Bloody diarrhoea: a rare presentation of a systemic disease.

Bloody diarrhoea in adolescents is usually due to enteric infection or inflammatory bowel disease. We describe a patient with bloody diarrhoea and endoscopic features of colitis in association with a systemic vasculitis. Positive anti-proteinase-3 antineutrophil cytoplasmic antibodies and cutaneous vasculitis on biopsy confirmed the diagnosis of Wegener's granulomatosis. He was started on high dose steroids and cyclophosphamide but required plasmapheresis for a declining renal function. The case highlights the need for vigilance with common clinical problems, because a life-threatening condition may be averted by prompt recognition and urgent therapy with immunosuppressants.

Colonic variceal bleeding in a patient with mesenteric venous obstruction due to an ileal carcinoid tumour.

Colonic varices are a recognized cause of rectal bleeding in portal hypertension. We report here a patient who presented with melaena several months after resection of an ileal carcinoid tumour. Subsequent colonoscopy for continued episodes of rectal bleeding demonstrated extensive colonic varices. In the absence of portal hypertension, the varices appeared to be related to mesenteric venous obstruction. The management of bleeding colonic varices, in these circumstances, is discussed.

Overview: the management of metastatic carcinoid tumors.

Chemotherapy, IFN, octreotide, and hepatic artery embolization can be useful for palliation, both of local symptoms and of the carcinoid syndrome, but they have little effect on tumor progression, MIBG therapy is still experimental but may have a future role. OLT should be considered as a palliative procedure in those patients with severe symptoms and no evidence of extrahepatic disease.

Symptom relief and quality of life after stenting for malignant bile duct obstruction.

Palliative treatment is appropriate for most patients with cancer of the head of pancreas. Insertion of a biliary stent relieves jaundice and pruritus but it is not known if stenting affects other symptoms or changes the quality of life. Nineteen patients have completed a standard questionnaire to assess symptom relief and quality of life after stent insertion. After stenting there was complete relief of jaundice and pruritus. Furthermore, there was also considerable improvement in anorexia and indigestion. All patients had anorexia before stent insertion, this was moderate/severe in 13 (68.4%). Anorexia was significantly better (p < 0.01) a week after stenting and this benefit was maintained at 12 weeks (p < 0.01). Sixteen (84.2%) patients complained of indigestion before stenting, moderate/severe in 11 (57.9%). This was significantly better (p < 0.01) a week after stenting with complete relief in six at eight weeks (p < 0.01). Fifteen (78.9%) felt that their mood was good/very good before stent insertion and this was unchanged even at the 12 week assessment. A similar result was obtained for physical health and level of activity. In conclusion stent insertion not only relieves jaundice and pruritus in these patients but also improves other symptoms and quality of life. The considerable improvement in appetite after stenting was of particular benefit.

Erythromycin induces supranormal gall bladder contraction in diabetic autonomic neuropathy.

Gall bladder motor function is impaired in some patients with diabetes. It has been suggested that the abnormalities of gall bladder motility are confined to those patients with autonomic neuropathy. Erythromycin, a motilin receptor agonist, causes gall bladder contraction in both normal subjects and patients with gall stones with impaired gall bladder emptying. The effect of erythromycin on gall bladder motility in seven patients with diabetes with an autonomic neuropathy, six patients with diabetes without autonomic neuropathy, and 17 normal subjects was studied using ultrasound. There was no significant difference in gall bladder fasting volume between the three groups, but the patients with diabetes with autonomic neuropathy had impaired postprandial gall bladder emptying compared with normal subjects (percentage emptied (SEM) 40 (10.3)% v 64 (2.8)%, p < 0.01) and those with autonomic neuropathy (48 (7.7)%, NS). Erythromycin produced a dramatic reduction in gall bladder fasting volume in patients with diabetes with an autonomic neuropathy, compared with either normal subjects or patients with diabetes without autonomic neuropathy (percentage reduction 62 (4.6)% in patients with autonomic neuropathy, v 37 (17.6)% in those without autonomic neuropathy, and 26 (7.3)% in the normal subjects, (p < 0.02) and returned gall bladder emptying to normal in all patients with impaired emptying. The pronounced effect of erythromycin in diabetic autonomic neuropathy suggests denervation supersensitivity and that the action of erythromycin on the gall bladder is neurally modulated.

Colorectal carcinoma in patients with ulcerative colitis and recent colonoscopy.

Longstanding ulcerative colitis, particularly pancolitis, is associated with an increased risk of colorectal neoplasia. For this reason surveillance colonoscopy at regular intervals has been recommended to identify early cancers or high grade dysplasia. Three cases are described of patients with ulcerative colitis of greater than 10 years duration who presented with colorectal carcinoma within three years of colonoscopy.

Dose-dependent stimulation of gallbladder contraction by intravenous erythromycin in man.

We have previously shown that a single oral dose of 500 mg erythromycin causes gallbladder contraction. The effect of intravenous erythromycin on antroduodenal motility is dose-dependent; < 3 mg/kg body weight stimulates propagated contractions in a fashion similar to motilin while doses > 7 mg/kg cause giant non-propagated antral contractions not seen with motilin. Using ultrasound, we have examined the effect of differing doses of intravenous erythromycin on gallbladder motility in man. Erythromycin (1 mg/kg) caused fasting gallbladder contraction to 52% of basal gallbladder volume (P < 0.001), and increased gallbladder emptying following a liquid meal (maximal percentage emptied 75 +/- 6.8% vs. 58 +/- 9.0% following saline, P < 0.05). Erythromycin (7 mg/kg) however, had no effect on gallbladder fasting or post-prandial motor activity. We conclude that the effect of erythromycin on gallbladder motility is dose-dependent, with higher doses having no effect. It is possible that at higher doses erythromycin stimulates other receptors in addition to the motilin receptor, and that the combined effect is different to the stimulation of the motilin receptor alone.

Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly.

Octreotide therapy in acromegaly is associated with an increased prevalence of gall stones, which may be the result of an inhibition of gall bladder motility. Gall stone prevalence in untreated acromegalic patients relative to the general population is unknown, however, and the presence of gall stones and gall bladder motility in these patients and in acromegalic patients receiving octreotide was therefore examined. Thirty four percent of 39 patients who had taken octreotide for a mean of 20 months had gall stones compared with 16% of 38 patients who had not been treated with octreotide (p < 0.005). In a subgroup of 21 patients studied prospectively over 4 to 18 months, two patients developed stones. No patient had symptoms referrable to their gall stones. In 31 untreated acromegalic patients, the mean fasting gall bladder volume was similar to that in normal subjects. Maximal percentage emptying, however, was impaired (34 v 64%, p < 0.001) and the mean postprandial residual gall bladder volume increased (21.7 v 9.0 ml, p < 0.001). Treatment with octreotide increased the mean postprandial residual volume further to 36.8 ml (p < 0.001). Gall bladder emptying in untreated acromegalic subjects is impaired. Octreotide further increases postprandial residual gall bladder volume and this may be a factor in the increased gall stone prevalence seen in these patients.

Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones.

The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P less than 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P less than 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P less than 0.05) and residual volume was 17.7 vs. 6.5 mL (P less than 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P less than 0.05) and residual volume was 17.2 vs. 5.0 mL (P less than 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P less than 0.001; residual volume, 3.7 mL, P less than 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects.

Biliary stents.

The management of extrahepatic biliary obstruction has been revolutionized by the development of endoprostheses which can be inserted endoscopically or percutaneously. Advances in the technology of stent insertion and in the stents themselves are likely to increase the therapeutic armamentarium of the endoscopist still further.

Erythromycin and the gut.

The commonly reported gastrointestinal side effects that occur with erythromycin are related to its prokinetic action on the gut, mediated, at least in part, by its motilin receptor stimulating activity. This action may be of clinical use in conditions associated with gastrointestinal hypomotility such as diabetic gastroparesis and intestinal pseudo-obstruction, although further work needs to be done to establish the long term therapeutic uses of erythromycin in these disorders. Macrolide compounds with no antibacterial properties but which have a pronounced prokinetic action on the gut have already been synthesised and are currently being developed for future use in man. These 'motilides' should provide a useful addition to our rather limited armamentarium of effective gastrointestinal prokinetic agents.

Indomethacin and postprandial gallbladder emptying.

Patients with gallstone disease commonly have impaired gallbladder emptying. To see whether non-steroidal anti-inflammatory drugs (NSAIDs) prevent gallstone formation by improving gallbladder emptying, we assessed the effect of indomethacin on postprandial emptying in healthy subjects and in patients with gallstone disease. Subjects received indomethacin 25 mg three times a day for a week and matching placebo for another week. Compared with placebo, indomethacin improved postprandial gallbladder emptying in all 7 patients with gallstone disease. This finding was not recorded in healthy subjects with normal gallbladders. The prevention of gallstone formation associated with ingestion of NSAIDs may be due mainly to a prokinetic effect on the gallbladder since there is no evidence to suggest that these drugs affect cholesterol crystal nucleation at ordinary therapeutic doses in man or animals.