[The study of gastric secretory function in Norway (a historical review)]. / Izuchenie sekretornoi funktsii zheludka v Norvegii (istoricheskii obzor).

The review summarizes the results of Norwegian investigations of gastric secretion and gastric secretory tests as a diagnostic procedure in peptic ulcer patients. The introduction of gastroscopy as a method of accurate diagnosis of gastric diseases made it less important to examine gastric secretory capacity in the clinical setting. The gastric secretory tests remain to be essential in defining the indications for and the impact of surgical interventions in intractable peptic ulcers. Gastric secretory studies are of great value in studying gastric physiology and pathophysiology and in evaluating the efficacy of the drugs that inhibit hydrochloric acid secretion.

Effects of the prostaglandin E2 analogue enprostil on the carbon tetrachloride-induced necrosis of liver cells in mice.

Female mice, eight weeks old, were injected with carbon tetrachloride (CCl4) (10 mg subcutaneously). Groups of mice (n = 10-30) were then injected with enprostil (E) 2, 20 or 50 micrograms/kg body weight (bw) intraperitoneally 15 min and two h after, or E 100 micrograms/kg bw two h after the CCl4 injection. The mice were killed after 24, 48 or 72 h. Plasma activity concentrations of alanine aminotransferase (ALAT) were determined in blood specimens from the iliac veins. The extent of liver cell necrosis in histological sections was recorded on a 100 mm Visual Analogue Scale (VAS) and measured using the electronic Mini Mop method. In the group given the highest single dose of E (100 micrograms/kg) a significant lowering of the CCl4-induced liver cell necrosis was found after 24 h. No significant differences were found after 48 and 72 h. In the other groups injected with lower doses of E after CCl4, no significant differences were found compared to groups injected with CCl4 alone.

Effect of the prostaglandin E1 analogue misoprostol on the carbon tetrachloride-induced injury of rat liver cells in culture.

Previous investigators have reported a protective effect of some prostaglandins and of the prostaglandin E2 analogue enprostil on carbon tetrachloride (CCl4)-induced injury of liver cells. In the present study liver cells were isolated from the rat liver by collagenase perfusion and suspended in F-10 medium, containing 20% foetal bovine serum, 1% gentamicin, and 1% glutamine. In the first study cells were cultured in T-flasks with 3 ml suspension of 6 x 10(6) cells/ml, and in the second study (extended dose response) cells were cultured in tissue culture wells with 0.5 ml cell suspension. Misoprostol was added to groups of cultures 15 min before CCl4, 2 microliters/ml, and the number of living cells was counted 45 min after the first addition. The number of living cells was compared with those of other groups with CCl4 only and control groups. In the first experiment misoprostol was given in doses of 200, 400, and 800 ng/ml medium and in the second experiment in 0.1, 1, 10, 100, and 1000 ng/ml medium. CCl4 is an agent well known to be toxic to liver cells, and in cultures to which only CCl4 was added, the number of living cells was significantly reduced compared with controls. When 0.1 ng misoprostol was added before CCl4, no significant difference in the number of living cells was shown compared with cultures with CCl4 only. On the other hand, misoprostol given in doses from 1 ng to 1000 ng before CCl4 resulted in a higher number of living cells, indicating a protective effect.

Liver cell necrosis and regeneration following injections of carbon tetrachloride. Effects of the thyrotropin-releasing hormone and somatostatin.

Mice were given 10 micrograms somatostatin or 25 micrograms TRH intraperitoneally 10 min before s.c. injection of 2 or 20 mg CCl4. The extent of liver cell necrosis and nuclear size were measured by the electronic Mini Mop method and the extent of necrosis and nuclear pleomorphism were estimated by a visual linear analogue scale of 100 mm, and compared to plasma concentrations of ASAT and ALAT. Pre-treatment with TRH or somatostatin resulted in significant reduction in the extent of necrosis 24 h after CCl4-injections (25%), with a lowering of ASAT from 13209 +/- 2955 U/l to 5144 +/- 924 after TRH and to 6186 +/- 966 after somatostatin, and of ALAT from 14343 +/- 3209 to 7718 +/- 1727 and 6494 +/- 1253 U/l, respectively. After 3 days the necroses were reduced from 16.5 +/- 1.7% by the Minimop method to 1.4 +/- 0.5% (90%) in mice given CCl4 alone, and from 12.3 +/- 1.7% to 3.8 +/- 1.2% in mice pretreated with TRH, and from 12.3 +/- 1.8% to 3.8 +/- 1.7% (70%) in mice pretreated with somatostatin. The plasma concentrations of ASAT and ALAT were reduced correspondingly. After 5 days no necroses were seen, and the plasma ASAT and ALAT were normal. After 6 months of weekly injections of TRH or somatostatin before 20 mg CCl4 the liver cell nuclear size (10.5 and 9.7 0.3 mu 2) was similar to that after CCl4 alone (9.7 0.3 mu 2), and twice that of controls (4.6-5.4 0.1 mu 2). Liver cell necrosis was not seen. The plasma concentrations of ASAT (131 8.6-162 11.3) and ALAT (98 8-104 9 Iu/l) were similarly 2-3 times those in controls. TRH and somatostatin thus reduced liver cell injury and delayed regeneration after single injections of CCl4. After 6 months of weekly injections no effects were observed.

Prostaglandins and CCl4-induced liver cell mortality. The effect of the prostaglandin analogue enprostil.

Prostaglandins have been reported to reduce the carbon tetrachloride (CCl4)-induced liver cell injury in rats. The object of the present experiments was to examine the effect of the prostaglandin E2 analogue enprostil on the survival of isolated liver cells exposed to CCl4. Liver parenchymal cells were isolated from rat livers by collagenase perfusion and released into a 'suspension' buffer. Aliquots of the cell suspension were incubated with 1 micrograms or 0.5 microgram CCl4, and to parallel test suspensions 20 ng enprostil was added 5-10 min before CCl4. Incubation was performed on ice, at room temperature, and at 37 degrees C. The average percentage of dead cells after CCl4 treatment was significantly reduced by pretreatment with enprostil at room temperature (1 microgram CCl4: 69 +/- 21% and 44 +/- 13%, respectively) and after 10 min of incubation at 37 degrees C (1 microgram Cl4: 56 +/- 25% and 37 +/- 27%; 0.5 microgram CCl4: 51 +/- 33% and 29 +/- 18%, respectively). When the liver cell mortality approximated 100% after long-term incubation at 37 degrees C, no protective effect of enprostil was observed.

Education and training in gastroenterology. Report from the OMGE symposia at the International Congress of Gastroenterology, Lisbon, Portugal, September 1984, and at the 8th World Congress of Gastroenterology, São Paulo, Brazil, September 1986.

Gastroenterology is recognized as a speciality in most countries, especially in Europe and North America. The requirements for being acknowledged as a specialist vary from 1 1/2 to 4 years of training and education in gastroenterology in addition to 1-6 years of training and education in internal medicine/surgery. The requirement of theoretical education varying from 40 to 300 h is practiced in some countries only. In some countries training in endoscopy is separated from gastroenterology. A formal examination and post-specialization training program is required in only some of the countries answering the questionnaire. The number of centres per million inhabitants recognized for training and education also varied greatly. The number of specialists per million inhabitants was 3.6 to 15. In the Middle and Far East the organisation of gastroenterology was much inferior to that in Europe and North America because of insufficient education and organization programs and lack of economic support to perform them. The answers from the gastroenterological associations and personal reporters agreed on the following: A speciality in medical and surgical gastroenterology should be established in all countries around the world. Programs for training and education should be agreed upon in recognized teaching and training institutions of gastroenterology, probably of 3 years' duration in combination with a speciality in internal medicine. A gastroenterologist will in most cases be dealing with other diseases as well. The number of specialists per million inhabitants may be estimated to 10, the exact number not being possible to determine at present. In most countries the post-specialization programs were not required but were offered, a problem that has to be clarified.(ABSTRACT TRUNCATED AT 250 WORDS)

The OMGE multinational inflammatory bowel disease survey 1976-1986. A further report on 3175 cases.

This presentation describes the progress during 1982-1986 of the OMGE Multinational Survey of patients with inflammatory bowel disease. After a brief description of the study design and protocol, the status of the survey in 1986 is presented. In all, 40 centres contributed 3175 cases at that time, data collection being meticulous via previously designed proformata. Diagnostic criteria are next discussed. Little change between 1976 and 1986 is noted, with wide congruence of diagnostic thought, now codified into a simple (and recommended) OMGE diagnostic scoring system. Patients seen prior to 1978 were reviewed in 1986. Where attempted, a follow-up of over 86% was achieved, usually more than 4 years after the original presentation involving no less than 5215 'patient-years' of observed follow-up. Following these overall considerations, details of four subprojects are annexed, each of which was presented as a 'free paper' at the 8th World Congress and concerning, respectively, the changing natural history of IBD, risks of perforation and toxic megacolon in the 1980s, IBD in elderly patients, and features associated with recurrence in Crohn's disease.

The natural history of inflammatory bowel disease: has there been a change in the last 20 years?

This presentation reviews the course and outcome of disease in 2657 cases of inflammatory bowel disease (IBD) registered into the OMGE multinational survey and considers whether there are differences between the natural history of IBD observed in this series and that observed in earlier large-scale series. It is concluded that several such differences exist. The current mortality from ulcerative colitis (4% in 10 years) is similar to that from Crohn's disease and quite different from that recorded in earlier series (over 20% in 10 years). This may be because the disease itself has changed (the proportion of patient-years with severe attack has fallen from 14.6% in the 1960s to under 10% in the present series). It may also be because of increasing use of maintenance sulphasalazine (since the attack rate per year is significantly lower than patients on maintenance therapy). Finally, cancer is now equally common in Crohn's disease and ulcerative colitis patients; whilst perforation is more common in Crohn's disease (possibly because ulcerative colitis patients now tend to come to surgery earlier).

Perforation of the intestine in inflammatory bowel disease. An OMGE survey.

This presentation assesses the incidence of perforation of the intestine in patients with inflammatory bowel disease by reviewing the incidence of this complication in a total of 3175 patients from the OMGE inflammatory bowel disease multi-national survey. Amongst 1928 patients with ulcerative colitis, perforation was noted in only 5 (0.3%), which is much lower than in previous series (from 1% to 2%). By contrast, 19 of 1247 patients with Crohn's disease had perforated (1.5%). The survey thus suggests that the incidence of perforation in ulcerative colitis has fallen in the last 2 decades, probably as a result of the widespread implementation of early surgery. The risk of perforation of Crohn's disease remains quite high.

Inflammatory bowel disease in the elderly patient.

Studies of inflammatory bowel disease (IBD) undertaken in the 1960s reported a highly unfavourable course and prognosis in patients over the age of 60 years. However, recent surveys have suggested that the pattern of IBD in the elderly patient is similar to the overall pattern of disease in other age groups. We have, therefore, reviewed data relating to 2657 patients from the OMGE series with particular reference to the pattern of disease in 244 patients (9.1% of the total group) aged over 60 years at the time of registration into the survey. The course and outcome of disease in these 244 patients were similar to other age groups in terms of response to therapy, major complications, and rate of recourse to surgery. However, the death rate in the elderly (2.4%) was higher than that in younger patients (0.8%). We concur with recent studies that the course of IBD is now more favourable in elderly patients than hitherto suspected. The cause is probably multifactorial, involving both a change in therapy and a change in the natural history of the disease.

Factors affecting recurrence after surgery for Crohn's disease.

The prospect of recurrence following surgery for Crohn's disease (CD) poses an important and difficult problem in routine clinical practice. Out of the 1247 CD patients registered in the OMGE multinational inflammatory bowel disease survey, a high proportion came to surgery. A detailed study has been undertaken of 154 patients (77 who did recur matched with 77 who did not recur) who had undergone surgery for CD. An assessment was made which established a 'risk factor' (RF) for each item of patient information. Findings indicated the risk of recurrence to be higher in patients under 20 years both at onset of disease (RF, 2.2:1) and at time of their operation (RF, 2.7:1) and in patients with distal colonic Crohn's disease (RF, 1.8:1). Histopathologic findings, number of previous operations, and symptomatic status prior to operation did not appear to affect the subsequent risk of recurrence. The margin of clearance at operation appeared to affect further recurrence. Amongst patients with 10cm or more margin of clearance (i.e. histopathologically normal bowel) only 21% recurred during follow-up, versus 50% in those with a smaller margin of clearance.

Treatment of reflux oesophagitis with a carbenoxolone/antacid/alginate preparation. A double-blind controlled trial.

Twenty-nine patients were treated with a carbenoxolone/antacid/alginate preparation (Pyrogastrone) and 30 with antacid/alginate alone four times each day for 8 weeks, in a double-blind study, to ascertain the value of carbenoxolone in the treatment of patients with endoscopically confirmed reflux oesophagitis. Symptom review every 2 weeks and endoscopic findings every 4 weeks were converted to a 6-point grading system to facilitate statistical comparison, using a stochastic model for predicting the rate of change in grades during treatment. Carbenoxolone-treated patients showed an 82% improvement in symptom grades over 8 weeks and improved 50% faster (P less than 0.01) than did control patients, who showed a 63% improvement. Endoscopic improvement was not significantly different in the first 4 weeks, although healing was better maintained in carbenoxolone-treated patients during the second 4 weeks (P less than 0.05). At the low doses used (5 X 20 mg daily) no significant side effects of carbenoxolone were encountered. Pyrogastrone should be considered as a therapeutic alternative in patients who fail to respond to routine management with antacids.