Levels of Lipoprotein (a) in patients with coronary artery disease with and without inflammatory rheumatic disease: a cross-sectional study.

OBJECTIVES: Patients with various inflammatory rheumatic diseases (IRDs) have increased risk of atherothrombotic disease. Lipoprotein (a) (Lp(a)) is a risk factor for atherosclerosis but its role in IRD with accompanying coronary artery disease (CAD) is still unclear. We aimed to examine if serum Lp(a) levels differed between CAD patients with and without accompanying IRD. DESIGN: A cross-sectional observational, patient-based cohort study. SETTING: Referred centre for coronary artery bypass grafting in the South Eastern part of Norway. PARTICIPANTS: 67 CAD patients with IRD (CAD/IRD) and 52 CAD patients without IRD (CAD/non-IRD). All patients were Caucasians, aged >18 years, without any clinically significant infection or malignancy. METHODS: Lp(a) levels in serum were analysed by particle enhanced immunoturbidimetric assay, and Lp(a) levels were related to clinical and biochemical characteristics of the patient population. RESULTS: We found no differences in serum levels of Lp(a) between CAD patients with and without IRD. In general, we found that Lp(a) correlated poorly with clinical and biochemical parameters including C reactive protein with the same pattern in the CAD/non-IRD and CAD/IRD groups. CONCLUSIONS: Our data do not support a link between inflammation and Lp(a) levels in CAD and in general Lp(a) levels were not correlated with other risk factors for cardiovascular disease.

Sequential ADP-stimulated light transmission and multiple electrode aggregometry in patients taking aspirin and clopidogrel after non ST-elevation myocardial infarction.

BACKGROUND: Fast platelet function tests can identify weak clopidogrel responders, but data on variability over time in clopidogrel responsiveness in several clinical settings are lacking. We wanted to explore long-term variability of multiple electrode aggregometry (MEA) measurements and the agreement between MEA and light transmission aggregometry (LTA) in patients with non-ST elevation myocardial infarction (NSTEMI) treated with aspirin and clopidogrel. METHODS: Parallel MEA and LTA were performed at baseline and after 6 and 12 weeks in 31 patients treated with percutaneous coronary intervention after NSTEMI. Adenosine diphosphate (ADP) concentrations 2 µM, 6.5 µM and 10 µM were used. Parallel testings in both arterial and venous blood were performed at baseline. MEA and LTA cut-off levels were applied to discriminate aggregation values suggesting presence or absence of high platelet reactivity (HPR). RESULTS: Arterial and venous MEA and LTA aggregation were similar. Within-subject variability in both MEA and LTA aggregation throughout the study was moderate. According to MEA, eight patients had HPR at baseline (MEA aggregation > 47 U). Defining > 47% as the LTA aggregation HPR cut-off level, the same number of patients (eight) had HPR according to LTA. Of the 93 MEA/LTA observations 81 (87.1%) gave the same HPR classification. MEA vs. LTA agreement at baseline was slightly inferior to that obtained after 12 weeks. CONCLUSIONS: MEA and LTA aggregation in arterial and venous blood seem similar. Within-subject variability over time was moderate, and the agreement between LTA and MEA was good, and stable in most patients.

Increased YKL-40 expression in patients with carotid atherosclerosis.

OBJECTIVE: We hypothesized a role for the inflammatory protein YKL-40 in atherogenesis and plaque destabilization based on its role in macrophage activation, tissue remodeling, and angiogenesis. METHODS: Serum YKL-40 levels were measured by enzyme immunoassay in 89 patients with carotid atherosclerosis and 20 healthy controls. Carotid expression of YKL-40 was examined by real time RT-PCR in 57 of the patients. Regulation and effect of YKL-40 were examined in THP-1 monocytes. RESULTS: Our main findings were: (1) serum YKL-40 levels were significantly elevated in patients with carotid atherosclerosis, with particularly high levels in those with symptomatic disease; (2) patients with recent ischemic symptoms (within 2 months) had higher YKL-40 mRNA levels in carotid plaque than other patients; (3) in vitro, the beta-adrenergic receptor agonist isoproterenol, toll-like receptor (TLR) 2 and TLR4 agonists, and in particular releasate from activated platelets significantly increased the expression of YKL-40 in THP-1 monocytes and (4) in vitro, YKL-40 increased matrix metalloproteinase-9 expression and activity in THP-1 monocytes, involving activation of p38 mitogen-activated protein kinase. CONCLUSIONS: Our findings suggest that YKL-40 might be a marker of plaque instability, potentially reflecting macrophage activation and matrix degradation within the atherosclerotic lesion.

Variability in aggregometry response before and after initiation of clopidogrel therapy.

BACKGROUND: Evaluation of clopidogrel therapy by in vitro methods has limitations which may be of clinical importance. We wanted to explore the variability in aggregometry response in aspirin sensitive patients before and after initiation of clopidogrel therapy. METHODS: ADP 9.37 microM, AA 1.2mM and TRAP 25 mM stimulated light transmissions aggregometry (LTA) were performed twice before (Exams 1 and 2; 3 weeks apart)-and within one year after-initiation of clopidogrel therapy (Exam 3) in 79 patients treated with PCI. Repeated ADP aggregometry was also performed in 16 healthy volunteers in order to estimate LTA measurement error. RESULT: Inter-individual differences in ADP aggregation e.g. at Exam 1 were substantial (range 17-77%, SD 15.8%). Intra-individual changes between Exams 1 and 2 were significant (-27 to +36%, SD 14.6%, p<0.05). Inter-individual differences at Exam 3 (on clopidogrel treatment) were larger than expected from Exams 1 and 2 (p<0.01). AA aggregation was the same before and during clopidogrel treatment. In controls, inter-individual differences were smaller at ADP 10 than at ADP 5 microM. CONCLUSIONS: Inter-individual differences in ADP aggregation were significant both before and during clopidogrel therapy, and there were significant intra-individual variations over time. Therefore, prediction of aggregometry response before or during clopidogrel therapy based on single tests may be unreliable. Inter-individual differences in healthy controls are smaller at high concentrations of ADP, and comparisons of aggregometry response should be performed with caution unless ADP concentrations are standardized.

Inflammatory interaction between LIGHT and proteinase-activated receptor-2 in endothelial cells: potential role in atherogenesis.

The interaction between inflammatory cytokines and endothelial cells is a critical step in atherogenesis leading to endothelial dysfunction and inflammation. We have previously reported that the tumor necrosis factor superfamily member LIGHT could be involved in atherogenesis through its ability to promote vascular inflammation. In the present study we identified proteinase-activated receptor (PAR)-2 as an inflammatory mediator that was markedly enhanced by LIGHT in endothelial cells. We also found that LIGHT acted synergistically with PAR-2 activation to promote enhanced release of the proatherogenic chemokines interleukin-8 and monocyte chemoattractant protein-1, underscoring that the interaction between LIGHT and PAR-2 is biologically active, promoting potent inflammatory effects. We showed that the LIGHT-mediated upregulation of PAR-2 in endothelial cells is mediated through the HVEM receptor, involving Jun N-terminal kinase signaling pathways. A LIGHT-mediated upregulation of PAR-2 mRNA levels was also found in human monocytes when these cells were preactivated by tumor necrosis factor alpha. We have previously demonstrated increased plasma levels of LIGHT in unstable angina patients, and here we show a similar pattern for PAR-2 expression in peripheral blood monocytes. We also found that LIGHT, LIGHT receptors, and PAR-2 showed enhanced expression, and, to some degree, colocalization in endothelial cells and macrophages, in the atherosclerotic plaques of ApoE(-/-) mice, suggesting that the inflammatory interaction between LIGHT and PAR-2 also may be operating in vivo within an atherosclerotic lesion. Our findings suggest that LIGHT/PAR-2-driven inflammation could be a pathogenic loop in atherogenesis potentially representing a target for therapy in this disorder.

Increased level of platelet microparticles in survivors of myocardial infarction.

Platelet microparticles (PMPs) are highly procoagulant and might therefore be important in the pathogenesis of arterial thrombotic diseases. The aim of this study was to determine plasma levels of PMPs in survivors of myocardial infarction (MI) and their relation to activation of primary (sCD40L) and secondary (thrombin-antithrombin (TAT) complexes) haemostasis. An observational, population-based case control study was conducted in 61 MI patients 1-4 years after the MI and 61 age-matched and sex-matched healthy controls. PMPs were quantified using an immunoassay that discriminates between small and large PMPs. MI patients had significantly higher total PMPs (314.3 microg/L, 273.1-361.4 microg/L versus 225.8 microg/L, 168.8-273.1 microg/L, p=0.009) (geometric mean and 95% CI) and larger PMPs (181.3 microg/L, 160.7-204.3 microg/L versus 134.3 microg/L, 104.6-174.9 microg/L) than controls. The differences between groups remained significant after adjustments for use of cardiovascular drugs, body mass index, blood pressure and serum lipids, but were weakened when smoking was included in the analysis. Multiple regression analysis revealed a significant independent association between large PMPs and plasma TAT and soluble CD40 ligand (sCD40L) in MI patients, but not in healthy controls. The independent association between large PMPs and thrombin generation supports the concept that formation of PMPs is important for increased coagulation activation in MI patients.

Raised LIGHT levels in pulmonary arterial hypertension: potential role in thrombus formation.

RATIONALE: Thrombus formation and inflammation are involved in the pathogenesis of pulmonary arterial hypertension (PAH), and LIGHT (Lymphotoxin-like Inducible protein that competes with Glycoprotein D for Herpesvirus entry mediator on T lymphocytes) has been shown to promote vascular inflammation. OBJECTIVES: We sought to investigate the role of the tumor necrosis factor superfamily ligand LIGHT in the pathogenesis of PAH. METHODS: We studied 73 patients with severe PAH and 10 control subjects. LIGHT and pro- and antithrombotic markers were assessed by enzyme immunoassays. MEASUREMENTS AND MAIN RESULTS: (1) Patients with idiopathic PAH (n = 21), patients with PAH related to risk factors or associated conditions (n = 31), and those with chronic thromboembolic PAH (n = 21) all had raised serum levels of LIGHT compared with control subjects (n = 10). (2) LIGHT levels in femoral artery were significantly related to mortality in the patients with PAH. (3) Immunostaining of LIGHT and its receptors was seen in alveolar macrophages, vascular smooth muscle cells, and endothelial cells in lungs from patients with PAH. (4) Thirteen patients received prostacyclin infusion (3 mo), and all showed hemodynamic improvement, accompanied by decreased LIGHT levels. (5) Prostacyclin abolished the release of LIGHT from activated platelets in vitro, suggesting that the decrease in LIGHT during prostacyclin therapy could involve direct effects on platelets. (6) LIGHT increased tissue factor and plasminogen activator inhibitor type 1 and decreased thrombomodulin levels in endothelial cells, inducing a prothrombotic state in these cells. CONCLUSIONS: Our findings suggest prothrombotic effects of LIGHT in PAH involving endothelium-related mechanisms, potentially contributing to the progression of this disorder.

Plasma levels of granzyme B are increased in patients with lipid-rich carotid plaques as determined by echogenicity.

Increased echolucency of carotid plaques is associated with an increased risk of ischemic stroke. Inflammation and apoptosis of vascular smooth muscle cells in the arterial wall are involved in the atherosclerotic process and destabilization of the plaque. Granzyme B (GrB) is a key mediator of T cell-mediated cytotoxicity, and we therefore hypothesized that this protease could distinguish echolucent from other plaques. Ultrasound-determined echolucency of atherosclerotic plaques was assessed prior to carotid endarterectomy/angioplasty in 57 consecutively recruited patients with high-grade internal carotid stenosis. Plasma levels of GrB were measured by enzyme immunoassay prior to surgery. Patients with carotid atherosclerosis had significantly higher plasma levels of GrB compared to healthy controls (n=16) (p<0.01), with particularly high levels in those with an echolucent lesion. While there were no differences in traditional cardiovascular risk factors or CRP between those with echolucent (n=16) and those with echogenic/heterogeneous (n=41) plaques, the echolucent group had markedly raised plasma levels of GrB (p<0.01). Patients with high levels of circulating granzyme B also had more ischemic lesions on cerebral MRI prior to surgery. Raised plasma levels of GrB in echolucent carotid plaques with increased frequency of cerebrovascular events suggest that GrB may be a marker of plaque instability.

Off-pump cardiac surgery abolishes complement activation.

BACKGROUND: This prospective randomized study compared the inflammatory response in patients undergoing elective on-pump and off-pump coronary artery bypass grafting. PATIENTS AND METHODS: Forty-four patients undergoing elective coronary artery bypass grafting were recruited with 22 patients randomized to on-pump heart surgery and 22 patients to off-pump coronary bypass surgery. Plasma levels of C3bc, the terminal SC5b-9 complement complex, myeloperoxidase, beta-thromboglobulin and prothrombin fragment F1 + 2 were measured before the operation, intraoperatively, at termination of the operation, and two hours post-operatively. RESULTS: Complement was markedly activated in the on-pump group as indicated by a significant increase in C3bc and SC5b-9 (p < 0.001 for both), whereas no complement activation was seen in the off-pump group (p = 0.001 between the groups). In contrast, both groups showed significant activation of neutrophils, platelets and coagulation, as indicated by an early increase in myeloperoxidase and a post-operative increase in beta-thromboglobulin and F1 + 2, respectively. Notably, there were no intergroup differences with regard to neutrophil and platelet activation, whereas coagulation activation was more pronounced in the off-pump group (p < 0.01). CONCLUSIONS: Off-pump surgery completely eliminated the heart-lung machine-induced complement activation. Neutrophils and platelets were equally activated in both groups, whereas coagulation was enhanced post-operatively in the off-pump group.

Triglyceride-rich HDL3 from patients with familial hypercholesterolemia are less able to inhibit cytokine release or to promote cholesterol efflux.

Familial hypercholesterolemia (FH) is associated with heterogeneity of the onset and severity of coronary heart disease (CHD). In this study, we investigated different low-grade proinflammatory markers and the atheroprotective function of the HDL3 subfraction in FH-patients (n = 13) with identical LDL-receptor mutations and in age- and sex-matched healthy controls (n = 11). Compared with healthy controls, FH-patients had greater gene expressions of the proatherogenic mediators TNF-alpha and IL-8 in circulating peripheral blood mononuclear cells. In addition, they had a higher serum concentration of intercellular adhesion molecule-1 (ICAM-1) and a lower net antioxidant capacity. FH-derived HDL3 with a high level of triglycerides had a reduced capacity to inhibit the release of IL-8 from TNF-alpha-stimulated human umbilical vein endothelial cells (HUVEC) [1.864 mg/L (1.461-2.208 mg/L) vs. 1.466 mg/L (1.225-1.643 mg/L); P < 0.05; median (range)], and a reduced capacity to promote cholesterol efflux from lipid-loaded macrophages [12% (12-14%) vs. 15% (14-18%); P < 0.05; median (range)] compared with HDL3 with a lower triglyceride content. Notably, the degree of inhibition of IL-8 release from HUVEC by HDL3 was correlated with the ability of HDL3 to promote cholesterol efflux (r = -0.80, P = 0.03). In conclusion, compared with healthy controls, FH-patients are characterized by higher levels of low-grade proinflammatory markers, and FH-derived HDL3 with high triglyceride content may be more proatherogenic. These triglyceride rich-HDL3 might be partly responsible for the phenotypic variation among FH-patients with identical LDL-receptor mutations.

Diagnostic value of family histories of thrombosis to identify children with thrombophilia.

Thrombophilia screening is a time-consuming and expensive procedure. Information about thromboembolism among relatives may be a simple method to identify those at risk of having thrombophilia. In a cross-sectional clinical study the authors have investigated the role of such family histories to detect children with thrombophilia. In 202 children a family history of venous or arterial thromboembolism was recorded. The participants were either children with congenital heart defects at the time of a scheduled cardiac catheterization (n=134) or children with newly diagnosed cancer (n=68). Questions were answered, on the spot, by the parents, at the same time as blood samples for thrombophilia screening were taken. Questions about family history of thromboembolism were completed in 184 children, of whom 114 children (62%) were positive, and 35 of these had relatives with venous thromboembolic events. Only one child had an affected first-degree relative. Thrombophilic alterations were observed in 60 children (30%), and 25 of these were defined as inherited. A positive family history of venous origin increased the relative risk of a child having inherited thrombophilia to 2.35 (95% confidence interval 1.1--5.2). Information about familial arterial thromboembolism was not useful in spotting children with prothrombotic risk factors. These results indicate that questioning about family history of venous thromboembolism may identify children with genetic thrombophilia, but the association is not strong. The authors encourage similar larger-scale studies to enlighten the issue fully.

[Frequent urination--an important diagnostic marker in fibromyalgia]. / Hyppig vannlating--viktig diagnostisk markør ved fibromyalgi.

BACKGROUND: Detailed studies of a family with a strong clustering of fibromyalgia revealed that the affected members had eight or more urinations per day and at least one per night. As this feature was not known to be an important symptom in this ailment, we carried out a questionnaire-based study. MATERIAL AND METHODS: Questionnaires were mailed to a random group of 285 subjects drawn from the member list of the Norwegian Fibromyalgia Association, and to 160 healthy females, free of urinary tract pains. Response rates were 70% and 74%. RESULTS: The fibromyalgia group reported 8 or more daily and 1 permanent nocturnal urinations; the corresponding figures for healthy females were 6 and 0.2. This corresponds to a sensitivity and specificity for fibromyalgia of 78 and 91% for daytime urinations, and to 89% and 92% for one or more permanent nocturia. INTERPRETATION: The study indicates that an abnormally high frequency of urinations is a characteristic feature in fibromyalgia and a useful diagnostic variable. It is also objectively verifiable by urodynamic investigation. The pattern is that of urge, sometimes with incontinence.

Comparison of a Duraflo II-coated cardiopulmonary bypass circuit and a trillium-coated oxygenator during open-heart surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) evokes a systemic inflammatory response. In attempting to improve the biocompatibility of the equipment, various methods to coat the inner surfaces of the CPB systems have been developed. The present study compares a Trillium Biopassive surface-coated Affinity oxygenator with a Duraflo II totally heparin-coated CPB system. METHODS: Low-risk patients admitted for primary coronary artery bypass grafting or aortic valve replacement were randomized to operation using the Trillium- or the Duraflo II-coated setups. Heparin concentration, complement activation (C3bc activation products and terminal complement complex (TCC)), platelet activation (platelet numbers and beta-thromboglobulin (BTG)), leukocyte activation (leukocyte numbers and myeloperoxidase (MPO)), coagulation (thrombin/antithrombin complexes (TAT)) and fibrinolytic activity (plasmin/alpha2-antiplasmin complexes (PAP)) were measured during CPB and two hours postoperatively. RESULTS: Platelet counts decreased during CPB, without significant intergroup differences. The median BTG concentration increased moderately in both groups and were slightly higher in the Trillium group during CPB (p < 0.05), but not postoperatively. Complement activation products (C3bc and TCC), leukocyte counts, MPO, TAT and PAP activity showed no differences between the two groups. CONCLUSIONS: There were small differences in the inflammatory response between the two extracorporeal circulation devices compared in this study.

Platelet activation in heart transplant recipients.

An inappropriate and persistent immune activation has been suggested to contribute to long-term mortality and morbidity after heart transplantation. Several lines of evidence suggest that platelets do not only promote thrombus formation, but also act as inflammatory cells. In the present study, we investigated if long-time survivors of heart transplantation (mean time since transplantation 6.5 yr) were characterized by enhanced platelet activation as assessed by different experimental approaches. Our main findings when comparing heart transplant recipients (n = 52) and age- and sex-matched healthy controls (n = 38) were: (i) platelets from heart transplant recipients showed enhanced expression of both P-selectin and CD63 as assessed by flow cytometry; (ii) platelets from these patients also contained significantly increased levels of soluble CD40 ligand and tended to release higher levels of this cytokine upon SFLLRN stimulation as assessed by enzyme immunoassay; (iii) heart transplant recipients had increased levels of soluble P-selectin in platelet-free plasma; and (iv) the enhanced platelet activation after heart transplantation was most pronounced in those with concomitant hypertension. These findings suggest that long-term survivors of heart transplantation are characterized by enhanced activation of platelets, possibly contributing to the persistent immune activation and clinical complications in these patients.

Quality of intraoperative autologous blood withdrawal used for retransfusion after cardiopulmonary bypass.

BACKGROUND: Intraoperative autologous blood withdrawal protects the pooled blood from the deleterious effects of cardiopulmonary bypass. Following reinfusion after cardiopulmonary bypass, the fresh autologous blood contributes to less coagulation abnormalities and reduces postoperative bleeding and the need for allogeneic blood products. However, few data have been available concerning the quality and potential activation of fresh blood stored at room temperature in the operating room. METHODS: Forty coronary artery bypass grafting patients undergoing a consistent intraoperative and postoperative autotransfusion protocol had a median of 1,000 mL of autologous blood withdrawn before cardiopulmonary bypass. After heparinization the blood was drained from the venous catheter via venous cannula into standard blood bags and stored in the operating room until termination of cardiopulmonary bypass. Samples for hemostatic and inflammatory markers were taken from the pooled blood immediately before it was returned to the patient. RESULTS: There was some activation of platelets in the stored autologous blood, as measured by an increase of beta-thromboglobulin. Indications of thrombin formation, as assessed by plasma levels of thrombin-antithrombin complex and prothrombin fragment 1.2 were not seen, and there was no fibrinolytic activity. The red blood cells remained intact, indicated by the absence of plasma free hemoglobin. As for the inflammatory response, the levels of the terminal complement complex remained stable, and the cytokines tumor necrosis factor-alpha and interleukin 6 levels were not increased during storage. The complement activation products increased minimally, but remained within normal ranges. CONCLUSIONS: Except for slight activation of platelets, there was no indication of coagulation, hemolysis, fibrinolysis, or immunologic activity in the autologous blood after approximately 1 hour of operating room storage. The autologous blood was preserved in a condition of high quality, and retransfusion after cardiopulmonary bypass represents an uncomplicated and almost costless procedure for blood conservation.

Systemic inflammatory responses in African tick-bite fever.

Information regarding the inflammatory response in African tick-bite fever (ATBF), an emerging spotted-fever-group rickettsiosis, in international travelers to sub-Saharan Africa, is scarce. Plasma/serum levels of von Willebrand factor (vWF), soluble (s) E-selectin, tumor necrosis factor-alpha, interleukin (IL)-6, interferon-gamma, IL-10, IL-13, IL-8, RANTES, macrophage inflammatory protein-1alpha, and C-reactive protein were studied, at both first presentation and follow-up, in 15 patients with travel-associated ATBF and in 14 healthy travelers who served as control subjects. Our main and novel findings are the following: (1) patients with ATBF had increased levels of vWF and sE-selectin, with a subsequent decrease at follow-up; (2) with the exception of IFN-gamma, levels of cytokines and chemokines were also increased in these patients at the first presentation; and (3) IL-10 and IL-13 tended to increase during follow-up, whereas most of the inflammatory cytokines decreased. The induction of these mediators and the balance between them may be critical both for the regulation of inflammation and for protective immunity in ATBF.

Tranexamic acid given into the wound reduces postoperative blood loss by half in major orthopaedic surgery.

OBJECTIVE: To evaluate the effect of locally applied tranexamic acid on postoperative blood loss and measures of fibrinolysis in drained blood. DESIGN: Prospective study. SETTING: University hospital, Norway. PATIENTS: 30 patients operated on for low back pain by screw fixation of the lumbar spine, 16 of who were randomised to be given topical tranexamic acid. MAIN OUTCOME MEASURES: Postoperative blood loss after 18 hours. Concentrations of plasmin/alpha2-antiplasmin (PAP) and D-dimer in arterial and drained blood at the time of wound closure and in drained blood after 1 hour. RESULTS: In the tranexamic group median (interquartile) blood loss was reduced by half from 525 (325-750) ml to 252 (127-465) ml, p = 0.02. In drained blood after one hour the increase in the concentration of PAP was 150 (109-170)% and D-dimer 150 (107-272)% in the tranexamic group compared with the control group where the increase in PAP was 320 (140-540)% and D-dimer 260 (161-670)%. CONCLUSION: Tranexamic acid applied in the wound inhibits blood loss by up to a half in major orthopaedic surgery probably because it prevents excessive fibrinolysis.

Universal solvent/detergent-treated fresh frozen plasma (Uniplas--rationale and clinical properties.

Transfusions with incompatible blood products including plasma are a well-known problem. The present study was performed to test the effects of Uniplas, universal plasma that can be transfused regardless of a patient's blood group, with respect to bleeding and hemostatic activity. The study comprised 84 adult patients scheduled for elective openheart surgery. A total of 55 patients received plasma transfusions, while 29 patients not requiring plasma served as controls. If plasma transfusion was indicated during operation or over the two following days, patients were randomised 2:1 to receive Uniplas or Octaplas of blood group AB. Relevant clinical observations were recorded and blood tests taken repeatedly. The transfused patient groups were comparable, and no significant differences were observed with respect to activated clotting time (ACT), activated partial thromboplastin time (APTT) or postoperative bleeding into chest drains. The median number of transfused units of Uniplas was 3, with a range of 1-23, while the median for Octaplas was 2 with a range of 1-11. These differences were not significant.Thus, Uniplas has a similar effect as Octaplas in the treatment of bleeding in patients undergoing openheart surgery. Uniplas can therefore substitute for Octaplas and eliminate the risk of ABO-incompatible transfusions.

Absence of enhanced systemic inflammatory response at 18 weeks of gestation in women with subsequent pre-eclampsia.

OBJECTIVE: To compare indicators of systemic inflammatory response in the second trimester in women who developed pre-eclampsia with normal pregnancies. DESIGN: Prospective nested case control study derived from a cohort of 2190 pregnant women. Blood samples were obtained at 18 weeks of gestation. The following inflammatory parameters were measured: tumour necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor-1 (PAI-1), interleukin-1beta (IL-1beta), IL-6, IL-10, microCRP and tissue factor (TF). SETTING: Institute of Medical Genetics, University of Oslo, and Department of Medical Genetics, Ullevål University Hospital and Departments of Obstetrics and Gynecology, Aker University Hospital, Oslo, Norway. SAMPLE: The cases were 71 women who subsequently developed pre-eclampsia. The controls were 71 healthy, pregnant women matched for age, parity and first trimester body mass index (BMI). METHODS: Venous blood was drawn from fasting subjects into 5 mL test tubes containing EDTA. Samples were analysed for inflammatory parameters: IL-1-beta, IL-6, IL-10, TNF-alpha, PAI-1, TF (ELISA-technique) and CRP (latex-enhanced immunonephelometric assay), strictly according to the manufacturer's recommendation. MAIN OUTCOME MEASURES: The matched case and control subjects were compared by the paired two-tailed Wilcoxon signed rank test. All P values were two-tailed and P < 0.05 was deemed statistically significant. RESULTS: We found no differences in plasma concentrations of PAI-1, IL-1beta, IL-6,IL-10, microCRP, TNF-alpha or TF at 18 weeks of gestation between women who subsequently developed pre-eclampsia and matched control women. CONCLUSION: In contrast to findings from women with overt pre-eclampsia, the present study indicates that there are no indications of intensified systemic inflammatory response at 18 weeks of gestation in women who later develop pre-eclampsia.