ceruletide and Exocrine-Pancreatic-Insufficiency

There is controversy about the cholecystokinin (CCK)-induced decrease of plasma amino acids for the diagnosis of pancreatic insufficiency in that it is unclear whether the conflicting results are due to different degrees of stimulation by CCK. We have therefore evaluated the amino acid consumption test by examining the dose-response relation among increasing doses of cerulein and plasma amino acids compared with the release of pancreatic polypeptide in six healthy volunteers and six patients with severe pancreatic insufficiency proven by a pathological para-aminobenzoic acid test.. Stepwise increasing doses of cerulein (10-80 pmol/kg/h) were given i.v., each for 60 min with a secretin background (1 CU/kg/h). In the volunteer group, an additional experiment with infusion of placebo (saline 0.9%) was performed.. CCK-induced amino acid changes were small in volunteers (maximum decrease: 8.4 +/- 0.9%; mean +/- SEM), tended to be more pronounced in patients (maximum decrease: 13.8 +/- 2.8%; NS), and did not permit a distinction among volunteers and patients. There was no dose-response relationship between CCK and plasma amino acids in either group. In contrast, pancreatic polypeptide levels increased markedly and dose-dependently in volunteers and patients and tended to be lower in patients with pancreatic insufficiency.. The decrease of plasma amino acid levels in response to cerulein does not reflect pancreatic function and does not permit the diagnosis of pancreatic insufficiency.

Topics: Adult; Aged; Amino Acids; Ceruletide; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreatic Polypeptide

In order to determine whether the doses of cerulein generally used in the secretin-cerulein test are supramaximal, the pancreatic secretion of enzymes and bicarbonate in response to intravenous infusion of cerulein plus secretin was studied in 6 subjects on two separate days at the respective doses of 50 ng/kg/h and 0.5 CU/kg/h on one day, and 100 ng/kg/h and 1 CU/kg/h on the other. In all subjects studied, the infusion of cerulein at the dose of 100 ng/kg/h caused a pancreatic enzyme response significantly higher than that produced by 50 ng/kg/h, demonstrating that the doses of cerulein generally used in clinical practice to explore the exocrine pancreatic function are not supramaximal.

Topics: Adult; Bicarbonates; Ceruletide; Chronic Disease; Chymotrypsin; Clinical Trials as Topic; Exocrine Pancreatic Insufficiency; Humans; Infusions, Intravenous; Lipase; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; Random Allocation

Detecting and monitoring exocrine pancreatic damage during nonclinical and clinical testing is challenging because classical biomarkers amylase and lipase have limited sensitivity and specificity. Novel biomarkers for drug-induced pancreatic injury are needed to improve safety assessment and reduce late-stage attrition rates. In a series of studies, miR-216a and miR-217 were evaluated as potential biomarkers of acute exocrine pancreatic toxicity in rats. Our results revealed that miR-216a and miR-217 were almost exclusively expressed in rat pancreas and that circulating miR-216a and miR-217 were significantly increased in rats following administration of established exocrine pancreatic toxicants caerulein (CL) and 1-cyano-2-hydroxy-3-butene (CHB) as well as in rats administered a proprietary molecule known to primarily affect the exocrine pancreas. Conversely, neither microRNA was increased in rats administered a proprietary molecule known to cause a lesion at the pancreatic endocrine-exocrine interface (EEI) or in rats administered an established renal toxicant. Compared with amylase and lipase, increases in miR-216a and miR-217 were of greater magnitude, persisted longer, and/or correlated better with microscopic findings within the exocrine pancreas. Our findings demonstrate that in rats, miR-216a and miR-217 are sensitive and specific biomarkers of acute exocrine pancreatic toxicity that may add value to the measurement of classical pancreatic biomarkers.

Topics: Acute Disease; Alkenes; Animals; Biomarkers; Ceruletide; Exocrine Pancreatic Insufficiency; Humans; Male; Mice, Inbred C57BL; MicroRNAs; Nitriles; Organ Specificity; Pancreas, Exocrine; Rats, Sprague-Dawley; Rats, Wistar; Sensitivity and Specificity

Consistent, sensitive biomarkers of exocrine pancreatic injury (EPIJ) in animal models and humans have historically represented a poorly met need for investigators and clinicians.. Sprague-Dawley CD/International Genetic Standard system (IGS) rats were administered cerulein or cyanohydroxybutene (CHB) to induce EPIJ. Serum samples were taken at time points between 1- and 168-hr postinjection (PI), and rats were sacrificed between 24- and 168-hr PI.. We investigated a series of serum-based biomarkers including amylase, lipase, pancreas-enriched microRNAs (miRs) and inflammation biomarkers compared with concurrent hematology and pancreatic histology.. Microscopic EPIJ was not associated with consistent changes in hematology or inflammation biomarkers. Increased severity scores for EPIJ correlated with increased amylase and lipase values, although severity of EPIJ did not always correlate with the magnitude of enzyme increases. Microscopic EPIJ was most severe at 24 to 48 hr; increases in miR-216a (32-fold) and miR-375 (23-fold) were present at 24 hr and, along with enzymes, were normalized by 48 hr in the cerulein study. MiRs-216a and 375 were increased by ∼800- and 500-fold, respectively, at 24 hr while miR-375 remained elevated until 72 hr in the CHB study. Impact statement: Pancreas-enriched miRs hold promise as novel serum-based biomarkers for EPIJ.

Topics: Acute Disease; Alkenes; Amylases; Animals; Biomarkers; Ceruletide; Disease Models, Animal; Dose-Response Relationship, Drug; Exocrine Pancreatic Insufficiency; Lipase; Male; MicroRNAs; Nitriles; Pancreas; Rats; Rats, Sprague-Dawley

The clinical relevance of pancreatic exocrine insufficiency (PEI) in diabetic patients is unclear mostly because established function tests are invasive and expensive or lack sensitivity and specificity. A modified version of the noninvasive 13C-mixed triglyceride breath test (13C-MTGT) has recently been shown to detect moderate PEI reliably in patients with chronic pancreatitis. Its sensitivity and specificity in other patient groups are unknown. We therefore aimed to clarify the significance of this test for patients with diabetes mellitus (DM).. A secretin cerulein test and a modified 13C-MTGT were performed in 14 patients with DM (10 patients with type 1 DM) and 10 healthy volunteers.. Secretin cerulein test showed significantly lower outputs of amylase, trypsin, and lipase in DM compared with healthy volunteers (P < 0.05). Likewise, 13C-MTGT showed significantly lower maximal and cumulative 13C-exhalation in DM (P < 0.005). Stimulated lipase output correlated with cumulative 13C-exhalation (P < 0.05). However, when compared with normal values, only 2 patients with diabetes had abnormally low lipase output, whereas cumulative 13C-exhalation was pathologically decreased in 8 patients, including those with decreased lipase output.. The noninvasive 13C-MTGT can detect mild to moderate PEI in DM. However, the specificity of the 13C-MTGT is low in these patients probably because nonpancreatic mechanisms contribute to decreased intestinal lipolysis.

Topics: Adult; Aged; Breath Tests; Carbon Isotopes; Ceruletide; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreas, Exocrine; Pancreatic Function Tests; Quality of Life; Reproducibility of Results; Secretin; Sensitivity and Specificity; Surveys and Questionnaires; Triglycerides; Young Adult

There have been various studies of exocrine pancreatic function after acute pancreatitis, but few have examined the relationship between this function and the etiology of the pancreatitis. The aim of this work was to study pancreatic function in patients who had had acute alcoholic or acute biliary pancreatitis.. Seventy-five patients who had had a single attack of acute pancreatitis were studied. The etiology was alcohol in 36 and cholelithiasis in 39. Pancreatic function was studied between 4 and 18 months after pancreatitis by duodenal intubation in 18 patients (8 alcohol, 10 lithiasis) and by the amino acid consumption test (AACT) in the remaining 57 (28 alcohol, 29 lithiasis). For those who underwent AACT, the test was repeated 1 year after the first examination.. Among the 36 patients with alcoholic pancreatitis, most had impaired pancreatic function at both duodenal intubation (8/8, 100%) and at AACT (22/28, 78.6%); at the second test, the AACT remained pathological (18/23, 82.1%). Of the 39 patients with biliary pancreatitis, only 4 of the 10 (40%) who underwent duodenal intubation and only 5 of the 29 (17.2%) who performed AACT had pancreatic insufficiency; at the second test, only 4 of the 26 (15.4%) who repeated the AACT were pathological. The differences in the frequency and degree of pancreatic insufficiency between patients with alcoholic and those with biliary pancreatitis were statistically significant.. The results show that after alcoholic acute pancreatitis, the pancreatic insufficiency was significantly more frequent and more severe than after biliary pancreatitis. These findings together with the fact that the insufficiency was also more persistent suggest that acute alcoholic pancreatitis may occur in a pancreas that already has chronic lesions.

Topics: Acute Disease; Adolescent; Adult; Aged; Amino Acids; Bicarbonates; Ceruletide; Cholelithiasis; Chymotrypsin; Exocrine Pancreatic Insufficiency; Female; Humans; Lipase; Male; Middle Aged; Pancreas; Pancreatitis; Pancreatitis, Alcoholic

Tubeless pancreatic function tests measuring the content of elastase-1 and the activity of chymotrypsin in stool are used with different cut-off levels and with varying success in diagnosing functional impairment of the pancreas. The aim of our study was to re-evaluate the sensitivity and specificity of elastase-1 and chymotrypsin in stool in the assessment of exocrine pancreatic insufficiency.. In 127 patients displaying clinical signs of malassimilation, the secretin-caerulein test ('gold standard'), fecal fat analysis, fecal chymotrypsin activity and fecal elastase-1 concentration were performed. Exocrine pancreatic insufficiency was graded, according to the results of the secretin-caerulein test, into mild, moderate and severe. Chymotrypsin and elastase-1 in stool were estimated using two commercially available test kits. Fecal elastase-1 concentration of 200 and 100 microg/g stool and chymotrypsin activity of 6 and 3 U/g stool were used separately as cut-off levels for calculation.. 1) In 65 patients, a normal pancreatic function was found using the secretin-caerulein test. In 62 patients, an exocrine pancreatic insufficiency was found and classified into severe (n = 25), moderate (n = 14) and mild (n = 23). 2) The correlation between fecal elastase-1 and chymotrypsin with duodenal enzyme outputs of amylase, lipase, trypsin, chymotrypsin and elastase-1 ranged between 33% and 55% and 25% and 38%, respectively. 3) Using a cut-off of 200 microg elastase-1/g, stool sensitivities of fecal elastase-1 and fecal chymotrypsin (cut-off: 6 U/g) were 100% and 76%, respectively (P < 0.0001 and P < 0.001 respectively) in severe exocrine pancreatic insufficiency, 89% and 47% respectively (P < 0.001; P = 0.34, respectively) in moderate and 65% for both in mild pancreatic insufficiency. Specificities of elastase-1 and chymotrypsin in stool were 55% and 47%, respectively. 4) Elastase-1 based diagnostic provided a positive predictive value of 50% using a cut-off' 200 microg/g stool in a representative group of consecutively recruited patients with gastroenterological disorders.. Determination of fecal elastase-1 is highly sensitive in the diagnosis of severe and moderate exocrine pancreatic insufficiency and is of significantly higher sensitivity than fecal chymotrypsin estimation. Specificity for both stool tests is low. Correlation between elastase-1 and chymotrypsin in stool and duodenal enzyme outputs is moderate. Neither test is suitable for screening, as they provide a pathologic result in roughly half of 'non-pancreas' patients.

Topics: Biomarkers; Ceruletide; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Humans; Logistic Models; Pancreatic Elastase; Pancreatic Function Tests; Secretin; Sensitivity and Specificity

Breath tests using stable isotopes of carbon or hydrogen are increasingly becoming established for the evaluation of various gastrointestinal functions, including measurement of exocrine pancreatic insufficiency. We wanted to evaluate the clinical relevance of the non-invasive, non-radioactive 13C-mixed triglyceride breath test in comparison with the secretin-caerulein test as the 'gold standard' of pancreatic function testing and with faecal chymotrypsin and elastase 1 in patients with mild and severe exocrine pancreatic insufficiency.. The secretin-caerulein test, faecal fat analysis, 13C-mixed triglyceride breath test, faecal elastase 1, and chymotrypsin and various morphologic investigations were done in 26 patients with mild (n = 13) or severe (n = 13) exocrine pancreatic insufficiency and 25 patients with gastrointestinal diseases of non-pancreatic origin. Twenty-seven healthy volunteers served as normal controls. After a 12-h fast 200 mg mixed triglyceride (1,3-distearyl,2(carboxyl-13C)octanoyl glycerol) were orally administered with a test meal, and breath samples were taken before and at 30-min intervals for 5 h thereafter, and the increase in 13C/12C isotopic ratio in breath was analysed by mass spectrometry. Various modifications of the test procedure were investigated.. Specificity for impaired pancreatic function was higher for faecal elastase (90%) and equal for faecal chymotrypsin (82%) as compared with the various variables of the 13C-mixed triglyceride breath test (69-85%). The sensitivity of the 13C-mixed triglyceride breath test for total and separately for mild and severe exocrine pancreatic insufficiency was higher (total, 69-81%) than that of faecal chymotrypsin (total, 56%) but lower than faecal elastase (total, 92%).. The 13C-mixed triglyceride breath test very sensitively reflects severe exocrine pancreatic insufficiency (steatorrhoea) but has limited sensitivity for the detection of mild cases. With regard to the higher sensitivity and specificity, the higher practicability, and the much lower cost, determination of faecal elastase 1 concentrations is superior to the 13C-mixed triglyceride breath test and therefore remains the most reliable indirect pancreatic function test available today.

Topics: Adult; Breath Tests; Carbon Isotopes; Ceruletide; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Male; Middle Aged; Pancreatic Elastase; Secretin; Sensitivity and Specificity; Triglycerides

In previous studies we reported evidence of subclinical exocrine pancreatic insufficiency in primary or secondary Sjögren's syndrome (SSI, SSII) and rheumatoid arthritis (RA). In present study we evaluated the occurrence of pancreatic duct antibodies (PDA), and their relationship to exocrine pancreatic function in 36 women. Of these patients, 12 were classified as SSI, 12 as SSII, and 12 as RA. Exocrine pancreatic function was evaluated using the Secretin-Caerulein test (S.Cae test). The indirect immunofluorescent technique was used to evaluate patient sera for PDA. S.Cae test results, compared to controls, showed a statistically significant decrease in duodenal juice volumes, bicarbonates and enzymes in 58.3% of SSI, in 58.3% of SSI and in 30% of RA, according to our previous trials. PDA were found in two patients, the former with SSI and the latter with SSII, both asymptomatic with regard to pancreatic diseases but with impaired exocrine pancreatic function as evaluated by S.Cae test. We discuss the possible causes of these results.

Topics: Adult; Aged; Autoantibodies; Ceruletide; Exocrine Pancreatic Insufficiency; Female; Fluorescent Antibody Technique, Indirect; Humans; Middle Aged; Pancreatic Ducts; Pancreatic Function Tests; Secretin; Sjogren's Syndrome

Exocrine pancreatic function was studied in a homogeneous group of 33 female patients aged 42-67 years. Of these patients, 11 were classified as rheumatoid arthritis (RA), 11 as Sjögren's syndrome I (SSI) and 11 as Sjögren's syndrome associated with RA (SSII). Clinical features, laboratory tests and special instrumental techniques excluded gastroenteric-hepatobiliary causes of pancreatic diseases. These patients were subjected to direct pancreatic stimulation with secretin and caerulein (S. Cae test). Test results, compared to control-group (10 voluntary healthy females) showed, in the last 30 m of stimulation, a statistically significant decrease (p < 0.05) in duodenal juice volume, bicarbonates and trypsin in 6 cases (54.5%) of SSI and in 3 cases (27.2%) of RA. SSII S. Cae test showed a decrease of volume and bicarbonates in 6 patients (54.5%) and in only 4 of these (36.4%) it was associated with a concomitant decrease in trypsin levels. Authors discuss the subclinical exocrine pancreatic function in relationship to sicca-syndrome, possible immunological factors and primary disease of pancreatic ducts.

Topics: Adult; Aged; Arthritis, Rheumatoid; Bicarbonates; Ceruletide; Exocrine Pancreatic Insufficiency; Female; Humans; Middle Aged; Pancreas; Pancreatic Function Tests; Secretin; Sjogren's Syndrome; Trypsin

The clinical relevance of the 13C-starch breath test was evaluated in comparison to the secretin-caerulein test as the "gold standard" of pancreatic function testing, fecal elastase concentration, and fecal chymotrypsin activity in 30 patients with mild (n = 15) or severe (n = 15) exocrine pancreatic insufficiency. 23 patients with gastrointestinal diseases of non-pancreatic origin and 31 healthy volunteers served as controls. 50 g of natural starch of maize were orally administered after a 12-h fast and breath samples were taken before and in 30 min intervals for five hours after oral ingestion and the increase of 13C/12C-isotopic ratio was analyzed by mass spectrometry. Specificity of fecal elastase (93%) and fecal chymotrypsin (93%) for impaired pancreatic function were much higher compared to the various parameters of the 13C-starch breath test (69-74%). Sensitivities of the 13C-starch breath test for all and separately for mild and severe exocrine pancreatic insufficiency were higher (total 70-77%) compared to fecal chymotrypsin (total 60%), but lower compared to fecal elastase (total 93%). With regard to the higher sensitivity and specificity, the higher practicability, and the lower costs determination of fecal elastase concentrations is superior to the 13C-starch breath test and therefore remains to be the most reliable indirect pancreatic function test available today.

Topics: Adult; Breath Tests; Carbon Radioisotopes; Ceruletide; Chronic Disease; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Mass Spectrometry; Middle Aged; Pancreatic Function Tests; Pancreatitis; Reference Values; Secretin; Sensitivity and Specificity; Starch

Subsequent to total gastrectomy, many patients develop maldigestion and weight loss. The mechanisms that underlie these changes are not known. Therefore, in a prospective study, we have analyzed endocrine and exocrine pancreatic function in patients before and 3 months after total gastrectomy.. In 15 patients (12 male, three female, median age 62.4 yr) undergoing total gastrectomy due to gastric cancer, a direct exocrine pancreatic function test (secretin-cerulein test) was performed. In addition, a standard test meal was given to all patients to study endocrine pancreatic function and the pattern of hormones that influence exocrine pancreatic secretion. In nine patients, both function tests were repeated 3 months after total gastrectomy. Before and at 11 points after the application of the test meal, blood samples were taken for the measurement of glucose, insulin, glucagon, gastrin, pancreatic polypeptide, and cholecystokinin. In addition, a secretin-cerulein test was performed to analyze trypsin, chymotrypsin, amylase, bicarbonate, and the juice volume in the duodenal aspirates.. Three months after total gastrectomy, all patients exhibited severe primary exocrine pancreatic insufficiency. Secretin-cerulein tests revealed that pancreatic juice secretion, trypsin, chymotrypsin, and amylase were significantly reduced by 76%, 89%, 91%, and 72%, respectively, 3 months after total gastrectomy and secretin and cerulein stimulation. Post-operatively, the patients had a pathological glucose tolerance with increased postprandial insulin and glucagon secretion. The baseline and postprandial gastrin and pancreatic polypeptide secretion were significantly decreased after total gastrectomy. In contrast, early postprandial cholecystokinin secretion was significantly increased postoperatively.. After total gastrectomy, patients develop severe primary exocrine pancreatic insufficiency with decreased gastrin, decreased late postprandial pancreatic polypeptide, and increased cholecystokinin levels. These findings may explain why many patients with total gastrectomy have maldigestion and weight loss postoperatively. Therefore, gastrectomized patients should be given pancreatic enzymes to avoid these symptoms.

Topics: Ceruletide; Cholecystokinin; Exocrine Pancreatic Insufficiency; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Malabsorption Syndromes; Male; Middle Aged; Pancreatic Function Tests; Pancreatic Polypeptide; Postgastrectomy Syndromes; Prospective Studies; Secretin; Time Factors; Weight Loss

To determine the relationship between pancreatic secretory capacity and nutritional status in celiac patients, we studied 52 patients with celiac disease (24 males, 28 females; age range 6-36 months) and 30 healthy control subjects (14 males, 16 females; age range 6-42 months). A secretin-cerulein test was performed on all patients, and levels of serum albumin and plasma fibronectin were assayed. In addition, weight/height ratios were calculated in the celiacs, who were then divided into three groups on this basis, as follows: celiacs with weight/height ratio < or = 3rd percentile; those with weight/height ratio between the 4th and 10th percentiles; and those with weight/height ratio > 10th percentile. There was no significant difference in the duodenal output of chymotrypsin, phospholipase and lipase between these groups. When the total celiac group was compared to control subjects, only lipase levels were significantly lower (P < 0.009). However, subnormal values in one or more pancreatic enzymes were observed in 15/52 celiacs (29%). A residual enzyme activity < 10% of normal secretory capacity, was also found in 4/52 patients. There was no correlation between the output of the various pancreatic enzymes and levels of albumin, fibronectin, and weight/height ratios in the patients. Furthermore, there was no difference in weight/height ratios and levels of albumin and fibronectin between the celiac subjects with pancreatic deficiency and those with normal pancreatic function. We conclude that a mild/moderate pancreatic insufficiency is quite frequent in celiacs, but that it may be completely independent of nutritional status; further studies are therefore required to shed light on its pathogenesis.

Topics: Biopsy; Celiac Disease; Ceruletide; Chi-Square Distribution; Child, Preschool; Exocrine Pancreatic Insufficiency; Female; Humans; Infant; Intestine, Small; Male; Nutritional Status; Pancreatic Function Tests; Prospective Studies; Secretin; Statistics, Nonparametric

This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal.

Topics: Adolescent; Celiac Disease; Ceruletide; Child; Child, Preschool; Chymotrypsin; Duodenum; Exocrine Pancreatic Insufficiency; Feces; Female; Glutens; Humans; Infant; Intestinal Mucosa; Male; Pancreas; Secretin

After stimulation with a Lundh test meal, plasma concentrations of cholecystokinin (CCK) and pancreatic polypeptide (PP) and output of pancreatic enzymes were measured in 33 patients with exocrine pancreatic insufficiency and 26 healthy subjects. Patients with impairment of pancreatic function were subdivided into those with moderate and severe insufficiency. Plasma CCK and PP were measured by radioimmunoassay. Fasting plasma CCK in patients with pancreatic insufficiency (5.8 +/- 1.1 pmol/liter) did not differ significantly from controls (4.2 +/- 0.6 pmol/liter). After endogenous stimulation with a Lundh meal, plasma CCK increased in both groups without significant differences over 2 hr. Basal and stimulated plasma levels of pancreatic polypeptide (PP) were markedly decreased only in patients with severe pancreatic insufficiency. Our results demonstrate that basal and meal-stimulated CCK levels in patients with pancreatic insufficiency do not differ from controls. Furthermore the extent of functional impairment of the exocrine pancreas did not influence basal and postprandial CCK release.

Topics: Adult; Ceruletide; Cholecystokinin; Exocrine Pancreatic Insufficiency; Female; Food; Humans; Male; Pancreas; Pancreatic Function Tests; Pancreatic Polypeptide; Radioimmunoassay; Secretin

We determined by the ninhydrin method the plasma amino acid (AA) levels prior to, during and following, a 1-hour i.v. infusion of 1 U/kg body weight each of secretin and pancreozymin in patients with normal (n = 74) or reduced (n = 39) exocrine pancreatic function, as assessed by the duodenal aspiration test. The results of the two tests correlated significantly with each other (p less than 0.001). A maximum AA decrease of greater than or equal to 12% was observed in all patients with a normally functioning pancreas (specificity 100%), and of less than 12% in all patients with medium to high-grade impairment of pancreatic function (sensitivity 100%). Since, however, low-grade pancreas insufficiency (20-40% of the mean normal enzyme output) is recognized in fewer than one-half of the cases, the overall sensitivity of the AA-consumption test decreases to 69%. The results can, however, be improved by: 1) Calculating the mean percentage AA decrease with a limit value of 5% (sensitivity 90%); 2) determining individual AA with pancreas-specific absorption, such as serine (sensitivity 92%); 3) dropping the lower normal value of exocrine pancreatic function to 25% of the normal mean enzyme output (sensitivity 96%). Diseases that may be associated with the most common condition that causes pancreatic insufficiency--chronic pancreatitis--and which have an influence on AA metabolism, such as cirrhosis of the liver and diabetes mellitus, have no influence on the accuracy of the AA consumption test, which, considered overall, represents a competitive alternative to other tubeless tests of pancreatic function.

Topics: Adult; Aged; Amino Acids; Ceruletide; Cholecystokinin; Chronic Disease; Exocrine Pancreatic Insufficiency; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Nitrogen; Pancreatic Function Tests; Pancreatitis; Secretin

Chronic pancreatic insufficiency (CPI) was induced in male Wistar rats by the injection of a zein-oleic acid-linoleic acid solution into their pancreaticobiliary ducts. Animals injected developed severe pancreatic atrophy with fibrosis and greater than 90% loss of pancreatic enzyme content. The animals also developed malabsorption of fat and bentiromide. Three weeks after the CPI lesion was induced, animals were randomized to receive cerulein 2 micrograms/kg twice daily subcutaneously or saline twice daily subcutaneously for 2 weeks. Cerulein significantly increased pancreatic trypsinogen (p less than 0.03), amylase (p less than 0.01), lipase (p less than 0.02), DNA (p less than 0.02), and RNA (p less than 0.01) content and improved fat and bentiromide malabsorption as compared to saline (p less than 0.05). We conclude that cerulein therapy can cause significant hyperplasia of pancreatic acinar parenchyma in an animal model of CPI and that this therapy can partially reverse malabsorption.

Topics: Animals; Ceruletide; Chronic Disease; Disease Models, Animal; Drug Combinations; Exocrine Pancreatic Insufficiency; Hyperplasia; Linoleic Acid; Linoleic Acids; Male; Oleic Acid; Oleic Acids; Pancreas; Rats; Rats, Inbred Strains; Zein

Forty-six subjects (20 chronic pancreatitis, 7 chronic liver disease, 7 recovered from acute pancreatitis, 2 Crohn's disease, and 10 healthy controls) classified by S-C test as having normal pancreatic function (26 subjects), or moderate (10 subjects) and severe (10 cases) pancreatic insufficiency, were given, on different days, 1 g of oral PABA or 348 mg of oral fluorescein dilaurate. At the 1st, 2nd, and 4th hours (PABA) and the 2nd, 4th, and 6th hours (fluorescein) serum samples were taken for assay. In the presence of severe exocrine pancreatic insufficiency, the sensitivity of the fluorescein serum levels was higher than that observed for the PABA (100% and 80%, respectively), and quite similar to that shown by the urinary tests (100% and 70%, respectively). On the contrary, in presence of moderate pancreatic insufficiency, both the urinary test (pancreolauryl and (PABA) give a sensitivity higher than that found in the serum tests (30-40% and 10-30%, respectively). The parallel combination of both the serum or urinary tests does not significantly improve the sensitivity of the single test. These results suggest that the serum PABA and serum fluorescein tests can be valid choice when a prolonged urinary collection is difficult, i.e., in children and in elderly patients. However, the slight diagnostic gain does not justify the routine use of both urinary and serum tests.

Topics: 4-Aminobenzoic Acid; Adult; Aminobenzoates; Ceruletide; Chymotrypsin; Exocrine Pancreatic Insufficiency; Female; Fluorescein; Fluoresceins; Humans; Lipase; Male; Middle Aged; para-Aminobenzoates; Secretin

Topics: Bicarbonates; Ceruletide; Child; Child, Preschool; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Humans; Infant; Male; Pancreas; Pancreatic Function Tests; Secretin

A quantitative correlation between computer-tomographic (CT) findings and exocrine pancreatic function following secretin-ceruletide stimulation was performed in 48 patients with chronic pancreatitis; thereby a significant correlation between the degree of morphological changes in CT and the stage of functional impairment was found (r = 0,7841, p less than 0,001). Bicarbonate secretion/h showed the strongest correlation to CT findings (r = -0,7193, p less than 0,001) within the single functional parameters. CT showed a limited sensitivity (50%) in detecting chronic pancreatitis in cases with a slight functional impairment (stage 1). Morphological signs as calcifications, pancreatic duct ectasia were constantly coupled with a severe degree of functional impairment, whereas enlargement and cysts were found throughout the different functional stages.

Topics: Adult; Aged; Amylases; Bicarbonates; Ceruletide; Chronic Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreas; Pancreatitis; Secretin; Tomography, X-Ray Computed; Trypsin

The reliability of the para-aminobenzoic acid (PABA) test (performed in the conventional manner, i.e. without control day) and of the pancreolauryl test was assayed in respect of the exocrine pancreatic capacity measured by using the secretin-caerulein test in 57 subjects, 22 of which were suffering from chronic pancreatitis. When 50 and 20% urinary excretion of the orally administered Bz-Ty-PABA and pancreolauryl, respectively, were chosen as the lower normal limits, the PABA test showed a specificity quite similar to that of the pancreolauryl test (97 and 95%, respectively) despite the lack of a control day test, but a lower sensitivity (39 vs. 83%). The association of both tests was not advantageous compared with the pancreolauryl test alone.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Ceruletide; Chronic Disease; Exocrine Pancreatic Insufficiency; Humans; Pancreas; Pancreatic Extracts; Pancreatic Function Tests; Pancreatitis; para-Aminobenzoates; Secretin