Acute pancreatitis. With special reference to the activation peptide from carboxypeptidase B (CAPAP) as a predictor of severity

There is a wide range in the reported annual incidence of acute pancreatitis (AP). A minority of these patients develop a severe disease characterised by a high mortality and morbidity. In order to improve the outcome for patients with an attack of severe AP it is important to identify these patients early in the course of disease. A prediction of severity is especially important for selection of patients for therapeutic trials. The present study was undertaken to establish the indicence and aetiology of AP in Malmö, between 1985-94. To assess the incidence of severe AP, the mortality, causes of death and long-term outcome after a severe attack. To develop a method for early prediction of severity, measurement of levels of the activation peptide from the pancreatic enzyme carboxypeptidase B (CAPAP) in serum and urine. A high incidence of AP was found. The annual incidence of first attacks was 23.4/100 000 (men 58.1% and women 41.9%) and including relapses the corresponding figure was 38.2/100 000. Gallstones were the predominant aetiology in first attacks and with relapses included alcohol was the main aetiological factor. In more than 50% (16/31) of the fatal cases the diagnosis was established first at autopsy, 10 of these were found in the forensic material. Twelve cases were associated with pancreatic carcinoma. Severe AP developed in 8.9% of the cases. At follow-up of these cases, a median 7 years after the attack 14 out of 35 patients had developed diabetes and another 4 had impaired glucose tolerance, 9 had signs of severe exocrine dysfunction. The activation peptide from carboxypeptidase B (CAPAP) was purified from human pancreatic juice. The molecular mass of the protein was established to 9398+_ 5 Da corresponding to an 81 aminoacid activation peptide also in man. A radioimmunoassay for CAPAP was developed. The assay showed a slight (10%) cross-reaction with the proenzyme. In urine the assay only measures CAPAP as the proenzyme is not excreted in the urine. A high accuracy of 89.5% at a specificity of 95.9% was obtained resulting in a 85% risk of developing a severe attack for a patient with a CAPAP value above 100 nmol/l whereas a CAPAP value below 100 nmol/l indicates a less than 3% risk

Studies on the turnover of procarboxypeptidase B, its active enzyme and the activation peptide in the pig

Recent developments in the treatment of acute pancreatitis have focused on the importance of early determination of the severity of an attack. Measuring levels of activation peptides from pancreatic proenzymes seems to be one way to predict severity. Levels of the activation peptide from procarboxypeptidase B, in both serum and urine on admission, have been shown to correlate to the outcome. To be able to interpret levels of this peptide in serum and urine under normal and in various acute abdominal conditions, we need knowledge about its turnover in the circulation. Procarboxypeptidase B, active carboxypeptidase and the activation peptide were therefore purified from porcine pancreatic juice. These proteins were labelled with 125I or 131I and their turnovers were studied in vivo in the pig. The proenzyme and the activation peptide were eliminated without interaction with any substance in the circulation. The active enzyme was to some degree bound to a substance with a molecular mass of 10-20 kDa. Active CPB was eliminated more slowly than proCPB and the activation peptide. Five percent of the activation peptide was detected nondegraded in the urine. After intraduodenal administration of the activation peptide there was no sign of the peptide in the urine

Incidence, aetiology and mortality rate of acute pancreatitis over 10 years in a defined urban population in Sweden

BACKGROUND: There is a wide range (5-50 per 100 000) in the reported annual incidence of acute pancreatitis. Furthermore, the predominant aetiology varies in different reports. This study was undertaken to establish the current incidence, aetiology and associated mortality rate in a defined population. METHODS: A retrospective study of all cases of acute pancreatitis admitted over a 10-year period to a single institution was performed. In addition the autopsy and forensic materials were reviewed. RESULTS: Altogether 883 attacks of acute pancreatitis were recorded, of which 547 were first attacks. The annual incidence of first attacks was 23.4 per 100 000. Including relapses, the incidence was 38.2 per 100 000. Biliary disease was the main aetiological factor in first attacks whereas alcohol was the predominant factor when relapses were included. The mean annual mortality rate for acute pancreatitis in the population was 1.3 per 100 000. Of 31 patients who died from acute pancreatitis only 15 were diagnosed before death. For recurrent disease the mortality rate was 0.3 per cent. In 12 patients the pancreatitis was associated with pancreatic carcinoma. CONCLUSION: It is important to differentiate between first attacks and relapses, since both incidence and aetiology figures are influenced by this, and it is important to include autopsy and forensic material in population-based mortality studies

Short and long term outcome of severe acute pancreatitis.

OBJECTIVE: Between 1985 and 1994, 883 cases of acute pancreatitis were treated in Malmö, Sweden (population 233,000). The purpose of this study was to report the short- and long-term outcome of the 79 cases that were severe, according to the Atlanta classification. DESIGN: Retrospective and follow-up study a median time of 7 years since the attack. SETTING: University hospital, Sweden. SUBJECTS: 79 patients with severe acute pancreatitis. MAIN OUTCOME MEASURES: Mortality, cause of death, organ failure, local complications, surgical procedures, mortality since the attack, and endocrine and exocrine dysfunction. RESULTS: Twenty-one patients died from their attack. Organ failure was the predominant cause of death in the 13 patients who died during the first 10 days after admission, whereas infection was the most common cause of death in patients who died later. Mortality was low under the age of 60 and increased with age. Organ failure developed in 72 patients. Twenty-four patients developed pancreatic necrosis or abscesses and 18 patients were treated by necrosectomy and open or closed drainage. At follow-up, 13 patients had died, 2 from pancreatic carcinoma. 35 patients were included in the follow-up survey. 15 of these had diabetes and an additional 4 had impaired glucose tolerance. 9 patients had signs of severe exocrine dysfunction. CONCLUSIONS: There was a high incidence of endocrine and exocrine dysfunction together with, in many patients, ongoing social problems related to chronic alcoholism several years after an attack of severe acute pancreatitis

Makt och religion i könsskilda världar : religionsfilosofiska perspektiv

I denna samlingsvolym belyser några svenska religionsvetenskapliga forskare hur religion, kön och makt som oupplösligt förenade begrepp berör varandra ur religionsfilosofiska perspektiv. Religion kan inte uttömmande beskrivas utan att dess hierarkiska strukturer och dess roll som maktfaktor i samhället berörs. Förhållandena mellan könen formuleras ofta i religiösa termer och underliggande maktaspekter kommer till uttryck i religiöst laddat språkbruk. Man kan inte tala om makt utan att erkänna att religionen genom historien har varit och fortfarande är en legitimerande faktor för maktutövning; allt ifrån mannen som hänvisar till sin gudomliga auktoritet att styra över kvinnan, till hela samhällens direkta eller indirekta beroende av religiösa normer i sin lagstiftning och sina värderingar. Bidragen exemplifierar den religionsfilosofiska forskningens relevans för dagens samhälle genom att granska och reflektera över förutsättningarna för olika debatter och företeelser i religion och samhälle, deras ideologiska och filosofiska grunder, livsåskådningsmässiga relevans, etiska konsekvenser och inre sammanhang. Bidragen behandlar bland annat arbetet med att utforma en ny kyrkohandbok med ett inklusivt språk, svensk politisk strävan efter jämställdhet, kvinnors position i fundamentalistiska religiösa grupperingar, förståelse av existentiella upplevelser av liv, kärlek och död, och förnuftets funktion, betydelse och räckvidd när det gäller att förändra konservativa gruppers värderingar eller motverka religiös intolerans

Different patterns in immunoreactive anionic and cationic trypsinogen in urine and serum in human acute pancreatitis

BACKGROUND: Acute pancreatitis (AP) results in elevated concentrations of trypsinogen (T) isoenzymes in serum. Immunoreactive anionic trypsinogen in urin (irAT/u) is elevated in AP, and has recently been proposed as a rapid diagnostic instrument and severity predictor. These results have not been confirmed by other groups, and irAT/u has not been further characterized. The concentration of immunoreactive cationic trypsinogen in urine (irCT/u) and the serum irAT/irCT ratio in AP have not been extensively examined. METHODS: Levels of irAT and irCT were studied in urine and serum from 50 AP patients and in urine from 41 non-AP patients. Severity was assessed according to the Atlanta classification. irAT/u was characterized by gel filtration. RESULTS: Gel filtration revealed only AT in the urine. Highly significant differences in irAT/u were seen between AP/non-AP (p < 0.0001) and mild/severe disease (p = 0.0012). The irAT/irCT ratio in serum changed from normal 0.8 to 1.3 in AP. CONCLUSIONS: IrAT and only traces of irCT were found in the urine in AP. IrAT/u was higher in AP than in other acute abdominal disorders (non-AP) and also higher in severe than in mild AP. IrAT in serum (irAT/s) increased proportionally more than irCT/s in AP, but did not discriminate mild from severe forms. High levels of irAT/u in some non-AP cases and a wide range in AP cases make the clinical value of the test questionable

A prospective cohort study on risk of acute pancreatitis related to serum triglycerides, cholesterol and fasting glucose

Background/objectives: To investigate risk for acute pancreatitis related to moderately elevated triglycerides, cholesterol and fasting glucose. Methods: This was a prospective cohort study in Malmo, Sweden of 33 346 subjects investigated 1974 - 1992 and followed until December 31, 2006. Baseline investigation included a self-administered questionnaire and analysis of serum triglycerides, cholesterol and fasting glucose. Cases of acute pancreatitis (n = 277, median time since baseline investigation 15.6 years) were identified in diagnosis registries and validated retrospectively. Attacks were classified as obstructive or non obstructive (alcohol or non alcohol related). Cox proportional hazards analysis was used to calculate hazard ratios (HR) for acute pancreatitis related to relevant risk factors, adjusting for age, sex, smoking habits and alcohol consumption. Results: Triglycerides were associated with overall, non obstructive and non obstructive non alcohol related acute pancreatitis with adjusted HRs of 1.21 (95% confidence interval (CI), 1.07-1.36), 1.23 (95% CI, 1.06-2.43) and 1.34 (95% Cl, 1.11-1.62) per 1 mmol/l increment, respectively. Corresponding HRs for forth versus first quartile of triglycerides were 1.55 (95% Cl, 1.09-2.21), 1.60 (95% Cl, 1.60-1.01-1.35) and 2.07 (95% Cl, 1.13-3.79). Triglycerides were not associated with obstructive acute pancreatitis and there were no associations between glucose or cholesterol and the risk of acute pancreatitis. Conclusions: We found an association between prediagnostic levels of triglycerides and risk for acute pancreatitis. This association was most pronounced in the non obstructive non alcohol related group. Our findings suggest that triglycerides may be a more important risk factor for acute pancreatitis than what has previously been estimated. Copyright (c) 2012, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved

Activation peptide of carboxypeptidase B and anionic trypsinogen as early predictors of the severity of acute pancreatitis.

Summary Background Early prediction of severity is important in the management of patients with acute pancreatitis. The presence of activation peptides and certain pancreatic proenzymes in plasma and urine has been shown to correlate with severity. This study was designed to assess the value of measuring levels of the activation peptide of carboxypeptidase B (CAPAP) and of anionic trypsinogen. Methods Concentrations of CAPAP and anionic trypsinogen were measured in the urine and serum in 60 patients with acute pancreatitis. Preset cut-off levels were used to analyse the accuracy of the tests. Severity was classified retrospectively according to the Atlanta classification. Results Concentrations of CAPAP in urine and serum and of anionic trypsinogen in urine correlated with the severity of the pancreatitis. CAPAP in urine showed the highest accuracy. The overall accuracy was 90 per cent, with a positive predictive value of 69 per cent and a negative predictive value of 98 per cent. Conclusion In this study, measurement of CAPAP in urine was an accurate way to predict the severity of acute pancreatitis, and was superior to assay of anionic trypsinogen in urine and serum. Measurement of CAPAP in urine may be of value in the management of individual patients with pancreatitis and in the selection of patients for therapeutic trials