Biomedical subjects
Publications and source records attributed to Jørgen Gram.
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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.
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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.
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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.
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.
Genetic analyses are increasingly integrated in the clinical laboratory, and internal quality control programmes 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) by ammonium acetate precipitation 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 microg/ml blood, A260/A280 ratio >1.75, negative DNAsis tests), and the reagent blank was contaminated in <1% of the results. Occasionally, results were re-analysed because of positive reagent blanks (< 1%) or because of problems with the controls (<5%). On confirmation, we observed 4 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.