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198-Au-gold colloid liver scans and 75-Se-selenomethionine pancreas scans in 72 patients with extrahepatic obstructive jaundice were assessed by blind marking. They were compared with liver and pancreas scans from 20 control patients and liver scans from 33 patients with diffuse liver disease. 56 per cent of the liver scans in extrahepatic obstructive jaundice showed a filling defect in the hilar region of the liver. This was most frequently seen in the most deeply jaundiced patients, and was reported in 80 per cent of patients with a serum bilirubin greater than 15 mg/100 ml. The liver scan alone cannot distinguish between different forms of extrahepatic obstructive jaundice although severe loss of left lobe uptake appeared to favour a diagnosis of carcinoma of the bile or hepatic ducts. A normal pancreas scan virtually excludes a pancreatic carcinoma as the cause of obstructive jaundice. A pancreas scan showing severely reduced uptake suggests a carcinoma of the pancreas or of the lower end of the common bile duct.

It is suggested that duodenal polyps are more frequent in Gardner's syndrome than previously recognized. The polyps have a particular tendency to undergo malignant change. Two patients with Gardner's syndrome are reported in whom duodenal polyps were associated in one patient with periampullary cancer and in the other with a possible adenocarcinoma of the duodenum.

The oral ingestion of naturally occurring purified trypsin inhibitors from soybean, ovomucoid, and bovine pancreas has been demonstrated to be a potent stimulus to pancreatic digestive enzyme synthesis. This effect may be so marked as to lead to impairment of growth in the rat and chicken through the faecal loss of essential amino acids. This is thought to be due to the markedly potentiated secretion of pancreatic digestive enzyme protein overwhelming the normal digestive capacity of the gastrointestinal tract and resulting in a pancreatogenous protein-losing enteropathy. Experimental evidence is presented to suggest that this response to the trypsin inhibitors requires the mediation of the gastrointestinal tract and is independent of vagal innervation to the pancreas. The most satisfactory hypothesis would favour the release of a trophic stimulus from the intestinal mucosa (possibly pancreozymin-cholecystokinin) to the acinar cell of the pancreas in response to the presence of the trypsin inhibitor in the bowel lumen. It is suggested that a primary function of the endogenously secreted pancreatic trypsin inhibitor may be to potentiate enzyme synthesis by the acinar cell, providing an important stimulus for the repletion of the digestive enzymes. Some of the potential physiological and clinical implications of such a mechanism are discussed.

1. 1. Calculous and acalculous natural bile, and aqueous dispersions of cholesterol, conjugated bile salts and phospholipid which resemble both kinds of natural bile, have been investigated by the negative-staining technique of electron microscopy, with the aim of obtaining data on the shape and size of mixed micelles of lipid and bile salts occurring in normal and pathological bile. 2. 2. Two main kinds of macromolecular assembly were seen. One of these, which was present in both calculous and acalculous bile, apparently owes its characteristic appearance to the presence of bile salts, since similar structures were observed in “artificial” bile. This assembly was interpreted in terms of a specific arrangement of disc-shaped, mixed micelles of lipid and bile salt molecules. The structure of the other assembly observed closely resembles that of “liposomes” which occur in dispersions of phospholipid and cholesterol free from bile salts. 3. 3. No significant differences were found between the negatively stained preparations of calculous and acalculous bile. It is suggested, however, that the growth of cholesterol-containing gall stones in pathological bile which is relatively deficient in bile salts may be associated with the presence of liposomes.

The Lundh test meal was administered to 32 normal subjects and 53 patients with suspected pancreatic disease. Tryptic activity was measured in the recovered duodenal juice. The level of activity distinguished the normal subjects from those with independently confirmed pancreatic disease, particularly chronic pancreatitis and carcinoma of the pancreas. The advantages and disadvantages of the test are discussed.

A new test of pancreatic exocrine function is described in which radioselenium is measured in duodenal aspirate after an intravenous injection of (75)Se-selenomethionine and administration of a Lundh test meal. Duodenal (75)Se activity gave good separation between normals and subjects with disease of the exocrine pancreas and correlated well with trypsin levels in the aspirate.

Hepatic bile biochemistry has been studied by aspiration of the common bile duct at the time of cholecystectomy in 23 patients with cholesterol gallstones and by duodenal aspiration in 17 patients 3 or more months after cholecystectomy, and in 10 control subjects without gallbladder disease. In 10 of the cholesterol gallstone patients, bile was studied both at the time of cholecystectomy and again 3 to 6 months after surgery. The results confirmed previously reported findings that hepatic bile from patients with cholesterol gallstones at surgery contains an excess of cholesterol relative to bile salts and phospholipids. Calculation of the bile salts + phospholipid-cholesterol and phospholipid-cholesterol ratios, and plotting the data on triangular coordinates indicated that, after the removal of the gallbladder, the hepatic bile was better able to maintain cholesterol in solution. It is suggested that the biochemical abnormality reported in hepatic bile of patients with cholesterol gallstones is not necessarily continuous and that in some patients the lipid composition of the bile reverts to a more normal pattern following cholecystectomy.

1. 1. Filtration of human gallbladder and hepatic bile samples on Sephadex gels was undertaken in an attempt to study pigment-binding micelles in human bile. Two portions of pigment-material were identified when concentrated gallbladder bile samples were eluted on G75 columns: P-V which was excluded from the gel bed, having an apparent molecular weight greater than 50000; and P-G which entered the gel bed, having an apparent molecular weight less than 50000. P-G contained over 70% of the bile pigments. Only one portion of pigment-material, which all entered the gel bed (P-G), was obtained when dilute gallbladder and hepatic bile samples were filtered. 2. 2. The initial eluant fractions of the more concentrated bile samples were turbid. The turbid material was composed mainly of cholesterol with little phospholipids and no bile salts, and was the consequence of bile salts being removed from the micellar aggregates by the gel. 3. 3. Sephadex gel filtration resulted in a significant reduction in the size of the micelles, the greater the quantity of gel used, the greater the reduction in the size of the aggregate eluted off the columns. 4. 4. It was concluded that Sephadex gel filtration caused degradation of the micelles in bile, and that such techniques, if used to measure the molecular weight of bile micelles, must be evaluated in the light of these findings.

1. 1. A macromolecular aggregate associated with bile pigments has been isolated from human gallbladder and hepatic bile, using isopycnic gradient ultracentrifugation in caesium chloride. Sixty-six percent of the total bile pigments, 66% of the total cholesterol, 69% of the total phospholipids and 65% of the total bile salts present in bile were associated with this polymolecular aggregate. 2. 2. The percentage contribution of each of the components measured in the macromolecule was 14.5% cholesterol, 16% phospholipids, 66% bile salts, 3% bile pigments and 0.5% protein. 3. 3. The molecular weights of the macromolecular aggregate varied with the source of the bile, being from 11000 to 20000 in hepatic bile; from 35000 to 75000 in bile samples from gallbladders containing gallstones; and from 65000 to 75000 in bile samples from normal gallbladders. The molecular weight of the aggregate varied with the concentration of the bile. Heavier complexes were present in the more concentrated bile samples. 4. 4. It was suggested that the macromolecule represented the micellar aggregation of cholesterol, phospholipids, bile salts and pigment in bile.