The histological classification of duodenitis in fibreoptic biopsy specimens.

Recent advances in biopsy techniques using fibreoptic instruments have refocussed attention on the condition on non-specific duodenitis. Investigation of the topography of duodenitis and its relationship to possible aetiological factors and to duodenal ulcer calls for a proper histological classification. Such a classification is proposed based on the subjective appearances and a quantitative examination of 747 fibreoptic biopsy specimens in a wide range of clinical conditions.


Carcinoma of pancreas, A study based on autopsy data from 1928 to 1972 in Vienna, Austria.

The analysis of autopsy data from 1928 to 1972 shows that the relative frequency of carcinoma of pancreas has undergone a threefold increase during the past 30 years. During period B (1953--1972) there has been a real increase (twofold) for the middle and higher age groups as compared with that during period A (1928-1952). Further, it seems that the frequency rises non-linearly with age and that the higher age groups are relatively more prone to a malignant change of the pancreas. The pattern of pathological manifestations has been discussed and its practical importance pointed out.


Action of intragastric ethanol on the pancreatic secretion of conscious rats.

A surgical procedure has been disigned which permits injection in the stomach and the duodenum by separate catheters, collection of the pancreatic juice during the experiments, recirculation of the pancreatic juice into the duodenum between experiments, and a normal circulation of bile in rats. Experiments were performed in conscious rats given either 20% ethanol or water. In rats submitted to daily ethanol consumption for 13 months, the intragastric injection of 2 g/kg 20% ethanol considerably increased the pancreatic secretion of protein and, to a lesser extent, of water. In control non-alcoholic rats, a short period of increased secretion is followed by a major inhibition of pancreatic secretion, this reverse reaction to ethanol of pancreatic secretion according to whether or not rats are adapted to regular ethanol consumption is similar to what has been previously observed in dog. In chronic alcoholic rats, the release of secretin is probably not very different from controls.


Calcium-binding activity of rat intestinal mucosa after massive small bowel resection.

Male Sprague-Dawley rats underwent resection of 50 cm of either proximal or distal small intestine or sham-operation. 6-7 weeks after operation mucosal calcium-binding activity was measured in segments of duodenum ileum and remaining 'midgut'. Similar measurements were obtained from weight and age-matched unoperated rats. There was no difference in calcium-binding activity between unoperated and sham-operated animals. After proximal resection the binding activity increased significantly in duodenum and midgut but did not change in ileum. After distal resection the binding activity decreased in duodenum but was unchanged in midgut and ileum. These studies show that mucosal calcium-binding activity undergoes changes but alteration of the binding activity in remaining gut varies with the location of the small bowel resection.


Endoscopic diagnosis of advanced gastric cancer. Factors influencing yield.

Factors influencing diagnostic yield by directed endoscopic biopsy and cytology were studied in 50 patients with advanced gastric cancer using a forward-viewing panendoscope. The diagnostic yield was higher for exophytic lesions than for infiltrative tumor, and directed brush cytology alone was more productive than directed biopsy alone. The lesions that provided non-diagnostic tissue were mostly recurrent or infiltrative cancers, and were most often in the cardia, antrum, or were of the linitis plastica type. The combination of infiltrative character and location in antrum or cardia, especially if recurrent, often resulted in non-diagnostic biopsy and cytology specimens.


Serial insulin tests over a five-year period after highly selective vagotomy for duodenal ulcer.

Twenty-one patients underwent serial insulin testing, approximately 1 week, 1 year, 3 years, and 5 years after highly selective vagotomy (HSV) for duodenal ulcer (DU). They were thought to be representative of the much larger number of patients who have undergone HSV for DU in Leeds. The results obtained were compared with the responses to insulin of 40 other DU patients who were tested before HSV. Before operation, all tests were positive in the 1st hr after insulin ("early-positive") by Hollander's criteria and the mean peak acid response to insulin after subtraction of basal acid output (PAO1) was 33 mEq per hr. One week after HSV, all 21 tests were negative and mean PAOI was 0.05 mEq per hr. One year after HSV, 62% OF 21 tests were Hollander-positive and PAOI had increased significantly (P less than or equal to 0.001) to a mean of 2.3 mEq per hr. Three years after HSV, 15 of 17 tests (94%) were Hollander-positive and mean PAOI was 3.1 mEq per hr (0.1 greater than or equal to P greater than or equal 0.05, compared with PAOI at 1 year). Five years after HSV, 65% of 20 tests were positive and mean PAOI was 3.5 mEq per hr, a significant increase (P less than or equal 0.05) compared with PAOI at 1 year. Only 2 patients (10%) had consistently negative insulin tests over the 5-year period and neither of them was tested 3 years after operation. Thus, HSV was found to abolish consistently the acid response to insulin soon after operation, but on serial testing 90% of the patients eventually developed positive responses to insulin by Hollander's criteria. Most of the acid responses to insulin after HSV were small and the mean reduction in PAOI 5 years after compared with PAOI before operation is approximately 90%. The positive responses to insulin in the long term after HSV could be due to vagal nerve regeneration or to other causes. After a mean period of follow-up of 5 years (range 3 1/2 to 6 1/2 years), only 1 of the first 100 patients who were treated by HSV for DU in Leeds has so far developed recurrent ulceration. The findings of a positive response to insulin by Hollander's criteria more than 1 year after HSV appears to have no prognostic significance.


A study of the relationship between serum group I pepsinogen levels and gastric acid secretion.

Serum group I pepsinogen (PG I) levels, basal acid output, and peak acid output (PAO) have been determined in 120 patients, 54 with duodenal ulcer, 14 with prepyloric ulcer, 12 with gastric ulcer, and 40 without ulcer. The correlation between serum PG I and PAO was statistically significant (r = 0.736, P less than 0.001) up to a serum PG I level of 250 ng per ml. Serum PG I levels above 250 ng per ml were associated with a plateau in the PAO. Each of 8 patients with a serum PG I of less than 40 ng per ml had a PAO of less than 10 mEq per hr. Of 34 patients with a serum PG I over 200 ng per ml, 29 (85.3%) had a PAO of greater than 40 mEq per hr and all had a PAO above 34 mEq per hr. Of 51 patients with a serum PG I between 60 and 150 ng per ml, 47 (92.2%) had a PAO of between 10 and 40 mEq per hr. The results indicate that a significant relationship exists between the concentration of PG I in serum and the acid secretory capacity of the gastric mucosa.


Distribution of parietal cells in the antral mucosa of human stomachs.

The distribution of parietal cells in the antral mucosa was examined in 118 stomachs obtained at necropsy from persons of both sexes and all ages in whom death resulted from a wide variety of causes, except gastric lesions. The parietal cells appeared in the antrum in 116 out of 118 cases (98.3%). The patterns of distribution of parietal cells were divided into 4 groups. The most frequent pattern (76.3%) was that in which the parietal cells were distributed in all regions of the antrum including just proximal to the gastro-duodenal junction. Parietal cells were found most frequently in the area just proximal to the junction at 20 to 40 years of age and also at 70 years of age. In 18 of the 118 stomachs the focal concentration of the parietal cells near the duodenum was greater than the other part of the antrum, reaching more than 50% of the parietal cells of the average fundic gland. The density increased in slight antral gastric and decreased in cases with moderate to severe antral gastritis. On the other hand, clustered parietal cells were present in the proximal part of the duodenum in 27 of 118 cases. Parietal cells were found also in the antrum of stomachs from newborns and infants, thus this is not metaplasia or dystopia, but is a physiological finding. Therefore the parietal cells in the antrum were considered as a usual cell component of the pyloric gland.


Ultrastructural and physiological changes in piglet oxyntic cells during histamine stimulation and metabolic inhibition.

Neonatal pig gastric mucosa was studied in order to correlate electrophysiological and secretory parameters with ultrastructural changes in membrane components of oxyntic cells. The non-stimulated tissue had a transmucosal resistance of about 130omega - cm2 while the oxyntic cells were characterized by numerous cytoplasmic tubulovesicles and short microvilli extending into patent glandular and canalicular lumina. Upon histamine-stimulation, the average rate of H+ secretion was 8.1 mueq - cm2 - hr-1 and the resistance decreased to 77omega - cm2. The changes were coupled with an immense elaboration of the oxyntic cell apical and canalicular surfaces with a concomitant decrease of  tubulovesicles. Thus, the observed decrease in resistance was correlated to large increases in secretory membrane area. Anoxia inhibited H+ secretion while resistance increased to 211omega - cm2. Anoxic oxyntic cells were characterized by swollen mitochondria and occlusion of the lateral intercellular space and basal infoldings. Little change in the configuration of the secretory surfaces was noted, thereby suggesting that restriction of lateral and basal membranes might be responsible for the observed resistance increase. An electrical analogue of gastric mucosa is proposed on the basis of these morphological observations.


Intestinal uptake of macromolecules. IV.--The effect of pancreatic duct ligation on the breakdown of antigen and antigen-antibody complexes on the intestinal surface.

We have previously shown a consistent decrease in antigen absorption in vitro by ileal and jejunal gut sacs from orally or parenterally immunized rats in contrast to controls. In immunized rats, antigen appeared to be retained on the surface of the intestine and to be retained on the surface of the intestine and to undergo enhanced degradation by local proteases. This study was concerned with the role of pancreatic enzymes in degradation of antigen and antigen-antibody complexes. The breakdown of [125I]bovine serum albumin (BSA) by jejunal and ileal gut sacs from BSA-immunized, pancreatic duct-ligated rats was significantly decreased in comparison to that of BSA-immunized, sham-operated controls. Treatment of the immunized, pancreatic duct-ligated rats with pancreatic extracts prior to removal of the gut sacs, led to an increase in breakdown of [125I]BSA by the gut sacs in vitro. These findings suggest that pancreatic enzymes adsorbed to the surface of the intestine contribute to the proteolysis of antigens and antigen-antibody complexes at this site.


Gastric emptying and small intestinal mucosal injury in rats.

A technique was developed to produce small intestinal mucosal injury in vivo by perfusing the mid-small intestine of rats with HCl, NaOH, FeSO4, and AgNO3. Three hours following injury, gastric emptying and small intestinal transit were measured by examining the gastrointestinal distribution of a non-absorbable radioisotope which had been placed in the stomach for 1 hour. There was a strong association between the villus injury produced by various concentrations of the injurious agents and the degree of gastric retention. Necrosis of villus tips, as produced by AgNO3, was sufficient to cause marked gastric retention. Injury to the small intestinal mucosa of one parabiotic rat did not produce gastric retention in the partner. It is concluded that injury to small intestinal villi is sufficient to induce gastric retention and that the effect is most likely nerve-mediated.


Short chain fatty acids in rats with jejunal blind loops. I. Analysis of SCFA in small intestine, cecum, feces, and plasma.

The luminal and plasma levels of short chain fatty acids (SCFA), products of bacterial fermentation, were measured in rats with surgically produced, self-filling blind loops located in the proximal small intestine. High levels of acetic, propionic, and butyric acids were detected in the blind loop segment and in the distal small bowel, regions which in normal and sham-operated rats contain no SCFA. Isobutyric, isovaleric, and valeric acids were also present. Feeding or fasting made little difference in the amount or composition of luminal SCFA. Although the amount of SCFA in each animal varied, the ratio of these acids was relatively constant. The ceca of the blind loop rats had relatively less acetic acid (48% of total SCFA) than did normal rats (64%) and proportionately more isobutryic, isovaleric, and valeric acids. The concentrations of SCFA increased in the feces of blind loop rats. The acetic acid concentration was 50% higher in blind loop rat feces; propionic, isobutryic, and isovaleric acids were elevated to a greater extent. The total output of most of the SCFA was also of acetic acid (137 +/- 32 mug per ml), the rest being isovaleric (5.2 +/- 2.6 mug per ml) and isobutyric (1.4 +/- 0.7 mug per ml) acids. Blind loop animals had nearly twice the concentration of acetic acid in the plasma (240 +/- 29 mug per ml) as normal animals, while the other acids were unchanged. The present study suggests that endogenous substances may be important substrates for the production of SCFA in the intestinal lumen. The high levels of SCFA in the small intestine and in feces and the substantial increase in the concentration of acetic acid in thvergrowth syndrome if the same relationships were found in man.


Role of cholinergic mechanisms in the response to secretin of isolated canine pancreas.

The effects of carbamylcholine (CCH, 100 mug per hr) and of atropine (0.25, 1.0, and 10.0 mg per hr) on the response of the exocrine pancreas to secretin (0.1, 0.5, and 5.0 clinic units per hr) were studied using the isolated canine pancreas perfused with whole heparin-treated blood. CCH induced a sharp decrease in D50 (dose of secretin which elicits half the calculated maximal response) but no increase in maximal response to secretin. Experiments performed under different haemodynamic conditions show that this potentiating effect (synergism) is partly due to vasomotor modifications and chiefly to the action of CCH on the receptor of secretin. Although this work indicates that cholinergic tone is not necessary for secretin-induced hydrelatic response to occur, it evidences that this cholinergic tone plays a major role in modulating the pancreatic response to submaximal doses of secretin. It has also been found that large doses of atropine (10 mg per hr) were necessary to achieve a complete inhibition of enzymatic response to CCH. Even at these high doses, however, enzymatic response to secretin and cholecystokinin-pancreozymin were not significantly inhibited.


Arthritis associated with chronic active hepatitis: complement activation and characterization of circulating immune complexes.

Circulating immune complexes were identified in cryoproteins isolated from serial serum samples from 6 to 10 patients with chronic active hepatitis (CAH) with frank arthritis and arthralgias. These immune complexes were not detectable in patients with uncomplicated CAH. Only cryoprecipitates from CAH patients with frank arthritis contained IgG, IgM, IgA, and complement components C3, C4, and C5. Hepatitis B surface antigen was concentrated several-fold in the cryoprotein immune complexes as compared with the serum concentration. The C3 activator fragment of the properdin complex was found in fresh serum in all patients with arthritis but was undetectable in patients with arthralagias and uncomplicated CAH. Thus, the presence of circulating complement-fixing immune complexes in patients with alternate complement pathways, and suggests that they play an important role in the pathogenesis of the arthritis.


Dynamic studies on the portal hemodynamics of scintiphotosplenoportography. Streamline flow in the human portal vein.

To demonstrate streamline flow in the human portal vein, the hepatic lobar distribution of splenic flow was studied in 6 patients without liver disease and 4 patients with chronic hepatitis using a new technique, scintiphotosplenoportography, followed by 198Au-colloid liver scintigraphy. In two patients, a 99mTcO4-bolus injected into the spleen drained predominantly into the left lobe of the liver. A repeat examination performed in one patient revealed that the bolus was chiefly directed to the other lobe, the right lobe. In 3 patients, the distribution of 99mTcO4- radioactivity was the same as that observed with 198Au-colloid. In the other 5 patients the predominant distribution of 99mTcO4- was observed in the right lobe. In 8 of 11 studies, splenic flow was distributed either to the right or left lobe instead of diffusely to both lobes. This result suggests that flow in the human portal vein is streamline rather than turbulent.


Effect of primary bile acid ingestion on bile acid metabolism and biliary lipid secretion in gallstone patients.

Bile acid kinetics were measured by isotope dilution, and hourly outputs of bile acid, cholesterol, and phospholipid were quantified by duodenal perfusion over 24 hr including three liquid meals and an overnight fast in 6 gallstone patients during a pretreatment period and two randomized treatment periods with chenodeoxycholic (chenic) acid or cholic acid. During chenic acid ingestion, bile contained predominantly chenyl conjugates. During cholic acid ingestion, bile was composed of about equal amounts of cholyl and deoxycholyl conjugates; chenyl conjugates decreased markedly due in part to a 50% decrease in chenic acid synthesis. Total bile acid pool size doubled in half the patients receiving either bile acid and was not different during treatment with chenic or cholic acid. Compared to cholic acid, chenic acid caused decreased cholesterol output with no difference in bile acid or phospholipid output. Therefore, bile unsaturated with cholesterol entered the duodenum for more hours per day during chenic acid ingestion than during the cholic or pretreatment periods. There was no relationship among bile acid pool size, bile acid output, and hours per day of supersaturated bile; there was an inverse relationship between total pool size and recycling frequency such that bile acid output remained stable over a wide range of pool sizes. Fasting-state gallbladder bile was supersaturated during the cholic and pretreatment periods, but became unsaturated during chenic acid ingestion. However, hours per day of supersaturated bile could not be reliably predicted from the degree of saturation of fasting-state gallbladder bile (r = 0.62). The efficacy of chenic acid and the lack of efficacy of cholic acid for gallstone dissolution appear related to their different specific effects on biliary cholesterol secretion and not to any effect on bile acid and phospholipid secretion or bile acid pool size.


Bile-salt metabolism in the primate fetus.

Fetal bile salt metabolism was assessed by the intravenous infusion of e114C]cholate into 6 monkey fetuses. The placental transfer, fetal plasma clearance, and fetal hepatic excretion of the administered radiolabeled bile salt were measured. Placental transfer averaged 30% of the injected dose, while biliary excretion averaged 36%. Of the amount excreted by the fetal liver, 78% was in the form of [14C]taurocholate. The findings suggest that bile salt metabolic and excretory mechanisms are undergoing developmental maturation at birth.


Ischemic colitis after abdominoperineal resection.

Four cases of ischemic colitis occurring at intervals from 3 months to 7 years after abdominoperineal resection are described. In 3 of the 4 cases patency of the direct arterial supply to the ischemic segment was documented. The lack of collateral circulation provided by the resected colon probably increases the risk of developing ischemic colitis in the remaining colon.


Adenosquamous carcinoma of the liver.

A rare case of adenosquamous carcinoma of the liver is reported. An 85-year-old white man presented with a 6-month history of weight loss and an enlarged liver. A biopsy demonstrated a squamous cell carcinoma which was presumed to be metastatic with an occult primary. At autopsy, the liver was partially replaced by a focally cystic tumor. Histologically, the neoplasm demonstrated both malignant squamous and glandular contradistinctionmponents as well as foci of transition between the two. This is in co to the 5 previous reported cases of primary hepatic squamous cell carcinomas or tumors containing a squamous component. It is suggested that this neoplasm arose from malignant transformation of squamous metaplasia in a pre-existing cholangiocarcinoma.


Metastatic malignant melanoma of the esophagus: a case report.

This report documents the 4th case in the world literature of a malignant melanoma metastatic to the esophagus. The value of gallium scanning in the evaluation of known cancer patients is exemplified by this patient.


Evidence for the existence of definitive hepatic cholesterol precursor compartments for bile acids and biliary cholesterol in man.

A bile fistula patient was administered intravenously a constant infusion of [3H]mevalonic acid for 4 hrs, and then after 2 weeks he was given a pulse of [3H]mevalonic acid. Bile and blood were collected at frequent intervals. The specific activity-time course curves did not show a precursor-product relationship between biliary cholesterol, plasma free cholesterol and bile acids. Both the constant infusion and pulse labeling data indicated that the bile acid precursor had a more rapid rate of turnover than plasma or biliary cholesterol; the biliary cholesterol precursor turned over more rapidly than plasma cholesterol. The data suggest the presence of multiple hepatic cholesterol precursor compartments. Bile acids may be derived predominantly from newly synthesized cholesterol in man.


Effect of pentagastrin and caerulein on intragastric pressure in the dog.

When gastric acid was not neutralized, doses of pentagastrin as small as 1 mug kg-1 hr-1 decreased intragastric pressure in dogs. When gastric acid was neutralized the smallest effective dose of pentagastrin was 8 mug kg-1 hr-1 which is 16 times the D50 for acid secretion. Thus the decrease in intragastric pressure by small doses of pentagastrin is mediated at least in part by acid secretion. Even with gastric neutralization, a dose of caerulein as small as 63 ng kg-1 hr-1, which is the D50 for pancreatic protein secretion, decreased intragastric pressure. These findings support the view that inhibition of gastric pressure occurs with physiological doses of the cholecystokinin-like peptide caerulein but only with pharmacological doses of pentagastrin.