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Objective: To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology., Research Design and Methods: For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg ( n = 19), sitagliptin 100 mg ( n = 19), or matching placebos ( n = 17) once daily for 12 weeks. The primary end point was change in exocrine function (intraduodenal pancreatic fluid secretion, lipase activity, fecal elastase-1, and chymotrypsin). Secondary end points included changes in plasma enzyme concentrations and pancreatic morphology (per MRI)., Results: No patient developed pancreatitis. Sitagliptin increased intraduodenal pancreatic fluid secretion by 16.3 mL (95% CI -0.3 to 32.9; P = 0.05), whereas liraglutide did not change exocrine pancreatic function. Neither therapy increased lipase/amylase levels after 12 weeks. However, liraglutide increased lipase levels after 6 weeks (23.5 U/L [95% CI 2.1-44.8]; P = 0.03) and sitagliptin increased amylase levels after 2 and 6 weeks (13.7 U/L [95% CI 3.4-23.9]; P = 0.03). Both drugs increased plasma trypsinogen after 12 weeks (liraglutide: 34.6 µg/mL [95% CI 15.1-54.2], P = 0.001; sitagliptin: 23.9 µg/mL [95% CI 4.9-42.9], P = 0.01). Neither changed pancreatic morphology, although liraglutide tended to increase pancreatic volume (7.7 cm 3 [95% CI -1.2 to 16.6]; P = 0.09). Treatment-induced volume expansion was associated with increased amylase levels., Conclusions: A 12-week treatment with liraglutide or sitagliptin only resulted in a brief and modest increase of plasma pancreatic enzyme concentrations in patients with type 2 diabetes. Apart from a minimal sitagliptin-induced increase in intraduodenal fluid secretion, pancreatic exocrine function was unaffected. The long-term clinical consequences of these discrete changes require further study., (© 2017 by the American Diabetes Association.)

Aim: To examine whether rendezvous endoscopic retrograde cholangiopancreatography (ERCP) is associated with less pancreatic damage, measured as leakage of proenzymes, than conventional ERCP., Methods: Patients (n = 122) with symptomatic gallstone disease, intact papilla and no ongoing inflammation, were prospectively enrolled in this case-control designed study. Eighty-one patients were subjected to laparoscopic cholecystectomy and if intraoperative cholangiography suggested common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n = 40). Patients with a negative cholangiogram constituted the control group (n = 41). Another 41 patients with CBDS, not subjected to surgery, underwent conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2 levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were determined in-house with a double-antibody enzyme linked immunosorbent assay. Pancreatic amylase was measured by an enzymatic colourimetric modular analyser with the manufacturer's reagents. All samples were blinded at analysis., Results: Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated with conventional ERCP and none in the rendezvous group. Increased serum levels indicating pancreatic leakage were significantly higher in the conventional ERCP group compared with the rendezvous ERCP group regarding pancreatic amylase levels in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4- and 8-h samples (P < 0.0001; P < 0.0001) and trypsinogen-2 in the 24-hour samples (P = 0.03). No differences in these markers were observed in patients treated with rendezvous cannulation technique compared with patients that underwent cholecystectomy alone (control group). Post procedural concentrations of pancreatic amylase and procarboxypeptidase B were significantly correlated with pancreatic duct cannulation and opacification., Conclusion: Rendezvous ERCP reduces pancreatic enzyme leakage compared with conventional ERCP cannulation technique. Thus, laparo-endoscopic technique can be recommended with the ambition to minimise the risk for post ERCP pancreatitis.

Objectives: Most patients with cystic fibrosis (CF) have pancreatic insufficiency; however, 15% of the patients are pancreatic sufficient (PS). Several laboratory tests have been developed to distinguish between pancreatic insufficiency and PS. The gold standard to determine pancreatic function apart from direct pancreatic stimulation test is the 72-hour fecal fat excretion, expressed as coefficient of fat absorption (CFA). The aim was to test the correlation between 2 other tests, fecal elastase-1 and serum immunoreactive trypsinogen (IRT), as compared with fecal fat excretion., Patients and Methods: 21 patients with CF-PS performed the 3 tests of fecal fat excretion, fecal elastase-1, and IRT. Correlation between the tests was evaluated by the kappa statistics test, sensitivity and specificity, and positive and negative predictive values., Results: CFA was abnormal in 5 patients, elastase was <200microg/g in 4 patients, and IRT was <20 ng/mL in 2 patients. The correlation between CFA and IRT was negative(kappa=-0.154), and between CFA and fecal elastase-1 was poor (kappa=0.213). The sensitivity, specificity, and positive and negative predictive values of IRT versus CFA were 0%, 88%, 0%, and 78%, and for fecal elastase-1 were 40%, 81%, 40%, and 81%, respectively., Conclusions: In CF-PS, poor correlation was found between IRT, fecal elastase-1, and CFA, therefore neither fecal elastase-1 in the stool nor IRT in the serum reaches the sensitivity or the specificity of the fecal fat excretion. Thus, fecal fat excretion is required in patients with CF for evaluation of pancreatic function.

Serum feline trypsinogen-like immunoreactivity (fTLI) concentrations and abdominal ultrasound have facilitated the noninvasive diagnosis of pancreatitis in cats, but low sensitivities (33% and 20-35%, respectively) have been reported. A radioimmunoassay has been validated to measure feline pancreatic lipase immunoreactivity (fPLI), but the assay's sensitivity and specificity have not been established. In human beings, the sensitivity of computed tomography (CT) is high (75-90%), but in a study of 10 cats, only 2 had CT changes suggestive of pancreatitis. We prospectively evaluated these diagnostic tests in cats with and without pancreatitis. In all cats, serum was obtained for fTLI and fPLI concentrations, and pancreatic ultrasound images and biopsies were acquired. Serum fPLI concentrations (P< .0001) and ultrasound findings (P = .0073) were significantly different between healthy cats and cats with pancreatitis. Serum fTLI concentrations (P = .15) and CT measurements (P = .18) were not significantly different between the groups. The sensitivity of fTLI in cats with moderate to severe pancreatitis was 80%, and the specificity in healthy cats was 75%. Feline PLI concentrations were both sensitive in cats with moderate to severe pancreatitis (100%) and specific in the healthy cats (100%). Abdominal ultrasound was both sensitive in cats with moderate to severe pancreatitis (80%) and specific in healthy cats (88%). The high sensitivities of fPLI and abdominal ultrasound suggest that these tests should play an important role in the noninvasive diagnosis of feline pancreatitis. As suggested by a previous study, pancreatic CT is not a useful diagnostic test for feline pancreatitis.

Objective: To evaluate the role of serum enzymes for defining the pancreatic phenotype in Shwachman-Diamond syndrome (SDS), an inherited multisystem condition., Study Design: Serum pancreatic trypsinogen and isoamylase were measured in 164 patients known or presumed to have SDS. The diagnosis was confirmed in 90 patients. Among 74 unconfirmed cases, 35 ("probable SDS") had hematologic dysfunction but lacked documented pancreatic dysfunction, whereas 39 patients ("improbable SDS") lacked both documented pancreatic and hematologic dysfunction. Classification and regression tree (CART) analysis was performed in 90 patients with SDS and 134 control patients to establish a rule for defining the pancreatic phenotype of SDS; the rule was then applied to the patients with unconfirmed diagnosis., Results: In the control patients, serum trypsinogen showed little variation with age, whereas serum isoamylase values rose from birth on, attaining adult values by 3 years. For patients with SDS, serum trypsinogen values were low in young patients and tended to increase with age, whereas serum isoamylase values remained low at all ages. The CART rule combined results from both enzymes and classified the pancreatic phenotype in all but one SDS patient, who was <3 years of age. Excluding patients <3 years of age, CART identified the pancreatic phenotype in 82% and 7% of the "probable SDS" and "improbable SDS" cases, respectively., Conclusions: Serum pancreatic enzymes are useful for determining the pancreatic phenotype and confirming the diagnosis of SDS.

Objective: We investigated whether the timing of administration of contrast medium after onset of acute pancreatitis is critical in determining the magnitude of microcirculatory derangement., Methods: An acute pancreatitis model in male Sprague-Dawley rats (225-275 g) was established by continuous infusion of cerulein (15 mg/kg per hour). The mean arterial pressure was monitored continuously by means of a femoral artery catheter. Diatrizoate (Hypaque-76), a water-soluble contrast medium, was delivered through a femoral vein catheter at doses corresponding to those given to humans, either 1, 2, or 3 hours after pancreatitis induction. In vivo microscopy and laser-Doppler flowmetry were used to investigate microcirculatory derangement. The water contents of the pancreas and lung, the malondialdehyde levels of the pancreas, and the trypsinogen activation peptide levels in the serum were measured at the end of the experiment (8 hours after infusion of cerulein)., Results: Early administration of contrast medium (1 hour after pancreatitis induction) resulted in significantly greater changes in microcirculation and mean arterial pressure than did late administration (2 or 3 hours after pancreatitis induction). Rats given contrast medium 1 hour after induction also had highest pancreas and lung water contents, the highest pancreas malondialdehyde levels, and the highest serum trypsinogen activation peptide levels., Conclusion: These results show that a water soluble contrast medium that is often used for computed tomographic imaging of the pancreas can adversely affect the pancreatic microcirculatory parameters, such as tissue perfusion and leukocyte sticking, and hemodynamics in a cerulein-induced model of acute pancreatitis. Early administration seems to cause more severe derangement of the pancreatic microcirculation.

Trypsin and chymotrypsin readily bind to human erythrocyte ghosts and to resealed right-side-out ghosts, but not to intact erythrocytes, as followed with [3H]trypsin and [3H]chymotrypsin and with cold proteases in a caseinolytic assay. The proteases freely reacted with casein in the presence of intact cells. Trypsin activated trypsinogen over an 8-hr time course at a faster rate in the presence of erythrocytes than in the absence thereof, after a slight initial delay. Trypsinogen did not bind to intact erythrocytes, thereby behaving comparably to trypsin. These results suggest that different microenvironments exist about the erythrocyte ghosts and the intact erythrocytes, thereby permitting the proteases to bind to the former but not to the latter. Hence, in the absence of considerable ghosts in circulating blood, which may mask the binding site of the proteases, the proteases may be more readily accessible for interaction with circulating serpins, leading to inactivation of the proteases and protection from their degradative potential. The presence of the serpins in circulating blood may assist in the control of the degradative power of the pancreatic proteases in pancreatitis and may negatively modulate such processes as thrombosis, activation of the complement system, and vascular remodeling.

Although serum amylase and lipase levels have been studied extensively in patients with renal disease, there are fewer data regarding trypsinogen levels in patients with end-stage renal disease (ESRD) treated with different dialytic modalities. We therefore evaluated the blood concentrations of trypsinogen, amylase, and lipase in asymptomatic patients with chronic renal insufficiency (CRI) and ESRD, to determine whether treatment modality or renal handling of these enzymes is important in determining steady-state levels in asymptomatic patients with chronic renal disease. Mean trypsinogen concentration levels were higher in hemodialysis (HD) patients and patients with CRI compared with normal subjects when values in the different groups were compared. There was no difference in the mean trypsinogen levels between patients treated with HD and those with CRI, between patients treated with chronic ambulatory peritoneal dialysis (CAPD) and those treated with HD, or between CAPD patients and patients with CRI. The mean circulating trypsinogen concentration was elevated more frequently and to a higher level than amylase or lipase in patients with CRI and ESRD. HD treatment did not result in a lowering of mean circulating pancreatic enzyme levels. We propose that decreased peripheral clearance, pancreatic overproduction, increased release from the pancreas, or a combination of these mechanisms is responsible, at least in part, for the increased plasma concentration of trypsinogen in patients with CRI, rather than simply a decrease in renal clearance.

We compared pancreatic acinar and ductal secretion in two patients with Johanson-Blizzard syndrome, age-matched control subjects, and patients with other primary pancreatic diseases. Patients with Johanson-Blizzard syndrome had preservation of ductular output of fluid and electrolytes, as in patients with Shwachman syndrome but differing from those with cystic fibrosis, who have a primary ductular defect. They also had decreased acinar secretion of trypsin, colipase and total lipase, and low serum immunoreactive trypsinogen levels, consistent with a primary acinar cell defect.

Homologous and heterologous (human) pure pancreatic juice was infused into dogs to compare the behaviour of pancreatic enzymes in the circulation. This was achieved by estimating the magnitude of elevation and speed of disappearance of pancreatic enzymes in plasma. The half-lives of the plasma enzymes did not differ significantly between dogs and humans. However the half-lives of other enzymes (longest for amylase and shortest for trypsinogen) did differ. The magnitude of elevation expressed as a ratio of peak (5 min) to basal level was greatest for trypsinogen (28 times) and least for amylase (1.4 times). However, 289% and 410% of the initial lipase enzyme activity was recovered 5 min after infusion of dog and human pure pancreatic juice, respectively (44% when measured by immunoreactive human lipase activity). The excess recovery requires re-evaluation of diagnostic value of turbidimetric activity of plasma pancreatic lipase.

We examined the incidence and spectrum of pancreatic disease in pediatric systemic lupus erythematosus (SLE). We measured serum immunoreactive cationic trypsinogen (IRT) in 185 samples obtained from 35 patients with SLE. Fifteen patients (43%) had elevated IRT levels on at least one occasion. Serum samples were obtained in 20 of 35 patients before start of treatment. Seven of these 20 patients (35%) had elevated IRT levels at diagnosis, which slowly returned to normal as their disease was controlled with treatment. A further 3 of these 20 patients in whom we had sera at diagnosis had elevated levels at some course during their illness. Of the remaining 15 patients in whom sera was not available at diagnosis, 5 patients had increased IRT levels on at least one occasion. We show that elevated IRT levels are common in pediatric SLE, but there was no apparent association with drugs such as prednisone and azathioprine. However, high levels of IRT at the time of diagnosis may be related to an underlying disease component such as vasculitis.

Serum amylase, pancreatic isoamylase, lipase, trypsinogen and elastase-1 were measured in 100 consecutive patients who were emergency admissions to a surgical department, and in 27 selected patients with proven acute pancreatitis who served as controls. The final diagnoses in the 100 patients of the study group were: acute pancreatitis in eight patients, other digestive diseases in 87, and urogenital tract diseases in five. In the control group, pancreas-specific enzymes were abnormally high in all patients and amylase in 26 out of 27. In the study group, all enzymes were markedly high in all eight patients with acute pancreatitis. In the remaining 92 patients, serum amylase was abnormally high in seven, and at least one pancreatic enzyme was elevated in 16. These elevations were generally mild. The diagnostic efficiency, i.e., the percentage of patients correctly classified, was 96% for pancreatic isoamylase and lipase, 93% for amylase, 91% for elastase-1, and 84% for trypsinogen. We conclude that serum lipase turbidimetric assay is the most suitable test for emergency diagnosis of acute pancreatitis, because it is highly sensitive and specific and simply and quickly performed.

Pancreatic exocrine dysfunction has been frequently recorded in protein-energy malnutrition in underdeveloped countries. In addition, the pancreas requires optimal nutrition for enzyme synthesis and potentially correctable pancreatic enzyme insufficiency may play a role in the continuation of protein-energy malnutrition. This problem has not been previously evaluated in Australian Aborigines. We have applied a screening test for pancreatic dysfunction (human immunoreactive trypsinogen [IRT] assay) to the study of 398 infants (6-36 months) admitted to the Alice Springs Hospital over a 20-month period. All infants were assessed by anthropometric measures and were assigned to three nutritional groups (normal, moderate or severely malnourished) and two growth groups (stunted or not stunted). Of the 198 infants who had at least a single serum cationic trypsinogen measurement taken, normal values for serum IRT (with confidence limits) were obtained from 57 children, who were normally nourished. IRT levels were significantly correlated with the degree of underweight but there was no correlation with the degree of stunting or age. Mean IRT levels for the moderate and severely underweight groups were significantly greater than the mean for the normal group (P less than 0.01). Seventeen children (8.6%) had trypsinogen levels in excess of the 95th percentile for the normally nourished group, reflecting acinar cell damage or ductal obstruction. We conclude that pancreatic dysfunction may be a common and important overlooked factor contributing to ongoing malnutrition and disease in malnourished Australian Aboriginal children.

Serum immunoreactive pancreatic lipase and cationic trypsinogen are elevated in young infants with cystic fibrosis (CF) and may be useful neonatal screening tests for CF. We compared lipase measured by a recently developed ELISA immunoassay with trypsinogen measured by radioimmunoassay in 70 children (ages 0.1 to 9.9 years) with CF who had various degrees of pancreatic dysfunction and in 79 similarly aged children without CF (controls). In the control children, lipase activity increased with advancing age, whereas trypsinogen showed no age-related trend. Lipase and trypsinogen were significantly elevated in the infants with CF who were younger than 1 year, irrespective of pancreatic function (trypsinogen, P less than 0.001; lipase, P less than 0.05). Sensitivities in detecting CF were 76% and 90% for lipase and trypsinogen, respectively. After the first year of life, lipase and trypsinogen values declined toward normal, the rate of decline of lipase being greater than that of trypsinogen; 67% of lipase values were within or below the normal range by 3 years, whereas 67% of trypsinogen values continued to be elevated. We conclude that trypsinogen is an excellent screening test for CF in young infants regardless of pancreatic function, and that the addition of a serum pancreatic lipase determination does not improve the accuracy of trypsinogen as a screening test for cystic fibrosis.

The kinetics and mechanism of clearance of pancreatic cationic and anionic trypsinogens from the circulation have been investigated in a rat model. 125I-labeled rat cationic trypsinogen is cleared from the bloodstream with a half-life of approximately 4 min. In contrast, 125I-labeled rat anionic trypsinogen has a half-life in the circulation of approximately 55-60 min. The major site of clearance for both enzymes is the kidney. Neither zymogen binds to plasma proteins to a significant extent over a period of three half-lives. The relative rates of clearance of these zymogens from the circulation appears to correlate with their respective isoelectric points.

We used a sensitive probe of pancreatic dysfunction, serum immunoreactive cationic trypsinogen, to study 50 infants and children with varying degrees of malnutrition. Patients were classified into subgroups according to the severity of malnutrition. Mean serum trypsinogen concentration was significantly elevated in 25 patients with "severe" malnutrition (77.4 +/- 42.0 ng/ml, P less than 0.001) and in 23 with "moderate" malnutrition (55.2 +/- 16.1 ng/ml, P less than 0.02) compared with the mean value (32.5 +/- 10.4 ng/ml) for well-nourished controls. The level of circulating trypsinogen tended to rise with increasing severity of malnutrition. There was no relationship between serum trypsinogen and other variables such as age, specific diagnosis, or mode of feeling. Elevated serum trypsinogen levels could not be attributed to renal disease or cystic fibrosis. In patients who showed an improvement in nutritional status, serum trypsinogen tended to revert toward normal. Elevated serum trypsinogen values in acutely malnourished infants and children may result from pancreatic acinar cell damage or regurgitation of enzymes from obstructed pancreatic ducts.

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P less than .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

The secretory pancreatic proteins in serum were analyzed in a group of cigarette smokers and a control group of nonsmokers before and after intravenous secretin stimulation. None of these persons had any signs of pancreatic disease. In the control group, serum total amylase activity, pancreatic isoamylase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor concentrations varied within the normal range before and after secretin injection. In contrast, the concentrations of these pancreatic proteins in all the cigarette smokers elevated from normal to abnormally high serum concentrations after secretin stimulation. The results indicate a probable toxic effect of cigarette smoking on the exocrine pancreas.

In patients with CF, serum pancreatic cationic trypsinogen has proven to be useful for newborn diagnostic screening and also as a test of pancreatic function in the older patient. However, an assay for serum anionic trypsinogen is of no value as a test of pancreatic function in CF due to an apparent artifactual elevation of this enzyme in some patients. In this study, we evaluated the extent of the abnormality in the anionic trypsinogen assay and also elucidated the nature of the interfering material. CF patients were grouped according to the presence (pancreatic insufficiency) or absence (pancreatic sufficiency) of steatorrhea. In CF infants, both serum cationic and anionic trypsinogen levels were greatly elevated. Serum cationic trypsinogen declined with age in patients with pancreatic insufficiency, reaching low or undetectable levels after 6 years. In contrast, serum anionic trypsinogen levels remained normal or elevated in 33% of those over 6 years of age. There was no age-related change in either cationic or anionic trypsinogen among the CF patients with pancreatic sufficiency, and the majority had normal or elevated levels. Serum samples from selected CF patients were separated into IgG and non-IgG fractions using Staph. Protein A columns. Immunoreactive cationic and anionic trypsinogen were detectable in the non-IgG fractions of sera from CF infants and older patients with pancreatic sufficiency. In older CF patients with undetectable serum cationic and anionic trypsinogen, no immunoreactive material was detectable in either the IgG or non-IgG fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

In 13 patients with severe pre-eclampsia mean serum concentrations of cationic trypsinogen and amylase were statistically significantly higher at 64 ng/ml and 1.6 mumol/l, respectively, than the corresponding mean serum concentrations in 30 normal pregnancies, 22 ng/ml and 1.1 mumol/l respectively. These rises exceeded the expected increased values due to the slight reduction of the renal function in the pre-eclamptic patients, and therefore indicate a concomitant injury of the pancreas.

A specific radioimmunoassay has been developed for human pancreatic cationic trypsin. The assay has been employed for the determination of immunoreactive forms of pancreatic cationic trypsin in blood. The trypsin employed as radioiodinated tracer in the assay was inactivated with tosyl-L-lysine chloromethyl ketone (TLCK) to prevent binding of the tracer to the serum inhibitors while maintaining its immunoreactivity. The average normal serum level determined was 26 ng/ml, with a range of 12--41 ng/ml. Eight of nine patients with acute pancreatic inflammation had at least a 15-fold elevation of total serum immunoreactive cationic trypsin. Cationic trypsinogen and cationic trypsin bound to alpha1-antitrypsin cross-react strongly in the radioimmunoassay. Thus it is possible to measure these potential molecular forms of cationic trypsin in serum. When normal human serum was fractionated on Sephadex G-200, all of the immunoreactive material eluted as a single peak of approximately 23,000 mol wt. No cationic trypsin could be detected in association with alpha1-antitrypsin or alpha2-macroglobulin. The 23,000-mol-wt peak was definitively shown to contain trypsinogen by affinity chromatography and by activation with human enteropeptidase. The identification of cationic trypsinogen in blood implies that the zymogen is secreted into the circulation by the pancreas rather than entering the bloodstream via absorption from the intestine.

To assess the relation between circulating cathodic trypsinogen (CT) levels and exocrine pancreatic function, and to compare the radioimmunological with the enzymatic measurement of duodenal trypsin, we evaluated exocrine pancreatic function in 34 controls and in 32 patients with proven chronic pancreatitis (CP). There was no relation between CT and the volume rate of pancreatic secretion, nor did serum CT levels correlate with the concentration output of duodenal bicarbonate in controls. However, in CP patients, there was a low value of the correlation coefficient. A good relationship between serum CT levels and duodenal trypsin secretion was detected when the trypsin content was expressed as the mean value of both concentration and output. The enzymatic estimation of duodenal trypsin was related closely to its radioimmunological measurement, but there was better correlation of serum CT to duodenal immunoreactive than to enzymatic trypsin. In patients with CP, low levels were observed in 29% of cases with serum CT estimation, in 75% with duodenal bicarbonate, and in 63% and 79% with enzymatic and immunoreactive trypsin outputs, respectively. We conclude that serum CT levels may reflect the functioning mass of pancreatic acinar cells and that in assessing pancreatic secretory capacity, the immunoreactive measurement of trypsin excretion is more sensitive than the enzymatic measurement and as accurate as bicarbonate output.

The levels of serum immunoreactive trypsinogen and P-isoamylase in response to Bombesin intravenous infusion were evaluated in 25 controls, 18 patients with documented chronic pancreatitis, and nine subjects with nonpancreatic gastroenterological diseases. Mean immunoreactive trypsinogen peak values were significantly higher in controls and gastroenterological diseases than in chronic pancreatitis, but there was marked overlap in individual values between the three groups. As for P-isoamylase, a statistical difference was detected only between mean peak concentrations of control versus chronic pancreatitis. Integrated responses for both enzymes did not result in a better discrimination between controls, chronic pancreatitis, and gastroenterological diseases. This study confirms that evocative tests are of limited value in the diagnosis of pancreatic disease.

We evaluated the development of the exocrine pancreas in 16 healthy preterm infants (29.3 +/- 1.6 weeks). The infants were fed breast milk with formula supplements (n = 8) or formula alone (n = 8). Growth was monitored weekly for 12 weeks then at 3, 6, 9, 12 months. At the same intervals sera were determined for pancreatic lipase and cationic trypsinogen. In addition, cord blood samples were analysed from another 33 preterm (27.6 +/- 5.2 weeks) and 75 healthy full-term infants. Serum pancreatic lipase in the cord blood of term (3.7 +/- 0.4 micrograms/l) and preterm infants (1.8 +/- 0.2 micrograms/l) was significantly below values reported for older children (10.5 +/- 0.9 micrograms/l; p less than 0.001). In the preterm infant, serum lipase was also significantly lower than values obtained at term (p less than 0.001). At birth, serum trypsinogen for preterm (16.8 +/- 1.3 micrograms/l) and term infants (23.3 +/- 1.9 micrograms/l) were below those for older children (31.4 +/- 3.7 micrograms/l; p less than 0.05). Over the first 3 weeks of life, serum lipase and trypsinogen increased significantly. From 3 weeks to 12 months of age, serum trypsinogen values remained unchanged, but serum lipase increased dramatically after 10 weeks of age. Thus, at 6 and 12 months of age, the preterm infants had significantly higher serum lipase values than infants of the same age born at term. These two pancreatic enzymes appear to show independent age-related maturation in infants born before term. The rate of maturation of lipase appears to be accelerated by exposure to the extrauterine environment.