triolein and Exocrine-Pancreatic-Insufficiency

Pancreatic functional status has a very strong effect on outcome in cystic fibrosis and pancreatic insufficiency requires lifelong treatment with pancreatic enzymes. Traditionally, clinical signs and symptoms have been used to decide who should be treated with pancreatic enzyme supplements; however, recent studies show that patients with cystic fibrosis are both undertreated and over-treated using this approach. This paper reviews recent progress in the development of noninvasive, indirect tests of pancreatic function for use as diagnostic tools for patients with cystic fibrosis.. Breath testing using C-labeled fat and measurement of several pancreatic enzymes in stool, such as chymotrypsin, lipase, and elastase have been explored as ways to define pancreatic functional status. Fecal elastase has good sensitivity, specificity, and positive and negative predictive value for defining severe pancreatic insufficiency in patients with cystic fibrosis and appears to be more useful than measurement of other fecal enzymes. Its role in milder pancreatic insufficiency and in disease states other than cystic fibrosis, such as chronic pancreatitis, is less clear.. Several new noninvasive, indirect tests of pancreatic function have been developed to aid in the definition of pancreatic functional status in patients with cystic fibrosis. An objective measure of pancreatic functional status should be obtained in all patients with cystic fibrosis, and the recent development of new screening tools such as fecal elastase makes this feasible.

Topics: Breath Tests; Cystic Fibrosis; Dietary Fats; Exocrine Pancreatic Insufficiency; Feces; Humans; Hydrolases; Pancreas; Pancreatic Function Tests; Triolein

The 13C-Hiolein breath test (98% [U-13C] labelled long chain triglyceride mixture (highly labelled triolein) was evaluated as a non-invasive, non-radioactive test for exocrine pancreatic insufficiency. Accuracy and clinical validity were examined with reference to both the secretin pancreozymin test and faecal fat analysis.. A secretin pancreozymin test and faecal fat analysis were performed in 46 patients, 30 with exocrine pancreatic insufficiency and 16 with normal pancreatic function. In all of these patients and in seven healthy volunteers (controls), a 13C-Hiolein breath test was performed using 2 mg/kg [U-13C] labelled Hiolein with a standard risk snack (1.5 g/kg; 25% fat). 13CO2/12CO2 enrichment in the exhaled breath was measured by isotope ratio mass spectrometry.. In patients with pancreatic steatorrhoea the 13CO2 response was below the 95% confidence interval of 13CO2 exhalation in the controls. These responses were also diminished (p < 0.001) compared with patients with impaired lipase output but normal fat excretion and with disease as well as healthy controls. There was a linear correlation between stimulated lipase output and the ratio of lipase output/13CO2 response (r = 0.95). Among the 40 patients in whom direct pancreatic function testing was clinically indicated, the sensitivity of the 13C-Hiolein test for detecting steatorrhoea was 91.7%, with a specificity of 85.7%.. In patients with pancreatic disease the 13C-Hiolein breath test reflects impaired lipase output and indicates decompensated lipolysis. The 13C-Hiolein breath test is a convenient alternative to faecal fat analysis.

Topics: Adult; Aged; Breath Tests; Carbon Isotopes; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Lipids; Male; Mass Spectrometry; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Triolein

Twenty-three outpatients with chronic pancreatitis and severe exocrine insufficiency were studied for the purpose of comparing the effect of Pancrease, Pankreon, and Pankreatin by estimation of duodenal enzyme activity, the faecal fat excretion, and the faecal 14C-triolein-3H-oleic acid test and, at the same time, to evaluate these tests when monitoring outpatients. The three preparations did not disclose any significant difference in treating steatorrhoea. Pankreatin increased the meal-stimulated duodenal enzyme activity (p less than 0.01) and caused reduction in the faecal fat excretion (p less than 0.05), whereas no change in these variables were observed with Pankreon or Pancrease. The faecal 14C-triolein-3H-oleic acid test showed significant improvement in the 14C-triolein digestion with all three preparations (p less than 0.01). The faecal 14C-triolein-3H-oleic acid test was the most reliable when monitoring outpatients.

Topics: Adult; Aged; Carbon Radioisotopes; Chronic Disease; Duodenum; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Lipid Metabolism; Male; Middle Aged; Monitoring, Physiologic; Oleic Acid; Oleic Acids; Pancreatin; Pancreatitis; Radionuclide Imaging; Triolein; Tritium

Patients with exocrine pancreatic insufficiency have steatorrhoea as well as vitamin B12 malassimilation. To investigate whether this is caused by the pancreatic insufficiency per se or whether intestinal bacterial overgrowth contributes to the condition, 10 patients with pancreatic steatorrhoea were studied. Intestinal culture was done. Lipid and vitamin B12 assimilation was estimated from faecal spot tests, using 14C-triolein and 58Co-vitamin B12 as tracers and 51CrCl3 as marker. Out of the 10 patients, 9 had either vitamin B12 malassimilation (n = 8), and/or bacterial overgrowth (n = 5). These 9 patients were retested with pancreatic enzyme therapy, with and without addition of the antibiotics metronidazole and cefalexin. The lipid assimilation was significantly increased by enzyme therapy but did not improve further on additional antibiotic treatment. The vitamin B12 assimilation did not improve significantly on enzyme therapy nor with additional antibiotic treatment.

Topics: Cephalexin; Cobalt Radioisotopes; Dietary Fats; Enzyme Therapy; Exocrine Pancreatic Insufficiency; Feces; Humans; Intestines; Metronidazole; Pancreas; Triolein; Vitamin B 12

The absorption of 14C triolein in a standard fat meal was measured in 60 controls and 66 patients with gastrointestinal disorders by 14CO2 breath sampling. A reference range based upon cumulative eight hour values of the controls was independent of height, weight, and sex. The range was of log normal distribution and declined with age (p less than 0.05). Acceptable 'within-day' and 'between-day' reproducibility was found. All patients tested with untreated coeliac disease, pancreatic insufficiency and most with symptomatic small intestinal Crohn's disease had subnormal values. Twenty per cent of those with irritable bowel syndrome had subnormal values. Patients with ulcerative colitis were all normal. The reagents used and the breath samples after collection were stable. In our experience the 14C triolein test is simple, inexpensive, and helpful in the detection of diseases associated with fat malabsorption. It is of value in monitoring the response to treatment of individual patients with coeliac disease.

Topics: Adolescent; Adult; Age Factors; Aged; Breath Tests; Carbon Radioisotopes; Exocrine Pancreatic Insufficiency; Female; Humans; Intestinal Diseases; Male; Middle Aged; Triolein

In totally pancreatectomized patients breath 14CO2 excretion after ingestion of 14C-labeled triolein was significantly increased by a granulated pancreatic enzyme preparation and was reduced when pectin was added to the enzyme supplement. In the same patients pectin reduced trypsin, lipase, and amylase activities of jejunal aspirates after a test meal supplemented with pancreatic enzyme substitution, which was shown to give good enzyme activities in the intestine. In patients with chronic pancreatitis, breath 14CO2 excretion was reduced by wheat bran, which also caused a reduction in lipase and amylase activities of duodenal aspirates after a test meal. The findings demonstrate the efficiency of treatment with a granulated pancreatic enzyme preparation in restoring intraluminal enzyme activities and fat absorption in patients with pancreatic insufficiency. They also show that pectin and wheat bran may induce fat malabsorption and inhibit digestive enzyme activities in vivo.

Topics: Adult; Amylases; Breath Tests; Dietary Fats; Dietary Fiber; Exocrine Pancreatic Insufficiency; Female; Humans; Intestinal Absorption; Lipase; Male; Middle Aged; Pancreas; Pectins; Triolein; Triticum; Trypsin

In 24 patients with malabsorption, [14C]triolein breath tests were conducted before and together with the administration of pancreatic enzymes (Pancrease, Johnson and Johnson, Skillman, N.J.). Eleven patients with pancreatic insufficiency had a significant rise in peak percent dose per hour 14CO2 excretion after Pancrease, whereas 13 patients with other causes of malabsorption had no increase in 14CO2 excretion (2.61 +/- 0.96 vs. 0.15 +/- 0.45, p less than 0.001). The two-stage [14C]triolein breath test appears to be an accurate and simple noninvasive test of fat malabsorption that differentiates steatorrhea secondary to pancreatic insufficiency from other causes of steatorrhea.

Topics: Breath Tests; Carbon Radioisotopes; Celiac Disease; Diagnosis, Differential; Exocrine Pancreatic Insufficiency; Humans; Malabsorption Syndromes; Pancreatin; Triolein

Three substrates labeled with nonradioactive 13C have been employed to establish a trilogy of noninvasive breath tests to detect fat malabsorption in children and then to differentiate the etiology of the steatorrhea. Administration of 17 mg/kg of (13C)triolein Lipomul (The Upjohn Co., Kalamazoo, Mich.) resulted in a peak excretion rate of 13CO2 greater than 2.7% dose/h in 10 normal subjects (mean value 4.96 +/- 2.2% dose/h) whereas all 17 subjects with fat malabsorption were below this value (mean value, 0.75% +/- 0.63% dose/h); p less than 0.001). For the detection of fat malabsorption, the discriminative value of (13C)triolein was superior, 100% sensitive, and 89% specific, while the use of (13C)palmitic acid (17 mg/kg) or (13C)trioctanoin (7.5 mg/kg) alone yielded both false-positive and false-negative results. In 6 out of 6 cases, pancreatic insufficiency could be differentiated from mucosal disease (7 patients) or bile salt deficiency (4 patients) by the presence of abnormal triolein or trioctanoin breath tests, or both but normal palmitic acid breath tests. However, further differentiation of mucosal disorders from bile salt disorders could not be achieved using either a single- or a multiple-substrate breath test. The use of the single triolein breath test in children offers an attractive, sensitive alternative to conventional fecal fat measurements to establish the presence of steatorrhea, and when using 12C-lipid with multiple substrates, the tests are capable of providing additional insight into the mechanism of fat malabsorption.

Topics: Adolescent; Biliary Tract Diseases; Breath Tests; Caprylates; Carbon Isotopes; Celiac Disease; Child; Child, Preschool; Exocrine Pancreatic Insufficiency; Humans; Infant; Intestinal Diseases; Palmitic Acid; Palmitic Acids; Triglycerides; Triolein

We used a rat model to investigate the phenomenon of increased steatorrhea associated with administration of calcium or magnesium containing antacids in humans with pancreatic insufficiency. Adult male rats with bile and pancreatic duct ligation were fed test meals containing 56 mumol [14C]triolein (0.5 ml), synthetic human bile (1.0 ml, 100 mumol bile salts, 75% glycine and 25% taurine conjugates, and 14.5 mumol lecithin), pancreatic enzymes (0.5 ml), and antacids (1.0 ml). The percent lipid malabsorbed when antacids were fed in addition to the test meal was: control 19.3 +/- 1%, NaHCO3 15.3 +/- 1% (P less than 0.05 vs. control), Al(OH)3 18.3 +/- 2%, Mg(OH)2 38.2 +/- 2% (p less than 0.001 vs. control), and CaCO3 42.4 +/- 1% (p less than 0.001 vs control). With NaCl, Al(OH)3, and NaHCO3 the malabsorbed fat was primarily triolein, whereas with Ca++ or Mg++ the majority of the lipid recovered was oleic acid. Calcium or magnesium administration was associated with precipitation of glycine-, but not taurine-, conjugated bile salts in the small intestine. When calcium was administered to animals in which the bile consisted entirely of glycine-conjugated bile salts, the lipid recovered (64.0 +/- 3% malabsorption) was almost entirely triolein suggesting reduced lipolysis. These studies suggest that these divalent cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.

Topics: Animals; Antacids; Bile Acids and Salts; Calcium; Celiac Disease; Dietary Fats; Exocrine Pancreatic Insufficiency; Intestinal Absorption; Lipolysis; Magnesium; Male; Oleic Acid; Oleic Acids; Rats; Rats, Inbred Strains; Triolein

It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.

Topics: 4-Aminobenzoic Acid; Amylases; Carbon Radioisotopes; Exocrine Pancreatic Insufficiency; Fats; Feces; Humans; Intrinsic Factor; Lipase; Malabsorption Syndromes; Pancreas; Pancreatic Function Tests; Pancreatin; Secretin; Triolein; Vitamin B 12

Topics: Celiac Disease; Cholelithiasis; Crohn Disease; Enteritis; Exocrine Pancreatic Insufficiency; Hyperlipidemias; Hyperlipoproteinemia Type I; Hyperlipoproteinemia Type III; Iodine Isotopes; Liver Diseases; Pancreatic Neoplasms; Pancreatitis; Radiometry; Sprue, Tropical; Triolein