Value of blood tests including serum group IIA phospholipase A2 and bactericidal/permeability-increasing protein in Crohn's disease.

OBJECTIVE: Determination of the activity of Crohn's disease at a defined time-point is a challenging task since only endoscopy guidelines are given and secondary clinical findings, subjective symptoms and non-specific laboratory tests have therefore to be relied on. The purpose of the current study was to investigate the ability of blood tests to differentiate patient groups with different clinical disease activity and different clinical outcomes during follow-up in Crohn's disease. MATERIAL AND METHODS: During a visit to hospital, 73 outpatients with Crohn's disease were examined, a clinical score was calculated and blood samples were collected for 22 laboratory tests. The patients were also grouped according to clinical outcome during a 6-year follow-up. RESULTS: Serum group IIA phospholipase A2 and alpha-1-antitrypsin values were outside the reference interval more frequently (62% and 42%, respectively) than the other tests in active Crohn's disease. Only weak correlations were found between the clinical score and the test values, and the best correlation was found with serum lysozyme (r = 0.40). In a logistic regression model, the best prediction of disease activity at entry to the study was reached with a model including serum orosomucoid and serum lysozyme and the best prediction of clinical outcome during follow-up was reached using a model including serum albumin. CONCLUSIONS: Serum group IIA phospholipase A2 appeared to be the most sensitive marker of inflammation in Crohn's disease among the 22 blood tests compared. No reliable predictions of disease activity at the time of blood sampling or clinical outcome later during follow-up could be made from the blood tests studied.

Electrophoretic signal comparison applied to mRNA differential display analysis.

Gene expression analysis by electrophoretic methods is currently limited by the labor-intensive visual evaluation of the electrophoretic signal profiles. For this purpose, we present a flexible approach to computer-assisted comparison of quantitative electrophoretic patterns between multiple expression signals. Gaussian curves are first fitted to the complex peak mixtures, and the resulting approximate signals are then aligned and compared on a peak-by-peak basis with respect to specific patterns defined by the investigator. The rationale of the method is to produce a compressed list of exceptional expression patterns quantified by a set of associated numeric features. A score value is attached to each pattern in such a way that large values identify the most potential findings to be focused on in visual analysis instead of the vast amount of original electrophoretic results. The validity of the method is demonstrated by analyzing a large set of electrophoretic data from mRNA differential display experiments monitoring changes in gene expression patterns in human colonic carcinoma. The automated identification of variously defined gene expression patterns agrees well with the visual evaluation of the same electropherograms. The general comparison approach may also be found useful with other gene expression profiling instruments.

Source of group II phospholipase A2 in gastric juice.

Gastric juice contains both pancreatic group I phospholipase A2 (PLA2-I) and synovial-type group II phospholipase A2 (PLA2-II), which may play a crucial role in Helicobacter pylori infection and gastric mucosal injury. PLA2-I present in gastric juice is derived from pancreatic acinar cells. The cellular source of PLA2-II found in gastric juice is unknown. A specific cell type of the intestinal mucosa, the Paneth cell, is known to secrete PLA2-II. The purpose of the present study was to define the source of PLA2-II present in gastric juice. For this purpose, gastric juice was collected from 29 individuals during gastroscopy, and mucosal biopsies were taken from the antrum and body of the stomach and from the duodenum as well as from the jejunum of individuals with resected stomach, for immunohistochemical detection of PLA2-II. The concentration of bilirubin in the gastric juice samples was determined to identify duodenogastric regurgitation. The PLA2-II content was significantly higher in bilirubin-positive than in bilirubin-negative gastric juice samples. PLA2-II was localized by immunohistochemistry in Paneth cells in three patients with areas of intestinal metaplasia of the gastric mucosa and in Paneth cells of duodenal and jejunal mucosa in all patients, but not in any other epithelial cell type of the mucosa of the stomach or the small intestine. Inflammatory cells did not contain PLA2-II. The current results suggest that PLA2-II found in gastric juice is derived from the Paneth cells of the small intestinal mucosa.

p38 MAPK regulates group IIa phospholipase A2 expression in interleukin-1beta -stimulated rat neonatal cardiomyocytes.

Group IIa phospholipase A(2) (GIIa PLA(2)) is released by some cells in response to interleukin-1beta. The purpose of this study was to determine whether interleukin-1beta would stimulate the synthesis and release of GIIa PLA(2) from cardiomyocytes, and to define the role of p38 MAPK and cytosolic PLA(2) in the regulation of this process. Whereas GIIa PLA(2) mRNA was not identified in untreated cells, exposure to interleukin-1beta resulted in the sustained expression of GIIa PLA(2) mRNA. Interleukin-1beta also stimulated a progressive increase in cellular and extracellular GIIa PLA(2) protein levels and increased extracellular PLA(2) activity 70-fold. In addition, interleukin-1beta stimulated the p38 MAPK-dependent activation of the downstream MAPK-activated protein kinase, MAPKAP-K2. Treatment with the p38 MAPK inhibitor, SB202190, decreased interleukin-1beta stimulated MAPKAP-K2 activity, GIIa PLA(2) mRNA expression, GIIa PLA(2) protein synthesis, and the release of extracellular PLA(2) activity. Infection with an adenovirus encoding a constitutively active form of MKK6, MKK6(Glu), which selectively phosphorylates p38 MAPK, induced cellular GIIa PLA(2) protein synthesis and the release of GIIa PLA(2) and increased extracellular PLA(2) activity 3-fold. In contrast, infection with an adenovirus encoding a phosphorylation-resistant MKK6, MKK6(A), did not result in GIIa PLA(2) protein synthesis or release by unstimulated cardiomyocytes. In addition, infection with an adenovirus encoding MKK6(A) abrogated GIIa PLA(2) protein synthesis and release by interleukin-1beta-stimulated cells. These results provide direct evidence that p38 MAPK activation was necessary for interleukin-1beta-induced synthesis and release of GIIa PLA(2) by cardiomyocytes.

Absence of group II phospholipase A2, a Paneth cell marker, from the epididymis.

Paneth cell-like metaplasia has been reported in the epithelium of the epididymis and prostatic adenocarcinomas. We studied the expression of group II phospholipase A2 (PLA2), a marker of Paneth cell differentiation, in six orchiectomy specimens with Paneth cell-like metaplasia. Both immunohistochemistry for group II PLA2 protein and in situ hybridization for the mRNA of group II PLA2 gave negative results in all six cases but positive reaction for lysozyme. The results show that the cells of the Paneth cell-like metaplasia are not true Paneth cells.

Pancreatic tissue perfusion in experimental acute pancreatitis.

OBJECTIVE: To investigate pancreatic tissue perfusion and oxygenation in severe and mild experimental acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. ANIMALS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: 24 pigs were randomised into severe acute pancreatitis, mild acute pancreatitis and control groups (n = 8 in each). The pancreatic duct of eight anaesthetised and mechanically ventilated pigs was cannulated and taurocholic acid was infused into the pancreatic duct to induce severe acute pancreatitis. Eight animals received intraductally infused saline and developed mild acute pancreatitis. Eight pigs had their ducts cannulated alone, and served as controls. MAIN OUTCOME MEASURES: Pancreatic tissue oxygenation, laser Doppler red cell flux, central haemodynamics. RESULTS: Intraductally infused taurocholic acid rapidly induced macroscopically and histologically proven severe necrotising acute pancreatitis. Histological changes characterising mild acute pancreatitis were seen in animals after intraductal saline infusion. Pancreatic tissue oxygen tension decreased in the severe group and increased in the mild group during the six-hour study period. Laser Doppler red cell flux decreased in the severe group. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. CONCLUSION: The present model of severe acute pancreatitis significantly impairs pancreatic oxygenation in the early phase. In mild acute pancreatitis, pancreatic oxygenation increases.

Bactericidal/permeability increasing protein and proinflammatory cytokines in synovial fluid of psoriatic arthritis.

OBJECTIVE: Bactericidal/permeability increasing protein (BPI) is a leukocyte product exerting antibacterial activity. Its production may be stimulated by cytokines, mainly Tumor Necrosis Factor (TNF) alpha. We studied BPI in the synovial fluid (SF) of psoriatic arthritis (PsA), a disease suspected to be influenced by infectious agents. METHODS: The levels of BPI and various indices of SF inflammation, including cytokines and its receptors, were determined in the SF of 18 patients with PsA and compared with those of 12 patients with rheumatoid arthritis (RA) and 9 with osteoarthritis (OA). RESULTS: The lowest SF levels of BPI were found in PsA (145.3 +/- 97.3 ng/ml), significantly lower than in RA (307.7 +/- 42.8 ng/ml, p = 0.0001) and similar to those in OA (151.1 +/- 52.4 ng/ml). Furthermore, only in PsA, and not in the RA and OA subgroups, correlations were observed between BPI and the indices considered, including TNF alpha (r = 0.746, p = 0.0004). CONCLUSION: Due to its relationship with local inflammation, SF BPI may play a role in the pathogenesis of arthropathies, in particular PsA.

Roles of secretory phospholipases A(2) in inflammatory diseases and trauma.

Six distinct secretory small molecular weight phospholipases A(2) (PLA(2)) have been cloned and characterized from human tissues. Two of them, pancreatic group IB PLA(2) (PLA(2)-IB) and synovial-type group IIA PLA(2) (PLA(2)-IIA) have been studied as to their association to various inflammatory diseases. PLA(2)-IB is a digestive enzyme synthesized by pancreatic acinar cells. In acute pancreatitis, which is characterized by destruction of pancreatic tissue, PLA(2)-IB is released into the circulation, but its role in pancreatic and other tissue damage is still hypothetical. The concentration of PLA(2)-IIA increases in blood plasma in generalized inflammatory response resulting from infections, chronic inflammatory diseases, acute pancreatitis, trauma and surgical operations. PLA(2)-IIA is synthesized in a number of gland cells and is present in cellular secretions on mucosal surfaces including Paneth cells of intestinal mucosa, prostatic gland cells and seminal plasma, and lacrimal glands and tears. PLA(2)-IIA is expressed in hepatoma-derived cells in vitro and hepatocytes in vivo. PLA(2)-IIA is regarded as an acute phase protein and seems to function as an antibacterial agent especially effective against Gram-positive bacteria. Other putative functions in the inflammatory reaction include hydrolysis of cell membrane phospholipids and release of arachidonic acid for prostanoid synthesis.

Single doses of FK506 and OKT3 reduce severity in early experimental acute pancreatitis.

OBJECTIVE: To find out if two immunomodulatory drugs used in organ transplantation (FK506 (tacrolimus) and OKT3 (Orthoclone) would reduce early inflammatory complications in experimental acute pancreatitis. DESIGN: Laboratory study. SETTING: University hospital, Germany. ANIMALS: 36 Balb/c mice. INTERVENTIONS: Pancreatitis induced by 7 intraperitoneal injections of cerulein 50 microg/kg at hourly intervals followed by FK506 0.32 mg/kg, OKT3 0.6 mg/kg, or 0.9% sodium chloride (controls) (n = 12 in each group). 12 hours after induction of pancreatitis the animals were killed. MAIN OUTCOME MEASURES: Serum amylase activity and interleukin-6 (IL-6) concentrations; histological damage to pancreas and lungs, apoptotic cells in pancreas; and myeloperoxidase activity in lungs. RESULTS: No animal died during the experiment. At 12h serum amylase activity and IL-6 concentrations were increased in all 3 groups, but highest in the OKT3 group. The pancreatic histological score, apoptosis, and inflammatory infiltration were lower in the two experimental groups than controls, but the degree of vacuolisation of acinar cells was similar. Packed cell volume was higher in the control than the experimental groups, and pulmonary damage and myeloperoxidase activity were less in the experimental groups than the controls. CONCLUSION: Single therapeutic doses of FK506 and OKT3 reduced the early severity of pancreatitis, pulmonary damage, and haemoconcentration in mice. Single doses of FK506 or OKT3 may therefore be effective in preventing the early complications of pancreatitis.

Immunohistochemical labelling for prostate-specific antigen in breast carcinomas.

Immunohistochemical detection of prostate-specific antigen (PSA) is an aid in determining the prostatic origin of metastatic cells. However, small amounts of PSA have also been found in non-prostatic tissues and tumors, for example in some breast carcinomas, by highly sensitive immunofluorometric methods, but also by immunohistochemistry. Our aim was to evaluate the prevalence and prognostic value of histologically confirmed PSA immunoreactivity in breast carcinoma. Sections of formalin-fixed, paraffin-embedded samples from 171 breast carcinomas were immunostained for PSA. The staining results were compared with the mitotic activity, tumor size, histological grade, steroid receptors and follow-up data. For analysis the material was divided into subgroups according to the patients' age (pre- and postmenopausal). PSA was found by immunohistochemistry in 54 (32%) breast carcinomas. In survival analysis of the whole patient material PSA positivity did not show prognostic value. Among premenopausal patients concomitant estrogen receptor and PSA-negativity proved to be associated with high risk of breast cancer death (RR 6.2), also after adjustment for tumor size, histological grade, and axillary lymph node status. Among postmenopausal patients PSA positivity was associated with progesterone receptor positivity and high differentiation but not with age, nodal status, or mitotic activity. PSA can be detected by immunohistochemistry in a considerable number of breast carcinomas. PSA immunoreactivity alone does not seem to have any value as general prognosticator of breast carcinoma patients. However, concomitant absence of PSA and estrogen receptors was an indicator of unfavourable prognosis among premenopausal patients.

Phospholipase A2 in serum and colonic mucosa in ulcerative colitis.

Group II phospholipase A2 is involved in the pathogenesis of various inflammatory diseases and in the host defence against bacteria. The enzyme is expressed in the epithelial cells of colonic mucosa in ulcerative colitis. In this study, we measured the concentration of group II phospholipase A2 in serum and colonic mucosa of patients with ulcerative colitis of different severity and of control patients without any inflammatory disease. The activity of ulcerative colitis was assessed by endoscopy. The concentration of group II phospholipase A2 was measured with an immunoassay. The concentrations of group II phospholipase A2 in serum and colonic mucosa were significantly higher in patients with active and inactive ulcerative colitis than in controls. However, the group II phospholipase A2 levels did not separate patients with different disease activity. The concentration of group II phospholipase A2 in colonic mucosa corresponded with the mucosal inflammatory activity (higher in active colonic areas) intra-individually, but not between different patients with ulcerative colitis. Serum group II phospholipase A2 values were above the normal reference range more often than the values of 11 standard laboratory blood tests widely used for the follow-up of inflammatory activity in ulcerative colitis. These results indicate that the concentration of group II phospholipase A2 is increased in serum and colonic mucosa of patients with ulcerative colitis. The clinical value of the measurement of group II phospholipase A2 in the follow-up of ulcerative colitis remains to be clarified.

Central haemodynamics in experimental acute pancreatitis.

OBJECTIVE: To investigate central haemodynamics in severe and mild acute pancreatitis in pigs. DESIGN: Randomised controlled experiment. SETTING: Animal laboratory, Finland. SUBJECTS: 24 domestic pigs weighing 21-27 kg. INTERVENTIONS: In 8 anaesthetised and mechanically ventilated pigs the pancreatic duct was cannulated and taurocholic acid was infused to induce severe acute pancreatitis. Eight animals received intraductal saline infusion and developed mild acute pancreatitis. Eight pigs were cannulated alone and served as controls. MAIN OUTCOME MEASURES: Cardiac index, heart rate, mean arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, haemoglobin, arterial blood gases and acid base balance. RESULTS: Intraductally infused taurocholic acid rapidly induced severe necrotising acute pancreatitis as assessed both macroscopically and histologically. Histological changes of mild acute pancreatitis were seen in animals after intraductal saline infusion. Central haemodynamics, arterial blood gases, and acid base balances were stable throughout the study period in all groups. The main finding was haemoconcentration as indicated by the increase in arterial haemoglobin concentration in pigs with mild and severe acute pancreatitis. CONCLUSION: Haemoconcentration precedes central haemodynamic alterations in experimental acute pancreatitis.

Gene expression of group II phospholipase A2 in intestine in Crohn's disease.

OBJECTIVE: Phospholipase A2 (PLA2) has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases. Our aim was to identify cells that express group II phospholipase A2 (PLA2-II) at the mRNA and enzyme protein levels in the intestine in Crohn's disease. METHODS: Tissue samples were obtained from the intestine of 20 patients with Crohn's disease (seven operated and 13 colonoscopied) and from eight control patients without inflammatory diseases. The samples were studied by immunohistochemistry for PLA2-II enzyme protein and in situ hybridization for PLA2-II mRNA. RESULTS: PLA2-II protein and mRNA were detected in the Paneth cells of the small intestinal mucosa in all patients and controls. PLA2-II protein and mRNA were found in the columnar epithelial cells of the small intestinal mucosa in six of eight and eight of eight patients with Crohn's ileitis, respectively. In the eight control patients PLA2-II protein and mRNA were not found in these cells (p = 0.007 and p < 0.001, respectively). Metaplastic Paneth cells, which consistently contained PLA2-II mRNA, were found in the colonic mucosa in five of six patients with Crohn's colitis and of one of eight control patients (p = 0.026). The columnar epithelial cells of the colonic mucosa contained PLA2-II protein in three of six and PLA2-II mRNA in six of six patients with Crohn's colitis, whereas the protein was found in these cells in none of eight of the controls (p = 0.055) and the mRNA in only one of eight (p = 0.005) controls. CONCLUSIONS: In Crohn's disease, Paneth cells and columnar epithelial cells of the small and large intestinal mucosa synthesize PLA2-II at the site of active inflammation.

Elevated group II phospholipase A2 mass concentration in serum and colonic mucosa in Crohn's disease.

Group II phospholipase A2 has been proposed to play an important role in the pathophysiology of inflammatory bowel diseases. This enzyme has also been linked to host defence mechanisms against bacteria. The current study aimed at measuring the mass concentrations of group II phospholipase A2 in serum and colonic mucosa of patients with Crohn's disease of different severity and of appropriate control patients without any inflammatory disease. The activity of the disease was determined by clinical factors (the simple index score) and endoscopic and histological scoring. The mass concentration of group II phospholipase A2 was measured by a time-resolved fluoroimmunoassay. The mass concentrations of group II phospholipase A2 in serum and colonic mucosa were significantly higher both in patients with active and inactive Crohn's disease when compared with controls. There was statistically significant difference in the mass concentration of group II phospholipase A2 in colonic mucosa but not in serum between inactive and active Crohn's disease. The current results indicate that the mass concentration of group II phospholipase A2 is increased in serum and colonic mucosa of patients with Crohn's disease and that the latter is associated with the degree of the inflammatory activity in the intestinal wall. These results support the idea that group II phospholipase A2 is involved in the local and generalised pathological processes of Crohn's disease.

Secretory phospholipase A2 in patients with infected pancreatic necroses in acute pancreatitis.

Secretory synovial-type PLA2 (sPLA2-II) in peripheral blood is known to be associated with systemic complications in patients with severe diseases. Being the pacemaking enzyme in eicosanoid synthesis, sPLA2-II is a mediator of the inflammatory response and plays a role in host defense against bacterial infection. We evaluated the clinical role of systemic sPLA2-II in bacterial infection of pancreatic necroses in severe acute pancreatitis. In 58 patients with acute pancreatitis, pancreatic and sPLA2-I and sPLA2-II were measured daily for the first 14 days of hospital treatment by a time-resolved fluoroimmunoassay. All 36 patients with necrotizing pancreatitis underwent regular fine needle aspiration (FNA) to monitor bacterial infection. In 10 patients, infected necroses were found on FNA and postoperative examination. On admission and at most days throughout the observation period, systemic sPLA2-II was significantly higher in patients with infected necroses than in patients with sterile necroses or interstitial pancreatitis. This difference was not found for sPLA2-I, but values were higher in necrotizing pancreatitis than in interstitial pancreatitis at the first 2 days of hospital treatment. If sPLA2-II was >300 ng/ml on 2 successive days within the first 4 days, infected necroses could be predicted with a sensitivity of 89%, a specificity of 88%, and a negative predictive value of 95%. Systemic sPLA2-II has the potential to identify patients at risk of bacterial infection of pancreatic necroses and its routine measurement may therefore, in combination with FNA, offer a valuable tool in monitoring patients with acute necrotizing pancreatitis.

Expression of group II phospholipase A2 in Paneth cells of an adenoma of the rectum. A case report.

A case of tubulovillous adenoma in the rectum of a 51-year-old man is presented. The tumour contained numerous Paneth cells which formed well-developed glands in the basal areas. Group II phospholipase A2 and lysozyme were found in the tumour cells by immunohistochemistry. mRNA of group II phospholipase A2 was localized in the tumour cells by in situ hybridization. It was concluded that a considerable part of this rare type of tumour consisted of Paneth cells which were capable of synthesizing group II phospholipase A2.

Experimental study of a novel phospholipase A2 inhibitor in acute pancreatitis.

BACKGROUND: In acute pancreatitis, two different types of secretory phospholipase A2 (PLA2) have been found: pancreatic type I PLA2 and non-pancreatic type II PLA2. In this study a potent new PLA2 inhibitor effective against type II PLA2 was used in an experimental model of acute pancreatitis. METHODS: In 70 rats the efficacy of the compound was analysed in two experimental models of acute pancreatitis: cerulein- and taurocholate-induced acute pancreatitis, imitating mild and severe disease respectively. Serum rat type I PLA2 protein concentration and type I and type II PLA2 catalytic activities were measured while giving the inhibitor therapeutically. In a prophylactic protocol the effect on histology was analysed. RESULTS: In the taurocholate model, type II PLA2 activity was found to be nine-fold higher than in the cerulein model (P < 0.002), whereas the activity of type I PLA2 was not increased. The inhibitor significantly decreased serum type II PLA2 activity in the taurocholate model of acute pancreatitis (P < 0.05) but type I PLA2 protein concentration and type I PLA2 activity were not affected. The inhibitor also reduced histological tissue damage, with significant differences at 3 and 12 h (P < 0.01). CONCLUSION: The PLA2 inhibitor significantly reduced type II PLA2 activity and was able to protect the pancreas against tissue damage. PLA2 inhibition offers the possibility of a treatment for acute pancreatitis.

Group II phospholipase A2 in human male reproductive organs and genital tumors.

BACKGROUND: Group II phospholipase A2 (PLA2) is a lipolytic enzyme suggested to play a role in inflammation and antibacterial defence. In seminal fluid, the concentration of PLA2 is exceedingly high under normal circumstances (about 1,000 times the concentration in blood plasma of healthy humans). To elucidate the origin of the enzyme present in seminal plasma, we investigated the expression of group II PLA2 in male reproductive organs both at protein and mRNA levels. In addition, the presence of the enzyme was studied in common male genital tumors. METHODS: The methods used were immunocytochemistry, in situ hybridization, and Northern blotting. RESULTS: Northern blotting gave positive results for group II PLA2 mRNA in normal prostate, whereas other normal genital tissues gave negative results. Immunohistochemistry and in situ hybridization of group II PLA2 gave identical results. The enzyme was produced exclusively by the secretory epithelial cells of the prostatic gland. Surprisingly, expression was restricted to the posterior lobe and paraurethral glands of the prostate. Cells of prostatic adenocarcinoma expressed group II PLA2, whereas cells of other male genital tumors contained neither the enzyme protein nor the mRNA of group II PLA2. In some cases prostatic cancer cell seemed to express group II PLA2 at a higher rate than normal prostatic gland cells. CONCLUSIONS: The high content of group II PLA2 in seminal plasma is due to the local production and secretion of the enzyme by the epithelial cells of the prostatic glands. Group II PLA2 is expressed focally, suggesting that specialized prostatic glands secrete this enzyme. All prostatic adenocarcinomas tested expressed group II PLA2 in variable amounts.

Hyperamylasemia after cardiopulmonary bypass: pancreatic cellular injury or impaired renal excretion of amylase?

BACKGROUND: Postoperative hyperamylasemia and even acute pancreatitis are associated with coronary artery bypass grafting (CABG). The mechanism of hyperamylasemia and pancreatic acinar cell damage was studied in 20 patients undergoing CABG. METHODS: Serial blood and urine samples at eight time points before, during, and 24 hours after the CABG were collected. Salivary and pancreatic isoamylases, the fractional clearance of isoamylases (i.e., relative to creatinine clearance), pancreatic phospholipase A2 (a specific serum marker of pancreatic acinar cell injury), and cystatin C (a sensitive marker of glomerular filtration rate) were measured. RESULTS: Mild serum hyperamylasemia (300 to 1000 units/L) was found in 11 of 20 (55%) and severe (> 1000 units/L) in 6 of 20 (30%) patients with no signs of clinical acute pancreatitis. Hyperamylasemia occurred from 6 to 24 hours after the CABG and was mainly caused by pancreatic isoamylase. Serum pancreatic phospholipase A2 concentration remained unchanged, which excludes acinar cell damage. Although renal glomerular filtration was normal during CABG as measured by serum cystatin C and creatinine clearance, the fractional clearance of isoamylases decreased. CONCLUSIONS: The decreased rate of excretion into urine, rather than pancreatic cellular damage, is the major source of hyperamylasemia after CABG.

Serum phospholipases A2 in patients undergoing panproctocolectomy because of severe ulcerative colitis.

A major role has been proposed for group II phospholipase A2 in the pathogenesis of local and generalised inflammatory reactions. Elevated catalytic activity and mass concentrations of this enzyme have been found in serum and tissue samples of the colon in patients with active ulcerative colitis. The cellular source(s) of group II phospholipase A2 in the blood circulation is (are) unknown. In the current prospective study, we investigated the mass concentration of group II phospholipase A2 and the catalytic activity concentration of phospholipase A2 in serial serum samples of 15 consecutive patients who underwent a standard panproctocolectomy operation for severe ulcerative colitis. Both the catalytic activity concentrations of phospholipase A2 and the mass concentrations of group II phospholipase A2 increased rapidly in serum samples to maximum values on the first postoperative day and then decreased (p = 0.002 and p < 0.001, respectively) in patients who recovered uneventfully. Three patients had postoperative complications that further increased the enzyme concentrations at the time of respective complications. The pattern of group II phospholipase A2 mass concentration profiles was similar to the profiles of C-reactive protein. The results show that the removal of the large bowel does not eliminate the potential to secrete group II phospholipase A2 into the blood circulation in these patients. Secretion of group II phospholipase A2 into the circulation after surgery seems to be a normal host response to a major abdominal operation and postoperative complications. Consequently, we conclude that the large bowel is not an important source of group II phospholipase A2 in sera of patients with ulcerative colitis. The results also support the assumptions that the catalytic activity of phospholipase A2 in serum is attributable to group II phospholipase A2 and that this enzyme is an acute phase protein.