Virtual biopsies in Barrett's esophagus using an impedance probe.

Preliminary results of electrical impedance measurements in squamous and columnar epithelia in rat and human tissues are presented. The aim of this work is to show the possibility of differentiating these two types of epithelia in terms of their electrical characteristics. For the measurements, we employed a 1.95-m-long, 3.2-mm-diameter, four-electrode probe designed to be used transendoscopically in the diagnosis of Barrett's esophagus (BE). BE is a condition in which the normal squamous epithelium of the esophagus is replaced by columnar epithelium of the intestinal type. This metaplasia is considered as a premalignant condition that puts patients at a 30-125-fold risk of developing adenocarcinoma of the esophagus. The diagnosis and surveillance of BE involve taking multiple biopsies, an expensive and time-consuming procedure. This study constitutes the first stage in the replacement of tissue biopsy by "virtual biopsies".

Assessing the conditions for in vivo electrical virtual biopsies in Barrett's oesophagus.

It has previously been shown that it is possible to differentiate between squamous and columnar epithelia in rat and resected human tissues using an impedance probe to make in vitro measurements. This probe can be passed down an endoscope allowing measurements to be made in patients. However, the probe emerges parallel to the oesophageal wall, with little room to manoeuvre. The conditions of control required to give reliable readings have been investigated. The importance of pressure applied and the angle of approach to the oesophagus was assessed. Pressures in the range 26.6 Pa to 46.3 kPa and angles in the range 15-90 degrees were considered. In in vitro studies it was observed that it was possible to obtain consistent readings with pressures greater than 2.9 kPa and with angles greater than 15 degrees between the probe and the oesophagus. These conditions can be achieved in vivo, and readings obtained from twelve patients are shown (45 readings on normal squamous, 34 on Barrett's oesophagus and 22 on stomach). At low frequencies (9.6-153.2 kHz), a Mann-Whitney test shows a significant difference (p < 0.001) when comparing the means from squamous and columnar, and also when readings from Barrett's and normal gastric epithelia are compared (p < 0.001).

Treatment of duodenal ulcer with cimetidine.

In a small open trial nineteen patients with active duodenal ulceration shown by fibreoptic endoscopy were treated with a 6-week course of cimetidine 1.6 g daily. Seventeen had healed ulcers on repeat endoscopy at 6 weeks. Seven of these have relapsed symptomatically within a month of withdrawal of cimetidine. No statistically significant change in the haemoglobin, white-blood-cell count, urea and electrolytes, or liver-function tests was associated with treatment. Plasma-creatinine showed a very small but significant rise but the mean level remained within the normal range. The significance of this is not clear.

Respiratory failure in acute pancreatitis.

There are a number of important pulmonary complications of acute pancreatitis which make a significant contribution to the morbidity and mortality of the condition. The pathophysiology and management guidelines are given for each and approaches towards better treatment in the future are discussed.

H2-antagonists in the treatment of recurrent ulceration after vagotomy.

Twenty-two patients with recurrent ulceration following vagotomy with and without a drainage procedure have been treated with histamine H2-antagonists and followed for up to 3 years. Four of a group of 6 patients responded to a single therapeutic course. Ten of 16 patients assigned to long term maintenance treatment remain symptom-free. Cimetidine may be an alternative to further surgery in the treatment of some patients with recurrent ulceration after vagotomy.

Clinical experience with metiamide.

The new histamine H2-receptor antagonist, metiamide, was shown to inhibit acid and pepsin secretion in gastric secretion studies performed on patients suffering from peptic ulceration. The new drug was administered intravenously in these experiments, but effective plasma levels could also be produced by oral administration. When symptomatic patients were treated with the drug nearly all experienced marked symptomatic relief, and there was some evidence that ulcer healing occurred during treatment. When the drug was withdrawn symptoms tended to return. No toxic reactions were encountered in this trial. Double-blind studies are now being made in Britain to establish the place metiamide may have in the treatment of duodenal ulceration.

Double-blind comparison of cimetidine and placebo in the maintenance of healing of chronic duodenal ulceration.

Patients suffering from chronic duodenal ulceration were allocated at random to treatment with either cimetidine (400 mg twice daily) or matching placebo for six months. Before entry to the trial all patients were shown to have healed ulcers on endoscopy. Most of the patients had participated in a one-month trial of cimetidine during which their ulcers healed. The trial showed that four of 29 patients relapsed on maintenance treatment with cimetidine, which therefore did not confer complete immunity from relapse. However, cimetidine treatment was very much better than placebo treatment, on which 18 of 31 patients relapsed. Of the 22 patients who relapsed clinically, 20 were submitted to endoscopy and 19 of these were shown to have ulcerated again. Endoscopy at the end of the trial showed that ulcers had also redeveloped in five of 28 asymptomatic patients. Length of previous dyspeptic history had no bearing on the results of the trial but there was evidence that relapse on placebo was less likely if the ulcer had originally healed on a high dose of cimetidine. Clinical relapse was associated with worsening duodenitis. Symptoms, clinical observation, and laboratory tests showed no important abnormalities in the patients.

Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man.

Cimetidine, a new H2-receptor antagonist, was safely administered to eighteen healthy man by the intravenous, intraduodenal or oral route. 2 When gastric secretion was maximally stimulated by either histamine or pentagastrin, the simultaneous administration of cimetidine produced marked inhibition of both acid and pepsin secretion. 3 Cimetidine was well absorbed by mouth and had a blood half-life of 2 hours. 4 Cimetidine was rapidly excreted via the kidneys and about 70% of the excreted material was unchanged drug. 5 Clinical evaluation of cimetidine in patients with peptic ulceration is recommended.

Controlled trial of cimetidine in upper gastrointestinal haemorrhage.

One hundred and one patients were studied in a double-blind controlled trial to assess the role of oral cimetidine in preventing the continuation or recurrence of acute upper gastrointestinal haemorrhage from various sources, chiefly peptic ulcer. The dose of cimetidine was 800 mg on entering the study followed by 400 mg six hourly. The source of bleeding was identified endoscopically in 96% of patients, peptic ulcer comprising 70%. Bleeding continued or recurred in 11 of 51 (21.5%) of patients on cimetidine and in 12 of 50 (24%) of patients on placebo. Analysis of the effect of cimetidine according to age or severity of bleeding showed no significant advantage for the drug.