The effect of a sleep-dose of etomidate on the plasma concentrations of cortisol, 11-deoxycortisol and 17 alpha OH-progesterone was investigated in eight patients; two other patients received thiopentone. Blood samples were collected at 0, 15 and 30 min after etomidate or thiopentone when an injection of tetracosactrin was given and a final sample was collected at 60 min. The plasma cortisol response to tetracosactrin was depressed below normal in patients given etomidate, and the 11-deoxycortisol response was very high, ranging from 36.4 to 184.7 nmol/l. The two patients that received thiopentone had a normal response to all steroids. The identity of the plasma 11-deoxycortisol in two patients was confirmed by high-performance liquid chromatographic separation and quantification by both spectrophotometric and radioimmunoassay measurements. These results suggest that a single dose of etomidate inhibits 11 beta-hydroxylation of cortisol.

Summary.Pituitary responsiveness to thyrotrophin releasing hormone (TRH) and luteinizing hormone releasing hormone (LHRH) was studied in thirty one male diabetics, of whom sixteen were insulin-dependent and fifteen on oral ant• agents. Ten age-matched controls were also studied. TRH and LHRH were simultaneously administered intravenously, each in a small dose of 10 ~tg followed two hours later by 190 ~tg and 90 ~tg respectively. Basal hormone levels were measured in a further group of thirty six patients (twelve on insulin, twelve on oral agents and twelve on dietary restrictions alone).Higher thyrotrophin (TSH) response was observed following the small dose of TRH in the patients treated with oral agents than in the control subjects. The response of prolactin was lower in patients treated with oral agents compared with those treated with insulin. There was no difference in plasma 73 and T 4 levels in the patients treated with insulin or oral agents. Significantly higher basal growth hormone (GH) levels were observed in the diabetics. The insulin-dependent group showed a more marked response of GH to TRH/LHRH. No response was observed in the controls. Plasma testosterone levels were significantly lower in the oral agent group (13.8 nmol/1) than in the insulin group (19.4 nmol/1), patients on dietary restrictions (18.4 nmol/1) and the control subjects (19.0 nmol/1). The LH response to the smaller dose of LHRH was impaired in patients on insulin and oral agents. There was a significant difference in FSH response between impotent and sexually normal patients.

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Summary. Climacteric symptomatology was investigated in a group of non‐selected women aged between 54 and 56 years of age, Vasomotor complaints and dyspareunia, in particular, were noted and related to plasma hormone levels and vaginal cytology. Only 33% of those women who were within 5 years of the menopause had symptoms of a magnitude that might require hormone replacement therapy. Neither the vasomotor complaints nor dyspareunia correlated with the hormone levels or cytology findings to such an extent as to be helpful in planning treatment. Aarently only a minority of women in their middle 50s demonstrate a symptomatic need for hormone replacement therapy and laboratory investigations are of little use in their identification.

SUMMARY A double-blind cross-over trial between pheneturide and phenytoin in ninety-four outpatients with epilepsy is described. There was no significant difference between the frequency of seizures in the two groups. The difficulties in comparing two anticonvulsants of similar efficacy are discussed particularly in relation to ethical problems, the selection of patients and trial design.Recent research in anticonvulsant drugs has concentrated on their mode of action, their absorption, metabolism and elimination. Thus while the pharmacokinetics of these drugs are well understood, there are few adequate trials to test their efficacy in the management of epilepsy,' 2 possibly because ethical and design difficulties frequently

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The effect of dosage frequency of carbamazepine (CBZ) (brand name Tegretol) on pseudo-steady state drug serum levels were studied in 14 male (16-18 years) epileptics. They had already been receiving CBZ (mean dose 13.7 mg/kg) for an average period of 2.3 years in combination with other antiepileptic drugs. During this investigation, total daily CBZ dose was kept unaltered, but they received medication in thrice, twice and once daily dosage regimes. Each treatment period lasted for 4 weeks. The profiles of 24 h serum drug levels as assessed at the end of each treatment period, were observed to be within the therapeutic range during these 3 regimes. However, as expected, there were higher fluctuations of serum CBZ concentrations during once daily medication than during divided dosage regimes. Other concomitant antiepileptic drugs were continued in 2-3 divided daily doses during these 3 treatment periods, and the serum drug levels were measured at 8 h prior to the morning dosing. The concentrations of other drugs remained unchanged apart from a slight decrease in the serum sodium valproate levels during once daily medication. No clinical or electroencephalographic adverse effects were observed and there was no significant change in the fit frequency. In view of this observation, CBZ (Tegretol tablet) is probably effective as a single daily dose, but further long-term controlled clinical trial is necessary.

Urine was collected over 24 h from 40 patients with advanced malignant disease who had received a known four‐hourly oral dose of either diamorphine or morphine in an elixir or of diamorphine by injection for at least 3 days. Samples were assayed for total urinary morphine (free and conjugated) by gas‐liquid chromatography. The percentage of the administered dose recovered as morphine was: diamorphine hydrochloride by injection: 70% (s.d. 25) diamorphine hydrochloride by mouth: 77% (s.d. 27) morphine sulphate by mouth: 56% (s.d. 21) It is suggested that diamorphine hydrochloride is completely absorbed by the ***gastro‐intestinal tract but that morphine sulphate is only some two‐thirds absorbed.