cholecystokinin and Exocrine-Pancreatic-Insufficiency

Topics: Animals; Cholecystokinin; Chronic Disease; Chymotrypsin; Enzyme Therapy; Exocrine Pancreatic Insufficiency; Feedback; Female; Humans; Male; Pain; Pancreas; Pancreatitis; Rats; Trypsin

The Food and Drug Administration in 2006 required that all pancreatic enzyme products demonstrate bioavailability of lipase, amylase, and protease in the proximal small intestine.. In this phase I open-label, randomized, crossover trial, 17 adult chronic pancreatitis (CP) patients with severe exocrine pancreatic insufficiency (EPI) underwent two separate gastroduodenal perfusion procedures (Dreiling tube suctioning and [. Zenpep administration with a test meal was associated with significant increase in duodenal aspiration of lipase (p = 0.046), chymotrypsin (p = 0.008), and amylase (p = 0.001), compared to the test meal alone, indicating release of enzymes to the duodenum. Lipase delivery was higher in the pH subpopulation (the efficacy population with acid hypersecretors excluded) (p = 0.01). Recovery of [. In CP patients with severe EPI, lipase, chymotrypsin and amylase were released rapidly into the duodenum after ingestion of Zenpep plus meal compared to meals alone. Results also reflected the known pH threshold for enzyme release from enteric coated products.

Topics: Adult; Aged; Amylases; Biological Availability; Cholecystokinin; Chymotrypsin; Cross-Over Studies; Drug Delivery Systems; Duodenum; Exocrine Pancreatic Insufficiency; Female; Humans; Intestine, Small; Lipase; Male; Middle Aged; Pancreatic Extracts; Pancreatitis, Chronic; Trypsin; Young Adult

Direct measurement of pancreatic enzymes after administration of pancreatic secretagogues is the gold standard in the assessment of exocrine pancreatic function. Recent experience at the authors' institution showed that endoscopic collection of pancreatic secretions 5, 10, and 15 minutes after intravenous administration of secretin is useful in screening for pancreatic insufficiency. Concomitant administration of intravenous cholecystokinin has been a subject of debate. The purpose of this study was to compare pancreatic enzyme levels after administration of secretin versus secretin plus cholecystokinin and to validate the timing of collection of duodenal fluid.. A prospective, randomized, double-blind study was conducted from September 1997 through September 1998. Patients scheduled for pancreatic enzyme sampling were randomly assigned to receive intravenous secretin (2 U/kg) plus placebo (group 1) or intravenous secretin (2 U/kg) plus cholecystokinin (0.02 microg/kg [Group 2]). Duodenal fluid was collected 5, 10, and 15 minutes later and placed in dry ice. Samples were measured for the levels of trypsin, amylase, lipase, and chymotrypsin.. Twenty patients were assigned to each group. The age range was similar in both groups: 12 months to 16 years, 8 months in group 1 (median, 2.1 years) and 15 months to 13 years, 7 months in group 2 (median, 2.5 years). Group 2 had a greater number of patients with all four enzymes at normal levels during at least one of the time points, 75% versus 50% (P = 0.102). The difference in enzyme levels at the 5-, 10-, and 15-minute collections was statistically significant. For all four enzymes in both groups, values varied from highest to lowest with time (P = 0.0001). The enzyme levels at 10 minutes were close to the enzyme levels at 5 minutes; the lowest values occurred at 15 minutes.. Higher pancreatic enzyme levels were obtained after administration of secretin plus cholecystokinin, although the trend did not reach statistical significance. Pancreatic enzyme levels are highest at 5 and 10 minutes, indicating that collections of duodenal fluid should be completed within 10 minutes of the administration of the secretagogues.

Topics: Adolescent; Child; Child, Preschool; Cholecystokinin; Double-Blind Method; Duodenum; Endoscopy, Digestive System; Exocrine Pancreatic Insufficiency; Female; Humans; Infant; Male; Pancreas; Pancreatic Function Tests; Prospective Studies; Secretin; Sensitivity and Specificity; Time Factors

The secretin-cholecystokinin (CCK) test is the gold standard in the evaluation of exocrine pancreatic insufficiency. Because of its invasive character, it is of limited value in cystic fibrosis (CF) patients, especially in those with severe respiratory disease. The aim of the study was to evaluate the sensitivity of fecal elastase-1 in relation to the secretin-CCK test and quantitative fecal fat excretion in CF patients.. The study comprised 28 patients (11 females and 17 males) aged 4 to 20 years. In all patients the secretin-CCK test and determination of fecal elastase-1 concentration (with enzyme-linked immunosorbent assay) and fecal fat excretion were performed.. The range of fecal elastase-1 was from undetectable to 485 microg/g (mean, 84.6+/-119.9 microg/g) and of fecal fat excretion from 1.0 to 55.1 g/day (mean, 15.0+/-12.2 g/day). On the basis of the results of the secretin-CCK test (and fecal fat analysis) exocrine pancreatic insufficiency was divided into three subgroups: mild (I), moderate (II), and severe (III). Four patients were classified in subgroup I, 4 in II and 20 in III. Fecal elastase (elastase-1) results were 332.0+/-124.9 microg/g in subgroup I, 96.9+/-45.7 microg/g in subgroup II, and 32.1+/-41.2 microg/g in subgroup III. The fecal elastase-1 sensitivity with a cut-off point of 200 microg/g was 89.3% for all patients, 100% for patients in subgroups II and III, but only 25.0% for patients in subgroup I; the specificity was 96.4%. Linear regression analysis showed a statistically significant correlation between fecal elastase (elastase-1) and duodenal volume, bicarbonate, amylase, lipase, and trypsin secretion (in all cases P < 0.001).. Measurement of fecal elastase-1 is simple and very useful for assessing the exocrine pancreatic function in CF patients. Elastase is highly specific in severe and moderate exocrine pancreatic insufficiency, but it is rather unspecific for milder forms of pancreatic insufficiency.

Topics: Adolescent; Adult; Child; Child, Preschool; Cholecystokinin; Clinical Enzyme Tests; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Male; Pancreatic Elastase; Secretin; Sensitivity and Specificity

PABA-serum and urine-concentration were studied in patients with normal, pathologic and pharmacologically inhibited pancreatic function. Secretin-pancreozymine test was selected as reference method. In patients with normal pancreas function and volunteers, PABA-serum-concentration was characterized by a rapid increase during the first 1 1/2 hours. A maximum increase of 32.42 +/- 10.04 mumol/l was reached after 90 minutes. In patients with exocrine pancrease insufficiency, difference to the control group was greatest after 30, 60, 90, and 120 min. Pharmacologic inhibition of the exocrine pancreas using pirenzepine also resulted in a significantly reduced PABA-serum-concentration after 30, 60 and 90 min. In correspondence to the delayed and smaller serum PABA increase, urine-PABA-concentrations were also diminished. Our results indicate that the optimal interval to differentiate between normal and impaired pancreas function with use of serum PABA determination is at 90 min after test begin.

Topics: 4-Aminobenzoic Acid; Adult; Cholecystokinin; Dose-Response Relationship, Drug; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreatic Function Tests; Pirenzepine; Randomized Controlled Trials as Topic; Ranitidine; Secretin

Long-term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism.. Forty-eight healthy male Wistar rats were divided randomly into 4 groups: 6-month control, 6-month ethanol, 9-month control, and 9-month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK-A receptors was quantitatively analyzed by Western blot.. Alcohol-induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence. The outputs of amylase and lipase, FFA content in intestinal chyme, and the intestinal and the pancreatic CCK levels in rats were reduced after chronic alcohol intake and were still lower than the control after cessation of alcohol use. Chronic ethanol intake or abstinence did not induce any change in the expression of CCK-A receptors.. Exocrine pancreatic insufficiency was irreversible in alcoholic rats without CP after alcohol withdrawal. It may be attributed to reduced pancreatic CCK, long-standing fatty infiltration, ultramicrostructure injuries in pancreatic acinar cells, and aging.

Topics: Alcoholism; Amylases; Animals; Blotting, Western; Central Nervous System Depressants; Cholecystokinin; Energy Intake; Ethanol; Exocrine Pancreatic Insufficiency; Fatty Acids, Nonesterified; Immunohistochemistry; Intestinal Mucosa; Lipase; Male; Pancreas; Pancreatitis; Pancreatitis, Chronic; Rats; Rats, Wistar; Receptor, Cholecystokinin A; Substance Withdrawal Syndrome; Triglycerides; Weight Gain

Exocrine pancreatic insufficiency is considered an inherited disease in several dog breeds. Affected dogs show polyphagia, weight loss and voluminous faeces of light colour due to the lack of pancreatic enzymes. In the study described herein, we performed a segregation analysis using the singles method for three families of the Eurasian dog breed. Our data were consistent with an autosomal recessive mode of inheritance. In addition, we performed a linkage analysis in these families using four microsatellite markers on CFA3 and two microsatellites on CFA23. Based on our results, we excluded the canine orthologs of the human cholecystokinin (CCK) and the cholecystokinin A receptor (CCKAR) genes as candidates for exocrine pancreatic insufficiency.

Topics: Animals; Cholecystokinin; Chromosome Mapping; Dog Diseases; Dogs; Exocrine Pancreatic Insufficiency; Genes, Recessive; Inheritance Patterns; Microsatellite Repeats; Pedigree; Receptor, Cholecystokinin A

This study investigated the effects of cholecystokinin-octapeptide (CCK-8) on pancreatic juice flow and its contents, and on cytosolic calcium (Ca2+) and magnesium (Mg2+) levels in streptozotocin (STZ)-induced diabetic rats compared to healthy age-matched controls. Animals were rendered diabetic by a single injection of STZ (60 mg kg(-1), I.P.). Age-matched control rats obtained an equivalent volume of citrate buffer. Seven weeks later, animals were either anaesthetised (1 g kg(-1) urethane; IP) for the measurement of pancreatic juice flow or humanely killed and the pancreas isolated for the measurements of cytosolic Ca2+ and Mg2+ levels. Non-fasting blood glucose levels in control and diabetic rats were 92.40 +/- 2.42 mg dl(-1) (n = 44) and >500 mg dl(-1) (n = 27), respectively. Resting (basal) pancreatic juice flow in control and diabetic anaesthetised rats was 0.56 +/- 0.05 ul min(-1) (n = 10) and 1.28 +/- 0.16 ul min(-1) (n = 8). CCK-8 infusion resulted in a significant (p < 0.05) increase in pancreatic juice flow in control animals compared to a much larger increase in diabetic rats. In contrast, CCK-8 evoked significant (p < 0.05) increases in protein output and amylase secretion in control rats compared to much reduced responses in diabetic animals. Basal [Ca2+]i in control and diabetic fura-2-loaded acinar cells was 109.40 +/- 15.41 nM (n = 15) and 130.62 +/- 17.66 nM (n = 8), respectively. CCK-8 (10(-8)M) induced a peak response of 436.55 +/- 36.54 nM (n = 15) and 409.31 +/- 34.64 nM (n = 8) in control and diabetic cells, respectively. Basal [Mg2+]i in control and diabetic magfura-2-loaded acinar cells was 0.96 +/- 0.06 nM (n = 18) and 0.86 +/- 0.04 nM (n = 10). In the presence of CCK-8 (10(-8)) [Mg2+]i in control and diabetic cells was 0.80 +/- 0.05 nM (n = 18) and 0.60 +/- 0.02 nM (n = 10), respectively. The results indicate that diabetes-induced pancreatic insufficiency may be associated with derangements in cellular Ca2+ and Mg2+ homeostasis.

Topics: Amylases; Animals; Calcium; Cholecystokinin; Diabetes Mellitus, Experimental; Exocrine Pancreatic Insufficiency; Islets of Langerhans; Magnesium; Male; Pancreas; Pancreatic Juice; Peptide Fragments; Proteins; Rats

To determine the exocrine pancreatic function in critically ill patients.. Prospective cohort study.. Medical intensive care unit.. A total of 18 critically ill patients (11 patients with septic shock according to the criteria of the American College of Chest Physicians/Society of Critical Care Medicine, 7 nonseptic patients). The results obtained in these subjects were compared with the data obtained in seven healthy volunteers.. Examination of exocrine pancreatic function was done by means of a cholecystokinin-secretin test. Intravenous stimulation of the exocrine pancreas with cholecystokinin and secretin (1 unit/kg body weight/hr each) and aspiration of duodenal fluid by a gastroscopically inserted oroduodenal tube was done during a period of 1 hr.. The content of amylase, chymotrypsin, and trypsin in aspirated duodenal fluid was significantly reduced in patients with septic shock compared with nonseptic patients as well as healthy subjects (p < .01). The volume of aspirated fluid was significantly reduced in patients with septic shock compared with healthy controls (p = .03), but not in nonseptic patients. The content of bicarbonate was not statistically different in the three groups. No significant correlation was to find between variables of exocrine pancreatic function and Acute Physiology and Chronic Health Evaluation III score, sepsis-related organ failure assessment score, systolic arterial pressure and mean arterial pressure in septic shock patients. Positive end-expiratory pressure was significantly correlated with the content of trypsin (r2 = 0.52; p = .02). Postmortem examinations of five septic patients who died during the intensive care stay did not reveal gross morphologic alterations of pancreatic tissue.. The study shows two pancreatic enzyme systems, namely, amylase as a carbohydrate splitting enzyme and the proteolytic enzymes trypsin and chymotrypsin, strongly affected in critically ill patients with septic shock.

Topics: Aged; Amylases; Cholecystokinin; Chymotrypsin; Cohort Studies; Critical Care; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Prospective Studies; Secretin; Shock, Septic; Trypsin

Patients with chronic pancreatitis and exocrine insufficiency have lower intraduodenal pH compared to controls. It has been assumed that abnormal low intraduodenal pH in these patients not only results from impaired pancreatic bicarbonate secretion but also from an increased gastric acid load to the duodenum.. We have tested this hypothesis by combined intragastric and intraduodenal 24 h pH monitoring in nine chronic pancreatitis patients with exocrine pancreatic insufficiency and nine healthy control subjects during standardized test conditions. Postprandial gastrin and cholecystokinin release were also determined.. Median 24-h intraduodenal pH (5.90 vs. 6.00) and intragastric pH (1.60 vs. 1.70) were not significantly different between patients and controls. However, in the 2-h postprandial periods intraduodenal pH was below five for a significantly higher percentage of time in chronic pancreatitis patients compared to controls (lunch: 14.5% vs. 0.17%, P=0.011; dinner: 24.1% vs. 5.75%, P=0.05). The post-dinner intragastric pH was below three for a significantly higher percentage of time in chronic pancreatitis patients vs. controls (72.2 vs. 48.9%, P=0.04). Postprandial gastrin release was not significantly different between the two groups. Postprandial secretion of cholecystokinin (CCK), as enterogastrone, was significantly (P < 0.01) reduced in chronic pancreatitis patients (78 +/- 13 pmol/L, 120 min) compared to controls (155 +/- 14 pmol/L, 120 min).. Median intraduodenal and intragastric pH are not significantly decreased in patients with chronic pancreatitis and exocrine insufficiency but the postprandial time with an acidic pH in the duodenum (pH < 5) and in the stomach (pH < 3) is significantly (P

Topics: Adult; Case-Control Studies; Cholecystokinin; Chronic Disease; Duodenum; Exocrine Pancreatic Insufficiency; Female; Gastric Mucosa; Gastrins; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Pancreatitis; Postprandial Period; Time Factors

Gastrin is an important stimulator of gastric lipase secretion in man. In advanced pancreatic insufficiency gastric lipases might compensate for the lack of pancreatic lipases, but the role of gastrin in such compensation remains to be evaluated. The aim of this study was to examine the effect of gastrin on the gastric lipase secretion in patients with pancreatic insufficiency.. Eight patients with pancreatic insufficiency secondary to alcohol abuse were studied, and six healthy subjects volunteered as controls for the study. All volunteers received identical doses of intravenous gastrin-17 (10, 30, and 60 pmol/kg/h). The gastric content was measured, using a nasogastric tube for aspiration, and the amount and activity of gastric lipase output were determined. Plasma concentrations of gastrin, secretin, and cholecystokinin were measured by radioimmunoassays.. The increased plasma levels of gastrin were accompanied by a dose-dependent increase in the amount and activity of gastric lipase in controls, but in the patients the response was almost abolished.. Gastrin in postprandial concentrations does not influence the secretion of gastric lipase in patients with pancreatic insufficiency due to chronic pancreatitis.

Topics: Adult; Case-Control Studies; Cholecystokinin; Exocrine Pancreatic Insufficiency; Female; Gastric Mucosa; Gastrins; Hormones; Humans; Lipase; Male; Middle Aged; Pancreatitis, Alcoholic; Secretin

Regulation of pancreatic exocrine secretion is controlled by vagovagal reflexes and hormones. A negative feedback control mechanism exists between the intraduodenal protease concentration and pancreatic enzyme secretion. In man cholecystokinin (CCK) is the major regulator of postprandial pancreatic enzyme secretion. There is a 50% reduction of meal-stimulated secretion by the specific CCK receptor antagonist loxiglumide, whereas atropine completely blocks postprandial secretion. Neurotensin is released postprandially by nerval reflexes and fat. It has been claimed that both hormones are increased in patients with pancreatic insufficiency.. We investigated CCK and neurotensin levels in patients with cystic fibrosis and pancreatic insufficiency. In 35 patients (2-24 years old) with cystic fibrosis with steatorrhea and in 15 patients (1.5-24 years old) with cystic fibrosis without pancreatic insufficiency pre- and post-prandial CCK and neurotensin plasma levels were measured 3 days after pancreatic enzyme therapy had been withdrawn. Nine patients (3-14 years old) who had no complaint of abdominal disease served as controls.. Basal and postprandial CCK plasma levels did not differ statistically in the three groups, whereas basal and postprandial neurotensin levels were significantly increased in the cystic fibrosis groups. The severity of the disease had no effect on the neurotensin levels.. Cystic fibrosis patients with severe pancreatic insufficiency did not have increased CCK plasma levels, suggesting that a CCK-mediated feedback mechanism of pancreatic enzyme secretion does not operate in our patients. In contrast, basal and postprandial neurotensin plasma levels were significantly increased in patients with cystic fibrosis but were independent of the severity of the pancreatic insufficiency.

Topics: Adolescent; Case-Control Studies; Child; Cholecystokinin; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Feedback; Female; Humans; Male; Neurotensin; Pancreas; Radioimmunoassay

Duodenum-preserving resection of the head of the pancreas (DPRHP) is performed in patients with chronic pancreatitis (CP) localized in the head of the pancreas. It has been suggested that functional integrity of the upper digestive tract is preserved after DPRHP. We tested this hypothesis with regard to gallbladder motility.. Gallbladder motility and cholecystokinin (CCK) secretion were studied fasting, after cephalic vagal stimulation with sham feeding, and after regular feeding in 9 patients after DPRHP, in 6 unoperated patients with CP, and 9 healthy control subjects.. Mean fasting gallbladder volume in patients after DPRHP (49 +/- 10 cm3) and patients with CP (53 +/- 10 cm3) was larger than in controls (33 +/- 3 cm3). Sham-feeding gallbladder contraction did not differ between patients after DPRHP, patients with CP, and controls. Both postprandial CCK secretion and gallbladder contraction in patients after DPRHP (78 +/- 16 pM. 120 min; 47% +/- 6%) and patients with CP (72 +/- 18 pM.120 min; 40% +/- 7%) were significantly reduced (P < 0.05) compared with controls (151 +/- 13 pM.120 min; 74% +/- 4%). Fasting gallbladder volume, sham feeding, and regular-feeding-induced gallbladder contraction and postprandial CCK secretion did not differ between operated and unoperated patients with CP.. Gallbladder motility and CCK secretion are reduced in patients with pancreatic insufficiency. A DPRHP procedure does not further influence these results. These findings support the concept that gallbladder motor function is preserved after DPRHP.

Topics: Adult; Cholecystokinin; Chronic Disease; Duodenum; Exocrine Pancreatic Insufficiency; Fasting; Female; Gallbladder; Gallbladder Emptying; Humans; Male; Middle Aged; Pancreas; Pancreatitis; Postprandial Period; Ultrasonography

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

In a follow up study 19 patients after Billroth-I, 22 patients after Billroth-II-resection and 38 patients after total gastrectomy (23 with Roux-Y-reconstruction and 15 with Longmire-Gütgemann) underwent a stool fat determination and an indirect pancreatic function test with fluorescein dilaurate in serum und urine. In 9 of 19 cases (47.3%) after B-I-resection and 14 of 22 patients (63.5%) after B-II-resection there were pathological results of the PLT-test in urine. After total gastrectomy as well with reconstruction of the duodenal passage as with its exclusion the PLT-test results were pathological in 60% resp. 87%. These results indicate a secondary pancreatic insufficiency following gastric resection.

Topics: Adult; Aged; Anastomosis, Roux-en-Y; Cholecystokinin; Exocrine Pancreatic Insufficiency; Female; Fluoresceins; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Neurotensin; Pancreatic Function Tests; Postoperative Complications; Stomach Neoplasms; Stomach Ulcer

The study was conducted on five healthy subjects and six patients with calcifying pancreatitis (CP) and steatorrhea. Following overnight fasting, one tube each was placed in the stomach and the upper of the small intestine, respectively. Through the gastric tube, a test meal that included 30 g of fat (total calories, 625 kcal, 500 mL) was infused over a span of 30 min. Every 30 min (up to 150 min), fluid samples in the upper small intestine were collected and chilled, and the amylase, trypsin, and lipase levels were determined. In addition, in the case of the CP patients, a high-potency pancreatin preparation was infused into the stomach together with the test meal. In order to determine the plasma CCK level, blood sample were collected before test meal infusion and at 10, 20, 30, 45, 60, 90, 120, and 150 min subsequent to infusion. The plasma CCK was extracted using a Sep-Pak C-18 cartridge and analyzed with radioimmunoassay using an OAL-656 antibody. The result was converted to the CCK-8 level and expressed in pg/mL. The enzyme activities in the upper small intestine of the CP patients after test meal administration amounted to 22.8 (amylase), 10.8 (trypsin), and 16.9% (lipase) compared with the corresponding figures for the normal subjects. Following administration of a high-potency pancreatin in patients with CP, enzyme activities in the upper small intestine increased to 132.2 (amylase), 38.7 (trypsin), and 45.3% (lipase) compared with levels in the normal subjects. However, the healthy subjects and the CP patients, both with and without treatment with supplementary exogenous enzymes, all exhibited similar profiles in the plasma CCK response to stimuli. Based on these findings, we concluded that a negative feedback mechanism does not exist between the tryptic activity of the upper small intestine and the CCK secretory response in patients with chronic pancreatitis.

Topics: Adult; Amylases; Cholecystokinin; Chronic Disease; Exocrine Pancreatic Insufficiency; Feedback; Food; Humans; Intestine, Small; Lipase; Male; Middle Aged; Pancreatin; Pancreatitis; Trypsin

The reduced decrease of plasma alpha-amino nitrogen after hormonal stimulation of the pancreas has been characterized as a valid and simple test of pancreatic function. Aim of this study was to reassess the clinical value of the alpha-amino nitrogen test and to evaluate the role of different modes of hormonal secretion. Therefore, we have investigated the relationship of plasma alpha-amino nitrogen responses and pancreatic secretion, stimulated by either bolus injection (n = 25) or continuous infusion (n = 32) of cholecystokinin-pancreozymin in patients with and without exocrine pancreatic insufficiency as determined by the secretin-pancreozymin test. Of the 57 patients referred to the secretin-pancreozymin-test, 18 had pancreatic insufficiency, each 9 in the group with continuous and bolus stimulation.. Basal alpha-amino nitrogen concentrations were almost identical in patients with and without impaired pancreatic function (2.66 +/- 0.12 mmol/l vs. 2.73 +/- 0.08 mmol/l [SEM]; p > 0.05). Both, the bolus dose and infusion of cholecystokinin induced similar (log-normally distributed) maximum decreases of alpha-amino nitrogen concentrations (-SD; mean; + SD: 3.6; 9.0; 22.3% vs. 6.0; 10.5; 18.5%, respectively) in the patients without exocrine pancreatic insufficiency. This was in tendency more pronounced compared to those with impaired pancreatic secretion (cholecystokinin bolus; 2.7; 5.2; 9.9%; infusion: 5.0; 7.7; 11.6%). The difference (+/- exocrine pancreatic insufficiency) was significant (p < 0.05) for the infusion mode only. Moreover, the time course of alpha-amino nitrogen concentration-profiles was more homogenous after hormone infusion as compared to bolus stimulation. Sensitivities to detect exocrine pancreatic insufficiency by the alpha-amino nitrogen test were < 50% with either test modification.. The decrease of plasma alpha-amino nitrogen after stimulation with cholecystokinin is no accurate indicator of exocrine pancreatic function, regardless of whether hormonal stimulation is by bolus or by infusion.

Topics: Adult; Aged; Cholecystokinin; Chronic Disease; Diabetes Mellitus; Exocrine Pancreatic Insufficiency; Humans; Infusions, Intravenous; Middle Aged; Pancreatic Function Tests; Pancreatic Juice; Pancreatitis; Reference Values; Secretin

Topics: Adult; Amino Acids; Cholecystokinin; Chronic Disease; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; Predictive Value of Tests

Application of pancreatic digestive enzymes is indicated in cases of a quantitatively decreased exogenous secretion or an asynchronous secretion of enzymes with regard to the duodenal passage of chyme. A clear indication for therapy is a proven steatorrhea, a relative indication loss weight of and/or uncharacteristic abdominal discomfort in patients with proven pancreatic disease, i.e. chronic pancreatitis. Uncharacteristic abdominal discomfort alone, which is regarded as a consequence of 'maldigestion' without proven pancreatic disease, is not an indication for therapy. To prevent a destruction of exogenously applied lipase by gastric acid and to enable a synchronous gastroduodenal passage of the enzymes together with food, acid-protected micropellets or -tablets with an ideal diameter around 1.4 mm containing high amounts of lipase are requested. In cases of anacidity i.e. gastrectomy or type-A gastritis, lipase rich 'conventional' enzymes applied as granulate are sufficient. Combinations (pancreatic enzymes with bile acids) or fungal lipases have either more side effects (diarrhea) or are less efficient when compared to porcine enzymes. Acid-resistant microbial lipases may be useful in the near future. Application of pure proteases or pancreatic enzymes with high concentrations of proteases as treatment of pain in chronic pancreatitis ('negative feedback regulation') are a rather expensive form of treatment when compared to analgetics and are probably ineffective.

Topics: Cholecystokinin; Enzyme Therapy; Exocrine Pancreatic Insufficiency; Humans; Lipase; Pain Management; Pancreas; Pancreatic Diseases; Pancreatin; Pancreatitis

To describe the secretory responses to physiological stimulation of the exocrine pancreas after partial pancreatectomy in conscious animals.. Controlled study.. Thirteen mongrel dogs.. Partial pancreatectomy (n = 4), and creation of gastric and pancreatic (Herrera) fistulas (n = 13). Collections of duodenal juice at 15 minute intervals after an oral meal or during intraduodenal infusion of sodium oleate, and blood samples.. Protein concentration in duodenal juice and cholecystokinin 33/39 concentrations in plasma one and three months after partial pancreatectomy, and secretion of fluid by the pancreas.. Pancreatic protein output after a meal was significantly reduced at one and three months in dogs after partial pancreatectomy compared with control animals. Protein output in response to an intraduodenal infusion of oleate was also reduced at both time points. In contrast, secretion of fluid after a meal or during infusion of oleate was unchanged by removal of the distal lobe. There was no correlation between the effects of partial pancreatectomy on protein output and plasma concentrations of cholecystokinin 33/39.. Pancreatic exocrine deficiency, particularly the reduction in secretion of protein, results directly from the partial pancreatectomy and persists for at least three months after the operation.

Topics: Animals; Cholecystokinin; Dogs; Eating; Exocrine Pancreatic Insufficiency; Oleic Acid; Oleic Acids; Pancreatectomy; Pancreatic Juice; Proteins

Pancreatic function can only be determined exactly via the pancreozymin-secretin test. We conducted this test in two versions: (1) under conditions of continuous perfusion with the possibility of volume correction and (2) as a simple tubing. We compared the results of 86 tubings with the results of 87 examinations under perfusion. For that purpose all patients were classified into four groups: group a) with 46 and 10 examinations, respectively, in patients suffering from cholestasis in early infancy, group b) with 7 and 12 examinations, respectively, in older patients with liver diseases, group c) with 8 and 17 examinations, respectively, in patients suffering from cystic fibrosis or Shwachman's syndrome and group d) with 25 and 48 examinations, respectively, in children with normal pancreatic function. Both examination methods nearly identical mean values of the enzyme activities in all four patient groups. However, mean variations were found to be higher in case of tubing. Therefore the lower limits (x - 2s) of this test were defined at a lower level than those of the tests under perfusion.

Topics: Amylases; Child; Child, Preschool; Cholecystokinin; Cystic Fibrosis; Diagnosis, Differential; Exocrine Pancreatic Insufficiency; Humans; Infant; Infant, Newborn; Intestinal Secretions; Jaundice, Neonatal; Lipase; Liver Diseases; Pancreatic Function Tests; Reference Values; Secretin; Trypsin

Traditional methods for collecting duodenal fluid are time consuming and technically difficult. A simple endoscopic method is proposed in this report as a means of collecting duodenal fluid to perform exocrine pancreatic function tests. Thirty-five patients between 24 and 36 months of age were studied for pancreatic exocrine function. Twenty-seven presented with chronic diarrhea and 8 with failure to thrive. In 20 patients (group 1), duodenal fluid was collected by means of a double-lumen tube and sequential administration of pancreozymin (PZN) and secretin (SEC). The rest (group 2) had duodenal aspiration from the level of the papilla of Vater through a fiberoptic endoscope following administration of SEC only. The procedure took approximately 3 h in group 1 and 45 min in group 2. Secretin administration produced comparable levels of enzymes in both groups. Pancreozymin produced the highest enzyme levels, but this was only significantly higher than SEC-induced levels in the case of lipase. Endoscopic collection of duodenal fluid following SEC administration is a safe, quick, and reliable method of collecting pancreatic secretion.

Topics: Child, Preschool; Cholecystokinin; Duodenum; Endoscopy; Exocrine Pancreatic Insufficiency; Fiber Optic Technology; Humans; Intestinal Secretions; Male; Pancreatic Function Tests; Pediatrics; Secretin; Suction

The entero-insular hormonal axis was studied in eleven conscious Beagle dogs, loaded with glucose orally and intravenously. In five of them, exocrine pancreatic atrophy was induced by pancreatic duct occlusion with prolamine, and documented by means of the p-amino-benzoic acid test. After oral glucose, the duct-occluded dogs displayed higher blood glucose (log area 4.12 +/- 0.07 versus 3.76 +/- 0.10; p less than 0.01), less plasma insulin (log area 3.56 +/- 0.08 versus 3.99 +/- 0.08; p less than 0.01) and less cholecystokinin-like immunoreactivity (log area 2.64 +/- 0.09 versus 3.10 +/- 0.14; p less than 0.01) than controls. In controls, the peripheral venous insulin concentrations were higher after oral than after isoglycaemic intravenous glucose, and this difference was no longer demonstrable in duct-occluded dogs. In the latter, gel permeation chromatography of pool plasma after oral glucose revealed a relative decrease of cholecystokinin-like immunoreactivity species, which eluted at the positions of sulphated cholecystokinin octapeptide, cholecystokinin-33 and cholecystokinin-39, and at a position intermediate between these two. Also in the duct-occluded animals, intravenous infusion of sulphated cholecystokinin octapeptide, in addition to oral glucose, resulted in an increase in plasma insulin (log area 3.83 +/- 0.10 versus 3.64 +/- 0.06; p less than 0.01) and an improvement in oral glucose tolerance. It is concluded that in the dog 1) the absence of pancreatic acinar tissue is associated with a loss of gastrointestinal factors mediating glucose-induced insulin secretion, and 2) reduction of circulating endogenous cholecystokinin species may account at least in part for this defect.

Topics: Animals; Blood Glucose; Cholecystokinin; Chromatography, Gel; Dogs; Exocrine Pancreatic Insufficiency; Gastric Inhibitory Polypeptide; Gastrins; Glucose; Insulin; Insulin Secretion; Male; Sincalide

Oral pancreatic enzyme replacement therapy generally benefits patients with severe pancreatic deficiency. However, the fate of oral pancreatic supplements in the digestive lumen and their possible effects on circulating gut hormones are only partially known. The purpose of this article is to validate an experimental model that produces total pancreatic insufficiency in pigs, and to study the fate of orally administered Eurobiol, a whole pancreas lyophilized preparation, and its effects on circulating plasma levels of five digestive hormones. Pancreatic insufficiency was created by pancreatic duct ligation, and the duodenal, jejunal and ileal contents were sampled through cannulas before a normal meal and 0.5-24 h later. Blood samples were taken at the same times, and plasma neurotensin, pancreatic polypeptide, secretin, cholecystokinin (CCK), and gastrin were measured. In pigs with pancreatic insufficiency, Eurobiol, given during the meal, induced a significant increase in all enzyme activities in the duodenum and the jejunum, and in the levels of amylase, trypsin, and chymotrypsin in the ileum, relative to placebo. In the duodenum, the peak concentrations of enzyme activities were 19, 11, 17, and 29% (p less than 0.001) of the postprandial peak activities measured in control pigs with an intact pancreas for lipase, amylase, trypsin, and chymotrypsin, respectively. In the jejunum, the same activities were, respectively, 30, 11, 25, and 36% (p less than 0.01-0.001) of normal peaks. In pigs with pancreatic insufficiency, basal and integrated meal-stimulated neurotensin levels were increased; basal, peak, and integrated meal-stimulated pancreatic polypeptide and secretin levels were increased, whereas gastrin and CCK were not different from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Amylases; Animals; Cholecystokinin; Chymotrypsin; Disease Models, Animal; Exocrine Pancreatic Insufficiency; Gastrins; Intestines; Lipase; Male; Neurotensin; Pancreas; Pancreatic Extracts; Pancreatic Polypeptide; Secretin; Swine; Trypsin

The present study was undertaken to examine the intestinal phase of cholecystokinin (CCK) secretion and gall bladder contraction in patients with severe pancreatic insufficiency. Plasma CCK concentrations, measured by radioimmunoassay, and gall bladder contraction by cholescintigraphy were studied in response to intraduodenal fat with and without addition of pancreatic enzymes. Fasting plasma CCK concentrations were in the same range in six patients with pancreatic insufficiency with (2.6 (0.2) pmol/l) and without (2.6 (0.3) pmol/l) addition of pancreatic enzymes and in six healthy subjects (2.0 (0.4) pmol/l). The integrated plasma CCK secretion in response to intraduodenal fat was significantly (p less than 0.005) reduced in the patients without addition of enzymes (46 (13) pmol/1.90 min) compared with healthy subjects (199 (22) pmol/1.90 min), but increased significantly (p less than 0.01) by the addition of pancreatic enzymes (174 (25) pmol/1.90 min) to values not significantly different from healthy subjects. Similarly, gall bladder emptying in response to intraduodenal fat was significantly (p less than 0.01) reduced in patients with pancreatic insufficiency without addition of enzymes (at 90 min: 35 (11)%) compared with healthy subjects (at 90 min: 66 (7)%) but significantly (p less than 0.01) increased by addition of pancreatic enzymes (at 90 min: 70 (8)%) to values not significantly different from healthy subjects. These results indicate that patients with severe pancreatic insufficiency have impaired gall bladder emptying after intraduodenal fat, which can be normalised by the addition of pancreatic enzymes. This impaired gall bladder emptying appears to be the result of a reduced plasma CCK response. Thus, intra-intestinal pancreatic enzymes play an important role in the intestinal phase of CCK secretion and gall bladder emptying.

Topics: Adult; Cholecystokinin; Exocrine Pancreatic Insufficiency; Gallbladder; Humans; Male; Middle Aged

In the present study we examined the effect of Thr28 Nle31-CCK 25-33 (CCK-9) on pancreatic exocrine function in man. In subjects without pancreatic disease CCK-9 together with i.v. secretin (0.5 CU/kg/h) elicited a maximal stimulation of amylase output at a dose of 10 pmol/kg/h while trypsin and chymotrypsin were stimulated maximally at a dose of 30 pmol/kg/h. Higher doses of 60 and 100 pmol/kg/h had no additional effects. Lipase secretion was stimulated by secretin alone with no additional effect of CCK-9. During all doses of CCK-9 no side effects were observed. In patients with chronic pancreatitis a dose of 30 pmol/kg/h was also sufficient to obtain maximal enzyme output. In conclusion this derivative of CCK can be considered as a potent and useful alternative to amphibian caerulein in direct pancreatic function tests.

Topics: Alcoholism; Cholecystokinin; Exocrine Pancreatic Insufficiency; Humans; Infusions, Intravenous; Pancreatic Function Tests; Pancreatitis; Peptide Fragments

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

Simultaneous measurements of duodenal and faecal chymotrypsin were made in 30 children aged 3 weeks to 14 years. Apparent chymotrypsin secretion rates measured after stimulation with pancreozymin were compared with the mean faecal chymotrypsin concentration derived from three stool specimens collected at random within 72 hours of the intraduodenal test. In the 25 children who responded to pancreozymin stimulation the mean faecal chymotrypsin concentration was significantly positively correlated with the apparent chymotrypsin secretion rate. Correlation using single specimen stools collected at random was appreciably poorer. In the five children with undetectable or only traces of chymotrypsin in the duodenum after stimulation, the mean faecal chymotrypsin concentrations were only 3-10% of the lower limit of the reference interval. In a second group of 46 children with cystic fibrosis proved by sweat tests and clinical evidence of malabsorption, the chymotrypsin concentration measured in a single stool specimen collected at random was unequivocally subnormal in each case. Faecal chymotrypsin measurement is a rapid, simple, cheap, readily repeated, non-invasive test of high specificity and sensitivity. Faecal chymotrypsin should be measured before contemplating intraduodenal tests of pancreatic function.

Topics: Adolescent; Child; Child, Preschool; Cholecystokinin; Chymotrypsin; Duodenum; Exocrine Pancreatic Insufficiency; Feces; Humans; Infant; Infant, Newborn; Intestinal Secretions; Pancreas; Pancreatic Function Tests

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

A sufficient number of good retrieval rates (median value 88.9%) could be achieved by means of radiovitamin B12 in 20 patients who underwent a secretin-pancreozymin test. Losses of this amount can be tolerated for practical purposes. As a rule, marker losses are caused by a flow-off into deeper intestinal sections. The marker technique raises a great number of unexplained issues.

Topics: Cholecystokinin; Chronic Disease; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; Secretin; Secretory Rate

Serum fluorescein and p-aminobenzoic acid were measured during a urine pancreolauryl and an N-benzoyl-l-tyrosyl-p-aminobenzoic acid (NBT-PABA) test in 22 healthy controls, 17 patients with gastrointestinal nonpancreatic diseases (normal secretin-pancreozymin test), and 31 patients with abnormal exocrine pancreatic function due to chronic pancreatitis. The optimal cutoff point for separating normal from abnormal pancreatic function was after 210 min in the pancreolauryl test and after 150 min in the NBT-PABA test. The latter test was slightly less sensitive and specific than the pancreolauryl test. Serum tests seem to offer a practicable alternative to the established indirect pancreatic function tests in urine and may be used in the elderly and severely ill, as well as in outpatients in whom correct collection of the urine may be difficult.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Cholecystokinin; Exocrine Pancreatic Insufficiency; Feces; Fluoresceins; Humans; Indicators and Reagents; Pancreatic Function Tests; para-Aminobenzoates; Secretin

Salivary isoamylase was measured in duodenal aspirates of 124 consecutive patients during a secretin-pancreozymin test, using an inhibitor method. The isoenzyme was found in 22 patients (17.7%), more often in the patients with abnormal pancreatic function (40.5%) than in those with normal function (8.0%). Before the subtraction of the salivary isoamylase component, total amylase output was falsely normal in three of 37 patients with exocrine pancreatic insufficiency. It is concluded that measurement of amylase isoenzymes rather than of total amylase during the secretin-pancreozymin test may be recommended for scientific purposes. It may also improve discrimination between normal and abnormal exocrine pancreatic function if amylase is chosen as the only parameter for evaluation of pancreatic enzyme secretion.

Topics: Adolescent; Adult; Aged; Bicarbonates; Cholecystokinin; Duodenum; Exocrine Pancreatic Insufficiency; False Negative Reactions; Female; Glycoside Hydrolases; Humans; Intestinal Secretions; Isoamylase; Lipase; Male; Middle Aged; Pancreatic Function Tests; Saliva; Secretin; Trypsin

Previous studies have suggested that intraduodenal protease suppression of pancreatic exocrine secretion may be mediated through cholecystokinin (CCK) release. Our study compares basal plasma immunoreactive CCK concentrations in normal human subjects with those obtained in patients with chronic pancreatitis. Fasting plasma samples were collected from 18 normal subjects and from 18 patients with chronic pancreatitis. Eight patients had mild to moderate pancreatic exocrine impairment, and 10 had severe exocrine insufficiency. Venous plasma immunoreactive CCK concentrations were measured with two distinct peptide region-specific antibodies. Basal plasma CCK concentration in controls was 14.3 +/- 1.3 fmol/ml (mean +/- SEM), a value significantly less than that obtained in all patients with chronic pancreatitis, 30.1 +/- 4.0 fmol/ml (p less than 0.001). Patients with mild to moderate impairment had a fasting plasma CCK concentration of 32.8 +/- 7.9 fmol/ml (vs. control p less than 0.01), and those with severe disease 27.9 +/- 3.6 fmol/ml (vs. control p less than 0.001). In five patients with mild to moderate impairment of exocrine function and pancreatic extract-responsive abdominal pain, there was a 39 +/- 11% decrease in basal CCK levels during extract therapy (p less than 0.05). Results of this study indicate that pancreatic exocrine impairment is associated with elevated basal CCK levels, which may reflect a failure to provide feedback downmodulation of CCK release.

Topics: Adult; Cholecystokinin; Chronic Disease; Exocrine Pancreatic Insufficiency; Fasting; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Diseases; Pancreatic Extracts; Pancreatitis; Radioimmunoassay

Topics: Adult; Cholecystectomy; Cholecystokinin; Cholelithiasis; Exocrine Pancreatic Insufficiency; Female; Humans; Postoperative Complications; Secretin

Topics: Adolescent; Child; Child, Preschool; Cholecystokinin; Exocrine Pancreatic Insufficiency; Gastrins; Glucagon; Humans; Insulin; Insulin Secretion; Stimulation, Chemical

The case history of a 34-year-old patient with precirrhotic idiopathic haemochromatosis and severe chronic steatorrhoea is presented. The pancreas had a normal appearance on ultrasonography and endoscopic retrograde pancreaticography. However, pancreatic function tests revealed significant abnormalities. The pancreatic output of trypsin, amylase, lipase and bicarbonate was deficient and basal and stimulated serum pancreatic polypeptide levels were subnormal. In contrast, the oral glucose tolerance test was unimpaired. The pancreatic insufficiency had started suddenly during a summer vacation and may have had a viral aetiology. The hypothesis is advanced that in haemochromatosis the iron-laden pancreatic acinar and PP-producing cells are more susceptible to damage by viruses than normal pancreatic cells.

Topics: Adult; Cholecystokinin; Exocrine Pancreatic Insufficiency; Hemochromatosis; Humans; Male; Pancreatic Function Tests; Pancreatic Polypeptide; Secretin

It has been claimed that plasma cholecystokinin (CCK) concentrations are raised in patients with pancreatic insufficiency. We have measured plasma CCK concentrations in 32 patients with pancreatic insufficiency (22 alcoholic pancreatitis and 10 cystic fibrosis) and in 30 normal subjects by radioimmunoassays using antibodies with different specificities. Antibody 1703 binds to COOH-terminal forms of CCK containing at least 14 amino acid residues and does not cross-react with gastrins. Antibody T204 binds to all CCK-peptides containing the sulfated tyrosyl region and shows low cross-reactivity with sulfated gastrins but no binding to nonsulfated gastrins. Antibody 5135 binds to all COOH-terminal CCK-peptides and shows full cross-reactivity with gastrins. In patients with pancreatic insufficiency, plasma CCK concentrations (1.2 +/- 0.1 pmol/liter, antibody 1703; 2.0 +/- 0.2 pmol/liter, antibody T204; 12.5 +/- 1.4 pmol/liter, antibody 5135) were not significantly different from those in normal subjects (1.1 +/- 0.1 pmol/liter, antibody 1703; 2.2 +/- 0.3 pmol/liter, antibody T204; 10.5 +/- 0.9 pmol/liter, antibody 5135). Furthermore, plasma CCK concentrations in patients with pancreatic insufficiency due to alcoholic pancreatitis (1.2 +/- 0.1 pmol/liter, antibody 1703; 1.9 +/- 0.2 pmol/liter, antibody T204; 14.0 +/- 1.9 pmol/liter, antibody 5135) were not significantly different from those in patients with cystic fibrosis (1.2 +/- 0.2 pmol/liter, antibody 1703; 2.4 +/- 0.4 pmol/liter, antibody T204, 9.1 +/- 1.0 pmol/liter, antibody 5135). Cross-reactivity with gastrin accounted for almost all CCK-like-immunoreactivity measured with antibody 5135.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Alcoholism; Antibodies; Antibody Specificity; Binding Sites, Antibody; Cholecystokinin; Cross Reactions; Cystic Fibrosis; Diabetes Mellitus; Exocrine Pancreatic Insufficiency; Female; Gastrins; Humans; Male; Middle Aged; Pancreatitis; Radioimmunoassay

Pancreatic polypeptide (PP) was measured in 74 patients with normal and in 42 patients with abnormal pancreatic function under fasting conditions (before and after duodenal intubation) and following secretin and cholecystokinin (CCK) stimulation. Fasting PP values of patients with severe but not with moderate exocrine pancreatic insufficiency were significantly lower than those of controls. Duodenal intubation led to a significant increase in fasting PP values. Both CCK and, to a lesser extent, secretin led to an increase in PP values. PP increase was significantly lower in patients with severe and not with moderate exocrine pancreatic insufficiency compared to controls following stimulation. Therefore, while fasting serum levels of PP and those following low stimulation indicate severe exocrine pancreatic insufficiency in the absence of previous vagotomy, PP estimations do not enable diagnosis of moderate functional impairment of the pancreas.

Topics: Adult; Aged; Cholecystokinin; Exocrine Pancreatic Insufficiency; Female; Gastrointestinal Hormones; Humans; Male; Middle Aged; Pancreatic Polypeptide; Secretin

Assessment of the clinical value of the pancreolauryl test (PLT) in the literature range from "useless" to a specifity of 95% and a sensitivity of 98%. In this work, our own data are presented in relation to various reference methods. The results are derived from the largest collective investigated to data, comprising 40 controls and 391 patients (108 with chronic pancreatitis and 283 with other gastrointestinal disorders). The specifity of the the PLT varies between 81% and 95% according to the "quality" of the control collective. The PLT is particularly frequently pathological in patients with diseases in the region of the gallbladder/bile duct and the gastrointestinal tract. The sensitivity of the PLT for chronic pancreatitis varies between 68% and 100%, depending on 9 different reference methods employed. Based on the prevalence of chronic pancreatitis with exocrine insufficiency in various patient collectives, the predictive value of the PLT for the presence of this disorder can be calculated using our data.

Topics: Cholangiopancreatography, Endoscopic Retrograde; Cholecystokinin; Cholelithiasis; Chronic Disease; Chymotrypsin; Diagnosis, Differential; Exocrine Pancreatic Insufficiency; Gastrointestinal Diseases; Humans; Liver Diseases; Pancreatic Diseases; Pancreatic Function Tests; Pancreatitis; Secretin; Tomography, X-Ray Computed

After the development of reliable, highly sensitive, specific radioimmunologic methods for measuring physiologic CCK concentrations in human plasma, we have been able to study the importance of CCK in the postprandial activation of pancreatic enzyme secretion. In man, food causes a threefold increase in the basal plasma CCK concentration with a peak at about 60 minutes. The highest CCK concentrations are observed after intraduodenal fat infusion. Selective proximal vagotomy results in a significant increase in basal CCK concentrations in duodenal ulcer patients without altering the postprandial CCK output. After gastric resection (Billroth I or Billroth II) an initial greater postprandial CCK output is observed. In patients with chronic pancreatic insufficiency without enzyme substitution, basal plasma CCK concentrations and the early postprandial CCK output were elevated which indicated a feedback mechanism between pancreatic enzyme secretion and CCK release from the mucosa of the upper small intestine.

Topics: Cholecystokinin; Duodenal Ulcer; Eating; Exocrine Pancreatic Insufficiency; Humans; Pancreas; Postgastrectomy Syndromes; Radioimmunoassay

In 72 patients with chronic pancreatitis results of tbe secretin-cholecystokinin test were compared with those of several indirect test of pancreatic function (faecal fat content, chymotrypsin activity in faeces, peptide-PABA test, fluorescein-dilaurate test and weight of faeces). In 46 patients with markedly impaired pancreatic secretion the indirect tests were abnormal in 56-83% of cases. In 26 patients with normal or upper-limit-of-normal excretory function the same tests were abnormal in 15-77%. These results indicate that indirect tests of pancreatic function are of only limited value in the early diagnosis of pancreatic insufficiency.

Topics: Adult; Cholecystokinin; Chronic Disease; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; Secretin

The validity of oral pancreatic function tests (fluoresceine dilaurate-[FDL-], N-benzoyl-L-tyrosyl-para-amino-benzoic-acid-[PABA-]test) was assessed intra-individually in 67 patients in comparison with the secretin-pancreozymin test corrected for volume loss. Faecal chymotrypsin (CH-F) estimation was included in the comparison. According to the result of the secretin-pancreozymin test, patients were divided into those with normal pancreatic function (n = 28), those with borderline restricted function (n = 18), and those with manifest exocrine insufficiency (n = 21). Results show that in borderline decreased pancreatic function the diagnostic value of all screening tests is limited. The sensitivity (true pathological results) was 38% in the FDL-test, 40% in the PABA-test, and 31% in CH-F. In manifest exocrine pancreatic insufficiency FDL- and PABA-test as well as CH-F showed similar sensitivity of 67, 63, and 62%, respectively. Results show that oral pancreatic function tests, particularly the simple FDL-test, represent a diagnostic alternative to the relatively complicated CH-F assessment. However, none of the tests are able to replace the secretin-pancreozymin test as the most valid diagnostic investigation.

Topics: 4-Aminobenzoic Acid; Adult; Aged; Cholecystokinin; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Fluoresceins; Humans; Male; Middle Aged; Pancreatic Function Tests; Secretin

The diagnostic value of the fecal chymotrypsin test (FCT) was reevaluated with regard to (a) proved pancreatic hypofunction of different severity (183 pancreozymin-secretin tests); (b) the final clinical diagnosis, and (c) fecal fat excretion (208 patients with chronic pancreatitis; CP). Progressive pancreatic disease (cancer, CP) was mainly associated with moderate or severe pancreatic hypofunction (119/138; 86.2%) and a low incidence of false-normal FCT values (14/138; 10.1%). Miscellaneous disorders (mainly reversible pancreatic hypofunction) were mainly associated with slight pancreatic hypofunction and a high incidence of false-normal FCT values (17/45; 37.8%). Pancreatic steatorrhea (greater than 10 g/day) was found only in patients with markedly depressed FCT values. Progressive deterioration of pancreatic function was demonstrated by repeated FCT in CP (n = 220).

Topics: Celiac Disease; Cholecystokinin; Chronic Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; False Negative Reactions; Feces; Humans; Lipids; Pancreatic Function Tests; Pancreatitis; Secretin

In many ways diagnosis of pancreatic disorders in children is difficult. Since pancreatic parameters are age-dependent, reliable laboratory parameters are not easily established. Children are less likely than adults to endure tolerance tests and invasive test methods should therefore be used only in special situations. Estimation of chymotrypsin in faeces seems to be an earlier indicator of pancreatic insufficiency than the PABA-peptide-test. A secretin-pancreozymin test can only be advised for first diagnosis after screening has repeatedly indicated pathological values and malabsorption has more or less been ruled out. A threefold rise in serum amylase values - matched for age - suggests pancreatitis and sonography should then be applied to obtain further clarification.

Topics: 4-Aminobenzoic Acid; Age Factors; Amylases; Child; Child, Preschool; Cholecystokinin; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Humans; Infant; Infant, Newborn; Pancreatic Diseases; Pancreatitis; Secretin

The NBT-PABA test, an oral pancreatic function test, was performed in 67 patients with proven chronic pancreatitis (secretin pancreozymin test or intraoperatively) and was pathological in 60 (89.6%). Prolongation of urinary collection period from 6 to 9 hours did not improve the diagnostic value. In comparison with the NBT-PABA test the sensitivity of trypsin and chymotrypsin determination in stool was 40.6% and 62.2%, respectively. In severe exocrine pancreatic insufficiency when pathological fecal fat excretion was demonstrable (steathorrhea) the accuracy of fecal enzyme determination was clearly higher (59.1% and 91.8%, respectively). Thus the NBT-PABA test is an alternative diagnostic tool for exocrine pancreatic insufficiency when the secretin-pancreozymin test, and fecal enzyme and fecal fat determination are too complicated. However, as intact absorption of NBT-PABA is possible, the test only provides a qualitative and limited quantitative evaluation of pancreatic function.

Topics: 4-Aminobenzoic Acid; Adolescent; Adult; Aged; Aminobenzoates; Cholecystokinin; Chronic Disease; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Lipids; Male; Middle Aged; Pancreatic Function Tests; Pancreatitis; para-Aminobenzoates; Secretin