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PubMed1982

The influence of oral contraceptives on the composition of bile.

The increased risk of cholelithiasis during intake of oral contraceptives may be due to estrogen-induced saturation of the bile with cholesterol. In a randomized, prospective, crossed-over double-blind study 20 healthy women after roentgenological exclusion of gall-stones received either 1.0 mg of norethindrone acetate and 50 microgram ethinyl estradiol daily - as usual in oral contraception - for 21 days with 7 days of placebo treatment in each cycle or one fifth of this hormone dose in form of a continuous daily medication. After a 4 month's treatment the medication form was crossed-over. At the beginning of the study, before the cross-over and after the study bile was collected by duodenal intubation after a 12-h fast and the lithogenic index as a measure for cholesterol saturation of the bile was determined. No correlation between the dose and the lithogenic index was demonstrated, neither in 15 women, who had used oral contraceptives before the study nor in five women without any previous hormonal contraceptives.

Adult↗

PubMed1988

A new faecal chymotrypsin method for evaluating the exocrine pancreatic function in patients with different pancreatic diseases.

Using a new colorimetric method we measured the faecal chymotrypsin in 407 subjects, divided as follows: 252 adult subjects with a normal exocrine pancreatic function as shown by duodenal intubation, 24 adult patients with a mild to moderate pancreatic insufficiency, and 26 adult patients with severe pancreatic insufficiency. In addition, 40 healthy children, 50 children with chronic diarrhoea, and 15 with cystic fibrosis were studied before and after substituting enzyme therapy. Faecal chymotrypsin was found to be useful in evaluating the degree of exocrine functional insufficiency in subjects with diseases of the pancreas that had already been clinically ascertained. The same cannot be said for its ability to provide an early diagnosis of subjects with a slight-moderate insufficiency in exocrine pancreatic function.

Adult↗

PubMed1987

Fatty acid composition of phospholipids in bile in man: promoting effect of deoxycholate on arachidonate.

Ninety-five percent of phospholipids (PLs) in bile is secreted as phosphatidylcholine or lecithin. The study of fatty acid patterns of phospholipids present in gallbladder bile could help clarify whether a preponderance of certain fatty acids could play a role in cholesterol gallstone formation in man. In acute bile acid-exchange experiments, it was found that more hydrophobic bile acids did promote the excretion in bile of PL rich in arachidonic acid (a prostaglandin precursor) and stearic acid. We studied, therefore, bile acid, cholesterol and phospholipid fatty acid patterns (measured by gas chromatography) in gallbladder bile, obtained by duodenal intubation and cholecystokinin-stimulation of 24 healthy volunteers with normal liver/gallbladder function (ultrasound). PL-fatty acid composition (mean % +/- SD) was 41.40 (+/- 1.41) for palmitic acid, 2.68 (+/- 0.82) for palmitoleic acid, 5.50 (+/- 1.55) for stearic acid, 12.09 (+/- 0.98) for oleic acid, 32.83 (+/- 3.04) for linoleic acid and 5.64 (+/- 1.59) for arachidonic acid. The proportion of biliary deoxycholate was positively correlated with arachidonic acid (r = 0.71; p less than 0.01), whereas chenodeoxycholate was inversely correlated with arachidonic acid (r = -0.53; p less than 0.01). There was a positive correlation between biliary chenodeoxycholate and linoleic acid (r = 0.48; p less than 0.05) and a negative correlation between biliary deoxycholate and linoleic acid composition (r = 0.68; p less than 0.01). Also a correlation was found between palmitic acid and cholesterol saturation index (r = 0.49; p less than 0.05). We conclude that the hydrophobic bile acid deoxycholate, which does not desaturate cholesterol in bile, promotes the biliary excretion of arachidonic acid. Since arachidonic acid could induce the gallbladder mucosa to produce prostaglandins and mucus, increased biliary PL-arachidonic acid composition might be a factor in cholesterol gallstone disease.

Adult↗

PubMed1989

On optimising the diagnostic yield of secretin pancreozymin tests.

The results of 407 secretin-pancreozymin tests were analysed by a variety of statistical methods, in an attempt to optimize diagnostic yield. The best diagnostic yield accrued from selection of a point corresponding to 95% specificity and 60% sensitivity on each of two virtually superimposable receiver-operator curves--using either bicarbonate output or a discriminant function derived from multivariate analysis--and the anticipated yield approximated to that realised in a further prospective series of 150 cases. At a 25% hypothetical local prevalence of chronic pancreatic disease (including chronic pancreatitis and pancreatic cancer), the positive predictive value was 80%, the negative predictive value 88% and the efficiency was 86%--values that are not dissimilar to those reported in a study in which both hormones were given simultaneously by constant intravenous infusion for 105 min with multivariate analysis of the results. We conclude that (a) measurement of bicarbonate output in 30 min after an appropriate dose of secretin given as a bolus injection yields results that are comparable to those obtained when secretin and pancreozymin are given by constant intravenous infusion in doses to evoke maximal secretory responses; and (b) the yield of hormone tests using duodenal intubation is far from ideal.

Cholecystokinin↗

PubMed1993

Biochemical tests in the diagnosis of chronic pancreatitis and in the evaluation of pancreatic insufficiency.

Chronic pancreatitis (adults) and cystic fibrosis (children) are the most common diseases leading to exocrine pancreatic insufficiency that, when reduced to < 5% of normal function, is characterised by steatorrhoea. The pathogenesis of the former condition is outlined, and recent concepts are emphasized. Biochemical tests to detect pancreatic insufficiency and to identify pancreatic disease as the cause of steatorrhoea include: serum enzyme tests (lipase, amylase, trypsin); stool chymotrypsin; isotopic tests based upon the assimilation of [14C] lipids and starch or excretion of the isotope as breath CO2, as well as the dual-labelled Schilling test; oral function tests utilising substrates hydrolysed by pancreatic enzymes such as benzoyl tyrosyl-p-aminobenzoic acid and fluorescein dilaurate; and duodenal intubation studies following meal-induced or hormonal stimulation of the pancreas. The rationale for these tests and the cumulative clinical experience of their utility are reviewed. A recommended diagnostic strategy is briefly presented. The role of various biochemical procedures to evaluate the efficacy of pancreatic enzyme replacement therapy is also described.

4-Aminobenzoic Acid↗

PubMed1986

Decrease in plasma amino acid level after secretin and pancreozymin as an indicator of exocrine pancreatic function.

Total plasma amino acids were determined by the ninhydrin method in 37 controls and 30 patients with chronic pancreatitis and normal (n = 7) pancreatic enzyme output or mildly (n = 6), moderately (n = 8), and severely (n = 9) reduced pancreatic enzyme output. Intravenous injection of synthetic secretin did not change plasma amino acid levels. During a combined intravenous infusion of secretin (1 CU/kg X h) and pancreozymin (1 Ivy dog unit/kg X h), amino acid concentrations decreased maximally by 31% +/- 19% (mean +/- SD) in controls, but only by 6.3% +/- 4.7% in patients with exocrine pancreatic insufficiency (p less than 0.001 vs. controls). At a cutoff limit of less than or equal to 12% for the decrease in total amino acids, mild exocrine insufficiency (20%-40% of mean normal chymotrypsin output) was identified with a sensitivity of 67%, whereas moderately to severely impaired function was detected in every case (overall sensitivity 91%). Pancreatic function, as assessed by duodenal intubation and the tubeless amino acid test, was significantly correlated (e.g., rs = 0.73 for chymotrypsin output, p much less than 0.001). In 15 controls and 13 patients with mildly (n = 5) to severely impaired pancreatic function, individual amino acids were estimated. Plasma serine kinetics completely distinguished both groups. Kinetics of serine, valine, isoleucine, and histidine correlated even better with pancreatic function than those of total amino acids.

Adult↗

PubMed1990

Effects of ursodeoxycholic acid on gallbladder contraction and cholecystokinin release in gallstone patients and normal subjects.

It has been previously suggested that treatment with ursodeoxycholic acid leads to decreased gallbladder emptying. The proposed mechanism is decreased release of cholecystokinin through negative feedback control by an increased amount of intraduodenal bile acids. In the present study we examined cholecystokinin release and gallbladder contraction after oral administration of a commercial fatty meal (Sorbitract; Dagra, Diemen, The Netherlands) using ultrasonography in eight normal subjects and eight gallstone patients before and after 1 and 4 weeks of treatment with ursodeoxycholic acid (10 mg kg-1.day-1). Fasting gallbladder volume increased in 15 of 16 subjects during treatment (P less than 0.01). Minimal volume did not change. Therefore, both absolute and relative gallbladder emptying increased during therapy. Maximal decrement of gallbladder volume in milliliters and percentage as well as integrated gallbladder contraction during 90 minutes in milliliters and percentage were significantly increased after 1 and 4 weeks of treatment with ursodeoxycholic acid when compared with data before therapy. Gallstone patients tended to have larger fasting and residual gallbladder volumes than normal subjects, whereas parameters for the amount of bile expelled (maximal decrement of gallbladder volume and integrated gallbladder contraction in milliliters and percentage) did not differ. Release of cholecystokinin did not change during treatment and did not differ significantly between patients and normal subjects. Mean relative percentage of ursodeoxycholic acid in bile during treatment in 13 subjects consenting to have duodenal intubation was 47% (range 31%-60%). Changes of fasting gallbladder volume after institution of bile acid treatment correlated significantly (r = 0.74, P less than 0.01) with changes of cholesterol saturation index but not with relative percentage of ursodeoxycholic acid in bile. This study indicates that gallbladder emptying does not decrease during treatment with ursodeoxycholic acid. Moreover, there is no evidence of decreased cholecystokinin release.

Adult↗

PubMed1994

Is the plasma amino acid consumption test an accurate test of exocrine pancreatic insufficiency?

BACKGROUND/AIMS: The amino acid consumption test has been proposed as an accurate test of exocrine pancreatic function. The diagnostic accuracy of this test was determined by simultaneously measuring plasma amino acids and enzyme secretion during stimulation of the pancreas with cholecystokinin octapeptide (CCK-OP) in 60 consecutive patients suspected of having pancreatic insufficiency. METHODS: All patients underwent duodenal intubation and intravenous infusion of CCK-OP (40 ng.kg-1.h-1). Pancreatic enzyme (lipase and trypsin) outputs and plasma amino acids were measured for a period of 1 hour. Total and individual plasma amino acids were quantitated by ion-exchange chromatography. The severity of pancreatic insufficiency was graded on the basis of enzyme output during CCK-OP infusion. RESULTS: There was no relationship between pancreatic enzyme output and plasma concentrations of individual or total amino acids before or during CCK-OP stimulation. Using a total amino acid decrease of 12% as the cutoff, the amino acid consumption test was 91% sensitive, but very nonspecific (21% specificity) for detection of pancreatic insufficiency. CONCLUSIONS: The amino acid consumption test with CCK-OP stimulation does not discriminate between patients with normal and impaired exocrine pancreatic secretion.

Adult↗

PubMed1980

Prostaglandins in human duodenal secretions.

Prostaglandins E1, E2 and F2 alpha were measured in duodenal secretions from two healthy, fasting male subjects. Secretions were collected by duodenal intubation prior to, and following, stimulation by secretin and cholecystokinin. Prostaglandins were measured with a radioimmunoassay technique. The ranges of concentrations found were PGE1: 2.4-110 ng/ml, PGE2: 0.004-1.51 ng/ml, and PGG2 alpha: 0.44-14.6 ng/ml.

Adult↗

PubMed2004

Fecal chymotrypsin and elastase-1 determination on one single stool collected at random: diagnostic value for exocrine pancreatic status.

OBJECTIVE: 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. DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Adolescent↗

PubMed1985

Effect of secretin upon the levels of pancreatic enzymes in blood serum.

We have evaluated the serum changes of trypsin, pancreatic isoamylase and lipase, after rapid infusion of secretin, in 45 patients with chronic pancreatitis compared with 35 healthy control subjects. On the basis of duodenal intubation results, chronic pancreatitis patients were divided into two subgroups at different levels of functional impairment. Using the peak activities of the enzymes we have been able to separate the two chronic pancreatitis subgroups by statistical difference; only trypsin distinguishes healthy control subjects from mild to moderate chronic pancreatitis. Therefore, we propose to put into clinical practice this serum provocative test to evaluate the functional damage of an established chronic pancreatitis.

Adult↗

PubMed1985

Clinical significance of serum pancreatic enzymes in the quiescent phase of chronic pancreatitis.

The most commonly used serum enzymes in pancreatic diseases are total amylase, pancreatic isoamylase, lipase and trypsin. To determine which of these enzymes is the most useful in the diagnosis of clinically quiescent chronic pancreatitis and which enzyme best reflects exocrine functional reserve, we studied 22 healthy control subjects, 44 patients with gastrointestinal, liver and biliary tract diseases, and 25 patients with chronic pancreatitis. On the basis of duodenal intubation, the latter were divided into two subgroups: one group of 13 patients with slight to moderate secretion deficiency and another of 12 patients with severe exocrine insufficiency. Of the enzymes studied, lipase, trypsin and pancreatic isoamylase are equally suitable for the evaluation of function in severe chronic pancreatitis, but not for the early diagnosis of the disease. Results for total amylase are not reliable so that its use in the study of chronic pancreatitis is not advisable.

Adult↗

PubMed1997

Induction of creatininase activity in chronic renal failure: timing of creatinine degradation and effect of antibiotics.

Creatinine degradation was prospectively studied in four healthy subjects and 35 patients with varying degrees of chronic renal failure by measuring creatininase activity in stool isolates. Patients were subdivided into those with serum creatinine above and below 6 mg/dL. Creatinine degradation in the former group of patients who had not taken antibiotics in the previous 3 months was significantly greater than the latter (64% v 26%; P < 0.001), which was similar to healthy controls. This degradation was abolished when antibiotics were added directly to the patient's stool during incubation (P < 0.002). In a subset of five patients, duodenal intubation demonstrated small bowel bacterial overgrowth associated with high concentrations of toxic methylamines generated there from and increased stool creatinine consumption. We conclude that retained creatinine in advanced chronic renal failure induces bacterial creatininase activity throughout the bowel, causing creatinine degradation and subsequent potential loss of creatinine to the creatinine pool. The modifying effects of antibiotics on creatinine degradation has important clinical implications for the interpretation of serum creatinine measurements in renal failure.

Amidohydrolases↗

PubMed1997

Effect of oral pancreatic enzyme administration on digestive function in healthy subjects: comparison between two enzyme preparations.

BACKGROUND: Intraduodenal proteases exert a negative feedback on pancreatic secretion. AIM: To investigate the effect of two pancreatic enzyme preparations (enteric-coated tablets, and capsules with enteric-coated microtablets) on postprandial pancreatic and bile acid secretion, gastroduodenal motility and release of gastrin and pancreatic polypeptide in healthy humans. METHODS: Twenty healthy males were studied on two different days one week apart. After an overnight fast a nine-lumen motility tube was positioned with the distal tip at the Treitz angle. On each study day, 30 min after an interdigestive migrating motor complex-phase III, a semi-liquid test meal was given either alone (n = 20) or with enzymes (3 tablets (n = 10) or 2 capsules with microtablets (n = 10); 40,000 U lipase and 2000 proteases) in a randomized order, and the study continued over 2 h. Motility was continuously recorded with four ports in the antrum and three in the duodenum, using a low-compliance pneumohydraulic perfusion system. Secretion of human-specific pancreatic elastase and bile acids was measured by a standard duodenal intubation perfusion technique. Plasma concentrations of gastrin and pancreatic polypeptide were measured by specific radioimmunoassays. RESULTS: Postprandial pancreatic secretion was significantly reduced by administration of microtablets (median 82 mg/2 h vs. 70 mg/2 h, P < 0.02) but not by tablets (median 59 mg/2 h vs. 58 mg/2 h. N.S.). No changes were observed in bile acid secretion, antroduodenal motility or release of gastrin and pancreatic polypeptide. CONCLUSIONS: Oral administration of pancreatic enzymes at normal therapeutic doses significantly inhibits postprandial pancreatic secretion in healthy humans, when capsules with enteric-coated microtablets are given. Exogenous pancreatic enzymes have no significant effect on bile acid secretion, gastroduodenal motility and hormone release.

Administration, Oral↗

PubMed2002

Iron-deficiency anemia complicating AL amyloidosis with recurrent small bowel pseudo-obstruction and hindgut sparing.

AL amyloidosis complicating multiple myeloma is rare but well recognized. Endoscopic appearances of amyloid in the gastrointestinal tract can, however, be highly variable. Macroscopic appearances of the duodenum can range from scalloping (often seen in celiac disease) to that of duodenitis; erosive disease, frank ulceration and even protruberant masses. The importance of small bowel biopsies at the time of duodenal intubation and in gastroscopic examinations for iron deficiency anemia, must therefore be stressed.

Amyloidosis↗

PubMed1980

Cholesterol crystals and the formation of cholesterol gallstones.

To examine the relation of cholesterol crystallization to the formation of gallstones, gallbladder bile was obtained by means of duodenal intubation in 54 patients (eight with asymptomatic gallstones) and from 17 patients undergoing cholecystectomy for cholelithiasis. Hepatic bile was obtained from nine patients with common-duct stones. Bile samples were examined for cholesterol monohydrate crystals and analyzed to determine the percentage of cholesterol saturation. Intubation in the eight patients with asymptomatic gallstones revealed a cholesterol saturation of 142 +/- 42 per cent (mean +/- S.D.) and crystals in five patients. Crystals were absent in the other 36 patients with supersaturated bile (cholesterol saturation, 166 +/- 44 per cent) and in the 10 patients with undersaturated bile (cholesterol saturation, 81 +/- 24 per cent). In the 26 patients with symptomatic cholelithiasis or common-duct stones, crystals were not seen in the bile of the seven patients with pigment stones but were present in the bile of all 19 patients with cholesterol stones. (In some cases crystals appeared only after 24 to 48 hours of incubation.) Cholesterol crystallization is probably a prerequisite for the formation of cholesterol gallstones; however, many subjects have no crystallization despite marked supersaturation.

Adult↗

PubMed1997

Determination of the exocrine pancreatic function with the NBT-PABA test using a novel dual isotope technique and gas chromatography-mass spectrometry.

We describe a tubeless test of exocrine pancreatic function based on a new dual isotope technique, using N-benzoyl-L-tyrosyl-p-aminobenzoic acid (NBT-PABA) as a substrate for intestinal chymotrypsin activity and the stable isotope, 13C-PABA as marker. Gas chromatography-mass spectrometry (GC-MS) was used for the quantification of PABA and 13C-PABA in blood. The method involves hydrolysis, extractions, separation by HPLC, and methyl ester formation of the test substances before GC-MS analysis. The test is precise and shows good separation of healthy volunteers from patients with pancreatic insufficiency. The PABA/13C-PABA ratios in serum after 1.5 h were 2.64 +/- 0.14 (mean +/- SEM) in 10 healthy volunteers and 1.26 +/- 0.22 in 10 patients with exocrine pancreatic insufficiency. We present a sensitive and specific assay, which is free of analytical interference and radiation hazards and, additionally, it illuminates extrapancreatic pharmacokinetic conditions. This test can eliminate the need for duodenal intubation, which makes it very acceptable to the patients.

4-Aminobenzoic Acid↗

PubMed2005

Magnetic resonance imaging of the small bowel in Crohn's disease.

OBJECTIVE: There may be advantages in using magnetic resonance imaging (MRI) in small-bowel disease. The aims of this study were to optimize the MRI examination technique and to evaluate the capabilities of MRI compared with those of conventional enteroclysis (CE). MATERIALS AND METHODS: MRI and CE were performed in 36 patients suspected of Crohn's disease. Based on 26 pilot studies optimal oral administration of plum juice and bulk fibre laxative was found. T2-weighted and gadolinium enhanced T1-weighted images were obtained using a breath-holding technique and butylscopolamine. Virtual endoscopy was performed. Conventional enteroclysis entailed duodenal intubation and administration of barium and air. Two radiologists evaluated the examinations independently. Finally, each patient scored the degree of discomfort, and preference for either MRI or CE was found. RESULTS: The MRI technique ensured sufficient distension of the small bowel and small-bowel changes were found in 12 patients. In 3 patients this was not seen on conventional enteroclysis, which did not reveal any pathology that was not already seen on MRI. Pathological abdominal changes were found in 70% more patients during MRI than during conventional enteroclysis (p < 0.001). Endoscopic examination corresponded with the MRI findings. The examination quality decreased with increasing age (p = 0.002) and the interobserver agreement of the pathological changes was high (p < 0.001). Virtual endoscopy resulted in excellent demonstration of the mucosal surface. The examination discomfort scores obtained during the MRI were lower than those during conventional enteroclysis (p < 0.001). CONCLUSIONS: MRI using the current technique is preferable to conventional enteroclysis because of superior demonstration of the entire small-bowel pathology, low level of patient discomfort and absence of radiation exposure.

Administration, Oral↗