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- Bajc, Marika, et al.
(författare)
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Lung ventilation/perfusion SPECT in the artificially embolized pig.
- 2002
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Ingår i: Journal of Nuclear Medicine. - 0161-5505. ; 43:5, s. 640-647
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Tidskriftsartikel (refereegranskat)abstract
- Planar lung scintigraphy is a standard method used for the diagnosis of lung embolism, but it is hampered by the high incidence of nondiagnostic tests. Ventilation/perfusion SPECT may possibly improve this situation. The objective of this study was to compare planar lung scintigraphy with ventilation/perfusion SPECT using pigs with artificially engendered lung emboli labeled with (201)Tl. METHODS: Sixteen anesthetized pigs were each injected with zero to 4 latex emboli. Cylindric emboli were used in the first 7 pigs and flat 3-tailed emboli were used in the remaining 9 pigs. The pigs spontaneously inhaled 30 MBq (99m)Tc-diethylenetriaminepentaacetic acid aerosol for ventilation scintigraphy. Planar scintigraphy and SPECT were performed using a double-head gamma camera in (99m)Tc and (201)Tl windows. Immediately thereafter, 100 MBq (99m)Tc-labeled macroaggregated albumin were injected intravenously followed by SPECT and, finally, planar scintigraphy. The ventilation background was subtracted from the perfusion tomograms for calculation of a normalized ventilation/perfusion (V/P) quotient image set. RESULTS: The cylindric emboli caused artifacts in the ventilation images; therefore, these were excluded from the final analysis. However, for the planar perfusion images of these pigs, sensitivity and specificity were 71% and 91%, respectively, whereas SPECT yielded 100% for both. For the 3-tailed emboli and ventilation/perfusion images, the sensitivity and specificity were 64% and 79%, respectively, for the planar modality, whereas SPECT yielded values of 91% and 87%, respectively. CONCLUSION: V/P SPECT may improve the diagnostic power of lung scintigraphy.
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- Eriksson, Ulf G, et al.
(författare)
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Pharmacokinetics of melagatran and the effect on ex vivo coagulation time in orthopaedic surgery patients receiving subcutaneous melagatran and oral ximelagatran : a population model analysis
- 2003
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Ingår i: Clinical Pharmacokinetics. - 0312-5963 .- 1179-1926. ; 42:7, s. 687-701
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: Ximelagatran, an oral direct thrombin inhibitor, is rapidly bioconverted to melagatran, its active form. The objective of this population analysis was to characterise the pharmacokinetics of melagatran and its effect on activated partial thromboplastin time (APTT), an ex vivo measure of coagulation time, in orthopaedic surgery patients sequentially receiving subcutaneous melagatran and oral ximelagatran as prophylaxis for venous thromboembolism. To support the design of a pivotal dose-finding study, the impact of individualised dosage based on bodyweight and calculated creatinine clearance was examined. DESIGN AND METHODS: Pooled data obtained in three small dose-guiding studies were analysed. The patients received twice-daily administration, with either subcutaneous melagatran alone or a sequential regimen of subcutaneous melagatran followed by oral ximelagatran, for 8-11 days starting just before initiation of surgery. Nonlinear mixed-effects modelling was used to evaluate rich data of melagatran pharmacokinetics (3326 observations) and the pharmacodynamic effect on APTT (2319 observations) in samples from 216 patients collected in the three dose-guiding trials. The pharmacokinetic and pharmacodynamic models were validated using sparse data collected in a subgroup of 319 patients enrolled in the pivotal dose-finding trial. The impact of individualised dosage on pharmacokinetic and pharmacodynamic variability was evaluated by simulations of the pharmacokinetic-pharmacodynamic model. RESULTS: The pharmacokinetics of melagatran were well described by a one-compartment model with first-order absorption after both subcutaneous melagatran and oral ximelagatran. Melagatran clearance was correlated with renal function, assessed as calculated creatinine clearance. The median population clearance (creatinine clearance 70 mL/min) was 5.3 and 22.9 L/h for the subcutaneous and oral formulations, respectively. The bioavailability of melagatran after oral ximelagatran relative to subcutaneous melagatran was 23%. The volume of distribution was influenced by bodyweight. For a patient with a bodyweight of 75kg, the median population estimates were 15.5 and 159L for the subcutaneous and oral formulations, respectively. The relationship between APTT and melagatran plasma concentration was well described by a power function, with a steeper slope during and early after surgery but no influence by any covariates. Simulations demonstrated that individualised dosage based on creatinine clearance or bodyweight had no clinically relevant impact on the variability in melagatran pharmacokinetics or on the effect on APTT. CONCLUSIONS: The relatively low impact of individualised dosage on the pharmacokinetic and pharmacodynamic variability of melagatran supported the use of a fixed-dose regimen in the studied population of orthopaedic surgery patients, including those with mild to moderate renal impairment.
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- Hashemi, J, et al.
(författare)
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Haplotype analysis and age estimation of the 113insR CDKN2A founder mutation in Swedish melanoma families.
- 2001
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Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 31:2, s. 107-16
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Tidskriftsartikel (refereegranskat)abstract
- Germline mutations in the CDKN2A tumor suppressor gene located on 9p21 have been linked to development of melanomas in some families. A germline 3-bp insertion in exon 2 of CDKN2A, leading to an extra arginine at codon 113 (113insR), has been identified in 17 Swedish melanoma families. Analysis of 10 microsatellite markers, spanning approximately 1 Mbp in the 9p21 region, showed that all families share a common allele for at least one of the markers closest to the CDKN2A gene, suggesting that the 113insR mutation is an ancestral founder mutation. Differences in the segregating haplotypes, due to meiotic recombinations and/or mutations in the short-tandem-repeat markers, were analyzed further to estimate the age of the mutation. Statistical analysis using a maximum likelihood approach indicated that the mutation arose 98 generations (90% confidence interval: 52-167 generations), or approximately 2,000 years, ago. Thus, 113insR would be expected to have a more widespread geographic distribution in European and North American regions with ancestral connections to Sweden. Alternatively, CDKN2A may lie in a recombination hot spot region, as suggested by the many meiotic recombinations in this narrow approximately 1-cM region on 9p21.
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- Johansson, Ulrika, 1974-, et al.
(författare)
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Inflammatory mediators expressed in human islets of Langerhans : implications for islet transplantation
- 2003
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - 0006-291X .- 1090-2104. ; 308:3, s. 474-479
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Tidskriftsartikel (refereegranskat)abstract
- Expression of immune modulating mediators in human Islets of Langerhans could have important implications for development of autoimmunity in type 1 diabetes and influence the outcome of clinical islet transplantation. Islets obtained from five donors were analyzed at various times after isolation using cDNA array technology. The Atlas Human Cytokine/Receptor and Hematology/Immunology nylon membranes representing 268 genes and 406, respectively, were used and the relative expression of each gene analyzed. Of the 51 gene products identified, high mRNA expression of MCP-1, MIF, VEGF, and thymosin beta-10 was detected in all islet samples. IL-8, IL-1-beta, IL-5R, and INF-gamma antagonist were expressed in islets cultured for 2 days. IL-2R was expressed in islets cultured for more than 6 days. In conclusion, several inflammatory mediators were expressed in isolated islets, particularly at an early stage after isolation, indicating that a few days of culture could be beneficial for the outcome of islet transplantation.
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- Karlsson, Ulrika, et al.
(författare)
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Lärares personbedömningar av elever
- 2002
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Syftet är att undersöka hur lärares personbedömningar av elever ser ut. Totalt intervjuades 20 st lärare (10 män, 10 kvinnor) på 10 olika skolor. Lärarna ombads beskriva 10 pojkar och 10 flickor vardera. Det förekom könsskillnader och skillnader mellan individer. Kvinnliga lärare nämner fler problem som eleverna har och lärare tar oftare upp flickors sjukdomar och handikapp än pojkars.
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