Duodenal secretion of phospholipase A2, amylase, and bicarbonate in chronic pancreatitis

Phospholipase A₂ has been suggested to be involved in the pathogenesis and pathophysiology of acute pancreatitis. We determined phospholipase A₂ and amylase activities in duodenal juice collected during a secretin test from 30 consecutive patients who were suspected to have chronic pancreatitis or biliary disease. The patients underwent endoscopic retrograde cholangiopancreatography (ERCP) the following day. In the 8 patients with ERCP findings of advanced chronic pancreatitis, the mean outputs of phospholipase A₂, amylase, and bicarbonate were reduced by 74%, 72%, and 60% compared to the respective values in the 13 (control) patients without a diagnosis of any pancreatic disorder or jaundice. In the 3 patients with recurrent pancreatitis but normal ERCP findings and in the 6 patients with jaundice the output values were not significantly reduced compared to those in the patients without any pancreatic disorder or jaundice. The outputs of amylase and phospholipase A₂ were not significantly interrelated, whereas the outputs of phospholipase A₂ and bicarbonate correlated well. Receiver characteristic (ROC) curves confirmed the high specificity and sensitivity of phospholipase A₂ or bicarbonate output in patients with ERCP findings of advanced chronic pancreatitis compared to those with no changes in pancreatic ducts, with similar probability values of 0.880 ± 0.111 (SEM), compared to the respective lower value of amylase, 0.676 ± 0.118. Phospholipase A₂ and bicarbonate output proved of equal value as markers of chronic pancreatitis and were superior to amylase output in the secretin test. (Received Mar. 12, 1997; accepted Aug. 22, 1997)     

Duodenal bile acid output in gastroenterologic diseases

The biliary secretion of bile acids was measured with the modified secretin-pancreozymin test in 50 patients with various gastroenterological diseases and in a control group. In the control group the highest bile acid output and the lowest G/T quotient was estimated. In comparison to the control group, the bile acid output in the patients with gastroenterological disorders was reduced significantly to a varying degree. Except in postcholecystectomy patients, it was proved that the G/T quotient was significantly increased compared to that in the control group. The estimation of bile acid output and the G/T quotient presented here shows an easier extension of the validity of the secretin-pancreozymin test which does not indice any additional burden to the patients.     

Duodenal total and ionised calcium secretion in normal subjects, chronic alcoholics, and patients with various stages of chronic alcoholic pancreatitis.

Previous studies have shown increased secretion of total calcium in the duodenal juice of patients with chronic alcoholic pancreatitis compared with healthy subjects. In order to get more detailed information on calcium secretion and pancreatic stone formation in chronic alcoholic pancreatitis, ionised and total calcium concentrations were determined in the duodenal juice of normal subjects, chronic alcoholics, and patients with various stages of chronic alcoholic pancreatitis. Total calcium secretion was in agreement with previously published data. Chronic alcoholics presented a significant increase of ionised calcium. In the course of pancreatitis all calcium fractions increased progressively revealing highest concentrations in patients with severe exocrine insufficiency. In non-calcified and calcified pancreatitis all calcium fractions were identical. It is suggested that the increase of ionised calcium originates from serum ionised calcium passing by diffusion into the damaged pancreatic duct system.     

Increased lithogenicity of bile on fasting in normal subjects

The effect of fasting on bile lithogenicity was studied in 19 normal men and 22 normal women. The molar percentages of bile acid, phospholipid, and cholesterol, determined after random overnight fasts of 9, 12, and 16 hr, were plotted on triangular coordinates. The molar percentage of cholesterol increased in both men and women. Analysis using Admirand and Small's criteria for cholesterol saturation revealed that 4.50% of normal women were lithogenic at 9.1 hr and 54.5% at 16.5 hr (P<0.005). A similar trend in men was not significant. The mean values for both sexes were lithogenic at 16 hr only. Lithogenic bile was present in 4 men and 1 woman at 9 hr fasting and became more lithogenic with longer fasting. Analysis using the criteria of Hegardt and Dam revealed an increased proportion of both sexes moving into the metastable-labile and supersaturated zones on fasting, again with significant changes for women (P<0.01). The duration of fasting is important in interpreting the presence of lithogenic bile; although more pronounced in women, both sexes showed increased cholesterol saturation in bile with fasting.This work was supported (in part) by the National Health Grant No. 603-1008-30 made by the Department of National Health and Welfare, Canada and by Dalhousie University Internal Medicine Research Foundation.     

Indomethacin inhibits duodenal mucosal bicarbonate secretion and endogenous prostaglandin E2 output in human subjects

Nonsteroidal anti-inflammatory drugs are a frequent cause of gastric and duodenal mucosal injury. We examined the effect of indomethacin on duodenal mucosal bicarbonate secretion and prostaglandin output in healthy subjects. Subjects received either 50 mg of indomethacin or placebo orally 13 hours and 1 hour before study. A 4-cm segment of proximal (the duodenal bulb) or distal (10 to 14 cm beyond the pylorus) duodenum was isolated and perfused with 154 mM NaCl containing a nonabsorbable marker. In the proximal duodenum indomethacin reduced both basal and acid-stimulated bicarbonate secretion by approximately 65% (p less than 0.01); in the distal duodenum indomethacin decreased basal and acid-stimulated bicarbonate output by approximately 45% (p less than 0.01). Oral indomethacin inhibited basal and acid-stimulated duodenal prostaglandin E2 output in both the proximal and distal duodenum. We conclude that, by decreasing duodenal mucosal bicarbonate production and prostaglandin output in humans, oral indomethacin, in two doses of 50 mg each, impairs an important duodenal defense mechanism.     

Duodenal bile acid conjugation patterns and dietary sulphur amino acids in the newborn.

Patterns of glycine and taurine conjugation of bile acids in duodenal juice have been studied in 20 low birth weight babies at 12 and 22 days of age. They were fed from birth on one of three feeds containing different amounts of taurine and its precursors, cysteine and methionone. Taurine conjugation predominated in those fed on human milk throughout the first three weeks of life. In those fed on SMA or S26 infant feeding formulae, both of which contain very little taurine, concentrations of glycine conjugates were found to exceed those of taurine conjugates by the 12th day. The low glycine-taurine conjugate ratios previously described in newborn babies are, therefore, probably related to the taurine content of the milk which they received. Glycine-taurine conjugate ratios less than 1.0 occur in breast fed infants during the first three weeks of life.     

Do bile acids reflux into the esophagus? A study in normal subjects and patients with gastroesophageal reflux disease

To determine if bile acids reflux into the esophagus in patients with gastroesophageal reflux disease and in normal subjects during physiological gastroesophageal reflux episodes, esophageal aspiration and pH monitoring were performed simultaneously in 16 patients with gastroesophageal reflux disease and 8 normal subjects. Esophageal samples were collected for 30 min in the fasting state and for 3 h (as hourly samples) after the ingestion of a test meal (egg salad sandwich, peaches, and milk). Bile acids were assayed by a standard enzymatic assay and also by a sensitive and specific assay, liquid secondary ion mass spectrometry. Bile acids were not detected by enzymatic assay in any of the fasting samples. In 6 of the 8 normal subjects and 15 of the 16 patients with gastroesophageal reflux disease, bile acid-like reactivity was detected by the enzymatic assay in postprandial samples. However, bile acid-like reactivity was also found by enzymatic assay in aliquots of the homogenized test meal in concentration similar to the highest concentrations detected in esophageal aspirates. Bile acids were not detected by the liquid secondary ion mass spectrometry method in any of the fasting or postprandial esophageal aspirates (limit of detection greater than 2 microM). However, this assay accurately identified samples to which exogenous bile acids were added as controls. Our results suggest that bile acids did not reflux into the esophagus of patients with gastroesophageal reflux disease whom we studied and caution must be exercised in the use of enzymatic assay for bile acids in postprandial gastrointestinal fluids, as the commonly used hydroxysteroid dehydrogenase assay is not specific for bile acids alone.     

The effects of two dietary fiber supplements on gastrointestinal transit,stool weight and frequency,and bacterial flora,and fecal bile acids in normal subjects

The effects of dietary supplements of sugar-cane fiber (bagasse), on stool weight, solids, and water content were studied in normal ambulant volunteers over a 9-mo period; a second inpatient study was done with bran supplements. The addition on 10.5 g of bagasse containing 5.1 g of crude fiber to a normal diet containing 3.7 g of crude dietary fiber daily raised the mean fecal weight from 88.3 ± 6.4 g to 139.7 ± 10.2 g/day (p < 0.005). There was also a significant rise in fecal solids and fecal water, although the percentage of water in the stools remained unchanged. Bagasse supplements accelerated gastrointestinal transit when measured by the carmine marker technique. Radiopaque “shapes” showed a trend toward more rapid transit with bagasse supplements. Daily supplements of 39 g of wheat bran or 10.5 g of bagasse increased the total daily excretion of fecal bacteria, but there were no changes in bacteria excreted per gram of feces. The composition of the bacterial flora showed no change. There was increased excretion of fecal acid sterols on the bagasse supplement, but this failed to occur with bran. No changes attributable to fiber supplements occurred in the plasma triglycerides or cholesterol. Future work may define specific dietary fiber supplements for different therapeutic purposes. One fiber may be used as a bulk expander in diverticular disease and another as a hypocholesteremic fiber.     

Duodenal lactoferrin in patients with chronic pancreatitis and gastrointestinal diseases

Lactoferrin (LF), chymotrypsin and lipase activity were measured in duodenal juice during pancreatic stimulation. Secretin (0.5 CU/kg/h) plus cerulein (75 ng/kg/h) were infused intravenously in 98 subjects: 33 patients without organic diseases (C), 40 patients affected by chronic pancreatitis (CP), and 25 patients with different gastrointestinal diseases (GID). LF was determined by means of a new noncompetitive immunoenzymatic assay with a sensitivity in the duodenal juice of 5 ng/ml. Duodenal LF concentrations were significantly higher in CP than in C or GID (p less than 0.001). LF was in a normal range in acute relapsing pancreatitis due to biliary stones or pancreas divisum. In the diagnosis of the chronic pancreatitis, LF/lipase ratios showed a specificity of 93% and a sensitivity of 95%. Our results show that LF immunoassay in duodenal juice is a sensitive and accurate assay to apply in pancreatic function tests involving duodenal content analysis.     

Influence of fiber on postprandial intragastric juice acidity, pepsin, and bile acids in healthy subjects

The effect of a fiber-enriched wheat bran product, Fiberform, and a guar gum preparation, Guarem, on postprandial intragastric juice acidity and pepsin and bile acid concentrations was studied in healthy subjects. Fiber-enriched wheat bran prolonged significantly the meal-induced elevation of pH and decrease in pepsin. Both fiber products reduced postprandial intragastric bile acid concentration.     

正常胰胆管汇合患者胆汁淀粉酶升高与胆道疾病关系的研究

目的探讨正常胰胆管汇合（NPBJ）者胆汁淀粉酶升高与胆道疾病的关系。方法连续202例患者（胆管胆汁组）在内镜治疗胆道疾病时抽取胆管胆汁检测淀粉酶,其中68例同时检测胆汁脂肪酶,149例做胆汁细菌培养,27例测Oddi括约肌压力（SOM）,38例测胆管压力。另外73例（胆囊胆汁组）经皮经肝胆囊镜治疗胆囊结石,取胆囊中胆汁检测淀粉酶,31例进行胆囊黏膜活检。两组病例均除外先天性胰胆管汇合异常、胆肠吻合术和既往内镜乳头切开治疗者。结果胆管胆汁组95例（47．0％）淀粉酶升高,其中肿瘤（56．9％,29／51）与非肿瘤疾病（43．7％,66／151）差异无统计学意义（P〈0．05）,但肝门部胆管癌大多数（7／9）淀粉酶值升高;胆汁脂肪酶水平与淀粉酶有明显的相关性（r=0．561）;淀粉酶水平与Oddi括约肌和胆管压力无明显关联;胆汁细菌培养阳性率在淀粉酶值正常和升高者之问无明显差异。胆囊胆汁组34．3％淀粉酶升高,其中87．5％见胆囊上皮细胞异型增生,与淀粉酶正常者差异有统计学意义（P〈0．01）。结论NPBJ胆道疾病患者胰液向胆管逆流发生频度较高,淀粉酶升高者中肿瘤和非肿瘤疾病无显著差异,但淀粉酶升高者胆囊上皮细胞异型增生和肝门部胆管癌发生频度高。     

Persisting ratio of total amylase output in drain fluid can predict postoperative clinical pancreatic fistula

Background/purpose

A consistent predictor for pancreatic fistula (PF) development in the early period after pancreatic resection is still lacking.

Patients and methods

A total of 54 consecutive patients undergoing pancreatic resection were enrolled between June 2007 and April 2010. Pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) were performed in 38 and 16 patients, respectively. For the purpose of finding an early predictor for PF development, we investigated drain amylase levels (d-Amy, IU/mL), drain output volume (d-Vol, mL/day) and drain amylase output (Amy-V, IU/day) on postoperative days (POD) 1 and 3. Amy-V was calculated as the product of d-Amy and d-Vol, and was expressed as the sum of values obtained from all drains. In addition, the ratio of d-Amy or Amy-V on POD3 to that on POD1 was calculated as the persisting ratio in each patient.

Results

The overall incidence of clinical PF (International Study Group on Pancreatic Fistula Grade B and C) was 16.7%, occurring in 13.1% after PD and 25% after DP. All PF occurred in cases with a remnant pancreas of soft texture. There was no significant difference in d-Amy, d-Vol, or Amy-V on POD1 and POD3 between patients with and without clinical PF. The persisting ratio of Amy-V was significantly lower in patients without clinical PF compared to those with clinical PF (P?=?0.029). Furthermore, the persisting ratio of Amy-V was significantly lower in patients with Grade A PF compared to those with Grade B PF (P?=?0.03).

Conclusion

The persisting ratio of drain amylase output is a new significant predictive factor for clinical PF development.     

Calorimetric results in man: energy output in normal and overweight subjects.

In order to test the practicability of 24-hr investigations with the gradient-free Vienna Whole-Body Calorimeter, energy output was measured over 24-hr periods in 18 human subjects. Heat loss was partitioned into dry and evaporative components. Sixteen female subjects were divided into normal-weight (less than 100% according to the Broca index), overweight (100%--120%), and obese (over 120%) groups. A male with severe hypothyroidism, and a female with no signs of impairment of thyroid function who had weight problems that were suspected to be due to low energy expenditure, were studied separately. Subjects reported that the calorimeter chamber was sufficiently comfortable for at least a 24-hour investigation. Overweight and obese subjects showed both greater total heat output and greater inter-individual variability than the normal weight group. Normal and overweight subjects were on steady levels of food intake that were representative of usual intake. For normal subjects there was a relatively close correspondence between energy intake and output, but not for overweight subjects. Thyroid hormone therapy produced a large increase in energy output in the hypothyroid patient. Energy expenditure was found to be unusually low in the patient with weight problems and was increased by about 50% after thyroid hormone administration.     

Effect of inspiratory flow rate on respiratory output in normal subjects.

We wished to determine the independent effect of inspiratory flow rate (VI) on respiratory output in the awake state. Seven normal subjects were connected to a volume-cycled ventilator in the assist/control mode. While the tidal volume setting remained constant, inspiratory flow rate was increased in steps (3 to 4 min each) from 30 to 90 L/min and then back to 30 L/min. Flow pattern was square, and all breaths were subject-triggered. Spontaneous respiratory rate (f) increased in all subjects as VI increased. Mean (+/- SD) f at 30 and 90 L/min were 8.8 (+/- 1.7) and 14.1 (+/- 4.4) min-1, respectively (p less than 0.01). VE increased (10.1 +/- 1.9 at 30 L/min to 16.3 +/- 5.6 at 90 L/min p less than 0.01) and the percentage of end-tidal CO2 decreased (4.7 (+/- 0.5) at 30 L/min to 3.3 (+/- 0.7) at 90 L/min (p less than 0.01)). The response was graded and reversible. The change in f was nearly complete within the first two breaths after transition, and there was no systematic tendency for f to change beyond this early response. The rate of change in airway pressure prior to triggering (dp/dt) increased as VI increased (5.3 +/- 2.0 cm H2O/s at 30 L/min to 10.8 +/- 2.6 cm H2O/s at 90 L/min; p less than 0.01). We conclude that inspiratory flow rate exerts an excitatory effect on respiratory frequency and on the rate of rise of inspiratory activity in conscious humans. This may be relevant to the mechanism of ventilatory response to various respiratory stimuli and to the management of patients receiving mechanical ventilation.     

Diurnal changes in serum unconjugated bile acids in normal man.

Unconjugated bile acids were measured using gas chromatography-mass spectrometry in the serum of two subjects throughout a 24 hour period and in two other subjects over a six hour period after breakfast. Unconjugated bile acids were found in all samples of serum and included cholic, chenodeoxycholic, deoxycholic, 3 beta, 7 alpha-dihydroxy-5 beta-cholanic (iso-chenodeoxycholic), ursodeoxycholic, 3 beta, 7 beta-dihydroxy-5 beta-cholanic (iso-ursodeoxycholic), 3 beta-hydroxy-5-cholenoic, and lithocholic acids. The maximum concentration of each bile acid generally occurred between breakfast and dinner and total unconjugated bile acid concentrations attained levels of between 2-3 mumol/l. Concentrations increased after breakfast and were often as high as 30-40% of the conjugated bile acid glycocholate, but returned to fasting levels in the absence of lunch. The intestinal absorption of unconjugated bile acids is therefore of greater quantitative importance than was previously thought.     

Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects

BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. METHODS: UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. RESULTS: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment (p < 0.05). CONCLUSIONS: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.