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Biomedical subjects

B Risberg

Publications and source records attributed to B Risberg.

At least 127 records · Page 7Linked to original sources

Expression of plasminogen activator inhibitor-1 mRNA in healthy, atherosclerotic and thrombotic human arteries and veins.

Plasminogen activator inhibitor-1 (PAI-1), specific inhibitor of plasminogen activators (PA), plays an important role in the regulation of fibrinolysis. Increased levels of PAI-1 have been associated with vascular disease such as thrombosis and atherosclerosis. In the present study the expression of PAI-1 mRNA in human healthy, atherosclerotic and thrombotic blood vessel walls was quantified by RNA-RNA hybridization in solution and localized by in situ hybridization. The mean expression of PAI-1 mRNA was significantly higher in healthy arteries (0.86 pg/microgram total RNA) than in healthy veins (0.29 pg/microgram total RNA), p < 0.01. The mean PAI-1 mRNA expression in thrombotic arteries (1.72 pg/micrograms total RNA) was significantly higher than that in healthy arteries, p < 0.05, and the mean PAI-1 mRNA expression in thrombotic veins (1.29 pg/micrograms total RNA) was significantly higher than that in healthy veins, p < 0.01. By in situ hybridization PAI-1 mRNA was detected in the intima, media and adventitia of healthy arteries and healthy veins. In atherosclerotic arteries PAI-1 mRNA was detected in the atherosclerotic plaque and in the medial and adventitial layers below the plaque. An increased expression of PAI-1 mRNA was found in the intimal layer of a thrombotic vein. The increased expression of PAI-1 mRNA in thrombotic arteries and veins indicates a role for PAI-1 in thrombogenesis.

Arteries↗

Endothelial prostacyclin production, synergistic effect between adrenergic stimulating and blocking drugs.

Endothelial cells (EC) produce prostacyclin (PGI2) in high quantities which at the luminal surface decreases platelet aggregation and adhesion and basal to the cell relaxes smooth muscle cells (SMC). Connections have been reported between prostacyclin production, hypertension and the degree of adrenergic activation. The present study tested the hypothesis that prostacyclin production by EC could be regulated by adrenergic mechanisms. EC were isolated from human umbilical cord veins. Washed cells were seeded and grown to confluency on tissue culture dishes. The test drugs were simultaneously added to parallel dishes. Samples were collected from the conditioned medium and analyzed for 6-keto-PGF1a with RIA technique. Endothelial cells pretreated with the betaadrenoceptor blocking drugs metoprolol or propranolol synergistically increased basal prostacyclin production when exposed to betaadrenergic stimulation. However, using isomers with high or low betaadrenoblocking effect, this synergism was demonstrated not to be associated to the betaadrenoceptor blocking effect of the drugs per se. These findings may have implications on the arterial hypertensive state characterized by high sympathetic tonus and low PGI2 production. The data may offer an explanation why hypertensive individuals react with increased PGI2 production, upon betaadrenoceptor blocking therapy.

1-Methyl-3-isobutylxanthine↗

In vitro studies on the effect of thromboxane receptor blockade on platelet deposition on vascular surfaces.

The efficacy of platelet inhibition by a thromboxane receptor antagonist (Bay U3405) and acetylsalicylic acid was investigated in vitro using a new perfusion system. Rabbit 51Cr-labeled platelets were suspended in saline as perfusate. Vascular grafts, PTFE or Dacron (precoated with blood or uncoated) as well as native aorta were perfused in vitro. Three sets of grafts (vessels) were perfused simultaneously with either acetylsalicylic acid (10(-5) M), Bay U3405 (10(-6) M) treated or untreated (control) labeled platelets. Platelet deposition on the grafts (vessels) was measured in a gamma counter. Values were normalised to graft weight or vessel surface area respectively and to the platelet concentration of perfusate. The results of these experiments indicated that thromboxane receptor inhibition was superior to cyclooxygenase blockade in preventing platelet deposition on synthetic grafts and native aorta vessels in vitro. Whether this is valid in vivo has to be confirmed.

Animals↗

Granulosa cell tumors of the ovary: prognostic factors and outcome.

Granulosa and theca cell tumors of the ovary account for 2-3% of ovarian malignancies. This study includes 54 patients with the diagnosis of granulosa cell tumors of the ovary treated between 1953 and 1987. Median age at diagnosis was 57 (27-83) years. The lesions were staged according to FIGO. The number of patients in various stages was IA, 41; IB, 3; IC, 3; IIB, 6; and III, 1. Median tumor size, 11 cm; range, 0.5-30 cm. Post-menopausal bleeding was diagnosed in 48%, MHC in 37%, proliferative endometrium in 32%, and atypia of endometrial cells in 13% of the cases. Fifty patients were treated with primary surgery, 48 patients were treated with adjuvant external radiotherapy, and 3 patients received complementary chemotherapy. The survival rates in stage I were 94 and 88% after 5 and 10 years, respectively, and in stages II-III were 44% after 5 and 10 years. Overall survival was 90% at 5 years. The frequency of observed mitosis influenced the survival rate: with less or equal 4/10 HPF the survival was 100% in 5 years, with 5-9/10 HPF the survival was 80% in 5 years with a median survival time of 9 years, and with more or equal 10/10 HPF the longest survival was 4 years. At the end of the study, 45 patients (83%) are alive with no evidence of disease, 1 patient is alive with disease, 4 patients are dead of recurrent disease, and 4 patients are dead from intercurrent disease. Endometrial carcinoma was detected in 5 patients. The total survival is better than that with epithelial ovarian cancer as the hormonal symptoms make an early diagnosis possible. Stage for stage the survival is equal. There is an increased incidence of endometrial carcinoma and concomitant other malignancies. The mitotic rate is a well-defined parameter and influences the survival significantly and should be considered the most important prognostic factor at treatment planning.

Abdominal Pain↗

Fibrinolysis during cardiac surgery. Release of tissue plasminogen activator in arterial and coronary sinus blood.

Endothelial release of tissue plasminogen activator (t-PA) may initiate fibrinolysis. Fibrinolysis and coagulation were investigated in 12 patients undergoing elective coronary artery bypass surgery. Cardiopulmonary bypass (CPB) was 108 +/- 7 min (mean +/- SEM), the time of cold, crystalloid, retrograde cardioplegia 53 +/- 5 min. Arterial and coronary sinus blood were sampled concomitantly before cardioplegia and after release of the aortic cross-clamp, for measurement of t-PA antigen (Ag) and activity, plasminogen activator inhibitor (PAI-1) Ag and activity, t-PA/PAI-1 complex, single chain urokinase (sc-uPA) and urokinase (uPA) plasminogen activators, the fibrin split product D-dimer, thrombin-antithrombin complex (TAT), and the prothrombin split product F 1 + 2. Cardiopulmonary bypass significantly increased t-PA Ag and activity, t-PA/PAI complex, D-dimer, TAT, and F 1 + 2, and decreased PAI-1 Ag and activity in arterial blood; uPA and sc-uPA were unchanged. The tissue plasminogen activator antigen was higher in coronary sinus than arterial blood after 1 (39 +/- 5 vs 24 +/- 4 ng/ml, P < 0.003), 4 (P < 0.003), and 10 min (P < 0.004) reperfusion. Tissue plasminogen activator activity and t-PA/PAI complex increased, PAI-1 activity decreased, while all other parameters were unchanged across the coronary circulation. In conclusion, CPB induces fibrinolysis and coagulation. Cold cardioplegia induces t-PA release in the coronary circulation, denoting a postischemic antithrombotic function of the coronary endothelium. Tissue plasminogen activator may be used to evaluate endothelial stimulation or injury induced by CPB, or by different regimens of myocardial protection.

Aged↗

Role of fibrinolysis in the formation of postoperative adhesions.

It has been hypothesized that peritoneal hypofibrinolysis is of importance in the formation of postoperative adhesions, but results from experiments with fibrinolytic modulators are conflicting. We tested this hypothesis in a controlled prospective study in rabbits, comparing the effects of fibrinolytic inhibition (tranexamic acid) to fibrinolysis enhancement by local instillation of gel containing tissue-type plasminogen activator. Adhesion formation was measured after 1 week in a strictly standardized way and is presented as a percentage of an induced lesion that was covered by adhesions. Fibrinolytic inhibition significantly increased adhesion formation, both to the parietal peritoneum (34.2%+/- 3.2%) compared with untreated control (19.7%+/- 3.3%, p < 0.01) and to the bowel (76.3%+/- 5.8%) compared with untreated control (51.2%+/- 8.7%, p < 0.05). Control gel significantly increased adhesions to the parietal peritoneum (35.6%+/- 4.6%) versus untreated control (19.7%+/- 3.3%, p < 0.05), whereas gel containing tissue-type plasminogen activator significantly reduced the amount of adhesions to the parietal peritoneum (4.9%+/- 1.7%) compared with untreated control (19.7%+/- 3.3%, p < 0.01) and abolished adhesion formation to the injured bowel. The fibrinolytic system thus seems to be intimately involved in the early formation of intraabdominal adhesions.

Journal Article↗

Blocking of endothelial-leukocyte interaction (rolling) does not improve reflow in the rat gastric mucosa after hemorrhagic shock and retransfusion.

The polymorphonuclear neutrophilic granulocyte (PMN) has been implicated as one possible cause of the no-reflow phenomenon seen upon reperfusion after ischemia, by, for instance, the release of toxic substances and/or microvascular flow obstruction. In the present study we studied the effects of ascorbate (an antioxidant) and fucoidin (an inhibitor of leukocyte rolling in microvessels) on the rat gastric mucosal and submucosal PMN content and vascular patency (the latter assessed as the surface density of perfused vessels) in connection with hemorrhagic shock (15 min) and retransfusion (5 or 10 min). The effect of fucoidin on the leukocyte rolling in small venules was studied separately with vital microscopy in the rat mesentery. As found in earlier studies, shock and retransfusion led to a decrease in the surface density of perfused vessels, whereas the number of PMNs in the mucosa or the submucosa was not affected by shock and retransfusion. Ascorbate improved vascular patency without affecting the PMN content. In the mesentery, fucoidin caused a 76% reduction in the number of rolling PMNs and it reduced significantly the number of PMNs in the mucosa, but not in the submucosa, after 10 min of retransfusion. Fucoidin had no effect on the vascular patency at that or any other time point. On the basis of these experiments it is concluded that PMN accumulation cannot be singled out as the cause of no-reflow in the rat gastric mucosa after shock and retransfusion of the degree and duration analyzed in this investigation.

Animals↗

Can laboratory testing improve screening strategies for deep vein thrombosis at an emergency unit?

OBJECTIVES: To study various markers of blood coagulation and fibrinolysis in relation to the extension of deep vein thrombosis (DVT), and to compare the diagnostic usefulness of these markers as screening tests for excluding DVT. DESIGN: A clinical study of patients admitted to an emergency unit. SETTING: Ostra Hospital, Göteborg, Sweden. SUBJECTS: One hundred and five patients with a clinical suspicion of DVT. MAIN OUTCOME MEASURES: Phlebography was used as the reference method for a diagnosis of DVT. Small distal thromboses as well as large proximal thromboses were included. Plasma D-dimer as well as other markers of coagulation and fibrinolysis were analysed. RESULTS: Twenty-eight proximal and 20 distal DVTs were found. Plasma D-dimers (one ELISA and two latex assays), fibrin monomer, prothrombin fragment 1 + 2 (F1+2), thrombin-antithrombin III complex (TAT) and the t-PA-PAI-1 complex were all significantly correlated to the extension of DVT, whilst fibronectin, tissue-type plasminogen activator (t-PA), single-chain urokinase-type plasminogen activator (scru-PA) and plasminogen activator inhibitor 1 (PAI-1) were not. The sensitivity was 94% for the D-dimer ELISA and one of the latex methods (latex-B), at a specificity of 60% and 68%, respectively. The negative predictive value was 92% for ELISA and 93% for latex-B, and both assays showed a negative predictive value of 100% for proximal DVTs. Fibrin monomer, F1+2, TAT, D-dimer (latex-S) and the t-PA-PAI-1 complex all showed lower negative predictive values (88, 84, 79, 78 and 65% respectively). CONCLUSIONS: Sensitivity and negative predictive values for a latex assay (D-dimer latex-B) was similar to that of a D-dimer ELISA: With a sensitivity of 94% (100% for proximal DVTs) such a latex assay may be included in a screening strategy for DVT at an emergency unit. However, the safety of such an approach has to be tested in other prospective studies.

Adult↗

Ascorbate reduces gastric bleeding after hemorrhagic shock and retransfusion in rats.

The rat gastric mucosa, superfused with 0.1 N HCl, was investigated following 15 min of hemorrhagic shock and 30 min of retransfusion after pretreatment with ascorbate (1 mg/100 g b.w. or 5 mg/100 g b.w.). The size of the ischemic areas and the amount of mucosal bleeding using 51Cr labeling of red blood cells were assessed. Ischemic areas developed during shock. Following retransfusion, bleedings occurred at the border zones between ischemic and surrounding circulated areas. Ascorbate in both doses protected the gastric mucosa by reducing the amount of bleeding following 30 min of retransfusion as well as by reducing the area of ischemia 5 min after retransfusion.

Animals↗

Experimental models for quantitative studies on adhesion formation in rats and rabbits.

Postoperative formation of adhesions is a common complication in abdominal surgery. The aim of the present study was to develop standardized experimental models for quantitative studies of the formation of adhesions in rats and rabbits. In rats the suturing of a peritoneal wound increased adhesion formation significantly compared to leaving it open, 77.9 +/- 4.8 and 5.3 +/- 2.8%, respectively (p < 0.001). The suturing technique, when comparing the interrupted and continuous method after 1 week, had no influence, 84.5 +/- 6.3% and 73.1 +/- 11.2%, respectively (p > 0.05). Different types of trauma resulted in differences in adhesion formation to noninjured parts in the abdominal cavity, adhesions in 17.5 and 2.5% of the animals, respectively (p < 0.05). In rabbits adhesions formed more frequently (p < 0.001) to visceral peritoneum (59.3 +/- 3.7%) than to the parietal one (22.3 +/- 1.6%) indicating a different propensity of tissues to have adhesions. These models enable detailed quantitative studies on experimental formation of adhesions.

Animals↗

Leukotriene receptor antagonism prevents lung protein leakage and hypoxaemia in a septic cat model.

Products of the arachidonic acid cascade have been found to play an important role in the pathophysiology in experimental shock and in ARDS. The effect of cysteinyl-leukotriene (cLT) blockade on the development of respiratory failure during septic shock was examined. Ventilated cats received an infusion of Escherichia coli bacteria. Pretreatment was given with diethylcarbamazine (DEC), a leukotriene synthetase inhibitor, or a new potent cLT receptor antagonist, ICI 198,615. With a gamma camera, the distributions of plasmatransferrin radiolabelled with indium-113m chloride (113mIn) and erythrocytes radiolabelled with technetium-99m (99mTc) were measured over the lungs. A normalized slope index (NSI) reflecting protein leakage, based on the transferrin extravasation, was calculated. In the nonseptic control group (n = 7) NSI was 4.4 x 10(-4) +/- 0.7 x 10(-4).min-1 (mean +/- SEM). Unpretreated septic animals (n = 7) showed a protein leakage after bacterial infusion, with a NSI of 34 +/- 3.5 x 10(-4).min-1. Pretreatment with DEC (n = 6) significantly reduced NSI to 16 +/- 1.5 x 10(-4).min-1. In the group pretreated with ICI 198,615 (n = 8), NSI was 9 +/- 1.2 x 10(-4).min-1. Arterial oxygen tension (PaO2) remained at baseline level of 20 +/- 1.0 kPa during the experimental period in both the nonseptic control group and the ICI 198,615 pretreated group. In the unpretreated septic group, PaO2 fell progressively from a preseptic value of 21 +/- 0.9 to 12 +/- 1.5 kPa after 3 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

The impact of starch-powdered gloves on the formation of adhesions in rats.

OBJECTIVE: To assess the influence of starch powdered surgical gloves on the postoperative formation of adhesions in a standard rat model. DESIGN: Prospective, randomised, double-blind study. MATERIAL: 197 rats. INTERVENTIONS: Abdominal cavity was exposed to gloves during the induction of adhesions and for an additional two minutes. Animals were operated on with the operator wearing either starch-powdered or powder-free gloves. MAIN OUTCOME MEASURES: Formation of adhesions and starch particles present in the adhesions after one, three, 12, or 24 weeks. RESULTS: When powdered gloves were worn the percentage of adhesions formed was significantly greater (n = 197, p < 0.01) than when powder-free gloves were worn. Starch particles were found in biopsy specimens from rats operated on with powdered gloves, but not when powder-free gloves were used. CONCLUSION: Even the small amount of starch that settles in the abdominal cavity during an operation increases the amount of adhesions formed.

Abdomen↗

Inter-institutional reproducibility of flow cytometric DNA-analysis in breast carcinomas.

In order to study interinstitutional reproducibility of flow cytometric DNA-analysis (DNA-FCM), frozen pieces from 30 consecutive breast carcinomas were analysed by 5 laboratories. Different instruments, preparation and DNA staining methods were used. A concordance in DNA-ploidy status was obtained in 26 of the 30 tumours. The discrepancy can mainly be explained by intratumoural DNA-heterogeneity since a complete agreement in ploidy status was obtained when four of the laboratories analysed the same cell suspension, where solid bits showed differing results. The sampling method seems therefore to be a crucial step for the results and needs further studies. As far as the estimation of S-phase fraction was concerned, one laboratory obtained significantly higher values compared to the other four. The correlation between the other four laboratories varied between r = 0.66-0.92.

Academies and Institutes↗

Reactive oxygen intermediates and ischemia-reperfusion injury release tissue plasminogen activator from isolated rat hearts.

Tissue plasminogen activator (t-PA) is a marker of endothelial cell injury or activation. The release of t-PA from isolated rat hearts (Langendorff model) subjected to ischemia-reperfusion or reactive oxygen intermediates (ROI) generated by H2O2 was investigated. H2O2 (200 microM) increased t-PA activity in the coronary effluent to 305 +/- 84% of initial value (mean +/- SEM, p < 0.04 vs controls) at the end of a 10 min intervention. The hydroxyl radical scavenger thiourea (10 mM) only partially inhibited the increase (175 +/- 27%, p < 0.01 compared to controls). 20 min normothermic ischemia increased t-PA activity to 416 +/- 108% (p < 0.005 compared to controls) at the start of reperfusion. In conclusion, cardiac injury by ischemia-reperfusion or ROI increases release of t-PA.

Animals↗

Hemofiltration modifies complement activation after extracorporeal circulation in infants.

Complement and fibrinolytic factors were measured in 9 infants undergoing hemofiltration immediately after cardiopulmonary bypass in an attempt to reduce activation of these systems. Plasma levels of C3a, C5a, and terminal complement complexes increased during bypass by 460%, 85%, and 745%. Plasma levels were reduced after hemofiltration in 8 of the 9 infants, and C3a and C5a fractions were recovered in the ultrafiltrate. The observed activation of the fibrinolytic system seemed to be unaltered by hemofiltration. Fibrinolytic factors were not filtered. Our study shows that increased concentrations of complement factors in the plasma after bypass in infants may be reduced by hemofiltration.

Complement Activation↗

Lung protein leakage in feline septic shock.

The aim of the present study was to explore lung microvascular leakage of protein and water in a feline model of septic shock, using a double isotope technique with external gamma camera detection and gravimetric lung water measurements. The experiments were performed on artificially ventilated cats. One group of cats (n = 8) was given an infusion of live Escherichia coli bacteria, and another group (n = 5) served as a control group receiving saline. Plasma transferrin was radiolabeled in vivo with indium-113m-chloride, and erythrocytes were labeled with technetium-99m. The distribution of these isotopes in the lungs was continuously measured with a gamma camera. A normalized slope index (NSI) was calculated, indicative of the transferrin accumulation corrected for changes in local blood volume that reflect protein leakage. In the septic group there was a protein leakage after bacterial infusion, with a NSI of 39 x 10(-4) +/- 5 x 10(-4) min-1 (mean +/- SEM), and the PaO2 diminished from 21 +/- 1 to 9.5 +/- 1 kPa. In control cats a slight protein leakage with a NSI of 9 +/- 10(-4) +/- 2 x 10(-4) min-1 was detected, probably caused by the operative procedure, but PaO2 did not change. Wet-to-dry-weight ratios of postmortem lungs were not significantly different between the groups. It was concluded that an intravenous infusion of live E. coli bacteria induces a lung capillary protein leakage without increased lung water and a concomitantly disturbed gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗