Usefulness of carbohydrate-deficient transferrin and trypsin activity in the diagnosis of acute alcoholic pancreatitis.

OBJECTIVE: The aim of this study was to assess if carbohydrate-deficient transferrin (CDT) and trypsin activity differentiate acute alcoholic pancreatitis from nonalcohol-related pancreatitis, and as a secondary goal to evaluate its use in comparison to healthy controls. METHODS: Serum levels of CDT and trypsin activity were measured in frozen sera from 70 nonconsecutive patients with acute pancreatitis and in 16 healthy controls. RESULTS: Causes of pancreatitis were gallstones in 51%, chronic alcoholism in 23%, and other or unknown causes in 26% of the patients. Serum CDT was significantly higher in alcoholic pancreatitis than in the nonalcoholic disease (p < 0.0001) with a median (interquartile range) of 30.8 U/L (23.6-41.7 U/L) in chronic alcoholism, 16.7 U/L (13.05-21.1 U/L) in gallstones, 17.5 U/L (15.9-21.6 U/L) in unknown cause, 19.3 U/L (15.1-27.7 U/L) in other etiologies, and 16.1 U/L (12.1-18.8 U/L) in controls. At a cutoff over 22.5 U/L, CDT showed a sensitivity of 87.5% and a specificity of 85.2%. Serum levels of trypsin activity were significantly higher (p = 0.0007) in alcoholic pancreatitis, median 165 U/L (76-405 U/L) than in nonalcoholic pancreatitis, median 73 U/L (46.5-100.5 U/L). At a cutoff value over 152 U/L, the sensitivity of trypsin activity was 60% with a specificity of 100%. In the multivariate analysis, patient's age (< or = 44 yr), CDT (>22.5 U/L), and trypsin activity (>152 U/L) enabled correct prediction of acute alcoholic pancreatitis in 98% of the cases. CONCLUSION: Serum CDT and trypsin activity are of clinical utility in differentiating alcoholic from nonalcoholic acute pancreatitis.

Activation of cellular immune response in acute pancreatitis.

BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity.

Biochemical model of logistic regression for early prediction of the etiology of acute pancreatitis.

OBJECTIVE: To define a simple model for the early prediction of the biliary or alcoholic etiology in acute pancreatitis, according to the results of several biochemical variables. PATIENTS AND METHODS: Forty-five patients with acute pancreatitis were included in the study (33 of biliary and 12 of alcoholic etiology). Plasma levels of standard biochemical parameters (glucose, urea, albumin, calcium and C-reactive protein), liver function tests (glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, (gamma-glutamyl-transpeptidase, lactic dehydrogenase, bilirubin and bile acids) and pancreatic enzymes (lipase, amylase and p-amylase) were measured daily throughout the first three days of hospitalization. The lipase/amylase ratio was also calculated. Univariate and logistic regression analyses were performed. RESULTS: Age, sex and plasma levels of C-reactive protein, glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase, (gamma-glutamyl-transpeptidase, bilirubin and amylase were significantly different in the two groups. The lipase/amylase ratio was not useful. Logistic regression analysis based on four variables: sex, age, C-reactive protein(day) 1 and glutamic pyruvic transaminase(day) 2 allowed the correct classification in 44 of 45 cases (97.7%). CONCLUSIONS: Biliary and alcoholic acute pancreatitis present differing biochemical profiles-Glutamic pyruvic transaminase(day)2 and C-reactive protein(day) 1 were the variables with the highest predictive value. Taking into account these two biochemical parameters plus age and sex, an accurate and early etiologic classification was possible in the vast majority of cases in the present study.

Inflammatory response in the initial phase of acute pancreatitis: relationship to the onset and severity of the disease.

Pathophysiological theories on acute pancreatitis and its complications have been always based on the harmful role played by the activated pancreatic digestive enzymes at local and systemic levels. However, acute pancreatitis is an inflammatory disease in which a complex systemic response is produced, which involves the interaction of cells (neutrophils, monocytes/macrophages, platelets, lymphocytes, endothelial cells and fibroblasts) and different proteolytic systems (coagulation, fibrinolysis, kallikrein and complement systems). The more or less severe evolution of the disease may depend on the intensity of this inflammatory response, according to the potential capacity of its mediators to cause significant damage at local and systemic levels. The initial mechanism of this response may be the release of oxygen free radicals by the damaged pancreatic cells, which are able to activate the cascade of digestive pancreatic enzymes and initiate chemotaxis and activation of inflammatory cells. Based on the actual knowledges, the present article aims to analyze the role of the inflammatory response on the severity of acute pancreatitis.

Inflammatory response in the early prediction of severity in human acute pancreatitis.

The role of the inflammatory response in acute pancreatitis and its relation with the clinical course was examined. This study examined if the serial measurement of polymorphonuclear granulocyte (PMN) elastase/A1PI complex, phospholipase A catalytic activity, C reactive protein, and other acute phase proteins, and the protease inhibitor alpha 2-macroglobulin, provides meaningful information for prognosis. Eighty non-consecutive patients with acute pancreatitis, classified according to their clinical outcome into mild (n = 40) and severe pancreatitis (n = 40), were followed up daily. Between 48 hours, median values of PMN-elastase, C reactive protein--and most of the acute phase proteins--and phospholipase A activity, were significantly higher in the severe pancreatitis group. PMN elastase shows a dynamic course and it reaches an early peak value at days 1-2, followed by C reactive protein (days 2-4) phospholipase A (day 3), and a negative peak for alpha 2-macroglobulin (days 4-5). PMN elastase (day 1) and C reactive protein (day 2) were selected by discriminant analysis as the most useful variables studied to allow the early accurate prediction of severity (sensitivity 100%, specificity 95%). Little or no predictive additional value was found for all other variables studied. These results strongly suggest a close relation between inflammatory parameters and clinical course in acute pancreatitis, and discriminant analysis of these variables provides a useful method to classify severity.

Determination of beta 2-microglobulin in serum by a microparticle-enhanced nephelometric immunoassay.

This fully automated nephelometric immunoassay to quantify beta 2-microglobulin in human serum measures the light-scattering signal produced by agglutination of commercially available latex microparticles (diameter 0.1 micron) coated with specific F(ab')2 against beta 2-microglobulin. The calibration curve, generated by serial dilutions of a beta 2-microglobulin standard of known concentration, is used to calculate beta 2-microglobulin concentrations in serum samples by the logit-log function and linear-regression analysis. The assay range (sample dilution 400-fold) extends from 0.3 to 40.0 mg/L. No antigen excess appears at beta 2-microglobulin concentrations up to 320 mg/L. Within-run CVs ranged from 1.0% to 3.4%, and between-days from 1.2% to 2.8%. Total imprecision (CV) was < 5%. Analytical recovery averaged 99.5% +/- 2.8%. Rheumatoid factor, complement, bilirubin (up to 340 mumol/L), and hemoglobin (up to 2.0 g/L) do not interfere. Strongly turbid lipemic samples must be cleared before analysis. Standard curve linearity was very good in samples covering the clinical useful range of concentrations. Results of the method correlated well with those of radioimmunoassay and microparticle enzyme-linked immunoassay (r = 0.979 and 0.975, respectively). The reference interval (nonparametric estimation) in apparently healthy adults (n = 303) was 0.87 (0.80-0.94) to 2.42 (2.28-2.45) mg/L; the median value was 1.54 mg/L.

Role of interleukin-6 in acute pancreatitis. Comparison with C-reactive protein and phospholipase A.

Plasma values of immunoreactive interleukin-6, C-reactive protein and phospholipase A have been determined in serial samples from 24 patients with acute pancreatitis ('mild' pancreatitis nine, 'severe' pancreatitis 15). Median plasma concentrations of interleukin-6, C-reactive protein, and phospholipase A activity were significantly higher in patients with 'severe' illness (p < 0.001) than those with 'mild' illness. A particularly marked increase in interleukin-6 was found in two patients with necrotising pancreatitis and fatal outcome. Significant correlations between plasma concentrations of interleukin-6 and phospholipase A (p = 0.0218) and C-reactive protein and phospholipase A activity (p < 0.0001) were found in patients with 'severe' disease. These findings in a limited number of patients with acute pancreatitis are promising in that raised interleukin-6 correlated with clinical severity and with two other established markers, C-reactive protein, and phospholipase A activity.

A new automated turbidimetric immunoassay for quantifying alpha 1-antitrypsin in serum.

This rapid, sensitive equilibrium turbidimetric immunoassay for quantification of alpha 1-antitrypsin involves a monospecific antibody, polyethylene glycol 6000 to accelerate and enhance the immunoprecipitation reaction, and Tween 20 surfactant to decrease and stabilize the sample-blank values. Turbidity at 334 nm is measured by an automated discrete analyzer. Grossly lipemic, icteric, or hemolyzed samples can be assayed. Correlation with results by radial immunodiffusion (RID) was excellent (r = 0.97, n = 84). Analytical recovery averaged 97.7 (SD 2.9)%. Within-run CVs ranged from 1.6 to 1.9%, between-day CVs from 2.0 to 3.5%. Reference values for healthy adults (n = 147) were determined by parametric estimation (for an assumed normal distribution of untransformed data). The lower limit (g/L) with its 0.90 confidence interval is 1.23 (range 1.18-1.28), the upper limit is 2.15 (2.10-2.20), and the mean is 1.69 g/L.