Practical Interpretation and Application of Exocrine Pancreatic Testing in Small Animals.

The pancreas remains a difficult organ to evaluate using laboratory methods alone. No single laboratory test is diagnostic of pancreatitis (chronic or acute) without other diagnostic modalities concurring with the diagnosis or ruling out other diseases. The diagnosis of pancreatitis is particularly difficult in cats, and pancreatitis often occurs with other diseases. The use of pancreatic cytology may be useful in diagnosing both inflammation and neoplasia. Exocrine pancreatic insufficiency (EPI) can be relatively easily diagnosed when clinically manifested by the measurement of trypsinlike immunoreactivity. Diagnosis is more difficult when EPI is subclinical.

NBT-PABA test to assess efficiency and kinetics of substituted proteolytic enzyme action in pancreatic duct ligated minipigs.

The NBT-PABA test is an established method for diagnosis of pancreatic exocrine insufficiency. In the present study the NBT-PABA test was used to test and compare the efficacy of two multienzyme preparations (product A and B) differing in galenic preparation in minipigs in which pancreatic exocrine insufficiency (PEI) was induced by pancreatic duct ligation. Without enzyme substitution no distinct increase in PABA was found in blood after oral administration of NBT-PABA. Administration of both enzyme preparations led to a clear dose dependent rise in PABA-concentrations in blood. Interestingly, the two preparations showed different time curves of serum PABA concentration, indicating differences in the kinetic of proteolytic enzyme action. It is concluded that the NBT-PABA test can be a very useful test for indirectly evaluating proteolytic enzyme efficacy in vivo, and also gives information about the kinetics of enzyme action, not only the end-result of enzyme action (like digestibility trials which were used traditionally). A single test is performed in a few hours and there is no need for fistulated animals.

[BT-PABA/xylose test in the cat?]. / BT-PABA-/Xylose-Test bei der Katze?

The BT-PABA/Xylose test was used in 10 healthy cats and 49 cats with chronic diarrhea. In seven cats the test was performed three times in order to investigate individual variability. There was a statistically significant difference between the control group and the patients in the mean peak concentration of xylose, but no difference between groups of different diseases. The mean peaks of PABA were not significantly different between the control group and the patient group. Due to high individual variation in healthy cats the BT-PABA/Xylose test cannot be considered to be a useful test in feline diagnosis.

Effect of exocrine pancreatic insufficiency on cobalamin absorption in dogs.

The possibility that the canine pancreas might have an important role in the physiologic absorption of cobalamin (vitamin B12) has been explored by determining the effect of exocrine pancreatic insufficiency on cobalamin absorption and by examining the subsequent influence of bovine pancreatic enzymes and canine pancreatic juice. Exocrine pancreatic insufficiency was induced by ligation of pancreatic ducts and confirmed by indirect assessment of exocrine pancreatic function. Cobalamin absorption was determined by oral administration of cyano[58Co]cobalamin and quantitation of radioactivity in blood, urine, and feces during 48 hours. Pancreatic duct ligation resulted in a significant (P less than 0.001) decrease in cobalamin absorption, which was not restored by oral administration of bovine pancreatic enzymes, despite considerable improvements in steatorrhea and in vivo proteolytic activities. In marked contrast, malabsorption of cobalamin was significantly (P less than 0.05) reversed by oral administration of canine pancreatic juice. These results indicate that pancreatic secretions have an important role in the normal absorption of cobalamin in the dog, a role that does not appear to be attributable to pancreatic enzymes, but is consistent with the existence of a pancreatic intrinsic factor in this species.

Evaluation of two forms of N-benzoyl-L-tyrosyl p-aminobenzoic acid in pancreatic function testing of dogs.

Plasma para-aminobenzoic acid (PABA) concentrations were compared in 12 dogs after oral administration of either a powdered suspension or a solution of N-benzoyl-L-tyrosyl-PABA. Peak PABA plasma concentrations were significantly higher at 30, 60 and 90 minutes after administration of the solution (P less than 0.05). As the solution may now be used as a clinical test, interpretation of the results by comparison with normal absorption curves obtained after administration of the suspension could contribute to a failure to diagnose canine exocrine pancreatic insufficiency.

Further evaluation of bentiromide in the diagnosis of canine exocrine pancreatic insufficiency.

The primary objective of this study was to evaluate the accuracy of the bentiromide test in differentiating between dogs with exocrine pancreatic insufficiency (EPI) and those with primary intestinal disease (PID). A secondary objective was to correlate the results of the commonly used diagnostic techniques with the results of the bentiromide test. This test consists of the oral administration of a synthetic peptide that is cleaved only by chymotrypsin. A subsequent rise in the plasma concentration of p-aminobenzoic acid (PABA) indicates the degree of cleavage, providing an in vivo assessment of chymotrypsin activity. Fourteen dogs with EPI and five dogs with PID were categorized on the basis of clinical signs, laboratory evaluations, and histologic examination of intestinal biopsies. Six normal dogs served as controls. The bentiromide test clearly identified the dogs with EPI and distinguished them from the dogs with PID and the control dogs. The results of the bentiromide test correlated well with the results of the clinical and laboratory evaluations. On the basis of these observations and conclusions, recommendations for the pragmatic application of the bentiromide test are offered.

Quantitative assessment of fat absorption and its diagnostic value in exocrine pancreatic insufficiency.

A new method of quantifying fat absorption based on the estimation of serum triglyceride levels is described. When long chain triglyceride (LCT) was fed to normal dogs a significant elevation of serum triglyceride concentration was recorded which was not observed in dogs with exocrine pancreatic insufficiency. When the test was repeated on the dogs with pancreatic insufficiency using the LCT together with lipase the serum triglyceride concentration increased, suggesting the failure in the initial test was caused by a deficiency in pancreatic lipase. Feeding medium chain triglyceride (MCT) did not raise the serum triglyceride levels in normal dogs.

Bentiromide:xylose test in healthy cats.

The N-benzoyl-L-tyrosyl-p-aminobenzoic acid (bentiromide):xylose test for simultaneous evaluation of pancreatic exocrine function and intestinal absorptive function was studied in 8 clinically healthy cats. Plasma p-aminobenzoic acid (PABA) and xylose concentrations were determined before, and at 30, 60, 90, 120, 150, and 180 minutes after, a solution of bentiromide (1 g/100 ml) and D-xylose (10 g/100 ml) was given orally at a dosage of 5 ml/kg of body weight. The peak plasma concentrations for PABA occurred between 60 and 120 minutes, with highest mean value at 90 minutes (7.5 +/- 3.2 micrograms/ml), and for xylose between 30 and 120 minutes, with the highest mean value at 60 minutes (42.6 +/- 17.8 mg/dl). Large SD in plasma PABA and xylose concentrations indicated marked individual variation between healthy cats. It was concluded that (i) large variations between clinically healthy cats may limit the diagnostic usefulness of the bentiromide:xylose test in the cat, and (ii) guidelines for interpretation of plasma PABA and xylose concentrations reported previously for clinically healthy dogs could not be applied to cats because values were lower in cats.

Evaluation of 60-minute blood p-aminobenzoic acid concentration in pancreatic function testing of dogs.

For evaluation of pancreatic function testing, a peptide that releases p-aminobenzoic acid (PABA) on digestion by chymotrypsin was given to clinically normal dogs and to dogs with unexplained diarrhea. Blood concentration of PABA and percentage of PABA excretion in the urine at 6 hours after oral administration were determined. One-hour blood values did not reflect pancreatic exocrine secretion as well as did the 6-hour urinary excretion values.

A method for quantitation of hepatic, pancreatic, and intestinal function in conscious Yucatan miniature swine.

A right laparotomy was performed in anesthetized miniature swine. A hepatic vein was catheterized through the diaphragmatic surface of the left lateral lobe of the liver or through the cut surface of the right lateral lobe following a partial lobectomy. Continuous wave Doppler flow cuffs were applied to the hepatic artery and portal vein. Portal vein catheterization was accomplished through a stab incision made through the center of a preplaced purse string suture. Catheters and flow cuff wires exited the abdomen at the dorsal limit of the incision and were placed in nylon packs. Sterile surgery of the right ventro-lateral cervical region allowed catheterization of the right external jugular vein and carotid artery. These catheters were passed subcutaneously to the dorsum of the neck and inserted into another nylon pack. This method allowed repetitive experiments on conscious miniature swine after recovery from surgery. It allowed accurate quantitative determination of hepatic extraction of hormones as well as extraction of production of metabolites. Rates of intestinal absorption and pancreatic hormone secretion also could be assessed.

Specificity of the BT-PABA test for the diagnosis of exocrine pancreatic insufficiency in the dog.

Exocrine pancreatic insufficiency in the dog has been assessed by the oral administration of the synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA), a specific substrate for pancreatic chymotrypsin. The subsequent assay of PABA in either the plasma or the urine clearly differentiated control animals from those with exocrine pancreatic insufficiency (EPI), the results being unaffected by combination of this pancreatic function with a xylose absorption test. Possible interference with the specificity of the peptide test for the diagnosis of EPI was examined in six animals with small intestinal disease. In a group of four animals, with features resembling chronic tropical sprue in man, the results were comparable to those of the control group. In the fifth case, however, the results were indistinguishable from those of the EPI group, the estimation of sodium PABA absorption and the assay of proteolytic activity in the duodenal juice demonstrating that this was due to defective hydrolysis of the peptide. In the sixth case, diffuse intestinal lymphosarcoma and a marked villous atrophy were associated with an apparent reduction in the absorption of sodium PABA. However, although the plasma PABA concentrations following oral BT-PABA were subnormal, they were distinctly higher than those of the EPI group. These findings suggest that small intestinal abnormalities do not affect PABA absorption sufficiently to interfere with the specificity of the peptide test for the detection of severe EPI in the dog. This insufficiency may occasionally be secondary to small intestinal disease.