Fecal elastase-1 determination: 'gold standard' of indirect pancreatic function tests?

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Now that fecal elastase is available in the United States,should clinicians start using it?

Fecal elastase-1 estimation is an alternative fecal enzyme test for the detection of exocrine pancreatic insufficiency, which, in contrast to chymotrypsin estimation, uses monoclonal antibodies against human pancreatic elastase and is thus unaffected by simultaneous pancreatic enzyme replacement therapy. Similar to other indirect pancreatic function tests, it has a high sensitivity rate for detecting severe functional impairment of the gland. However, the two major problems for the clinician—namely diagnosing mild to moderate exocrine pancreatic insufficiency or chronic pancreatitis and differentiating pancreatic from nonpancreatic steatorrhea or diarrhea—cannot be solved by pancreatic elastase-1 determination. The test cannot be used in non-formed stool (ie, diarrhea) unless the stool is lyophilized. All in all, this new test does not seem to be the gold standard for pancreatic function that we have been waiting for.     

Fecal isoamylase activity in patients with pancreatic diseases.

Fecal isoamylase activity was studied in 93 consecutive patients (26 in the recovery stage of acute pancreatitis, 24 with chronic pancreatitis, 13 with pancreatic cancer, and 30 with other gastrointestinal diseases) and compared with fecal chymotrypsin activity and the results of the secretin test. Seventy-six healthy subjects were studied as controls. Both pancreatic (p)-type and salivary (s)-type isoamylase activities in stool were determined by inhibitor assay as well as cellulose acetate electrophoresis. The mean fecal amylase activity in healthy subjects was 757 +/- 88 IU/g (p-type isoamylase: 77 +/- 2%, s-type isoamylase: 23 +/- 2%). There was a good correlation between fecal p-type isoamylase and chymotrypsin activities (r = 0.625, p less than 0.001). Fecal p-type isoamylase activity in patients with chronic pancreatitis and pancreatic cancer was significantly lower than in healthy subjects (p less than 0.001). Patients with moderate and severe exocrine pancreatic insufficiency as determined by the secretin test had significantly lower fecal p-type isoamylase activity. Daily fat intake did not affect fecal amylase or isoamylase activities. Fecal s-type isoamylase activity in patients with hypoacidity was significantly higher than in patients with hyperacidity, but no difference in fecal p-type isoamylase activity was observed. It is concluded that analysis of fecal isoamylase activity is useful in the assessment of pancreatic function.     

Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test.

BACKGROUND: 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. AIM: 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'. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Faecal elastase 1 determination proved to be a highly sensitive and specific tubeless pancreatic function test.     

Fecal Elastase Test: Evaluation of a New Noninvasive Pancreatic Function Test

Objectives: Pancreatic elastase is highly stable along the intestinal tract. A new ELISA is commercially available to measure human specific elastase-1 concentration in stool. We evaluated the behavior of this fecal elastase test (FET) compared with other indirect pancreatic function tests in patients with chronic pancreatitis (CP).
Methods: A total of 69 patients were included in the study, 20 of whom were diagnosed with CP according to the findings on ERP and CT; 13 patients had other pancreatic diseases, and the remaining 36 patients had gastrointestinal or hepatic disorders. All patients' elastase-1 concentrations and chymotrypsin activities [fecal chymotrypsin test (FCT)] were measured, and the serum pancreolauryl test (PLT) was performed.
Results: Similar to PLT, fecal elastase concentration was significantly decreased in patients with moderate and severe CP (assessed by ERP) compared with patients with extra pancreatic disorders. However, and contrarily to PLT, FET was not affected by gastric resection, matabsorption due to intestinal disease, or marked alteration of the gastric motility. The sensitivity of FET was 100% for moderate to severe CP but 0% for mild CP; the specificity was 83%. Compared with other indirect pancreatic function tests, FET appears to be as sensitive as PLT and as specific as FCT, and it is clearly more specific than PLT and more sensitive than FCT. Unlike FCT, FET was not affected by oral enzyme supplementation.
Conclusion: FET is a simple and accurate functional test for CP, and it is hardly influenced by extrapancreatic disorders or therapy with exogenous enzymes.     

Update on the evaluation of pancreatic exocrine status in cystic fibrosis

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

Exocrine and Endocrine Pancreatic Function in 21 Patients Suffering from Autoimmune Pancreatitis before and after Steroid Treatment

Background/Aim: Autoimmune pancreatitis (AIP) responds rapidly and dramatically to steroid therapy. The aim of this study was to evaluate pancreatic exocrine and endocrine function in patients suffering from AIP both before and after steroid therapy. Patients and Methods: Fecal elastase 1 and diabetes were evaluated before steroid therapy and within 1 month of its suspension in 21 patients (13 males and 8 females, mean age 43 ± 16.5 years) diagnosed as having AIP between 2006 and 2008. Results: At clinical onset, fecal elastase 1 was 107 ± 126μg/g stool.Thirteen patients (62%) showed severe pancreatic insufficiency (<100 μg/g stool), 4 (19%) had mild insufficiency (100–200 μg/g stool), while 4 (19%) had normal pancreatic function (1200 μg/g stool). Before steroids, diabetes was diagnosed in 5 patients (24%), all of whom had very low levels of fecal elastase 1 (<19 μg/g stool). Following steroids, fecal elastase 1 increased in all patients (237 8 193 μg/g stool) and observed levels were significantly higher than those seen before steroids (p = 0.001). Conclusions: Patients suffering from AIP display exocrine and/or endocrine pancreatic insufficiency at clinical onset. These insufficiencies improve after steroid therapy.     

Faecal elastase 1: not helpful in diagnosing chronic pancreatitis associated with mild to moderate exocrine pancreatic insufficiency

Background/Aim—The suggestion that estimation offaecal elastase 1 is a valuable new tubeless pancreatic function testwas evaluated by comparing it with faecal chymotrypsin estimation inpatients categorised according to grades of exocrine pancreatic insufficiency (EPI) based on the gold standard tests, thesecretin-pancreozymin test (SPT) and faecal fat analysis.
Methods—In 64 patients in whom EPI was suspected,the following tests were performed: SPT, faecal fat analysis, faecalchymotrypsin estimation, faecal elastase 1 estimation. EPI was gradedaccording to the results of the SPT and faecal fat analysis as absent,mild, moderate, or severe. The upper limit of normal for faecalelastase 1 was taken as 200 µg/g, and for faecal chymotrypsin 3 U/gstool. Levels between 3 and 6 U/g stool for faecal chymotrypsin areusually considered to be suspicious for EPI. In this study, both 3 and 6 U/g stool were evaluated as the upper limit of normal.
Results—Exocrine pancreatic function was normal in34 patients, of whom 94, 91, and 79% had normal faecal elastase 1 andfaecal chymotrypsin levels (<3 U/g and <6 U/g) respectively. Thirtypatients had EPI, of whom 53, 37, and 57% had abnormal faecal enzymelevels (differences not significant). When EPI was graded as mild,moderate, or severe, 63% of patients had mild to moderate EPI, and37% had severe EPI. In the latter group, between 73 and 91% ofpatients had abnormal faecal enzymes. In the group with mild tomoderate EPI, abnormal test results were obtained for both faecalenzymes in less than 50% of the patients (differences notsignificant). Some 40% of the patients had pancreatic calcifications.There were no significant differences for either faecal enzyme between the two groups with and without pancreatic calcifications. In 62% ofthe patients who underwent an endoscopic retrogradecholangiopancreatography (ERCP), abnormal duct changes were found.Again, there were no significant differences for either faecal enzymebetween the two groups with abnormal and normal ERCP.
Conclusion—Estimation of faecal elastase 1 is notdistinctly superior to the traditional faecal chymotrypsin estimation.The former is particularly helpful only in detecting severe EPI, but not the mild to moderate form, which poses the more frequent and difficult clinical problem and does not correlate significantly withthe severe morphological changes seen in chronic pancreatitis.

Keywords:faecal elastase 1; faecal chymotrypsin; secretin-pancreozymin test; faecal fat analysis; exocrine pancreaticinsufficiency; diagnosis

     

Fecal chymotrypsin in alcoholic liver disease

Fecal chymotrypsin assays were done on 34 patients with alcoholic liver disease. Only one such patient had low fecal activity. Correlation of fecal chymotrypsin with fat malabsorption and duodenal drainage tests was undertaken. Although fat malabsorption was frequently encountered (13 of 34), the low incidence of abnormal fecal chymotrypsin suggests that severe pancreatic exocrine insufficiency is an unusual occurrence in this population. Six patients had pancreozymin-secretin tests and Lundh test meals and one showed abnormal results, but fecal chymotrypsin assays were uniformly normal in this small subgroup.     

A Single-Specimen Fecal Chymotrypsin Test in the Diagnosis of Pancreatic Insufficiency: Correlation with Secretin- Cholecystokinin and NBT-PABA Tests

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 NBTPABA 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 < 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 < 0.01) and with the percentage of recovery of urinary PABA (r = 0.44, p < 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.     

Exocrine pancreatic function in children and adolescents with insulin-dependent diabetes mellitus.

Exocrine pancreatic function was evaluated in 21 diabetic children on the basis of a p-aminobenzoic acid (PABA) test and a determination of fasting serum amylase, pancreatic isoamylase, lipase, trypsin and elastase levels. Fecal chymotrypsin was also measured. Compared to the controls, the diabetic children had significantly lower levels of trypsin (P less than 0.001) and elastase (P less than 0.02). Fecal chymotrypsin appeared to be significantly lower (P less than 0.01) in diabetic children than in controls but in all patients fecal chymotrypsin values registered above the limit considered to be normal. No significant correlation was observed between pancreatic enzyme concentrations, serum and urinary PABA values, and chronologic age, HbA1 and insulin requirement. Only for serum PABA a significant negative correlation with duration of disease (P less than 0.01) has been observed. These data show that exocrine pancreatic function may be abnormal in children with IDDM.     

Method of Measurement of Pancreatic Elastase II Activity and Postnatal Development of Proteases in Human Duodenal Juice and Bovine and Porcine Pancreatic Tissue

A specific method for pancreatic elastase IIactivity analysis was developed. True elastase IIactivity could be discriminated from that of elastase Iand chymotrypsin. The postnatal development of four pancreatic proteases in the duodenal juice ofchildren and in the pancreatic homogenates of calves andpiglets was measured. The study was carried out onpatients without (14 children) and with (5 children) pancreatic insufficiency. Calves and pigletswere either milk-fed or weaned until slaughter atdifferent ages. Profiles of enzyme development wereglobally similar in milk-fed piglets and calves, while in children without pancreatic insufficiency,no significant change was observed between 4 and 168months. 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 withthe digestion of milk protein. In contrast, elastase Iand trypsin activities increased markedly after weaning in connection with the intake of solidfood.     

A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency

OBJECTIVE: The safety and efficacy of Minimicrospheres, which are enteric-coated, delayed-release pancrelipase capsules, on fat absorption in pediatric/adolescent and adult cystic fibrosis (CF) patients was assessed. Exocrine pancreatic insufficiency, common in CF patients, causes steatorrhea due to insufficient release of pancreatic enzymes. METHODS: In the open-label phase, 97 CF patients with pancreatic insufficiency and steatorrhea were stabilized on a high-fat diet and administered pancrelipase. Seventy-four patients with >80% coefficient of fat absorption received placebo or pancrelipase in the double-blind phase. Fat intake and excretion, stool frequency and consistency, and clinical global improvement were recorded. RESULTS: Average daily fat intake was comparable between treatment groups within each age group (adults vs pediatric/adolescent), but placebo patients had a significant (p < 0.001) mean decrease in coefficient of fat absorption (adult, 36.9 percentage points; pediatric/adolescent, 34.9 percentage points) from open-label to double-blind treatment compared to pancrelipase patients (adult, 2 percentage points; pediatric/adolescent, 3.25 percentage points); this difference was caused by a greater (p < or = 0.001) increase in mean fecal fat excretion (grams per day) in the placebo groups compared to pancrelipase groups (adult: 61.9 vs 2.3; pediatric/adolescent: 45.4 vs 4.1). Change in mean stool frequency from open-label to double-blind phases was significantly different (p < or = 0.002) between treatment groups, with increases in placebo groups and no difference (adult) or decrease (pediatric/adolescent) in pancrelipase groups. Pancrelipase patients' stool consistency remained about the same from open-label to double-blind. Placebo patients' stool consistency decreased (became softer) from open-label pancrelipase to double-blind placebo. Clinical global improvement data showed that > or =83% of pancrelipase patients improved or remained unchanged. CONCLUSIONS: Enteric-coated, delayed-release (Minimicrospheres) pancrelipase capsules are an effective treatment for steatorrhea associated with pancreatic insufficiency in patients with cystic fibrosis.     

Quantitative Analysis of Stool Losses in Adult Celiac Disease: Use of Near-Infrared Analysis Reconsidered

Background: An attempt has been made to establish whether near-infrared stool analysis is more suitable for quantifying malabsorption than the traditional stool fat analysis. A group of celiac disease (CD) patients was used as index population. Methods. Stool fat, nitrogen, and water were measured with near-infrared analysis of 1- and 3-day stool collections in 96 celiac disease patients on a free diet (in 39 also on gluten-free diet) and in 96 matched controls and 14 patients with latent CD. Results. The fecal output of fat, nitrogen, and water was significantly increased in free-diet CD, whereas their percentage content was only slightly modified compared with controls. None of the variables under consideration differed significantly between the 24-h and 72-h stool specimens. Conclusion. Our data show that the high value of fecal fat, nitrogen, and water, in celiac disease, are mainly due to the fecal weight, whereas the percentage composition of stool does not offer additional diagnostic information. Furthermore, 3-day stool collection is not necessary to confirm or rule out malabsorption in most patients. Near infrared analysis of 24-h specimens is time- and cost-effective and may increase the use of stool analysis and be usefully employed to monitor the clinical follow-up of patients with chronic diarrhea.     

Anti-obesity effects of lipase inhibitor CT-II, an extract from edible herbs, Nomame Herba, on rats fed a high-fat diet

OBJECTIVE: To investigate the inhibitory effects of CT-II, extract of Nomame Herba, on lipase activity in vitro and on obesity in rats fed a high-fat diet in vivo. DESIGN: The assay for the inhibitory effect of CT-II on lipase activity was performed by measuring released free fatty acids after the incubation of the medium with CT-II, porcine pancreatic lipase and triolein (experiment 1). In vivo experiments, lean rats or obese rats (570-718 g) were fed a high-fat diet containing 60% fat with or without CT-II for 8 weeks (experiment 2), for 14 days (experiment 3) or for 12 weeks (experiment 4), respectively. MEASUREMENT: The time course of body weight, food intake, organ weight (parametrial fat, liver, heart and kidney) and plasma parameters (triglyceride, total cholesterol, glucose, AST, ALT and insulin), fecal output of total fat and total cholesterol were measured. Hepatic histological examinations were also performed. RESULTS: CT-II inhibited the porcine lipase activity dose-dependently in vitro (experiment 1). Body and liver weight were reduced and hepatic histological examination showed an amelioration of fatty liver in CT II treated animals (experiment 2). CT-II significantly inhibited body weight gain and plasma triglyceride elevation in a dose-dependent manner, without affecting food intake in lean rats fed the high-fat diet. Elevated plasma AST and ALT were also decreased (experiment 3). When obese rats fed the high-fat diet were treated with CT-II for up to 6 months, body weight was initially reduced and thereafter weight gain was significantly suppressed. Total body fat was also significantly reduced and significant reduction of plasma AST and ALT was observed (experiment 4). CONCLUSIONS: These results demonstrated that the lipase inhibitor CT-II is effective in preventing and ameliorating obesity, fatty liver and hypertriglyceridemia in rats fed a high-fat diet.     

Comparison of fecal elastase-1 determination with the secretin-cholecystokinin test in patients with cystic fibrosis

BACKGROUND: The secretin-cholecystokinin (CCK) test is the gold standard in the evaluation of exocrine pancreatic insufficiency. Because of its invasive character, it is of limited value in cystic fibrosis (CF) patients, especially in those with severe respiratory disease. The aim of the study was to evaluate the sensitivity of fecal elastase-1 in relation to the secretin-CCK test and quantitative fecal fat excretion in CF patients. METHODS: The study comprised 28 patients (11 females and 17 males) aged 4 to 20 years. In all patients the secretin-CCK test and determination of fecal elastase-1 concentration (with enzyme-linked immunosorbent assay) and fecal fat excretion were performed. RESULTS: The range of fecal elastase-1 was from undetectable to 485 microg/g (mean, 84.6+/-119.9 microg/g) and of fecal fat excretion from 1.0 to 55.1 g/day (mean, 15.0+/-12.2 g/day). On the basis of the results of the secretin-CCK test (and fecal fat analysis) exocrine pancreatic insufficiency was divided into three subgroups: mild (I), moderate (II), and severe (III). Four patients were classified in subgroup I, 4 in II and 20 in III. Fecal elastase (elastase-1) results were 332.0+/-124.9 microg/g in subgroup I, 96.9+/-45.7 microg/g in subgroup II, and 32.1+/-41.2 microg/g in subgroup III. The fecal elastase-1 sensitivity with a cut-off point of 200 microg/g was 89.3% for all patients, 100% for patients in subgroups II and III, but only 25.0% for patients in subgroup I; the specificity was 96.4%. Linear regression analysis showed a statistically significant correlation between fecal elastase (elastase-1) and duodenal volume, bicarbonate, amylase, lipase, and trypsin secretion (in all cases P < 0.001). CONCLUSIONS: Measurement of fecal elastase-1 is simple and very useful for assessing the exocrine pancreatic function in CF patients. Elastase is highly specific in severe and moderate exocrine pancreatic insufficiency, but it is rather unspecific for milder forms of pancreatic insufficiency.     

The assay of chymotrypsin in stool as a simple and effective test of exocrine pancreatic activity in cystic fibrosis

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.     

Pancreolauryl test

The sensitivity and specificity of the pancreolauryl test was evaluated in comparison with the NBT-PABA test, the estimation of fecal chymotrypsin and fat, and the secretin-pancreozymin test in 168 patients with and without pancreatic disease. The overall sensitivity rate was as follows: pancreolauryl test 90%, NBT-PABA test 86%, fecal chymotrypsin 66%. In patients with pancreatic steatorrhea the sensitivity of the pancreolauryl test was 100%, the NBT-PABA test 97%, and the fecal chymotrypsin estimation 92%. The specificity of these tests was: pancreolauryl test 97.6%, fecal chymotrypsin 87%, and NBT-PABA test 81.8%. The pancreolauryl test may be recommended as a noninvasive easy-to-perform tubeless pancreatic function test with a sufficiently high sensitivity and specificity.     

Fecal chymotrypsin: study on some characteristics of the enzyme.

A Lineweaver-Burk plot demonstrated that the apparent Michaelis constants are identical for chymotrypsin (CT) in duodenal juice and in feces of the same patient. CT in fecal homogenates exhibits exhibits a remarkable stability and is bound to particles to a considerable but variable extent. The pH optimum of CT in human feces is somewhat higher as compared to pure bovine pancreatic CT. All measurements of fecal CT activity should, therefore, be performed at pH 9.0. The distribution of CT among the fecal mass has been investigated. There were considerable differences between CT activities in random fecal specimens and in the corresponding stool collections. However, if the results were expressed in terms of 'normal' and 'abnormal', 113 out of 120 random fecal specimens gave the same results as the corresponding stool collections. It is concluded that the risk of 'false-normal' values cannot be effectively reduced by determination of CT outputs in stool collections (or by using continuous markers) instead of CT activities in random stool specimens.     

-Carnitine treatment in the hyperlipidemic rabbit

A study was designed to examine the hypolipidemic effect of -carnitine treatment (4 weeks, 170 mg/kg/d) in rabbits fed a high fat diet (5% corn oil/0.5% cholesterol, w/w). Eight weeks of exposure to the high fat diet significantly increased plasma total cholesterol and triglycerides. VLDL associated triglycerides, cholesterol, apo-B, and total protein were also significantly increased with the diet. There was no change in HDL-cholesterol levels. Plasma concentration of carnitine (free, acyl, and total) all increased significantly with the high fat diet. The content of free, short-chain, and total carnitine were decreased in the liver whereas the content of long-chain acylcarnitines was increased. The diet generated a significant steatosis within the livers of these animals. Four weeks of treatment of -carnitine reduced the extent of the liver steatosis and significantly decreased plasma total cholesterol, triglycerides, VLDL associated triglycerides, cholesterol, and total protein. HDL-cholesterol levels were unaffected by the treatment. All plasma fractions of carnitine (free, acetyl, acyl, and total) were significantly increased above those levels seen after 8 weeks of the high fat diet alone. The content of liver carnitine and its esters was normalized following treatment. The high fat diet decreased liver HMG-CoA reductase activity and increased the activities of 7-α-hydroxylase and acylcholesterol acyltransferase (ACAT). -Carnitine treatment blunted the magnitude of the diet induced increase in 7α-hydroxylase activity, yet overall the activity still remained elevated relative to controls. ACAT activity increased (1.5 times) with the high fat diet and increased further (4.5 times) following carnitine treatment. The mechanism(s) underlying the hypolipidemic effect of -carnitine treatment in this animal model remain to be elucidated.