Leucocytoclastic vasculitis in a patient with azathioprine hypersensitivity.

We report the case of a 77-year-old man admitted nine days after being commenced on azathioprine with symptoms initially thought to be secondary to sepsis but in fact due to azathioprine hypersensitivity. He developed histologically proven cutaneous leucocytoclastic vasculitis following the re-introduction of azathioprine. We review the literature concerning adverse reactions to azathioprine and the problems of making the diagnosis as well as highlighting azathioprine as a novel cause of leucocytoclastic vasculitis.

Superficial thrombophlebitis, dysplasia, and cholangiocarcinoma in primary sclerosing cholangitis.

Cholangiocarcinoma occurs in approximately 10% of patients with primary sclerosing cholangitis. Usually, liver failure, rapidly progressing jaundice, and an increase in alkaline phosphatase levels are suggestive diagnostic features. We report two cases of patients with primary sclerosing cholangitis who developed cholangiocarcinoma without jaundice and with no changes in their serum biochemistry. Both patients were taking ursodeoxycholic acid at the time of tumor diagnosis. Initial suspicion of malignancy was based on the development of superficial thrombophlebitis. Liver histology showed evidence of bile duct epithelial dysplasia in areas free from tumor in one patient, and in the other, bile duct epithelial dysplasia preceded the appearance of cholangiocarcinoma by at least 18 months. In one of the cases, the dysplastic epithelium stained positively for carcinoembryonic antigen. The histological finding of bile duct epithelial dysplasia in patients with primary sclerosing cholangitis may suggest either imminent or actual development of cholangiocarcinoma and may thus affect consideration of orthotopic liver transplantation. In addition, the development of superficial thrombophlebitis in patients with primary sclerosing cholangitis should arouse suspicion of the presence of cholangiocarcinoma even if there is no evidence of deterioration of the liver function or a dominant stricture on endoscopic retrograde cholangiography.

The diagnosis and management of perforations of esophagus and pharynx sustained during intubation of neoplastic esophageal strictures.

Twenty-six esophageal and eight pharyngeal perforations sustained during palliative intubation of esophagogastric neoplasms have been reviewed. The majority of the tears were recognized either endoscopically or by the immediate development of subcutaneous emphysema. However, 15 perforations were first identified by radiology, and 10 of these 15 patients were initially asymptomatic. In the years 1976-1979 with conservative management, three patients of eight died from the perforation and none had a pneumothorax. From 1980 a more aggressive nonsurgical approach was used, and of 26 patients who sustained a perforation, there were six deaths before leaving hospital but only four deaths were directly related to the perforation and each of these had sustained a pneumothorax. Pharyngeal tears invariably did well with conservative management. Our experience favors conservative management for instrumental esophageal perforation.

Somatostatin in treatment of haematemesis and melaena.

630 patients with haematemesis and melaena were randomly allocated to treatment by a constant intravenous infusion of either somatostatin or an apparently identical placebo in a double-blind controlled trial. Rebleeding was less common in treated patients (70 episodes in 315 individuals compared with 89 episodes in 315 controls) but the difference was not significant. Operation rates were virtually identical (35 treated patients and 34 controls), while there were slightly more deaths in the treated group than in the controls (31 and 25, respectively). These results are in clear disagreement with those of other smaller series. Though it is not possible to be completely sure that treatment is not useful in some individuals, earlier claims of marked benefit seem unlikely to be justified.

The effects of ranitidine on pituitary-thyroid function.

Although several studies have examined the effects of cimetidine on pituitary-thyroid function, few have investigated ranitidine in this respect. We found no changes in thyroid-stimulating-hormone (TSH) or prolactin responses to TSH-releasing-hormone (TRH) in 10 patients with peptic ulcer disease given oral ranitidine. Serum total and free thyroxine (TT4 and FT4) concentrations declined slightly, whereas total and free triiodothyronine (TT3 and FT3) increased slightly following ranitidine. None of these changes achieved statistical significance. Both the ratio of TT4/TT3 and FT4/FT3, however, declined (P less than 0.05) following ranitidine. Thus ranitidine may have a minor influence on peripheral deiodination of thyroxine but has little effect on hormone production from the thyroid gland. The diagnostic value of biochemical tests of thyroid function is not seriously compromised in patients receiving ranitidine.

Comparison of the Eder-Puestow and Celestin techniques for dilating benign oesophageal strictures.

The Celestin and Eder-Puestow methods of dilating benign oesophageal strictures have been compared prospectively in a randomised trial. One hundred and thirty three dilatations were performed on 72 patients. There was no significant difference between the two techniques with regard to the long term relief of symptoms. Celestin dilatation was quicker, less likely to cause pharyngeal trauma, and less damaging to guide wires. It could not be used, however, in those patients in whom only a short length of guide wire could be passed through the stricture.

Serum CEA testing in the post-operative surveillance of colorectal carcinoma.

Six hundred and sixty-three patients were followed with serial serum CEA measurements in addition to routine clinical surveillance after radical resection of colorectal carcinoma. Of 626 available for analysis, 366 (58.4%) remained clinically free of recurrence and had a normal CEA (less than 20 ng ml-1) throughout and 89 (14.2%) had a temporary non-progressive rise in CEA with no evidence of secondary disease. Of 171 patients who developed proven or suggestive recurrence, 114 had a preceding rise in the serum CEA and in further 21 the CEA rose simultaneously with recurrence. In 36 patients secondary disease was detected while the CEA was still within normal limits. CEA was more effective as an early index of distant metastasis, thus in 76% of those patients with a preceding rise in CEA, the secondary disease was disseminated, whereas only 20% had localised recurrence. The pattern of rise in CEA was of no practical value in distinguishing localised from distant recurrence.

Prospective randomised trial of early cytotoxic therapy for recurrent colorectal carcinoma detected by serum CEA.

Of 663 patients treated with radical surgery for colorectal cancer, 52 showed a progressive rise in serum carcinoembryonic antigen (CEA) with no other evidence of recurrent disease and were randomised in a prospective study of chemotherapy. Twenty six patients in the treatment group received 5FU and methyl CCNU from the time of randomisation and the remaining 26 controls were given further therapy only if there were clinical indications. All patients were followed for five years or until their death and all but one (control) developed clinical evidence of recurrence. Overall there was no significant difference between the two groups with respect to disease free interval and survival. Whereas the rise in CEA in controls was generally progressive, marked inflections on the CEA curves were seen in the majority of patients receiving early treatment. Eight of 26 treated patients showed a fall in CEA of greater than 20% two months after starting therapy. These patients had a median disease free interval of 90 weeks and a median survival of 107 weeks, these figures being longer than those of treated patients who did not show a fall in CEA and control patients. The serum CEA therefore appeared to give important prognostic information in patients receiving cytotoxic treatment. Early therapy was generally well tolerated.

Ranitidine: prophylaxis of duodenal ulcer recurrence.

Ninety-two patients with healed duodenal ulcer received prophylactic treatment with ranitidine, 150 mg at night, to prevent relapse. Patients were reviewed at 4-monthly intervals for clinical assessment and endoscopy. Eighty-two patients completed the trial. After one year sixty-two patients (76%) were in endoscopic remission; ten patients (12%) suffered symptomatic relapse and ten others had asymptomatic ulcers during treatment. There were no clinically significant untoward effects associated with the drug. A single nocturnal dose of 150 mg ranitidine reduces the relapse rate after duodenal ulcer healing.

Myoglobin concentration, creatine kinase activity, and creatine kinase B subunit concentrations in serum during thyroid disease.

Changes in values for myoglobin, total creatine kinase (EC 2.7.3.2), and creatine kinase B-subunit in the serum of patients with thyroid disease are compared with values for these during the 24-h after myocardial infarction. Concentrations of all three of these muscle-derived proteins were significantly higher than normal in patients with primary hypothyroidism, and declined with treatment. Values for total creatine kinase activity were below-normal in hyperthyroid patients, but increased after treatment. Values for total creatine kinase and, to a lesser extent, myoglobin in hypothyroidism extend into the range of values observed after myocardial infarction. The mechanism of the changes in these analytes in hypothyroidism may be related to increased leakage from skeletal-muscle cells or diminished clearance from the circulation, or both.

Ranitidine in reflux oesophagitis. A double-blind placebo-controlled study.

This study was designed to assess the effect of ranitidine on patients with symptomatic oesophageal reflux. In a double-blind comparative trial in 46 patients a twice daily dose of 150 mg ranitidine was compared with placebo. Relief of pain, endoscopic healing and histological improvement were significantly better in those treated with ranitidine. Thus, ranitidine is of value in the management of patients with reflux oesophagitis and may prevent the development of peptic stricture.

Comparison of twice-daily ranitidine and placebo in the treatment of duodenal ulcer--a multicentre study in the United Kingdom.

Treatment of duodenal ulcer with the H2-receptor antagonist ranitidine, 150 mg twice daily has been assessed in a double-blind, placebo controlled study at seven centres in the United Kingdom. One hundred-and-twenty-nine patients entered the trial with endoscopically confirmed duodenal ulcer. Five patients did not comply with the protocol and were excluded from the analysis. Nine patients (1 ranitidine, 8 placebo) did not complete the initial 4 weeks' treatment due to poor symptomatic response; one hundred-and-fifteen (58 ranitidine, 57 placebo) were endoscopically assessed after 4 weeks. The average 4-week healing rate among patients on ranitidine (83%) was significantly greater than that for the placebo group (32%, p less than 0.01). Forty-four patients whose ulcers had not healed received further treatment with ranitidine 150 mg b.d. on an open basis. After a total of up to 8 weeks' active treatment only three patients had not healed. Ulcer symptoms resolved or improved in a greater proportion of patients on ranitidine, and this was associated with a significantly lower antacid consumption. There was no serious unwanted effect associated with ranitidine treatment, and the twice daily dose of 150 mg is apparently a safe and effective short-term treatment for duodenal ulceration.