Satiation, the process that brings eating to an end, and satiety, the state of inhibition over further eating, may be influenced by cholecystokinin (CCK). In animal and human studies, it has been shown that infusion of exogenous CCK decreases food intake, but the doses given may well have led to supraphysiological plasma concentrations. This study was done to discover if a low dose of intraduodenal fat releasing physiological amounts of endogenous cholecystokinin exerts satiation or satiety effects, or both and if these effects could be inhibited by the CCK receptor antagonist loxiglumide. In 10 healthy lean volunteers (5 F, 5 M, mean age 26) three tests were performed in a randomised blind fashion. Intralipid 20% (6 g/h) (experiments A and C) or saline (experiment B) were given intraduodenally from 1030 until 1300. The subjects received saline (experiments A and B) or loxiglumide (experiment C) a specific CCK-receptor antagonist (10 mg/kg/h) intravenously from 0930 until 1300. At 1200 a meal was served. At regular time intervals hunger feelings were measured using visual analogue scales and food selection lists and plasma CCK was measured by radioimmunoassay. Food intake (mean (SEM)) during intraduodenal fat (206(35)g) was lower than in the control study (269(37)g, p = 0.09). Loxiglumide largely prevented the inhibitory effect of intraduodenal fat on food intake (245(30)g). From 1030 until the meal at 1200 there was a significant satiating effect of intraduodenal fat compared with the control and loxiglumide experiments according to the food selection lists, which was because of the satiating effect for the fat rich items (p<0.05). Also feelings of fullness were significantly higher during intraduodenal fat than in the control or loxiglumide experiments (p<0.05). During intraduodenal fat there was a significant increase of plasma CCK from 2.4(0.3) to 4.8(0.4) pM (p<0.001). Loxiglumide led to an exaggerated CCK release to a peak concentration of 16(2.4) pM before the meal. This study shows that in humans low dose intraduodenal fat increases satiety and satiation, mainly through the effect of CCK.

Parenteral 5-hydroxytryptamine stimulates small intestinal motility, but the effect of continuous stimulation with 5-hydroxytryptamine on the human migrating motor complex is unknown. Using a selective 5-hydroxytryptamine reuptake inhibitor, paroxetine, this study investigated the effect of indirect 5-hydroxytryptamine agonism on fasting small intestinal motility and transit. Eight healthy subjects were studied while receiving paroxetine 30 mg daily for five days and while receiving no treatment, in random order. Ambulant small intestinal motility was recorded from five sensors positioned from the duodenojejunal flexure to the ileum for 16-18 hours. Paroxetine reduced the migrating motor complex periodicity mean (SEM) from 81 (6) min to 67 (4) min (p < 0.05), and increased the propagation velocity of phase III from 3.1 to 4.7 cm/min in the proximal jejunum (p < 0.01), and from 1.6 to 3.4 cm/min distally (p < 0.001). Orocaecal transit time measured by lactulose hydrogen breath test was reduced by paroxetine from 70 (9) min to 48 (7) min (p < 0.05). These data suggest that 5-hydroxytryptamine participates in the control of migrating motor complexes in humans, and that selective 5-hydroxytryptamine reuptake inhibitors have a prokinetic action in the human small intestine.

Gastric acid suppression could improve heartburn by healing oesophagitis or by reduction of oesophageal sensitivity to acid. To independently assess changes in oesophageal sensitivity, it would be necessary to study patients with reflux disease but no oesophagitis. The aim of this study was to investigate the effect of acid suppression on oesophageal sensitivity and to assess the time course of any measured effect. Twenty seven patients were recruited, of whom 25 completed the study (14 men and 11 women, mean (SD) age 50 (15) years). All had classic symptoms of gastro-oesophageal reflux but normal results of upper gastrointestinal endoscopy and oesophageal mucosal histological tests. Each had abnormal 24 hour pH studies and a positive acid perfusion tests. Subjects were assigned double blind to placebo (n = 11) or famotidine 40 mg twice daily (n = 14) for four weeks. Acid perfusion tests were carried out at 0, 4, 5, and 8 weeks and time to heartburn recorded. Time to heartburn (mean (SEM)) was 124 (78) seconds in the famotidine and 187 (154) in the placebo group at week 0 (NS). Compared with baseline, significant increases in time to heartburn was found with famotidine at weeks 4 (383 (102), p < 0.01) and 5 (344 (92), p < 0.01) but not week 8 (336 (90) seconds). No significant effects were found with placebo (219 (41), 146 (23), and 144 (25) seconds for weeks 4, 5, and 8). Heartburn symptom score decreased significantly with famotidine (mean scores 3.6, 1.9, 2.1, and 2.6 at weeks 0, 4, 5, and 8 (p=0.001)) and showed a significant negative correlation with time to heartburn (r(s)=-0.60; p<0.0001). It is concluded that oesophageal sensitivity to acid is reduced by famotidine independent of and effect on oesophagitis; the effect wanes one to four weeks after the end of treatment and correlates with change in heartburn score.

Patients having endoscopic retrograde cholangiopancreatography (ERCP) are generally elderly and require sedation while in the prone position. These factors may be expected to aggravate any risk of arterial hypoxia. This study evaluated two protocols of oxygen administration, one with and one without pre-oxygenation. In 25 patients in whom pre-oxygenation with 4 litres/minute for five minutes before sedation was used, followed by continuous oxygen administration, arterial oxygen saturation did not fall below 90% at any stage during the procedure. By contrast, in 25 patients who were not pre-oxygenated oxygen saturation fell below 90% in nine (36%). As expected, hypoxia occurred most frequently during the early stages of sedation and endoscope insertion. Hypoxia did not occur in association with operations such as sphincterotomy, stone extraction or stent insertion. This study confirms that arterial hypoxia is a common event during ERCP and can be completely prevented by pre-oxygenation with four litres of oxygen given intranasally for five minutes before sedation.

One hundred and thirty patients with active symptoms of Crohn's disease were treated in a double blind randomised controlled trial with rifampicin, isoniazid, and ethambutol, or identical placebos for up to two years. All other treatment considered necessary was continued. Analyses were based on 126 patients, 63 in each treatment group. Thirty seven in the active and 30 in the placebo group had previous surgical procedures. There was no difference in concomitant treatment between the two groups. Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial. Forty eight of 63 patients in the active and 49 of 63 in the placebo group, completed at least 12 months' therapy. Reasons for early withdrawal included pregnancy, adverse reaction, and failure to comply. There was no significant difference in the mean number of months completed between the two groups. Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo. All of the nine patients withdrawn early because of adverse reactions were in the active group. Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups. Radiological assessments based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease. More patients developed strictures on placebo compared with active treatment but without a statistically significant difference. No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above. Serial measurements of body weight and Crohn's disease activity index (CDAI) together with blood values for albumin, haemoglobin, white cell count, and platelets showed no consistent different differences between groups. There were occasional significant differences for some of these values between groups, which were not sustained. The trail provides little evidence of tangible benefit from the trail treatment.

This study was designed to determine if the differential effect of high fat and high carbohydrate meals on mesenteric blood flow is a result of changed gastric emptying rate. Eight healthy men were studied twice. Superior mesenteric artery blood flow (Doppler ultrasound) was measured before and after a 2.5 MJ meal (either 74% of the energy as carbohydrate or 71% as fat). Emptying of meals was followed by gamma-scintigraphy. The pattern of the superior mesenteric artery blood flow response was different after the two meals (interaction effect p < 0.001 analysis of variance), with a far more sustained response after fat. The time by which half the meal had emptied (t50) was also significantly greater after fat (p < 0.02). Superior mesenteric artery blood flow corresponding to t50 was 449 ml/min after carbohydrate and 592 ml/min after fat. There was a significant curvilinear relation between the superior mesenteric artery blood flow response and gastric emptying after carbohydrate (r2 = 0.94) and no relation at all after fat. This study confirms the finding that ingestion of meals with a high fat content slows gastric emptying compared with meals with a high carbohydrate content in healthy volunteers. A more sustained mesenteric hyperaemia was also recorded after the fat meal compared with the carbohydrate meal. The relation, however, between the volume of meal remaining in the stomach and the mesenteric response was considerably different after the two meals. Further study is required to elucidate the mechanism behind the vascular responses recorded in the mesenteric bed after food in humans.

This study aimed to record 24 hour jejunal motility in healthy ambulant subjects and to analyse changes in motility caused by the oral administration of an anticholinergic agent, the quaternary ammonium compound, trospium chloride. In a placebo-controlled, double blind crossover trial, 24 hour jejunal motility was recorded in 12 healthy volunteers, aged 25 (21-30) years, using a digital data logger connected to two strain-gauge transducers mounted 20 cm apart in a flexible nasojejunal catheter. A computer program was developed to determine contraction parameters. Trospium chloride (15 mg orally thrice daily) prolonged the duration of irregular contractile activity after meals (p < 0.02) and reduced its contraction frequency and amplitude (p < 0.001). In the fasting state, the cycle length of the migrating motor complex was prolonged (p < 0.01) by an extended phase I (p < 0.025). Phase III was shortened (p < 0.005) and showed a slower aboral migration velocity (p < 0.005). Clustered contractions were less frequent during postprandial and fasting periods (p < 0.01). Runs of clustered contractions were completely absent with trospium chloride. Digital manometry was useful for long term recordings of jejunal motility and enabled the motor effects of an anticholinergic agent to be characterised in ambulant subjects.

The extent of duodenal bacterial overgrowth during the pronounced inhibition of acid secretion that occurs with omeprazole treatment is unknown. The bacterial content of duodenal juice of patients treated with omeprazole was therefore examined in a controlled prospective study. Duodenal juice was obtained under sterile conditions during diagnostic upper endoscopy. Aspirates were plated quantitatively for anaerobic and aerobic organisms. Twenty five outpatients with peptic ulcer disease were investigated after a 5.7 (0.5) weeks (mean (SEM)) treatment course with 20 mg (nine patients) or 40 mg (16 patients). The control group consisted of 15 outpatients referred for diagnostic endoscopy without prior antisecretory treatment. No patient in the control group had duodenal bacterial overgrowth. In the omeprazole group bacterial overgrowth (> or = 10(5) cfu/ml) was found in 14 (56%) patients (p = 0.0003). The number of bacteria (log10) in duodenal juice in patients treated with omeprazole was distinctly higher (median 5.7; range < 2-8.7) when compared with the control group (median < 2; range < 2-5.0; p = 0.0004). As well as orally derived bacteria, faecal type bacteria were found in seven of 14 and anaerobic bacteria in three of 14 patients. Bacterial overgrowth was similar with the two doses of omeprazole. These results indicate that duodenal bacterial overgrowth of both oral and faecal type bacteria occurs often in ambulatory patients treated with omeprazole. Further studies are needed to determine the clinical significance of these findings, particularly in high risk groups during long term treatment with omeprazole.

The effects of octreotide on six normal subjects and five patients with scleroderma were investigated. Changes in intestinal motility and in plasma motilin were examined after a single injection of octreotide. Octreotide stimulated intense intestinal motor activity in normal subjects. Motility patterns in the scleroderma patients were chaotic and non-propagative, but, after octreotide was given, became well coordinated, aborally directed, and nearly as intense as in normal volunteers. Clinical responses and changes in breath hydrogen were also evaluated in the five scleroderma patients who had further treatment with octreotide at a dose of 50 micrograms/day subcutaneously for three weeks. A reduction in symptoms of abdominal pain, nausea, vomiting, and bloating was seen. Additionally, there was an improvement in bacterial overgrowth as objectively measured by breath hydrogen testing. The effects of octreotide (100 micrograms/day subcutaneously) on the perception of rectal distension were investigated in a double blind, placebo controlled study in healthy volunteers. Octreotide was shown to reduce the perception of rectal distension without affecting motor pathways or local rectal reflexes. This enhanced tolerance to volume distension seems to result from inhibition of sensory afferent pathways as shown by electroencephalographic studies showing diminished evoked spinal and cortical potentials after octreotide. In irritable bowel syndrome patients with rectal urgency, octreotide reduces rectal pressures and perception after rectal distension to near normal values.

Over the past 10 years, several clinical and experimental studies report the potential benefit of enteral nutrition as primary therapy after multiple system trauma. In this study, 98 patients sustaining blunt and penetrating trauma were randomised to receive either enteral or parenteral feeding for 15 days. There were significantly fewer infectious complications in patients randomised to receive enteral feeding with particular benefit shown in the most severely injured patients. Serum protein concentrations correlated with the clinical outcome with an increase in constitutive protein and decrease in acute phase protein concentrations occurring in the enteral group through a decrease in septic complications and possible direct hepatic 'reprioritisation'. Enteral feeding serves as a primary therapy affecting the outcome of critically ill patients.

Maintenance treatment of duodenal ulcer (DU) with ranitidine 150 mg/day was compared with placebo in a two year prospective multicentre randomised study. Three hundred and ninety nine patients were included (mean age: 44.7 years, M/F ratio = 2.47/1; 37.6% of smokers) in placebo (n = 202) and ranitidine (n = 197) groups. Efficacy was assessed by the length of time to the first ulcer pain attack (with or without endoscopic confirmation) or DU complication. One hundred and fourteen patients of 399 (28.6%) had incomplete follow up. Actuarial survival curves of patients without ulcer pain (26 and 53% at two years in placebo and ranitidine groups, respectively) were significantly different (p < 0.0001). Endoscopies were performed depending on physicians' decision (mainly where there was severe pain or complication). Patients without relapses from endoscopy were more frequent in the ranitidine group (83%) than in the placebo group (47%, p < 0.0001). A greater incidence of complications, mainly bleeding, was also seen in the placebo group (13 complications v two in the ranitidine group, p < 0.002). No factor predicting DU relapse was identified. No important side effect was encountered. Ranitidine 150 mg/day is effective and well tolerated in preventing ulcer pain attacks and DU complications for up to two years.

Lipiodol injected into the hepatic artery is selectively retained in hepatomas so has been used as a vehicle for cytotoxic drugs. This study compared treatment with 5-epidoxorubicin emulsified in lipiodol and infused into the hepatic artery with symptomatic treatment alone in a randomised trial. Of 136 patients with hepatoma 78 (57%) were not eligible, eight (6%) refused to take part, and 50 entered the trial (chemotherapy: n = 25, symptomatic treatment: n = 25). The two groups had similar prognostic indices. Seven of 25 patients allocated to chemotherapy were unable to receive it. The slight survival disadvantage associated with chemotherapy was not significant (median survival 48 days compared with 51 days, log rank chi 2 = 0.07, p > 0.05). Patients given chemotherapy spent significantly longer in hospital, however (median three days compared with one, p = 0.0008). Changes in symptoms and indices of tumour growth did not differ significantly between the two groups. It is concluded that infusion of 5-epidoxorubicin emulsified in lipiodol for hepatoma increased morbidity but did not affect survival. In addition, most patients were unsuitable for this treatment because of advanced disease. The patients in the trial had a short median survival time so the conclusions may not be valid for other patients with hepatoma.

This study aimed to investigate the effects of chronic ingestion of small amounts of gliadin on children with coeliac disease. A four week challenge was performed on 20 children who had been on a gluten free diet for mean (SD) 14 (3) months. They were given a daily dose of either 100 mg (group A, n = 10, mean age 4 (2) years) or 500 mg of gliadin (group B, mean age 5 (3) years). The effects of the gliadin were monitored by morphometric study of the jejunal mucosa, intestinal permeability test with cellobiose/mannitol, and serum antigliadin antibody test. After the challenge, group A patients showed a significant increase in the mean intraepithelial lymphocyte count (before challenge 11 (3), afterwards 19 (6)) and a decrease in the villous height/crypt depth ratio (beforehand 1.5 (0.1), afterwards 1.3 (0.2)), while the intestinal permeability test remained normal and the IgA-antigliadin antibody increased in four of 10 children. After the challenge group B showed more pronounced histological changes, an increase in the mean urinary cellobiose/mannitol % (beforehand 0.028 (0.020), afterwards 0.058 (0.028)), and IgA-antigliadin antibody positivity in six of eight subjects. The discriminant analysis function showed that the pretreatment group, group A after challenge, and group B after challenge were correctly classified in 90% of cases by functions based on the individual intraepithelial lymphocyte count and the villous height/crypt depth ratio. This study shows that chronic ingestion of small amounts of gluten causes dose-dependent damage to the small intestinal mucosa in children with coeliac disease. The predictive value of laboratory tests, such as the antigliadin antibody test and the intestinal permeability test seems to be lower in treated patients than in those with active coeliac disease.

A controlled, randomised study was performed to evaluate the efficacy of treatment with heater probe in the prevention of rebleeding from peptic ulcer with a non-bleeding visible vessel. One hundred and one patients were randomised into two groups: patients to be treated by heater probe (n = 51) and controls without active treatment (n = 50). In the heater probe group rebleeding occurred in five patients (10%) v 13 (26%) in the control group (p = 0.03), with a comparative risk of 0.38 in favour of the heater probe group. The difference in proportions of successful treatment for each group was 16.2% in favour of the heater probe (95% CI = 2 to 31%). Haemorrhage directly related to heater probe treatment occurred in four patients. In three of them bleeding was easily controlled by further heater probe pulses. There were no other complications and no death in the heater probe group. One patient in the control group died of pulmonary embolism. No significant differences in the length of stay in hospital, blood transfusions, surgical rates, or death were found; the design of the study, however, precluded an adequate assessment of these variables, because the heater probe was an optional rescue treatment when high surgical risk patients rebled. These results suggest that the heater probe is an effective and safe procedure in the prevention of recurrent haemorrhage in peptic ulcer with a non-bleeding visible vessel.

To investigate the effects of supplemental oxygen on cardiac rhythm during gastroscopy, 103 patients aged over 60 were randomised to receive either supplemental oxygen or air at 2 litres/minute during the procedure. Pulse rate, blood pressure, oxygen saturation, and a Holter cardiac trace were monitored before, during, and for one hour after the gastroscopy. A wide range of electrocardiographic abnormalities were recorded in both oxygen and air groups, of which ventricular and supraventricular ectopic beats were the most common. There were no significant differences in the rate of occurrence of any clinically important cardiac abnormality either between the oxygen and air groups or between the three monitored periods before, during, and after gastroscopy. There were significantly fewer patients, however, with supraventricular extra systoles when oxygen was given during gastroscopy (p < 0.05). Although supplemental oxygen during gastroscopy significantly improved oxygen saturation (p < 0.001; 95% confidence intervals for the difference between the means: 2.9 to 4.7), there was no correlation between oxygen saturation and any electrocardiographic changes. It is concluded that electrocardiographic abnormalities are common in patients over 60, but this study found no evidence that they are induced by gastroscopy. Supplemental oxygen increases oxygen saturation but does not reduce the incidence of clinically important cardiac arrhythmias.

The purpose of this study was to compare duodenal ulcer healing, symptom relief, and safety of lansoprazole (a new proton pump inhibitor) given at doses of 30 mg and 60 mg, in the morning with ranitidine 300 mg at bedtime. Two hundred and eighty nine patients were enrolled over a 20 month period in a double blind randomised parallel group comparative study set in outpatient endoscopy units of six United Kingdom medical centres. Patients were randomised to receive lansoprazole 30 mg in the morning (n = 95), 60 mg in the morning (n = 96), or ranitidine 300 mg at bedtime (n = 98) for four weeks. Efficacy was assessed by gastroscopy at study entry and after two and four weeks of treatment. Symptom relief was monitored by patient diaries and physician review at two and four weeks. Both doses of lansoprazole resulted in significantly greater ulcer healing than ranitidine after two and four weeks. Respective healing rates on lansoprazole 30 mg, 60 mg, and ranitidine 300 mg were 78%, 80%, and 60% after two weeks and 93%, 97%, and 81% after four weeks. Patients on lansoprazole 30 mg (p = 0.002) and lansoprazole 60 mg (p = 0.026) also recorded greater relief of night time pain in the diary cards during the first seven days of treatment than those on ranitidine. Patients on lansoprazole 60 mg reported significantly better pain relief at their two week visit compared with those receiving ranitidine (p = 0.007). There were no differences between treatment groups in the occurrence or pattern of adverse drug reactions during the trial. It is concluded that for patients with duodenal ulcer, lansoprazole 30 mg or 60 mg is associated with faster ulcer healing and better symptom relief than ranitidine 300 mg at bedtime. There were no significant differences between lansoprazole 30 mg and 60 mg. These data indicate that lansoprazole should be used at a once daily dose of 30 mg for the treatment of duodenal ulcer.

The British/Belgian Gall Stone Study Group (BBGSG) post-dissolution trial was a prospective, multicentre, randomised, double blind trial of: (i) low dose ursodeoxycholic acid, (ii) placebo, and (iii) a high fibre, low refined carbohydrate diet in the prevention of gall stone recurrence in patients with complete gall stone dissolution. Further aims included establishing the timing and frequency of recurrence and its association with biliary symptoms, a comparison of the sensitivity of ultrasonography v oral cholecystectography in detecting recurrent stones, and a search for risk factors predicting recurrence. Ninety three patients entered the study, and 82 were followed up for up to five years (mean (SEM) 28 (1.5) months) with six monthly ultrasonography and yearly oral cholecystectography. There were 21 recurrences (26 by oral cholecystectography or ultrasonography, or both), only two of which were symptomatic, which were detected between 12 and 42 months after trial entry. This corresponded to an actuarial recurrence rate of 33.9 (7.0%) by lifetable analysis at 42 months and subsequently. There were four recurrences in the ursodeoxycholic acid, six in the placebo, and 11 in the diet groups, corresponding to 21.9 (9.9)%, 27.4 (10.1)%, and 45.8 (12.4)% respectively at 42 months by lifetable analysis (NS). Variables including age, obesity, menopausal state, pregnancy, and oestrogen containing drugs were not shown to affect recurrence rate. Men had more frequent recurrence than women (NS). Patients who had had multiple stones experienced more recurrences than did those with single stones (NS). Recurrence did not occur in patients who took non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.02). The stone free interval between stone dissolution and trial entry proved to be important--those stone free > nine months had a recurrence rate of only 12.7 (6.0)% at 42 months compared with 55.4 (12.5)% in those stone free < nine months (p < 0.01). There was imbalance between the ursodeoxycholic acid and placebo groups for this factor, and after applying a statistical correction, the adjusted recurrence rate in the ursodeoxycholic acid group was 15% compared with 30% in both placebo and diet groups (NS). These data suggest that after medical dissolution, the risk of gall stone recurrence is not reduced by a high fibre, low refined carbohydrate diet: it may be lowered, but not abolished, by low dose ursodeoxycholic acid.

Elemental diet is as effective as corticosteroids in the treatment of previously untreated Crohn's disease. It is unclear whether a poor nutritional state is a prerequisite for efficacy of elemental diet, whether previously treated patients respond as well, or how duration of remission using elemental diet compares with corticosteroid induced remission. Forty two patients with active Crohn's disease were stratified for nutritional state and randomised to receive Vivonex TEN 2.1 l/day for four weeks, or 0.75 mg prednisolone/kg/day for two weeks and subsequent reducing doses. Nine of 22 (41%) patients assigned to nutritional treatment were intolerant of the diet. Thirty patients completed four weeks treatment. Disease activity decreased on elemental diet from mean (SEM) 4.8 (0.9) to 1.7 (0.6), p < 0.05, and on prednisolone from 5.3 (0.5) to 1.9 (0.6), p < 0.05. For each treatment, nourished and malnourished patients responded similarly. Patients with longstanding disease responded as well as newly diagnosed patients. The probability of maintaining remission at six months was 0.67 after prednisolone, 0.28 after elemental diet, and at one year was 0.35 after prednisolone and 0.09 after elemental diet, p < 0.05. When tolerated, elemental diet is as effective in the short term as prednisolone in newly and previously diagnosed Crohn's disease, and its benefit is independent of nutritional state. The subsequent relapse rate after elemental diet induced remission, however, is greater than after treatment with prednisolone.

Whether the long acting somatostatin analogue SMS 201-995 (octreotide, Sandostatin) could inhibit the basal and meal stimulated hypergastrinaemia and hyperpepsinogenaemia induced by omeprazole was investigated. Eight healthy subjects were randomised to receive five day courses of SMS 201-995 (25 micrograms subcutaneously three times daily), omeprazole (40 mg once a day), a combination of both drugs, or placebo. Basal and meal stimulated serum gastrin and basal serum pepsinogen A and C values were measured the day before treatment, on day five of treatment, and the day after each course of treatment. Omeprazole caused significant increases in basal and meal stimulated peak and integrated serum gastrin values and pepsinogen A and C levels, which were still significantly raised the day after stopping omeprazole treatment. Giving SMS 201-995 with omeprazole significantly reduced any omeprazole induced increases in basal and meal stimulated peak and integrated serum gastrin levels; serum pepsinogen A and C values were significantly inhibited too. Serum gastrin values during combined therapy were not significantly different from those during placebo treatment, whereas pepsinogen A and C levels were still significantly raised. On the day after stopping combined therapy, basal and meal stimulated peak and integrated serum gastrin and serum pepsinogen C (but not pepsinogen A) levels were not significantly different from values obtained on the day after stopping omeprazole alone. SMS 201-995 without omeprazole significantly inhibited basal and meal stimulated peak and integrated serum gastrin levels. Pepsinogen A was also significantly inhibited by SMS 210-995, but the reduction in pepsinogen C failed to reach statistical significance. In conclusion, SMS 201-995 prevents basal and meal stimulated increases in serum gastrin during omeprazole therapy. This finding may have clinical importance in the few patients who have pronounced hypergastrinaemia because of profound long acting acid inhibition.

A prospective, randomised, comparative study was performed to assess the need for a pure alcohol injection after an epinephrine injection in the arrest of active peptic ulcer bleeding. Sixty four patients with active ulcer bleeding were enrolled in the study. The two groups (epinephrine and epinephrine plus pure alcohol) were matched for sex, age, site of bleed, endoscopic findings, shock, haemoglobin, and concomitant illness at randomisation. The volume of injected epinephrine in the epinephrine and the epinephrine plus pure alcohol groups mean (SD) was 6.0 (3.0) ml and 5.5 (3.0) ml respectively (p > 0.05). The volume of injected pure alcohol in the epinephrine plus pure alcohol group was 1.9 (1.1) ml. Bleeding was initially controlled in 31 (97%) of the epinephrine group and all of the epinephrine plus pure alcohol group. Rebleeding occurred in 11 (36%) of the epinephrine group and in five (16%) of the epinephrine plus pure alcohol group (p > 0.05). Rebleeding was successfully controlled in some patients with treatment by a second injection. Other patients had heat probe thermocoagulation or surgery. Ultimate haemostatic rates were 69% (22/32) and 88% (28/32) for the epinephrine and the epinephrine plus pure alcohol groups respectively (p > 0.05). The epinephrine plus pure alcohol group achieved a better haemostatic effect for spurting haemorrhage (9/10 v 5/11, p < 0.05). The need for emergency operations and blood transfusions were comparable in both groups. The stay in hospital were less in the epinephrine plus pure alcohol group (mean 4.3 v 7.1, p < 0.05). It is concluded that pure alcohol injection after an epinephrine injection can improve the haemostatic rate in patients with spurting haemorrhage and shorten the hospital stay for patients with active bleeding.