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Biomedical subjects

Jørgen Jespersen

Publications and source records attributed to Jørgen Jespersen.

At least 19 recordsLinked to original sources
PubMed2007

A comparative study of the effect of continuous combined conjugated equine estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability.

BACKGROUND: Hormone therapy (HT) after the menopause is associated with increased risk of venous thromboembolism (VTE). Tibolone has pharmacodynamic properties different from other hormone preparations. We compared the effect of a combined HT and tibolone on the inhibition of haemostasis. METHODS: Thirty-eight post-menopausal women were randomly assigned to 1.25 or 2.5 mg per day of tibolone or oral continuous combined conjugated equine estrogen plus medroxyprogesterone acetate (CEE/MPA). Inhibitors of haemostasis were measured at baseline and after 12 months. RESULTS: Results from the two groups of women receiving tibolone were not significantly different and, to improve the power of the study, the two groups were merged. Higher concentration of protein S (1.16 versus 1.00 IU ml(-1); P = 0.005) and higher activated protein C resistance ratio (APC-R) (4.2 versus 3.65; P = 0.04) were observed in the tibolone group than in the CEE/MPA group. Both doses of tibolone increased APC-R significantly (P < 0.01). Tissue factor pathway inhibitor (TFPI) was lower in the CEE/MPA group than in the tibolone group (67.8 versus 79.9 ng ml(-1); P = 0.03). CEE/MPA reduced the concentration of antithrombin (P = 0.002), protein S (P < 0.001) and TFPI (P < 0.001). Both preparations reduced the concentration of plasminogen activator inhibitor 1 (P < 0.05). CONCLUSIONS: Tibolone induces fewer pharmacological alterations on blood coagulability than CEE/MPA and has a potentially favourable effect on APC-R. This may translate into a corresponding low risk of VTE, as also indicated from the existing clinical data.

Aged↗
PubMed2006

Associations between aortic calcification and components of body composition in elderly men.

OBJECTIVE: To investigate associations among body composition, cardiovascular risk factors, and atherosclerosis in middle-aged and elderly men for the identification of potential pathogenic links. RESEARCH METHODS AND PROCEDURES: The study included 168 white men 44 to 86 years old. Severity of aortic calcification (AC) was graded on lateral radiographs, and body fat and lean mass were measured by DXA. Information on demographic and lifestyle characteristics also was gathered. RESULTS: A strong and independent inverse association was found between AC and peripheral lean mass (PLM), even after adjusting for age and BMI (p < 0.05). Independently of the influence of PLM, AC was directly correlated with truncal fat mass (p < 0.05). Furthermore, AC was inversely associated with tertiles of the free androgen index (p < 0.05). In a multiple regression model, age and serum cholesterol (p < 0.01) contributed directly, and truncal fat mass tended also to contribute directly (p = 0.09), whereas PLM contributed borderline inversely (p = 0.06) to the variation of AC (R = 0.635, p < 0.0001). DISCUSSION: Severity of AC is strongly dependent on age and further modulated by an array of traditional cardiovascular risk factors. Sarcopenia and truncal fat mass are reciprocal correlates of atherosclerosis of borderline statistical significance in multivariate models. To clarify whether sarcopenia is an atherogenic risk factor or rather a parallel consequence of low-grade inflammation also promoting atherogenic trends, further longitudinal studies in larger sample sizes of men and women are needed.

Absorptiometry, Photon↗
PubMed2006

A national field study of quality assessment of CoaguChek point-of-care testing prothrombin time monitors.

A system for quality assessment (QA) of the CoaguChek (Roche Diagnostics, Mannheim, Germany) point-of-care testing prothrombin time monitor has been developed by the European Concerted Action on Anticoagulation. Hitherto there has not been an adequate rapid method for CoaguChek QA. Sets of 5 certified international normalized ratio (INR) plasma samples were tested on 539 CoaguChek monitors by experienced staff at 9 Netherlands Thrombosis Centers and results compared with certified INR. A 15% or more deviation has been classified as significant deviation. Overall mean and certified INR values were similar, but 20.3% of participants showed a 15% or more deviation from the certified INR on at least 1 of the 5 QA plasma samples. Statistically significant differences in results with different lots of CoaguChek test strips were found. There is need for large scale QA of CoaguChek monitors. The importance of the 5 CoaguChek certified INR QA plasma samples being tested on a single occasion is demonstrated.

International Normalized Ratio↗
PubMed2006

Quality assessment of CoaguChek point-of-care prothrombin time monitors: comparison of the European community-approved procedure and conventional external quality assessment.

BACKGROUND: There is a need for dependable quality assessment (QA) of the widely used CoaguChek point-of-care testing prothrombin time monitor. By use of the prescribed set of 5 CoaguChek certified international normalized ratio (INR) QA plasmas, we compared the reliability of the immediate QA of individual monitors described in the European Community-recommended Technology Implementation Plan with conventional external QA analysis. METHODS: Experienced staff tested CoaguChek point-of-care monitors in routine use for controlling oral anticoagulant dosage at 9 Netherlands Thrombosis Service Centres. Testing was performed with both the certified CoaguChek INR for a set of 5 QA individual plasmas from the Eur Con Action on Anticoag (ECAA) and conventional external QA analysis. RESULTS: Patients brought 523 CoaguChek monitors to our service centers for assessment. The proportion with unsatisfactory performance indicated by a 15% deviation from the ECAA set was compared with 15% deviation from overall median INR of all CoaguChek monitors in the survey, as in conventional QA analysis. The results were similar (20.3% and 18.5%, respectively). Interlot differences of CoaguChek test strips were detected, but the incidence of unsatisfactory performance was similar with both analyses, from 6.5% to 37.5% with the certified INR method and from 5.9% to 33.3% with the overall median analysis. CONCLUSIONS: The results validate the use of the European Action on Anticoagulation rapid single-instrument QA-specific procedure for CoaguChek users compared with the nonspecific conventional QA analysis that relies on deviation from the overall median INR.

Administration, Oral↗
PubMed2005

Intraperitoneal heparin ameliorates the systemic inflammatory response in PD patients.

BACKGROUND: Patients with end-stage renal disease (ESRD) suffer from high mortality rates of cardiovascular diseases, conditions closely linked to the magnitude of their chronic low-grade inflammation. As heparins have been suggested to possess anti-inflammatory properties, we set out to investigate the impact of long-term treatment with intraperitoneal heparin on local and systemic inflammation in peritoneal dialysis (PD) patients. METHODS: In a double-blinded cross-over study, 21 PD patients with ESRD were randomised to inject either 4,500 anti-Xa IU tinzaparin or placebo (isotonic saline) into their morning dialysis bags every day for two periods of 3 months separated by a 1-month wash-out period. Blood and dialysate samples were analysed for inflammatory markers at the start and end of each treatment period. In dialysate, the appearance rates of the inflammatory markers were calculated to adjust for ultrafiltration variations. RESULTS: Eleven patients completed the trial. Treatment with intraperitoneal tinzaparin was accompanied with a median 25.8% reduction of the plasma C-reactive protein concentration (p = 0.032), a 7.3% reduction of the plasma fibrinogen concentration (p = 0.042) and a 54.5% reduction of the dialysate interleukin 6 appearance rate (p = 0.007) compared with placebo. CONCLUSION: Long-term treatment with intraperitoneal tinzaparin of ESRD patients on PD reduces local and systemic concentrations of inflammatory markers.

Adult↗
PubMed2005

A 1-year study to compare the hemostatic effects of oral contraceptive containing 20 microg of ethinylestradiol and 100 microg of levonorgestrel with 30 microg of ethinylestradiol and 100 microg of levonorgestrel.

OBJECTIVES: To comparatively evaluate the impact of a balanced one-third dose-reduced oral contraceptive on hemostatic variables. METHODS: In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg of ethinylestradiol (EE) and 100 microg of levonorgestrel (LNG) was compared with a reference preparation containing 30 microg of EE and 150 microg of LNG. One-year data were obtained from 48 volunteers. RESULTS: The direction and magnitude of the changes (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. The majority of changes of all investigated variables remained within the reference ranges of variation. The procoagulatory variables increased to some extent from baseline to treatment cycle 13, while the anticoagulatory variables slightly decreased. In particular, thrombin turnover measured by prothrombin fragments 1+2 increased during treatment by 35% in the 20 microg of EE group and by 38% in the 30 microg of EE group. Statistically significant differences between the two treatment groups were found only for TAT. For the profibrinolytic variables, plasminogen was increased by 42% (20 microg of EE) and 49% (30 microg of EE). While the plasma levels of tPA antigen were reduced during treatment, the levels of its activity were increased by 54% (20 microg of EE) and 20% (30 microg of EE). For PAI, both antigen and activity were decreased, somewhat more pronounced with 20 microg of EE. D-Dimer remained virtually unchanged. Finally, the median FbDP levels were elevated by 30% (20 microg of EE) and 38% (30 microg of EE).

Adult↗
PubMed2004

Genetic influence on inflammation variables in the elderly.

BACKGROUND: Inflammation variables (C-reactive protein [CRP], fibrinogen, and soluble intercellular adhesion molecule-1 [sICAM-1]) have been identified as risk factors for cardiovascular disease. It is still not known how much the regulation of inflammatory risk factors is determined by genetic factors, and the aim of this study was to determine the heritability of these inflammation variables and of the acute phase regulating cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) at older ages. METHODS AND RESULTS: The heritability of CRP, fibrinogen, sICAM-1, IL-6, and TNF-alpha was determined in a twin study consisting of 129 monozygotic twin pairs and 153 dizygotic same-sex twins aged 73 to 94 years who participated in the Longitudinal Study of Aging of Danish Twins. Furthermore, we determined the influence of selected genetic polymorphisms on the plasma level variations. Genetic factors accounted for 20% to 55% of the variation in plasma levels of the inflammation variables. The highest heritability was found for sICAM-1. The genetic polymorphisms we studied explained only a small, insignificant part of the heritability. CONCLUSIONS: This study in elderly twins provides evidence for a substantial genetic component of inflammatory cardiovascular risk factors among the elderly.

Acute-Phase Proteins↗
PubMed2004

Intraperitoneal heparin reduces peritoneal permeability and increases ultrafiltration in peritoneal dialysis patients.

BACKGROUND: Patients on long-term treatment with peritoneal dialysis (PD) suffer from increasing peritoneal permeability and loss of ultrafiltration as a result of persistent inflammation, which may be triggered by bioincompatible dialysis fluids. Heparins have anti-inflammatory and anticoagulant properties. We have examined the effect of intraperitoneal (IP) low-molecular weight heparin (tinzaparin) on peritoneal permeability and ultrafiltration in PD patients. METHODS: By means of a double-blinded cross-over design, 21 PD patients were randomized to receive either placebo or tinzaparin intraperitoneally once a day for two treatment periods of 3 months, separated by a wash-out period. The effect of heparin on peritoneal permeability and ultrafiltration was assessed using the 4 h standard peritoneal equilibration test. RESULTS: IP tinzaparin reduced significantly the dialysate-to-plasma ratios (D/P) of creatinine (P < 0.01), urea (P < 0.01) and albumin (P<0.05). In addition, the ratio of glucose concentration in dialysate at 4 h dwell to that of 0 h dwell (D(4)/D(0)) was increased (P<0.05) along with an increase in ultrafiltration volume (P<0.05). CONCLUSIONS: IP tinzaparin reduces peritoneal permeability to small solutes and increases ultrafiltration in PD patients.

Adult↗
PubMed2003

Lack of difference among progestins on the anti-atherogenic effect of ethinyl estradiol: a rabbit study.

BACKGROUND: Progestins in combination with estrogen are believed to have different effects on the cardiovascular system. The aim of this study was to investigate the influence of different oral contraceptive formulations on the development of experimental atherosclerosis and vascular reactivity. METHODS: A total of 160 sexually mature rabbits were ovariectomized and randomly assigned to equally large groups: (i) a cholesterol-rich diet (320 mg/day), either given alone (placebo), or together with (ii) ethinyl estradiol (EE 70 micro g/day, oral), (iii) desogestrel (DSG 525 micro g/day, oral), (iv) gestodene (GSD 262.5 micro g/day, oral), (v) levonorgestrel (LNG 525 micro g/day, oral), (vi) EE + DSG, (vii) EE + LNG, or (viii) EE + GSD. After 31 weeks of treatment, aortic accumulation of cholesterol and vascular vasoreactivity (in vitro) were determined. RESULTS: Progestins alone did not reduce the accumulation of cholesterol. EE alone or in combination with a progestin reduced the accumulation of cholesterol relative to placebo (P < 0.0001). Isolated vessels from EE-treated animals relaxed significantly more to physiological concentrations of acetylcholine than did placebo (P < 0.001), whereas vessels treated with EE plus a progestin showed an intermediate response. CONCLUSION: The progestins investigated can be combined with EE without attenuating the anti-atherogenic effect of EE.

Animals↗
PubMed2002

Internal quality control of PCR-based genotyping methods: practical experiences.

Internal quality control programmes for genetic analyses are needed. We have focused on quality control aspects of selected polymorphism analyses used in thrombosis research. DNA was isolated from EDTA-blood (n = 500) and analysed for 18 polymorphisms by polymerase chain reaction (PCR), i.e. restriction fragment length polymorphisms, allele specific amplification, or amplification of insertion/deletion fragments. We evaluated the following aspects in the analytical procedures: sample handling and DNA-isolation (pre-analytical factors), DNA-amplification, digestion with restriction enzymes, electrophoresis (analytical factors), result reading and entry into a database (post-analytical factors). Furthermore, we evaluated a procedure for result confirmation. Isolated DNA was of good quality (42 micrograms/ml blood, A260/A280 ratio > 1.75, negative DNAsis tests). Occasionally, results were reanalysed because of positive reagent blanks (< 1%) or because of problems with the controls (< 5%). On confirmation, we observed four genotyping discrepancies. Control of data handling revealed 0.1% reading mistakes and 0.5% entry mistakes. Based on our experiences, we propose an internal quality control programme for widely used PCR-based haemostasis polymorphism analyses.

Genotype↗
PubMed2002

Hormone replacement therapy: estrogen and progestin effects on plasma C-reactive protein concentrations.

OBJECTIVE: Our purpose was to assess the effect of hormone replacement therapy (HRT) on C-reactive protein blood concentrations with special reference to the progestin component. STUDY DESIGN: Changes from baseline and between groups in blood concentrations of C-reactive protein were determined during 12-month periods in 6 groups of postmenopausal women. Group A (the reference group) received no HRT; group B received 2 mg of estradiol valerate (E2V) daily combined with 1 mg of cyproterone acetate (CPA) for 10 days (28/10 days); group C received 2 mg of E2V plus 1 mg of CPA sequentially (21/10 days); group D received a combination of 2 mg of E2V and 1 mg of norethindrone acetate continuously; group E received 2 mg of E2V in combination with local delivery of levonorgestrel (20 microg/24 h); and group F received a long-cycle regimen consisting of 2 mg of E2V (84/91 days) plus 20 mg of medroxyprogesterone (14/91 days). RESULTS: No significant variation in CRP levels was observed in the reference group. HRT resulted in a significant increase in CRP concentrations in the women receiving the continuous combination of E2V plus norethindrone acetate and the continuous regimen of E2V plus local delivery of levonorgestrel. Cyclic or continuous intake of E2V plus CPA did not change CRP levels significantly. During the long-cycle regimen, the concentrations of CRP showed a significant variance over time. The concentrations increased during the estrogen phase but were modulated by the progestin intake throughout the study period. CONCLUSION: HRT can increase CRP levels in healthy women, and both the estrogen and the progestin component are of importance for the change. Whether the increase in CRP levels only reflects a changed steady-state metabolism is unknown. However, the clinical significance should be viewed from the perspective of changes in other inflammatory risk markers of importance for the evolution of cardiovascular disease.

Adult↗
PubMed2002

Effect of long-term hormone replacement therapy on plasma homocysteine in postmenopausal women: a randomized controlled study.

OBJECTIVE: The purpose of this study was to investigate the long-term effect of hormone replacement therapy on total homocysteine and to study whether there was any difference in effect between opposed and unopposed hormone replacement therapy or whether the methylenetetrahydrofolate reductase C677T polymorphism was associated with the effect of hormone replacement therapy on total homocysteine. STUDY DESIGN: Two hundred nine healthy postmenopausal women were randomized to hormone replacement therapy (n = 103) or no substitution (n = 106) 5 to 7 years earlier. RESULTS: Women who received hormone replacement therapy had significantly lower total homocysteine concentrations than women in the control group; median total homocysteine values were 8.6 micromol/L and 9.7 micromol/L, respectively, in a per-protocol analysis (P =.02). The effect was comparable in all methylenetetrahydrofolate reductase genotypes, and no difference between unopposed and opposed hormone replacement therapy could be demonstrated. Similar results were obtained when an intention-to-treat analysis was performed. CONCLUSION: Long-term hormone replacement therapy results in lower total homocysteine concentrations in all methylenetetrahydrofolate reductase genotypes without demonstrable difference in effect between unopposed and opposed hormone replacement therapy.

Estradiol↗
PubMed2002

European concerted action on anticoagulation. Use of plasma samples to derive international sensitivity index for whole-blood prothrombin time monitors.

BACKGROUND: To simplify International Sensitivity Index (ISI) calibration, the possibility of substituting fresh plasma for fresh whole-blood samples with point-of-care testing (POCT) whole-blood monitors was investigated in a three-center study of three different POCT systems. METHODS: A modified full WHO calibration procedure based on 20 healthy controls and 60 coumarin-treated patients was performed on three monitoring systems with whole-blood and plasma samples against plasma tested using the European Concerted Action on Anticoagulation (ECAA) rabbit reference plain thromboplastin and the manual prothrombin time (PT) method. RESULTS: With one of the three systems, the mean ISI was 1.51 for whole blood and 1.49 for plasma; with the second system, the mean ISI was 1.08 for both whole blood and plasma. With the third system, however, the difference between the mean ISI for whole blood and that for plasma was greater (1.15 and 1.01, respectively). Overall, the precision of the calibrations was less than with traditional manual plasma PT testing. CONCLUSIONS: Provided that an appropriate calcium chloride concentration is used, the plasma PT results can be used for accurate ISI calibration of two of these three whole-blood POCT systems. Precision criteria need to be modified for POCT monitors.

Administration, Oral↗