Antimicrobial susceptibility of Brachyspira hyodysenteriae in Switzerland.

INTRODUCTION: Brachyspira (B.) hyodysenteriae is the causative agent of swine dysentery (SD), a severe mucohaemorrhagic diarrheal disease in pigs worldwide. So far, the antimicrobial susceptibility patterns of B. hyodysenteriae in Switzerland have not been investigated. Therefore, a panel of 30 porcine B. hyodysenteriae isolates were tested against 6 antimicrobial agents by using the VetMIC Brachy panel, a broth microdilution test. Tiamulin and valnemulin showed high antimicrobial activity inhibiting all isolates at low concentrations. The susceptibility testing of doxycycline revealed values from ≤0.25 µg/ ml (47%) to 2 µg/ml (10%). The MIC values of lincomycin ranged between ≤0.5 µg/ml (30%) and 32 µg/ml (43%). For tylosin, 57% of the isolates could not be inhibited at the highest concentration of ≥128 µg/ml. The MIC values for tylvalosin were between ≤0.25 µg/ml (10%) and 8 µg/ml (20%). These findings reveal Switzerland's favourable situation compared to other European countries. Above all, tiamulin and valnemulin are still effective antimicrobial agents and can be further used for the treatment of SD.

INTRODUCTION: Brachyspira (B.) hyodysenteriae est l'agent de la dysenterie porcine, une affection diarrhéique muco-hémorragique grave des porcs connue dans le monde entier. Jusqu'à ce jour, la sensibilité aux antibiotiques B. hyodysenteriae n'avait pas été étudiée en Suisse. C'est pour cela qu'on a examiné, au moyen du test de micro dilution VetMIC Brachy panel, un choix de 30 isolats porcins de B. hyodysenteriae quant à leur sensibilité face à 6 substances antimicrobiennes. La Tiamuline et la Valnémuline ont montré une activité antimicrobienne élevée, bloquant tous les isolats à de faibles concentrations. Les tests de sensibilité vis-à-vis de la Doxycilline ont donné des valeurs comprises entre ≤0.25 µg/ml (47%) et 2 µg/ml (10%). Les valeurs de CMI de la Lincomycine variaient entre ≤0.5 µg/ml (30%) et 32 µg/ml (43%). Avec la Tylosine, 57% des isolats n'ont pas pu être bloqués avec la concentration la plus élevée de ≥128 µg/ml. Les valeurs de CMI pour la Tylvalosine se situaient entre ≤0.25 µg/ml (10%) et 8 µg/ml (20%). Ces résultats montrent que la situation suisse est favorable en regard d'autres pays européens. La Tiamuline et la Valnémuline en particulier restent des substances antimicrobiennes efficaces qui peuvent continuer à être utiliser pour lutter contre la dysenterie porcine.

Bleeding peptic ulcer - time trends in incidence, treatment and mortality in Sweden.

BACKGROUND: The incidence of peptic ulcer disease was expected to decrease following the introduction of acid inhibitors and Helicobacter pylori eradication. AIM: To analyse possible changes in the incidence of bleeding peptic ulcer, treatment and mortality over time. METHODS: Residents of Malmö hospitalized for bleeding gastric or duodenal ulcer disease during 1987-2004 were identified in hospital databases (n = 1610). The material was divided into 6-year periods to identify changes over time. All patients who had been submitted to emergency surgery (n = 137) were reviewed. RESULTS: The incidence rate for bleeding gastric or duodenal ulcers decreased by one half in males and by one-third in females and emergency operations decreased significantly (9.2%, 7.5% and 5.7% during the three time periods, respectively (P < 0.05). The post-operative mortality tended to decrease (9.7, 2.4 and 3.7%, respectively) and the 30-day mortality rates in the whole material were 1.2%, 3.6% and 3.4% during the different time periods. CONCLUSION: The incidence of bleeding gastric and duodenal ulcer disease has decreased markedly. Operative treatment has been replaced by endoscopic treatment. The bleeding ulcer-related mortality was less than 4% and has not changed over time.

Protease activation, pancreatic leakage, and inflammation in acute pancreatitis: differences between mild and severe cases and changes over the first three days.

BACKGROUND/AIMS: The pathophysiology of acute pancreatitis (AP) may be studied using markers of protease activation (active carboxypeptidase B (aCAP), the activation peptide of carboxypeptidase B (CAPAP)), leakage of pancreatic enzymes (trypsinogen-2, procarboxypeptidase B (proCAP), amylase), and inflammation (monocyte chemoattractant protein-1 (MCP-1), CRP). METHODS: This prospective study included 140 cases of AP. Mild (n = 124) and severe (n = 16) cases were compared with respect to serum levels of trypsinogen-2, proCAP, amylase, aCAP, CAPAP (serum/urine), MCP-1 (serum/urine) and CRP on days 1, 2 and 3 from onset of symptoms. All patients with information on all 3 days were included in a time-course analysis (n = 44-55, except amylase: n = 27). RESULTS: High levels in severe versus mild cases were seen for trypsinogen-2, CAPAP in serum and urine, and MCP-1 in serum on days 1-3. No differences were seen for proCAP, amylase and aCAP. MCP-1 in urine was significantly elevated on day 1-2, and CRP on day 2-3. CAPAP and MCP-1 levels peaked early and stayed elevated for 48 h in serum. CONCLUSION: Protease activation and inflammation are early events in AP, with high levels of these markers within 24 h. Protease activation declines after 48 h, whereas inflammation is present for a longer time.

Monocyte chemoattractant protein 1, active carboxypeptidase B and CAPAP at hospital admission are predictive markers for severe acute pancreatitis.

BACKGROUND: CAPAP, the activation peptide of procarboxypeptidase B, is a predictor of severe acute pancreatitis (AP). Active carboxypeptidase (aCAP) may be a better predictor, as its turnover is slower. Monocyte chemotactic protein-1 (MCP-1) is an early inflammatory marker and increases before complications in severe AP. We conducted a cohort study to evaluate these markers as predictors for severe AP. METHOD: 140 patients with AP were included, retrospectively grouped as severe or mild by the Atlanta classification. CAPAP, MCP-1 and aCAP were analyzed in admission samples. Receiver operating characteristic curves determined high vs. low levels. RESULTS: The levels of all markers were significantly higher in patients with severe disease. High levels of serum MCP-1 was associated with a high risk of developing severe AP (OR 40.8; 95% CI 8.5-195). High ORs were also seen for urine MCP-1 (OR 7.3; 95% CI 2.2-24.3), serum CAPAP (OR 5.4; 95% CI 1.6-17.7), urine CAPAP (OR 4.8; 95% CI 1.6-14.2), and serum aCAP (OR 3.7; 95% CI 1.2-11.3). CONCLUSION: Serum MCP-1 at admission was strongly associated with development of severe AP. MCP-1 in urine, CAPAP in serum and urine and aCAP may also be useful for predicting severe AP. and IAP.

Dexamethasone affects inflammation but not trypsinogen activation in experimental acute pancreatitis.

BACKGROUND/AIMS: Trypsinogen activation and inflammation are early events in acute pancreatitis. This experimental study aimed to show the effects of dexamethasone on them. METHODS: Cerulein and taurocholate pancreatitis were induced in 2 groups of 12 Wistar rats each. Six animals per group were injected with dexamethasone 1 h prior to the induction of acute pancreatitis. Amylase, phospholipase A2, TNF-alpha, IL-6, IL-10, alpha2-antiplasmin in plasma and trypsinogen activation peptide (TAP) in urine were measured in healthy rats, then 0.5 and 6 h after pancreatitis induction. A severity score based on edema, necrosis and ascites was calculated at 6 h. TNF-alpha, IL-6 and IL-10 were measured 0.5 h after laparotomy in a control sham-operated group of 6 rats. RESULTS: Inflammatory markers increased early in the course of both mild and severe acute pancreatitis and were significantly lowered by dexamethasone. The severity score was higher in taurocholate than in cerulein pancreatitis. It was significantly decreased by dexamethasone only in rats with mild pancreatitis. TAP remained unchanged in mild pancreatitis compared to healthy animals but increased late in the course of taurocholate pancreatitis. Trypsinogen activation was not affected by dexamethasone at all. CONCLUSION: Inflammation occurred earlier than the increase in urinary TAP in severe pancreatitis in rats. Dexamethasone inhibited inflammation but had no influence on TAP levels in experimental mild and severe acute pancreatitis.

Synthesis and localization of pancreatic secretory proteins in pancreatic acinar-like metaplasia in the distal part of the oesophagus. Pancreatic acinar metaplasia: another source of pancreatic enzymes!

BACKGROUND: Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells. METHODS: Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization. RESULTS: Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus. CONCLUSION: Pancreatic acinar-like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.

Synthesis and Localization of Pancreatic Secretory Proteins in Pancreatic Acinar-like Metaplasia in the Distal Part of the Oesophagus.

BACKGROUND: Pancreatic acinar-like metaplasia has previously been described in the gastric mucosa and in the distal part of the oesophagus. The resemblance to pancreatic acinar cells prompted us to study the possible occurrence of secretory pancreatic proteins in these cells. METHODS: Seven specimens obtained from the distal oesophagus at gastroscopy where routine microscopy showed pancreatic acinar-like metaplasia were selected for this study. Sections were subjected to immunohistochemical detection of trypsinogen, pancreatic elastase, procarboxypeptidase B and pancreatic secretory trypsin inhibitor using specific antisera. An alkaline-phosphatase-conjugated oligodeoxynucleotide probe, complementary to the transcript for trypsinogen 2 (anionic) was used for in situ hybridization. RESULTS: Cells with pancreatic acinar-like metaplasia were immunoreactive to all pancreatic secretory proteins studied. In situ hybridization showed the presence of trypsinogen 2 mRNA in pancreatic acinar-like metaplasia. The pancreatic proteins were not seen in other cells in the distal oesophagus. CONCLUSION: Pancreatic acinar- like metaplasia is common in the distal oesophagus and pancreatic secretory proteins, including trypsininogen 2, are produced in the oesophageal metaplastic acinar cells. The biological significance of this finding has yet not been thoroughly studied.

Serum levels of procarboxypeptidase B and its activation peptide in patients with acute pancreatitis and non-pancreatic diseases.

BACKGROUND: Carboxypeptidase B from the pancreatic gland may exist in three different molecular and immunoreactive forms: the proenzyme, the active enzyme, and the activation peptide. AIMS: To investigate levels of procarboxypeptidase B (proCAPB) and its activation peptide in serum in acute pancreatitis to test the accuracy of these two variables as markers for the diagnosis of acute pancreatitis and for prediction of pancreatic necrosis. To elucidate whether leakage of proenzymes and activation of proenzymes reflect two different pathophysiological events in acute pancreatitis. METHODS: Sera from patients with acute pancreatitis (n=85) and acute abdominal pain of non-pancreatic origin (n=53) were analysed for proCAPB and its activation peptide. Patients with pancreatitis were divided into necrotising (n=33) and oedematous attacks (n=52) using contrast enhanced computed tomography. Accuracy was determined using receiver operating characteristic curve analysis. RESULTS: Immunoreactive carboxypeptidase B activation peptide (ir-CAPAP) concentration in serum on admission was 0.7 nmol/l (0-18.1) in patients with oedematous pancreatitis compared with 5.8 nmol/l (1.9-34) in patients with later development of pancreatic necrosis. Elevated levels of the activation peptide on admission correlated with an accuracy of 92% to later development of pancreatic necrosis. Ir-proCAPB concentration in serum on admission was 16.0 nmol/l (1.4-50.5) in all patients with acute pancreatitis versus 0.3 nmol/l (0-3.6) in patients with non-pancreatic acute abdominal disorders. Cases with oedematous pancreatitis had ir-proCAPB levels of 15.4 nmol/l (1.4-50.5) versus 19.1 nmol/l (2.7-36.1) in cases with later development of pancreatic necrosis. Measurement of the proenzyme can thus be useful for the diagnosis of acute pancreatitis (accuracy 99%) but levels did not correlate with later development of pancreatic necrosis (accuracy 56%). CONCLUSION: Leakage of proenzymes occurs in acute pancreatitis, irrespective of severity, while development of pancreatic necrosis occurs only when there is activation of the proenzymes.

Splenic rupture following ESWL for a pancreatic duct calculus.

Extracorporeal shock wave lithotripsy (ESWL) is an established and extensively used treatment alternative for urinary calculi. It is also an established method of dealing with pancreatic duct calculi complementing endoscopic techniques in selected cases. Three reports of splenic injury following and probably caused by ESWL for urinary calculi have previously been published. We report a case of splenic rupture presenting with life-threatening hemorrhage 6 days after a single ESWL therapy session for pancreatic duct calculi.

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.

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

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.

Expression and characterization of trypsinogen produced in the human male genital tract.

Trypsinogen is a serine proteinase produced mainly by the pancreas, but it has recently been found to be expressed also in several cancers such as ovarian and colon cancer and in vascular endothelial cells. In this study, we found that trypsinogen-1 and -2 are present at high concentrations (median levels, 0.4 and 0.5 mg/L, respectively) in human seminal fluid and purified them to homogeneity by immunoaffinity and anion exchange chromatography. Purified trypsinogen isoenzymes displayed a M(r) of 25 to 28 kd in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Most of the trypsinogen-1 purified from seminal fluid was enzymatically active whereas trypsinogen-2 occurred as the proform, which could be activated by enteropeptidase in vitro. Immunohistochemically, trypsinogen protein was detected in the human prostate, urethra, utriculus, ejaculatory duct, seminal vesicles, deferent duct, epididymal glands, and testis. Expression of trypsinogen mRNA in the same organs was demonstrated by in situ hybridization. Trypsinogen mRNA was also detected in the prostate and seminal vesicles by reverse transcriptase-polymerase chain reaction and Northern blotting. Isolated trypsin was shown to activate the proenzyme form of prostate-specific antigen. These results suggest that trypsinogen isoenzymes found in seminal fluid are produced locally in the male genital tract and that they may play a physiological role in the semen.

[Acute pancreatitis--clinical and technical laboratory diagnostic and prognostic assessment]. / Akute Pankreatitis--klinische und labortechnische Diagnose- und Prognosestellung.

The incidence of acute pancreatitis within 100,000 inhabitants a year differs between 5 (Bristol) and 80 (USA). Even though the diagnosis of pancreatitis has become easier by the measurement of specific pancreatic enzymes there are still 30-40% of the fatal cases which are first diagnosed at autopsy. It is of utmost importance to assess the diagnosis and the severity of acute pancreatitis in the beginning to identify those patients with severe or necrotising disease who benefit from an early initiated intensive care therapy. Additionally, in view of new therapeutical concepts (e.g. antibiotic therapy in severe forms) and for the evaluation of new drugs, patients should be staged into mild and severe disease as early as possible. In most cases it is not possible to assess the severity clinically on hospital admission. Up to now the "gold standard" are imaging procedures (contrast-enhanced CT and MRI) which should be reserved for the severe cases to estimate the extent of pancreatic necrosis. The ideal predictor in blood or in urine should be objective, reliable, inexpensive, easy to measure, widely available, sensitive and specific. There are a variety of mediators of the "systemic inflammatory response syndrome" which are elevated in this disease (C-reactive protein, antiproteases, enzyme activation peptides like trypsinogen activation peptide (TAP) and carboxypeptidase B activation peptide (CAPAP), PMN-elastase, complement factors, chemokines and interleukins and others). Among all these mediators, C-reactive protein is the parameter best analysed. It has to be taken into account that it is not specific for AP and it's highest efficacy is reached after > 48 hours after the onset of disease. However, because usually a certain time elapses (approximately 24-48 hours) until patients are hospitalised the time delay seems not to a major disadvantage.

[Guidelines for management of patients with acute pancreatitis]. / Riktlinjer för handläggning av patienter med akut pankreatit.

During recent years new concepts and methods have been introduced in the management of acute pancreatitis. Severity and risk of complications show wide variation. Outcome is also dependent on the physician's experience and on his local resources. In this light the Swedish Society of Upper Abdominal Surgery has elaborated national guidelines for management. Attention is paid to diagnosis, severity assessment and etiology. Furthermore, guidelines are offered for treatment of mild and severe pancreatitis, as well as for the management of pseudocysts. The role of multidisciplinary intensive care specialist teams in the management of severe disease is emphasized. The guidelines are supported by the Swedish Society of Gastroenterology, the Swedish Society of Gastroenterology, the Swedish Society of Anesthesiology and Intensive Care and by experts from other Nordic countries.

Mesenteric vein thrombosis due to factor V Leiden gene mutation.

BACKGROUND: Mesenteric venous thrombosis is a rare cause of acute abdominal pain that may be the result of coagulation abnormalities. METHODS: Four consecutive patients with mesenteric venous thrombosis underwent haematological evaluation. RESULTS: All four had activated protein C resistance resulting from a single mutation in the gene coding for coagulation factor V. Three had surgery; in one patient the diagnosis was made by ultrasonography. One of the patients who had surgery died but the other three survived and were treated with long-term anticoagulation. CONCLUSION: Activated protein C resistance may be an important pathogenetic factor in primary mesen-teric vein thrombosis.

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.

Long-term effects on the regulation of pancreatic secretion after gastric surgery.

BACKGROUND: Apart from smoking, known risk factors for the development of pancreatic carcinoma are few, gastric resection being proposed as one. The trophic effect of cholecystokinin (CCK) on the pancreatic gland is well known from animal experience and increased concentrations of CCK in plasma have been shown to induce pancreatic neoplasia experimentally. In several studies the release of CCK in response to food ingestion has been shown to be increased following gastric surgery. However, in those studies, the time between surgery and investigation of the CCK response was short, and methods of CCK analysis have since improved. PATIENTS AND METHODS: In patients, partially gastrectomized 8 years (median) earlier, we studied the plasma concentrations of CCK, insulin and gastrin, as well as some specific pancreatic enzymes. The findings were compared to an age-matched control group of individuals not subjected to gastric surgery. RESULTS: Basal CCK concentrations in the operated group were found to be lower, but increased postprandially to the same level as in controls. Serum levels of specific pancreatic enzymes were equal in the 2 groups. CONCLUSION: It is possible that a disturbed regulation of pancreatic secretion, or a secretory dysfunction within the gland, following partial gastrectomy, could contribute to the development of pancreatic carcinoma. However, our findings do not favor the idea of plasma CCK as a promotor of pancreatic carcinoma.

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.

Peritoneal lavage with aprotinin in patients with severe acute pancreatitis. Effects on plasma and peritoneal levels of trypsin and leukocyte proteases and their major inhibitors.

CONCLUSION: Although high-dose aprotinin given intraperitoneally to patients with severe acute pancreatitis seems to inhibit activated trypsin in the peritoneal cavity, the treatment has little effect on the balance between proteases and antiproteases. Plasma levels of leukocyte proteases were high in all the patients, indicating leukocyte activation to be an important feature of the pathophysiology of severe acute pancreatitis. A surprise finding was that the patients had higher peritoneal levels of pancreatic secretory trypsin inhibitor (PSTI) after the lavage procedure. BACKGROUND: Although most studies have shown protease inhibitor therapy to have little or no effect on acute pancreatitis, in an earlier study we found that very high doses of the protease inhibitor aprotinin given intraperitoneally to patients with severe acute pancreatitis seemed to reduce the need of surgical treatment for pancreatic necrosis. In the present study we have further analyzed plasma and peritoneal samples from the same patients to ascertain whether the aprotinin treatment affects the balance between proteases and endogenous antiproteases. METHODS: In a prospective double-blind randomized multicenter trial, 48 patients with severe acute pancreatitis were treated with intraperitoneal lavage. One group (aprotinin group, n = 22) was also treated with high doses (20 million KIU given over 30 h) of aprotinin intraperitoneally. The remaining 26 patients made up the control group. The protease-antiprotease balance was studied by measuring immunoreactive anionic trypsin (irAT), cationic trypsin (irCT), complexes between cationic trypsin and alpha 1-protease inhibitor (irCT-alpha 1 PI), leukocyte elastase and neutrophil proteinase 4 (NP4), as well as the endogenous protease inhibitors, pancreatic secretory trypsin inhibitor (PSTI), alpha 2-macroglobulin (alpha 2M), alpha 1-protease inhibitor (alpha 1 PI), antichymotrypsin (ACHY), and secretory leukocyte protease inhibitor (SLPI). Intraperitoneal levels were studied before and after the lavage procedure, and plasma levels were followed for 21 d. RESULTS: The control group had lower plasma levels of SLPI and analysis of peritoneal fluid showed the reduction of irCT-alpha 1 PI to be more pronounced in the aprotinin group. None of the other variables measured differed significantly between the two groups. All patients had very high levels of leukocyte elastase and NP4 both in peritoneal exudate and in plasma. Peritoneal levels of PSTI were higher after the lavage procedure in contrast to the other measured variables that all showed lower peritoneal levels after the lavage.