alpha-chymotrypsin and Exocrine-Pancreatic-Insufficiency

The aim was to review evidence about diabetes secondary to hereditary pancreatitis, seeking novel diagnostic and treatment features.. Hereditary pancreatitis (HP) is an autosomal dominant condition, characterized by recurrent episodes of acute pancreatitis, progression to fibrosis, and chronic pancreatitis. Clinical presentation includes diabetes of the exocrine pancreas (DEP). HP prevalence ranges from 0.3 to 0.57 per 100,000 people, with up to 80% of these develop DEP. This condition often requires specific interventions: with regard to metabolic control, metformin is the first choice for those with mild DEP, and for those in advanced disease, insulin is considered the first-line therapy. Insulin analogues and insulin pump therapy are preferred due to the brittle glycemic pattern and risk of hypoglycemia. In case of exocrine insufficiency, pancreatic enzyme replacement therapy is recommended. Pancreatic polypeptide administration is a promising novel treatment feature. DEP due to HP appears to be a misdiagnosed condition. The requirement of specific management demonstrates the importance of this matter; therefore, appropriate recognition and classification are important.

Topics: Acute Disease; Carcinoma, Pancreatic Ductal; Chymotrypsin; Diabetes Complications; Diabetes Mellitus; Exocrine Pancreatic Insufficiency; Fibrosis; Humans; Pancreas, Exocrine; Pancreatic Neoplasms; Pancreatitis, Chronic; Recurrence; Risk Factors; Trypsin; Trypsin Inhibitor, Kazal Pancreatic

Exocrine pancreatic insufficiency in children can lead to lifelong complications related to malnutrition and poor growth. The clinical presentation can be subtle in the early stages of insufficiency as the large functional capacity of the pancreas is gradually lost. The pediatrician plays a crucial role in the early identification of these children to ensure a timely referral so that a diagnosis can be made and therapy initiated. Early nutritional therapy allows for prevention and correction of deficiencies, which leads to improved outcomes and survival. When insufficiency is suspected, the workup should start with an indirect test of exocrine pancreatic function, such as fecal elastase, to establish the diagnosis. Once a diagnosis is established, further testing to delineate the etiology should be pursued, with cystic fibrosis being high on the differential list and assessed for with a sweat test. Assessment of anthropometry at every visit is key, as is monitoring of laboratory parameters and physical examination findings that are suggestive of malabsorption and malnutrition. The mainstay of management is administration of exogenous pancreatic enzymes to facilitate digestion and absorption. [Pediatr Ann. 2019;48(11):e441-e447.].

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Anus, Imperforate; Child; Child Nutrition Disorders; Chymotrypsin; Congenital Bone Marrow Failure Syndromes; Cystic Fibrosis; Dietary Fats; Ectodermal Dysplasia; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Feces; Growth Disorders; Hearing Loss, Sensorineural; Humans; Hypothyroidism; Intellectual Disability; Lipid Metabolism, Inborn Errors; Mitochondrial Diseases; Muscular Diseases; Nose; Nutrition Assessment; Pancreas; Pancreatic Diseases; Pancreatic Elastase; Pancreatic Function Tests; Pancreatitis, Chronic; Shwachman-Diamond Syndrome; Steatorrhea; Trypsinogen

Several non invasive tests are available to assess pancreatic function, but no one is routinely used in clinical practice to diagnose chronic pancreatitis, due to their poor sensitivity in diagnosing mild pancreatic insufficiency. (13)C breath tests share the same limits of the other non invasive functional tests, but the mixed triglyceride breath test seems to be useful in finding the correct dosage of enzyme substitutive therapy to prevent malnutrition in patients with known pancreatic insufficiency.

Topics: Biomarkers; Breath Tests; Carbon Dioxide; Carbon Radioisotopes; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Gases; Humans; Pancreas, Exocrine; Pancreatic Elastase; Pancreatic Function Tests; Predictive Value of Tests; Prognosis

Economic function of the exocrine pancreas is based on non-parallel synthesis, transport and secretion of pancreatic enzymes during basal state and postprandially. Reserve capacity of acinar cells is also augmented by adaptation to the diet as well as by regeneration. In mild pancreatic insufficiency complex dietetic considerations help to maintain the necessary secretory capacity of the pancreas. In severe cases effective substitution therapy is mandatory and increasing lipase survival by dietetic maneuvers, by optimizing trypsin and chymotrypsin levels as well as acid and bile secretion can significantly ameliorate results of replacement therapy of steatorrhea. However, in painful chronic pancreatitis high protease activities seem to be beneficial. Individual replacement therapy with pancreatin preparations adapted to the requirements of the patient has to be chosen in difficult cases.

Topics: Chymotrypsin; Exocrine Pancreatic Insufficiency; Humans; Pancreatic Juice; Pancreatitis; Trypsin

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

To establish the diagnosis of acute pancreatitis the estimation of amylase in serum and urine, lipase and radio-immunoreactive trypsin in the serum are useful. Lipase estimations are more helpful than measuring amylase values. Trypsin-RIA-tests are increasingly important adults. But in chronic pancreatitis and inborn secretory insufficiencies of the pancreas these methods are less helpful. PABA-test, pancreolauryl-test (PLT), and the estimation of chymotrypsin in faeces are screening procedures, although their results correlate well amongst each other. As compared to the chymotrypsin estimation in faeces PABA test and PLT allow for some semiquantitative estimation of the secretory function and dynamics of the gland. The influence of malabsorption, liver and kidney diseases on these parameters is not yet quite clarified. Besides screening they are undoubtedly of value for judging the course and therapy of cystic fibrosis, Shwachman-syndrome, iatrogenic lesions by cytostatics (immunosuppressives and corticosteroids). Quantitative estimations of fat in faces and the pancreozymin test are no longer of significance.

Topics: 4-Aminobenzoic Acid; Acute Disease; Aminobenzoates; Amylases; Child; Child, Preschool; Chronic Disease; Chymotrypsin; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Feces; Humans; Infant; Lipase; Pancreatic Function Tests; Pancreatitis; Trypsin

Topics: 4-Aminobenzoic Acid; Alkaline Phosphatase; Amylases; Animals; Atrophy; Carnivora; Chymotrypsin; Dog Diseases; Dogs; Exocrine Pancreatic Insufficiency; Feces; Lipase; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; 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

Nutrient malabsorption is a negative prognostic factor in acquired immunodeficiency syndrome and recent studies have shown that pancreatic insufficiency is a codetermining factor of malabsorption.. To evaluate the effectiveness of open-label oral pancreatic enzyme supplementation therapy in acquired immunodeficiency syndrome patients with fat malabsorption.. Twenty-four consecutive patients with human immunodeficiency virus infection and fat malabsorption were recruited (11 males, 13 females; median age, 9.1 years). Faecal fat loss was evaluated by steatocrit assay at entry to the study (T-0), after 2 weeks (T-1) without pancreatic enzyme treatment and after a further 2 weeks (T-2) of treatment with pancreatic extracts (Creon 10 000 at a dose of 1000 units of lipase per gram of ingested dietary fat). Faecal elastase-1 and chymotrypsin were assayed at entry.. Six patients (25%) had abnormally low elastase-1 and/or chymotrypsin faecal concentration. In all patients, steatocrit values were elevated at both T-0 and T-1. Five patients proved intolerant to pancreatic enzyme treatment because of the onset of abdominal pain, and therapy was discontinued. In the 19 patients who concluded the study, steatocrit values during pancreatic enzyme treatment (T-2) were significantly lower than at entry (P < 0.0001). At T-2, in eight of 19 patients, steatocrit values were within the normal limit and the frequency of cases cured or improved on pancreatic enzyme therapy (at T-2) was significantly higher than that observed during the previous study period without enzyme treatment (T-1) (P < 0.01). A positive significant correlation was found between steatocrit values at entry and the Centers for Disease Control class (P < 0.0005); also, the decrease in steatocrit values during pancreatic enzyme therapy (difference between steatocrit value at T-2 and steatocrit value at T-0) positively correlated with the Centers for Disease Control class (P < 0.05).. This pilot, open-label study showed that pancreatic enzyme supplementation therapy is highly effective in reducing faecal fat loss in human immunodeficiency virus-infected patients with nutrient malabsorption. Further double-blind studies must be undertaken to verify these results and, if they are confirmed, pancreatic enzymes can be added to our weapons in the fight against human immunodeficiency virus-associated nutrient malabsorption.

Topics: Adolescent; Celiac Disease; Child; Child, Preschool; Chymotrypsin; Exocrine Pancreatic Insufficiency; Fats; Feces; Female; HIV Infections; Humans; Infant; Intestinal Absorption; Male; Pancreatic Elastase; Pancreatic Function Tests; Pancrelipase; Treatment Outcome

During two treatment periods (4 weeks each), serum immunoreactive trypsin (IRT), immunoreactive human lipase in stool (IRL), and chymotrypsin (CT) activity in stool were determined in 16 cystic fibrosis patients and compared with fecal fat excretion (72-h sampling). Fecal fat estimation revealed mild to severe steatorrhea in all 16 patients (X = 13.7 +/- 9.0 g/24 h) in at least one study period. Stool fat excretion was highest in underweight adolescents and adults. Comparison of IRT and IRL with stool fat values showed no significant statistical correlation. IRT values revealed an inverse exponential correlation with age, with a steep decline at the age of 5 years. CT levels were very high in 14 of our 16 patients during supplementation therapy, whereas 2 patients showed subnormal CT values. We conclude that since indirect parameters of pancreatic function do not correlate with stool fat excretion, stool fat remains the best indirect parameter for the assessment of pancreatic insufficiency in cystic fibrosis. Leaving pancreatic enzyme supplementation in cystic fibrosis patients on the basis of normal serum trypsin or fecal lipase values does not appear to be adequate.

Topics: Adolescent; Adult; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Double-Blind Method; Exocrine Pancreatic Insufficiency; Feces; Female; Gastrointestinal Agents; Humans; Lipase; Lipids; Male; Pancreas; Pancreatin; Trypsin

In spite of having been the object of a number of studies, the association of morphologic and functional alterations of the pancreas with liver cirrhosis is as yet controversial. Therefore, the authors have studied exocrine pancreatic function in 40 patients: 8 with alcoholic cirrhosis, 18 with non-alcoholic cirrhosis, and 14 without evidence of hepatobiliary and pancreatic pathology. Pancreatic function was studied by the fecal chymotrypsin test which is sufficiently sensitive and specific and has been preferred in view of its practicability and non-invasiveness. Analysis of the results showed pathologic values to be significantly more frequent in subjects with alcoholic cirrhosis (50%, p < 0.05) compared to non-alcoholic cirrhotics (11.11%) and to controls (7.2%). These findings go to show that pancreatic exocrine deficit is frequently associated with alcoholic cirrhosis, thus confirming what has already been known about the pathogenetic role of alcohol which is apt to provoke both hepatic and pancreatic damage. Finally, it should be pointed out that pancreatic exocrine deficit is a purely functional alteration without clinical manifestations.

Topics: Aged; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Pancreatic Diseases; Pancreatic Function Tests

The effect on steatorrhoea of a pH-sensitive enteric-coated pancreatic preparation (Eurobiol 25,000) was compared with a conventional pancreatic enzyme preparation (Eurobiol) in six adult patients with exocrine pancreatic insufficiency. In addition, the fate of orally ingested pancreatic enzymes in the upper digestive tract was evaluated by measuring gastric and duodenal pH, amount of enzymes in the stomach, duodenal enzyme output, and fat absorption at the angle of Treitz for the 4 hours following a standard meal. When compared with placebo, Eurobiol and Eurobiol 25,000 reduced daily faecal fat excretion by 24% (not significant) and 43% (P less than 0.05), respectively. With the conventional preparation, enzyme output and fat absorption at the duodeno-jejunal flexure were significantly improved (P less than 0.05). Marked inter-individual differences in duodenal enzyme recovery (lipase 3% to 80%; chymotrypsin 26% to 100%) and, consequently, in the reduction of steatorrhoea (0% to 67%) were observed, with the gastric emptying rate emerging as a key determinant factor. With the enteric-coated preparation, enzyme output and fat absorption at the duodenojejunal flexure were not significantly improved. Discrepancy between the marked reduction of faecal fat excretion and the low duodenal enzyme recovery could indicate that enzyme delivery from microtablets occurs further down in the small bowel. Efficacy of enteric-coated preparations could be enhanced by adding unprotected enzymes, especially in patients with rapid gastric emptying.

Topics: Adult; Bile Acids and Salts; Celiac Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Gastric Emptying; Humans; Lipase; Male; Middle Aged; Pancreatic Extracts; Tablets, Enteric-Coated

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

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

The study evaluates two methods of assay of fecal chymotrypsin (titrimetric and spectrophotometric method) as an index of exocrine pancreatic function. The assay was performed on 101 control subjects and 128 cystic fibrosis (CF) patients by the first method, and 75 controls and 102 CF patients by the second method. CF subjects were subdivided into four groups based on pancreatic function: total pancreatic insufficiency in the first group, partial pancreatic insufficiency in the second group, normal pancreatic function in the third group, and pancreatic insufficiency plus enzymatic treatment in the fourth group. Fifty-four CF patients were examined in the first group, 27 in the second group, 19 in the third group, and 28 in the fourth group by the titrimetric method; 23, 25, 50, and 65, respectively by the spectrophotometric method. The spectrophotometric method was highly reproducible and more sensitive and specific. With such a method the assay on stool random sampling correlated with the duodenal output of chymotrypsin after hormonal stimulation as well as fecal output of 72 h. The test had sensitivity and specificity of 100% if referred to CF patients with total pancreatic insufficiency. It was calculated that CF patients with normal fecal chymotrypsin have a probability of 76% to have a normal pancreatic function and a probability of 24% to have a partially compromised pancreatic function. The assay separates distinctly CF patients with a fat absorption coefficient greater than 90% from those with a coefficient less than 90%. The test is proposed for current clinical use in diagnosis and treatment of pancreatic insufficiency in cystic fibrosis.

Topics: Adolescent; Adult; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Dietary Fats; Duodenum; Exocrine Pancreatic Insufficiency; Feces; Humans; Infant; Methods; Pancreas

Altered pancreatic exocrine function can be observed in patients with type 1 or type 2 diabetes. In the present study, we evaluated the potential nutritional consequences of this dysfunction.. Serum concentrations of nutritional markers, including albumin, cholesterol, triacylglycerol, vitamins A, D, and E, were assessed in a cohort of 468 patients (137 with type 1 diabetes and 331 with type 2 diabetes), after exclusion of the patients with a CRP > 10 mg/l. These patients were compared with 47 patients with diseases of the exocrine pancreas and diabetes (type 3c diabetes or pancreatogenic diabetes). Fecal elastase-1 and chymotrypsin concentrations were measured and patients with type 1 and type 2 diabetes were divided into three groups according to whether zero (group NN), one (group LN), or both (group LL) concentrations were decreased.. Several markers differed significantly between the groups of patients, including BMI, albumin, phosphorus, and fat-soluble vitamins. Patients with pancreatogenic diabetes had markedly more profound alterations than patients with type 1 or type 2 diabetes and altered exocrine function. However, patients with type 1 or type 2 diabetes and decreased concentrations of both elastase-1 and chymotrypsin had lower albumin, phosphorus, and vitamin A than patients with normal pancreatic exocrine function.. Modest nutritional alterations were found in patients with type 1 or type 2 diabetes and altered exocrine function. Patients with type 1 or type 2 diabetes and altered exocrine function may thus deserve to be screened for nutritional deficiencies.

Topics: Adult; Aged; Biomarkers; Chymotrypsin; Diabetes Complications; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Male; Middle Aged; Pancreatic Elastase; Vitamins

Exocrine pancreatic insufficiency (EPI) can have a significant impact on a child's growth and nutrition. Our aim was to evaluate the utility of direct endoscopic pancreatic function testing (ePFT) in pediatrics.. A single-center retrospective chart review was performed of children who underwent ePFT from December 2007 through February 2015. Endoscopic pancreatic function testings were performed by 1 of 2 methods: (1) intravenous cholecystokinin, followed by the collection of a single duodenal aspirate at 10 minutes, or (2) intravenous cholecystokinin or secretin, followed by the collection of 3 duodenal aspirates at a 5, 10, and 15 minutes. Samples were tested for pH and enzyme activities.. A total of 508 ePFTs were performed (481 single-sample tests, 27 multiple-sample tests). Based on the multiple-sample group, enzyme levels for chymotrypsin, amylase, and lipase peaked at 5 minutes, followed by a decrease in activity over time. Exocrine pancreatic sufficiency was identified in 373 (73.4%) and EPI in 93 (18.3%). Exocrine pancreatic sufficiency analysis found all pancreatic enzyme activities significantly increase with age: trypsin, chymotrypsin, amylase, and lipase, (P < 0.05).. Endoscopic pancreatic function testing can be used in the evaluation of EPI in children. Normative data suggest that pancreatic enzyme activities mature with age.

Topics: Amylases; Child; Child, Preschool; Chymotrypsin; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Female; Humans; Infant; Lipase; Male; Pancreatic Function Tests; Retrospective Studies; Trypsin

Decreased function of the exocrine pancreas is frequent in patients with diabetes. Our aim was to investigate clinical correlates of pancreatic exocrine failure in patients with diabetes.. We investigated exocrine function by assaying both elastase-1 concentration and chymotrypsin activity in 667 patients. We conducted separate analysis on patients with Type 1 diabetes and patients with Type 2 diabetes. Patients were separated into three groups according to whether both elastase-1 concentration and chymotrypsin activity were normal, or one or both were altered.. A total of 667 consecutive patients were analysed, including 195 with Type 1 and 472 with Type 2 diabetes. Elastase-1 concentration was <200 μg/g in 23% of the patients. Chymotrypsin activity was <6 U/g in 26% of the patients. In 66% of the patients elastase-1 concentration was >200 ug/g and chymotrypsin activity >6 U/g. One test was below threshold in 19%, both in 15%. In patients with Type 1 diabetes, the three groups defined by results of elastase-1 concentration and chymotrypsin activity differed with regard to duration of diabetes and prevalence of glutamic acid decarboxylase antibodies, but not BMI or HbA(1c) , or prevalence of retinopathy, neuropathy, nephropathy or vascular disease. In patients with Type 2 diabetes, the three groups differed with regard to BMI, use of insulin and vascular disease, but not known duration.. Factors associated with pancreatic exocrine failure differ in patients with Type 1 diabetes compared with patients with type 2 diabetes. In patients with Type 2 diabetes, association of decreased pancreatic exocrine function with BMI and vascular disease suggests a role of pancreatic arteriopathy.

Topics: Adult; Aged; Antibodies; Body Mass Index; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exocrine Pancreatic Insufficiency; Feces; Female; Glutamate Decarboxylase; Humans; Male; Middle Aged; Pancreas, Exocrine; Pancreatic Elastase

Yarrowia lipolytica lipase has been assumed to be a good candidate for the treatment of fat malabsorption in patients with pancreatic insufficiency. Nevertheless, no systematic studies on its stability under physiological conditions pertaining to the human GI (gastrointestinal) tract have been published. Stability of various Y. lipolytica lipase powder formulations at various physiological pH values as well as the effect of digestive proteases and bile salts on enzyme activity were investigated. Results were compared with those obtained from another competing fungal lipase sourced from Candida rugosa. Among the studied formulations, Y. lipolytica lipase stabilized with gum arabic and skimmed milk powder was the most promising powder formulation. Under acidic conditions (pH 3-5), this formulation showed higher stability than those observed with the other Y. lipolytica lipase formulations and C. rugosa lipase. In addition, in the presence of gum arabic and skimmed milk powder as additives, Y. lipolytica lipase exhibited markedly higher resistance to pepsin, trypsin and chymotrypsin actions. Resistance to proteolytic degradation by digestive proteases was also by far higher than that observed with C. rugosa lipase. Similar behaviour was, however, observed when these two fungal lipases were incubated with increased concentrations of bile salts. Residual lipase activity of both fungal lipases showed a slight decrease in NaTDC (sodium taurodeoxycholate) concentration above 4 mM. Consequently, Y. lipolytica lipase formulated with gum arabic and milk powder seemed to have great potential for use as a therapeutic tool for patients with pancreatic insufficiency.

Topics: Animals; Bile Acids and Salts; Candida; Chemistry, Pharmaceutical; Chymotrypsin; Enzyme Replacement Therapy; Enzyme Stability; Exocrine Pancreatic Insufficiency; Gum Arabic; Hydrogen-Ion Concentration; Lipase; Milk; Pepsin A; Trypsin; Yarrowia

Various pancreatic enzyme preparations are used for the treatment of pancreatic insufficiency but their bioequivalence is often unknown.. To determine in vitro the pH-dependent release and acid resistance of enzymes from three commercially available pancreatin capsules, two containing enteric-coated (Creon 25000; Eurobiol 25000) and one uncoated (Eurobiol 12500) microspheres.. Dissolution experiments were performed at pH values ranging from 4.0 to 5.8. Lipase, chymotrypsin and amylase activities were measured in the solution as a function of time.. Eurobiol 25000 started to release its enzymes significantly at pH 5.0 (t(1/2) = 71 min), whereas the enzymes from Creon 25000 were only released at higher pH value (5.4; t(1/2) = 49.2 min). Unlike chymotrypsin, lipase and amylase were highly sensitive to acidic conditions at the lowest pH values tested. Both enzymes were also found to be sensitive to proteolytic inactivation at the highest pH values tested. Overall, Eurobiol 25000 released higher amounts of active amylase and lipase than Creon 25000 at the pH values usually found in duodenal contents. The uncoated Eurobiol 12500 preparation was, however, the only one that could immediately release rather high levels of active chymotrypsin and lipase at low pH (4.5).. These findings suggest that pH-sensitive enteric-coated pancreatin products containing similar amounts of enzymes might not be bioequivalent depending on the pH of duodenal contents.

Topics: Amylases; Animals; Biological Availability; Chymotrypsin; Duodenum; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Humans; Hydrogen-Ion Concentration; Lipase; Microspheres; Pancreatic Extracts; Pancrelipase; Solubility; Tablets, Enteric-Coated

Pancreatic resections for benign diseases may lead to long-term endocrine/exocrine impairment. The aim of this study was to compare postoperative and long-term results after different pancreatic resections for benign disease.. Between 1990 and 1999, 62 patients underwent pancreaticoduodenectomy (PD), 36 atypical resection (AR) and 64 left pancreatectomy (LP) for benign tumours. Exocrine and endocrine pancreatic function was evaluated by 72-h faecal chymotrypsin and oral glucose tolerance test.. The incidence of pancreatic fistula was significantly higher after AR than after LP (11 of 36 versus seven of 64; P = 0.028). The long-term incidence of endocrine pancreatic insufficiency was significantly lower after AR than after PD (P < 0.001). Exocrine insufficiency was more common after PD (P < 0.001) and LP (P = 0.009) than after AR. The probability of developing both endocrine and exocrine insufficiency was higher for PD and LP than for AR (32, 27 and 3 per cent respectively at 1 year; 58, 29 and 3 per cent at 5 years; P < 0.001).. Different pancreatic resections are associated with different risks of developing long-term pancreatic insufficiency. AR represents the best option in terms of long-term endocrine and exocrine function, although it is associated with more postoperative complications.

Topics: Aged; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Risk Factors; Treatment Outcome

To study fecal elastase-1 (E1F) and chymotrypsin (ChT) in stools for the diagnosis of pancreatic insufficiency in pediatric practice.. E1F and ChT were measured in stools of 198 children divided in 3 groups: 49 children without any digestive disease (group A), 71 children with pancreatic diseases (group B), and 78 children with non-pancreatic digestive diseases (group C).. In group B, E1F values were very low in 64 children and normal in 7 children without pancreatic insufficiency (6 children with cystic fibrosis and 1 with chronic pancreatitis). ChT values were normal in children without pancreatic insufficiency but also in half of children treated with pancreatic enzymes. Decreased E1F values were seen in 2 children (4%) in the group A and 22 children (28%) in the group C, especially those with acute gastroenteritis or celiac disease.. E1F is a simple, non-invasive, useful tool for the diagnosis of pancreatic insufficiency in children with growth failure or chronic diarrhea, and those with cystic fibrosis. Nevertheless, low values may be found in diseases with villous atrophy or very liquid stools.

Topics: Adolescent; Biomarkers; Child; Child, Preschool; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Infant, Newborn; Male; Pancreatic Elastase; Pancreatic Function Tests

Topics: Adolescent; Adult; Child; Child, Preschool; Chymotrypsin; Diet, Vegetarian; Exocrine Pancreatic Insufficiency; Feces; Humans; Middle Aged; Pancreatic Elastase; Pancreatic Function Tests; Secretin; Sensitivity and Specificity

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

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

The secretin-cholecystokinin test is the "gold standard" to evaluate exocrine pancreatic function. But this direct duodenal intubation test is invasive, particularly in children, time-consuming, and expensive. For several years, indirect noninvasive tests of pancreatic insufficiency have been developed, such as fecal chymotrypsin (FChT) and fecal elastase-1 (FEL-1) measurements. Generally, elastase-1 is truly admitted to be the most relevant test of exocrine pancreatic status. However, so far, no consensus for stool collection protocol exists. The aim of our study was to investigate the diagnostic advantage from measuring fecal proteases in stool samples collected for two or three consecutive days in comparison to one single stool sample collected at random.. A total of 69 children were divided into group A (stool samples collected for three consecutive days) and group B (stool samples collected for two consecutive days). These two groups included pancreatic-sufficient patients (PS) and severe pancreatic-insufficient patients (PI). One single determination of fecal chymotrypsin activity and of fecal elastase-1 concentration was realized on each stool.. The same relatively important intraindividual variability of fecal proteases was observed in group A and B (mean coefficients of variation (CVs) 36% vs. 40.2% for chymotrypsin, 22.2% vs. 26.8% for elastase-1). No significant PS or severe PI diagnostic discordance was observed between 1, 2, or 3 days of stool collections.. Our study clearly shows that the determination of fecal proteases on one single stool collected at random is sufficient to evaluate pancreatic exocrine status for PS and severe PI.

Topics: Adolescent; Child; Child, Preschool; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Infant, Newborn; Male; Pancreas, Exocrine; Pancreatic Elastase; Random Allocation; Reproducibility of Results

Exocrine pancreatic function in patients with cystic fibrosis (CF) can be evaluated by direct and indirect tests. In pediatric patients, indirect tests are preferred because of their less invasive character, especially in CF patients with respiratory disease. Fecal tests are noninvasive and have been shown to have a high sensitivity and specificity. However, there is no comparative study in CF patients. Therefore, the aim of the present study was to compare the sensitivity and the specificity of the fecal elastase-1 (E1) test with the fecal chymotrypsin (ChT) test in a large cohort of CF patients and healthy subjects (HS).. One hundred twenty-three CF patients and 105 HS were evaluated. In all subjects, E1 concentration and ChT activity were measured. In the CF group, fecal fat excretion was also determined. The sensitivity and specificity of the fecal E1 test and ChT test were compared.. With a cutoff level of 3 U/g, ChT specificity in HS was similar to that of E1, but E1 sensitivity in CF patients was significantly higher (90.2% vs 81.3%). With a cutoff level of 6 U/g, ChT and E1 sensitivity in CF patients was identical, but E1 specificity in HS was again significantly higher (98.1% vs 90.5%). In all CF patients with severe steatorrhea (>15 g/d), E1 concentrations were abnormal and ChT activity was lower than 3 U/g. In contrast, in pancreatic-sufficient patients and patients with mild steatorrhea (< or =15 g/d), the E1 sensitivity was significantly higher compared with ChT (69.2% vs 41.0%).. The fecal E1 test is superior to fecal ChT determination in the assessment of CF pancreatic involvement in pancreatic-sufficient patients and those patients with mild steatorrhea.

Topics: Adolescent; Adult; Celiac Disease; Child; Child, Preschool; Chymotrypsin; Clinical Enzyme Tests; Colorimetry; Cystic Fibrosis; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Male; Pancreas; Pancreatic Elastase; Pancreatic Function Tests; Sensitivity and Specificity

In recent years, a number of studies have been carried out, the results of which suggest that the exocrine function of the pancreas is significantly more frequently impaired than is the case in healthy controls. In particular when a patient presents with gastrointestinal complaints of unclear origin, unexplained fluctuations in blood sugar, or loss of weight, the possibility of pancreatic exocrine insufficiencyshould be included in differential diagnostic considerations. Abnormal stools and intolerance of dietary fat can be clarified on the basis of a careful history. The diagnosis is confirmed with the aid of simple laboratory tests, for example the chemotrypsin test or the detection of elastase 1 in the stools. By way of treatment, pancreatic enzyme replacement can be applied.

Topics: Adolescent; Adult; Child; Cholangiopancreatography, Endoscopic Retrograde; Chymotrypsin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Enzyme Therapy; Exocrine Pancreatic Insufficiency; Feces; Humans; Pancreas; Pancreatic Elastase; Prevalence

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

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

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

Treatment of human exocrine pancreatic insufficiency is suboptimal. This study assessed the effects of bacterial lipase, porcine lipase, and diets on carbohydrate, fat, and protein absorption in pancreatic-insufficient dogs.. Dogs were given bacterial or porcine lipase and 3 diets: a 48% carbohydrate, 27% fat, and 25% protein standard diet; a high-carbohydrate, low-fat, and low-protein diet; or a low-carbohydrate, high-fat, and high-protein diet (66%/18%/16% and 21%/43%/36% calories).. With the standard diet, coefficient of fat absorption increased dose-dependently with both lipases (P < 0.05), but more fat was absorbed with porcine lipase (P < 0.05); 600, 000 IU of bacterial lipase (240 mg) and 300,000 IU of porcine lipase (18 g) nearly abolished steatorrhea. With 300,000 IU of bacterial lipase or 135,000 IU of porcine lipase, fat absorption was greater with the high-fat and -protein diet (P < 0.05 vs. low-fat and -protein diet). There were no interactions among carbohydrate, fat, and protein absorption.. Correcting steatorrhea requires 75 times more porcine than bacterial lipase (18 vs. 240 mg). High-fat and high-protein diets optimize fat absorption with both enzymes. High-fat diets with bacterial or porcine lipase should be evaluated in humans with pancreatic steatorrhea.

Topics: Animals; Bacteria; Bacterial Proteins; Celiac Disease; Chymotrypsin; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Dogs; Dose-Response Relationship, Drug; Exocrine Pancreatic Insufficiency; Intestinal Absorption; Lipase; Swine; Trypsin

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

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

A specific method for pancreatic elastase II activity analysis was developed. True elastase II activity could be discriminated from that of elastase I and chymotrypsin. The postnatal development of four pancreatic proteases in the duodenal juice of children and in the pancreatic homogenates of calves and piglets was measured. The study was carried out on patients without (14 children) and with (5 children) pancreatic insufficiency. Calves and piglets were either milk-fed or weaned until slaughter at different ages. Profiles of enzyme development were globally similar in milk-fed piglets and calves, while in children without pancreatic insufficiency, no significant change was observed between 4 and 168 months. In children with pancreatic insufficiency, enzyme activity was low. In animals, elastase II and chymotrypsin activities were maximal at birth, decreased with age, and probably were associated with the digestion of milk protein. In contrast, elastase I and trypsin activities increased markedly after weaning in connection with the intake of solid food.

Topics: Adolescent; Animals; Case-Control Studies; Cattle; Child; Child, Preschool; Chymotrypsin; Duodenum; Exocrine Pancreatic Insufficiency; Humans; Infant; Intestinal Secretions; Pancreas; Serine Endopeptidases; Swine; Trypsin

Recently, a new ELISA kit for determination of elastase 1 in faeces has become commercially available. Studies in patients with chronic pancreatitis have indicated that it is a simple and sensitive test of exocrine pancreatic function. The aim of this study was to assess the clinical value of this new test in cystic fibrosis. A total of 72 children were studied: 27 who were healthy, 22 with cystic fibrosis and 23 with non-pancreatic disorders. Oral pancreatic extracts were not discontinued in the children with cystic fibrosis. A small sample of faeces was collected from each subject for elastase 1 concentration and chymotrypsin activity determination. In all of the healthy children and most of those with non-pancreatic disorders (20/23), elastase 1 concentrations were greater than 500 microg/g; in contrast, the vast majority (20/22) of children with cystic fibrosis had very low values (less than 20 microg/g). The differences between children with cystic fibrosis and the other two groups were highly significant (P < 0.001). With a cut-off level of 132 microg/g, the sensitivity and specificity of faecal elastase 1 for the determination of exocrine pancreatic insufficiency were 96% and 100%, respectively. The specificity of faecal chymotrypsin was 96%, but its sensitivity was not calculated since the children with cystic fibrosis continued to take pancreatic extracts during the study.. The determination of faecal elastase 1 concentration is a simple and reliable means of assessing exocrine pancreatic function in children with cystic fibrosis. Results are not influenced by non-pancreatic disorders or by enzyme supplementation.

Topics: Adolescent; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Enzyme-Linked Immunosorbent Assay; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Male; Pancreatic Elastase; Pancreatic Function Tests; Reagent Kits, Diagnostic; Sensitivity and Specificity

This study, using indirect tests, demonstrated that exocrine pancreatic function is impaired in a proportion of patients with beta-thalassemia major (TM), though this impairment is generally mild or moderate.. Impaired structure and function of the exocrine pancreas has been reported in patients with Beta-thalassemia major.. In this study we measured fecal fats and serum and fecal pancreatic enzymes in 30 patients (13 M, 17 F) with TM, mean age 22.1 yr (range 14-39) and compared them with those of a matched group of healthy controls. Results were correlated with age, serum ferritin, blood transfusion, and various nutritional parameters. Enzymes assays included: serum pancreatic amylase (PA), lipase (L), trypsin (T), fecal chymotrypsin (FCT), and fecal elastase (FE).. No patient was positive for steatorrhea. Comparison of the mean values showed a significant difference only for FE (p < 0.002). Using only the fecal tests as a reference, we found that 12 patients had FE values below the cutoff limit; of these, five had values between 100 and 185 micrograms/g, three between 50 and 99 micrograms/g and four below 50 micrograms/g. Ten patients had FCT values below the cutoff limit; seven presented impairment in both tests and six of them had FE values below 100 micrograms/g (including four diabetics). No correlations were found between enzyme values and mean serum ferritin values or mean blood consumption over the previous 3 yr. No correlation was found between FE and FCT levels or between enzymes and age.

Topics: Adolescent; Adult; Amylases; beta-Thalassemia; Chymotrypsin; Exocrine Pancreatic Insufficiency; Fats; Feces; Female; Humans; Hydrolases; Lipase; Male; Pancreatic Elastase; Trypsin

We have evaluated the diagnostic value of the fecal elastase test in comparison with the secretin-pancreozymin test in the diagnosis of exocrine pancreatic insufficiency. Pancreatic elastase was measured immunologically. Immunoreactive elastase activity in spot stools from controls ranged from 136 to 4440 microgram/g; 95% of all values were within 175 to 1500 microgram/g. The elastase assay CVs ranged from 3.3% to 6.3% (intraassay) and from 4.1% to 10.2% (interassay). The output of elastase correlated well with those of amylase, lipase, and trypsin, yielding respective correlation coefficients of 0.83, 0.82, and 0.84 in controls and 0.86, 0.91, and 0.91 in patients with impaired pancreatic function. In contrast to fecal chymotrypsin, the test results were unaffected by pancreatic enzyme replacement therapy. These results indicate that fecal immunoreactive elastase may be recommended as a new, noninvasive tubeless test of pancreatic function.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Chymotrypsin; Clinical Enzyme Tests; Enzyme Stability; Evaluation Studies as Topic; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pancreas; Pancreatic Elastase; Pancreatic Function Tests; Prospective Studies; Reference Values; Sensitivity and Specificity

Indirect pancreatic function tests available today are unreliable for clinical practice in early chronic pancreatitis due to their low sensitivity in mild and moderate exocrine pancreatic insufficiency.. To evaluate the sensitivity, specificity, and practicability of faecal elastase 1 determination in patients with mild, moderate, and severe exocrine pancreatic insufficiency categorised according to the secretin-caerulein test as "gold standard'.. Faecal and duodenal elastase 1 concentration (commercial enzyme linked immunosorbent assay (ELISA)), faecal chymotrypsin activity, faecal fat analysis, and the secretin-caerulein test were performed on 44 patients with mild (n = 8), moderate (n = 14), and severe (n = 22) exocrine pancreatic insufficiency and 35 patients with gastrointestinal diseases of non-pancreatic origin. Fifty healthy volunteers were studied as normal controls. Morphological examinations were carried out to definitely confirm or exclude chronic pancreatitis.. With a cut off of 200 micrograms elastase 1/g stool the sensitivity was 63% for mild, 100% for moderate, 100% for severe, and 93% for all patients with exocrine pancreatic insufficiency, and specificity was 93%. Values for chymotrypsin were 64% (sensitivity) and 89% (specificity). Significant (p < 0.001) correlations were found for faecal and duodenal elastase with duodenal lipase, amylase, trypsin, volume, and bicarbonate output. Individual day to day variations of faecal elastase 1 concentrations were very low (mean CV = 15%) and sample storage at room temperature is possible for at least one week.. Faecal elastase 1 determination proved to be a highly sensitive and specific tubeless pancreatic function test.

Topics: Adult; Chronic Disease; Chymotrypsin; Duodenum; Evaluation Studies as Topic; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Lipids; Male; Pancreatic Elastase; Regression Analysis; Sensitivity and Specificity

Previous reports suggest that vitamin B-6 deficiency contributes to pancreatic insufficiency. However, the susceptibility of pancreatic function to marginal vitamin B-6 intake has not been defined. The present study examines digestive enzyme activity and steady-state mRNA levels, as well as antioxidant enzyme status from rats fed different vitamin B-6 diets. Groups (n = 12) of adult female Long-Evans rats were assigned to five dietary groups and fed their respective diets for 6 wk. Control and food-restricted rats were fed the control diet (7 mg pyridoxine/kg diet) freely, or food intake was restricted to the lowest intake of the experimental groups. The experimental groups were fed purified diets containing 0 (deficient), 0.25 or 1 (marginal) mg pyridoxine/kg diet. Plasma amylase and pancreatic amylase, trypsin and chymotrypsin activities were significantly lower in deficient rats compared with rats fed the control diet. Lower enzyme activities were accompanied by 83 and 55% lower amylase and trypsinogen mRNA levels compared with levels in rats fed the control diet. Other than low glutathione reductase in deficient rats, pancreatic antioxidant enzyme activity was similar in all dietary groups. These data suggest that the exocrine pancreas is impaired by vitamin B-6 deficiency, but marginal pyridoxine intake maintains function.

Topics: Amylases; Animals; Chymotrypsin; Exocrine Pancreatic Insufficiency; Female; Gene Expression Regulation, Enzymologic; Glutathione Reductase; Pancreas; Random Allocation; Rats; RNA, Messenger; Trypsin; Trypsinogen; Vitamin B 6 Deficiency

It has recently been shown that the infusion of oleic acid into the rat pancreaticobiliary duct causes a reproducible and long-lasting atrophy of the exocrine pancreas. The effects of this pancreatic atrophy on non-invasive pancreatic function tests have not been fully characterized. This study was undertaken to determine which pancreatic function test was most useful in determining pancreatic insufficiency in this model. Pancreatic insufficiency (PI) was induced in male Wistar rats by oleic acid infusion and three pancreatic function tests were compared in these animals and saline controls. The coefficient of fat absorption on a 5 or 45% fat diet and bentiromide testing could not differentiate animals with or without PI, but fecal chymotrypsin levels were excellent discriminators. All animals with PI had fecal chymotrypsin levels below 67 U/g feces whereas all saline controls were above this level. We conclude that, in this model of PI, the fecal chymotrypsin concentration is the best non-invasive test to determine pancreatic insufficiency.

Topics: Absorption; Animals; Chronic Disease; Chymotrypsin; Chymotrypsinogen; Dietary Fats; Disease Models, Animal; DNA; Exocrine Pancreatic Insufficiency; Feces; Lipase; Male; Oleic Acid; Oleic Acids; Pancreas; Pancreatic Function Tests; Rats; Rats, Wistar

In vitro behaviour of the enteric-coating of a new pancreatic enzyme containing preparation in enteric-coated microtablets was evaluated, by incubating at 37 degrees C, under gentle agitation, the preparation under study in buffered gastric (pH 2, 3, 4, 5, 6) and in buffered duodenal juice (pH 3, 4, 5, 6, 7, 8) for 30, 60, 90, 120 minutes. Lipase and chymotripsin activities were measured at each time and pH in the solution and in the undissolved microtablets. The drug under study showed a good enteric-coating, preserving about 100% of the enzyme content, when incubated in buffered gastric juice, up to pH 6, and releasing in the solution, during incubation in buffered duodenal juice, 75% of its enzyme content at pH 7 and 8. Therefore, the pancreatic enzymes contained in this new enteric-coated microtablet preparation are well protected against inactivation from acid and are bioavailable for digestion of alimentary substrates at optimal or near optimal pH in duodenal juice.

Topics: Biological Availability; Buffers; Chymotrypsin; Drug Evaluation; Duodenum; Exocrine Pancreatic Insufficiency; Gastric Juice; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Intestinal Secretions; Lipase; Tablets, Enteric-Coated

For assessment and monitoring of adequate enzymatic substitution the authors used repeated examinations of chymotrypsin in the faeces of 19 patients with insufficiency of external secretion (17 patients with chronic pancreatitis and two after duodenopancreatectomy on account of carcinoma of the pancreas). Adequate substitution (chymotrypsin > 6U/g faeces) is individual (1.8-7.2 g pancreatin--Kreon/day). The required dose may be higher in patients with chronic pancreatitis than in conditions following duodenopancreatectomy. When receiving adequate substitution treatment, the patients reported milder complaints, regression of pain and diarrhoea. In two patients with severe signs of malnutrition a satisfactory condition was achieved and their loss of body weight was arrested. The necessary dose of insulin in diabetic patients declined by 4-12 u/day. During treatment no adverse side-effects were found.

Topics: Adult; Aged; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Male; Middle Aged; Pancreatin

The chymotrypsin in the stool test was used to monitor adequate enzymatic substitution in treating exocrine pancreatic insufficiency with 18 patients (16 suffering from chronic pancreatitis and 2 having passed duodenopancreatectomy due to pancreatic cancer). This test helps to identify pancreatic insufficiency and can be successfully used in monitoring the adequate amount of pancreatic substitute, which, we have found, differs from patient to patient. The dosage can be higher in cases of chronic pancreatitis than in those required after duodenopancreatectomy.

Topics: Adult; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Humans; Male; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatin; Postoperative Complications

In 96 consecutive patients who underwent a 72-h faecal fat determination because of suspected nutrient malassimilation (maldigestion and/or malabsorption) faecal chymotrypsin (F-Chym) was estimated with a commercial photometric test (Monotest Chymotrypsin), comparing F-Chym concentrations in the first 24-h stool with the total 72-h F-Chym output. In the first 24-h faeces, the F-Chym concentration, calculated as a mean of three random samples, did not significantly differ from a single value obtained after homogenization. In known pancreatic disease, a F-Chym concentration less than 3.0 U/g wet faeces distinguished well between steatorrhoic patients (n = 12) and nonsteatorrhoic (n = 13) (positive predictive value (PV), 91%; negative PV, 86%) but was less suitable as a screening test for pancreatic steatorrhoea in the unselected patient group (positive PV, 61%; negative PV, 98%). Although the estimation of 72-h F-Chym output could differentiate between various subgroups of patients to a certain extent, the positive PV for discovery of pancreatic steatorrhoea in a single patient was low. Four patients had excessively high F-Chym output and increased bile acid excretion after ileal resection (n = 3) and radiation ileitis (n = 1), respectively, possibly indicating the removal of an inhibitory mechanism of pancreatic and biliary secretion in these conditions.

Topics: Adult; Celiac Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Intestinal Diseases; Male; Middle Aged; Postgastrectomy Syndromes; Predictive Value of Tests; Sensitivity and Specificity; Weight Loss

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

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

Topics: Chymotrypsin; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Feces; Humans; Infant; Malabsorption Syndromes; Sensitivity and Specificity

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 determination of fecal chymotrypsin is a suitable noninvasive screening test for the evaluation of exocrine pancreatic function. Using a photometric assay we found a specificity of 87.5% and a sensitivity of 80%. Beyond the first year of life the lowest limit of normal values is 72 micrograms chymotrypsin/g stool. The method is reproducible, and a 72-hour stool collection is unnecessary when several fecal chymotrypsin determinations in spot stool samples are performed.

Topics: Adolescent; Child; Child, Preschool; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Male; Pancreatic Function Tests; Reference Values

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

The fecal chymotrypsin (FC) levels in samples collected over 24 h were determined by a new commercial colorimetric method from Boehringer Mannheim in 82 children suffering from various pancreatic disorders. The patients were divided into 4 groups, in accordance with the following etiologies: cystic fibrosis of the pancreas (CFP), chronic severe hepatic disorders (CSH), primary malabsorption syndrome (PMS) and malnutrition due to nondigestive causes (M). The control group comprised 48 children of similar ages. The 24th FC levels as U/g (mean +/- SD) were: 34 +/- 6 in the control group, 2 +/- 2 in the CFP group, 15 +/- 6 in the M group, 19 +/- 9 in the CSH group and 43 +/- 13 in the PMS group. The differences between the CFP patients and all the other groups were statistically significant. These results indicate that the FC levels may be suitable as a diagnostic indication of CFP and capable of differentiating between this disorder and other causes of pancreatic insufficiency.

Topics: Adolescent; Child; Child, Preschool; Chymotrypsin; Colorimetry; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Feces; Humans; Infant; Malabsorption Syndromes

The advantages of the photometrical analysis of chymotrypsin in stool of dogs are: the short duration of procedure, the small amount of stool necessary and the simplified manner of measurement at 405 nm. The test was performed in healthy as well as in chronically pancreatic insufficient dogs and those with other origins of diarrhea. The normal value for healthy dogs was more than 1 U chymotrypsin/g stool. Because of distinct individual ranges of chymotrypsin activities a single detection is not sufficiently diagnostic. Several results below 1 U/g stool indicate a great likelihood of chronic pancreatic insufficiency.

Topics: Animals; Chronic Disease; Chymotrypsin; Dog Diseases; Dogs; Exocrine Pancreatic Insufficiency; Feces; Photometry

In the fluorescein dilaurate test fluorescein dilaurate is cleaved by the pancreas specific cholesterol ester hydrolase activity and the liberated fluorescein is absorbed and excreted in the urine. Fluorescein recovery is a reflection of exocrine pancreatic function. The test was evaluated in 14 patients with cystic fibrosis and 16 healthy volunteers. The test was well tolerated by patients, was easy to perform, and gave significantly lower values in the patients suffering from cystic fibrosis. The result of the pancreolauryl test was also correlated with the result of the faecal chymotrypsin test in 11 of the patients suffering from cystic fibrosis. A positive correlation was found between the two test results. The test is a practical and reliable index of pancreatic exocrine function and may have a useful role as a screening procedure.

Topics: Adolescent; Adult; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Feces; Fluoresceins; Humans; Reference Values

Topics: 4-Aminobenzoic Acid; Chronic Disease; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Humans

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

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

An investigation of fecal chymotrypsin activity on spot fecal specimens was carried out in three groups of subjects, divided as follows: 45 healthy controls (group C); 36 patients with gastroenterological diseases of extrapancreatic origin (group VP); and 42 patients with chronic pancreatitis (group CP). Nineteen patients of group CP underwent pancreozymin-secretin and NBT-PABA tests. The following results, expressed as mg of chymotrypsin/g of feces, were obtained: C = 0.610 +/- 0.203; CP = 0.291 +/- 0.154, p less than 0.001; VP = 0.560 +/- 0.234. FCT showed a sensitivity rate of 78.5% and a specificity rate of 71.6%. The fecal output of chymotrypsin correlated well with the pancreatic secretion of chymotrypsin (r = 0.59, p less than 0.01) and with the percentage of recovery of urinary PABA (r = 0.44, p less than 0.05). We conclude that chymotrypsin assay by the described method on spot stool specimens is a simple, reliable technique which may be considered a good screening test for pancreatic insufficiency. The test will not detect minimal pancreatic disease or minimal pancreatic dysfunction.

Topics: 4-Aminobenzoic Acid; Chymotrypsin; Clinical Enzyme Tests; Drug Stability; Exocrine Pancreatic Insufficiency; Feces; Humans; Pancreatic Juice; para-Aminobenzoates; Secretin

PABA test has proved to be an easy and reliable test for determination of exocrine pancreatic insufficiency. N-benzoyl-L-tyrosyl-p-aminobenzoic acid or 4-(N-acetyl-L-tyrosyl) aminobenzoic acid are split by action of chymotrypsin in the small intestine. N.O-diacetyl-L-tyrosyl-p-aminobenzoic acid is converted easy in vivo in 4(N-acetyl-L-tyrosyl) aminobenzoic acid. The amount of 4-aminobenzoic acid (PABA) in urine collected for 6-10 hours is used as an index of chymotrypsin production. The concentration of PABA (and aromatic amines) is estimated in urine by the Bratton and Marshall method. p-dimethylamino cinnamaldehyde is less useful for the determination of urinary PABA. 60 min are necessary as time for acid hydrolysis of conjugated PABA metabolites. False abnormal test results are found for instance in patients with inflammatory bowel diseases, small bowel resection, impaired liver function, anorexia nervosa, lambliasis or renal insufficiency. The PABA test appears in consideration of these restrictions to be an useful simple method in the assessment of exocrine pancreatic function.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Biotransformation; Chymotrypsin; Exocrine Pancreatic Insufficiency; Humans; Intestinal Absorption; Pancreatic Function Tests

Topics: Chymotrypsin; Diarrhea; Esters; Exocrine Pancreatic Insufficiency; Feces; Humans; Pancreatic Diseases; Photometry; Tyrosine

Two newly developed photometric assays for the estimation of faecal chymotrypsin were studied in comparison with the established titrimetric method in 46 patients and 8 healthy volunteers, who had undergone a secretin-pancreozymin test for diagnostic purposes. The correlation between the two photometric methods and the titrimetric method was good (r = 0.90 and r = 0.91), revealing similar diagnostic sensitivity and specificity. As both photometric methods are less time-consuming and may be performed using a standard laboratory equipment, they offer a good alternative to the established titrimetric method for faecal chymotrypsin estimation.

Topics: Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Humans; Pancreatic Function Tests; Pancreatitis; Photometry

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

Topics: Adult; Chymotrypsin; Duodenogastric Reflux; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Postoperative Complications

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

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

The 6-h urine recovery of p-aminobenzoic acid (PABA) following the administration of a standard dose of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BTPABA) was performed in 13 control subjects and two siblings with Shwachman's syndrome. The control subjects showed a recovery of 67 +/- 12.1% (mean +/- 1 SD) of the administered dose, consistent with previously reported values. Unexpectedly, the recovery of PABA in two siblings with Shwachman's syndrome was found to be 67 and 63%, respectively. The values are well within the normal range. In these siblings, fecal chymotrypsin activities were very low when measured with N-acetyl-L-tyrosyl-ethyl ester (ATEE) as substrate, but were normal when BTPABA was the substrate. The duodenal juice of the younger affected child following pancreozymin-secretin stimulation showed very low chymotrypsin activity against ATEE, BTPABA, and N-benzoyl-L-tyrosyl-ethyl ester. These findings suggest that there may be BTPABA-splitting activity in the lower bowel of these siblings with Shwachman's syndrome. This activity might be that of enteric bacteria or of the intestinal mucosa.

Topics: 4-Aminobenzoic Acid; Agranulocytosis; Aminobenzoates; Child; Child, Preschool; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Humans; Infant; Male; Neutropenia; para-Aminobenzoates; Syndrome

In 25 patients with chronic exocrine pancreatic insufficiency and 37 controls, the PABA test was compared with the concentration of chymotrypsin in stool. In additional 16 patients the test could not be evaluated (rate 21%). By determination of the PABA levels in serum before and one hour after ingestion of N-benzoyl-L-tyrosyl-PABA the test can be shortened and simplified: 1 hour serum levels in 9 patients with exocrine pancreatic insufficiency were 0.5 +/- 0.5 nMol/ml compared with 8 controls with 6.4 +/- 2.0 nMol/ml. PABA serum levels correlated significantly with chymotrypsin in stool. Compared with the conventional PABA test, since it is easily applicable in outpatients and the results are not influenced by medication or food.

Topics: 4-Aminobenzoic Acid; Aminobenzoates; Chymotrypsin; Exocrine Pancreatic Insufficiency; Humans; Pancreatic Function Tests; para-Aminobenzoates

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.

Topics: 4-Aminobenzoic Acid; Absorption; Aminobenzoates; Animals; Chymotrypsin; Dog Diseases; Dogs; Duodenum; Exocrine Pancreatic Insufficiency; Female; Intestinal Diseases; Intestinal Secretions; Lipid Metabolism; Male; Pancreatic Function Tests; para-Aminobenzoates; Trypsin; Xylose

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

Forty-eight patients with chronic recurrent pancreatitis treated by resection of the head of the pancreas were restudied more than a year post-operatively. In addition to general features such as symptoms, alcohol consumption and work ability, faecal weight, its fat content, fat and fatty acid balance and faecal chymotrypsin were measured. According to the patients' own estimate, late results were good or very good in 70-90%. Faecal fat content and balance indicated high-grade exocrine pancreatic insufficiency in 80 and 90%, respectively. But it was easily controlled by drugs. In a third of the cases there was the need to supplement the diet with medium-chain triglycerides. Its components are satisfactorily absorbed even when the fat utilisation is severely abnormal.

Topics: Chronic Disease; Chymotrypsin; Duodenum; Exocrine Pancreatic Insufficiency; Feces; Humans; Lipids; Pancreatectomy; Pancreatitis; Postoperative Complications

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 sensitivity of human intestinal lactase to pancreatic proteases was tested both in vitro and in vivo. Lactase specific activity in brush border membranes was decreased by 26%-27% during incubation with trypsin at pH 7.0 in patients with normal intestinal lactase levels, whereas in patients with lactase deficiency the inactivation was 75%. However, when lactase levels from deficient patients' mucosa were increased relative to trypsin during incubation so that they were comparable to the levels of activity in normal mucosa, inactivation of lactase in deficient patients was only 45%. Therefore, in these patients the greater in vitro lactase inactivation by trypsin could be explained at least in part by an increased trypsin/lactase ratio. Sucrase levels were decreased in vitro by trypsin (about 40%), but maltase activity was unaffected. The effect of pancreatic proteases was tested in vivo in patients with pancreatic insufficiency. After the addition of pancreatic enzymes (Viokase), lactase specific activity fell by 16% in patients with normal lactase, and by 38.5% in patients with lactase deficiency. In both groups of patients, lactase levels fell to a greater extent than did sucrase or maltase. These data demonstrate that pancreatic proteases can alter intestinal lactase activity in humans. Moreover, in lactase-deficient patients, lactase activity decreases to a greater extent than in patients with normal lactase, resulting in further deficiency of this enzyme.

Topics: Adult; alpha-Glucosidases; beta-Galactosidase; Chymotrypsin; Exocrine Pancreatic Insufficiency; Galactosidases; Humans; Hydrogen-Ion Concentration; Intestinal Mucosa; Jejunum; Lactose Intolerance; Male; Microvilli; Middle Aged; Pancreas; Pancreatic Elastase; Peptide Hydrolases; Sucrase; Trypsin

Topics: 4-Aminobenzoic Acid; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Humans; Trypsin

The efficacy of pancreatin in vivo was determined in 14 patients with advanced pancreatic insufficiency using a peroral test with 2 g of chymotrypsin substrate, 4-(N-acetyl-L-tyrosyl)aminobenzoic acid, the Lundh test meal and 1000 ml tea. Chymotrypsin hydrolysis was quantified by 4-aminobenzoic acid excreted in 6-hr or 8-hr urine samples. After a control test without pancreatin, one or two tablets of Panpur (Nordmark-700 mg of pancreatin and 50 mg of bile per tablet) were applied simultaneously with the Lundh meal on repeated examinations. The urinary excretion of 4-aminobenzoic acid was restored to normal values in 5 subjects during both sampling periods. With this method, stimulated and substituted chymotrypsin is measured at the same time. The conditions of the tests, both with and without pancreatin replacement, are fully comparable and thus the significance of factors modifying the activity of enzymic components in the digestive tube is limited. The method appears appropriate for the institution of an effect pancreatin therapy and its control in vivo.

Topics: 4-Aminobenzoic Acid; Adult; Aged; Aminobenzoates; Bile; Chymotrypsin; Drug Combinations; Exocrine Pancreatic Insufficiency; Female; Food; Humans; Male; Middle Aged; Pancreatin; para-Aminobenzoates; Tissue Extracts; Tyrosine; Water

Topics: Adolescent; Child; Cholelithiasis; Chymotrypsin; Clinical Enzyme Tests; Cystic Fibrosis; Diagnosis; Exocrine Pancreatic Insufficiency; Feces; Gastrointestinal Diseases; Geriatrics; Humans; Infant; Intubation; Intubation, Gastrointestinal; Liver Diseases; Pancreatic Neoplasms; Pancreatitis; Trypsin

Topics: Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Pancreatic Neoplasms; Pancreatitis; Trypsin

Topics: Chymotrypsin; Diagnosis; Exocrine Pancreatic Insufficiency; Feces; Humans; Pancreas; Pancreatic Juice; Trypsin