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  • 1.
    Ahlner, Johan
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Bertilsson, Leif
    Karolinska Institute.
    Editorial Material: CYP2D6, serotonin and suicide2010In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 11, no 7, p. 903-905Article in journal (Other academic)
    Abstract [en]

    n/a

  • 2.
    Bendroth, Peter
    et al.
    Department of Forensic Medicine, Lund, Sweden.
    Kronstrand, Robert
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Helander, Anders
    Department of Clinical Neuroscience, Alcohol Laboratory, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
    Greby, Jesper
    Department of Forensic Medicine, Lund, Sweden.
    Stephanson, Nikolai
    Department of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
    Krantz, Peter
    Department of Forensic Medicine, Lund, Sweden.
    Comparison of ethyl glucuronide in hair with phosphatidylethanol in whole blood as post-mortem markers of alcohol abuse2008In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 176, no 1, p. 76-81Article in journal (Refereed)
    Abstract [en]

    Ethyl glucuronide (EtG) is a direct metabolite of ethanol and has been used as a marker of alcohol abuse in both urine and hair. This study investigated the value of EtG testing in post-mortem hair for diagnostic improvement of alcohol abuse in forensic medicine. Material from 70 consecutive medico-legal autopsies was collected in accordance with the recommendations on ethics by the Swedish National Board of Forensic Medicine. A method for determination of EtG in hair samples was developed using ultra performance liquid chromatography/electrospray tandem mass spectrometry (UPLC/ESI-MS/MS; LOQ, 2.5 pg/mg). The result of the EtG analysis was compared with the findings of phosphatidylethanol (PEth) in femoral whole blood, as measured by high performance liquid chromatography with an evaporative light-scattering detector (HPLC–ELSD; LOQ, 0.22 μmol/l). Evaluation of liver histology and anamnestic evidence of alcohol abuse of the deceased were taken in consideration for the interpretation. Measurable levels of EtG were present in 49 of the 70 autopsy cases whereas PEth was present in 36. Thirty-nine cases had EtG levels above the cutoff limit (≥30 pg/mg) compared with 29 for PEth (≥0.7 μmol/l). Fifteen cases had EtG as exclusive indicator for alcohol abuse compared with four cases for PEth. These findings suggest that measurements of EtG in hair may provide improved diagnostic information on alcohol abuse, due to a long retrospective time-window for detection and stability of EtG in hair in the decaying cadaver. However, an EtG level below the cutoff does not completely exclude previous alcohol abuse.

  • 3.
    Holmgren, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Carlsson, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna-Lena
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Dahl, Marja-Liisa
    Department of Medical Sciences, Clinical Pharmacology, University Hospital, Uppsala, Sweden.
    Scordo, Maria Gabriella
    Department of Medical Laboratory Sciences and Technology, Division of Clinical Pharmacology, Karolinska Institutet, University Hospital, Stockholm, Sweden.
    Druid, Henrik
    National Board of Forensic Medicine and Department of Forensic Medicine, Karolinska Institutet, Solna, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Forensic Science and Toxicology . Linköping University, Faculty of Health Sciences.
    Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C192004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 2, p. 94-104Article in journal (Refereed)
    Abstract [en]

    Citalopram, a selective serotonin reuptake inhibitor, is one of the most commonly found drugs in Swedish forensic autopsy cases. Citalopram is a racemic drug with 50:50 of the S- and R- enantiomers. Enantioselective analysis of citalopram and its metabolites desmethylcitalopram and didesmethylcitalopram were performed in femoral blood from 53 autopsy cases by a chiral high-performance liquid chromatography (HPLC) method. The mean (± standard deviation) S/R ratio for citalopram was 0.67 ± 0.25 and for desmethylcitalopram, 0.68 ± 0.20. We found increasing S/R ratios with increasing concentrations of citalopram. We also found that high citalopram S/R ratios were associated with a high parent drug-to-metabolite ratio and may be an indicator of recent intake. Citalopram is metabolized by cytochrome P450 (CYP) 3A4, 2C19, and 2D6. Genotyping for the polymorphic CYP2C19 and CYP2D6 revealed no poor metabolizers regarding CYP2C19 and only 2 (3.8%) poor metabolizers regarding CYP2D6. The presence of drugs metabolized by and/or inhibiting these enzymes in several of the cases suggests that such pharmacokinetic interactions are a more important (practical) problem than metabolic deficiency. Enantioselective analysis of citalopram and its metabolites can provide additional information when interpreting forensic toxicology results and might be a necessity in the future.

  • 4.
    Jablonowska, Barbro
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Selbing, Anders
    Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Bäckström, Gerd Margareta
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Molecular and Clinical Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Analyses of human leukocyte antigen (HLA-DRB1 and HLA-G alleles in couples with unexplained recurrent spontaneous abortion: typing by using the Polymerase Chain Reaction methodManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased parental Human Leukocyte Antigen (HLA) sharing has been repmted in couples witb history of unexplained recurrent spontaneous abmtion (RSA). Parental HLA sharing increases the risk of feto-matemal histo-compatibility and potentially affects maternal alia-recognition of the fetus. HLA-G is expressed on trophoblast and is expected to play an important role during placental and fetal development. The aim of the present study was to investigate the compatibility of HLA-DRB1 alleles in the couples with unexplained RSA and to investigate the frequency of HLA-DRB1 alleles and HLA-G alleles in these couples compared with fertile controls.

    Methods: The frequency of HLA-DRB1 alleles in 36 couples with unexplained recurrent spontaneous abmtion, and the compatibility of HLA-DRB1 alleles between patient couples were studied using a polymerase chain reaction-sequence specific primers (PCR- SSP) method. The frequency of HLA-G alleles in 35 couples were studied using a polymerase chain reaction - single nuclotide polymorphism (PCR-SNP). As controls we used 40 fertile couples who were typed for HLA-DRB1 and HLA-G alleles.

    Results: There were no significant differences for HLA-DRB1 and HLA-G allele frequencies in RSA couples compared with fertile controls. There was no significant HLA-DRB1 allele sharing between the RSA couples and fertile controls.

    Conclusions: There is no higher HLA-DRB1 allele sharing in couples with unexplained RSA than in fettile couples. The association on allelic level between RSA and HLA-G gene was not supported by our data.

  • 5.
    Montelius, Kerstin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    DNA analysis in disaster victim identification2012In: FORENSIC SCIENCE MEDICINE AND PATHOLOGY, ISSN 1547-769X, Vol. 8, no 2, p. 140-147Article, review/survey (Refereed)
    Abstract [en]

    DNA profiling and matching is one of the primary methods to identify missing persons in a disaster, as defined by the Interpol Disaster Victim Identification Guide. The process to identify a victim by DNA includes: the collection of the best possible ante-mortem (AM) samples, the choice of post-mortem (PM) samples, DNA-analysis, matching and statistical weighting of the genetic relationship or match. Each disaster has its own scenario, and each scenario defines its own methods for identification of the deceased.

  • 6.
    Perskvist, Nasrin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Skoglund, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Edston, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Medicine. Linköping University, Faculty of Health Sciences.
    Bäckström, Gerd
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Lodestad, Iréne
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Palm, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    TNF-α and IL-10 gene polymorphisms versus cardioimmunological responses in sudden infant death2008In: Fetal & Pediatric Pathology, ISSN 1551-3815, Vol. 27, no 3, p. 149-165Article in journal (Refereed)
    Abstract [en]

    We hypothesized that genetic variations of cytokines could contribute to the risk of developing a fatal immunological reaction in the heart of infants. Thus, tumor necrosis factor (TNF)-α and interleukin (IL)-10 gene polymorphisms versus induction of cardioimmunologxical responses in victims of sudden infant death syndrome (SIDS) were explored. We genotyped 35 infants (23 cases of SIDS and 12 infants with a known cause of death), and 100 healthy adult controls for IL-10 –1082 G/A, −592 C/A and TNF-α-238 G/A, −308 G/A. We found a higher frequency of the ATA haplotype and ATA/ATA genotype of IL-10 associated with SIDS (13%). The frequency of homozygote infants for IL-10 haplotypes in SIDS was higher (52%) than the control group (34%). All SIDS cases were homozygotice for the TNF-α-238 G allele and 20 infants were homozygous for the TNF-α-308 G allele in the same group. None of the infants with higher levels of infiltrated T-cells (n=8) was homozygous for IL-10 gene polymorphisms, whereas in contrast 3 cases of the 6 that displayed higher levels of cardiac mast cells were homozygous. In this study, the increased number of interstitial T-cells, mast cells, and macrophages in the myocardial interstitium demonstrated no correlation with the genotype for either cytokines.

  • 7.
    Tillmar, Andreas
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics.
    Egeland, Thore
    University of Oslo, Institute of Forensic Medicine, Oslo, Norway.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Holmlund, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics.
    Mostad, Petter
    Mathematical Sciences, Chalmers University of Technology, and Mathematical Sciences Göteborg University, Göteborg, Sweden.
    Using X-chromosomal markers in relationship testing: How to calculate likelihood ratios taking linkage and linkage disequilibrium into account2011In: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 5, no 5, p. 506-511Article in journal (Refereed)
    Abstract [en]

    X-chromosomal markers in forensic genetics have become more widely used during the recent years, particularly for relationship testing. Linkage and linkage disequilibrium (LD) must typically be accounted for when using close X-chromosomal markers. Thus, when producing the weight-of-evidence, given by a DNA-analysis with markers that are linked, the normally used product rule is invalid. Here we present an efficient model for calculating likelihood ratio (LR) with markers on the X-chromosome which are linked and in LD. Furthermore, the model was applied on several cases based on data from the eight X-chromosomal loci included in the Mentype® Argus X-8 (Biotype). Using a simulation approach we showed that the use of X-chromosome data can offer valuable information for choosing between the alternatives in each of the cases we studied, and that the LR can be high in several cases. We demonstrated that when linkage and LD were disregarded, as opposed to taken into account, the difference in calculated LR could be considerable. When these differences were large, the estimated haplotype frequencies often had a strong impact and we present a method to estimate haplotype frequencies. Our conclusion is that linkage and LD should be accounted for when using the tested set of markers, and the presented model is an efficient way of doing so.

  • 8.
    Tillmar, Andreas
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Mostad, Petter
    Mathematical Sciences, Chalmers University of Technology, and Mathematical Sciences Göteborg University, Göteborg, Sweden.
    Egeland, Thore
    Department of Medical Genetics, Ullevaal University Hospital, Oslo, Norway.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics . Linköping University, Faculty of Health Sciences.
    Holmlund, Gunilla
    National Board of Forensic Medicine, Department of Forensic Genetics and Forensic Toxicology, Linköping, Sweden.
    Montelius, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Analysis of linkage and linkage disequilibrium for eight X-STR markers.2008In: Forensic science international. Genetics, ISSN 1878-0326, Vol. 3, no 1, p. 37-41Article in journal (Refereed)
    Abstract [en]

    X-chromosomal short tandem repeats (X-STR) have proven to be informative and useful in complex relationship testing. The main feature of X-STR markers, compared to autosomal forensic markers, is that all loci are located on the same chromosome. Thus, linkage and linkage disequilibrium may occur. The aim of this work was to study population genetic parameters of eight X-STR markers, located in four linkage groups. We present haplotype frequencies, based on 718 Swedish males, for the four linkage groups included in the Argus X-8 kit. Forensic efficiency parameters have been calculated as well as the allelic association between the tested markers for detection of linkage disequilibrium. To study the occurrences of recombination between the loci, both Swedish and Somali families were typed. A mathematical model for the estimation of recombination frequencies is presented and applied on the family samples. Our study showed that the tested markers all have highly informative forensic values and that there is a significant degree of linkage disequilibrium between the STR markers within the four linkage groups. Furthermore, based on the tested families, we also demonstrated that two of the linkage groups are partially linked. A consequence of these findings is that both linkage and linkage disequilibrium should be accounted for when producing likelihood ratios in relationship testing with X-STR markers.

  • 9.
    Tomas, C
    et al.
    University of Copenhagen.
    Axler-DiPerte, G
    New York City Off Chief Med Examiner.
    Budimlija, Z M
    New York City Off Chief Med Examiner.
    Borsting, C
    University Copenhagen.
    Coble, M D
    Armed Forces Institute of Pathology.
    Decker, A E
    US Natl Institute Stand and Technology.
    Eisenberg, A
    University of North Texas Human Identification.
    Fang, R
    Appl Biosyst Inc.
    Fondevila, M
    University Santiago de Compostela.
    Frisk Fredslund, S
    University Copenhagen.
    Gonzalez, S
    University of North Texas Human Identification.
    Hansen, A J
    University Copenhagen.
    Hoff-Olsen, P
    University of Oslo.
    Haas, C
    University of Zurich.
    Kohler, P
    University of Oslo.
    Kriegel, A K
    University Hospital, Cologne.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics. Linköping University, Faculty of Health Sciences.
    Manohar, F
    Appl Biosyst Inc.
    Maronas, O
    University Santiago de Compostela.
    Mogensen, H S
    University Copenhagen.
    Neureuther, K
    Fed Criminal Police Off, Wiesbaden.
    Nilsson, H
    National Board for Forensic Medicine.
    Scheible, M K
    Armed Forces Institute of Pathology.
    Schneider, P M
    University Hospital, Cologne.
    Sonntag, M L
    Fed Criminal Police Off, Wiesbaden.
    Stangegaard, M
    University Copenhagen.
    Syndercombe-Court, D
    Barts and London Queen Marys School of Medicine and Dentistry.
    Thacker, C R
    Barts and London Queen Marys School of Medicine and Dentistry.
    Vallone, P M
    US Natl Institute Stand and Technology.
    Westen, A A
    Netherlands Forensic Institute.
    Morling, N
    University Copenhagen.
    Autosomal SNP typing of forensic samples with the GenPlex (TM) HID System: Results of a collaborative study2011In: Forensic Science International: Genetics, ISSN 1872-4973, E-ISSN 1878-0326, Vol. 5, no 5, p. 369-375Article in journal (Refereed)
    Abstract [en]

    The GenPlex (TM) HID System (Applied Biosystems - AB) offers typing of 48 of the 52 SNPforID SNPs and amelogenin. Previous studies have shown a high reproducibility of the GenPlex (TM) HID System using 250500 pg DNA of good quality. An international exercise was performed by 14 laboratories (9 in Europe and 5 in the US) in order to test the robustness and reliability of the GenPlex (TM) HID System on forensic samples. Three samples with partly degraded DNA and 10 samples with low amounts of DNA were analyzed in duplicates using various amounts of DNA. In order to compare the performance of the GenPlex (TM) HID System with the most commonly used STR kits, 500 pg of partly degraded DNA from three samples was typed by the laboratories using one or more STR kits. The median SNP typing success rate was 92.3% with 500 pg of partly degraded DNA. Three of the fourteen laboratories counted for more than two thirds of the locus dropouts. The median percentage of discrepant results was 0.2% with 500 pg degraded DNA. An increasing percentage of locus dropouts and discrepant results were observed when lower amounts of DNA were used. Different success rates were observed for the various SNPs. The rs763869 SNP was the least successful. With the exception of the MiniFiler (TM) kit (AB), GenPlex (TM) HID performed better than five other tested STR kits. When partly degraded DNA was analyzed, GenPlex (TM) HID showed a very low mean mach probability, while all STR kits except MiniFiler (TM) had very limited discriminatory power.

  • 10.
    Winskog, Carl
    et al.
    University of Adelaide.
    Nilsson, Helena
    National Board of Forens Medicine.
    Montelius, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Genetics . Linköping University, Faculty of Health Sciences.
    The use of commercial alcohol products to sterilize bones prior to DNA sampling2010In: FORENSIC SCIENCE MEDICINE AND PATHOLOGY, ISSN 1547-769X, Vol. 6, no 2, p. 127-129Article in journal (Refereed)
    Abstract [en]

    In disaster situations it is not always possible to maintain an adequate supply of standard equipment and sterilizing solutions. We have compared bone samples from cadavers cleaned in commercial white alcohol to samples from the same individuals cleaned with 95% surgical spirit. We have found that it is possible to use a commercial, white spirit to clean specimens taken from human cadavers femoral diaphysis collected for DNA analysis.

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