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A new oral agent, S15261 (the L-isomer of 3-[2-[2-[4-[2-[alpha-fluorenyl acetyl amino ethyl] benzoyloxy] ethyl amino] 1-methoxy ethyl] trifluoromethyl-benzene), has been developed for the treatment of the so-called "insulin resistance syndrome". In obese, insulin-resistant ageing Sprague-Dawley rats, chronic treatment with S15261 (0.5-2.5 mg.kg-1.day-1 twice per day, for 14 days) resulted in dose-dependent decreases in plasma insulin (43%), and triglyceride levels (36%), and in an increase of the glucose disposal rate during an intravenous glucose tolerance test (IVGTT) (48.5%). An increase in peripheral insulin sensitivity produced by S15261 was revealed by the glucose clamp technique. Thus, the glucose infusion rate was increased by 20% whilst steady-state insulin levels decreased by 15%. At the higher doses S15261 led to a decrease in body weight (3%), plasma glucose (13%) and blood pressure (8 mm Hg) in mildly hypertensive animals. At the doses used to achieve these results, the compound has no hypoglycaemic activity in normoglycaemic animals. Acute administration of S15261 directly into the portal vein provoked a marked increase in glucose disappearance rate during an intravenous glucose tolerance test (60%) and also in the pancreatic response to the glucose challenge. Thus, acute administration of the compound has a direct effect on glucose metabolism. These data suggest that S15261 could be a useful agent for the treatment of the insulin resistance syndrome.

Recently publications have advocated earlier weaning and early extubation of the trachea in patients after cardiac surgery. Greater comfort of the patients is one of the advantages claimed for this policy. One hundred consecutive adult patients were questioned on the fifth postoperative day to assess the relative comfort or discomfort of the patients during tracheal intubation and ventilation. Overnight tracheal intubation and ventilation were easily tolerated by over 90 per cent of patients who had received morphine and diazepam. There was a high incidence of amnesia. Some of the other claimed advantages appear inconclusive and further study is desirable to elucidate the effect of early removal of the tracheal tube upon the indicence of pulmonary complications.

Recent data suggest that in a proportion of NIDDM patients there is a slowly evolving insulitis which results in a latent autoimmune diabetes leading to full insulin-dependence. Many animal models exist of NIDDM but none have reported the spontaneous existence of a similar phenomenon. We have re-examined the histology of pancreata from a few Psammomys obesus who had become insulin-dependent in the late stages of NIDDM. We report here the unexpected finding of the presence of insulitis in these animals and suggest that they could be a model for the clinical observation of latent IDDM in NIDDM patients.

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