A phase I study of immunostimulation and toxicity in patients with colorectal carcinoma using the immunomodulator 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride (CL 246738).

Seventeen patients with residual or recurrent colorectal carcinoma were given a new synthetic immunomodulator [3,6-bis(2-piperidinoethoxy) acridine trihydrochloride CL246738) as part of a phase I clinical trial. No patients had undergone previous immunotherapy or chemotherapy. Detailed immunological studies including interferon levels, interleukin 2 levels, natural killer cell function, mitogen responses of lymphocytes, immunoglobulin levels and lymphocyte subpopulation levels were analysed in the patients who received this drug in an attempt to find out whether there was any biological activity identifiable in humans. None of the subjects showed any significant increases in post treatment values of the immunological parameters studied. Toxic effects of the drug at high doses included nausea, diarrhoea and decreased levels of consciousness. In conclusion, no immunological effects were identified following the administration of CL 246738 in human subjects with recurrent or residual colorectal cancer.

Soft tissue trauma: a randomised controlled trial of the topical application of felbinac, a new NSAID.

Two hundred and thirty-one patients with acute soft tissue injuries were treated in a double-blind placebo-controlled study of felbinac (biphenylacetic acid) gel applied three times daily to the injured site. Those treated with felbinac had significantly greater improvement at Day 4 (p less than 0.001) and Day 7 (p less than 0.02) than those who received placebo. Patients' self-assessment diary cards confirmed superiority of the active treatment as early as Day 2 of the study. Local skin reactions were few (three per cent), mild and recovered spontaneously. Felbinac is an effective management for acute soft tissue injuries and because of its topical application may be safer than oral non-steroidal anti-inflammatory drugs for the treatment of these conditions.

Insulin sensitivity in third trimester pregnancy. A randomized study of dietary effects.

The metabolic effects of three diets were investigated in a randomized study in 15 non-pregnant women and 14 pregnant women in the third trimester; all the women were of normal weight. After 2-week periods of habituation to each diet, metabolic profiles were performed on standardized intakes. Diet 1 contained 40% of energy as carbohydrate and 10 g dietary fibre representing typical Western intakes. Diet 2 contained 40% energy as carbohydrate and 52 g dietary fibre and diet 3 contained 60% of energy as carbohydrate and 84 g dietary fibre, representing typical developing world intakes. No deterioration in glucose homeostasis in pregnancy was seen on any of the three diets in contrast to previous work. On diet 1 there was a loss of insulin sensitivity in pregnancy, but not on diets 2 and 3. The loss of insulin sensitivity which is typical of Western women in the third trimester of pregnancy and is considered to be physiological, may be a diet-induced artefact.

Individual variation in gonadotrophin and steroid concentrations and in the lengths of the follicular and luteal phases in women with regular menstrual cycles.

Two cycles each with full endocrine profiles from 17 subjects were examined for within-subject (between cycles) and between-subject variability (one way analysis of variance) and for the degree of correlation between pairs of cycles (regression analysis, Pearson's correlation coefficient). LH concentrations were significantly correlated within subjects for the mid cycle (P less than 0.0001) and luteal phases (P less than 0.05) whereas FSH concentrations were significantly correlated throughout the cycle (P less than 0.01). Oestradiol, however, was only weakly correlated (P less than 0.05) and then only during mid-follicular and luteal phases. Progesterone concentrations were highly significantly correlated (P less than 0.0001) during the luteal phase as were both follicular (P less than 0.01) and luteal phase length (P less than 0.0001) and prolactin concentrations (P less than 0.001). All the reproductive hormones showed less variation within an individual than between individuals. This was particularly marked for FSH and prolactin (throughout the cycle) LH (during the mid-cycle surge) and progesterone concentrations (luteal phase). It is likely that the peripheral plasma levels of these hormones are characteristic of the individual and do accurately reflect the state of equilibrium existing between all of the physiological regulatory mechanisms. Further, the current practice of describing endocrine profiles in regularly cycling but infertile women in an attempt to understand possible causes of their infertility is, in the light of these findings, a physiologically justifiable procedure.

Feto-maternal consequences of high-dose glucose infusion during labour.

The effects on the fetus of high doses of glucose given to the mother in labour to correct maternal ketonuria were investigated. Three groups of patients were compared: one group received 1 litre of 10% (w/v) glucose intravenously over 1 h, the second group received 1 litre of 0.9% sodium chloride solution intravenously over 1 h and the final group had no supplementary infusion. It was observed that whereas glucose administration rapidly corrected maternal ketonaemia, there was a significant fall in pH and a rise in lactate in fetal blood. These effects were not observed in the other two groups. It was concluded that the use of high doses of intravenous glucose in labour should be avoided.

An assessment of continuous fetal heart rate monitoring in labor. A randomized trial.

Intrapartum continuous fetal heart rate monitoring has been routinely performed at the Jessop Hospital for Women for some years. However, no controlled trials had ever been performed to show its advantages over intermittent auscultation in low-risk patients. A prospective randomized study of 504 patients compared continuous fetal heart rate monitoring with intermittent auscultation. There was no significant difference between the two groups in neonatal deaths, Apgar scores, maternal and neonatal morbidity, and cord blood gases. The cesarean section rate was significantly increased (p less than 0.05) in the monitored patients but this did not seem attributable to fetal monitoring. No beneficial or deleterious effects of continuous fetal heart rate monitoring in labor were shown.