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As a simple non-invasive test of possible pancreatic insufficiency 10 healthy infants, 13 infnts with cystic fibrosis, and nine infants with unexplained diarrhoea and failure to thrive were given an emulsion containing fluorescein dilaurate and mannitol by mouth. A spot urine specimen was collected and results expressed as urinary fluorescein to mannitol ratios. Sensitivity of the test was 96% and specificity was 95%. (Arch Dis Child 1995; 72: 233-234) Nine infants with unexplained diarrhoea and failure to thrive (six boys, three girls) aged 2-42 months (median 16 months) were studied each on one occasion. Two children had steatorrhoea, two children chronic diarrhoea, one had juvenile chronic arthritis with failure to thrive, and four children had unexplained failure to thrive with weights below the third centile. TEST PROCEDUREThe studies were made in the morning after an overnight fast unless the infants were still receiving regular milk feeds in which case the fast did not exceed four hours. Fluorescein dilaurate (0-134 mmol) and mannitol (6-7 mmol) in 10 ml of emulsion were given by mouth followed by a milk feed. The emulsion was formed of the water insoluble fluorescein dilaurate ester dissolved in a medium chain triglyceride, using a soya bean based lecithin as emulsifier. Ultrasonication or microfluidisation produced an extremely fine dispersion of the triglyceride in the aqueous phase, which contained the second marker, mannitol. The emulsion was physically stable, resistant to heat sterilisation, and readily dispersible in infant milk formulas by simple shaking.Feeds were given thereafter as desired with or without pancreatic supplements as required. The two 5 year old children studied were allowed breakfast of tea, toast, and cereal two hours after taking the test substrates. Specimens of urine were collected as voided, into a urine bag, or using cotton wool balls enclosed in the napkins in infants,5 including in each study a specimen produced after two, but before five, hours after substrate ingestion. Urine was frozen at -20°C until analysis. BIOCHEMICAL MEASUREMENTSFluorescein concentration was measured spectrophotometrically. An aliquot of 0 5 ml urine was added to 4-5 ml 0-1 M sodium hydroxide and incubated at 70°C for 10 minutes to hydrolyse any fluorescein glucuronide (which is colourless) to free fluorescein. After centrifugation the absorbance (A) of the supernatant was measured at 492 nm against water. Fluorescein concentration was calculated from the equation:(((A492X 100)/35) x (50 42/100)) X 50The denominator and multiplication factors were determined from the dose administered, the dilution, and the absorption coefficient. Mannitol concentration was measured enzymatically using a method previously described. 1 4 The test result was expressed as a ratio of 233 on 7 May 2018 by guest. Protected by copyright.

There is a pressing need for a simple noninvasive test of exocrine pancreatic function for use in children. The pancreolauryl test has been modified by the addition of a second marker (mannitol) to achieve a single day test without the need for two timed urine collections. Six healthy subjects and nine patients with cystic fibrosis were studied. Fluorescein, fluorescein dilaurate, and mannitol were taken by mouth, alone or in combinations, followed by 10 hour urine collections in two hourly aliquots to study the comparative pharmacokinetics of these markers. by the development of a dual marker system which involves the inclusion of a second marker with absorption, distribution, and excretion characteristics similar to that of free fluorescein, to eliminate the second day of the test and to shorten the duration of the collection of urine. Mannitol, which has been used extensively for the measurement of intestinal permeability in infancy and childhood,'"' has been chosen as such a marker.The aims of this study were to compare fluorescein and mannitol as markers and to establish the suitability of the latter for combination with fluorescein dilaurate in a simplified one day test ofexocrine pancreatic function. We have used the new test to measure exocrine pancreatic function in healthy controls and in those with depressed function due to cystic fibrosis. Subjects and methods SUBJECTSSix healthy adults (four men, two women, aged 29-40 years) were studied, and nine subjects with cystic fibrosis (six male, three female, aged 6-25 years). All the patients with cystic fibrosis had had the diagnosis confirmed by sweat test and were judged clinically to require pancreatic enzyme supplementation.