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Biomedical subjects

A Lasson

Publications and source records attributed to A Lasson.

At least 19 recordsLinked to original sources

Screening of concentrations of C-reactive protein and various plasma protease inhibitors preoperatively for the prediction of postoperative complications.

OBJECTIVE: To find out whether concentrations of albumin (reflecting nutritional state), C-reactive protein (reflecting an acute phase reaction) or plasma protease inhibitors (reflecting ongoing proteolysis) are good predictors of postoperative complications, and whether other biochemical tests may improve diagnostic accuracy. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 260 patients undergoing elective surgery for malignant (n = 149) or benign (n = 111) disease. MAIN OUTCOME MEASURES: Preoperative biochemical plasma measurements and postoperative complications. RESULTS: 192 patients recovered uneventfully and 35 had minor and 33 major postoperative complications. An increased plasma C-reactive protein concentration preoperatively, as well as a reduced albumin concentration, predicted the risk of developing major postoperative complications. Measurement of plasma protease inhibitors (C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin III), specific biochemical studies of microheterogeneity, or comparison of quantitative and functional concentrations of the inhibitors gave no additional information. CONCLUSION: One measurement of the C-reactive protein and albumin concentrations preoperatively will identify patients at risk of developing severe postoperative complications.

Adult

Alterations in the functions of the reticuloendothelial and protease-antiprotease systems after intraperitoneal injection of zymosan in rats.

OBJECTIVE: To evaluate alterations in the function of the reticuloendothelial system (RES) and potential protective effects of pretreatment with the antioxidants: N-acetyl-L-cysteine (NAC) or dimethyl sulphoxide (DMSO), after intraperitoneal injection of zymosan (0.50 mg/g body weight) in rats. DESIGN: Experimental study. SETTING: University hospital, Sweden. ANIMALS: 81 male Sprague-Dawley rats. INTERVENTION: Intraperitoneal injection of either 4 ml saline or zymosan suspension (0.50 mg/g body weight). One hour before the intraperitoneal injection, 1 ml of saline, or a solution of NAC (150 mg/kg) or DMSO (80 mg/kg) were given intravenously. MAIN OUTCOME MEASURES: Systemic arterial pressure, packed cell volume, concentrations of plasma proteins and plasma protease inhibitors, uptake of 125I-labelled Escherichia coli in organs, blood clearance and body uptake rate of radiolabelled E. coli, and blood flow in organs at 3, 6, and 12 hours after injection. RESULTS: The uptake of radiolabelled E. coli in the liver, spleen and lungs decreased significantly from 3 hours onwards after zymosan challenge (p <(0.05). Blood clearance and body uptake rate also decreased significantly from 3 hours onwards (p < 0.05), but this did not correlate with the reduction in organ blood flow. Significant falls in plasma concentrations of prekallikrein (p < 0.01) and protease inhibitors (p <0.05) suggested possible contact-phase activation and activation of the kallikrein-kinin and fibrinolytic system. Pretreatment with NAC, and to a less extent DMSO, significantly prevented these alterations in RES function. CONCLUSION: Zymosan induced an impairment in RES function that was not initially associated with a reduction in blood flow. Plasma proteolytic activity seems to be involved in the impaired RES function. Pretreatment with NAC or DMSO effectively improved RES function.

Acetylcysteine

The influence of intestinal ischemia and reperfusion on bidirectional intestinal barrier permeability, cellular membrane integrity, proteinase inhibitors, and cell death in rats.

Intestinal ischemia and reperfusion injury (I/R) is probably involved in the pathogenesis of intestinal barrier dysfunction, associated with the concomitant translocation of enteric bacteria and toxins and the potential development of multiple organ failure. The intestinal endothelial and epithelial layers play a major role preventing the entry of toxic substances from the gut, but the influence of protease-antiprotease systemic balance on these barrier functions and the relationship between epithelial DNA synthesis, apoptosis, and endothelial and epithelial barrier macromolecule permeability are not fully investigated. Endothelial and epithelial barrier macromolecular permeability, epithelial DNA synthesis, the endothelial and epithelial plasma membrane system, apoptosis and oncosis, plasma levels of proteinase inhibitors, and proenzymes were measured in rats subjected to 20 and 40 min intestinal ischemia and 1, 3, 6, or 12 h reperfusion. Endothelial permeability increased after both 20 and 40 min intestinal ischemia. Epithelial permeability significantly increased during 1-6 h reperfusion after 20 min ischemia and during 1-12 h reperfusion after 40 min ischemia. Epithelial DNA synthesis increased in animals with 20 min ischemia followed by 12 h reperfusion. Plasma levels of prekallikrein, C1-esterase inhibitor, and alpha1-macroglobulin were significantly lower following both 20 and 40 min ischemia from 3 h reperfusion and on. Apoptotic epithelial cells significantly increased in animals subjected to 20 min ischemia followed by 12 h reperfusion. The severity of reperfusion injury in the intestinal endothelial and epithelial barrier seems to correlate with the period of ischemia and the pathway of cell damage and death, together with proteinase-antiproteinase imbalance.

Albumins

Pre-operative plasma levels of C-reactive protein, albumin and various plasma protease inhibitors for the pre-operative assessment of operability and recurrence in cancer surgery.

Pre-operative levels of the acute phase protein C-reactive protein (CRP), albumin (assessing nutritional status), the tumour marker CEA and three plasma protease inhibitors, i.e. C1-esterase inhibitor, alpha-2-macroglobulin and antithrombin III, were prospectively studied in 183 patients with various solid cancers. First, the predictive value of abnormal levels for operability at the primary operation was studied. Secondly, the predictive value of abnormal levels for cancer recurrence and metastases was evaluated during 2 years of follow-up. The results show that malignancy induces increased CRP and C1-esterase inhibitor levels and decreased albumin levels in serum. These changes, as well as raised alkaline phosphatase and lowered haemoglobin levels, also correlate to the 'overall' tumour burden. The most important conclusion is, that increased pre-operative CRP levels (CRP > or = 10 mg/l; sensitivity, 79%; specificity, 71%) and/or low albumin levels (albumin <37 g/l; sensitivity, 94%; specificity, 54%) are seen in inoperable cancer patients compared with patients having operable cancers. The second main important conclusion is, that high pre-operative C1-esterase inhibitor levels (C1-esterase inhibitor >152%; sensitivity, 45%; specificity, 90%), and in some patients a high alkaline phosphatase level, are seen in patients exhibiting early cancer recurrence (within 2 years post-operatively).

Aged

Ultrasonography in gallstone ileus: a diagnostic challenge.

OBJECTIVE: To describe our experience with ultrasound diagnosis of gallstone ileus in six cases, and to assess the impact of our findings in the light of published reports. DESIGN: Open study. SETTING: Teaching hospital, Sweden. SUBJECTS: Six patients with gallstone ileus. INTERVENTION: Abdominal ultrasound examination. MAIN OUTCOME MEASURES--Correlation with plain abdominal films and with findings at laarotomy. RESULTS: In all six cases ultrasound gave a precise diagnosis of gallstone ileus, together with the exact location of the gallstone, whereas plain films usually indicated only intestinal obstruction of unknown cause. There was not mortality and only one postoperative complication, and all patients were alive and well at the time they were last seen. These results compare well with those of other reported series. CONCLUSION: The high morbidity and mortality of gallstone ileus may be reduced if ultrasonography is used in cases of undiagnosed abdominal pain, particularly in elderly patients with protracted symptoms.

Aged

Proteolytic activity in pancreatic pseudocyst fluid.

Pancreatic pseudocyst fluids from 15 patients were biochemically analyzed, especially concerning proteolytic activity and protease inhibitors, and correlated to the clinical course. The pseudocyst fluid was a mixture of pancreatic juice and plasma possessing a high proteolytic activity against high- as well against low-mol-wt proteins. There was practically no functional protease inhibitory capacity left, although immunoreactive inhibitors were present. No distinct biochemical findings differed between fluids from "acute" or from "chronic" pseudocysts. It is concluded, that high proteolytic activity within a pancreatic pseudocyst could well explain symptoms as well as complications caused by the pseudocyst. Biochemical analysis of the pseudocyst fluid cannot, however, be used to differentiate between pseudocysts with a harmless or a complicated course.

Acute Disease

The proteolytic effect of pancreatic pseudocyst fluid on vessel walls.

The possible in vivo consequences of proteolytic activity found in pancreatic pseudocyst fluid was investigated experimentally using fresh vessels from rabbit and humans. Proteolytic pseudocyst fluid caused a pronounced and time-dependent decrease in breaking strength of fresh vessels. A destruction of the normal histological architecture and fragmentation of the elastic tissue of the vessel wall paralleled the mechanical findings. The proteolytic digestion was caused by the low-mol-wt fraction of the pseudocyst fluid, corresponding to free proteases. Part of this proteolysis was probably caused by pancreatic proteases, since pancreatic juice also caused a decrease in breaking strength and a destruction of the histologic architecture of the vessel wall. Proteases bound to protease inhibitors, i.e., to alpha-2-macroglobulin, had no proteolytic activity. It is concluded that the proteolytic digestion caused by proteolytic pancreatic pseudocyst fluid may well explain severe complications of pancreatic pseudocysts, like bleeding within the pseudocyst and rupture of the entire pseudocyst wall, although the proteolytic digestion is probably counteracted by a constant regeneration of the pseudocyst wall in vivo.

Adult

Ipsilateral multiple groin hernias.

BACKGROUND: Recurrence rates after surgical repair of groin hernia vary between 3% and 20%. One possible reason for recurrent hernias are ipsilateral multiple hernias, which might have been overlooked at the primary operation. METHODS: In the present series 1010 patients with unclear groin pain underwent herniography. RESULTS: A total of 314 patients had hernias, and seventy-one (23%) of these had multiple hernias. Ipsilateral multiple hernias were found in 18 (6%) patients. Ipsilateral multiple hernias were present in 9 (6%) of 144 patients with an indirect hernia, in 17 (12%) of 144 patients with a direct hernia, in 5 (21%) of 24 patients with a femoral hernia, and in 3 (23%) of 13 patients with an obturator hernia. The hernias were of indirect, direct, femoral, and obturator types. CONCLUSIONS: The frequency of ipsilateral multiple hernias is much higher than the frequency reported during herniorrhaphy. Such overlooked ipsilateral multiple groin hernias may account for some of the so-called recurrences after herniorrhaphy. Therefore a careful exploration of the groin is mandatory. Preoperative herniography may also prove to be useful in patients with recurrent groin symptoms after herniorrhaphy.

Adult

Uptake of immunoreactive leukocyte elastase-inhibitor complexes in macrophage-like cells in abscesses.

Leukocyte elastase was demonstrated immunohistochemically not only in PMN-leukocytes in subcutaneous abscesses but also in scattered macrophage-like cells which in addition contained immunoreactive alpha 1-proteinase inhibitor (alpha 1PI) and alpha 2-macroglobulin (alpha 2M). These cells were located mainly in the marginal region of the abscess. It is concluded that the intracellular deposits in the macrophage-like cells represent phagocytized elastase and/or elastase-alpha 1PI and elastase-alpha 2M complexes. A contributing, local production of the inhibitor is, however, not excluded by the present findings.

Abscess

Alpha-2-macroglobulin decreases parallel to albumin and haemoglobin after elective surgery.

Plasma levels of the plasma protease inhibitor alpha-2-macroglobulin (alpha 2-M) were followed for 7 days in 90 patients subjected to various surgical procedures. Alpha 2-M was found to decrease strictly in parallel with the decrease seen for haemoglobin and albumin levels in all patients. Changes were most pronounced after extensive operations; total hip replacement (n = 7), pulmonary resection (n = 11), extensive colo-rectal resection (n = 15), and less pronounced after 'minor' operations; mastectomy (n = 23) proximal gastric vagotomy (n = 5) and moderate colo-rectal resection (n = 29). Levels were lowest on the second to third postoperative day, whereafter they slowly returned to normal, preoperative levels during the 7-day study period. Functional and quantitative alpha 2-M levels almost paralleled each other throughout the 7 days studied. Chromogenic peptide substrate assays indicated circulating plasmin-alpha 2-M complexes, while no protease-alpha 2-M complexes could be demonstrated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) or isoelectric focusing (IEF) analyses. Local accumulation and consumption of proteins within wounded tissues, together with haemodilution, were probably the major factors responsible for the decreased plasma levels seen. It is concluded that the plasma levels of alpha 2-M decrease after major elective surgery strictly in parallel with the decrease seen in haemoglobin and albumin levels, and that circulating plasmin-alpha 2-M complexes are probable. The decrease seems to be graded, that is, proportional to the extent of the operative trauma, similar to the postoperative increase seen in positive acute-phase proteins. Thus, alpha 2-M cannot be used as an internal, unchanged plasma protein standard for other protein changes seen after trauma.

Adult

Pancreatic pseudocyst fluid--a mixture of plasma proteins and pancreatic juice possessing a high proteolytic activity.

Pancreatic pseudocyst fluid from eight patients was examined biochemically. The fluid was found to be a mixture of plasma proteins and pancreatic juice, possessing a high proteolytic activity against high- as well as low-molecular-weight proteins. The proteolytic activity was found to be trypsin-, kallikrein- and plasmin-like. Gel filtration studies showed proteolytic activity to be present corresponding to alpha-2-macroglobulin-bound proteases and also to free proteases. Quantitative immunochemical levels were about 30-100% of normal plasma levels for alpha-2-macroglobulin, C1 inhibitor, antithrombin III and alpha-2-antiplasmin. However, there was practically no functional inhibitory capacity left in the pseudocyst fluid, except for alpha-1-protease inhibitor, which retained its inhibitory capacity. Neither native kininogen nor complement factor C3 was found: this was probably a result of the proteolytic activity. It is concluded, that a continuing proteolytic activity within the pseudocyst, although decreasing with aging of the cyst, could explain symptoms and complications caused by the pseudocyst.

Adult

Abnormal proteolysis (DIC)--successful treatment with antithrombin III concentrate and a concentrate containing F XIII and native von Willebrand factor.

Two patients with life-threatening disseminated intravascular coagulation (DIC) syndrome, one caused by Gram-negative bacteria and one by premature separation of the placenta, are described. Specific substitution was given by antithrombin III concentrate and AHF-Kabi, a low purity factor VIII concentrate containing native von Willebrand factor and factor XIII. The treatment quickly returned the extremely low levels of antithrombin III, factor VIII:C, fibrinogen and factor XIII, initially found, to normal, and also returned the multimeric pattern of von Willebrand factor to normal. This resulted in diminished bleeding, enabling surgical treatment of the underlying disease.

Adult

Early diagnosis and classification in acute pancreatitis. A comparison of clinical outcome with findings at computed tomography and Ranson's prognostic signs.

The clinical outcome in 52 consecutive episodes of suspected acute pancreatitis was compared with Ranson's prognostic signs and findings on noncontrast and contrast-enhanced computed tomography (CT) scans performed within 24 h of patient admission. The predictive value of CT scan for diagnosis was 95% for positive results and 53% for negative results. In providing an accurate prognosis of a single attack, scoring of extrapancreatic signs was as good as that of Ranson's prognostic signs. CT with contrast medium revealed pancreatic ischaemia in 3 cases of 4 with clinically severe disease. The risk of developing severe pancreatitis was 23% in first attacks and 6% in relapses. Early CT scan is recommended in most patients with suspected pancreatitis to confirm diagnosis and to predict the severity of an attack.

Acute Disease

Pathobiochemistry and early CT findings in acute pancreatitis.

Extrapancreatic findings at computed tomography (CT), performed within 24 h in 42 consecutive episodes of acute pancreatitis, were classified according to a scoring system (EP score) and were correlated to Ranson's prognostic signs, to duration of hospital stay, biochemical changes in plasma and pancreatic ischaemia found at CT with contrast enhancement. Increasing EP score was found to be related to increasing number of positive Ranson's signs, longer hospital stay and pancreatic ischaemia. Plasma levels of immunoreactive cationic trypsin and amylase were not proportional to EP score. alpha 1-protease inhibitor, antichymotrypsin but not immunoreactive pancreatic secretory trypsin inhibitor increased proportionally to EP score. No changes related to EP score were seen in alpha 2-macroglobulin levels. Serum levels of trypsin-alpha 1-protease inhibitor complex were maximal after 3 days and most pronounced in cases with high EP scores. Plasma levels of factor X, alpha 2-antiplasmin and C1-esterase inhibitor were found to be inversely proportional to EP score.

Acute Disease

Patterns of immunoreactive trypsin in serum from patients with acute abdominal disorders.

Immunoreactive trypsin in serum can be divided into trypsinogen and trypsin-alpha 1-proteinase inhibitor (alpha 1PI) complexes. These were studied separately in serum from 204 patients with acute gastro-intestinal symptoms. Elevated levels of both trypsinogen and trypsin-alpha 1PI complexes were seen in patients with acute pancreatitis. Elevated levels of trypsinogen and normal or slightly elevated levels of trypsin-alpha 1PI complexes were seen in patients with biliary tract diseases. An isolated increase in the concentration of trypsin-alpha 1PI complexes with normal trypsinogen and amylase levels were seen in patients with perforated ulcer. This third cluster may result from an absorption of active trypsin from the peritoneal cavity. Small amounts of trypsin-alpha 1PI complexes were present also in serum from patients free from pancreatic disease. The results in this study show that high levels of trypsin-alpha 1PI complexes in serum are seen mainly in patients with acute pancreatitis. However, elevated levels are also seen in other pathological conditions in the upper gastrointestinal tract; therefore an assay for these complexes is not a specific diagnostic test for acute pancreatitis.

Abdomen, Acute

Local administration of human pancreatic secretory trypsin inhibitor prevents the development of experimental acute pancreatitis in rats and dogs.

The objective of this investigation was to test the capacity of recombinant human pancreatic secretory trypsin inhibitor (rhPSTI) to provide prophylaxis against experimental pancreatitis. Acute hemorrhagic pancreatitis was induced by intraductal injection of sodium taurocholate in rats and by intraductal injection of bile in dogs. In one treatment group of rats the injection of taurocholate was preceded by injection of rhPSTI. In a second group of rats the rhPSTI was given intraperitoneally starting 15 min after the induction of acute pancreatitis. The survival rate in a control group of rats was 13%. In contrast, the survival rate in groups receiving rhPSTI intraductally or intraperitoneally was 80% and 63%, respectively. The survival rate in a control group of dogs was 40% at 24 h and 0% at 48 h. In contrast, all the dogs receiving a single intraductal dose of rhPSTI, either immediately before the bile injection or mixed with the bile, survived for up to 6 weeks. Detailed biochemical and immunohistologic studies in the dog indicate that, whereas rhPSTI cannot prevent the initial bile-induced injury, it does prevent the subsequent development of that injury to the point where there is massive damage to the pancreas and the surrounding tissues, and changes in blood chemistry. The development of the initial injury is, therefore, presumed to involve activation of trypsinogen. Since rhPSTI prevents the serious consequences of experimental pancreatic injury by blocking the action of trypsin, and since the pathobiochemistry of human acute pancreatitis also implies an important role for trypsin, it is possible that rhPSTI could protect humans from the pancreatitis that complicates endoscopic retrograde cholangiopancreatography and endoscopic papillotomy.

Acute Disease

Proteases and protease inhibitor balance in peritonitis with different causes.

Protease activation and protease-antiprotease interactions were sequentially studied in two different groups of patients with peritonitis. The biochemical changes were related to the cause of the disease and to the clinical course. Protease activation and protease inhibitor consumption were most pronounced in the peritoneal fluid, especially in bacterial peritonitis. Plasma changes also indicated activation of the complement, kinin, and fibrinolytic systems and protease inhibitor consumption, especially of alpha 2-macroglobulin and antithrombin III. There was no significant difference between chemical and bacterial peritonitis regarding these plasma changes. Immunohistologic studies showed evidence of active uptake of protease-antiprotease complexes in macrophage-like cells in the peritoneum in both groups. It is concluded that peritonitis results in protease activation and protease inhibitor consumption, especially in the peritoneal fluid. The peritoneum has an active role in the clearance of protease-antiprotease complexes. The intensity, not the type, of the intra-abdominal challenge determines the biochemical changes in peritonitis.

Adult