Chronic pancreatitis with biliary obstruction.

In a 4-year review of 509 patients with chronic pancreatitis, the incidence of clinically manifest fixed common bile duct (CBD) stenosis was 9% (45 patients). In 76% this was alcohol related, and pancreatic calcification was present in 51%. All patients presented with unrelenting jaundice and five (11%) had cholangitis. The mean serum bilirubin (165 +/- 108, normal 0-17 mumol/l), alkaline phosphatase (1790 +/- 1143, normal 73-207 U/l) and gamma glutamyl transferase (798 +/- 660, normal 7-64 U/l) were markedly raised. Diabetes occurred in 8 (18%). A biliary drainage operation was performed in 43 patients and 11 had concomitant pancreaticojejunostomy. Endoscopic retrograde cholangiopancreatography (ECRP) provided valuable information preoperatively in outlining both biliary and pancreatic disease in selecting patients for dual ductal drainage. Minor complications not related to biliary anastomosis occurred in 14%. Four patients died (9%), two from pseudocyst-related haemorrhage. Jaundice was successfully relieved in all and did not recur during follow-up. No secondary biliary cirrhosis was encountered, but varying degrees of portal fibrosis were present in 75% of liver biopsies. The commonest biliary pathogen was E. coli. It is recommended that a biliary bypass operation be performed when the diagnosis is radiologically confirmed and no improvement occurs within 1 month.

Alterations in the cytological composition of the juxta-scar villous mucosa after ulcer therapy with sucralfate or cimetidine.

A comparative light-microscopic morphometric analysis of non-metaplastic mucosa obtained from the pretreatment juxta-duodenal ulcer (DU) villous mucosa of 10 patients and from the first part of the duodenum of 5 normal volunteers revealed a significant increase (P less than 0.01) in the number of goblet cells (GCs) per 100 microns of villous mucosa (GC/100 microns). Such an increase was thought to represent a mucoprotective response by the mucosa to the corrosive lumenal factors that may cause or maintain ulceration. A similar morphometric analysis was performed on the endoscopically healed juxta-scar villous mucosa of 11 patients successfully treated for 6 weeks with sucralfate (5 patients) or cimetidine (6 patients). After treatment with cimetidine, GC/100 microns was reduced to near-normal levels, whereas after sucralfate therapy it was significantly raised (P less than 0.05). The difference in GC/100 microns after treatment with either sucralfate or cimetidine was significant at the P less than 0.02 level. The apparent drug-mediated difference in the cytological composition of the healed mucosa was thought to be a function of the pharmacodynamic mechanisms of action of the two drugs in promoting DU healing. It is proposed that the retention of GC hyperplasia after curative therapy with sucralfate may predisposed patients so treated to extended periods of remission.

Comparative study of sucralfate 2 grams twice daily versus sucralfate 1 gram four times daily in the treatment of benign gastric ulcers in outpatients.

In a double-blind, randomized study, we compared the healing of gastric ulcer during a twice-daily regimen of 2 g sucralfate or sucralfate 1 g q.i.d. Patients receiving the former therapy received the tablets one-half hour before breakfast and at bedtime. Patients receiving sucralfate 1 g q.i.d. received their therapy 30 minutes before breakfast, lunch, and supper, and at bedtime. The study included 52 patients with endoscopically proven gastric ulcer; 41 patients completed the study. Healing was endoscopically assessed at 8 weeks and 12 weeks. After 8 and 12 weeks the healing rate for sucralfate 2 g b.i.d. was 67% and 92%, respectively; the healing rate of sucralfate 1 g q.i.d. was 59% and 71%, respectively. No statistically significant difference was found between the two regimens. The results suggest that 2 g sucralfate twice daily is as effective in the healing of gastric ulcer as 1 g sucralfate q.i.d.

Incidence of Campylobacter pylori in patients with upper gastro-intestinal symptoms.

Antral mucosal biopsy specimens were examined microbiologically and histologically for the presence of Campylobacter pylori in 224 patients with upper gastrointestinal symptoms. The gastric mucosa of 183 patients (82%) were found to harbour C. pylori. C. pylori was strongly associated with the presence of histological gastritis (93%) and was detected in only 10% of 30 patients in whom histological examination of gastric biopsy specimens was negative. Endoscopically diagnosed duodenal lesions were more strongly associated with the presence of C. pylori than gastric lesions (P less than 0.001). The histological demonstration of spiral bacteria in biopsy specimens was a more sensitive method for the diagnosis of C. pylori than culture (80% v. 65%).

Pirenzepine and cimetidine for duodenal ulcers. A comparative randomised double-blind controlled study.

A double-blind controlled trial was undertaken to compare the relative effectiveness of pirenzepine (Gastrozepin; Boehringer Ingelheim) and cimetidine (Tagamet; SK & F) in healing endoscopically proven duodenal ulcers. Thirty patients with duodenal ulcers were treated with pirenzepine 50 mg twice daily and 30 patients with cimetidine 400 mg twice daily. Endoscopy was repeated after 4 weeks. Ulcers healed completely in 15 patients on pirenzepine and 21 patients on cimetidine (chi-square test 3.05; P less than 0.1); this difference was not significant. Treatment resulted in endoscopic improvement in 25 patients on pirenzepine and in 26 patients on cimetidine; this difference was also not statistically significant (chi-square test 1.18; P less than 0.5). No adverse effects were seen with cimetidine. Mild and reversible side-effects were seen in 4 patients on pirenzepine. The efficacy of pirenzepine appears similar to that of cimetidine in the healing of duodenal ulcers.

Variations in the morphology of villous epithelial cells within 8 mm of untreated duodenal ulcers.

In order to investigate the bio-mechanics of duodenal ulcerogenesis and compare the 'quality' of drug mediated mucosal healing, it is necessary to define the morphological appearance of ulcerative mucosae. This report describes the morphological appearance of pre-therapy, juxta-duodenal ulcer (DU) villous epithelia. Biopsies made at endoscopy from the first part of the duodenum in four healthy volunteers and 3-8 mm from the edge of the DU in 97 patients were examined by light and electron microscopy. Irrespective of whether biopsies were made from the normal or juxta-DU mucosa, the villous epithelium was populated by one, or more, of six, morphologically identifiable cell types. Control epithelia were populated with normal goblet and absorptive cells. Based on the fine-structural characteristics of the predominant cell type, pathological specimens were divided into two groups: metaplastic (Group 1) and non-metaplastic (Group 2). Group 1 specimens were either exclusively populated with fully differentiated metaplastic gastric surface mucus secreting cells (GMC) (Group 1A), or GMC in various phases of metaplastic differentiation together with abnormal goblet cells (Group 1B). Group 2 specimens were populated with 'pathological' absorptive and normal goblet cells. It is postulated that the group variations in pre-therapy juxta-DU morphology represent various phases in the natural history of duodenal ulcerogenesis and healing.

A comparative study of misoprostol and ranitidine in the healing of duodenal ulcers. A double-blind controlled trial.

This study was undertaken to evaluate the safety and therapeutic efficacy of the prostaglandin E1 analogue, misoprostol, when compared with ranitidine in the healing of duodenal ulcers. Sixty patients with endoscopically proven duodenal ulcers participated in a double-blind controlled randomised trial comparing misoprostol 400 microgram and ranitidine 150 mg, both given twice daily orally for up to 8 weeks. Patient characteristics at entry into the trial were similar in the two treatment groups, except that there were 6 women in the ranitidine-treated group and none in the misoprostol-treated group. Ulcers were 0.3 - 2.0 cm in length. Healing was determined by endoscopy at 4 weeks; if ulcers were not healed, endoscopy was repeated at 8 weeks. All patients were given antacid tablets to be used as needed for pain up to a maximum of 8 tablets per day. Healing rates at 4 weeks for a total of 58 evaluate patients in the two treatment groups were: misoprostol (15/29; 51.7%) and ranitidine (20/29; 69.0%). Healing rates at 8 weeks for a total of 55 evaluable patients in the two treatment groups were: misoprostol (21/27; 77.8%) and ranitidine (24/28; 85.7%). The healing rate for misoprostol did not differ significantly from that for ranitidine at both the 4-week (P = 0.28) and the 8-week assessment (P = 0.68). Diarrhoea was the most common side-effect but was usually mild. It occurred in 11 patients on misoprostol and 1 patient on ranitidine. These results indicate that misoprostol 400 micrograms was taken twice daily orally for up to 8 weeks is effective and safe for the treatment of duodenal ulcer.

Stressful life situations and perception of stress in black and Indian duodenal ulcer patients.

The stressful life situations of 87 patients with endoscopically confirmed recent duodenal ulceration (DU) were compared with those of 75 essentially orthopaedic non-DU controls. Results indicated a statistically significant difference in the reporting of low income and dissatisfaction, including tensions related to considerable responsibility in the work situation but no authority, by both Indian and black DU patients. Indian DU patients reported significantly more family conflict and problems than controls, while black DU patients reported living in single hostels or in split families to a significantly greater degree than controls. Overall, DU patients experienced significantly greater stress in more areas of their lives than controls.

Dysphagia and dystrophia myotonica. A case report.

A 26-year-old Indian man who presented with a long history of vomiting, upper abdominal pain and dysphagia is described. The dysphagia had been largely overlooked and investigation delayed. The diagnosis of dystrophia myotonica (DM) was apparent on clinical examination and his symptoms responded well to phenytoin therapy. The cause of his symptoms is discussed and the importance of recognizing dysphagia and other gastro-intestinal manifestations of DM is emphasized.

Misoprostol, a synthetic prostaglandin E1 analogue, in the treatment of duodenal ulcers. A double-blind, cimetidine-controlled trial.

The effects of two dosage levels of a synthetic prostaglandin E1 analogue, misoprostol, and cimetidine on short-term duodenal ulcer healing were compared in a double-blind, endoscopically controlled 4-week study. The 66 adult patients were randomly divided into three groups, receiving either misoprostol 200 micrograms 4 times a day, misoprostol 50 micrograms 4 times a day or cimetidine 300 mg 4 times a day. Rates of healing were comparable in the three groups, with complete healing in 62% of those patients receiving cimetidine and high-dose misoprostol. Patients whose ulcers had healed were then followed up for a further 6 months in order to assess recurrence rates. Relapse rates were significantly higher in the cimetidine-treated group (85% within 6 months) than in the misoprostol-treated groups (50% in the low-dose and 38% in the high-dose group).

Double-blind placebo-controlled evaluation of one year therapy with sucralfate in healed duodenal ulcer.

Forty patients with duodenal ulcer, considered healed at endoscopy, were entered in a double-blind trial and treated for up to one year with sucralfate, 500 mg before breakfast, lunch, supper and 1000 mg on retiring, or with placebo. The subjects were interviewed and endoscopy was performed at 0, 3, 6, 9 and 12 months or at any time if pain recurred and they returned to the clinic. On relapse, the patients were withdrawn from trial. The remission rate maintained by sucralfate was superior to that achieved by placebo. The difference was significant (p less than 0.05) at 6 months (64% vs. 27%) and at 12 months (56% vs. 18%). No important side effects were noted.

Pirenzepine, cimetidine and placebo in the long-term treatment of duodenal ulceration. A comparative study.

Sixty patients with endoscopically proven healed duodenal ulcers were treated for a year with either pirenzepine (Gastrozepin; Boehringer Ingelheim) 100 mg daily, cimetidine 400 mg at night, or placebo, The monthly relapse rate (patients per month) in the first 3 months (pirenzepine 2,3, cimetidine 2,3, placebo 3,0) and in the next 9 months (pirenzepine 0,33, cimetidine 0,44, placebo 0,56) is lower for pirenzepine and cimetidine than for placebo. This trend is in favour of pirenzepine and cimetidine as effective means of keeping duodenal ulcers in remission. Asymptomatic relapses were also less common with pirenzepine (50%) and cimetidine (45%) than with placebo (64%). No serious side-effects of pirenzepine were observed during the trail.

The effect of tri-potassium di-citrato bismuthate on the duodenal mucosa during ulceration. An ultrastructural study.

The manner in which tri-potassium di-citrato bismuthate (TDB) promotes duodenal ulcer healing is not known. Endoscopic biopsy specimens were taken from the edges of duodenal ulcers from 5 patients before and after treatment with TDB. Using the bismuth contained within this drug as an electron-dense marker, the mode of action of TDB was determined by transmission electron microscopy. TDB was found to promote ulcer healing by adhering to the ulcerative mucosa, thereby providing an effective barrier to the substances which cause and maintain ulceration.

Changes in the morphology of villar epithelial cells adjacent to duodenal ulcers during the process of healing.

Fifteen patients with active duodenal ulcers were treated for 6 weeks with ulcerone, aluminium sucrose sulphate, or bromazepam to promote healing. Biopsies taken from the edge of ulcers before treatment showed an epithelium exclusively populated with cells of a mucus-secreting type which resembled those normally found in the gastric antrum. Biopsies taken at endoscopy from the edge of ulcers or scars at time intervals during treatment to endoscopic healing showed, irrespective of the drug used, a sequence of ultrastructural changes in villar epithelial cells, from a gastric secretory to a duodenal absorptive cell type. We suggest that the gastric cells in the duodenum are derived from stem cells in the crypts of Lieberkühn surrounding an ulcer and are produced in response to luminal fluids of abnormally low pH. Their function is probably protective, in that they isolate regions of ulceration from the healthy mucosa and, by the continuous secretion of gastric mucin, protect the ulcer from the harmful effects of luminal acids. Their transformation to absorptive cells during ulcer healing is part of a natural sequence that is aided by, but not dependent on, drug therapy.

Factors affecting duodenal ulcer healing. Four double-blind trials in 193 patients.

An analysis of four double-blind endoscopically controlled trials carried out in 1978 -1980 is presented. Drugs utilized were (patient numbers in brackets): a new histamine H2-receptor antagonist ranitidine (25) v. placebo (22), the colloidal bismuth ulcer-coating preparation bicitropeptide (24) v. cimetidine (26), the tricyclic antidepressant trimipramine (20) v. placebo (19), and the disaccharide coating preparation sucralfate (29) v. placebo (28). Factors analysed were smoking, alcohol consumption, age, length of history, sex and race. The prevalence of smoking and alcohol use, age and length of history varied in the four trials. Pronouncements regarding these factors based on small trials are therefore unreliable. There were no overall diffeences in healing rates whether the patient smoked, consumed alcohol, was above or below 40 years of age, or had a history shorter or longer than 1 year. Comparison of drug and placebo responses revealed that the differences between these were most significant in: non-smokers (P=0,0010) compared with smokers (P=0,0288); teetotallers (P<0,005) compared with alcohol consumers (NS); history under 1 year (P<0,005) compared with over 1 year (P<0,025); males (<0,01) compared with females (NS); and Indians (P<0,005) compared with Blacks (NS).