bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in acid/peptic disorders: a symposium overview
Authors: CLEARFIELD H. R. 
Published: July 2010

SUMMARYBefore 1977, the treatment of peptic ulcer disease consisted primarily of dietary, antacid, and anticholinergic programmes. There were heated controversies regarding rigid vs. liberal ulcer diets, a variety of antacids and dosing patterns to choose from, and conflicting claims over the benefit of various anticholinergic therapies. It was hoped that the dramatic introduction of the H2‐receptor antagonists would simplify our approach to the treatment of peptic ulcer and reflux oesophagitis. Standard doses of H2‐receptor antagonists are effective for acid/peptic disorders, yet it has become clear that some subsets of patients present special management problems, including recurrent ulcers, non‐steroidal anti‐inflammatory drug (NSAID)‐induced disease, stress ulcers, and refractory oesophagitis. New regimens, such as maintenance therapy and once‐daily nocturnal dosing, have been indicated for peptic ulcer disease. New drugs have been introduced, such as sucralfate, misoprostol, and omeprazole, each with a different mechanism of action. Therefore, while we have learned considerably more about the pathogenesis of peptic disease, treatment decisions have become more complicated.The Transatlantic Conference on Acid/Peptic Disorders was held on 19 21 January 1990, in Wesley Chapel, Florida. A faculty from the United Kingdom, the United States, and Canada reviewed pathophysiology and the role of pharmacologic agents in the treatment of acid/peptic disorders and outlined clinically useful treatment strategies. The conference was organized into five segments: acid suppression and ulcer healing; acid suppression and control of reflux disease; NSAID‐induced ulceration; stress ulceration, rationale for control of rebleeding, and drug interactions; and controversies. The proceedings of the symposium are presented in this supplement.
Maintenance therapy for peptic ulcer disease
Authors: WORMSLEY K. G. 
Published: July 2010

SUMMARYPeptic ulcers tend to recur; recurrence may be associated with an increased risk of potentially lethal complications, such as haemorrhage or perforation. Therapy aims to keep ulcers in remission. Currently, the optimal maintenance therapy is long‐term, continuous administration of antisecretory drugs. More than 80% of patients remain in remission during maintenance therapy. Maintenance therapy may be required for the life of the patient, but it is acceptable to patients and is safe.
Experience with omeprazole in erosive oesophagitis
Authors: ROBINSON M. G. , DECKTOR D. L. 
Published: July 2010

SUMMARYOmeprazole is a potent, highly specific, and clinically efficacious antisecretory agent. Current clinical data suggest that omeprazole could be a useful drug in the short‐term treatment of patients with severe erosive oesophagitis resistant to standard H2‐receptor antagonist therapy. The magnitude of omeprazole's eventual role in the treatment of acid secretory‐related disorders will depend on the results of its expanded postmarketing clinical experience and upon resolution of concerns regarding potential adverse effects associated with long‐term administration.
Quality of gastric ulcer healing: histological and ultrastructural assessment
Authors: TARNAWSKI A. , DOUGLASS T. G. , STACHURA J. , KRAUSE W. J. 
Published: July 2010

SUMMARYIt has long been assumed that the mucosa in areas of grossly ‘healed’gastric or duodenal ulcers returns to normal, either spontaneously or after treatment. This assumption is based almost entirely upon visual, superficial examination by endoscopy. Few, if any, histological and ultrastructural studies examined the deeper mucosa in the areas of grossly healed ulcers. In several experimental studies, we analysed the development, evolution, and healing of acetic acid‐induced gastric ulcers in rats and assessed the histological and ultrastructural features (structure and cellular composition) of the gastric mucosa in areas of grossly healed ulcers. The gastric mucosa of grossly ‘healed’ulcers showed re‐epithelialization of the mucosal surface at every study interval (2 weeks, 2, 3, and 4 months), but the subepithelial mucosa displayed prominent abnormalities. Two patterns of scarring were distinguished: (a) the mucosa in the area of healed ulcer was thinner (25–45 % thinner than normal mucosa) with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; and (b) the mucosa displayed a marked dilation of gastric glands with poor differentiation of the glandular cells and a reduction in the supportive microvascular network. It is theorized that these abnormalities could interfere with oxygenation, nutrient supply, and mucosal resistance and defence; therefore, they could be a basis for ulcer recurrence. These observations indicate that the quality of mucosal structural restoration rather than the speed of ulcer healing is the most important factor in determining risk of ulcer recurrence. The clinical relevance of these findings is supported by a preliminary study in which marked histological abnormalities were found in the subepithelial mucosa in patients with ‘healed’duodenal ulcers.
Stress ulceration in the intensive care unit: use of H2‐receptor antagonists
Authors: MOORE J.G. 
Published: July 2010

SUMMARYH2‐receptor antagonist drug therapy is the mainstay of peptic ulcer treatment in the USA. About 75 % of patients in intensive care units receive parenteral H2‐antagonists. The rationale for their use is that parenteral H2‐antagonists offer about a four‐fold protective effect compared with placebo against significant upper gastrointestinal haemorrhage. Parenteral administration of H2‐receptor antagonists appears to be preferred to oral antacid or sucralfate regimens because of ease of administration and, perhaps, lower treatment costs.Recommended dosage schedules for intravenously administered H2‐receptor antagonists are at fixed intervals, 6‐ to 8‐h intervals for cimetidine and ranitidine and 12‐h intervals for famotidine. These dosage schedules assume a fixed dose‐response relationship (i.e. a given dose of H2‐antagonist results in equivalent acid suppression throughout the circadian, or 24‐h, period). However, human basal gastric acid secretion exhibits circadian variation, with peak rates occurring during the evening hours. Recent evidence from 24‐h continuous intragastric pH studies in fasting patients with healed duodenal ulcer suggests that larger doses of intravenous H2‐antagonists are required in the evening than in the morning to achieve equivalent acid suppression. These findings are consistent with a changing H2‐antagonist dose/acid‐inhibiting response over the circadian period. Continuous infusion has the advantage of providing consistent and sustained suppression of gastric acid secretion in patients at risk for stress ulceration. Results of a double‐blind, randomized, crossover study indicated that equally effective suppression of acidity and time‐to‐onset of pharmacological effect can be achieved with and without priming bolus doses of ranitidine, and presumably other H2‐receptor antagonists as well. Furthermore, continuous intravenous H2‐antagonist therapy, compared with intravenous bolus administration, appears to offer more effective control of 24‐h pH at a reduced cost. These cost savings may be augmented by administration of the H2‐antagonist with the patient's total parenteral nutrition.
Helicobacter pylori: review of research findings
Authors: DOOLEY C. P. 
Published: July 2010

SUMMARY Helicobacter pylori attracted widespread interest from gastroenterologists because of its potential aetiologic role in disorders of the upper gastrointestinal tract. Based on extensive microbiological studies, Campylobacter pylori was renamed Helicobacter pylori, and the organism represents a new genus of bacteria. It is generally accepted that H. pylori causes chronic, non‐specific gastritis (type B gastritis). The inflammatory response occurs even though the bacterium does not penetrate the gastric epithelium; it is found on the surface of and adjacent to the epithelium. The clinical significance of histological gastritis is unknown. The bacterium is often found in asymptomatic subjects. In Caucasian adults, the prevalence of infection increases with increasing age. Higher rates of infection are found in blacks and Hispanics than would be expected for their age. Whether these different rates are the result of racial or socio‐economic factors is not known. It is theorized, but not proven, that high rates of infection with H. pylori at an early age may explain the high incidence of gastric carcinoma found in Hispanic populations. H. pylori is found in almost every patient with duodenal ulcer disease, although no direct evidence for a causal relationship exists. Indirect evidence is based on the findings that if H. pylori infection is eradicated, ulcer recurrence is less likely (up to one year of follow‐up). A small percentage of patients have a relapse despite eradication of the organism, suggesting a role for other factors in duodenal ulcer disease. The role of H. pylori in gastric ulcer disease is unknown. Seventy to eighty per cent of patients with gastric ulcer have evidence of H. pylori infection, and preliminary data seem to support the existence of two distinct aetiologic groups: those with gastric ulcers related to H. pylori infection and those with gastric ulcers related to use of non‐steroidal anti‐inflammatory drugs. The role of H. pylori in non‐ulcer dyspepsia is unknown. Some clinicians believe that H. pylori causes non‐ulcer dyspepsia and treat these patients for H. pylori infection. However, the data supporting this practice are poor. Treatment is only recommended for patients with resistant duodenal ulcers and patients who have frequent relapses of duodenal ulcers and who are willing to take triple‐drug therapy (bismuth compounds, metronidazole, tetracycline) for the infection. As 95% of patients with duodenal ulcer have evidence of H. pylori infection, there is probably little need to confirm the diagnosis of H. pylori infection.
Effects on the rat oxyntic mucosa of the histamine2‐antagonist loxtidine and the H+, K+‐ATPase inhibitor omepvazole
Authors: BRENNA E. , WALDUM H. L. , SANDVIK A. K. , SØGNEN B. SCHULZE , KRISTENSEN A. 
Published: July 2010

SUMMARYThe present study examined whether histamine could affect the growth of the enterochromaffin‐like (ECL) cell and the parietal cell. The effects of the unsurmountable histamine H2‐receptor antagonist loxtidine (80 mg/kg) and the H+, K+‐ATPase inhibitor omeprazole (100 μmol/kg) were compared in female Sprague‐Dawley rats. Both drugs were given by gavage once daily for 3 months. Omeprazole induced a more pronounced and sustained hypergastrinaemia than loxtidine. In spite of marked hypergastrinaemia during most of the day, even in the loxtidine‐treated rats, the weights of the stomach and oxyntic mucosa were elevated only in the omeprazole‐treated rats. The ECL cell density was slightly higher in the loxtidine‐ than in the omeprazole‐treated rats. Both treatments elevated the gastrin‐stimulated histamine release from the vascularly perfused stomach. The parietal cell density was unaffected by omeprazole treatment, whereas it tended to be reduced in the loxtidine‐treated rats. Simultaneous administration of loxtidine and omeprazole reduced the sustained hypergastrinaemia induced by omeprazole given alone. The present study may indicate that histamine inhibits the growth of the ECL cell, but further studies are needed to elucidate if histamine has any trophic effect on the parietal cells.
Night‐time or morning dosing with H2‐receptor antagonists: studies on acid inhibition in normal subjects
Authors: PATEL N. , WARD U. , ROGERS M. J. , PRIMROSE J. N. 
Published: July 2010

SUMMARYH2‐receptor antagonists are conventionally given at night. However, it remains unproven whether this regimen affords superior acid inhibition or healing rates for patients with duodenal ulcers compared to morning dosing. We have therefore examined the acid inhibitory effect of 300 mg ranitidine at night compared to 300 mg ranitidine in the morning in 8 normal male subjects. Intragastric acidity was measured by the radiotelemetry method and acid inhibition calculated from the percentage decrease in the area under the curve for hydrogen ion activity against time. Night‐time ranitidine resulted in a significantly better (P < 0.02) decrease of intragastric acidity than the same dose given in the morning (66.8 (61.8–77.6)%vs. 34 (15.5–49.1)%). This difference was found to be due to the fact that morning ranitidine inhibited gastric acid secretion when the intragastric acidity was already buffered by food. These data support the superiority of nocturnal dosing with H2‐antagonists.
Compliance with anti‐ulcer medication during short‐term healing phase clinical trials
Authors: FARUP P. G. 
Published: July 2010

SUMMARYNine hundred and sixty‐six patients’compliance with drug therapy of peptic ulcerations and reflux oesophagitis in four clinical trials were studied. The mean compliance rates varied from 90.5% (95% C.I. 89.0–92.1%) to 99.2% (95% C.I. 98.2–100.1%). Compliance declined significantly with increasing complexity of the dosage schedule in all trials, and toward the end of the treatment period in two of them. Patients with adverse events had a significant drop in compliance during the Iast part of the treatment period in one of the trials. There was a significant inter‐centre variation in compliance. Overall, the variation was of little clinical significance. Patient compliance was independent of age, sex, use of alcohol and tobacco, effect of treatment, concomitant drug therapy and whether the pill was active drug or placebo. The study shows that a simplified dosage schedule, shortening of the treatment period, use of drugs with minimal side‐effects, and meticulous selection of centres could improve patient compliance with drug therapy in clinical trials.
Antioxidant therapy for recurrent pancreatitis: biochemical profiles in a placebo‐controlled trial
Authors: UDEN S. , SCHOFIELD D. , MILLER P. F. , DAY J. P. , BOTTIGLIERI T. , BRAGANZA J. M. 
Published: July 2010

SUMMARYThe usefulness of micronutrient antioxidant therapy for recurrent (non‐gallstone) pancreatitis has recently been endorsed by a 20‐week double‐blind double‐dummy cross‐over trial in 20 patients. Treatment was delivered as two types of tablets, providing daily doses of 600 μ g organic selenium, 9000 i.u. β ‐carotene, 0.54 g vitamin C, 270 i.u. vitamin E and 2 g methionine. We report antioxidant profiles in blood samples collected before entry, at the cross‐over stage and upon completion of trial. Baseline serum concentrations of selenium, β ‐carotene and vitamin E in the patients were significantly lower than in healthy controls, were unaltered by placebo and normalized by active treatment, but reverted to basal values in the subgroup that received placebo subsequently. The baseline serum concentration of a free radical marker—the 9‐cis, II‐trans isomer of linoleic acid—was significantly higher in the patients than in controls, fell inexplicably in the placebo phase and fell further upon active treatment. Discriminant analysis eliminated the overlap in free radical marker and selenium concentrations between control sera on the one hand and baseline or post‐placebo samples from the patients on the other: antioxidant treatment normalized the relationship between these biochemical parameters. Subnormal baseline serum levels of S‐adenosylmethionine drifted downwards upon active treatment whereas a sharp rise was noted when a relapse of pancreatitis occurred during the placebo phase. The results confirm that adequate exposure to antioxidants in the active treatment phase was associated with amelioration of oxidative stress, and that there was no residual effect 10 weeks after switching over to placebo treatment. Furthermore, the paradoxical behaviour of S‐adenosylmethionine may imply that the beneficial effect of micronutrient antioxidants in recurrent pancreatitis is linked with preservation of the methionine trans‐sulfuration pathway in pancreatic acinar cells.
Comparison of one‐day oral dosing with three bismuth compounds for the suppression of Helicobacter pylori assessed by the13C‐urea breath test
Authors: PREWETT E. J. , LUK Y. W. , FRASER A. G. , LAM W. M. , POUNDER R. E. 
Published: July 2010

SUMMARYAssessment of intragastric urease activity by the 13C‐urea breath test was performed before and after one day of dosing with either De‐Noltabs (tripotassium dicitrato bismuthate, one tablet 1 q.d.s.), Pepto‐Bismol liquid (bismuth salicylate 30 ml q.d.s.), or Roter tablets (bismuth subnitrate, one tablet q.d.s.) in twelve Helicobacter pylori‐positive patient volunteers. There was a significant decrease in the excess of 13CO2 after one day of dosing with each of the three bismuth compounds, but analysis of variance could detect no difference between the effects of the three compounds.Systemic absorption of bismuth following oral dosing with either Pepto‐Bismol or Roter is minimal, yet both compounds have a suppressive effect on H. pylori similar to that of De‐Noltab. This study suggests that the action of all three bismuth compounds is within the gastric lumen, and that systemic absorption of bismuth is not necessary for activity against H. pylori.
Improved maintenance of remission in ulcerative colitis by balsalazide 4 g/day compared with 2 g/day
Authors: GIAFFER M. H. , HOLDSWORTH C. D. , LENNARD‐JONES J. E. , RODRIGUES C. A. , MCINTYRE P. B. , MANJUNATHA S. , BARON J. H. , BARRISON I. G. , POLSON R. J. , HOARE A. M. , DAVIES G. S. R. , THORNTON P. C. 
Published: July 2010

SUMMARYThe efficacy of two doses of balsalazide for the maintenance of remission in patients with ulcerative colitis was compared in a double‐blind multicentre trial. Sixty‐five patients received a 2 g daily dose, and 68 a 4 g dose. The patient groups were similar at entry for sex, age, and disease distribution. Clinical assessment was carried out at 3‐monthly intervals, with sigmoidoscopy, rectal biopsy, and blood tests on entry and at 26 and 52 weeks. Clinical relapse over twelve months was significantly less common on the 4 g dose (36%), than on the 2 g dose (55%), P < 0.01. There were eight withdrawals on 2 g daily and 13 on 4 g daily, six and nine respectively being mainly due to gastrointestinal intolerance. It is concluded that balsalazide is a well‐tolerated drug, and is effective for the maintenance of remission in patients with ulcerative colitis, the optimal dose being greater than 2 g daily.
Review article: the treatment of alcoholic liver disease
Authors: BLENDIS L. M. 
Published: July 2010

SUMMARYOver the past 20 years we have moved from a situation in which we had no therapy for alcoholic liver disease, through a period when any therapy we had was purely empirical, to an era where we have specific therapies for different aspects of this disease based upon sound pathogenic principles. In this short review, an attempt has been made to summarize these advances in the understanding of the pathogenesis of alcoholic liver disease. In particular, they explain why patients with severe acute alcoholic hepatitis continue to deteriorate in hospital despite withdrawal from alcohol, why they respond to corticosteroids, why only a small percentage of patients develop cirrhosis, and why propylthiouracil may offer Protection.
Comparison between a standard pancreatic supplement and a high enzyme preparation in cystic fibrosis
Authors: MORRISON G. , MORRISON J. M. , REDMOND A. O. B. , BYERS C. A. , McCRACKEN K. J. , DODGE J. A. , GUILFORDS S. A. , BOWDEN M. W. 
Published: July 2010

SUMMARYThis study compared the relative effectiveness of a standard pancreatic enzyme supplement (‘Creon’, Duphar) and a new preparation (‘Pancrease HL’, Cilag) containing about 3 times the lipase and more than 5 times the protease activity. Capsule dosage was adjusted to a ratio of approximately 3:1. Fat balances showed that absorption of fat did not change significantly on conversion to the new high‐lipase product, and the coefficient of absorption of total energy was similarly maintained. The coefficient of protein absorption was significantly enhanced with the high enzyme preparation (P < 0.01), which may explain the reported subjective improvement in stool odour. No adverse effects were recorded. Patient acceptability of the new compound was high; the great reduction in the number of capsules required at each meal was cited by all patients as the reason for their preference.
Omeprazole in the long‐term treatment of severe gastro‐oesophageal reflux disease in patients with systemic sclerosis
Authors: HENDEL L. , HAGE E. , HENDEL J. , STENTOFT P. 
Published: July 2010

SUMMARYTwenty‐five patients with systemic sclerosis and severe gastro‐oesophageal reflux disease were treated with 20–80 mg omeprazole daily for up to 5 years. Efficacy of treatment was assessed by symptom score, by endoscopic and histopathological surveillance of the oesophageal and gastric mucosa, and by laboratory screening including serum gastrin concentration.Statistically significant relief of symptoms and healing of oesophagitis confirmed the efficacy of this treatment. However, complete healing of oesophagitis was not achieved in half of the patients due to residual gastro‐oesophageal acid reflux. Repeated adjustments of the maintenance dose of omeprazole may be needed for this group of patients. From the safety point‐of‐view, nothing was observed to discourage the long‐term use of omeprazole in this group of patients.
The effects of 5‐aminosalicylic acid and acetyl‐5‐aminosalicylic acid on lipid peroxidation in erythrocytes and prostaglandin production by mononuclear cells
Authors: GREENFIELD S. M. , BOSWELL D. J. , PUNCHARD N. A. , THOMPSON R. P. H. 
Published: July 2010

SUMMARYIn parallel studies, the effects of 5‐aminosalicylic acid (5‐ASA) and acetyl‐5‐aminosalicylic acid (acetyl‐5‐ASA) on peroxidation of red‐cell membrane lipids and production of prostaglandins by peripheral blood mononuclear cells were assessed. 5‐ASA at concentrations of 10‐5, 10‐4 and 10‐3m significantly inhibited erythrocyte lipid peroxidation, measured as malondialdehyde production, by 20%, 56% and 63%, respectively, (P < 0.05, P < 0.002, P < 0.001, respectively) while acetyl‐ 5‐ASA had no effect. 10‐5 and 10‐4m 5‐ASA significantly increased production by stimulated peripheral blood mononuclear cells of PGE2 (by 31% and 30%, P < 0.01, P < 0.05, respectively) and PGF2α (by 30% and 25%, P < 0.05, P < 0.01, respectively). 10‐4 M 5‐ASA also significantly stimulated prostacyclin production measured as 6KF1α by 10% (P < 0.05). At 10‐3 M 5‐ASA there were significant falls in 6KF1α (by 37%) PGE2 (by 45%) and PGF2α (by 47%) (P < 0.01, P < 0.001, P < 0.001, respectively) although this was accompanied by a decrease in cell viability. Acetyl‐5‐ASA had little effect upon prostaglandin production. 5‐ASA scavenges free radicals and stimulates production of cyto‐protective prostaglandins.
Ranitidine, cimetidine, famotidine have no effect on post‐prandial absorption of ethanol 0.8 g/kg taken after an evening meal
Authors: FRASER A. C. , HUDSON M. , SAWYERR A. M. , SMITH M. , ROSALKI S. B. , POUNDER R. E. 
Published: July 2010

SUMMARYForty‐seven healthy male subjects were studied twice using a randomized, placebo‐controlled design. Each subject took an 8‐day course of two of the following four regimens; 300 mg ranitidine, 800 mg cimetidine, 40 mg famotidine or placebo (identical either to 300 mg ranitidine or 800 mg cimetidine). The systemic bioavailability of ethanol (integrated 6‐h plasma ethanol concentration, peak plasma ethanol concentration, and the time to peak plasma ethanol concentration) was measured after the oral ingestion of 0.8 g of ethanol per kg body weight, given one hour after an evening meal on Day 8 of each regimen.There was no significant difference of integrated 6‐h plasma ethanol concentration, peak ethanol concentration, or time to reach peak ethanol concentration after dosing with either ranitidine, cimetidine or famotidine or placebo.