Antide-induced suppression of pituitary gonadotropin and ovarian steroid secretion in cynomolgus monkeys: premature luteolysis and prolonged inhibition of folliculogenesis following single treatment

Administration of high-dose Antide to ovariectomized monkeys results in rapid, prolonged, and reversible inhibition of gonadotropin secretion. The present study examined whether similar long-term control would be manifested in the menstrual cycle of intact primates. Antide administration at a dose of either 3.0 or 18.0 mg/kg induced rapid suppression of bioassayable LH concentrations, precipitating a concurrent fall in serum progesterone concentrations from 7.9 +/- 3.6 and 5.8 +/- 1.0 ng/ml (mean +/- SEM) on the day of injection to 0.6 +/- 0.2 and 0.5 +/- 0.1 ng/ml by 2 days post-treatment, respectively. This Antide-induced luteolysis was accompanied by the premature onset of menses within 3 days. The next menses following Antide administration was delayed. Ultimately, folliculogenesis culminating in normal follicular-phase estradiol production, ovulation, and subsequent normal luteal-phase progesterone production did occur in all treated monkeys. Menses resumed 54 +/- 9 and 75 +/- 13 days after treatment with 3.0 and 18.0 mg/kg Antide, respectively. No allergic cutaneous or peripheral reactions were seen, even at the highest dose of Antide. Thus, the long duration of action of high-dose Antide reported earlier in ovariectomized monkeys is also demonstrated in intact primates. These findings, along with the apparent absence of histamine-release effects even at high doses, suggest that Antide is a GnRH antagonist deserving clinical evaluation.     

Consensus finally achieved on resuscitative interventions.

A joint policy statement on the resuscitation of patients is published in this issue of CMAJ. Dr. John Williams, the CMA''s director of ethics and legal affairs, discusses how it differs from the joint statement published last year.     

Characteristics of patients aged over 75 not seen during one year in general practice.

A study was carried out in two large urban practices to determine the number of patients aged over 75 years who had had no contact with the primary care team during one year and to examine their medical and social characteristics. Although their general health was considered to be good, over half needed treatment or other action and half had no identifiable career.     

Generation of aspartate aminotransferase multiple forms by deamidation.

The development of aspartate aminotransferase subforms in vitro was followed by densitometry after thin-film isoelectric focusing. At the same time ammonia production was measured. Each reaction can be expressed in terms of a first-order process in which 2 mol of glutamine or asparagine/mol of dimer are deamidated with a half time of 22 days. The more negatively charged subforms developed in vitro were almost fully active. Another process occurred leading to inactivation by coenzyme modification, and this was independent of deamidation. Although the enzyme formed absorbed maximally at 340nm, it was different from the naturally occurring inactive enzyme that absorbs at this wavelength.