocity (CLV), path length, track linearity and curvature rate. RESULTS: All H. pylori were motile in methylcellulose solutions, and had optimal motilities at a viscosity of 3 cp (CLV in methylcellulose of 41 kDa, for instance, was 33 +/- 1.4 microm/s (mean +/- SEM) and the path length in methylcellulose of 41 kDa was 22.4 +/- 2 microm). At higher viscosities, mean CLVs, path lengths and curvature rates decreased, and track linearities increased in direct proportion to the increase in methylcellulose viscosity. Bacteria become non-motile at a viscosity of 50 cp in methylcellulose of 14 kDa, and at 70 cp in methylcellulose of 41 kDa. Mean CLVs, path lengths and curvature rates (but not track linearities) were greater in methylcellulose of 41 kDa than in methylcellulose of 14 kDa at each viscosity tested. Motilities of H. pylori from patients with duodenal ulcer or non-ulcer dyspepsia in methylcellulose solutions were not significantly different. H. pylori had poor motility in biopsied mucus, but became highly motile when biopsied mucus was diluted with saline. CONCLUSIONS: The viscosity-motility profiles of H. pylori in methylcellulose and the motilities of H. pylori in biopsied mucus suggest (1) that H. pylori may have poor motility in mucus at the epithelial surface, but high motility at the luminal surface of the mucus layer, and (2) that the increased mucus viscosity and decreased mucin size in patients with gastroduodenal disease act in combination to decrease H. pylori motility in vivo.

Investigation of ranitidine 150 mg bd or 300 mg bd in the treatment of reflux disease.

Twenty patients with symptoms and endoscopic changes of gastro-oesophageal reflux were randomly allocated to treatment with either ranitidine 150 mg bd, or 300 mg bd for 8 weeks. Symptoms, endoscopic appearances, histopathology of oesophageal biopsies and 22-h intra-oesophageal pH profile in ambulant patients on standard diets were recorded before and at the end of the treatment period. Symptoms improved rapidly and markedly on either dose of ranitidine. Both doses produced significant improvement of the endoscopic appearances, but there were no differences in symptomatic and endoscopic improvement related to the dose. Biopsy appearances and the 22-h oesophageal pH profile remained unchanged on either dose of ranitidine.

Esophagogastrectomy: a consecutive single-center series.

We present a 7-year consecutive, nonselected, single-center series of patients (n = 140) submitted to surgery for esophageal or upper gastric malignancy. Follow-up data are complete for 96.4% of patients. Of 114 intrathoracic anastomoses, 74 (65%) were esophagogastric and 40 (35%) were esophagojejunal. Unresectable lesions were present in 26 (19%) patients. Age (mean +/- sd 64.6 +/- 11.1 years), and sex distribution were similar in all groups, while 36% of patients were over 70 years. There was no significant difference in the time from the onset of symptoms to presentation between the groups (p < 0.05). The values of admission hemoglobin, serum albumin, PaO2 or peak expiratory flow rate did not correlate with survival. There was no significant difference in 30-day operative mortality between the three procedures - esophagectomy 5%, thoraco-abdominal gastrectomy 10.8% and unresectable 11.5% (p > 0.05). The incidence of respiratory complications was the same whether a right (30%) or left (35%) thoracotomy was performed. Some 33% of patients were discharged from hospital after 14 days and 72% after 21 days (12.9% died in hospital). One-year survival was 33.4% for esophagectomy, 37.5% for total gastrectomy and 6% for unresectable lesions. The esophagectomy versus total gastrectomy survival curves were not significantly different, but there was a significant survival advantage when patients undergoing esophagectomy were compared with those who had unresectable tumors (0.02 > p > 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Helicobacter pylori: past, present, and future.

Helicobacter pylori has now been recognized as one of the most common chronic human infections. It has been accepted as an important aetiologic agent in non-immune chronic gastritis and plays a key role in the aetiology of duodenal ulcer. It may also be involved in the pathogenesis of gastric cancer.

Adaptation and change in gastroenterology.

Predicting the future is a chancy business. In line with other medical specialties, gastroenterology will be subject to rapid and profound changes in the coming decades and will have to adapt and renew its approach to the way medicine will be practised. The pressures to change will be in several areas. Global demographic, political and economic factors will become more intrusive and rapid communication will end isolationism. Developing EC structures and regulations are likely to increase mobility of medical staff and uniformity in the standards of training and practice. Rapid technological advances will have to be reconciled with finite resources and the ever increasing expectations of our aging population.

Future trends in the management of peptic ulcer disease.

Future trends in the short- and long-term management of peptic ulcer disease are considered. The present state of development of pharmacologic agents for the short-term healing of duodenal and gastric ulcer is impressive, and high rates of healing with rapid symptom relief can be safely achieved with several agents. The problem of ulcer recurrence has not been solved, although new work concerning the role of Campylobacter pylori holds promise. The mortality of acute gastrointestinal haemorrhage remains unacceptably high, especially in the elderly. Therapeutic endoscopy may be effective in decreasing the death rate from bleeding.