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Frank Brosstad

Publications and source records attributed to Frank Brosstad.

18 recordsLinked to original sources
PubMed2006

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.

Adult↗
PubMed2005

Intermittent saline flushes during haemodialysis do not alleviate coagulation and clot formation in stable patients receiving reduced doses of dalteparin.

BACKGROUND: Heparin-free haemodialysis (HD) with intermittent saline flushes (ISF) in patients with bleeding risk is widely used. The aim of this study was to investigate if ISF reduce coagulation and clotting in stable patients receiving reduced doses of dalteparin. METHODS: Inclusion criteria were stable chronic HD patients >or=18 years of age and haemoglobin >or=11 g/dl. Exclusion criteria were use of warfarin and acetylsalicylic acid. Six HD sessions were evaluated per patient. Dalteparin was given as one bolus dose at start of HD (50% of the conventional dose). In HD number 1, 3 and 5, 100 ml saline solution was flushed through the filter each 30 min. In HD 2, 4 and 6, no ISF were given. Potential clotting in the bubble trap was visually observed each hour and graded on a 4-point scale: 1 = normal, 2 = fibrinous ring, 3 = clot formation and 4 = coagulated system. The dialyser was visually inspected at the end of each session: 1 = normal, 2 = a few blood stripes (affecting less than 5% of the surface fibres), 3 = many blood stripes (more than 5% of the fibres) and 4 = coagulated filter. The coagulation marker PF1+2, the platelet activation marker beta-TG and anti-FXa activity were repeatedly measured during HD. RESULTS: Six men and two women were included. In four cases (four different patients), HD was stopped due to a coagulated system, all cases on days with ISF performed. Multiple linear regression analyses with repeated measurements showed that ISF adjusted for dalteparin dose/kg significantly increased mean clot in the bubble trap, estimate (B) = 0.717, P = 0.0001 and also showed that ISF increased PF1+2, B = 0.16, P = 0.001 when adjusted for anti-FXa activity and hours of dialysis, whereas beta-TG was only borderline increased, B = 0.09, P = 0.055. CONCLUSIONS: ISF during HD does not alleviate visible clotting or intravascular coagulation activity in stable patients receiving reduced doses of dalteparin and polysulphone dialysers. Whether this applies to unstable patients with increased bleeding risk not receiving any anticoagulation remains to be shown.

Adult↗
PubMed2005

Development of a time-resolved immunofluorometric assay for quantifying platelet-derived microparticles in human plasma.

Platelet-derived microparticles (PMPs) are considered a marker of platelet activation. They vary considerably in size, and flow cytometry, the predominant method used to assay PMPs, is only detecting larger PMPs (>0.1 microm). We describe here a method that quantifies the amount of PMP-located GPIIb antigen in detergent-treated platelet-free plasma (PPP) by means of a one-step time-resolved immunofluorometric assay (TR-IFMA). This assay uses a streptavidin-coated microwell plate and two different monoclonal antibodies to GPIIb (CD41), one conjugated to biotin and the other labeled with europium ion. A wide linear range standard curve with low background and a high sensitivity was obtained. Pre-assay ultracentrifugation or filtration of PPP extensively reduced the fluorometric signal, indicating that the GPIIb antigen is mainly particle-located. A strong correlation between the amount of GPIIb and PMP as detected by flow cytometry was found. Consequently, the assay can be used to study PMP-related phenomena and, in contrast to flow cytometry, can be used on frozen samples and is independent of PMP size.

Antibodies, Monoclonal↗
PubMed2005

[Frequent urination--an important diagnostic marker in fibromyalgia].

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.

Adult↗
PubMed2005

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.

Child↗
PubMed2004

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.

Blood Platelets↗
PubMed2004

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.

Blood Coagulation↗
PubMed2003

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.

Adult↗
PubMed2003

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.

Adult↗
PubMed2003

Results from clinical trials on ST-elevation myocardial infarction in a historic perspective with some pathophysiological aspects.

OBJECTIVE: Since the publication of the large trials on streptokinase and aspirin improving mortality related to an acute ST-elevation myocardial infarction (STEMI) there has been numerous studies on improving treatment results with new fibrinolytics, adjuvant heparin therapy and primary percutaneous intervention (PCI). The aim of the present overview is, in a historic perspective, to link some of the pathophysiology of mechanisms related to plaque rupture and following thrombosis to the effects of drug combinations and PCI observed in major clinical trials conducted in patients with STEMI. DESIGN: The overview comprises short analyses of the initial streptokinase trials (GISSI-1 and ISIS-2), the comparisons between streptokinase and tissue plasminogen activator (rt-PA) and the role of adjuvant heparin treatment (GISSI-2, ISIS-3, GUSTO I). Also included is the comparison between the new bolus-teplases and traditional, accelerated infusion of rt-PA (GUSTO III and ASSENT-2) and between unfractionated heparin (UFH) and low molecular weight heparin (LWMH) given in addition to tenecteplase (ASSENT-3). The pathophysiology of the antiplatelet and antithrombin effects is described, in order to elucidate the treatment differences observed in the trials. In addition, the role of primary PCI is discussed in view of the results in a recent meta-analysis of controlled comparisons with fibrinolytic therapy. RESULTS: Based upon these trials it seems that the optimal thrombolytic treatment is a combination of a bolus-teplase (tenecteplae) and LMWH given on top of aspirin. Primary PCI may be the most optimal treatment, provided given early following STEMI (<1 h), but whether PCI is the best alternative for all patients with STEMI is still a matter of debate. CONCLUSION: During the last 15 years the optimal antithrombotic treatment of STEMI has developed from a combination of streptokinase and aspirin to the new bolus-teplases combined with LMWH and aspirin. The use of primary PCI may be a better alternative than fibrinolytic therapy, but such a statement needs confirmation in a large comparison between PCI and a quick infusion of modern fibrinolytic agents.

Angioplasty, Balloon, Coronary↗
PubMed2003

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.

Administration, Topical↗
PubMed2002

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.

Aged↗
PubMed2002

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.

C-Reactive Protein↗
PubMed2002

Protein C deficiency caused by homozygosity for a novel PROC D180G mutation--in vitro expression and structural analysis of the mutation.

Homozygosity for a novel D180G mutation in the protease domain of protein C, associated with plasma protein C activity and antigen levels of 8% of normal was identified in a thrombosis prone family. Transient expression of protein C in HK-293 cells and analysis of protein C antigen in culture media and cell lysates showed that the secretion of mutant protein as compared with wild-type protein was reduced by 79% while the intracellular contents were similar. Computer analysis of the X-ray structure of activated protein C and of a theoretical model of the zymogen predicts that the mutation destabilises the molecule locally. Our results are compatible with a relatively unstable mutant molecule that could be trapped inside the cell and degraded. However, if secreted the mutant molecule could have a relatively normal catalytic activity and structure consistent with the plasma levels of protein C activity and the late onset of thrombosis.

Adult↗