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Biomedical subjects

L Nilsson

Publications and source records attributed to L Nilsson.

At least 19 recordsLinked to original sources
PubMed1999

Very low-density lipoprotein activates nuclear factor-kappaB in endothelial cells.

High plasma levels of VLDL are associated with increased risk for atherosclerosis. Here we show that VLDL (75 to 150 microg/mL) activates nuclear factor-kappaB (NF-kappaB), a transcription factor known to play a key role in regulation of inflammation. Oxidation of VLDL reduced its capacity to activate NF-kappaB in vitro, whereas free fatty acids such as linoleic and oleic acid activated NF-kappaB to the same extent as did VLDL. Intravenous injection of human VLDL (6 mg protein per kg) into rats resulted in arterial activation of NF-kappaB as assessed by electrophoretic mobility shift assay. Aortic endothelial cells showed positive nuclear staining for the activated RelA (p65) subunit of NF-kappaB at 6 to 24 hours after injection. There was also a parallel expression of the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, as well as the cytokine tumor necrosis factor-alpha. Pretreatment of the rats with diet containing 1% of the antioxidant probucol for 8 weeks did not inhibit arterial activation of NF-kappaB in response to injection of VLDL. Moreover, injection of triglycerides (10% Intralipid, 5 mL/kg) activated arterial expression of NF-kappaB to the same extent as VLDL. Our results suggest that VLDL may promote the development of atherosclerotic lesions by activation of the proinflammatory transcription factor NF-kappaB. The effect appears to be mediated by a release of VLDL fatty acids but not to involve VLDL oxidation.

Animals↗
PubMed1999

Effect of G40R mutation on the binding of human SRY protein to DNA: a molecular dynamics view.

Molecular dynamics simulation was conducted to investigate the reason why the mutant G40R of hSRY protein has a low affinity for DNA. Compared with the previous dynamics results of the wild-type hSRY-HMG-DNA complex, the results of molecular dynamics simulation on the mutant G40R hSRY-HMG-DNA system demonstrated that the whole structure of DNA (especially the second strand) had a major deviation away from the short arm of the HMG box. Consequently, the DNA and the mutant protein could not specifically recognize each other, that is, very different, and low-occupancy, direct, and water-mediated hydrogen bonds were detected at the protein-DNA interface, no conformational changes occurred at the loop region around Met9 during the simulation, and residue IIe13 did not intercalate between the bases of A5 and A6. These results indicated that the mutant G40R did not form a specific complex with the DNA target, hence led to complete gonadal dysgenesis. From the simulation, we realized that the residue Gly40 played a critical structural role in the hSRY-DNA recognition. It might be a structural supporting point of DNA binding because of the absence of a side chain. The reason for the difficulty of the mutant G40R to form a complex with DNA might be that the long and positively charged side chain of Arg40 by its bulk and positive charge hindered the DNA's access to the active sites of the protein.

DNA-Binding Proteins↗
PubMed1999

Risk factors for sudden unexpected death in epilepsy: a case-control study.

BACKGROUND: Sudden unexpected death is substantially more common in people with epilepsy than in the general population. Our objective was to investigate the association between some clinical variables and sudden unexpected death in epilepsy (SUDEP) to identify risk factors. METHODS: This nested case-control study was based on a cohort of people aged between 15 and 70 years, who, during 1980-89, had been admitted to and discharged with a diagnosis of epilepsy from any hospital in the county of Stockholm. The study population was followed up through the National Cause of Death Register until Dec 31, 1991. Cases were individuals who had died, with a diagnosis of epilepsy registered on the death certificate, and who after review of medical and necropsy records were found to meet our SUDEP criteria. Three control participants, who were living epilepsy patients matched for age and sex, were selected from the same cohort for each case. All medical records were examined. Clinical data were collected and analysed on a predesigned protocol. FINDINGS: 57 SUDEP cases were included, of whom 91% had undergone necropsy. The relative risk of SUDEP increased with number of seizures per year. The estimated relative risk was 10.16 (95% CI 2.94-35.18) in patients with more than 50 seizures per year, compared with those with up to two seizures per year. The risk of SUDEP increased with increasing number of antiepileptic drugs taken concomitantly--9.89 (3.20-30.60) for three antiepileptic drugs compared with monotherapy. Other major risk factors were early-onset versus late-onset epilepsy (7.72 [2.13-27.96]), and frequent changes of antiepileptic drug dosage compared with unchanged dosage (6.08 [1.99-18.56]). The association between SUDEP risk and early onset, and SUDEP risk and seizure frequency, was weaker for female than for male patients, whereas frequent dose changes showed a stronger association in female patients. INTERPRETATION: Our data suggest that SUDEP is a seizure-related event, although the pathophysiological substrate that predisposes individuals to SUDEP may be established at an early age, and there may be some sex differences. Improvement of seizure control and possibly the avoidance of polytherapy may be ways to reduce the risk of SUDEP.

Adolescent↗
PubMed1999

Structural and dynamic differences of the estrogen receptor DNA-binding domain, binding as a dimer and as a monomer to DNA: molecular dynamics simulation studies.

Molecular dynamics (MD) simulations of the estrogen receptor DNA-binding domain (ERDBD) as a dimer in complex with its DNA response element (ERE) show a significant difference in both structure and dynamics, compared to a MD simulation of monomeric ERDBD bound to its half-site response element (EREH). The C-terminal zinc binding domain (ZnII), including a region (helix II) which is in a helical conformation in ERE-(ERDBD)2, is considerably more flexible in EREH-ERDBD than in the dimeric complex. In EREH-ERDBD, all helical hydrogen bonds in helix II are broken and the entire ZnII region is detached from a hydrogen bonding network that in ERE-(ERDBD)2 connects to other parts of the protein as well as to the DNA. The regions that become flexible in EREH-ERDBD are identical to the regions where the NMR solution structure of free ERDBD is poorly ordered. This strongly suggests that dimerisation of ERDBD is required for ordering of the ZnII region and that monomeric binding to DNA is not sufficient for the ordering. This contrasts to the glucocorticoid receptor DNA-binding domain (GRDBD) which has essentially the same mobility (uniform and limited), regardless of whether it is free as a monomer in solution, bound as a monomer to its half-site response element or in a dimeric complex with the full response element. The hydrogen bonding network that connects ZnII with other parts of the protein and to DNA is almost identical in ERDBD and GRDBD. However, in GRDBD there is also a serine (in the N-terminal zinc coordinating region) with a central role in this network, connecting to the ZnII region. This serine is replaced by a glycine in ERDBD and we suggest that this substitution is sufficient for destabilisation of the network, thus leading to a more flexible ZnII region, which becomes ordered first upon forming a complex with another ERDBD and DNA.

Amino Acid Sequence↗
PubMed1999

Molecular dynamics simulations of the complex between human U1A protein and hairpin II of U1 small nuclear RNA and of free RNA in solution.

RNA-protein interactions are essential to a wide range of biological processes. In this paper, a 0.6-ns molecular dynamics simulation of the sequence-specific interaction of human U1A protein with hairpin II of U1 snRNA in solution, together with a 1.2-ns simulation of the free RNA hairpin, is reported. Compared to the findings in the x-ray structure of the complex, most of the interactions remained stable. The nucleotide U8, one of the seven conserved nucleotides AUUGCAC in the loop region, was unusually flexible during the simulation, leading to a loss of direct contacts with the protein, in contrast to the situation in the x-ray structure. Instead the sugar-phosphate backbone of nucleotide C15 was found to form several interactions with the protein. Compared to the NMR structure of U1A protein complexed with the 3'-untranslated region of its own pre-mRNA, the protein core kept the same conformation, and in the two RNA molecules the conserved AUUGCAC of the loop and the closest CG base pair were located in very similar positions and orientations, and underwent very similar interactions with the protein. Therefore, a common sequence-specific interaction mechanism was suggested for the two RNA substrates to bind to the U1A protein. Conformational analysis of the RNA hairpin showed that the conformational changes of the RNA primarily occurred in the loop region, which is just involved in the sites of binding to the protein and in agreement with experimental observation. Both the loop and stem of the RNA became more ordered upon binding to the protein. It was also demonstrated that the molecular dynamics method could be successfully used to simulate the dynamical behavior of a large RNA-protein complex in aqueous solution, thus opening a path for the exploration of the complex biological processes involving RNA at a molecular level.

Amino Acid Sequence↗
PubMed1999

Prospective study of the clinical and laboratory parameters of patients in whom ovarian hyperstimulation syndrome developed during controlled ovarian hyperstimulation for in vitro fertilization.

OBJECTIVE: To compare patient characteristics and clinical and laboratory parameters in patients in whom ovarian hyperstimulation syndrome (OHSS) develops with those in whom it does not develop. DESIGN: Prospective cohort study. SETTING: Reproductive medicine unit at a university medical center. PATIENT(S): All patients undergoing IVF (n = 428) who received controlled ovarian hyperstimulation during a 6-month period. INTERVENTION(S): Prospective data collection. MAIN OUTCOME MEASURE(S): Patient characteristics (age, body mass index, medical history, smoking habits) and clinical and laboratory data obtained during controlled ovarian hyperstimulation were evaluated in patients who had severe OHSS, any degree of OHSS, or a significant risk of OHSS and compared with the remaining populations. RESULT(S): Severe OHSS developed in 18 patients (4.2%) and mild or moderate OHSS developed in 7.3%. As a group, all the patients with OHSS were significantly younger, received lower doses of gonadotropins, had ovaries containing a higher number of total and large follicles, had a higher number of retrieved oocytes, and had a higher pregnancy rate than the patients without OHSS. The patients with severe OHSS also had an increased prevalence of allergy (56% versus 21%) and were more likely to ultimately give birth. CONCLUSION(S): The observed differences may be useful in elucidating the pathophysiology of OHSS and identifying patients who are at increased risk for OHSS.

Adult↗
PubMed1999

Allergic disease in teenagers in relation to urban or rural residence at various stages of childhood.

BACKGROUND: Higher prevalences of allergic diseases and IgE antibodies to inhalant allergens have been reported for persons living in urban areas than for persons living in rural areas. METHODS: Associations between cumulative incidences of allergic diseases in 1878 children aged 13-14 years and their place of residence (urban, semiurban, or rural) from birth were assessed by questionnaire (ISAAC), in order to find out whether there is a period of increased sensitivity to external influences during the first few years of life. Family history and exposure to pets, tobacco smoke, and damp were considered in multiple regression. RESULTS: There was a significantly higher prevalence of allergic diseases with urban residence than with rural residence during the first 2 years of life (e.g., for bronchial asthma, relative risk (RR) for the first year 2.1, 95% CI 1.2-3.7). An increased risk was still found after multiple regression (RR=1.7). Semiurban residence was associated with an intermediate cumulative incidence of allergic diseases. Maternal smoking during pregnancy was associated with asthma (RR=1.4, 95% CI 1.0-2.0). CONCLUSIONS: The findings support a period of increased susceptibility during the first years of life. Whether rural lifestyle protects against allergy or whether urban pollutants contribute to allergy has to be elucidated [corrected].

Adolescent↗
PubMed1999

Diagnostic epididymal and testicular sperm recovery and genetic aspects in azoospermic men.

Various procedures for sperm recovery in azoospermic men have been described, from open testicular biopsy to simple needle aspiration from the epididymis and the testis. Fifty-one obstructive and 86 non-obstructive azoospermic men were treated to compare the recovery of spermatozoa obtained by percutaneous aspiration from the epididymis (PESA) and aspiration/extraction from the testis (TESA, TESE) with histopathology. If TESA failed, the work up proceeded with TESE. All patients were karyotyped. Spermatozoa were recovered by PESA or TESA in all obstructive men (51/51 patients). In 22 out of 86 patients with non-obstructive azoospermia, testicular spermatozoa could be successfully recovered by TESA. In five additional patients TESE was successful in recovering spermatozoa where TESA had failed. In 43 patients, neither TESA nor TESE was successful. Sixteen patients chose not to proceed with TESE. Seven out of 86 patients had an abnormal karyotype in the non-obstructive group (8%), none in the obstructive group. In the non-obstructive patient group testicular histopathology showed hypospermatogenesis, incomplete maturation arrest and germ cell aplasia with focal spermatogenesis in cases where spermatozoa were recovered and complete germ cell aplasia, complete maturation arrest and fibrosis in cases where no spermatozoa were found. Spermatozoa were recovered by PESA or TESA from all patients with obstructive azoospermia and from approximately 40% of patients with non-obstructive azoospermia by TESA or TESE. Retrieval of viable spermatozoa in the infertility work-up was highly predictable for sperm recovery in subsequent ICSI cycles. TESA performed under local anaesthesia seems almost as effective as more invasive procedures in recovering testicular spermatozoa, both in obstructive and non-obstructive azoospermic men.

Epididymis↗
PubMed1999

Presence of uterine pinopodes at the embryo-endometrial interface during human implantation in vitro.

In order to study changes occurring on the surfaces of human endometrial epithelial cells in the presence of an implanted blastocyst, we used scanning electron microscopy for investigation of five endometrial biopsies and three human implantation sites obtained in vitro. All specimens showed areas with endometrial pinopodes, separated by cells displaying microvilli or cilia at the apical surface. Pinopode formation was more pronounced in endometrial biopsies than in cell cultures. All blastocysts adhered to pinopode presenting cells. Endometrial surface changes were not seen around the blastocysts. The results of this study demonstrate that cultured endometrial epithelial cells are capable of pinopode formation. Furthermore, endometrial epithelial pinopodes, generally considered as a marker of endometrial receptivity, seem to be directly involved in the adhesion of the blastocyst to the endometrial surface.

Blastocyst↗
PubMed1999

Obstetric outcome and psychological follow-up of pregnancies after embryo reduction.

The obstetric outcome and psychological follow-up of the parents after embryo reduction performed at Sahlgrenska University Hospital between 1993 and 1997 in 13 women treated for infertility is described. A comparison is made with non-reduced multiple pregnancies, both spontaneous and multiple pregnancies after assisted reproduction technology. Altogether 10 triplets, two quadruplets and one quintuplet pregnancy underwent embryo reduction. The surgical procedure was performed in gestation week 7-8 by transvaginal, ultrasound-guided aspiration of embryonic tissue. The psychological follow-up included personal interviews and psychological evaluations by a Psychological General Well-being Scale (PGWB) and Beck's Depression Inventory (BDI). In 11 cases reduction was performed to twin pregnancies. In two cases of triplets after in-vitro fertilization and transfer of two embryos, reduction was performed on the monozygotic, monochorionic twins. No complete miscarriages occurred. Ten women delivered twins and three women delivered singletons. The mean gestation length was 40.4 weeks for singletons and 35.9 weeks for twins. The mean birthweight was 3411 g for singletons and 2392 g for twins. No complications related to the reduction were detected in the children.The psychological follow-up showed that the psychological well-being of the parents was good. However, the events around the reduction were experienced as chaotic and emotionally disturbing. One woman regretted the reduction. All couples emphasized that avoidance of high order pregnancies should be of primary importance. In conclusion, embryo reduction appears to improve the perinatal outcome of multiple pregnancies obtained after assisted reproduction technology. It is important that the surgical procedure is performed at a centre with experience of this type of intervention, by a limited number of surgeons and in a regulated manner. Psychologically, however, the intervention is traumatic and psychological management is essential for good final outcome.

Adult↗
PubMed1999

Is allergy prevention realistic and beneficial?

Allergic diseases among children have shown a marked increase during the last two or three decades, despite increased awareness of possible preventive measures. Preventive efforts have focused on new-borns and infants with a biparental history of allergy as they are at particularly high risk of developing allergic disease (40-60%). No good intervention studies have been performed in the general population, only in high-risk families. Unfortunately, so far known risk factors can only explain a small part of the recent increase in allergic diseases. The most important recommendation for everyone is not to smoke during pregnancy and when living/working with young children. Breast milk is the best for every baby, even from an immunologic aspect. Humidity problems should be reduced in homes, day-care centres and schools. It is probably wise not to keep furred pets indoors in homes when babies have a family history of allergy. However, the effect of such advice should be assessed, including the acceptability, compliance, costs and effectiveness. There is no doubt that we should go on with preventive measures both in babies at high risk of allergy and also in the general population. At the same time, research should try to find even more efficient ways to reduce the current "allergy epidemic".

Adolescent↗
PubMed1999

Atopic eczema: how to tackle the most common atopic symptom.

The disease management of atopic eczema includes topical and systemic treatments as well as the control of allergic and non-allergic trigger factors. The basis for topical treatment is the regular use of emollients. In addition, anti-inflammatory treatment with -- preferably mild -- topical steroids is the treatment of choice. At least-one third of the children with atopic eczema during the first years suffer from clinically relevant food allergy requiring elimination diets for at least one or two years. The most common cause of superinfection is Staphylococcus aureus. Recent data suggests that it may induce purulent superinfection as well as enhance the inflammatory process by superantigen mediated T-cell activation. Also, a number of alternative treatment strategies have been investigated during the last decade: the use of gamma-linoleic acid has been shown to be of limited benefit, while studies on interferon-gamma and on high-dose intravenous gamma-globulin are still anecdotal. The long-term effectiveness of disease management in atopic eczema depends largely on the understanding of the disease process as well as on the compliance of the parents. Thus, coping with the problem will be easier if the patient or the parents have been educated in understanding the pathogenesis, the role of trigger factors, the possibilities of prevention and the different treatment strategies.

Adult↗
PubMed1999

Effects of native, triglyceride-enriched, and oxidatively modified LDL on plasminogen activator inhibitor-1 expression in human endothelial cells.

Whereas VLDL has consistently been shown to induce a concentration-dependent increase in the expression of plasminogen activator inhibitor-1 (PAI-1) in human umbilical vein endothelial cells (HUVECs) and liver cells, variable effects have been reported for native and oxidatively modified LDL. In the present study, activation of PAI-1 protein and mRNA expression by native LDL (nLDL), UV-oxidized LDL (uvLDL), and triglyceride (TG)-enriched LDL was studied in HUVECs by using different incubation times and a wide range of lipoprotein concentrations. No significant increase of PAI-1 protein expression was observed after 4 hours of incubation with nLDL or uvLDL. However, PAI-1 protein secretion from HUVECs was markedly enhanced after 18 hours of incubation with uvLDL (200% increase at 10 microg/mL). Stimulation of PAI-1 protein expression in HUVECs by nLDL was seen, however, after increasing the TG content of the LDL particle. LDL enriched in phospholipid had no effect on PAI-1 secretion. PAI-1 mRNA levels on northern blot increased in parallel with the activation of PAI-1 protein expression by native and modified forms of LDL. Low concentrations of TG-enriched LDL (10 microg/mL) and higher concentrations of nLDL and uvLDL (100 microg/mL) were found to increase the binding of a VLDL-inducible transcription factor to the PAI-1 promoter. These results indicate that the TG content of the LDL particle influences PAI-1 expression in endothelial cells. Low concentrations of uvLDL enhanced PAI-1 protein and mRNA expression in the HUVECs after an 18-hour incubation but did not influence the VLDL-inducible transcription factor. This suggests that low levels of oxidized LDL increase PAI-1 expression by a different mechanism than VLDL and TG-enriched LDL.

Cells, Cultured↗
PubMed1999

Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells.

The consistent positive correlation between triglyceride and plasminogen activator inhibitor-1 (PAI-1) levels in plasma and the fact that very low density lipoprotein (VLDL) induces secretion of PAI-1 from cultured human umbilical vein endothelial cells (HUVECs) and human hepatoblastoma cells have raised the question of whether fibrate treatment, the main effect of which is a profound lowering of plasma concentrations of VLDL, might improve fibrinolytic function by reducing the plasma levels of PAI-1. However, the findings of controlled clinical trials using various fibrate compounds have been discrepant. ECs express PAI-1 under normal conditions in humans. We therefore examined the effects of several fibrate compounds on PAI-1 expression and secretion by cultured HUVECs and the HUVEC-derived cell line EA.hy926. All fibrate compounds examined had significant effects on PAI-1 gene transcription in the EA.hy926 cells. Low concentrations of clofibric acid and bezafibrate increased PAI-1 transcription and secretion, whereas Wy-14643 increased PAI-1 synthesis in a dose-dependent way. In contrast, both fenofibric acid and gemfibrozil markedly decreased PAI-1 transcription and secretion from HUVECs and EA.hy926 cells. Thus, stimulation of the transcriptional activity of the PAI-1 gene by some fibrates is linked to increased secretion of PAI-1 protein by the cells, whereas the opposite effects occur with other fibrate compounds. Whether the different effects on PAI-1 transcription and secretion by ECs in vitro also reflect differences in treatment effects on the regulation of plasma PAI-1 activity in vivo will have to be determined in larger-scale, controlled clinical trials.

Bezafibrate↗
PubMed1999

Growth control of Listeria monocytogenes on cold-smoked salmon using a competitive lactic acid bacteria flora.

A Lactobacillus sake strain LKE5 and four strains of Carnobacterium piscicola were evaluated as biopreservation cultures to control the growth of Listeria monocytogenes on vacuum-packed, cold-smoked salmon stored at 5 degrees C. All five strains were antilisterial as live cultures in an agar diffusion assay. Cell-free supernatants of two strains of C. piscicola and L. sake LKE5 were also antilisterial because of the production of bacteriocins. The presence of high cell numbers of strains of C. piscicola had no influence on the sensory quality of cold-smoked salmon stored at 5 degrees C, but L. sake LKE5 caused strong sulfurous off-flavors and was rejected as a culture for biopreservation of cold-smoked salmon. A bacteriocin-producing strain of C. piscicola (A9b) initially caused a 7-day lag phase of L. monocytogenes, followed by a reduction in numbers of L. monocytogenes from 10(3) CFU/ml to below 10 CFU/ml after 32 days of incubation, coinciding with the detection of antilisterial compounds. The presence of a nonbacteriocin-producing strain of C. piscicola (A10a) prevented the growth of L. monocytogenes during the 32-day incubation. The growth of L. monocytogenes was strongly repressed on cold-smoked salmon in the presence of C. piscicola A9b and A 10a, respectively. The initial cell numbers of L. monocytogenes that were found on Oxford plates incubated at 25 degrees C reached low maximum cell counts of 10(4) and 2 x 10(3) after 14 and 20 days of storage in mixed culture with C. piscicola A9b and A10a.

Animals↗
PubMed1999

VLDL activation of plasminogen activator inhibitor-1 (PAI-1) expression: involvement of the VLDL receptor.

The potential role of the very low density lipoprotein (VLDL) receptor in mediating VLDL-induced plasminogen activator inhibitor-1 (PAI-1) expression was studied in vitro. Cultured endothelial cells incubated with VLDL showed an increased secretion of PAI-1. This response to VLDL could be completely prevented by the receptor-associated protein (RAP) and partially blocked by rabbit polyclonal anti-VLDL receptor IgG. Furthermore, Chinese hamster ovary (CHO) control cells and cells overexpressing the VLDL receptor were transiently transfected with a PAI-1 promoter-reporter construct and incubated with VLDL. The PAI-1 promoter activity in response to VLDL was significantly higher in the VLDL receptor overexpressing cells compared to the control cells. Addition of RAP completely blocked the VLDL-activated PAI-1 transcription. Electromobility shift assay was performed to investigate whether the enhanced PAI-1 promoter activity seen in the VLDL receptor overexpressing cells in response to VLDL involved induction of the previously described VLDL-inducible factor(s) binding to the -675 to -653 region of the PAI-1 promoter. We found that the binding of the VLDL-inducible factor in VLDL receptor overexpressing cells was markedly enhanced by addition of VLDL as compared to control cells where no increased binding could be seen in response to VLDL. In summary, these results indicate that the VLDL receptor is a strong candidate for mediating VLDL effects on PAI-1 synthesis and secretion in cells expressing this receptor.

Animals↗
PubMed1999

APC-resistance is a risk factor for postoperative thromboembolism in elective replacement of the hip or knee--a prospective study.

Postoperative venous thromboembolic complications are commonly seen after total replacement of the hip or knee. Recently, an inherited defect with resistance to the anticoagulant activity of activated protein C (APC-resistance) has been detected. APC-resistance seems to be a common risk factor, especially in Sweden, and it increases the propensity for venous thrombosis. This study assesses the prevalence of APC-resistance in a general population and its clinical significance for patients undergoing surgery associated with a high risk of thromboembolic complications. In a prospective cohort study, we analysed for APC-resistance in 645 consecutive patients before elective replacement of the hip or knee at 3 hospitals in southern Sweden. Thromboprophylaxis with LMWH-heparin was given to all patients throughout the hospitalisation period. We recorded events of clinical thromboembolism for 3 months postoperatively. Venography, ultrasonography or pulmonary scintigraphy was requested by the clinicians according to the existing routines, i.e. only patients with symptoms of thromboembolism were examined. A thromboembolic complication was registered in 20 (3.1%) patients. Fifty per cent of the venous thrombi had a proximal location. Only 0.3% of the patients had verified pulmonary embolism. APC-resistance was found in 14.1% of the patients, of whom 9.9% had experienced postoperative thromboembolism compared with 2.0% of the patients without APC-resistance (p<0.0007). We conclude that APC-resistance is a frequent risk factor for symptomatic postoperative deep venous thrombosis with an estimated relative risk of 5.0 (95% confidence interval: from 1.9 to 12.9) in elective replacement of the hip or knee.

Activated Protein C Resistance↗