Biomedical subjects

A O Aasen

Publications and source records attributed to A O Aasen.

At least 19 recordsLinked to original sources

PubMed1997

[Transplantation of animal organs (xenotransplantation). Status and future development].

The increasing shortage of human organs for allotransplantation has created intense interest for xenotransplantation. Pig organs have been suggested as suitable grafts for man. However, the immediate problem associated with discordant xenotransplantation is hyperacute rejection. Hyperacute rejection occurs because antibodies become attached to the endothelial cells of the xenotransplant organ, which activates the complement system, attracts platelets etc. This results in endothelial cell damage, oedema, loss of vascular integrity and thus rapid destruction of the graft. Organs from non-human primates often do not cause hyperacute rejection, but will probably not be acceptable donors. Transgenic pigs have been breeded which contain the genes for the human regulators of complement activation. It appears that insertion of such genes into pigs serves to prevent aggressive hyperacute rejection. Understanding the mechanisms of rejection gives cause for optimism. However, there are still many problems to evaluate and solve. One potential danger associated with xenotransplantation is the transmission of infectious disease from animals to man. Other problems relate to physiological adaptation of the xenograft. The legal, ethical, religious and economic aspects must also be taken into consideration. Despite the potential problems, it is likely that a xenotransplant of some kind will soon be attempted in man.

Cost-Benefit Analysis↗

PubMed1997

Percutaneous technique for venovenous bypass including a heat exchanger is safe and reliable in liver transplantation.

We have introduced and evaluated several modifications of the conventional venovenous bypass (VVBP) in 29 adult patients undergoing liver transplantation (OLT). A percutaneous technique for insertion of a jugular venous return cannula and a femoral vein cannula was applied. The inferior mesenteric vein (IMV) was used for splanchnic decompression, which facilitated dissection of the recipient liver and allowed portal anastomosis to be performed without disconnecting the portal bypass. A heat exchanger was introduced into the bypass circuit to prevent heat loss. The percutaneous technique prevented complications related to dissection in the axilla and groin. Hemodynamic characteristics corresponded to those found using the traditional technique. Complications related to the VVBP were seen in only one patient in whom the femoral catheter was accidentally introduced into the femoral artery. We conclude that percutaneous cannulas, use of the IMV for splanchnic decompression and the introduction of a heat exchanger offer significant benefits and that they are safe and reliable.

Adult↗

PubMed1997

An experimental study on effects of occlusion of the cystic duct in mice with or without emptying of the gallbladder.

To study consequences of cystic duct occlusion, 121 NMRI mice were operated: 40 had cystic duct ligature (L group), 41 had cystic duct ligature and evacuation of bile from the gallbladder (LE group), and 40 were sham-operated (S group). Ten mice from each group were sacrificed at 1 week, 1, 3 and 6 months, respectively. All but 2 mice showed signs of wellbeing during the observation time, and weight gain was the same in the three groups. Distended gallbladder occurred in 14 animals, 7 each in the L and the LE group, more frequent after 3 and 6 months. In the remainder mice the gallbladders were smaller than at the time of operation (p < 0.0001). Fibrosis and adhesions around the gallbladder were frequent in the L and the LE groups, and more pronounced in the latter (p = 0.0001). At microscopy there were signs of inflammation in the gallbladder wall in 16 cases in the L group, 28 in the LE group and 2 in the S group, and the degree of inflammation was more pronounced in the LE group than in the L group (p = 0.002). Eleven mice in the LE group had empyema, and slight intralumininal inflammation was more frequent in the LE group than in the L group (p < 0.0001). In conclusion, despite a high incidence of microscopic inflammation the study gave no indication that occlusion of the cystic duct did serious harm to the mice in this series.

Animals↗

PubMed1996

Quantification of kininogens in plasma. A functional method based on the cysteine proteinase inhibitor activity.

We have previously reported on a microassay based on human kininogens as cysteine proteinase inhibitors (CPIs), which could quantify partially purified kininogens from different biological fluids (J Pharmacol Meth 26, 113-124, 1991). In the present study we describe a functional method that, when assuming a 1:1 stoichiometry between papain and kininogen, allows a direct measurement of the molar concentration of kininogens in plasma. The principle of the method is that the target enzyme papain is inhibited by kininogens present in added diluted plasma. The residual activity of papain, not inhibited in this reaction, subsequently hydrolyzes the added peptide substrate (S-2302), generating a yellow colour which is read in a microplate reader at 405 nm. Relating the test samples to a standard curve established from known concentrations of E-64 (a selective low molecular weight inhibitor of cysteine proteinases), we could quantify kininogens on a molar basis. A major problem when first applying this method to plasma, was the interference of alpha 2-macroglobulin, which inhibited papain and generated a complex able to split the chromogenic substrate. The interference of alpha 2-macroglobulin was eliminated by an initial acid treatment of plasma followed by dilution with a buffer containing methylamine. The specificity for kininogens in this assay is demonstrated by the following observations: Commercial pooled normal plasma contained 3.2 microM CPI activity, in good agreement with the expected molar concentration of kininogens. After gel filtration of a plasma sample with a CPI activity of 3.4 microM, two peaks with CPI activity were identified as H-kininogen (0.9 microM) and L-kininogen (2.5 microM), both in good accordance with expected concentrations of the two kininogens. Plasma deficient of kininogens had a minimal inhibitory capacity towards papain.

Amino Acid Sequence↗

PubMed1996

Cleavage of plasma high molecular weight kininogen in surgical ICU patients.

OBJECTIVE: To characterize kininogens in plasma from surgical patients in the intensive care unit (ICU). DESIGN: Prospective study. SETTING: Surgical ICU. PATIENTS: 35 patients aged 19-79 years, divided into two groups: sepsis (defined by standard criteria) and nonsepsis. MEASUREMENTS AND RESULTS: Studies of proteolytic degradation of H-kininogen showed degradation in both patient groups compared to healthy controls. Functional quantification of prekallikrein showed a reduction of prekallikrein in plasma from both patients groups. Functional quantification of kininogens by a cysteine proteinase inhibitor assay showed no significant differences between the patients and the controls. Immunological levels of H-kininogen and total kininogen were not significantly different from normal plasma. No differences could be detected between the two patient groups in any of the parameters studied. CONCLUSIONS: This study showed that contact activation took place in surgical ICU patients: partial kinin release and consumption of prekallikrein took place in vivo.

Adult↗

PubMed1996

Human monocytes stimulation by particles of hydroxyapatite, silicon carbide and diamond: in vitro studies of new prosthesis coatings.

Aseptic loosening due to wear and debris formation constitutes the major problem in longevity of joint replacements. Diamond coated onto the prosthesis surface may reduce wear, owing to its excellent tribological properties. A thin diamond coating may be brittle, and we plan eventually to reinforce it with silicon carbide whiskers (SiC). In the present study we compared particles of diamond, SiC and hydroxyapatite (HA) in serum-free cultures of human monocytes. All particles were found to be phagocytozed, and monocyte morphology changed except after the ingestion of diamond. Interleukin-1 beta production was increased on average 30-fold and 38-fold in cultures exposed to HA and SiC, respectively, compared to control and diamond cultures (n = 6). Addition of the phagocytosis inhibitor cytochalasin B inhibited the morphological changes of the monocytes and reduced interleukin-1 beta production. In some experiments particles of polymethylmethacrylate were also included, and the interleukin-1 beta stimulation was in the same range as after HA and SiC stimulation. The results show that diamond particles in serum-free monocyte culture are inert, while SiC and HA have a stimulatory effect comparable to polymethylmethacrylate. With its excellent tribological and biocompatible properties, future studies with diamond coating are warranted.

Biocompatible Materials↗

PubMed1996

Bradykinin release from high molecular weight kininogen in surgical ICU patients.

The purpose of this prospective study was to characterize kininogens in plasma from surgical ICU patients. Thirty-five patients, ages 19-79 years, were divided into 2 groups: sepsis (defined by standard criteria) and nonsepsis. Studies of proteolytic degradation of H-kininogen showed degradation in both patient groups compared to healthy controls. Functional quantification of prekallikrein showed a reduction of prekallikrein in plasma from both patient groups. Functional quantification of kininogens by a CPI (cysteine proteinase inhibitor) assay showed no significant differences between the patients and the controls. Immunological levels of H-kininogen and total kininogen were not significantly different from normal plasma. No differences could be detected between the two patient groups in any of the parameters studied. In conclusion, this study supported contact activation taking place in surgical ICU patients, a partial kinin release and a consumption of prekallikrein has taken place in vivo.

Adult↗

PubMed1996

Nitric oxide synthase inhibition reduces venous return in porcine endotoxemia.

Mechanisms of circulatory effects induced by nitric oxide synthase inhibition in endotoxemia were investigated in 36 pigs randomized to 1) endotoxin infusion (1.7 micrograms.kg-1.h-1 iv) for 7 h and bolus NG-nitro-L-arginine methyl ester (L-NAME; 25 mg/kg iv) after 3 h; 2) endotoxin infusion for 7 h; 3) saline infusion for 7 h and L-NAME after 3 h; and 4) saline infusion for 7 h. Fifteen minutes after L-NAME injection during endotoxemia, reductions in cardiac output (41%, P < 0.05), portal venous flow (51%, P < 0.05), and hepatic artery flow (50%, P < 0.05) were observed. Systemic vascular resistance increased by 82% (P < 0.05), and the portocaval vascular resistance increased by 101% (P < 0.05). Despite marked vasoconstriction after L-NAME, left ventricular intracavitary filling pressure, central venous pressure, and arterial pressure remained unchanged. During endotoxemia, hematocrit increased from 38.4 +/- 1.4 to 41.9 +/- 1.2 after L-NAME, and blood volume (n = 3) was reduced by an average of 8.3 ml/kg body wt. These changes probably reflect transcapillary fluid loss as urine output was unchanged. In conclusion, L-NAME decreased intravascular blood volume and increased splanchnic venous resistance. These effects will tend to reduce venous return. Combined with a marked increase in left ventricular after-load, L-NAME may thus compromise cardiovascular function in endotoxemia.

Animals↗

PubMed1996

The NO donor sodium nitroprusside reverses the negative effects on hepatic arterial flow induced by endotoxin and the NO synthase inhibitor L-NAME.

In previous studies we have observed that the nitric oxide synthase inhibitor L-NAME induces a profound deterioration of liver circulation in experimental endotoxemia. Using the same porcine model we now have evaluated the possibility of modulating these effects with the nitric oxide donor sodium nitroprusside. Infusion of endotoxin led to a gradual deterioration of hemodynamic parameters, including liver blood flow. The decreases in portal blood flow paralleled and matched the decreases in cardiac output, and no compensatory increase in hepatic arterial flow occurred. L-NAME had detrimental effects on hemodynamics, including the liver circulation. The latter effects could, however, partially be reversed by sodium nitroprusside. Hepatic arterial flow increased from 1.9 to 7.2 ml/kg/min, with a concomitant decrease in hepatic arterial resistance from 5,364 to 1,746 dyn s/cm5 kg. A control group exhibited no significant change in either flow or resistance. The response to sodium nitroprusside was rapid and vigorous, and probably largely due to relaxation of the hepatic arterioles, and not to abatement of intrahepatic edema or plugging of the sinusoids. Furthermore, we conclude that the endotoxin-induced dysfunction of the hepatic arterial buffer response may be due to a selective inhibition of vascular endothelial function.

Animals↗

PubMed1996

The plasminogen activation system is upregulated in loosening of total hip prostheses.

Interface tissues and pseudocapsules from loose total hip replacements were removed during revision of 11 cases and were investigated for the plasminogen activation system and IL-1beta. Control samples of synovium were taken during knee arthroscopy (n 8), and from the hip joint during primary total hip replacement (n 5). The concentrations of urokinase plasminogen activator (uPA), tissue type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and interleukin 1beta were all found to be significantly different in interfaces and in pseudocapsules, compared to controls. Immunohistochemistry disclosed localization in periprosthetic tissues of uPA, uPA-receptor and tPA in macrophages with phagocytosed metal, polyethylene, cement particles or accompanying pieces of necrotic bone. PAI-1 staining was present in the neighboring areas that stained for uPA or tPA, but PAI-1 staining was also found overlapping and outside these areas. These findings suggest a role for the uPA/uPA- receptor and PAI-1 in activation and focalization of extracellular matrix degradation in periprosthetic tissues. The expression of the plasminogen activation system by macrophages containing phagocytosed material suggests undegradable microdebris as a possible initiating and perpetuating stimulus for a proteolytic activation cascade, which may contribute to loosening of the prosthesis.

Adult↗

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

SIDS cases have increased levels of interleukin-6 in cerebrospinal fluid.

Cerebrospinal fluid (CSF) from 20 infants who died of sudden infant death syndrome (SIDS), 7 cases of infectious death and 5 cases of violent death were examined with respect to concentrations of interleukin-6 (IL-6). The measurements were performed by ELISA. IL-6 levels in SIDS were significantly lower than in infectious death (p < 0.02), but significantly higher than in violent death (p < 0.02). Since IL-6 plays an important role in immune responses and may induce fever, the findings may suggest that immune activation plays a role in SIDS. The presence of cytokines in the central nervous system (CNS) may cause respiratory depression, especially in vulnerable infants.

Enzyme-Linked Immunosorbent Assay↗

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

The fibrinolytic system in human ascites.

BACKGROUND: We recently reported that the contact and kallikrein-kinin systems are activated in malignancy-related ascites. We have now studied the fibrinolytic system in ascites and plasma from patients with gastrointestinal cancer(n = 14) and non-malignant liver disease (n = 18). METHODS AND RESULTS: Enzyme immunoassays (EIAs) showed that urokinase and tissue plasminogen activators (uPA, tPA) and PA inhibitors (PAI-1, PAI-2) were present in ascites from both patient groups and that tPA was the predominant PA. uPA, tPA, and PAI-1, were detected in plasma from patients and controls. These EIA findings were supported by zymography studies. Functional assays showed considerable generation of plasmin-like activity and low plasminogen and antiplasmin values in malignancy-related ascites. The plasmin/antiplasmin and tPA/PAI-1 ratios were particularly high in malignancy-related ascites as compared with non-malignant ascites. Plasma from the liver disease patients showed a higher tPA/PAI-1 ratio and, thus a higher potential for plasminogen activation than plasma from cancer patients and controls. Patient plasma showed low values of plasmin-like activity, antiplasmin, and plasminogen. CONCLUSION: Our findings show that the fibrinolytic system is activated in malignancy-related ascites.

Adult↗

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↗