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Biomedical subjects

Finn Wisløff

Publications and source records attributed to Finn Wisløff.

14 recordsLinked to original sources
PubMed2006

Decreased anticoagulant response to tissue factor pathway inhibitor type 1 in plasmas from patients with lupus anticoagulants.

Inhibition of tissue factor pathway inhibitor type 1 (TFPI) is one of the mechanisms by which lupus anticoagulants (LA) may upregulate tissue factor (TF) activity. We wanted to examine whether purified immunoglobulin G (IgG) from patients with LA may interfere with the ability of TFPI to inhibit ex vivo TF-induced thrombin generation. The endogenous thrombin potential (ETP) in pooled normal plasma (PNP) supplemented with IgG from either patients with LA or controls was determined in the absence or presence of recombinant TFPI (rTFPI). In the presence of a heparin neutralizer, the ETP was also determined in plasmas from patients with LA and controls before and after heparin injection in order to quantify the anticoagulant effect of heparin-releasable TFPI in vivo. Compared with IgG from controls (n = 14), IgG from patients with LA (n = 28) induced a wide range of enhancing or inhibitory effects on the ETP in PNP. The response to rTFPI in PNP with IgG from patients with LA correlated inversely with thrombin generation (r(s) = 0.637, P = 0.0003). Correspondingly, the relative inhibition of ETP in postheparin plasmas was smaller for patients (n = 11) than for controls (n = 9) (32% vs. 68%, P = 0.007). Our findings support the hypothesis that TFPI anticoagulant activity is inhibited in some patients with LA.

Adult↗
PubMed2006

Serum calcium is an independent predictor of quality of life in multiple myeloma.

Bone disease is an important feature of multiple myeloma, and hypercalcaemia is a frequent complication of this disease. We examined the association between serum calcium and quality of life (QOL) scores of 686 multiple myeloma patients at the time of diagnosis. Data from two Nordic studies using the EORTC QLQ-C30 questionnaire were analysed by means of linear regression analysis and a curve fitting program. Serum calcium was independently related to appetite loss, nausea/vomiting and physical functioning (P < 0.001) and to cognitive functioning (P = 0.001), i.e. scores reflecting symptoms that are well known in non-malignant hypercalcaemia. In addition, we found a highly significant independent relationship between serum calcium and the scores for fatigue and pain (P < 0.001). Serum calcium appeared to be as strong a predictor for fatigue as the concentration of haemoglobin. A cubic model (y = a + bx3) fitted the data slightly better than the simple linear model (y = a + bx) and suggested worsening QOL scores at levels of serum calcium above 2.5-3.0 mmol/L. Hypercalcaemia in patients with multiple myeloma seems to be associated with the same symptoms as in non-malignant hypercalcaemia. In addition, an increased level of serum calcium may aggravate the pain and fatigue caused by the skeletal disease itself.

Adult↗
PubMed2006

Detection and quantification of lupus anticoagulants in plasma from heparin treated patients, using addition of polybrene.

BACKGROUND: Lupus anticoagulants prolong clotting times in phospholipid-dependent coagulation tests. Lupus Ratio assays are integrated tests for lupus anticoagulants that may be based on APTT, RVVT or dPT clotting times. If a patient is being treated with unfractionated heparin, however, the heparin prolong clotting times and the diagnosis of lupus anticoagulant is invalidated. Commercial assays may have heparin neutralising agents added to their reagents. However, the type and efficacy of the heparin neutralisation is often not documented. We wanted to test the influence and efficacy of heparin neutralisers in the Lupus Ratio assay. METHODS: Several heparin neutralisers were tested, and polybrene was chosen for further testing. Unfractionated heparin and/or polybrene were added to normal plasma and to plasma from patients with or without lupus anticoagulant and clotting times compared before and after the additions. Lupus anticoagulant-positive patients were given 5000 IU i.v. of unfractionated heparin and plasma was collected just before and five minutes after the injection. Lupus Ratios were calculated after polybrene was added to the postinjection samples. RESULTS: The Lupus Ratio became slightly lower when polybrene was added to plasma without heparin. Plasma heparinised in vitro and plasma from patients that had received heparin, both had Lupus Ratios nearly identical to the Lupus Ratios calculated before any additions. CONCLUSION: By addition of polybrene to a final concentration of 7.9 microg/ml in test plasma, Lupus Ratio may be determined in lupus anticoagulant-negative as well as positive plasmas irrespective of the presence of heparin 0.0-1.3 U/ml.

Journal Article↗
PubMed2005

[Antineoplastic agents targeting tyrosine kinases].

BACKGROUND: Drugs that target tyrosine kinases belong to a new class of antineoplastic therapeutics, directed at cellular signalling mechanisms. Notes on the use of these agents and some of the clinical data are discussed in this review. METHODS: The article is based on a review of recent literature and the authors' personal experience. RESULTS AND INTERPRETATION: Receptor tyrosine kinases and intracellular tyrosine kinases regulate cellular events that may be involved in tumour development, such as proliferation, survival, and angiogenesis. Some of these agents are established in clinical practice, in particular the small-molecular tyrosine kinase inhibitor imatinib in the treatment of chronic myeloid leukaemia and gastrointestinal stromal tumours and the antibody trastuzumab in the treatment of breast cancer. Inhibitors of epidermal growth factor receptor (EGFR) and other tyrosine kinases are either established in clinical practice or under clinical investigation.

Antibodies, Monoclonal↗
PubMed2005

Quality of life may be affected more by disease parameters and response to therapy than by haemoglobin changes.

Earlier studies showing a negative impact of anaemia on quality of life (QOL) lack adequate adjustment for confounding factors such as disease stage and tumour response. We examined the impact of haemoglobin concentration on QOL scores of 745 multiple myeloma patients followed from diagnosis, adjusting for objective disease parameters. Data from two Nordic studies with the EORTC QLQ-C30 questionnaire were analysed using linear regression analysis. Haemoglobin was independently related only to fatigue at baseline (P = 0.001) and at 12 months (P = 0.010). In multivariate analysis, extent of skeletal disease was at least as strong a predictor for fatigue at diagnosis as haemoglobin and was also related to other important QOL scores such as physical functioning, role functioning, global QOL and pain (P < 0.001). At 12 months' follow-up, response to therapy was related to physical functioning (P < 0.001) and pain (P = 0.001). In conclusion, haemoglobin and extent of skeletal disease were both predictors for fatigue in patients with newly diagnosed multiple myeloma, but extent of skeletal disease was also associated with other important QOL scores. During follow-up, response to therapy emerged as an important predictor variable. When examining the effect of haemoglobin on QOL, it is essential to adjust for disease parameters and response to therapy in order not to overestimate the impact of haemoglobin on QOL. Our findings imply that uncontrolled studies on the effect of erythropoietin (EPO) in cancer patients may be making exaggerated claims for the effect of EPO on QOL.

Adult↗
PubMed2004

Effect of subcutaneous administration of dalteparin on lupus anticoagulant assays.

INTRODUCTION: Treatment with unfractionated heparin (UH) is known to affect screening tests for lupus anticoagulant (LA). False positive test results are common because confirmatory steps lack sufficient specificity to distinguish between LA and the presence of heparin. In this study, we wanted to see if therapeutic levels of low-molecular weight heparin (LMWH) may cause false positive tests for LA or alter the LA test results in LA-positive patients. We also wanted to evaluate the need to include heparin-neutralizing agents in the reagents. MATERIALS AND METHODS: Six healthy subjects without LA and six LA-positive patients were given 100 IU/kg dalteparin subcutaneously (s.c.). Samples for three in-house and two commercially available LA tests were taken before and 4 h after the injection. LA test results were calculated as normalized screening/confirm ratios or as recommended by the manufacturers. RESULTS: With both healthy subjects and LA patients, only small and clinically unimportant differences in mean clotting times and final test results were seen 4 h after subcutaneous dalteparin injections, at anti-FXa activities within the therapeutic range. CONCLUSIONS: Our study with dalteparin suggests that LMWH therapy with plasma concentrations within the therapeutic range does not cause false positive tests for LA when normalized screening/confirm ratios are applied; nor do test results for LA-positive patients seem to be significantly altered. Heparin-neutralizing agents did not influence test performance.

Adult↗
PubMed2004

Interpretation of quality of life scores in multiple myeloma by comparison with a reference population and assessment of the clinical importance of score differences.

OBJECTIVES: Without clear guidelines, clinicians and health care providers are often uncertain how to interpret (quality of life) QOL scores. To facilitate the interpretation, QOL scores of multiple myeloma patients at diagnosis were compared with the scores of a reference population, and the clinical significance of QOL score differences and of changes in scores over time was assessed. METHODS: Data from two prospective Nordic Myeloma Study Group trials (221 patients <60 yr treated with high dose chemotherapy, and 203 patients >60 yr treated with melphalan and prednisone) were analysed. The EORTC QLQ-C30 questionnaire was used. The results were compared with the scores of an age- and gender-adjusted Norwegian reference population (n = 3000), using a regressional approach. The magnitude of the observed differences and of score changes during follow-up was estimated as effect size [score difference (SD)] and according to a subjective rating system as small, moderate or large. RESULTS: At diagnosis, the most distressing problems were pain and fatigue, reduced physical functioning, limitations in role functioning and reduced overall QOL. These differences from the reference population were statistically significant (P < 0.001), and large or moderate according to the rating systems. After the start of treatment, small to moderate improvement in mean QOL scores were observed for most domains. CONCLUSION: Comparison with a reference population eases the interpretation of QOL scores and prevents overestimation of symptoms and underestimation of subjective treatment response. The agreement between the two methods to evaluate the meaning of differences and changes in QOL scores was good.

Adolescent↗
PubMed2002

Dilute prothrombin time-based lupus ratio test. Integrated LA testing with recombinant tissue thromboplastin.

The lupus ratio (LR) test is a normalized ratio of the clotting times obtained with low and high phospholipid (PL) concentrations, where the test plasma is mixed 1:1 with normal pooled plasma (NP). As an integrated, automated, and computer-assisted assay, this principle has been applied to the dilute activated partial thromboplastin time (dAPTT) and dilute Russell viper venom time (dRVVT) test systems. In this study, we used recombinant thromboplastin to develop an automated LR test based on the dilute prothrombin time (dPT). Using plasma samples from a selected group of patients (N=92) with a well-defined lupus anticoagulant (LA) status, the dPT-based LR test showed fair agreement with the dAPTT-based LR test (kappa=.60, P<.001) and good agreement with the dRVVT-based LR test (kappa=.78, P<.001) regarding the classification of plasmas as LA-negative or -positive. Most discordant plasmas were low positive. Correlation between dPT- and dRVVT-positive LRs was only moderate (r(s)=.51, P=.002), and correlation between dPT- and dAPTT-positive LRs was nonsignificant (r(s)=.23, P=.18). Using dilutions of pooled LA-positive plasma, the dAPTT-based LR test appeared to be the most sensitive of the three tests. This study confirms the general validity of the LR principle and shows that the dPT-based LR test yields reproducible results. The low coefficients of variation (CV) of the LR assays, combined with a fairly low correlation among the three tests, support the assumption of antibody heterogeneity of LA-positive plasmas and the desirability of performing more than one test.

Adult↗