A lack of difference in peripheral IR, measured using HOMA-IR, in the CF group and healthy controls or within the CF group with differing glycaemic status suggests that IR does not have a significant role in the pathogenesis of CFRD. Pancreatic -cell function, already subnormal in CF patients with OGTT-defined normal glucose tolerance status, deteriorated further with worsening glycaemic status. This suggests that insulinopenia plays a prominent role in the pathogenesis of glucose intolerance and subsequent development of CFRD.

The diuretic activity of bumetanide has been studied in 16 Glasgow, London, and Sheffield, England Department of Medicine, Western Infirmary, Glasgow, Department of Therapeutics, Westminister Hospital, London, and Department of Pharmacology and Therapeutics, Royal Infirmary, Sheffield Bumetanide (3-n-butylamino-4-phenoxy-5-sulfamoylbenzoic acid, Brinex) is a derivative of metanilamide that displays potent diuretic activity on oral administration

1 The pharmacokinetic and pharmacodynamic properties of oral glibenclamide have been studied in 31 hospitalised in-patients and 79 ambulant out-patients with diabetes mellitus. 2 Breakfast was found to have no significant influence on the kinetic behaviour of glibenclamide or on the effect of this drug on blood glucose utilisation. 3 The time course of glibenclamide kinetics after 20 mg dosing was adequately described by a two-compartment open model, yielding mean half-lives of 3.3 ± 1.5 h (t½/,X) and 9.7 ± 1.2 (t½,z) for the initial and terminal elimination phases respectively. 4 No significant accumulation or change in kinetic profile occurred in patients who had normal renal and hepatic function, were treated continuously with glibenclamide, and then rechallenged after 8-12 weeks.5 Despite inter-individual variations in drug absorption, peak plasma concentrations (Cmax) and the area under the plasma concentration-time curve (AUC(0-24)) were dosedependent over the dose range 5-20 mg. No significant dose-response behaviour was observed in respect of glucose utilisation, suggesting that there is little clinical benefit in using doses of glibenclamide above 5 mg day-'. 6 Comparison of plasma glibenclamide concentrations at different time-bands following doses of 5 and 10 mg showed a wider range in ambulant out-patients than in age-, sexmatched in-patients treated with the same dosages of drug. Mean plasma drug concentrations attained at all time bands up to 8 h after dosing were higher in out-patients than in in-patients, suggesting a tendency to 'over-compliance' by patients in anticipation of attendance at clinic.

Enalapril, the ethyl ester of a potent angiotensin converting enzyme inhibitor, enalaprilat, was administered to healthy volunteers as a capsule containing 10 mg of the maleate salt, every 24h for eight doses. Serum profiles show little accumulation of enalaprilat following eight daily doses of enalapril maleate. An average effective half-life for accumulation of approximately 11h was calculated from urine data. Comparison of observed 24-h urinary recoveries of enalaprilat to predicted steady-state recovery indicates that an 'average' steady state for enalaprilat is attained by the third or fourth dose of enalapril maleate. Statistical comparison of daily urinary recoveries, as well as Cmin values for enalaprilat, confirm this. Observed fluctuations in serum and urine data during apparent steady state suggest some day-to-day variability in the absorption of enalapril maleate and/or its hydrolysis to enalaprilat. An accumulation ratio of 1.3 for enalaprilat was calculated from the predicted steady-state urinary recovery and observed urinary recovery for dose one.

No abstract

S U M MARY Serum concentrations of ,B-alanine and L-histidine are compared in five normal adults after ingestion of the dipeptide carnosine (/-alanyl-L-histidine) and after equivalent amounts of the constituent free amino acids. The results indicate that absorption is significantly more rapid after the ingestion ofthe amino acids than after the dipeptide. The use of the test in a case of Hartnup disease suggests that carnosine is taken up by intestinal cells as the dipeptide, but subsequent hydrolysis and delivery of the constituent amino acids to the portal blood is a slower process than transport of the free amino acids themselves.

SUMMARY The results of oral tolerance tests of two dipeptides and of their constituent amino acids are compared in normal subjects and in a case of Hartnup disease. In the control subjects the rate of absorption of phenylalanine from phenylalanyl-phenylalanine and of tryptophan from glycyl-tryptophan was slower than after the equivalent amount of the free amino acids. Absorption of the two essential amino acids (tryptophan and phenylalanine) in the patient was almost zero after administration in the free form, but was much greater after the dipeptide.

Ten patients attending one general medical hospital clinic who fulfilled operational criteria for the diagnosis of myalgic encephalomyelitis (ME) and with a history longer than three months, underwent a series of standardized neuropsychological and psychiatric tests. Nine were able to complete the tests and were individually matched with a normal control group for age, sex, educational background and premorbid intelligence. The ME subjects showed inferior performance to the controls on two tests of verbal memory. Their personality scores displayed less extraversion and less psychoticism. This is the first report of objective neuropsychological abnormalities in patients with ME, suggesting a discrete deterioration of short-term memory. The findings may also suggest a concurrent psychiatric component of the condition, but the direction of causality remains to be clarified.