alpha-chymotrypsin and Cystic-Fibrosis

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

In young adults with acute pancreatitis a wide etiologic spectrum has to be considered. Among the possible causes, cystic fibrosis is rare. Besides the typical clinical triad of pancreatic exocrine insufficiency, chronic obstructive pulmonary disease, and elevated sweat chloride levels, there is a wide spectrum of variants of the cystic fibrosis syndrome. Especially mild manifestations of the disease may, therefore, escape proper identification. Here we describe a young man who presented initially with recurrent acute pancreatitis without pulmonary disease and without a family history of cystic fibrosis, in whom the diagnosis of cystic fibrosis was established by slightly elevated sweat chloride levels and obstructive azoospermia. Five years after the first attack of pancreatitis the patient developed pancreatic exocrine insufficiency.

Topics: Adult; Chlorides; Chymotrypsin; Cystic Fibrosis; Duodenoscopy; Feces; Humans; Male; Oligospermia; Pancreatitis; Recurrence; Sweat; Ultrasonography

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

The hitherto existing results of determinations of enzymatic activities in stool are presented in this review. The chymotrypsin activity is diminished in advanced exocrine pancreatic insufficiency. The faecal alpha-amylase activity has up to now no significance in the diagnosis of pancreatic diseases. Up to five amylolytic enzyme activities are detectable. The alkaline phosphatase is mostly of intestinal origin. Up to 4 enzyme bands can be exhibited with the disc electrophoresis in polyacrylamide gel. Lysozyme and N-Acetyl-beta-D-glycosaminidase can also be detected in stool.

Topics: Alkaline Phosphatase; Amylases; Animals; Chymotrypsin; Colitis, Ulcerative; Cystic Fibrosis; Enzyme Induction; Feces; Hepatitis, Viral, Human; Hexosaminidases; Humans; Intestinal Mucosa; Malabsorption Syndromes; Muramidase; Pancreatic Diseases; Protozoan Infections; Rats; Trypsin

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

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

Cystic fibrosis (CF), the most common autosomal recessive disease in whites, is caused by mutations in the CF transmembrane conductance regulator (CFTR). So far, >1900 mutations have been described, most of which are nonsense, missense, and frameshift, and can lead to severe phenotypes, reducing the level of function of the CFTR protein. Synonymous variations are usually considered silent without pathogenic effects. However, synonymous mutations exhibiting exon skipping as a consequence of aberrant splicing of pre-mRNA differ. Herein, we describe the effect of the aberrant splicing of the c.273G>C (G91G) synonymous variation found in a 9-year-old white (ΔF508) patient affected by CF and pancreatitis associated with a variant in chymotrypsin C (CTRC). Magnetic resonance imaging showed an atrophic pancreatic gland with substitution of the pancreatic parenchyma with three cysts. Genetic examination revealed compound heterozygosity for the c.1521_1523delCTT (ΔF508) pathogenic variant and the c.273G>C (G91G) variant in CFTR. Sweat test results confirmed the diagnosis of CF. We have thus identified a synonymous variation (G91G) causing the skipping of exon 3 in a CF patient carrying the ΔF508 mutation. However, the clinical phenotype with pancreatic symptoms encouraged us to investigate a panel of pancreas-related genes, which resulted in finding a known sequence variation inside CTRC. We further discuss the role of these variants and their possible interactions in determining the current phenotype.

Topics: Child; Chymotrypsin; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Late Onset Disorders; Male; Pancreatitis, Chronic

In cystic fibrosis (CF) lung disease, the absence of functional CF transmembrane conductance regulator results in Cl(-)/HCO3 (-) hyposecretion and triggers Na(+) hyperabsorption through the epithelial Na(+) channel (ENaC), which contribute to reduced airway surface liquid (ASL) pH and volume. Prostasin, a membrane-anchored serine protease with trypsin-like substrate specificity has previously been shown to activate ENaC in CF airways. However, prostasin is typically inactive below pH 7.0, suggesting that it may be less relevant in acidic CF airways. Cathepsin B (CTSB) is present in both normal and CF epithelia and is secreted into ASL, but little is known about its function in the airways. We hypothesized that the acidic ASL seen in CF airways may stimulate CTSB to activate ENaC, contributing to Na(+) hyperabsorption and depletion of CF ASL volume. In Xenopus laevis oocytes, CTSB triggered α- and γENaC cleavage and induced an increase in ENaC activity. In bronchial epithelia from both normal and CF donor lungs, CTSB localized to the apical membrane. In normal and CF human bronchial epithelial cultures, CTSB was detected at the apical plasma membrane and in the ASL. CTSB activity was significantly elevated in acidic ASL, which correlated with increased abundance of ENaC in the plasma membrane and a reduction in ASL volume. This acid/CTSB-dependent activation of ENaC was ameliorated with the cell impermeable, CTSB-selective inhibitor CA074, suggesting that CTSB inhibition may have therapeutic relevance. Taken together, our data suggest that CTSB is a pathophysiologically relevant protease that activates ENaC in CF airways.

Topics: Animals; Cathepsin B; Cell Membrane; Cells, Cultured; Chymotrypsin; Cysteine Proteinase Inhibitors; Cystic Fibrosis; Dipeptides; Epithelial Sodium Channels; Female; HEK293 Cells; Humans; Hydrogen-Ion Concentration; Oocytes; Protein Subunits; Rats; Recombinant Proteins; Respiratory Mucosa; Sodium; Xenopus laevis

Loss-of-function mutations of the epithelial sodium channel (ENaC) may contribute to pulmonary symptoms resembling those of patients with atypical cystic fibrosis (CF). Recently, we identified a loss-of-function mutation in the alpha-subunit of ENaC (alphaF61L) in an atypical CF patient without mutations in CFTR. To investigate the functional effect of this mutation, we expressed human wild-type alpha beta gamma-ENaC or mutant alpha(F61L) beta gamma-ENaC in Xenopus laevis oocytes. The alphaF61L mutation reduced the ENaC mediated whole-cell currents by approximately 90%. In contrast, the mutation decreased channel surface expression only by approximately 40% and did not alter the single-channel conductance. These findings indicate that the major effect of the mutation is a reduction of the average channel open probability (P(o)). This was confirmed by experiments using the betaS520C mutant ENaC which can be converted to a channel with a P(o) of nearly one, and by experiments using chymotrypsin to proteolytically activate the channel. These experiments revealed that the mutation reduced the average P(o) of ENaC by approximately 75%. Na(+) self inhibition of the mutant channel was significantly enhanced, but the observed effect was too small to account for the large reduction in average channel P(o). The ENaC-activator S3969 partially rescued the loss-of-function phenotype of the alphaF61L mutation. We conclude that the alphaF61L mutation may contribute to respiratory symptoms in atypical CF patients.

Topics: Animals; Chymotrypsin; Cystic Fibrosis; Epithelial Sodium Channels; Female; Gene Expression; Humans; Mutation; Oocytes; Sodium; Xenopus laevis

Increased activity of the epithelial sodium channel (ENaC) in the respiratory airways contributes to the pathophysiology of cystic fibrosis (CF), a genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In some patients suffering from atypical CF a mutation can be identified in only one CFTR allele. We recently identified in this group of CF patients a heterozygous mutation (W493R) in the alpha-subunit of ENaC. Here, we investigate the functional effects of this mutation by expressing wild-type alpha beta gamma ENaC or mutant alpha(W493R)beta gamma ENaC in Xenopus oocytes. The alpha W493R mutation stimulated amiloride-sensitive whole-cell currents (Delta I(ami)) by approximately 4-fold without altering the single-channel conductance or surface expression of ENaC. As these data suggest that the open probability (P(o)) of the mutant channel is increased, we investigated the proteolytic activation of ENaC by chymotrypsin. Single-channel recordings revealed that chymotrypsin activated near-silent channels in outside-out membrane patches from oocytes expressing wild-type ENaC, but not in membrane patches from oocytes expressing the mutant channel. In addition, the alpha W493R mutation abolished Na(+) self inhibition of ENaC, which might also contribute to its gain-of-function effects. We conclude that the alpha W493R mutation promotes constitutive activation of ENaC by reducing the inhibitory effect of extracellular Na(+) and decreasing the pool of near-silent channels. The resulting gain-of-function phenotype of the mutant channel might contribute to the pathophysiology of CF in patients carrying this mutation.

Topics: Animals; Cells, Cultured; Chymotrypsin; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Epithelial Sodium Channels; Feedback, Physiological; Female; Humans; Mutation; Oocytes; Patch-Clamp Techniques; Phenotype; Plasmids; Sodium; Xenopus laevis

Recent studies have reported an imbalance between n6 and n3 fatty acids (AA and DHA) in subjects with CF. Alterations in fatty acid amounts are present in CFTR-expressing tissues, plasma and in circulating blood cells. It has been reported that the correction of polyunsaturated fatty acid deficiency reversed the organ pathologies observed in CF knockout mice. We describe a CF child with an unusual clinical course presenting high molar percentage of DHA in plasma and red cells membrane during supplementation with 5-methyltetrahydrofolate and vitamin B12.

Topics: Adult; Chymotrypsin; Cystic Fibrosis; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-6; Female; Folic Acid; Humans; Infant, Newborn; Methylation; Milk, Human; Tetrahydrofolates

In 105 pancreatic insufficient CF patients (steatorrhea and low fecal elastase-1 concentrations), the effectiveness of pancreatic enzyme therapy (PET) has been assessed (fecal fat losses and coefficient of fat reabsorption). Eight unresponsive subjects were checked for PET compliance with fecal chymotrypsin assay. Three patients were documented to be non-compliant. Unresponsive patients should undergo evaluation for PET compliance.

Topics: Adolescent; Adult; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Dietary Supplements; Feces; Female; Humans; Hydrolases; Male; Pancreatic Elastase; Pancreatic Function Tests; Patient Compliance; Steatorrhea; Treatment Outcome

Topics: Child; Chymotrypsin; Cystic Fibrosis; Feces; Female; Humans; Infant; Infant, Newborn; Lipids; Pancreas; Pancreatic Elastase; Predictive Value of Tests

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

We have previously reported the asymmetric synthesis of (alpha-aminoalkyl) diphenylphosphonate and phosphinate derivatives designed as inhibitors of chymotrypsin- and elastase-like proteases. This paper reports the first kinetic evaluation of individual epimers of the (alpha-aminoalkyl) diphenylphosphonates as inactivators of chymotrypsin, cathepsin G and neutrophil elastase (HNE). Results show that the (R)-epimers consistently function as more potent irreversible inactivators of their respective target proteases than the corresponding (S)-epimers. Additionally, phosphinate analogues were found to be consistently superior to their diphenylphosphonate counterparts. For example, Cbz. Phe(P)(OPh)-(CH(2))(2)-CO(2)Et inactivates cathepsin G approximately 45-fold more rapidly (k(i)/K(i) = 1.2 x 10(5) M(-1). min(-1)) than the analogous Cbz.Phe(P)(OPh)(2) (2.6 x 10(3) M(-1). min(-1)). Similarly, Cbz.Val(P)(OPh)-(CH(2))(2)-CO(2)Et was found to inactivate HNE some 3-fold more efficiently than Cbz.Val(P)(OPh)(2) (6.5 x 10(3) and 2.0 x 10(3) M(-1). min(-1), respectively).

Topics: Cathepsin G; Cathepsins; Child; Chymotrypsin; Cystic Fibrosis; Humans; Hydrolysis; Isomerism; Kinetics; Leukocyte Elastase; Organophosphonates; Phosphinic Acids; Serine Endopeptidases; Serine Proteinase Inhibitors; Substrate Specificity

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

We investigated the development of the exocrine pancreas in Cftr-/- mice in comparison with age-matched littermates (Cftr+/+, Cftr+/-) up to 100 d postnatally. Controls were weaned either to mouse chow or a liquid diet; Cftr-/- mice were weaned solely to a liquid diet. Solid-fed control mice gained weight and showed a progressive increase in pancreatic protein, DNA, amylase, lipase, trypsin, and chymotrypsin activities. Liquid-fed control mice showed similar postnatal somatic and pancreatic growth, except that amylase and lipase activities were lower than in the solid-fed controls. Cftr-/- mice exhibited significantly lower body and pancreatic weights than did controls. Pancreatic protein content and enzyme activities (notably amylase and lipase) were consistently lower than in the age-matched litter-mates fed either diet. The reduction in lipase activity in Cftr-/- mice was noted before weaning. We concluded that the liquid diet influenced postnatal exocrine pancreatic development in mice. However, a further reduction in postnatal pancreatic growth and enzymatic activities in the Cftr-/- mice was noted. These alterations could be due to the primary cystic fibrosis defect, although secondary factors, such as malnutrition induced by decreased dietary intake or abnormal absorptive capacity, may be responsible.

Topics: Amylases; Animals; Animals, Suckling; Chymotrypsin; Cystic Fibrosis; Diet; Lipase; Longevity; Mice; Mice, Inbred CFTR; Pancreas; Reference Values; Trypsin; Weaning

We previously suggested that an activation defect of pancreatic proteolytic zymogens in newborns suffering from cystic fibrosis (CF) might contribute (by an adaptative-like process) to the significant increase of the serum trypsin level observed in the disease at birth. To give support to this hypothesis we studied two pancreatic enzymes: trypsin 1 (IRT) and chymotrypsin A (IRChT) by noncompetitive enzyme immunoassays in amniotic fluids taken at 17-18 weeks of pregnancy. In normal fluids (102), the levels of the two enzymes were widely dispersed between 5 and 100 micrograms/L. A similar pattern was observed for the fluids with a 1 in 4 risk of CF with a normal outcome (24). In contrast, the levels of pancreatic enzymes in the fluids with affected fetus (40) were always below 45 micrograms/L for IRT and 55 micrograms/L for IRChT and most of them were under 20 micrograms/L for both enzymes. The molecular forms of IRT and IRChT in amniotic fluids were studied by gel filtration. In amniotic fluids with affected fetus, a major form of IRT was eluted in a position consistent with the elution of proteins around 25 kDa and two peaks of IRChT were eluted at 75 kDa and 25 kDa. These patterns are similar to those observed in normal serum when zymogens are present and are quite different from the patterns obtained by gel filtration of amniotic fluids with normal outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amniocentesis; Amniotic Fluid; Chromatography, Gel; Chymotrypsin; Cystic Fibrosis; Enzyme Precursors; Female; Humans; Pancreas; Pregnancy; Trypsin

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

Random fecal chymotrypsin activity and fecal alpha 1-antitrypsin (FA-1-AT) concentrations were determined in 11 children with cystic fibrosis, 5 children with Crohn's disease, 9 children with chronic aspecific diarrhea, 85 children with acute gastroenteritis, and 54 control children. Cystic fibrosis patients showed only very low fecal chymotrypsin values that did not overlap with values obtained in patients with either acute or chronic diarrhea. When compared with our control group, a significant increase of FA-1-AT concentrations was found only in children with Crohn's disease. Normal values were found in all patients with either chronic aspecific diarrhea or cystic fibrosis, while 12 of 85 children with acute gastroenteritis showed FA-1-AT concentrations above the 95th percentile of control children. We conclude that diarrhea (either acute or chronic) does not significantly decrease the clinical usefulness of fecal chymotrypsin activity measurements in the diagnosis of pancreatic insufficiency, while acute (gastroenteritis) but not chronic (chronic aspecific diarrhea, cystic fibrosis) diarrhea can give rise to protein losing and FA-1-AT concentrations similar to those found in Crohn's disease.

Topics: Adolescent; alpha 1-Antitrypsin; Child; Child, Preschool; Chymotrypsin; Crohn Disease; Cystic Fibrosis; Diarrhea; Feces; Female; Gastroenteritis; Humans; Male

Meconium specimens from 18 infants with cystic fibrosis (CF) had strong trypsin inhibitory activity (TIA). The same specimen, which contained increased quantities of undigested proteins, had normal concentrations of immunoreactive trypsin (IRT), but deficient trypsin catalytic activity (TCA). TIA was not detected in any specimen from non-CF infants who had high concentration of proteins comparable to that of CF infants. Subjecting meconium supernatant of CF infants to Sephadex G-75 gel filtration revealed that TCA was greatly enhanced in effluents after fractions were activated by porcine trypsin. TCA was present in the same fractions with IRT. The findings suggested that proteases were secreted into the intestinal lumen in CF infants prior to birth. Deficient proteolysis in the disease might be due to the presence of a trypsin inhibitor.

Topics: alpha 1-Antitrypsin; alpha-Macroglobulins; Catalysis; Chymotrypsin; Cystic Fibrosis; Humans; Infant, Newborn; Meconium; Trypsin; Trypsin Inhibitor, Kazal Pancreatic; Trypsin Inhibitors

Specimens of meconium and random stools were collected sequentially from 25 healthy newborn babies over the first 8-14 days of life. The stool chymotrypsin concentrations increased from birth to a maximum at 4 days of age and then fell again over the next four days. The lowest individual stool concentrations either side of the four day peak were both, coincidentally, 120 micrograms/g stool. In a second group of 22 newborn babies suspected of meconium ileus and later confirmed to have cystic fibrosis, faecal chymotrypsin concentrations were all appreciably reduced. In eight babies, also with suspected meconium ileus but with negative sweat tests, chymotrypsin concentrations were within the healthy newborn range. Measuring faecal chymotrypsin concentrations is a reliable procedure for identifying pancreatic exocrine insufficiency in the newborn.

Topics: Birth Weight; Chymotrypsin; Cystic Fibrosis; Feces; Humans; Infant, Newborn; Pigmentation; Reference Values

This study compares the diagnostic utility of fecal chymotrypsin (CT) output in timed stool collections and random stools using a new photometric enzyme assay. The CT output (mean +/- SD, U/24 h) was 1,487 +/- 1,980 in 127 children with normal fat absorption and negative sweat-chloride test (mean age 45 months), and 1,804 +/- 1,452 in 27 cases with fat malabsorption due to nonpancreatic disease (mean age 41 months). 66 cases of cystic fibrosis (CF) were examined (mean age 119 months). Stool output in 19 newly diagnosed patients before therapy was 85 +/- 94, in 42 patients receiving enzyme replacement therapy was 3,462 +/- 2,841, and in 5 patients with pancreatic sufficiency 1,754 +/- 1,482. Using nonparametric statistics, 120 U/24 h was defined as the lower limit of the 95-percentile for stool CT output. Only 5 of the 127 patients with normal fat absorption had output below that limit. None of the patients with nonpancreatic malabsorption and only 1 treated CF patient had lower values. Sixteen of the newly diagnosed CF patients had stool CT less than 120 U/24 h. The sensitivity of the test is therefore 84% and its specificity 97% at this decision threshold. However, no diagnostic advantage is gained from measuring CT output in timed stool collections as compared to random stools.

Topics: Age Factors; Child, Preschool; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Cystic Fibrosis; Feces; Humans; Infant; Pancreatitis; Random Allocation; Time Factors

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 aim of this study was to assess the analytical performance of the BMC stool chymotrypsin test and its accuracy in diagnosing pancreatic disease in infants. The test utilizes a detergent which solubilizes chymotrypsin bound to stool residues, and a tetrapeptide coupled to p-nitroaniline which is specifically cleaved by chymotrypsin. We employed the IL Multistat at 30 degrees C to monitor enzyme activity as an increase in absorbance at 405 nm. The reaction was linear to 600 U/g stool. Recovery of exogenous chymotrypsin with a single detergent extraction was 98-105%, and of endogenous chymotrypsin (as determined by multiple extractions) 80-97%. Imprecision (CV) was 2.2% within-day and 2.4% between-day for the BMC control, and 2.4-5.2% for stool chymotrypsin in the range 8.3-14.4 U/g. Since the test utilises only 100 mg of stool, inhomogeneity of enzyme distribution was assessed by multiple assays on a single stool, which revealed a range of activity from 4.2-150%. We therefore recommend sampling of each stool in triplicate. With this procedure, chymotrypsin was measured in 220 consecutive stool samples submitted for fat determination from children. Applying the manufacturer's lower reference limit of 4.1 U/g, the following results were obtained (number abnormal/total number): suspected intestinal disease with normal stool fat (5/127); proven intestinal disease and increased stool fat (1/26); untreated cystic fibrosis (CF) with (19/22), and without (0/3) steatorrhea; CF with pancreatic insufficiency on replacement therapy (4/42).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Chymotrypsin; Cystic Fibrosis; Fats; Feces; Humans; Infant; Malabsorption Syndromes; Pancreatic Diseases; 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; Aminobenzoates; Child; Child, Preschool; Cholecystokinin; Chymotrypsin; Cystic Fibrosis; Humans; Pancreas; Secretin

Fecal chymotrypsin (FCT) was determined in stool specimens of healthy children and those with gastro-intestinal disease, by a new photometric method. The values are comparable with chymotrypsin concentrations found by pH-stat method. The new test is cheap, reliable and easy to perform. For this reasons and for the sensitivity of all tubeless pancreatic function tests (NBT-PABA, FDL, FCT) is rather low (60-70%), the FCT-test may be preferred as diagnostic marker for differential diagnosis of exocrine pancreatic insufficiency.

Topics: Child; Child, Preschool; Chronic Disease; Chymotrypsin; Cystic Fibrosis; Feces; Humans; Infant; Infant, Newborn; Pancreatitis; Photometry

The purpose of this report is to evaluate whether a new, simple, non-invasive method for chymotrypsin measurement in stools is useful for the diagnosis of exocrine pancreatic insufficiency in cystic fibrosis (CF). A hundred children aged from 2 months to 12 years were tested: 50 children had been admitted for chronic diarrhoea, 15 for cystic fibrosis and 40 acted as controls. Chymotrypsin in stools was assayed using a kinetic measurement with Succ-Ala-Ala-Pro-Phe-pNa as substrate in a simple photometric assay. In 13 of 15 children with cystic fibrosis, stool enzyme levels were always remarkably low, while all control subjects and all children not presenting cystic fibrosis had normal stool levels of chymotrypsin. Our data suggest that stool chymotrypsin measurement is a simple and reliable "tubeless" test for the evaluation of exocrine pancreatic insufficiency in children with cystic fibrosis.

Topics: Child; Child, Preschool; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Cystic Fibrosis; Diarrhea; Feces; Humans; Infant; Pancreas; Reference Values

Duodenal fluids from control and cystic fibrosis (CF) patients were assayed for enterokinase (EK), trypsin and chymotrypsin activities. CF patients as a group were found to have higher basal EK activity in spite of low trypsin and chymotrypsin activities. In control patients, pancreozymin (CCK) injection led to increases in specific activities of trypsin and chymotrypsin and a decrease in EK but did not change the total EK activities. Secretin administration led to decreases in specific activities of trypsin and chymotrypsin compared to post-CCK levels. The total EK activities were greatly increased following secretin administration. Thus, secretin may have direct influence on the release of EK into the duodenum. CCK and secretin have no effect on the specific activities of trypsin, chymotrypsin and EK in CF patients. EK release in CF patients is either constitutive and therefore not affected by CCK and secretin or it has been fully induced by the low trypsin content and becomes unresponsive to further hormonal stimulation.

Topics: Adolescent; Child; Child, Preschool; Cholecystokinin; Chymotrypsin; Cystic Fibrosis; Duodenum; Endopeptidases; Enteropeptidase; Humans; Infant; Proteins; Secretin; Trypsin

Alterations in the pancreatic secretion of fluid and of enzymes in response to either pilocarpine (15 mg/kg) or an octapeptide of cholecystokinin (0.1 microgram/kg) have been found in rats that received daily injections of reserpine (0.5 mg/kg) for 7 days. During a 3-hr secretory period, significant reductions in the volume of pancreatic juice and in the total output of protein, amylase, and trypsin were observed in these animals. In the first hour of the secretory response, however, protease output was increased in the treated animals, particularly that of chymotrypsin, which was also increased in the longer secretory period following pilocarpine, but not cholecystokinin, stimulation. Zymogen granules isolated from the pancreas of the treated rats by differential centrifugation in a 0.3 M sucrose buffer had increased specific activities of the proteases when compared to those of untreated controls. Ultrastructurally, zymogen granules isolated from the pancreas of the treated rats showed changes in density, with bizonal and trizonal configurations being frequently observed, and had less distinct limiting membranes. In some, the membrane appeared broken at intervals, and there was granular material, presumably derived from the granule contents, lining the surface of the granule. It is concluded that pretreatment with reserpine inhibits fluid secretion and alters enzyme secretion in the rat exocrine pancreas. The latter effect is related to a nonparallel storage of amylase and proteases in the secretory granules induced by the drug treatment, probably through an action on protein synthesis or intracellular transport. An accumulation of proteases may lead to activation of these enzymes and to granule lysis. Inasmuch as the reserpine-treated rat has been proposed as an experimental model for cystic fibrosis, these findings are relevant in terms of possibly pathogenetic mechanisms in this disease.

Topics: Amylases; Animals; Cholecystokinin; Chymotrypsin; Cystic Fibrosis; Disease Models, Animal; Male; Pancreas; Pilocarpine; Rats; Reserpine; Trypsin

Topics: Child, Preschool; Chymotrypsin; Cystic Fibrosis; Fetal Blood; Follow-Up Studies; Humans; Infant; Trypsin; Trypsin Inhibitor, Kazal Pancreatic; Trypsin Inhibitors

The synthetic peptide N-benzoyl-L-tyrosyl-p-aminobenzoic acid is specifically cleaved by chymotrypsin to Bz-Ty and PABA. The liberated PABA is absorbed and excreted in the urine. Accordingly, PABA recovery reflects intraluminal chymotrypsin activity and is an index of exocrine pancreatic function. This test was evaluated in 24 patients with cystic fibrosis to determine its role in the diagnosis of exocrine pancreatic insufficiency. Cumulative percent PABA recovery in six hours was significantly lower in CF patients compared with the control group. No overlap was noted between the two groups. There was good correlation between PABA recovery, fecal chymotrypsin activity, and coefficient of fat absorption. These findings indicate that PABA recovery is significantly reduced in patients with CF and steatorrhea and may prove a practical and reliable test of pancreatic insufficiency.

Topics: 4-Aminobenzoic Acid; Adolescent; Adult; Aminobenzoates; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Feces; Humans; Lipids; Pancreatic Diseases; para-Aminobenzoates

P-Amino-benzoic acid (PABA) is split specifically by pancreatic chymotrypsin from the synthetic tripeptide N-benzoyl-L-tyrosyl-PABA. The urinary excretion of absorbed PABA serves as an index for exocrine pancreatic function. The peptide (0.015 g/kg) was administered orally to 20 controls (aged between 5 months and 16 years), 6 patients with exocrine pancreatic insufficiency caused by cystic fibrosis (CF), and 9 newborn infants. In the controls the mean 6-hour PABA recovery was 58.5% (+/- 11.2 SD). Recovery in patients with CF was lower (P less than 0.001) with no overlap. In newborn infants the mean 6-hour PABA recovery was 23.4 (+/- 17.7 SD); overlapping in 3 instances with the results in CF patients. This simple, noninvasive test thus appears promising and merits further investigation in younger infants, especially newborns.

Topics: 4-Aminobenzoic Acid; Adolescent; Aminobenzoates; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Female; Humans; Infant; Infant, Newborn; Male; Pancreas; Pancreatic Diseases

Seven children with cystic fibrosis (CF) have been treated for at least one year with intravenously administered soya oil emulsion. In all, an improvement of at least one biochemical abnormality in character with the disease appeared. The children's clinical course remains benign. This course is remarkably better than that of other children with CF treated without Intralipid in Auckland in the same period, though a placebo effect cannot be discounted. It is postulated that intravenous supplementation with essential fatty acid in CF may in turn partially correct an error of metabolism of prostaglandins present in the disease.

Topics: Body Weight; Chymotrypsin; Cystic Fibrosis; Fatty Acids; Feces; Humans; Infant; Linoleic Acids; Sodium; Sweat; Trypsin

Under certain conditions the determination of the tryptic activity, especially of the chymotryptic activity in the feces mostly of infants in the first 4-6 weeks of life is considered to be an important step in the diagnosis of cystic fibrosis. The tryptic anc chymotryptic activity in the feces of children with cystic fibrosis declines when the substitution of pancreatic enzymes is stopped. On resubstitution, the activity rises in relation to the dose and attains the activity related to age as found in healthy children. A comparison of the proteolytic activity with the fat content of the feces during the study period without the enzyme substitution and during the period when the enzyme dosage varied showed no significant correlation. It is not possible to postulate a poor excretion of fats merely from the high proteolytic activity of the feces because the fecal proteolytic activity and the fat excretion are not inversely proportional to one another. For this reason, one cannot conclude that the grade of the proteolytic activity in the feces of patients with cystic fibrosis is a yardstick for the total digestive process when they are under pancreatic enzyme substitution.

Topics: Age Factors; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Feces; Humans; Infant; Infant, Newborn; Infant, Premature; Lipids; Trypsin

A new technique of measuring stool enzyme activity on dry specimens of faeces from newborn children at 4-5 days of age has detected 3 cases of cystic fibrosis in the first 6000 tests. No known cases of cystic fibrosis have been missed. Additionally, one case of pancreatic achylia of at least 4 months' duration has been detected. It is proposed that the detection of cystic fibrosis by this technique is sufficiently practical to be acceptable as a worthwhile newborn screening programme. The screening test has been in use in Auckland for over a year and is now being set up in Hamilton, Wellington, and Dunedin (New Zealand), and Sydney (Australia).

Topics: Chymotrypsin; Clinical Enzyme Tests; Cystic Fibrosis; Feces; Humans; Infant, Newborn; Sweat; Trypsin

Topics: Child; Chymotrypsin; Cystic Fibrosis; Duodenum; Feces; Heterozygote; Humans; Hydrogen-Ion Concentration; Infant; Methods; Trypsin

A qualitative method of detecting elevated meconium protein concentration was compared with a method of determining meconium albumin concentration by electroimmunoassay since elevated meconium protein levels can indicate pancreatic insufficiency caused by cystic fibrosis. Between 5 and 10 per 1000 healthy infants passed meconium specimens that gave a false positive reaction with the Boehringer Mannheim test strip and contained a greater than expected concentration of albumin. It was possible to exclude pancreatic insufficiency in all of these children by determining the ratio, albumin : alpha1-antitrypsin in meconium and subsequent faecal specimens, since it was found that values of this ratio in excess of 2.0 suggested pancreatic insufficiency of the type associated with cystic fibrosis. Three of 14 neonates with subsequently proven cystic fibrosis yielded meconium specimens giving negative test strip results and low albumin concentrations. In two of these patients, the ratio, albumin : alpha1-antitrypsin in the meconium was within normal limits but, within two months of birth, the albumin : alpha1-antitrypsin ratio in the faeces of both children was greater than 3.0 suggesting that pancreatic insufficiency had developed.

Topics: Albumins; alpha 1-Antitrypsin; Chymotrypsin; Cystic Fibrosis; Feces; Humans; Immunoelectrophoresis; Infant, Newborn; Infant, Newborn, Diseases; Mass Screening; Meconium; Methods

Ten adolescent and young adults with cystic fibrosis (CF) have had well-documented recurrent attacks of acute pancreatitis. The diagnosis of CF in each patient was delayed because they did not have pancreatic insufficiency. The diagnosis of CF was documented by the typical pulmonary involvement and elevated sweat sodium and chloride levels in all cases and a positive family history in six of the ten patients. Two patients were diagnosed as having acute pancreatitis before the diagnosis of CF was made, thus indicating that acute pancreatitis may be the presenting complaint in the young adult with CF. The diagnosis of acute pancreatitis was based on the presence of severe abdominal pain, usually with vomiting, tenderness in the mid-epigastrium, elevated serum and urinary amylase and serum lipase. Attacks were precipitated by fatty meals, alcohol ingestion; postcholecystectomy and tetracycline administration. In some patients no precipitating event could be elicited. Intravenous secretin-pancreozymin stimulation tests revealed a diminished bicarbonate secretion with little effect on the secretion of the zymogen enzymes. A mild attack of pancreatitis occurred after secretin-pancreozymin stimulation. The endocrine pancreatic function tested in four patients was normal as revealed by the glucose tolerance tests and determinations of serum insulin, growth hormone and free fatty acid. Transduodenal pancreatograms were performed in three patients; one showed a normal pancreatic duct, one showed duct obstruction and in the third patient a beady type of narrowing was found. The selenomethionine Se 75 uptake of the pancreas was noted only in the head of the pancreas. This suggests that loss of function occurs initially to a greater extent in the tail and body of the pancreas. Three patients died and showed characteristic lesions of CF.

Topics: Acute Disease; Adolescent; Adult; Amylases; Chlorides; Cholecystokinin; Chymotrypsin; Cystic Fibrosis; Female; Glucose Tolerance Test; Humans; Intubation, Gastrointestinal; Lipase; Magnesium; Male; Methionine; Pain; Pancreas; Pancreatitis; Potassium; Recurrence; Secretin; Selenium; Sodium; Trypsin

Topics: Antigens; Beta-Globulins; Blood Proteins; Chymotrypsin; Cystic Fibrosis; gamma-Globulins; Humans; Immunoelectrophoresis; Immunoglobulin A; Immunoglobulin G; Infant; Meconium; Sodium Chloride; Sweat; Transferrin; Trypsin

Topics: Bone Marrow; Chymotrypsin; Cystic Fibrosis; Erythrocytes; Greece; Hematocrit; Hemoglobins; Hemosiderin; Humans; Infant; Iron; Pancreatic Elastase; Protein Binding; Trypsin

Topics: Chymotrypsin; Clinical Enzyme Tests; Costs and Cost Analysis; Cystic Fibrosis; Endopeptidases; False Negative Reactions; Feces; Humans; Indicators and Reagents; Infant, Newborn; Infant, Premature; Mass Screening; Metabolism, Inborn Errors; Pancreas; Trypsin

Topics: Adolescent; Adult; Body Height; Body Weight; Carboxypeptidases; Carotenoids; Celiac Disease; Child; Chymotrypsin; Cystic Fibrosis; Dietary Fats; Feces; Growth; Humans; Intestinal Secretions; Lipase; Lipids; Malabsorption Syndromes; Nitrogen; Nutritional Physiological Phenomena; Pancreatin; Prognosis; Trypsin; Xylose

Topics: Adolescent; Adult; Biopsy; Carbon Isotopes; Carboxypeptidases; Chymotrypsin; Cystic Fibrosis; Female; Humans; Immunoglobulin A; In Vitro Techniques; Intestinal Mucosa; Jejunum; Leucine; Male; Pancreatitis; Trypsin

Topics: Body Weight; Celiac Disease; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Duodenum; Feces; Humans; Infant; Intestinal Diseases; Liver Diseases; Pancreas; Pancreatic Diseases; Time Factors

Topics: Age Factors; Child; Chromatography, Affinity; Chymotrypsin; Cystic Fibrosis; Feces; Heterozygote; Homozygote; Humans; Trypsin

Topics: Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Respiratory Tract Infections; Tetracycline; Trypsin; Urinary Tract Infections

Topics: Adolescent; Amylases; Bicarbonates; Child; Child, Preschool; Cholecystokinin; Chymotrypsin; Cystic Fibrosis; Feces; Female; Humans; Infant; Infant, Newborn; Intubation, Gastrointestinal; Lipase; Male; Pancreas; Pancreatic Juice; Secretin; Trypsin; Viscosity

Topics: Amylases; Chymotrypsin; Cystic Fibrosis; Endomyocardial Fibrosis; Humans; Infant; Infant, Newborn; Lipase; Lipomatosis; Male; Myocardium; Pancreas; Pancreatic Diseases; Pancreatic Juice; Pancreatin; Trypsin

Topics: Adolescent; Adult; Amylases; Bicarbonates; Carboxypeptidases; Child; Child, Preschool; Chlorides; Cholecystokinin; Chymotrypsin; Cystic Fibrosis; Female; Humans; Lipase; Male; Pancreatic Juice; Secretin; Trypsin

Topics: Adolescent; Autoanalysis; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Feces; Humans; Infant; Malabsorption Syndromes; Secretory Rate; Trypsin

Topics: Adolescent; Adult; Aged; Aldosterone; Bronchitis; Chymotrypsin; Cystic Fibrosis; Electrolytes; Feces; Female; Heterozygote; Humans; Male; Middle Aged; Pancreas; Pancreatic Juice; Parotid Gland; Sweat Glands; Trypsin

Topics: Adolescent; Child; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Feces; Humans; Infant; Infant, Newborn; Pancreatic Juice; Trypsin

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; Cystic Fibrosis; Drug Combinations; Hematologic Tests; Humans; Trypsin

Topics: Amylases; Carboxypeptidases; Chymotrypsin; Cystic Fibrosis; Deoxyribonuclease I; Deoxyribonucleases; DNA; Endopeptidases; Humans; Hyaluronoglucosaminidase; In Vitro Techniques; Muramidase; Pancreas; Papain; Ribonucleases; Solubility; Sputum; Streptodornase and Streptokinase; Streptokinase; Trypsin

Topics: Chymotrypsin; Cystic Fibrosis; Disease; Duodenum; Humans; Intestinal Secretions; Pancreas; Pancreatic Diseases; Peptide Hydrolases