Biomedical subjects

A O Aasen

Publications and source records attributed to A O Aasen.

At least 19 recordsLinked to original sources

PubMed1995

Activation of the plasma contact system and hemodynamic changes after graft revascularization in liver transplantation.

In this study, the relation between activation of the plasma contact system and hemodynamic changes during orthotopic liver transplantation was evaluated. Nineteen consecutive courses of OLT in 17 adult patients were investigated. Veno-venous bypass was used in all patients. Blood samples were drawn through all phases of the procedure, and analyzed for the following parameters using functional techniques (chromogenic peptide substrate assays): plasma kallikrein (KK), prekallikrein, functional plasma kallikrein inhibition, C1 inhibitor, and alpha 2-macroglobulin. Plasma high molecular weight kininogen (HK) degradation was evaluated using the immunoblotting technique. An abrupt rise in KK activities occurred within 1 min after portal reperfusion of the liver graft (7-16 U/L, P < 0.05). Simultaneously, proteolytic breakdown of HK was seen. The elevated KK activities were maintained the next 1 1/2 hr. Ten min after graft reperfusion, a significant increase in cardiac output compared with the anhepatic phase (7.2-12.4 L/min, P < 0.05) was found. At the same time, systemic vascular resistance fell significantly (817-408 dynes x sec/cm-5, P < 0.05). The increase in plasma KK activities accompanied by simultaneous degradation of HK seen immediately after reperfusion of the liver graft may be due to contact activation as recipient blood contacts with the underlying basement membrane of injured sinusoidal endothelium in the transplanted liver. We suggest that hemodynamic changes associated with the postreperfusion syndrome seen after revascularization of the liver in OLT could at least be caused in part by bradykinin release due to contact activation.

Adult↗

PubMed1995

Antigen levels of urokinase plasminogen activator and its receptor at the tumor-host interface of colorectal adenocarcinomas are related to tumor aggressiveness.

The distributions of urokinase and tissue plasminogen activators (uPA, tPA), uPA receptor (uPAR), and plasminogen activator inhibitors (PAI-1, PAI-2) were studied immunohistochemically in two subsets of colorectal adenocarcinomas with low and high aggressiveness, respectively: nine Dukes' stage A tumors with additional other good prognostic markers and 13 Duke's stage C tumors with also other poor prognostic markers (referred to as Dukes' stage A and Dukes' stage C tumors). The results showed that these components of the tissue destructive plasminogen activation system were accumulated at the invading front of the tumors. Both tumor groups showed accumulations of uPA, uPAR, and PAI-1 at the tumor-host interface compared with the location within the tumor epithelium and the adjacent normal mucosa and muscularis propria (all P < .05). However, the uPA level at the tumor-host interface in the Dukes' stage C tumors was twice the level in the Dukes' stage A tumors (P < .05). The uPAR level was also significantly higher in the Dukes' stage C tumors (P < .05), whereas the PAI-1 level was not significantly higher. This may indicate that uPA in more aggressive tumors exceeds the inhibitory capacity represented by PAIs, resulting in enhanced tissue destructive potential that promotes tumor invasion. uPA and uPAR antigen levels and the uPA/PAI-1 ratio at the tumor-host interface appeared to be related to tumor aggressiveness in colorectal cancer.

Adenocarcinoma↗

PubMed1995

Effect of syringe-assisted liposuction on activation of cascade systems and circulating cells when using the superwet or tumescent technique.

Although liposuction is considered to be a relatively safe procedure, several deaths and nonfatal serious complications such as sepsis, toxic shock syndrome, thromboembolic disease, fat emboli, and adult respiratory distress syndrome have been reported. In the present study, we have investigated a wide variety of components belonging to the coagulation, fibrinolytic, plasma kallikrein-kinin, and complement systems in 22 patients undergoing syringe-assisted liposuction using the superwet or tumescent technique. In spite of a relatively high mean aspirate volume (2,648 ml), only small changes over time well within the normal range were found for the different parameters. In nine randomly selected patients, we also measured interleukin 6 and tumor necrosis factor-alpha. The size of the interleukin-6 peaks was found to be of the same order of magnitude as those measured in patients undergoing hernia repair or percutaneous cholecystectomy but lower than those in patients undergoing open cholecystectomy, breast reduction, or breast reconstruction. Tumor necrosis factor-alpha was not detected in any sample in any of the patients. We conclude that syringe-assisted liposuction with the present aspirate volumes using the superwet or tumescent technique represents a small to moderate surgical trauma without clinical significant activation of the cascade systems.

Adipose Tissue↗

PubMed1995

There is no difference in spontaneous and 17 beta-estradiol-induced interleukin-1 beta release by peripheral blood mononuclear cells from nonosteoporotic women with different rates of early postmenopausal bone loss.

Interleukin-1 (IL-1) is a potent stimulator of bone resorption, and a causal role for IL-1 has been suggested in postmenopausal bone loss. We have examined IL-1 beta release in vitro by peripheral blood mononuclear cells (PBMC) isolated from nonosteoporotic women 9-15 yr after menopause. These women had presented 6 yr previously with significant differences in the rate of early postmenopausal bone loss. Ten women with low rates of bone loss (median 2.0% per year) and 10 women with high rates of bone loss (median 4.9% per year) were included in the study. The women with a high rate of bone loss had a significantly lower bone mass of the lumbar vertebrae compared with that of the other group, but there were no differences in biochemical markers of bone metabolism between the groups (pyridinoline/creatinine ratio in urine and collagen 1 c-terminal telopeptide and bone gla protein in serum). Moreover, there was no difference in spontaneous IL-1 beta release by PBMCs between the two groups and no correlation between IL-1 beta release and present bone turnover, as judged by biochemical markers. Treatment of PBMCs with 10 nmol/L 17 beta-estradiol in vitro significantly stimulated IL-1 beta production in both groups. We conclude that IL-1 beta production by PBMCs in vitro does not correlate with the rate of early postmenopausal bone loss.

Amino Acids↗

PubMed1995

Complement activation and release of tumour necrosis factor alpha, interleukin-2, interleukin-6 and soluble tumour necrosis factor and interleukin-2 receptors during and after cardiopulmonary bypass in children.

C3 activation products, terminal complement complex (TCC), and cytokines including interleukins 6 and 2 (IL-6, IL-2) and tumour necrosis factor-alpha (TNF), and the soluble IL-2 and TNF receptors were determined serially during and up to 48 h after open heart surgery in children. Significant increases were noted in soluble TNF and IL-2 receptor levels postoperatively (p < 0.05). No significant increase over preoperative levels was seen in the cytokines, except for IL-6 which was significantly increased postoperatively (p < 0.01), reaching a maximum 2 h postoperatively. C3 activation products and TCC levels increased significantly after weaning from cardiopulmonary bypass (p < 0.05). The IL-6 response lagged behind the complement activation. We found a significant correlation between duration of cardiopulmonary bypass and IL-6 levels 48 h postoperatively (r = 0.852, p < 0.05). We conclude that the concentration of complement activation products, IL-6 and the soluble TNF and IL-2 receptors are significantly increased after open heart surgery in children. The cytokine receptor response probably reflects some sort of regulatory mechanism.

Cardiopulmonary Bypass↗

PubMed1995

Troublesome colostomies and urinary stomas treated with suction-assisted lipectomy.

OBJECTIVE: To investigate the effectiveness of liposuction as treatment in troublesome colostomies and urinary stomas in selected patients. DESIGN: Open clinical study. SETTING: University hospital, Norway. SUBJECTS: 8 consecutive patients with colostomies (n = 2) or urinary stomas (n = 6) who required treatment with liposuction above or around the stoma, mainly for leakage. INTERVENTIONS: Syringe-assisted liposuction under local anaesthesia. MAIN OUTCOME MEASURES: Change in stoma function, particularly reduction in the incidence of leakage, and by the patients' satisfaction graded according to a four point scale. RESULTS: All patients noted considerable improvements in stoma function, or abdominal contour, or both. CONCLUSION: Troublesome colostomies and urinary stomas can in selected patients be successfully treated with liposuction above or around the stoma.

Adult↗

PubMed1993

The contact system in human malignant and benign ascites.

The plasma contact system was studied in ascites and plasma from patients with gastrointestinal cancer and patients with liver failure. Our study demonstrates the presence of factor XII, factor XI, and prekallikrein and their main inhibitors in ascites and plasma from both patient groups. Both factor XII-like and plasma kallikrein-like activities were detected in the malignant ascites. The kallikrein-like activity in malignant ascites was found in complex with alpha 2-macroglobulin. In plasma samples from the patients functional values of factor XII and prekallikrein were decreased compared to controls. In benign ascites the proenzyme levels were significantly lower than in malignant ascites. Functional inhibition values in ascites and plasma from patients were unexpectedly high. Our findings indicate that the plasma contact system is activated in the ascites from cancer patients. Activation of the contact system generates vasoactive mediators, which may play a role in the accumulation of malignant ascites.

Aged↗

PubMed1993

Differential diagnosis of human ascites: inhibitors of the contact system and total proteins.

To assess their accuracies as markers for malignancy, we assayed alpha 2-macroglobulin, C1-inhibitor, alpha 1-protease inhibitor, and total proteins in ascites and plasma from patients with gastrointestinal cancer (n = 15) and non-malignant liver disease (n = 13), using functional and immunologic assays. For all inhibitors and total proteins determined in ascites, the values in the cancer group were significantly higher than the corresponding values in the group with non-malignant liver disease. The diagnostic accuracy for differentiating malignancy-related from non-malignant ascites was 93% for a alpha 1-protease inhibitor value > or = 50% of the pool plasma value and 90% for alpha 2-macroglobulin > or = 16%, C1-inhibitor > or = 40% (all functional assays), and total proteins > or = 20 g/l (biuret). In conclusion, functional assays for alpha 2-macroglobulin, C1-inhibitor, and alpha 1-protease inhibitor and determination of total proteins in ascites appeared to be very informative tests for the differential diagnosis of ascites. The test for alpha 1-protease inhibitor gave higher specificity (92% versus 77%) and likelihood ratio for a positive test (12 versus 4) compared with the other tests.

Adult↗

PubMed1992

[Pelvi-rectal abscesses. Diagnosis, treatment and follow-up by transrectal ultrasonography].

Pelvirectal abscess usually presents with vague symptoms which may delay diagnosis and subsequent treatment. However, it is important to recognize this condition since these abscesses may interfere with the sphincter function or give rise to chronic fistulo-in-ano. We describe two patients in whom transrectal ultrasound was applied for diagnosis, and who were treated for a pelvirectal abscess. Both patients were admitted to our hospital because of tumour of the rectum. There were few symptoms and signs of infection. Transrectal ultrasound examination of the rectum made a significant contribution to early diagnosis. We also point out the advantage of transrectal ultrasound examination during follow-up, mainly because we were able to rule out malignant neoplasm by obtaining an ultrasound-guided specimen for histological examination.

Abscess↗

PubMed1992

[Rectal cancer. Staging with transrectal ultrasonography].

30 patients with carcinoma of the rectum were examined preoperatively with endoluminal rectal ultrasound and digital examination in order to assess the stage of the tumour. The results were compared with the histopathological findings in the resected specimens from 23 patients. The following operations were performed: 11 abdominoperineal rectal amputations, five low anterior resections and seven local excisions. Discrepancies between the ultrasonic and histological staging occurred in seven patients, six tumours were overstaged and one understaged ultrasonically. Digital assessment overstaged eight tumours and understaged two. The ultrasonic examination provided additional information in 12 patients.

Adenocarcinoma↗

PubMed1992

[Intraoperative ultrasonography of the liver].

Intraoperative ultrasound is the most recent diagnostic tool in liver surgery. It presents the surgeon with a technique that can provide detailed information about liver tumours and their topography prior to surgery. It also provides very good visualization of the vascular tree of the liver. This article gives a detailed description of the technique of intraoperative ultrasound of the liver. It also presents results from two groups of patients: 30 patients who underwent laparatomy for colorectal cancer (n = 16) or for liver tumours (n = 14) were examined by intraoperative ultrasound of the liver. The results were compared with the observations made by preoperative ultrasound examination. In seven patients the intraoperative ultrasound examination showed liver tumors that had not been detected preoperatively. The intraoperative ultrasound was decisive for the operative strategy in three of the patients treated for liver tumours. In one of the patients operated on for colorectal cancer, in whom the intraoperative ultrasound examination revealed a previously unrecognized metastasis, a liver resection is now planned. Our study confirms that intraoperative ultrasound is a valuable form of examination in patients treated for colorectal cancer and is important for deciding the surgical strategy for patients treated for liver tumours.

Adult↗

PubMed1992

Different role of cytokine mediators in septic shock related to meningococcal disease and surgery/polytrauma.

So far, there has been a tendency towards a uniform concept of the role and kinetics of TNF and other cytokines in septic shock. However, our comparison of data from different groups of shock patients clearly demonstrates marked differences. On the one hand, the cytokine pattern in experimental septic shock and meningococcal disease has similarities which include early burst releases of TNF and IL-6. On the other hand, intensive care unit patients which includes patients with polytrauma, surgery, burns and other underlying diseases have a completely different pattern of appearance of TNF and IL-6 in the circulation. We have not been able to detect bioactive TNF in the circulation of these patients, whereas others have measured elevated levels of immunoreactive TNF. Bioactive IL-6 can be detected in serum; however, the levels are often fluctuating and there is no common pattern of appearance. These differences probably reflect differences in the release of endotoxin and the immunological status of the patients. TNF inhibitors and soluble TNF receptors probably play an important role. Experimental models for septic shock most commonly use administration of live bacteria or endotoxin to anesthesized healthy animals. This appears to be a good model for meningococcal disease, but not for intensive care unit patients.

Bacteremia↗

PubMed1992

Hemodynamic and proteolytic effects of intravenous injection of purified human plasma kallikrein.

To investigate the precise hemodynamic effects of purified human plasma kallikrein, small doses (0.3 U/kg) of this proteolytic enzyme were infused over 10 s in five pigs. Hemodynamic performance was evaluated by means of a Swan-Ganz catheter, and parameters of the plasma kallikrein-kinin, coagulation, and fibrinolytic systems were determined by means of chromogenic peptide substrate assays. The infusions of plasma kallikrein were followed by rapid decreases in mean arterial pressure (to 43 +/- 2% of baseline values) and increases in cardiac output (to 145 +/- 6% of baseline values), accounting for marked decreases in systemic vascular resistance, to 28 +/- 1% of initial values. Heart rate, mean pulmonary arterial, central venous, and pulmonary capillary wedge pressures did not change after the injection. Pulmonary vascular resistance decreased to 69 +/- 3% of baseline values. The hemodynamic changes gradually normalized during the following 10 min. Functional levels of prekallikrein, kallikrein, kallikrein inhibition, prothrombin, antithrombin III, plasmin, and antiplasmin were not affected by the injection or the resulting hemodynamic changes; the hematocrit and the number of circulating leukocytes or platelets were also unaffected.

Animals↗

PubMed1992

Effects of heparin on proteolytic activities in human plasma.

The influence of unfractionated heparin [average molecular weight (MW) 10,000-15,000 kD] and low-molecular-weight heparin (average MW 400-600 kD) on the plasma kallikrein-kinin and the fibrinolytic system was studied in vitro. Unfractionated heparin added to plasma gave an increase in kallikrein-like activity with a corresponding decrease of prekallikrein and functional kallikrein inhibition values. Plasmin-like activity was also increased, but minor changes in plasminogen and no change in antiplasmin values occurred. The changes were less pronounced with low molecular heparin compared with unfractionated heparin. The proteolytic changes were reversed by protamine sulfate but not influenced by the protease inhibitor aprotinin. Gel filtration yielded proteolytic activities able to split the plasma kallikrein substrate S-2305 and, to a minor degree, the plasmin substrate S-2251. The proteolytic activities were not due to complex formation with alpha 2-macroglobulin. We speculate that heparin binds to prekallikrein to form a heparin-prekallikrein complex which undergoes conformational changes and displays a kallikrein-like activity with the ability to split small synthetic substrates. Whether it is capable to split natural substrates remains unresolved.

Aprotinin↗

PubMed1992

Activation of the plasma kallikrein-kinin system in respiratory distress syndrome.

Components of the plasma kallikrein-kinin and fibrinolytic systems together with antithrombin III were measured the first days postpartum in 13 premature babies with severe respiratory distress syndrome (RDS). Seven of the patients received a single dose of porcine surfactant (Curosurf) as rescue treatment. Nine premature babies without lung disease or any other complicating disease served as controls. There were no differences in prekallikrein values between surfactant treated and non-treated RDS babies during the first 4 d postpartum. The controls had, however, significantly higher prekallikrein values than the RDS babies already at the first day of age (mean +/- SD 32 +/- 8% in controls versus 22 +/- 6 and 21.5 +/- 5% in the treated and nontreated RDS groups, respectively). Plasma kallikrein activities did not differ between RDS and control patients. Plasma kallikrein inhibition values, which increased steadily in all groups, were lower in the RDS babies treated with surfactant than in controls at d 2 and 4. The degree of degradation of plasma high molecular weight kininogen was measured in RDS patients treated with surfactant and was significantly higher when compared with controls at d 1, demonstrating an increased proteolysis of kininogen to kinin early in RDS. There were no differences in plasminogen and plasmin values between RDS and control babies. This study shows that the plasma kallikrein-kinin system is activated in RDS. This system as well as the fibrinolytic system does not seem to be influenced by rescue instillation of a single dose of porcine surfactant into the lungs of premature babies with RDS.

Antithrombin III↗

PubMed1992

Activation of the contact system in ascites from patients with gastrointestinal cancer.

Our observations indicates that the plasma contact system is activated in ascites from patients with gastrointestinal cancer: Factor XII is activated, plasma kallikrein is present in complex with the protease inhibitor alpha 2-macroglobulin, and the plasma kallikrein substrate high molecular weight kininogen, is highly degraded. Contact activation seems to take place in spite of a high level of inhibition. Activation of the contact system generates mediators, which may play a role in the accumulation of ascites.

Adult↗

PubMed1992

On the value of giving a combination of drugs for the treatment of endotoxaemia in pigs.

OBJECTIVE: To see if treatment with a combination of drugs each directed at a different mediator was successful in preventing activation of those mediators in experimental endotoxic shock. DESIGN: Controlled study. MATERIAL: 40 juvenile pigs. INTERVENTIONS: 33 animals received 0.01 mg/kg endotoxin infusion, the rest being given the same volume of saline; 10 of the 33 received no treatment. Of the remaining 23, 5 were given combination treatment with methylprednisolone, naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and aprotinin; 7 were given methylprednisolone only; 6 were given the three protease inhibitors (C1 esterase inhibitor, antithrombin III and aprotinin); and 5 were given naloxone, ketanserin and promethazine. MAIN OUTCOME MEASURES: Assessment of haemodynamic, proteolytic, and cellular effects of endotoxaemia. RESULTS: Only the combination treatment totally blocked all the effects of the infusion of endotoxin. CONCLUSION: As endotoxin affects several mediators, combination treatment is necessary to block all its deleterious effects in pigs.

Animals↗

PubMed1991

Characterization of kininogens in human malignant ascites.

Ascites from seven patients with advanced cancer were studied to characterize the kininogens. Immunological quantification of low molecular weight kininogen (L-kininogen) and high molecular weight kininogen (H-kininogen) by rocket immunoelectrophoresis showed values of 42% and 39%, respectively, compared to control plasma. Release of kinin from the ascites samples was assayed on an isolated rat uterus. The total kinin released from the kininogens was 39% of the value in control plasma, while release selectively from H-kininogen amounted to 25% of plasma. This indicates about 30% of the bradykinin in H-kininogen to be released in vivo in ascites, and points to kinins as possible mediators of the increased vascular permeability causing accumulation of ascites. The function of kininogens as cysteine protease inhibitors (CPIs) was assayed as well, indicating that both L- and H-kininogen function as cysteine protease inhibitors in human ascitic fluid. The proteolytic cleavage of H-kininogen in ascites was studied by polyacrylamide gel electrophoresis and subsequent immunoblotting. H-kininogen was extensively cleaved in ascites compared to control plasma, with large amounts present of a degraded form with Mr of 99 kDa. The bands observed compared well with those described in plasma, and are consistent with contact activation taking place in ascites.

Ascitic Fluid↗