Patrizia Priori

Comparative Study of Serum Pancreatic Isoamylase, Lipase, and Trypsin-Like Immunoreactivity in Pancreatic Disease

Serum total amylase, pancreatic and salivary isoamylase, lipase and trypsin-like immunoreactivity (TLI) were measured in 16 patients with acute pancreatitis, 37 patients with chronic pancreatitis, 11 patients with pancreatic cancer, and 53 control subjects in order to evaluate the relative value of these tests in the diagnosis of pancreatic disease. In acute pancreatitis patients studied within 2 days from the onset of pain all pancreatic enzymes were abnormally high. In chronic pancreatitis patients serum pancreatic isoamylase and TLI were abnormally low in 8 out of 10 patients with severely impaired pancreatic exocrine function, while lipase was abnormally low in 6 patients. During acute exacerbations of the disease elevated levels of pancreatic isoamylase and lipase, but not of TLI, were found in about one third of cases. In patients with pancreatic cancer the pattern of changes in serum pancreatic enzymes was variable since levels within, below and above the normal range were found. The results demonstrate that in acute pancreatitis all serum pancreatic enzymes had the same diagnostic sensitivity, however serum lipase determination is the most convenient because of its simplicity and low cost. In chronic pancreatitis serum pancreatic isoamylase and TLI may be useful in detecting severe pancreatic insufficiency. In pancreatic cancer serum pancreatic enzymes lack diagnostic specificity.

Inhibitory Effect of Atropine on Cholecystokinin-Induced Gallbladder Contraction in Man

We have studied the effect of atropine on cholecystokinin (CCK)-induced gallbladder contraction in 7 healthy volunteers by means of real-time ultrasonography. Two series of tests were carried out in random order and on separate days. In one series of tests, CCK alone was infused for 4 successive 15-min periods at sequentially increasing doses of 0.0021, 0.0042, 0.0084, and 0.0168 Ivy dog units (IDU) X kg-1 X min-1. In the other series of tests, an infusion of a low dose of atropine, 5 micrograms X kg-1 X h-1, was added to the hormone infusion. The smallest dose of CCK which significantly contracted the gallbladder was 0.0042 IDU X kg-1 X min-1. The highest dose of CCK infused, 0.0168 IDU X kg-1 X min-1, produced almost total contraction of the organ. In all subjects, the infusion of atropine completely blocked the gallbladder response to 0.0042 and 0.0084 IDU X kg-1 X min-1, and partially inhibited (by 52%) the response to the highest dose. In 2 subjects in whom a higher dose of atropine, 15 micrograms X kg-1 X h-1, was tested, gallbladder contraction was totally abolished, even when the largest dose of CCK was infused. Contrary to what is generally believed, the results indicate that the response of human gallbladder to CCK is largely dependent on cholinergic innervation.

Exocrine Pancreatic Function in the Elderly

We studied pancreatic bicarbonate and enzyme output in response to a continuous intravenous infusion of secretin, 1 CU/kg X h, and cerulein, 100 ng/kg X h, in 25 elderly subjects and in 30 young controls. Almost all elderly persons had pancreatic outputs within the range of controls. Only 3 aged individuals showed diminished enzyme output, but the reduction was very slight. We conclude that exocrine pancreatic function is not significantly influenced by aging.

Relationship between morphological changes detected by ultrasonography and pancreatic exocrine function in chronic pancreatitis

We have studied the degree of pancreatic secretory alterations assessed by secretin-cerulein test (S-C) in relation to various morphological changes detected by real-time ultrasonography (US) in 42 patients affected by chronic pancreatitis. Exocrine insufficiency was found in 41 patients (97.6%), while morphological alterations were detected in 32 (76.1%). In the 10 patients with normal US, a mild or moderate exocrine insufficiency was present. Significant negative linear correlations of decreasing volumes of duodenal aspirate (r = 0.528, p <0.001) and output of bicarbonate (r = 0.635, p <0.001), lipase (r = 0.583, p <0.001), and chymotrypsin (r = 0.592, p <0.001) were found with increasing ultrasonographic alterations. However, a wide overlap was found in the secretory behavior in the various categories of change as determined by ultrasound. Hence, the attempt to predict exocrine function on the basis of morphological alterations proved unsuccessful.

Effect of somatostatin 14 on pure human pancreatic secretion

While it is well known that large doses of somatostatin inhibit human pancreatic enzyme secretion, it is still unknown whether low doses are also effective and whether the peptide is able to inhibit bicarbonate production. Eight subjects with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery were studied. Somatostatin was infused at progressively increasing rates of 0.05, 0.15, 0.45, and 1.35 μg/kg/hr, for 30 min/dose, during pancreatic stimulation with secretin, 25 ng/kg/hr, and cerulein, 10 ng/kg/hr. Somatostatin, at the dose of 0.05 μg/kg/hr (shown to produce blood levels similar to those measured after a meal) did not affect pancreatic secretion in any of the subjects. The successive three higher doses caused a significant and dose-dependent inhibition of protein concentration and output and of bicarbonate output. Bicarbonate concentration was slightly but significantly reduced only by the two highest doses of somatostatin. At each dose level, the inhibition of protein output was much more marked than the inhibition of bicarbonate output. The maximal inhibition of protein output (at 1.35 μg/kg/hr somatostatin) was 73.9±5.4%, and that of bicarbonate output was 55.9±6.4%. The results demonstrate that: (1) the administration of somatostatin at a low dose level does not affect human exocrine pancreatic secretion, at least under the experimental conditions of this study; and (2) the administration of larger doses of somatostatin inhibits pancreatic secretion of both protein and bicarbonate dose-dependently. The inhibitory effect on protein output is significantly greater than that on water and bicarbonate production.

Effect of somatostatin and thyrotropin-releasing hormone on cholecystokinin-induced gallbladder emptying

The effect of somatostatin (0.05 and 1.5 μg/kg/hr) and of thyrotropin-releasing hormone (0.1 and 1.0 μg/kg/hr) on cholecystokinin-induced gallbladder emptying was studied in healthy volunteers by means of real-time ultrasonography. In addition, the action of increasing doses (0.05, 0.15, 0.45, and 1.35 μg/kg/hr) of somatostatin on resting gallbladder volume was also evaluated. Somatostatin, at the dose of 0.05 μg/kg/hr (shown to produce blood levels similar to those measured after a meal) significantly inhibited the gallbladder contraction in response to cholecystokinin. Kinetic analysis showed that the interaction of somatostatin and cholecystokinin is of the noncompetitive type. The higher dose of the peptide (1.5 μg/kg/hr) completely suppressed cholecystokinin-induced gallbladder contraction. In experiments carried out using somatostatin alone, a progressive increase in gallbladder volume in response to increasing doses of peptide was observed. The administration of either dose of thyrotropin-releasing hormone did not affect gallbladder emptying in any of the subjects studied. It is concluded that somatostatin is a potent inhibitor of cholecystokinin action on the gallbladder. The clear effectiveness of a very low, presumably physiological, dose indicates that somatostatin may play a physiological role in the regulation of gallbladder motor activity and provides further evidence that the peptide may act as a true hormone in man. Thyrotropin-releasing hormone does not seem to affect gallbladder motility, at least under the experimental conditions of the present study.

Pure Pancreatic Juice Collection Over 24 Consecutive Hours

We collected pure pancreatic juice during an entire day and examined pancreatic secretory changes induced by ordinary meals in a male patient having an external drainage of the main pancreatic duct. The ingestion of breakfast, lunch, and dinner each caused a marked increase in pancreatic secretion above basal levels. The increase in both bicarbonate and protein output was very prolonged. The highest secretory outputs induced by meals were slightly higher than those produced by exogenous administration of submaximal doses of secretin and cerulein. The profile and magnitude of bicarbonate and protein secretion were similar.

Pancreatic secretory response to ordinary meals: Studies with pure pancreatic juice

We have studied the pancreatic secretory response to a normal meal in 5 subjects with an external drainage of the main pancreatic duct carried out after biliary tract surgery. Pancreatic juice was collected at 60-min intervals from 10 AM to 7 PM, starting 2 h before and ending 7 h after lunch, and was analyzed for volume, bicarbonate content, and protein content. Large doses of pancreatic extract were given between and during meals. Both bicarbonate and protein output increased rapidly after the beginning of the meal and the increase persisted, with minor fluctuations, for the entire 7-h study period between lunch and dinner. The peak postprandial bicarbonate and protein outputs were higher (on average by 20% and 26%, respectively) than bicarbonate and protein outputs induced by exogenous infusion of submaximal doses of secretin and cerulein. The profile and magnitude of the bicarbonate secretory pattern elicited by food were not substantially different from those of protein secretion. In an additional patient who had undergone a duodenocephalopancreatectomy plus two-thirds distal gastrectomy before the study, the pancreatic response to meals showed an initial phase characterized by an increase in pancreatic secretion during the first postprandial hour followed by a tendency to decrease in the subsequent 2 h, and a later phase (from the fourth postprandial hour to the end of the study) characterized by a more marked and more persistent increase in pancreatic secretion than occurred in the initial 3 h. These data indicate that (a) the pancreatic secretory response to ordinary meals is much more prolonged than is generally believed. The late phase of the response is not dependent on gastric emptying of food into the duodenum, but is probably related to the arrival of chyme in the distal ileum. (b) The pancreatic secretory response to a normal meal is quantitatively slightly higher than that produced by exogenous pancreatic stimulation with submaximal doses of secretin and cerulein. (c) The pattern of postprandial bicarbonate secretion is similar to that for protein.

Influence of Adrenal Cortex on Exocrine Pancreatic Function

The exocrine pancreatic function of 8 patients with chronic adrenocortical insufficiency was studied and compared with 12 control subjects. The secretion of bicarbonate, lipase, and chymotrypsin in response to secretin and caerulein was significantly reduced in patients with adrenocortical insufficiency. The mean reduction in bicarbonate, lipase, and chymotrypsin output compared with the control values was 42%, 66%, and 53%, respectively. Chronic glucocorticoid substitution therapy restored pancreatic function almost to normal. It is concluded that the adrenal cortex plays an important role in maintaining the function of the exocrine pancreas in humans. The possible mechanisms are discussed.

Inhibition of pancreatic exocrine secretion and bile entry into the duodenum by isometheptene, a sympathomimetic agent.

We have studied the effect of isometheptene, an indirectly acting sympathomimetic with analgesic and antispastic properties, on secretin-cholecystokinin-stimulated pancreatic and biliary outputs. Isometheptene, infused intravenously at a dose of 100 mg in 30 min, significantly inhibited bicarbonate, enzyme, and bilirubin output in eight healthy subjects (compared to control values, the maximum percent inhibition was 34% for bicarbonate, 57% for lipase, 61% for chymotrypsin, and 86% for bilirubin). In four cholecystectomized subjects, the drug inhibited only pancreatic outputs. The inhibitory effect on pancreatic secretion, coupled with the analgesic action, suggest a potential benefit of this drug in acute pancreatic pathology.