J. A. Jones

The effect of tamoxifen and estrogen receptor status on survival in gastric carcinoma

One hundred patients were entered in a randomized, controlled study of adjuvant tamoxifen therapy in gastric carcinoma. Estrogen receptor status was established by an immunohistologic method (ERD5) and 55.8% of the tumors were positive. Tamoxifen had no overall effect on survival, but there was a significant decrease in the survival time of the patients with ERD5‐positive tumors. Estrogen receptor status (by the ERD5 method) is an independent prognostic factor in gastric cancer. Tamoxifen therapy does not prolong survival, and new therapeutic strategies require investigation.

High and prolonged pulmonary tissue concentrations of azithromycin following a single oral dose

Antibiotic concentrations in pulmonary tissue samples and plasma were studied in this open investigation. Twenty-nine patients scheduled for elective pulmonary surgery received a single oral dose of 500 mg azithromycin 24, 72, 96 or 120 h prior to the operation; two patients received 250 mg b.i.d. Blood samples were taken before and at the time of resection, and tissue was obtained during surgery. Plasma and tissue concentrations of azithromycin were measured by high performance liquid chromatography (HPLC) and a microbiological bioassay. Only one patient had a detectable plasma concentration of azithromycin (0.13 µg/ml), measured 24 h post-dose by HPLC. However, high and sustained levels were found in lung tissue: mean concentrations measured by HPLC were 3.10 µg/g (SD ± 2.17), 2.55 µg/g (SD ± 1.36), 3.94 µg/g (SD ± 2.40) and 3.13 µg/g (SD ± 0.50) at 24, 72, 96 and 120 h, respectively. Bioassay results were similar to those for the HPLC assay. In summary, azithromycin levels in pulmonary tissue remained close to 3 µg/g for up to 5 days after a single oral 500 mg dose, in contrast to plasma levels which were much lower. The lung concentrations found are inhibitory for many sensitive respiratory pathogens and short-course azithromycin therapy is therefore a possibility.

Azithromycin levels in plasma and gastric tissue, juice and mucus.

Azithromycin is the first member of a new class called the azalides. Its distribution in gastric tissues was studied in 27 patients (mean age 66 years) with proven gastric cancer due to be resected. Five groups of patients received a single 500 mg oral dose of azithromycin 24, 48, 72, 96 or 120 h pre-operatively. Samples of blood, gastric juice, mucus and gastric tissue were taken and azithromycin assayed by high performance liquid chromatography. There was an increase in the level of azithromycin in gastric juice up to the 73–96 h period reaching a median peak of 0.20 µg/ml. There were higher levels of azithromycin in gastric mucus (approximately double the maximum attained in gastric juice) at each of the time periods to 120 h after the dose of azithromycin. Much higher levels were seen in the gastric tissue (median peak of 4.6 µg/g), which were statistically significant compared with gastric juice for the first two time periods (24–48 h, p=0.005; 49–72 h, p=0.012). Concentrations seen in the gastric tissue specimens were between five- and 10-fold greater than those seen in gastric mucus, and approximately 20-fold greater than the levels seen in gastric juice at each of the time periods after dosing. It is concluded that remarkably high levels of azithromycin are found in gastric tissue within 24 h of a 500 mg oral dose and that these levels persist over a five-day period. There exists a significant concentration gradient from gastric tissue to gastric juice. Such levels may be advantageous in the therapy ofHelicobacter pylori infections.

The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma

Gastric cancer remains a disease with a very poor prognosis, and there is no safe and effective form of therapy for advanced disease. Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo, and that blockade of gastrin receptors can prolong survival in xenografted nude mice. We have thus performed a randomized, controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma. Proglumide had no overall effect on survival (Mantel‐Cox statistic = 0.5, P = 0.48). The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group. No significant difference was seen with proglumide, which has a relatively low affinity with the gastrin receptor and also has partial agonist activity. Drugs that are far more specific and potent gastrin receptor antagonists are becoming available, which may have a greater effect on survival, and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy.

Randomised study of prophylactic parenteral sulbactam/ampicillin and cephazolin in biliary surgery: Significant benefit in jaundiced patients

Two hundred consecutive patients undergoing biliary-tract surgery were entered into a randomized trial of prophylactic single dose cephazolin or sulbactam/ampicillin. There was no overall difference in the infection rates between the two antibiotic groups, but in the group of patients with jaundice there was an excess of wound infections in the cephazolin group compared to the sulbactam/ampicillin group (35% vs. 14%). We conclude that sulbactam/ampicillin is a satisfactory prophylactic agent for use in biliary-tract surgical sepsis, and that it may be superior to cephazolin in jaundiced patients.

A Short-Term Radiotelemetric Provocation Test for the Diagnosis of Gastroesophageal Reflux Disease

Gastro-oesophageal reflux (GOR) most commonly occurs postprandially especially during activities associated with increases in intra-abdominal pressure which may provoke reflux in susceptible subjects. Inflation of a gastric balloon, in increments up to 750 ml, significantly increases the frequency of transient lower oesophageal sphincter (LOS) relaxations in both normal subjects and patients with GOR [1]. These authors conclude that meal-induced gastric distension provokes LOS relaxations so contributing to postprandial reflux. We have developed a short-term acid reflux provocation test (ARPT) for diagnostic purposes.