Active and passive surveillance for bat lyssaviruses in Italy revealed serological evidence for their circulation in three bat species.

The wide geographical distribution and genetic diversity of bat-associated lyssaviruses (LYSVs) across Europe suggest that similar viruses may also be harboured in Italian insectivorous bats. Indeed, bats were first included within the passive national surveillance programme for rabies in wildlife in the 1980s, while active surveillance has been performed since 2008. The active surveillance strategies implemented allowed us to detect neutralizing antibodies directed towards European bat 1 lyssavirus in six out of the nine maternity colonies object of the study across the whole country. Seropositive bats were Myotis myotis, M. blythii and Tadarida teniotis. On the contrary, the virus was neither detected through passive nor active surveillance, suggesting that fatal neurological infection is rare also in seropositive colonies. Although the number of tested samples has steadily increased in recent years, submission turned out to be rather sporadic and did not include carcasses from bat species that account for the majority of LYSVs cases in Europe, such as Eptesicus serotinus, M. daubentonii, M. dasycneme and M. nattereri. A closer collaboration with bat handlers is therefore mandatory to improve passive surveillance and decrypt the significance of serological data obtained up to now.

Stimulation of gallbladder emptying by intravenous lipids.

BACKGROUND: Few studies have dealt with the effect of i.v. administration of lipids on gallbladder emptying, and the results have been conflicting. METHODS: Five healthy volunteers, three women and two men, aged 26 to 54 years, (mean, 29 years) were studied. Gallbladder emptying was assessed by means of real-time ultrasonography. RESULTS: In all subjects, the infusion of a 10% fat emulsion (Intralipid; Kabivitrum, Stockholm) over 3 hours caused a reduction in gallbladder volume. This effect was statistically significant at about 80 minutes of lipid infusion and became progressively more marked as the infusion progressed, reaching a reduction of approximately 30% during the third hour of infusion. A significant relationship (p < .001) was found between the concentration of serum triglycerides and the degree of gallbladder volume decrease. In control studies, infusion of physiologic saline containing glycerol, the excipient of intralipid, caused no significant changes in gallbladder volume. CONCLUSIONS: The results indicate that i.v. infusion of lipids is able to stimulate significantly contraction of human gallbladder.

Is chronic pancreatitis a cause of dyspepsia?

Chronic pancreatitis is commonly included among the organic causes of dyspepsia, however the frequency and characteristics of this association are ill-defined. One-hundred-fifteen consecutive patients with chronic pancreatitis and 85 healthy subjects were interviewed regarding their clinical history, with particular attention to dyspeptic symptoms. Attacks of prolonged upper abdominal pain, recurring at unpredictable intervals and in most cases without identifiable triggering factors, were the most frequent clinical manifestation (108, 94%). During the attacks, many patients (66, 61%) complained of vomiting, which was generally mild and of brief duration. Between the attacks, very few patients (12, 10%) complained of dyspeptic disturbances, mainly postprandial epigastric fullness and abdominal bloating. These complaints were episodic, usually after abundant meals, in 8, and persistent in the remaining 4. Among these 12 patients, there were no significant differences in the frequency of dyspeptic symptoms in relation to the severity of exocrine pancreatic insufficiency. The frequency of dyspeptic complaints among patients (10%) was significantly lower (p < 0.01) than the frequency of dyspeptic symptoms among the controls (25%). The results of this study indicate that, other than recurrent attacks of abdominal pain, dyspeptic symptoms are uncommon in chronic pancreatitis, and that impairment of digestion of pancreatic origin is not a cause of dyspepsia.

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.

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 micrograms/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 microgram/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 micrograms/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.

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.

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 less than 0.001) and output of bicarbonate (r = 0.635, p less than 0.001), lipase (r = 0.583, p less than 0.001), and chymotrypsin (r = 0.592, p less than 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.

Stimulation of exocrine pancreatic secretion by met-enkephalin.

The effect of met-enkephalin on pure exocrine pancreatic secretion was studied in five subjects with external transduodenal drainage of the main pancreatic duct carried out after biliary tract surgery. Intravenous infusion of a low dose of met-enkephalin (0.15 micrograms/kg/h) during submaximal pancreatic stimulation with secretin (25 ng/kg/h) and cerulein (10 ng/kg/h) significantly increased pancreatic outputs. Bicarbonate secretion increased 50% above control values, a more marked effect than the increase in enzyme secretion (maximal rise averaged 22%). The effect of the peptide was rapid, persisted for the duration of met-enkephalin infusion and then tended gradually to diminish.

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

The effect of somatostatin (0.05 and 1.5 micrograms/kg/hr) and of thyrotropin-releasing hormone (0.1 and 1.0 microgram/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 micrograms/kg/hr) of somatostatin on resting gallbladder volume was also evaluated. Somatostatin, at the dose of 0.05 microgram/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 microgram/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.

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.

Action of secretin on pancreatic enzyme secretion in man. Studies on pure pancreatic juice.

The action of pure, natural secretin on the pancreatic secretion of enzymes was investigated in six patients with external transduodenal drainage of the main pancreatic duct performed after biliary tract surgery. Secretin infused for five successive 50 minute periods at increasing doses of 0.03, 0.1, 0.3, 0.9 and 2.7 clinical units (CU)/kg/h, produce a dose dependent increase in protein and lipase output. A weak but significant (p less than 0.02) increase of enzyme output above the fasting level was already observed with the lowest dose. The maximal output of protein and lipase, observed with the highest dose of secretin infused, corresponded to about 50% of that induced by maximal doses of cerulein (100 ng/kg/h) plus secretin (1 CU/kg/h). As far as bicarbonate is concerned, the lowest dose of secretin (0.03 CU/kg/h) significantly (p less than 0.001) stimulated bicarbonate output. The dose of 0.9 CU/kg/h of secretin evoked a bicarbonate output of 526 +/- 49 micromol/min; trebling the dose of secretin did not significantly increase the output of bicarbonate above this value. Increasing doses of secretin induced a dose related increase in calcium output. There was a close parallel between calcium and protein outputs, suggesting that the increase in calcium output reflected primarily an increase in the enzyme-associated fraction of pancreatic juice calcium. It is concluded that secretin stimulates pancreatic enzyme secretion in man probably by a direct action on the acinar cells.

Serum immunoreactive trypsin response to secretin injection in patients with chronic pancreatitis.

Serum immunoreactive trypsin response to secretin injection (75 clinical units iv over a 2-min period) was studied in patients with chronic pancreatitis and in control subjects. Secretin stimulation caused a slight but significant increase of basal serum immunoreactive trypsin concentration in normal subjects and a marked increase in chronic pancreatitis patients with mild to moderate insufficiency. In patients with severe insufficiency and steatorrhea it had very little effect. The integrated immunoreactive trypsin response to secretin injection in patients with mild to moderate insufficiency was significantly higher compared to controls and to patients with severe insufficiency. In the latter patients it was significantly lower than in controls. A markedly elevated response of serum immunoreactive trypsin to secretin administration seems to differentiate chronic pancreatitis patients with mild to moderate insufficiency from those with severe insufficiency and from controls.

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.

Pancreolauryl test for pancreatic exocrine insufficiency.

Pancreolauryl test (PLT), a tubeless pancreatic function test, was performed in 40 consecutive patients suffering from chronic pancreatitis, in 21 patients with miscellaneous digestive diseases, and in 18 control subjects to assess its diagnostic sensitivity and specificity. N-benzoyl-L-tyrosyl-p-aminobenzoic acid test (PABA test) and secretin-cerulein test were also carried out to compare the diagnostic value of PLT with that of these two pancreatic function tests. PLT was abnormal in 22 of 40 patients with chronic pancreatitis (55%). In particular, pathological results were found in all patients with severe pancreatic insufficiency and only in four of 14 patients with mild to moderate insufficiency. PABA test showed a slightly lower sensitivity in severe insufficiency, and the same sensitivity in mild-moderate insufficiency. PLT was normal in all control subjects and in 17 of 21 patients with nonpancreatic digestive diseases. Its specificity (90%) was slightly higher than that of PABA test (82%). The results indicate that PLT may be used to support a diagnosis of severe pancreatic exocrine insufficiency, while in mild or moderate insufficiency its diagnostic value is limited.

Improvement of pancreatic ultrasound imaging after secretin administration.

The pancreas is usually well recognized by ultrasound, but in some cases it is obscured by the presence of gas in the stomach and duodenum. Water and other orally administered fluids produced poor results. In this study we stimulated pancreatic juice secretion by a standard dose of intravenous secretin in 24 normal subjects, and continuously monitored the pancreatic region for a period of 20 min. Four to five minutes after hormone administration pancreatic juice outflow into the duodenum generated a fluid-filled echofree area around the head of the pancreas, allowing excellent visualization of its boundaries and other channel structures (distal common bile duct, pancreatic duct and gastroduodenal artery). This method should be utilized in selected patients whenever a pathological condition of the pancreatic head region is suspected.

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.