Mesalazine 4 g daily given as prolonged-release granules twice daily and four times daily is at least as effective as prolonged-release tablets four times daily in patients with ulcerative colitis.

BACKGROUND: High doses of mesalazine usually result in an inconvenient dosage schedule and reduced compliance. The goal of this trial was to compare the effects of mesalazine 4 g daily given as prolonged-release granules in packets of 1 g with that of prolonged-release tablets of 0.5 g. METHODS: Two hundred twenty-seven patients with mild-to-moderate ulcerative colitis were randomized to treatment with two packets twice daily (Gr-b.i.d.), 1 packet four times daily (Gr-q.i.d.) or 2 tablets four times daily (Ta-q.i.d.) for 8 weeks. A disease activity index (ulcerative colitis disease activity index: UC-DAI) was calculated, and the granules were defined as noninferior to the tablets if the lower limit of the 95% CI for the differences was more than -1 UC-DAI score unit. RESULTS: Noninferiority of the granules compared with the tablets was demonstrated. The mean improvement in the UC-DAI in the treatment groups Gr-b.i.d., Gr-q.i.d., and Ta-q.i.d. were 3.2, 2.9, and 2.4, respectively; the proportion of complete responders in the three groups 39%, 37%, and 31%, respectively. There were no differences in side effects. CONCLUSION: Mesalazine 4 g daily given as prolonged-release granules twice and four times daily is at least as effective as prolonged-release tablets four times daily in patients with mild to moderate ulcerative colitis. The patients preferred the twice daily dosing.

Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen.

BACKGROUND: Selective inhibitors of cyclooxygenase (COX)-2 may provoke less gastric damage and platelet inhibition than conventional non-steroidal anti-inflammatory drugs. AIMS: We compared the biochemical and gastrointestinal effects of nimesulide, a potent and selective COX-2 inhibitor, with naproxen which exhibits no selectivity. SUBJECTS: Thirty six healthy volunteers were randomised to nimesulide 100 mg or naproxen 500 mg twice daily for two weeks in a double blind, crossover study with a washout between treatments. METHODS: Gastrointestinal side effects were assessed by endoscopy, and by estimation of small intestinal absorption-permeability and inflammation. Comparisons were made between variables at the end of each treatment phase. RESULTS: Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039). Nimesulide had lower visual analogue scores (VAS) for haemorrhage and erosive lesions in the stomach (p<0.001) and for mucosal injection in the duodenum (p=0.039). Naproxen increased excretion of calprotectin, a marker of intestinal inflammation (5.5 (1.2) to 12.1 (2.1) mg/l) while nimesulide had no effect (treatment difference p=0.03). Naproxen abolished platelet aggregation to arachidonic acid and suppressed serum thromboxane B(2) (TXB(2)) by 98%, indices of COX-1 activity. In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29%. Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide. COX-2 activity, determined as endotoxin induced prostaglandin E(2) formation in plasma, was markedly suppressed by both treatments. INTERPRETATION: Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term.

Inflammatory bowel disease in Iceland, 1980-89. A retrospective nationwide epidemiologic study.

BACKGROUND: A previous nationwide epidemiologic study of inflammatory bowel disease (IBD) in Iceland in 1950-79 showed a low but steadily rising incidence. The incidence of IBD in Iceland in 1980-89 was investigated and compared with reports from neighboring countries. METHODS: Cases were retrieved by a review of all small- and large-intestinal tissue specimens with any type of inflammation submitted to the only two departments of pathology in Iceland. All small-intestinal X-ray records suggestive of Crohn's disease (CD) in the three major hospitals were also screened. All hospital and outpatient records of cases suggestive of IBD were then reviewed using accepted criteria for confirmation or exclusion. RESULTS: The mean annual incidence of ulcerative colitis (UC) was 11.7/100,000, and that of CD 3.1/100,000. The highest age-specific incidence of UC was in the group 30-39 years old and for CD in the group 60-69 years old. The most frequent involvement at diagnosis of UC was proctitis only, in 54%, and in CD colon only, in 54.7% of the patients. CONCLUSIONS: This study shows a continuing increase in the incidence of both diseases. Compared with the period 1970-79, there has been an almost twofold increase in the mean annual incidence of UC and more than a threefold increase of CD, a statistically significant increase in both instances.

[Comparison of the efficacy of Losec/Lómex and Zantac/Famex by continuous 24 hour gastric pH-metry.].

OBJECTIVE: The study proposes to investigate the pharmacological efficacy of four commonly used acid inhibitory drugs. The effect on 24 hour gastric pH of seven days treatment was assessed for two omeprazole preparations, Losec(R) 20 mg (Hassle) and Lómex(R) 20 mg, (Omega Farma) and two H2 blockers, famotidine 40 mg (Famex(R), Omega Farma) and ranitidine 300 mg (Zantac(R), Glaxo). MATERIAL AND METHODS: Sixteen healthy volunteers participated in each experiment comparing blindly Losec(R) / Lómex(R) and Famex(R) / Zantac(R). The stomach was intubated with monocrystant antimony catheter and the pH sensor was placed 10 cm below the cardia. A 24 hour control pH-metry was performed followed by a 24 hour pH-metry on the seventh day of treatment with each drug. RESULTS: All four drugs gave significant acid inhibition compared to control. Zantac treatment resulted in a pH over 3 for 8.8 hours and correspondingly Famex(R) treatment for 11.2 hours, Losec(R) treatment for 17.5 hours and Lómex(R) for 18.3 hours. Famex(R) gave significantly greater inhibition than Zantac(R) but the difference between Lómex(R) and Losec(R) was not significant. CONCLUSION: The study shows the efficacy of com notmonly used acid lowering drugs on the Icelandic market. The relative efficacy is indicated by the fact that Zantac(R) increased the median time for pH over 3 by 2.6 hours, Famex(R) by 5.0 hours, Losec(R) by 11.3 hours and Lómex(R) by 12.1 hours.

[Arteriovenous fistula after partial gastrectomy. A case report.].

Portal arteriovenous fistulas are uncommon and are most often seen following trauma to the abdomen. In a few cases they have occurred as complications of abdominal surgery. In this report we present a 74 year old man with a fistula between the left gastric artery and vein, secondary to a Billroth I partial gastrectomy that was performed 32 years earlier. The patient complained of a diffuse abdominal pain for two weeks and mild cardiac failure symptoms. An epigastric bruit was heard and the abdomen was distended with transudatic ascitic fluid. The fistula was diagnosed by Doppler-ultrasound and the diagnosis confirmed by angiography. At laparotomy the fistula was excised and the patient's symptoms subsequently subsided.

[Endoscopic retrograde cholangio- pancreatography. An overview of procedures at the Natinal University Hospital in Reykjavik 1983-1992.].

INTRODUCTION: In this retrospective study we analysed all ERCP procedures performed at the National University Hospital in Reykjavik, Iceland, for the period 1983-1992. MATERIAL: A total of 644 procedures were performed on 477 patients. RESULTS: The main indication for a diagnostic ERCP was suspected choledocholithiasis in 58.8% of cases. Cannulation of the papilla of Vater was successfully achived in 94% of patients and in 82% the desired duct was visualised. Juxtapapillary diverticula were found in 14.5% of patients. The success at cannulation was significally less in that group. Choledocholithiasis was found in 19.4% more often in the patients with diverticula, 29.5 vs. 18.8%. The number of therapeutic interventions was 158 performed on 84 patients (24.5% of all ERCP). The most common procedure was sphincterotomy, performed in 84% of cases. Stone extraction was successfully achived in 58% of all attempts. The overall complications rate was 7%, most frequently acute pancreatitis (4.7%) followed by cholangitis (1.9%) and bleeding (0.3%). The complications were mild in the majority of cases but serious ones did occur and were fatal in three (0.5%) patients related to severe pancreatitis. CONCLUSION: The results of this retrospective study in Iceland are comparable to what others have reported previously.

[Ulcerative colitis in Iceland 1980-1989. A retrospective epidemiological study.].

OBJECTIVE: To find the incidence of ulcerative colitis in Iceland during the past decade for comparison with previous study and incidence figures from neighbouring countries. METHODS: This was a nationwide retrospective study of the period 1980-1989. Cases were retrieved by reviewing all reports on tissue specimens from the large and small intestine with any type of inflammation referred to the two departments of pathology in Iceland. All possible cases of ulcerative colitis were then followed by a review of the clinical information. Only those cases fulfilling accepted diagnostic criteria were included in the study. RESULTS: Thus 282 cases of ulcerative colitis were found, 166 men and 116 women, M/F ratio 1.43. The mean annual incidence for the 10 year period was 11.7/100,000. The highest age specific incidence was found in the group 30-39 years, 21/100,000/year. Most frequently the inflammation was limited to the rectum (proctitis), found in 53.9% of the patients. Proctosigmoiditis was seen in 29.8%, left-sided col notitis in 5.3% and extensive colitis in 11%. Approximately 63% of the patients had been symptomatic for less than six months before diagnosis. Information on familial cases of inflammatory bowel disease was obtained from 8.9% of the patients. CONCLUSION: There has been a steady and significant increase in the incidence of ulcerative colitis in Iceland in the past four decades and the mean annual incidence has almost doubled from the last decade 1970-1979. This increase in incidence is considered real, i.e. not due to better methods of detection or a change in diagnostic criteria.

[Crohn's disease in Iceland 1980-1989. A retrospective epidemiological study.].

OBJECTIVE: To find the incidence of Crohn's disease in Iceland during the past decade for comparison with previous study and incidence figures from neighbouring countries. METHODS: A nationwide retrospective study of the incidence of Crohn's disease in Iceland for the 10-year period 1980-1989 was conducted. New cases were retrieved by review of all small and large intestinal tissue specimens with any type of inflammation submitted to the two departments of pathology in Iceland. All cases with the slightest possibility of Crohn's disease were followed clinically by examining their hospital, outpatient and x-ray records. In addition all small intestinal x-rays with the diagnosis of Crohn's disease were screened. The criteria of Lennard-Jones were used to confirm or exclude Crohn's disease. RESULTS: Thus 75 patients were found, 36 men and 39 women, M/F ratio 0.9. The mean annual incidence was 3.1/100,000, which is a three fold increase compared to the period 1970-1979. The incidence of Crohn's disease in Iceland is still the lowest among the neighbouring countries. The highest age specific incidence was in the age group 60-69 years, 8.9/ 100,000, which is unusual. The most frequent localization of the intestinal inflammation at diagnosis was colon only (54.7%). The second most common localization was ileum only (25.3%), but in 18.7% of the patients the disease involved both ileum and colon. Inflammation limited to the colon was significantly more frequent in the older age groups. There was a family history of inflammatory bowel disease (IBD) in 8% of the cases. CONCLUSION: The incidence of Crohn's disease in Iceland, while still low compared to that of the neighbouring countries, is rising. The reason for this increase is unknown.

[Helicobacter pylori infection: the efficacy of a short course of azithromycin and fleroxacin treatment.].

The aim of this open pilot study was to assess the efficacy of a short course of fleroxacin and azithromycin in the treatment of Helicobacter pylori infection. Seventeen patients were included. All had H. pylori infection confirmed by urease test and culture. Eight patients had non-ulcer dyspepsia, 8 had duodenal ulcer and 1 had gastric ulcer. The patients were given omeprazole 40 mg on days 1-14, fleroxacin 400 mg on days 7-14 and azithromycin 500 mg on days 7 and 8. Side effects were assessed on a scale 0-4. The patients were gastroscoped 3 months after the treatment finished and urease test and H. pylori culture repeated. If both were negative eradication was regarded as successful. Six patients (35%) were H. pylori negative. However, only 1 (13%) of the patients with non-ulcer dyspepsia became H. pylori negative, whereas 5 (56%) with peptic ulcer did (P=0,131). The mean side effect score for patients with non-ulcer dyspepsia was 12.3, but 2.3 for patients with peptic ulcer (p<0,01). It is concluded that a short course with fleroxacin and azithromycin is inadequate for treatment of H. pylori infection.

Survey of prescriptions for peptic ulcer drugs (ACT class AOB2) in Iceland.

BACKGROUND: The consumption of peptic ulcer drugs in Iceland is 20 DDD/1000/day, which is two to three times higher than in other Scandinavian countries. This study was done to register the pattern of use and possibly to find reasons for the high consumption. METHODS: Prescriptions for peptic ulcer drugs (ACT class AO2B) were surveyed in Iceland during 1 month in 1991. All pharmacies in Iceland participated in the study, and information was obtained on about 90% of peptic ulcer drugs used outside hospitals. The pharmacists registered all prescriptions of peptic ulcer drugs with regard to the age and sex of the patient, speciality of the prescribing physician, and name, dose, and quantity of the drug. RESULTS: A total of 2021 prescriptions were registered, accounting for 15.4 DDD/1000/day. The prevalence of peptic ulcer drug use was 1.52%, but female use was 52.5%. The maximal use, 2.91% was in the age group 70-79 years. H2 blockers accounted for 79%, omeprazole for 17%, and other drugs for 4%. General practitioners prescribed 65% of the drugs, gastroenterologists 15%, and other specialists 14%. If the patient himself collected the drug, he was asked to fill out a questionnaire with regard to the reason for the prescription, previous prescriptions, and investigations. A total of 1131 (56%) of patient questionnaires were received. Only 1% of the patients did not know the reason for the prescription. The patients registered that 30% of the prescriptions were for peptic ulcer, 29% for heartburn, 21% for gastritis, 9% for dyspepsia, and 7% for prevention of side effects of other drugs. It was estimated from the data that about 40% of the prescriptions were for non-ulcer dyspepsia. Investigations were done in 67% of the patients, but 33% received the prescription only after an appointment with a physician. CONCLUSIONS: The results of the survey suggest that the extensive use of peptic ulcer drugs in Iceland is mostly due to excessive use in non-ulcer dyspepsia.

Does sucralfate prevent short-term NSAID induced damage to the gastroduodenal mucosa?

The objective of the study was to assess whether sucralfate can prevent or diminish short-term nonsteroidal anti-inflammatory drug (NSAID)-induced damage in the stomach and duodenum. Sixteen healthy subjects were randomly treated for 7 days with sucralfate 2 g b.d. or placebo in a double-blind cross-over manner. Naproxen 500 mg b.d. was given on days 3-7. Gastrointestinal endoscopy was performed before and after each treatment period. Mucosal damage was measured by counting erosions, submucosal hemorrhages or ulcers on a fixed point scale of 0-4 for stomach and duodenum separately. The mean posttreatment injury score in the stomach was 2.13 +/- 1.51 and 2.0 +/- 0.97 for the placebo and sucralfate periods, respectively (p = 0.72). The possibility of type II error was 7%. In the duodenum, the injury score was 1.69 +/- 1.08 and 1.06 +/- 0.93 for the placebo and sucralfate periods, respectively (p = 0.08). The possibility of type II error was 37%. Sucralfate has no efficacy as a prophylactic agent against short-term NSAID-induced gastroduodenal injury.

[The use of ulcer medication in Iceland]. / Användningen av ulcusmedicin på Island.

In Iceland, the consumption of pharmaceutics for lesions of the gastrointestinal tract is 20 DDD/1,000 inhabitant days, which is 2-3 times more than that of any of the other Nordic countries. A nationwide investigation showed 1.54 per cent of the Icelandic population to be on continuous ulcer medication, consumption being greatest in the 70-79-year-old age group. H2-blockers are used in 79 per cent of cases, omeprazole in 17 per cent, and other drugs in 4 per cent. Of the prescriptions, 65 per cent were issued by GPs, 15 per cent by gastro-enterologists and 14 per cent by other categories of physicians, the remaining 6 per cent being issued at hospitals. The reasons given by patients for the medication were ulcer problems (30 per cent), heartburn (29 per cent), gastritis (21 per cent), dyspepsia (9 per cent), and side-effects of other medication (7 per cent).

Efficacy of sucralfate in treatment of non-ulcer dyspepsia. A double-blind placebo-controlled study.

The object of this study was to assess the efficacy of sucralfate in the treatment of non-ulcer dyspepsia (NUD). The diagnosis of NUD was made by exclusion. All patients underwent an upper gastrointestinal endoscopy and abdominal ultrasound, and blood tests were done as clinically indicated. Patients with a history of peptic ulcer disease were not included. Symptomatic assessment was made at the beginning and at the end of the study. The patients registered their most prominent dyspeptic symptoms and whether they improved, were unchanged, or worsened. The study was double-blind. Placebo or 1 g sucralfate four times daily was given for 3 weeks. Over a 2-year period 104 patients were included in the study; 56 received sucralfate and 48 placebo. Nine patients were excluded because of poor compliance or side effects, six from the sucralfate group and three from the placebo group. The sucralfate and placebo groups were comparable with regard to symptom and clinical variables. Global assessment of symptoms showed that in the sucralfate group 34 improved (68%), 11 were unchanged, and 5 were worse. In the placebo group 31 improved (69%), 11 were unchanged, and 3 were worse. There was no statistically significant difference between the groups. The 3-week course of sucralfate in patients with NUD did not show symptomatic improvement over placebo.

Comparison between ranitidine and omeprazole for protection against gastroduodenal damage caused by naproxen.

Acute gastroduodenal injury is commonly associated with the use of nonsteroidal anti-inflammatory drugs. The mechanism of injury is not well understood. The objectives of this study were to evaluate the protective effect of two drugs that give different degrees of acid inhibition against naproxen-induced gastroduodenal injury. Fifteen volunteers aged 22-28 years underwent pre- and post-treatment gastroduodenoscopies during three treatment periods (that is, six examinations), and mucosal injury was graded on a Lanza scale ranging from 0 to 4. The subjects received placebo, 150 mg rantidine twice daily, or 40 mg omeprazole in a double-blind, random-order design for 7 days. Plain naproxen, 500 mg twice daily, was given on days 3-7. The mean injury score for the stomach during placebo treatment was 1.53, and ranitidine gave 44% and omeprazole 40% reduction compared with placebo, which did not reach statistical significance. About 70% of the stomach injury was located in the antrum. The mean injury score during placebo for the duodenum was 1.93, and ranitidine gave 80% and omeprazole 90% reduction (p = 0.004). In conclusion, a correlation between different degrees of acid suppression and a protective effect on the gastroduodenal mucosa could not be shown. The study suggests that acid plays a major role in acute naproxen-induced injury to the duodenal mucosa, and a moderate acid reduction is adequate for protection. In the stomach acid seems to play a minor role in the mucosal injury, but physiochemical contact with naproxen in the antrum and a cyclooxygenase inhibition are of greater importance.

Endoscopic findings in the stomach and duodenum after treatment with enteric-coated and plain naproxen tablets in healthy subjects.

To compare the damaging effect of enteric-coated and plain naproxen tablets on the gastric and duodenal mucosa, 12 healthy subjects were studied before and after 2 7-day treatment periods in a randomized, double-blind, double-dummy, crossover trial. Both preparations of the drug caused mucosal lesions, but the extent of the damage was significantly less in the stomach and duodenum after enteric-coated than after plain naproxen tablets. The subjects, however, did not have a preference for either preparation. The morning plasma naproxen concentration was significantly higher after treatment with enteric-coated naproxen than after treatment with plain tablets. The results of the study indicate that naproxen damages the mucosa of the stomach and duodenum through local and systemic effects. The local effect seems to be the more important and can at least be partially prevented by enteric-coating of the tablets.

Secretion rate of intestinal immunoglobulins, complement factor C3, "acute phase" reactants, and albumin in the perfused ileum and jejunum of normal man.

A new method for assessment of the intestinal secretion rate of immunoglobulins and other proteins is evaluated. The procedure involves a combination of luminal perfusion of a defined intestinal segment and analysis of the aspirated perfusates by rocket immunoelectrophoresis. The technique is sensitive and reliable. A material from the normal human jejunum and ileum is presented. The method is proposed as an investigative tool for characterization of the local immunological system of the small intestine.

A prospective comparative study of clinical and pathological characteristics in Icelandic and Danish patients with gastric ulcer, duodenal ulcer, and X-ray negative dyspepsia. II. Histological results.

The occurrence of gastritis in antral and body mucosa is compared in an Icelandic and a Danish group of patients with gastric ulcer, duodenal ulcer, and X-ray negative dyspepsia. In all 93 Icelandic and 88 Danish patients were examined. All signs of antral gastritis were more frequent in Icelandic than in Danish patients, but only the incidence of superficial inflammation and decreased mucus content in surface and crypt epithelium differed significantly. In body mucosa pseudopyloric metaplasia was more frequent in Iceland and occurred equally freqeuntly in all three diseases. A statistically significant correlation was found between macroscopic gastritis and occurrence of antral superficial inflammation and between smoking and superficial inflammation and decreased mucus content in the pyloric biopsy specimen. The presence of histological gastritis was not correlated to the intake of alcohol and salicylic acid, nor to the presence of pain at the time of investigation.

Transmural ionic fluxes and electrical potential difference in the human jejunum during perfusion with a dihydroxy bile acid.

Perfusion studies of the proximal jejunum were performed in healthy volunteers to define the influence of glycochenodeoxycholic acid (GCDC) 2.5 mmol/1 on the net movements of water and electrolytes, the bidirectional fluxes of sodium, potassium, and chloride, and the transmural electrical potential difference (PD). The flux data supported the notion that active sodium transport is inhibited by luminal GCDC, which on the other hand elicits active secretion of chloride. PD was 3 +/- 1 mV, lumen negative, and was not influenced by GCDC. The flux data fit a previously proposed model for the GCDC effect.