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Active and passive intestinal absorption and the efficiency of hepatic galactose clearance were studied in 12 patients with liver cirrhosis and 8 healthy control subjects using differential absorption techniques in which paired sugar markers were ingested simultaneously. Such differential absorption procedures overcome the effects of variation in gastric emptying, intestinal transit, distribution space and renal clearance which could invalidate tests incorporating a single marker only. In the cirrhotic group, active absorption of D-xylose (D-xyl) compared with that of 3-O-methyl-D-glucose (3-OMG), indicated by the ratio of D-xyl/3-OMG concentration in plasma, showed no reduction in respect to the control group. The passive intestinal permeability to lactulose (lac) compared with that of L-rhamnose (rham), indicated by urinary lac/rham excretion ratio, was not raised. These findings indicate no dysfunction of small intestinal mucosa in cirrhotic patients in spite of the clinical evidence of portal hypertension. Urinary galactose (gal) excretion after oral load was 10 times higher in the cirrhotic group (P less than 0.001). The gal/3-OMG excretion ratio correlated well with galactose elimination capacity as assessed by an intravenous method. Estimation of plasma D-xyl/3-OMG concentration and both urinary lac/rham and gal/3-OMG excretion ratios after appropriate oral loads provided a convenient and simultaneous evaluation of intestinal absorption, permeability and hepatic galactose elimination.

The influence of CDCA and UDCA administration on human intestinal permeability to lactulose, as disclosed by intravenous CCK, has been investigated. For this purpose the fraction of lactulose excreted in the urine during 5 h after an oral load of the disaccharide in hypertonic solution was measured in 12 healthy subjects, with and without intravenous CCK. The lactulose test was performed in each subject before and after a 7-day course of oral CDCA or UDCA (750 mg/day). Under basal conditions CCK induced a 100% increase in lactulose excretion. CDCA treatment further augmented the response to CCK by 33% (p less than 0.001) but UDCA produced no significant change. Finally, the effect of CDCA or UDCA added directly to the lactulose test solution was investigated in 4 subjects following oral and duodenal administration. CDCA only produced an increase in lactulose excretion (more than 100%) when given in hypertonic solution. The possible reasons for these findings are discussed.

Differential absorption of D-xylose and 3-O-methyl-D-glucose, and unmediated intestinal permeation of lactulose and L-rhamnose has been investigated in 14 patients with diarrhoea following tropical exposure and in 16 healthy control subjects. Five had malabsorption of fat, D-xylose and B12 ('tropical malabsorption' (TM) group), and that was absent or minimal in the others ('tropical diarrhoea' (TD) group). After combined ingestion of the four test sugars in iso-osmolar solution a marked depression in plasma D-xylose concentration (with a slow rise) occurred in all of the TM group; the TD group did not differ significantly from the controls. In contrast, 3-O-methyl-D-glucose absorption was similar in all three groups. Urine analysis demonstrated that intestinal permeation of lactulose was increased and that of rhamnose decreased in the TM group compared with the controls. Ingestion as a hyperosmotic solution further enhanced abnormal lactulose permeation in the TM group. Although some of the TD group showed one or the other of these changes, discrimination of the TM group from the TD and control groups was improved when results were expressed as lactulose/rhamnose differential permeation ratios, especially when using a hyperosmotic stress. Similar abnormalities have previously been demonstrated in untreated gluten-induced enteropathy (coeliac disease). The magnitude of the absorption defects demonstrated in TM are more severe than would be anticipated from the jejunal mucosal abnormalities alone; this suggests that there is probably significant pathology in the distal small intestine (including the ileum) in TM.

The effect of intravenous cholecystokinin (CCK) on intestinal permeability in normal subjects and patients after cholecystectomy has been studied by measuring the fraction of orally administered lactulose excreted in the urine. CCK induced a marked increase in lactulose excretion in normal subjects when given in a hyperosmolar solution (49.4 mg lactulose during 5 h rising to 114.3 mg with CCK, p less than 0.001). CCK failed to affect lactulose excretion when given to normal subjects in an isosmolar solution, and also when given to post-cholecystectomy patients in either hyper- or isosmolar solutions. The 'CCK effect' is therefore related to gallbladder emptying. It is suggested that conjugated bile acids released following gallbladder contraction can affect intestinal permeability by enhancing the action of hypertonic solutions on the small intestinal mucosa.

A system of quantitative paper chromatography is described in which compounds are directly scanned on the paper after a locating colour reaction. Sources of error arising at different stages are analysed and controlled by modifications in technique. Reproducibility is improved by using paper with uniform solvent flow characteristics, and the colour reaction controlled by choice of optimal reagent concentration, a modified dipping technique and rotation of the chromatogram during heating in the hot-air oven. After paper clarification by oiling, spots are sanned transversely, across the development axis, by double reflectance densitometry using a Joyce-Loebl Chromoscan, and calculations are based on comparison of peak areas. Most of the principles involved are generally appliable to paper chromatography. Sugar estimations in plasma and urine have a coefficient of variation between ± 2.0 and 3.5% when applications around 20 μg are used without replication. Sugar recoveries from urine are between 99 and 108% provided the desalting resin is correctly prepared; but from plasma and haemolysed whole blood recovery is higher due to a factor arising at the stage of deproteinization. The method has been used to estimate stachyose, raffinose, melibiose, lactose, lactulose, palatinose, sucrose, galactose, glucose, fructose, mannose, fucose, xylose, xylublose and 3-O-methyl glucose, either singly or in various combinations, in concentrations down to 1 mg/100 ml. The advantages of the method, in relation to other available techniques, are discussed.