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  • 1.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure2004In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 92, no 6, p. 1250-1258Article in journal (Refereed)
    Abstract [en]

    D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure. © 2004 Schattauer GmbH, Stuttgart.

  • 2.
    Andreen-Sachs, Magna
    et al.
    Hälso- och sjukvårdsnämndens stab, Stockholms läns landsting.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Overgripande kvalitetsindikatorer framtagna for halso- och sjukvarden2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 797-803Article in journal (Other academic)
  • 3. Axelsson Rosén, Stina
    et al.
    Hägg, Staffan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pharmacology.
    Eriksson, Andreas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Whiss, Per A
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Pharmacology.
    In vitro effects of antipsychotics on human platelet adhesion and aggregation and plasma coagulation2007In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 34, no 8, p. 775-780Article in journal (Refereed)
    Abstract [en]

    1. Several studies suggest an association between venous thromboembolism and the use of antipsychotic drugs, especially clozapine, but the biological mechanisms are unknown. It has been suggested that antipsychotic drugs enhance aggregation of platelets and thereby increase the risk of venous thrombosis. The purpose of the present study was to examine the effects of clozapine and its main metabolite, N-desmethyl clozapine, as well as olanzapine, risperidone and haloperidol, on platelet adhesion and aggregation and on plasma coagulation in vitro. 2. Blood was collected from healthy subjects free of medication. Platelet adhesion to different protein surfaces and aggregation were measured in microplates. The coagulation methods of activated partial thromboplastin time (APTT) and prothrombin time were performed in platelet-poor plasma. 3. Clozapine was the only compound that increased platelet adhesion and aggregation and shortened APTT. The effect appeared at therapeutic concentrations and was significant but weak. 4. This weak effect of clozapine on haemostasis may explain, in part, the association of this compound and venous thromboembolism. © 2007 The Authors.

  • 4. Ben Rayana, Mohammed C
    et al.
    Burnett, Robert W
    Covington, Arthur K
    DOrazio, Paul
    Fogh-Andersen, Niels
    Jacobs, Ellis
    Kataky, Rity
    Külpmann, Wolf R
    Kuwa, Katsuhiko
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lewenstam, Andrzej
    Maas, Anton H J
    Mager, Gerhard
    Naskalski, Jerzy W
    Okorodudu, Anthony O
    Ritter, Christoph
    St John, Andrew
    Recommendation for measuring and reporting chloride by ISEs in undiluted serum, plasma or blood2006In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 44, no 3, p. 346-352Article in journal (Refereed)
    Abstract [en]

    The proposed recommendation for measuring and reporting chloride in undiluted plasma† or blood by ion-selective electrodes (ISEs) will provide results that are identical to chloride concentrations measured by coulometry for standardized normal plasma or blood samples. It is applicable to all current ISEs dedicated to chloride measurement in undiluted samples that meet the requirements. However, in samples with reduced water concentration, results by coulometry are lower than by ion-selective electrode due to volume displacement. The quantity measured by this standardized ISE procedure is called the ionized chloride concentration. It may be clinically more relevant than the chloride concentration as determined by coulometry, photometry or by ISE after dilution of the sample. © 2006 by Walter de Gruyter.

  • 5.
    Bergdahl, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eintrei, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Läkarutbildningen i Linköpings förnyas. Problembaserat lärande, basvetenskap och folkhälsa förstärks2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 38, p. 2654-2658Article in journal (Other academic)
  • 6. Berois, Nora
    et al.
    Blanc, Etienne
    Ripoche, Hugues
    Mergui, Xénia
    Trajtenberg, Felipe
    Cantais, Sabrina
    Barrois, Michel
    Dessen, Philippe
    Kågedal, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Bénard, Jean
    Osinaga, Eduardo
    Raguénez, Gilda
    ppGalNAc-TI3: A new molecular marker of bone marrow involvement in neuroblastoma2006In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 52, no 9, p. 1701-1712Article in journal (Refereed)
    Abstract [en]

    Background: To identify new molecular markers of bone marrow dissemination in human neuroblastoma (NB), we studied the transcriptome profiles of malignant neuroblasts established from the human MYCN-amplified IGR-N-91 model. Methods: This experimental model includes human neuroblastoma cells derived from & subcutaneous stage 4 disease, myocardium (Myoc) and bone marrow (BM) metastatic cells. Results: Gene expression profiles obtained with Agilent oligo microarrays revealed a set of 107 differentially expressed genes in the metastatic neuroblasts. This set included up-regulated genes involved in chemoresistance, cell motility, neuronal structure/signaling, and the recently characterized GALNT13 gene encoding a glycosyltransferase that initiates mucin-type O-glycosylation. Because the glycosylation process is involved in the progression of primary tumor to metastatic disease, we investigated whether the most strongly upregulated gene, GALNT13, might be a marker of bone marrow involvement in stage 4 NB patients. Importantly, in the BM of healthy adults no GALNT13 transcript was detected with analysis by quantitative (n = 3) and nested reverse transcription-PCR (n = 4) assays. In contrast, GALNT13 transcripts were detected in 23/23 cytologically involved BM samples obtained at diagnosis of stage 4 NB patients and in 5/27 cytologically noninvolved BM samples obtained from patients with stage 1-4 and 4S and treated stage 4 NB. The quantitative measurements of tyrosine hydroxylase (TH), ganglioside D2 synthase, dopa decarboxylase, and GALNT13 transcript values were compared in the same NB patients, and the results showed that GALNT13 expression was most highly correlated to poor clinical outcome at diagnosis. Conclusion: We propose ppGalNAc-T13 as a new informative marker for the molecular diagnosis of BM involvement and the follow-up of minimal residual disease in NB patients. © 2006 American Association for Clinical Chemistry.

  • 7.
    Bobinski, L
    et al.
    Neurokirurgisk klinik Rekonstruktionscentrum.
    Boström, Sverre
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Postoperative pseudoaneurysm of the superficial temporal artery (S.T.A.) treated with Thrombostat® (thrombin glue) injection2004In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 146, no 9, p. 1039-1041Article in journal (Refereed)
    Abstract [en]

    Background. Pseudo-aneurysm is a rare complication of craniotomy. Blunt injury to the temporal artery region is the usual cause, but still a rare complication. Clinical presentation. A patient with subarachnoid hemorrhage was successfully treated by aneurysm clipping. The patient developed hydrocephalus, and was admitted for a shunt operation seventeen days later. The craniotomy had healed normally, but a palpable temporal lump was present in the skin incision. Intervention. The pulsating mass proved to be a postoperative aneurysm of the superficial temporal artery (S.T.A.) and was successfully occluded with 500 units Thrombostat® (thrombin glue) which was injected into the aneurysm sac using a 22-gauge needle guided by ultrasound. The permanency of the obliteration was verified by ultrasound examination.

  • 8. Bobinski, L
    et al.
    Boström, Sverre
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Leptomeningeal cyst due to vacuum extraction delivery in a twin infant2007In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 149, no 3, p. 319-323Article in journal (Refereed)
    Abstract [en]

    A rare case of a leptomeningeal cyst is reported in a twin male neonate delivered using a vacuum extractor, who presented a huge, non-pulsating, oedematous mass overlying the frontal fontanelle after birth. The mass was initially diagnosed as a cephalo haematoma. Ultrasonography indicated intracranial bleeding and a subsequent CT scan revealed an intraparenchymal bleeding above the left frontal horn, combined with a thin, left-sided, subdural haematoma and subarachnoid haemorrhage in the left Sylvian fissure. Apart from a bulging soft and round formation (2 × 2 × 3 cm) next to the anterior fontanel growing since birth, the neurological development of the infant was normal. MRI examination at the age of 7 months revealed that it consisted of a cystic mass (leptomeningeal cyst) connected to the left frontal horn, stretching right through the brain and also penetrating the dura mater. No signs of the perinatal haematomas were observed at this time. Surgical treatment, with fenestration of the cyst into the frontal horn and a watertight duraplasty with a periosteal flap and thrombin glue covered by small bone chips, was performed at 9 months of age. Due to a residual skull bone defect a second cranioplasty with autologous skull bone was performed three and half years later. During a follow-up period of 12 years the neurological and psychological development of the boy has been indistinguishable to that of his twin brother, indicating the satisfactory outcome of the treatment. © 2007 Springer-Verlag.

  • 9.
    Boström, Sverre
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Bobinski, Lukas
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Nilsson, Inge
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    A new scaled microgauge for use in neurosurgery2005In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 147, no 12, p. 1281-1282Article in journal (Refereed)
    Abstract [en]

    A new scaled microgauge is described for measuring anatomical structures during microsurgery. The instrument has a tip marked in millimetres, which can be positioned in any desired angle enabling measurement in confined areas. © Springer-Verlag 2005.

  • 10.
    Chaireti, Roza
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Arbring, Kerstin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Olsen, Ole H.
    Novo Nordisk A/S, Novo Nordisk Park, Måløv, Danmark.
    Persson, Egon
    Novo Nordisk A/S, Novo Nordisk Park, Måløv, Danmark.
    Lindahl, Tomas L.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Thrombin generation and levels of factor VII activity measured in the presence of rabbit and human thromboplastins in patients with mild factor VII deficiency – effects of mutations in factor VIIManuscript (preprint) (Other academic)
    Abstract [en]

    Background/Aim: It is known that spontaneous prolonged prothrombin time-international normalized ratio may be caused by deficiency of factor VII (FVII). The activity of FVII in the presence of thromboplastins of different origin is affected by the presence of specific mutations in the F7 gene. The present study aims to evaluate patients with mild FVII deficiency and somewhat discrepant FVII activity depending on the use of human or rabbit thromboplastin in relation to mutations in the FVII gene and markers of thrombin generation.

    Patients and methods: A cohort of 10 patients with mild deficiency of FVII and discrepant FVII activity was investigated. The median ratio of the FVII activity in the presence of human/rabbit thromboplastin was 1.4. All but 1 patient had mild to no bleeding symptoms. A genetic analysis of the F7 gene was performed. Thrombin generation was measured by the calibrated automated thrombogram in platelet poor plasma in the presence of human recombinant and different dilutions of rabbit thromboplastin and compared with thrombin generation in healthy controls (n=12). Thrombin generation was measured in 9 patients as 1 was treated with warfarin at the time of the blood sampling.

    Results: Six previously described mutations were found. Two of those (FVII Padua and FVII Shinjo) are known to affect the results for FVII activity dependent on the species origin of the thromboplastin. Nine out of 10 patients had one mutation in common (Arg353Gln), which however does not affect the binding site of FVII to tissue factor. Lagtime and ttpeak increased with decreasing concentrations of thromboplastin and total and maximum thrombin concentrations increased with increasing thromboplastin concentrations in the patients with FVII deficiency. ETP in patients with FVII deficiency was 86% of ETP in controls.

    Discussion: The Arg353Gln mutation was very common, however it does not appear to affect the reactivity towards thromboplastins of different origins. Although ETP was higher in the healthy controls, thrombin generation in FVII deficient patients was enough to sustain normal haemostasis. The expected thrombin generation patterns with increasing thromboplastin concentrations were confirmed for the patients in this study.

  • 11.
    Choremi-Papadopoulou, Helen
    et al.
    Immunologu Department Laiko General Hospital.
    Faure, Gilbert C.
    Laboratorie dImmunologie Université Henri Poincaré.
    Grunnet, Niels
    Department of Clinical Immunology Aarhus University Hospital.
    Madden, Michael
    Dept. Haematology Mercy University Hospital.
    Malenica, Branko
    Department of Immunology University Center Zagreb.
    Misbah, Siraj A
    Department of Clinical Immunology Oxford Radcliffe Hospitals.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Zlabinger, Gerhard J
    Institute of Immunology Medical University of Vienna.
    Position statement: Training programme in immunology of the European Board of UEMS Medical Biopathology [2]2005In: Immunology Letters, ISSN 0165-2478, E-ISSN 1879-0542, Vol. 96, no 2, p. 305-310Article in journal (Refereed)
  • 12. DOrazio, Paul
    et al.
    Burnett, Robert W
    Fogh-Andersen, Niels
    Jacobs, Ellis
    Kuwa, Katsuhiko
    Külpmann, Wolf R
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lewenstam, Andrzej
    Maas, Anton H J
    Mager, Gerhard
    Naskalski, Jerzy W
    Okorodudu, Anthony O
    Approved IFCC recommendation on reporting results for blood glucose (abbreviated)2005In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 51, no 9, p. 1573-1576Article in journal (Refereed)
    Abstract [en]

    In current clinical practice, plasma and blood glucose are used interchangeably with a consequent risk of clinical misinterpretation. In human blood, glucose, like water, is distributed between erythrocytes and plasma. The molality of glucose (amount of glucose per unit of water mass) is the same throughout the sample, but the concentration is higher in plasma because the concentration of water and, therefore, glucose is higher in plasma than in erythrocytes. Different devices for the measurement of glucose may detect and report fundamentally different quantities. Different water concentrations in calibrators, plasma, and erythrocyte fluid can explain some of the differences. Results of glucose measurements depend on sample type and on whether methods require sample dilution or use biosensors in undiluted samples. If the results are mixed up or used indiscriminately, the differences may exceed the maximum allowable error of glucose determinations for diagnosing and monitoring diabetes mellitus, and complicate the treatment. The goal of the IFCC Scientific Division Working Group on Selective Electrodes and Point of Care Testing (IFCC-SD, WG-SEPOCT) is to reach a global consensus on reporting results. The document recommends reporting the concentration of glucose in plasma (with the unit mmol/L), irrespective of sample type or measurement technique. A constant factor of 1.11 is used to convert concentration in whole blood to the equivalent concentration in the pertinent plasma. The conversion will provide harmonized results, facilitating the classification and care of patients and leading to fewer therapeutic misjudgments. © 2005 American Association for Clinical Chemistry.

  • 13.
    Egberg, N.
    et al.
    Departments of Clinical Chemistry, Karolinska Hospital, Stockholm.
    Fagerberg, I
    Sahlgrenska University Hospital, Gothenburg.
    Hillarp, A
    Malmö University Hospital, Malmö.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Stigendal, L
    Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweeden.
    Letter: Guidelines on preparation, certification, and use of certified plasmas for ISI calibration and INR determination - A rebuttal2005In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 3, no 10, p. 2370-2372Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 14.
    Ehrström, M
    et al.
    Division of Surgery Karolinska Institutet.
    Näslund, E
    Division of Surgery Karolinska Institutet.
    Levin, F
    Division of Surgery Karolinska Institutet.
    Kaur, R
    Department of Neurology GlaxoSmithKline.
    Kirchgessner, A L
    Department of Neurology GlaxoSmithKline.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hellström, P M
    Department of Gastroenterology and Hepatology Karolinska Institutet.
    Pharmacokinetic profile of orexin A and effects on plasma insulin and glucagon in the rat2004In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 119, no 3, p. 209-212Article in journal (Refereed)
    Abstract [en]

    Orexin A (OXA) is found in the central nervous system (CNS) and in the gut. Peripheral administration of OXA to rats results in an inhibition of fasting motility. Plasma OXA increases during fasting and central administration of OXA increases food intake. The aim of the present study was to assess the pharmacokinetic profile of OXA and the effect of intravenously (IV) administered OXA on plasma concentrations of insulin and glucagon concentrations. Rats were given OXA IV (100 pmol kg-1 min-1) for time periods of 0, 10, 20, 30 min and for 10, 20, 30 min after ceasing a 30-min infusion. After each time period, rats were then sacrificed and blood obtained. OXA was also administered at increasing doses (0, 100, 300 and 500 pmol kg-1 min-1) for 30 min and blood was obtained. Plasma OXA, insulin and glucagon levels were measured using commercially available radioimmunoassay (RIA) kits. The plasma half-life of OXA was 27.1±9.5 min. Stepwise increasing infusion rates of OXA confirmed a linear concentration-time curve and thus first-order kinetics. Its volume of distribution indicated no binding to peripheral tissues. Plasma glucagon decreased during infusion of OXA, while insulin was unaffected. Plasma OXA was raised fourfold after food intake. Thus, OXA has a longer plasma half-life than many other peptides found in the gut. This needs to be taken into account when assessing effects of OXA on biological parameters after peripheral administration.reserved.

  • 15.
    Eintrei, Christina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
    Bergdahl, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Fyrenius, Anna
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology.
    Hultman, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Revising a medical PBL-curriculum - the Linköping strategy2004In: Association for Medical Education in Europe,2004, 2004Conference paper (Other academic)
  • 16. Ellnebo-Svedlund, Katarina
    et al.
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Jonasson, Jon
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Molecular and Immunological Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Rapid genotyping of the osteoporosis-associated polymorphic transcription factor Sp1 binding site in the COL1A1 gene by pyrosequencing2004In: Molecular Biotechnology, ISSN 1073-6085, E-ISSN 1559-0305, Vol. 26, p. 87-90Article in journal (Refereed)
  • 17.
    El-Nour, H
    et al.
    Karolinska University Hospital.
    Lundeberg, L
    Karolinska University Hospital.
    Boman, A
    Unit of Occupational and Environmental Dermatology.
    Beck, O
    Unit of Clinical Pharmacology.
    Harvima, I T
    Department of Dermatology Kupio University Hospital.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Norlind, K
    Karolinska University Hospital.
    Study of innervation, sensory neuropeptides, and serotonin in murine contact allergic skin2005In: Immunopharmacology and immunotoxicology, ISSN 0892-3973, E-ISSN 1532-2513, Vol. 27, no 1, p. 67-76Article in journal (Refereed)
    Abstract [en]

    Density of nerve fibers, axonal growth, calcitonin gene-related peptide (CGRP), and substance P, and serotonin immunoreactivity as well as concentration were all determined in a murine model of contact allergy. Female Balb/c mice were sensitized on the back with oxazolone and 6 days later challenged with the same antigen on the dorsal surface of the ears, while control mice received the vehicle only. Then, 24 hr postchallenge, one ear was processed for immunohistochemical staining, while the other was frozen and processed for gas chromatography-mass spectrometry or radioimmunoassay (RIA). Protein gene product 9.5 (PGP 9.5) positive nerve fibers showed a tendency to increase in inflamed ears versus control ears in epidermis as well as the dermis. Growth-associated protein-43 (GAP-43) positive fibers in the epidermis were increased (p < .01) in inflamed ears, compared with control ears, as was the case for the dermal fibers, indicating increased axonal growth. Total (epidermis and dermis) numbers of CGRP and substance P positive nerve fibers tended to increase in the inflamed skin in contrast to control skin. In contrast, RIA demonstrated a lower (p < .05) concentration of CGRP in the inflamed ears compared with controls and a tendency for substance P to decrease in concentration in eczematous ears versus controls. There was no difference in serotonin concentration, or in the number of serotonin positive mast cells, between the inflamed and control skin, whereas semiquantification of serotonin positive platelets showed an increase in the inflamed (++) compared with control ears (+). Our results indicate that 24 hr after being challenged with the antigen, at the peak of murine skin inflammation, axonal growth, sensory neuropeptides, as well as serotonin may be involved. Copyright © 2005 Taylor & Francis Inc.

  • 18.
    El-Nour, Husameldin
    et al.
    Unit of Dermatology and Venerology Karolinska Institutet.
    Lundberg, Lena
    Unit of Dermatology and Venerology Karolinska Institutet.
    Boman, Anders
    Unit of Occupational and Environmental Dermatology Karolinska Institutet.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hökfelt, Tomas
    Department of Neuroscience Karolinska Institutet.
    Norlind, Klas
    Unit of Dermatology and Venerology Karolinska Institutet.
    Galanin Expression in a Murine Model of Allergic Contact Dermatitis2004In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 84, p. 428-432Article in journal (Refereed)
  • 19.
    El-Salhy, Magdy
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Tjomsland, Vegard
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Gastroenterology and Hepatology.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Effects of triple treatment with octreotide, galanin and serotonin on a human pancreas cancer cell line in xenografts2005In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, Vol. 20, no 3, p. 745-752Article in journal (Refereed)
    Abstract [en]

    Human pancreas cancer cells were implanted s.c. in nude mice. After 11 days, the mice were divided into two groups of 13. The first group received sterile saline solution and the second received triple therapy containing octreotide, galanin and serotonin, 40 μg/kg/day as a continuous i.p. infusion via an implanted osmotic pump for 14 days. Triple therapy prolonged the survival rate of the mice bearing human pancreatic carcinoma. Both the volume and weight of tumours in mice given triple therapy were less than in controls (not statistically significant). The proliferation index and the labelling index for epidermal growth factor (EGF) increased significantly in mice given triple therapy vis-á-vis controls. There was no statistically significant difference between control and treated tumours as regards, apoptotic index, necrosis, or number of tumour blood vessels. The increased survival rate was attributed to the reduced tumour load, since both weight and volume were reduced. It is most probable that octreotide was the responsible agent. Further investigation with single and double combinations of octreotide, galanin and serotonin are needed to identify the cause of increased cell proliferation in tumours subjected to these bioactive substances. Identifying the agent(s) inducing pancreatic cancer cell proliferation may be useful in combining a new treatment, as antagonists to these bioactive substances are available.

  • 20.
    Evaldsson, Chamilly
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Rydén, I.
    Division of Clinical Chemistry, Kalmar County Hospital, 391 85 Kalmar, Sweden.
    Uppugunduri, Srinivas
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Anti-inflammatory effects of exogenous uridine in an animal model of lung inflammation.2007In: International Immunopharmacology, ISSN 1567-5769, E-ISSN 1878-1705, Vol. 7, no 8, p. 1025-1032Article in journal (Refereed)
    Abstract [en]

    Nucleosides like adenosine, uridine and their nucleotide derivatives (e.g. ATP and UTP) play important roles in many cellular functions, sometimes by acting as signalling molecules through binding to specific P2 nucleotide receptors. P2 receptors are subdivided into P2X and P2Y subfamilies, the latter of which are G-protein coupled receptors. P2Y receptors and nucleoside transporters have been detected in human and rat lungs, where they mediate effects of interest in airway diseases. The aim of this study was to investigate whether uridine has any anti-inflammatory properties in an asthma-like animal model of lung inflammation.

    The Sephadex-induced lung inflammation model in Sprague-Dawley rats was chosen mainly due to its localised inflammatory response and uridine's limited oral bioavailability. The dextran beads, with or without the addition of uridine, were instilled intratracheally into the lungs, which were excised and examined after 24 h.

    Sephadex alone led to massive oedema and infiltration of macrophages, neutrophils and eosinophils. Microgranulomas with giant cell formations were clearly visible around the partially degraded beads. Uridine reduced both the oedema and the infiltration of leukocytes significantly, measured as lung wet weight and leukocyte counts in bronchoalveolar lavage fluid, respectively. Uridine appeared to affect the tumour necrosis factor (TNF) levels, although this could not be statistically confirmed due to large variations within the Sephadex control group.

    We conclude that uridine has anti-inflammatory effects, and that the exact mechanism(s) of action requires further study.

  • 21. Farley, JR
    et al.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Effects of tunicamycin, mannosamine, and other inhibitors of glycoprotein processing on skeletal alkaline phosphatase in human osteoblast-like cells2005In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 76, no 1, p. 63-74Article in journal (Refereed)
    Abstract [en]

    Skeletal alkaline phosphatase (sALP) is a glycoprotein - ∼20% carbohydrate by weight, with five presumptive sites for N-linked glycosylation, as well as a carboxy-terminal site for attachment of the glycolipid structure (glycosylphosphatidylinositol, GPI), which anchors sALP to the outer surface of osteoblasts. The current studies were intended to characterize the effects of inhibiting glycosylation and glycosyl-processing on the synthesis, plasma membrane attachment, cellular-extracellular distribution, and reaction kinetics of sALP in human osteosarcoma (SaOS-2) cells. sALP synthesis, glycosylation, and GPI-anchor attachment were assessed as total protein synthesis/immunospecific sALP synthesis, sialic acid content (i.e., wheat germ agglutinin precipitation), and insolubility (i.e., temperature-dependent phase-separation), respectively. sALP reaction kinetics were characterized by analysis of dose-dependent initial velocity data, with a phosphoryl substrate. The results of these studies revealed that the inhibition of either N-linked glycosylation or oligosaccharide synthesis for GPI-anchor addition could affect the synthesis and the distribution of sALP, but not the kinetics of the phosphatase reaction. Tunicamycin - which blocks N-linked glycosylation by inhibiting core oligosaccharide synthesis - decreased cell layer protein and the total amount of sALP in the cells, while increasing the relative level of sALP in the cell-conditioned culture medium (CM, i.e., the amount of sALP released). These effects were attributed to dose- and time-dependent decreases in sALP synthesis and N-linked glycosylation, and an increase in apoptotic cell death (P < 0.001 for each). In contrast to the effects of tunicamycin on N-linked glycosylation, the effects of mannosamine, which inhibits GPI-anchor glycosylation/formation, included (1) an increase in cell layer protein, (2) decreases in sALP specific activity, in the cells and in the CM, and (3) increases in the percentages of both anchorless and wheat germ agglutinin (WGA)-soluble sALP in the medium, but not in the cells (P < 0.005 for each). These effects of mannosamine were, presumably, a consequence of inhibiting the insertion/attachment of sALP to the outside of the plasma membrane surface. Neither mannosammine nor tunicamycin had any effect on the reaction kinetics of sALP or on the apparent affinity (the value of KM) for the phosphoryl substrate.

  • 22. Fransson, M
    et al.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Andersson, L
    Laboratory evaluation of a new evidential breath-alcohol analyser designed for mobile testing - The Evidenzer2005In: Medicine, Science and the Law, ISSN 0025-8024, E-ISSN 2042-1818, Vol. 45, no 1, p. 61-70Article in journal (Refereed)
    Abstract [en]

    The Evidenzer is a new kind of forensic breath-alcohol analyser, designed for use both at a police station (stationary) and also in a police vehicle (mobile) at the roadside. In this paper we report the accuracy and precision of the Evidenzer, determined under controlled laboratory conditions. The results were compared with a well-established breath-alcohol instrument (Intoxilyzer 5000S) and also with the concentration of alcohol in venous blood. Twenty healthy volunteers (10 men and 10 women) consumed ethanol (0.4 g/kg) in 15 minutes starting two to three hours after their last meal. Venous blood and breath were obtained for determination of ethanol at 15-30 minute intervals for up to four hours post-dosing. There was a good overall agreement between the two breath-alcohol instruments and the mean bias was only 0.003 mg/L (95% limits of agreement of -0.016 to 0.023 mg/L). The standard deviation (SD) of measuring ethanol in breath was about the same for both instruments, being 0.006 mg/L, and this corresponds to a relative precision or coefficient of variation (CV) of 4.7%. When the Evidenzer was used to analyse ethanol vapour (0.50 mg/L) generated from a wet-bath simulator, i.e. in-vitro conditions, the coefficient of variation was 0.7% indicating high analytical precision. The concentration of ethanol in venous blood and breath were highly correlated (r=0.95) although systematic differences existed depending on time after drinking when comparisons were made. Both breath-alcohol instruments gave results higher than venous blood alcohol in tests made at 15 minutes after the end of drinking whereas at all later times the venous blood-alcohol concentration was higher than the breath instrument readings. These observations can be explained by the time necessary for ethanol to equilibrate between arterial blood and tissue water and by the resulting arterial-venous differences. The time-course of alcohol concentration in arterial blood runs closer to the breath-alcohol concentration rather than the venous blood draining the forearm muscle tissue. The new Evidenzer instrument was easy to operate and gave accurate and precise results compared with Intoxilyzer 5000S.

  • 23. Fremner, Eva
    et al.
    Kalerud, Bo
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Total quality assurance in a distributed point-of-care testing laboratory organization in primary health care. A 10-year experience2004In: Point of care, ISSN 1533-029X, Vol. 3, p. 99-114Article in journal (Refereed)
  • 24.
    Grodzinsky, Ewa
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Wiréhn, Ann-Britt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Fremner, Eva
    Haglund, S
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Persson, L-G
    Borgquist, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, General Practice. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, Unit of Research and Development in Local Health Care, County of Östergötland.
    Point-of-care testing has a limited effect on time to clinical decision in primary health care2004In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 6, p. 547-551Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the clinical logistics of laboratory routines at primary health care centres (PHCs). Design and methods: Prospective registration was carried out for each PHC using questionnaires during 2-week intervals between the end of November 2001 and mid-January 2002. The study included 9 PHCs in the county of Östergötland and 4 in the county of Jönköping, Sweden, with different numbers of blood tests analysed using point-of-care testing (POCT). Data for B-glucose, HbA1c, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), thyroid-stimulating hormone (TSH), T4, cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were collected. Main outcome measures were median time from sampling to available test result (TATa) and median time from sampling to clinical decision (TATd), and the proportion of patients informed of the outcome of the blood test in question during the sampling occasion. Results: A total of 3542 samples were collected. The median TATa showed that B-glucose, ESR and CRP were immediately analysed at all 13 PHCs. For the other tests, TATa varied from immediately to about two days. The median TATd varied from immediately to about a week. When POCT was used, 30% of the patients were informed about the outcome of the test during the sampling occasion. Conclusion: POCT has a limited effect on the clinical logistics in PHCs.

  • 25.
    Haarhaus, Mathias
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Fernström, Anders
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Magnusson, Martin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology.
    Evaluation of bio-intact (1-84) parathyroid hormone, vitamin D status and bond mineral density in patients with predialysis chronic renal failure2004In: ASN Renal Week,2004, 2004Conference paper (Other academic)
  • 26.
    Hansson, Kenny
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Johansen, Knut
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Wetterö, Jonas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Klenkar, Goran
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics.
    Benesch, Johan
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
    Lundström, Ingemar
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics.
    Surface plasmon resonance detection of blood coagulation and platelet adhesion under venous and arterial shear conditions2007In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 23, no 2, p. 261-268Article in journal (Refereed)
    Abstract [en]

    A surface plasmon resonance (SPR) based flow chamber device was designed for real time detection of blood coagulation and platelet adhesion in platelet rich plasma (PRP) and whole blood. The system allowed the detection of surface interactions throughout the 6 mm length of the flow chamber. After deposition of thromboplastin onto a section of the sensor surface near the inlet of the flow chamber, coagulation was detected downstream of this position corresponding to a SPR signal of 7 to 8 mRIU (7 to 8 ng/mm2). A nonmodified control surface induced coagulation 3.5 times slower. Platelet adhesion to gold and fibrinogen coated surfaces in the magnitude of 1.25 and 1.66 mRIU was also shown with platelets in buffer, respectively. SPR responses obtained with PRP and whole blood on surfaces that were methylated or coated with von Willebrand factor (vWF), fibrinogen, or collagen, coincided well with platelet adhesion as observed with fluorescence microscopy in parallel experiments. The present SPR detection equipped flow chamber system is a promising tool for studies on coagulation events and blood cell adhesion under physiological flow conditions, and allows monitoring of short-range surface processes in whole blood. © 2007 Elsevier B.V. All rights reserved.

  • 27.
    Hansson, Kenny
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Tosatti, Samuele
    Isaksson, Joakim
    Linköping University, The Institute of Technology. Linköping University, Department of Science and Technology.
    Wetterö, Jonas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Textor, Marcus
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Tengvall, Pentti
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics.
    Whole blood coagulation on protein adsorption-resistant PEG and peptide functionalised PEG-coated titanium surfaces2005In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 26, no 8, p. 861-872Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate whole blood coagulation on low blood plasma protein adsorbing surfaces. For this purpose, the polycationic graft copolymer poly(L-lysine)-g-poly(ethylene glycol) (PLL-g-PEG), PLL-g-PEG grafted with a cell adhesive peptide containing the amino acid sequence -Arg-Gly-Asp- (RGD), and PLL-g-PEG with a control peptide -Arg-Asp-Gly- (RDG) were adsorbed onto titanium (oxide), forming stable monomolecular adlayers through electrostatic attraction. Free oscillation rheometry and complementary techniques were used to measure the coagulation time (CT) and other interactions of the surfaces with native whole blood, recalcified platelet-rich plasma (PRP), and recalcified citrated platelet-free plasma (PFP). The results show that the uncoated titanium surfaces (reference) activated platelets and quickly triggered the coagulation cascade via the intrinsic pathway, whereas the PLL-g-PEG surfaces displayed a prolonged CT, approximately 2-3 times longer compared to uncoated titanium. We hypothesise that blood coagulates outside the vascular system independent of low protein adsorption to or activation by surfaces, due to the absence of an active down-regulation of procoagulative processes by the vascular endothelium.

  • 28. Hillarp, Andreas
    et al.
    Egberg, Nils
    Nordin, Gunnar
    Stigendal, Lennart
    Fagerberg, Inger
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Local INR calibration of the Owren type prothrombin assay greatly improves the intra- and interlaboratory variation2004In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 91, no 2, p. 300-307Article in journal (Refereed)
    Abstract [en]

    In 1999, a simplified procedure for calibration of the Owren prothrombin time (Owren PT) assay was introduced by a working group of the organisation for national quality assurance in laboratory medicine in Sweden. The new protocol allowed local calibration by means of only two lyophilised national plasma calibrators and expression of results as an international normalized ratio (INR). This is our report of a three-year follow-up involving the analysis of data from all laboratories, in hospitals (n=88 in 2002) and primary health care units (n=246 in 2002) that perform the Owren PT assay in Sweden. The interlaboratory variation was significantly improved after the introduction of the new calibration procedure. For the larger hospital-based laboratories, the mean coefficient of variation (CV) was reduced from 7.9% to 5.2% (p<0.0001) when analysing test materials with INR range 2-4. In the higher INR range (>4), the CV was reduced even further, from 10.4% to 6.8% (p<0.0001). The corresponding results from smaller laboratories in the primary health care units showed a similar decrease in CV from 8.2% to 5.7% in the INR range 2-4 (p<0.0001). At the INR range >4, the CV was reduced from 9.5% to 7.8%. The intralaboratory variation was also improved for both types of laboratory categories. This study shows an improved precision, with CV less than 6% at the therapeutic INR range, for both hospital-based laboratories and smaller laboratories in the primary health care system. The results indicate that the Owren PT assay is well suited for local INR calibration employing only two calibrant plasmas in a simplified procedure.

  • 29. Holmberg, K
    et al.
    Kuteeva, E
    Brumovsky, P
    Kahl, U
    Karlström, H
    Lucas, G A
    Rodriquez, J
    Westerblad, H
    Hilke, Susanne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Berge, O-G
    Lendahl, U
    Bartfai, T
    Hökfelt, T
    Generation and phenotypic characterization of a galanin overexpressing mouse2005In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 133, no 1, p. 59-77Article in journal (Refereed)
    Abstract [en]

    In most parts of the peripheral nervous system galanin is expressed at very low levels. To further understand the functional role of galanin, a mouse overexpressing galanin under the platelet-derived growth factor-B was generated, and high levels of galanin expression were observed in several peripheral tissues and spinal cord. Thus, a large proportion of neurons in autonomic and sensory ganglia were galanin-positive, as were most spinal motor neurons. Strong galanin-like immunoreactivity was also seen in nerve terminals in the corresponding target tissues, including skin, blood vessels, sweat and salivary glands, motor end-plates and the gray matter of the spinal cord. In transgenic superior cervical ganglia around half of all neuron profiles expressed galanin mRNA but axotomy did not cause a further increase, even if mRNA levels were increased in individual neurons. In transgenic dorsal root ganglia galanin mRNA was detected in around two thirds of all neuron profiles, including large ones, and after axotomy the percentage of galanin neuron profiles was similar in overexpressing and wild type mice. Axotomy reduced the total number of DRG neurons less in overexpressing than in wild type mice, indicating a modest rescue effect. Aging by itself increased galanin expression in the superior cervical ganglion in wild type and transgenic mice, and in the latter also in preganglionic cholinergic neurons projecting to the superior cervical ganglion. Galanin overexpressing mice showed an attenuated plasma extravasation, an increased pain response in the formalin test, and changes in muscle physiology, but did not differ from wild type mice in sudomotor function. These findings suggest that overexpressed galanin in some tissues of these mice can be released and via a receptor-mediated action influence pathophysiological processes. © 2005 Published by Elsevier Ltd on behalf of IBRO.

  • 30. Holmgren, A
    et al.
    Holmgren, P
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Ahlner, Johan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Predominance of illicit drugs and poly-drug use among drug-impaired drivers in Sweden2007In: Traffic Injury Prevention, ISSN 1538-9588, E-ISSN 1538-957X, Vol. 8, no 4, p. 361-367Article in journal (Refereed)
    Abstract [en]

    Objective. After Sweden's zero-tolerance law came into force (1 July 1999), the number of cases of driving under the influence of drugs (DUID) submitted by the police for toxicological analysis increased more than 10-fold. This prompted an in-depth investigation into the kinds of drugs used by DUID offenders, whether licit or illicit, and the frequency of their occurrence. Methods. All blood samples from DUID suspects sent by the police for toxicological analysis over a 4-year period (2001-2004) were investigated (N = 22,777 cases). Specimens of blood or urine were subjected to a broad screening analysis by immunoassay methods aimed at detecting amphetamines, cannabis, opiates, cocaine metabolite, and the major benzodiazepines. All positive results from the screening stage were verified by use of more specific analytical methods (e.g., GC-MS, LC-MS, GC-FID, and GC-NPD). Results. Between 80 and 85% of all the blood samples contained at least one banned substance and many contained two or more therapeutic and/or illicit drugs. About 15% of cases were negative for drugs, although these frequently (30-50%) contained ethanol above the legal limit for driving in Sweden, which is 0.20 mg/g (0.02 g%). Amphetamine was the most prominent illicit drug seen in 55-60% of cases either alone or together with other drugs of abuse. Stimulants like cocaine and/or its metabolite were infrequently encountered (1.2% of cases). The next most prevalent illicit drug was cannabis, with positive results for tetrahydrocannabinol (THC) in blood either alone (4%) or together with other psychoactive substances (20%). Morphine, codeine, and/or 6-acetyl morphine were identified in 2% of all DUID suspects, being indicative of heroin abuse. The major prescription drugs identified in blood were benzodiazepines (10%) as exemplified by diazepam, alprazolam, nitrazepam, and flunitrazepam. Drugs for treating insomnia, zolpidem and zopiclone, were also identified in blood samples from DUID suspects over the study period. Other therapeutic agents were encountered in only 1-2% of all cases. Conclusions. The dramatic increase in DUID after the zero-tolerance law came into force probably reflects enhanced police activity and more enthusiasm to apprehend and charge individuals for this offence. Illicit drugs, particularly amphetamine and cannabis, and poly-drug use were predominant compared with use of scheduled prescription drugs. The typical DUID offender in Sweden abuses central stimulants, particularly amphetamine, and has probably done so over many years. Options for treating offenders for their underlying substance abuse problem should be considered instead of the more conventional penalties for drug-impaired driving.

  • 31.
    Håkansson, Annika
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Håkansson, Leif
    Gustafsson, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Kågedal, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Bcl-2 monitoring in malignant melanoma2004In: Hospital Pharmacy, ISSN 0018-5787, E-ISSN 1945-1253, p. 46-47Article in journal (Other academic)
  • 32. Ifversen, Marianne RS
    et al.
    Kågedal, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Christensen, Lisa D
    Rechnitzer, Catherine
    Petersen, Bodil L
    Heilmann, Carsten
    Comparison of immunocytochemistry, real-time quantitative RT-PCR and flow cytometry for detection of minimal residual disease in neuroblastoma2005In: International Journal of Oncology, ISSN 1019-6439, Vol. 27, no 1, p. 121-129Article in journal (Refereed)
  • 33.
    Islam, Quamrul
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Islam, Khaleda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Sharp, C A
    Epigenetic reprogramming of nonreplicating somatic cells for long-term proliferation by temporary cell-cell contact2007In: Stem Cells and Development, ISSN 1547-3287, Vol. 16, no 2, p. 253-268Article in journal (Refereed)
    Abstract [en]

    Embryonic stem (ES) cells are potential sources of tissue regeneration, however, transplanted ES cells produce tumors in the host tissues. In addition, transplantation between genetically unrelated individuals often results in graft rejection. Although the development of patient specific stem cell lines by somatic cell nuclear transfer (SCNT) represents a means of overcoming the problem of rejection, its human application has ethical dilemmas. Adult stem (AS) cells can also differentiate into specialized cells and may provide an alternative source of cells for human applications. In common with other somatic cells, AS cells have limited capacity for proliferation and cannot be produced in large quantities without genetic manipulation. We demonstrate here that nonreplicating mammalian cells can be reprogrammed for long-term proliferation by temporary cell-cell contact through co-culture of AS cells with the GM05267-derived F7 mouse cell line. Subsequent elimination of F7 cells from the co-culture allows proliferation of previously nonreplicating cells, colonies of which can be isolated to produce cell lines. We also demonstrate that the epigenetically reprogrammed AS cells, without the physical transfer of either nuclear or cytoplasmic material from other cells, are capable of long-term proliferation and able to relay signals to other nonreplicating cells to reinitiate proliferation with no addition of recombinant factors. The reported cell amplification procedure is methodologically simple and can be easily reproduced. This procedure allows the production of an unlimited number of cells from a limited number of AS cells, making them an ideal source of cells for applications involving autologous cell transplantation. © Mary Ann Liebert, Inc.

  • 34.
    Islam, Quamrul
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Meirelles, L DA S
    Nardi, NB
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Islam, Khaleda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Polyethylene glycol-mediated fusion between primary mouse mesenchymal stem cells and mouse fibroblasts generates hybrid cells with increased proliferation and altered differentiation2006In: Stem Cells and Development, ISSN 1547-3287, Vol. 15, no 6, p. 905-919Article in journal (Refereed)
    Abstract [en]

    Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into different cell lineages with the appropriate stimulation in vitro. Transplantation of MSCs in human and other animal models was found to repair tissues through the fusion of transplanted MSCs with indigenous cells. We have generated mouse-mouse hybrid cell lines in vitro by polyethylene glycol-mediated fusion of primary mouse MSCs with mouse fibroblasts to investigate the characteristics of hybrid cells, including their potentials for proliferation and differentiation. Similar to the parental MSCs, hybrid cells are positive for the cell-surface markers CD29, CD44, CD49e, and Sca-1, aed negative for Gr1, CD11b, CD13, CD18, CD31, CD43, CD45, CD49d, CD90.2, CD445M/B220, and CD117 markers. The hybrid cells also produce a high level of tissue nonspecific alkaline phosphatase compared to the parental cells. Conditioned medium of hybrid cells contain biologically active factors that are capable of stimulating proliferation of other cells. Although the parental MSCs can differentiate into adipogenic and osteogenic lineages, hybrid cells held disparate differentiation capacity. Hybrid cell lines in general have increased proliferative capacity than the primary MSCs. Our study demonstrates that proliferative hybrid cell lines can be generated in vitro by induced fusion of both im-mortal and primary somatic cells with primary MSCs. © Mary Ann Liebert, Inc.

  • 35.
    Islam, Quamrul
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Panduri, V
    Islam, Khaleda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Generation of somatic cell hybrids for the production of biologically active factors that stimulate proliferation of other cells2007In: Cell Proliferation, ISSN 0960-7722, E-ISSN 1365-2184, Vol. 40, no 1, p. 91-105Article in journal (Refereed)
    Abstract [en]

    Objective: Some normal somatic cells in culture divide a limited number of times before entering a non-dividing state called replicative senescence and fusion of normal cells with immortal cells claimed to produce hybrid cells of limited proliferation. We reinvestigated the proliferative capacity of hybrid cells between normal cell and immortal cell. Materials and Methods: Normal pig fibroblast cells and cells of immortal mouse fibroblast cell line F7, a derivative of GM05267, were fused by polyethylene glycol treatment and subsequently the fused cells were cultured in a selective medium containing hypoxanthine-aminopterin-thymidine in order to enrich the hybrid cells. The hybrid cells were then monitored for chromosome content and proliferation. Results: Cytogenetic analysis revealed that the hybrid cells contained polyploidy chromosomes derived from normal pig fibroblasts. These hybrid cells exhibit no sign of replicative senescence after more than 190 population doublings in vitro. Instead, these hybrid cells have an accelerated growth and proliferate even in the complete absence of glutamine. In addition, these hybrids produce biologically active factors in the conditioned media, which not only can accelerate their own proliferation but also can reinitiate mitotic activity in the senescent-like normal fibroblast cells. Conclusions: Our results question the validity of cellular senescence as a dominant trait. Additionally, the generation of hybrid cells using the specific mouse cell line can be applied to the generation of hybrids with other normal cell types and can be used to produce tissue-specific growth-factor(s) to extend the lifespan and/or improve the proliferation of various normal cells, including adult stem cells. © 2007 The Authors.

  • 36.
    Islam, Quamrul
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Ringe, J
    Reichmann, E
    Migotti, R
    Sittinger, M
    da S. Meirelles, L
    Nardi, N B
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Islam, Khaleda
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Functional characterization of cell hybrids generated by induced fusion of primary porcine mesenchymal stem cells with an immortal murine cell line2006In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 326, no 1, p. 123-137Article in journal (Refereed)
    Abstract [en]

    Bone marrow mesenchymal stem cells (MSC) integrate into various organs and contribute to the regeneration of diverse tissues. However, the mechanistic basis of the plasticity of MSC is not fully understood. The change of cell fate has been suggested to occur through cell fusion. We have generated hybrid cell lines by polyethylene-glycol-mediated cell fusion of primary porcine MSC with the immortal murine fibroblast cell line F7, a derivative of the GM05267 cell line. The hybrid cell lines display fibroblastic morphology and proliferate like immortal cells. They contain tetraploid to hexaploid porcine chromosomes accompanied by hypo-diploid murine chromosomes. Interestingly, many hybrid cell lines also express high levels of tissue-nonspecific alkaline phosphatase, which is considered to be a marker of undifferentiated embryonic stem cells. All tested hybrid cell lines retain osteogenic differentiation, a few of them also retain adipogenic potential, but none retain chondrogenic differentiation. Conditioned media from hybrid cells enhance the proliferation of both early-passage and late-passage porcine MSC, indicating that the hybrid cells secrete diffusible growth stimulatory factors. Murine F7 cells thus have the unique property of generating immortal cell hybrids containing unusually high numbers of chromosomes derived from normal cells. These hybrid cells can be employed in various studies to improve our understanding of regenerative biology. This is the first report, to our knowledge, describing the generation of experimentally induced cell hybrids by using normal primary MSC. © Springer-Verlag 2006.

  • 37.
    Jennersjö, Cecilia
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Fagerberg, Inger
    Karlander, Sven
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Normal D-dimer concentration is a common finding in symptomatic outpatients with distal deep vein thrombosis2005In: Blood Coagulation and Fibrinolysis, ISSN 0957-5235, E-ISSN 1473-5733, Vol. 16, no 7, p. 517-523Article in journal (Refereed)
    Abstract [en]

    The D-dimer analysis has been shown to have a high sensitivity and a high negative predictive value for the exclusion of deep vein thrombosis (DVT). However, most D-dimer studies, including recent clinical management studies, are performed without examination of the calf veins and/or performed on patient populations with a predominance of proximal DVT. The purpose of this study was to evaluate the diagnostic performance of the D-dimer test in a population with a suspected high incidence of distal DVT. In the present study, 393 outpatients with clinically suspected symptomatic DVT of the lower extremities were examined with whole-leg duplex ultrasonography. The D-dimer analysis was performed using an automated micro-latex assay (Tina-quant). A total of 137 of 393 patients had a proven DVT, with the majority presenting with distal DVT (59%). Twenty-eight out of 81 patients with distal DVT had a normal D-dimer, compared with two of 56 patients with proximal DVT. The sensitivity for distal DVT was only 65% compared with 96% for proximal DVT, the negative predictive values were 84 and 99%, respectively. In conclusion, the prevalence of distal DVT in a study population seems to have a great impact on the diagnostic performance of the D-dimer analysis. The study results also show that normal D-dimer levels do not exclude distal DVT in outpatients, instead, it can be hypothesized that normal D-dimer levels exclude DVT that require treatment, as indicated by the good outcome in recent management studies. © 2005 Lippincott Williams & Wilkins.

  • 38.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Age- and gender-related differences in blood amphetamine concentrations in apprehended drivers: Lack of association with clinical evidence of impairment2007In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 102, no 7, p. 1085-1091Article in journal (Refereed)
    Abstract [en]

    Background: New legislation aimed at combating driving under the influence of drugs (DUID) in Sweden stipulated zero-concentrations in blood for scheduled substances. DUID suspects (n = 300), with amphetamine as the only psychoactive drug identified in blood, were investigated in relation to age and gender. In a smaller retrospective sample (n = 70) the relationship between clinical tests of impairment were compared with the concentration of amphetamine in blood. Measurements: All forensic blood samples were subjected to a broad toxicological screening analysis by immunoassay methods [enzyme multiplied immunoassay technique/cloned enzyme donor immunoassay (EMIT/CEDIA)] and positive results were verified by gas chromatography-mass spectrometry (GC-MS). The limit of quantitation (LOQ) for determination of amphetamine in blood was 0.03 mg/l. People suspected of being under the influence of drugs were examined by a physician who asked various questions about state of health and use of drugs and also administered simple psychomotor and cognitive tests of impairment. After conducting these tests the physician concluded whether the suspects were not impaired, slightly, moderately or highly impaired by drugs other than alcohol. Findings: Among 300 DUID suspects with amphetamine in blood there were 246 men (82%) and 54 women (18%). Mean age (± SD) of the men was 37.1 ± 8.7 years compared with 35.5 ± 7.1 years for the women (P > 0.05). The frequency distribution of blood amphetamine concentration was positively skewed with mean, median and highest values of 1.0 mg/l, 0.9 mg/l and 7.1 mg/l, respectively. The mean concentrations were slightly higher in the women 1.11 mg/l (median 1.0 mg/l) compared with 0.97 mg/l (median 0.8 mg/l) in the men (P > 0.05). There was a weak but statistically significant correlation between the person's age and the concentration of amphetamine in blood (r = 0.18, P < 0.05). The results of clinical tests of impairment showed no relationship with the concentration of amphetamine in blood according to analysis of variance (P > 0.05). Conclusions: The lack of association between degree of drug influence and the concentration of amphetamine in blood speaks against the notion of introducing concentration per se limits or graded penalties depending on the blood-concentration of this stimulant. Zero-concentration limits or LOQ-limits are a much more pragmatic way to enforce DUID legislation. © 2007 The Author.

  • 39.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Are changes in blood-ethanol concentration during storage analytically significant? Importance of method imprecision2007In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 45, no 10, p. 1299-1304Article in journal (Refereed)
    Abstract [en]

    Background: Knowledge about the stability of drugs and metabolites in biological fluids is important information when the analytical results are evaluated and interpreted. This study examines changes in blood-ethanol concentration (BEC) during the storage of specimens for up to 12 months at 4°C. Methods: Venous blood samples were taken from drunk drivers in evacuated glass tubes containing sodium fluoride and potassium oxalate as chemical preservatives. The concentrations of ethanol in blood were determined in duplicate by headspace gas chromatography on arrival at the laboratory and again after storage in a refrigerator at 4°C for up to 12 months. Results: The relationship between the standard deviation (SD) of analysis of ethanol at concentration intervals of 0.2 mg/g (BEC) was defined by the linear regression equation SD=0.00243+0.0104 BEC (r=0.99). At a mean BEC of 1.64 mg/g, the SD was 0.019 mg/g which corresponds to a coefficient of variation of 1.1%. The mean decrease in BEC (±SD) between first and second analysis was 0.105± 0.0686 mg/g (t=19.3, d.f.=158, p

  • 40.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Crème de la crème in forensic science and legal medicine: The most highly cited articles, authors and journals 1981-20032005In: International journal of legal medicine (Print), ISSN 0937-9827, E-ISSN 1437-1596, Vol. 119, no 2, p. 59-65Article in journal (Refereed)
    Abstract [en]

    The importance and prestige of a scientific journal is increasingly being judged by the number of times the articles it publishes are cited or referenced in articles published in other scientific journals. Citation counting is also used to assess the merits of individual scientists when academic promotion and tenure are decided. With the help of Thomson, Institute for Scientific Information (Thomson ISI) a citation database was created for six leading forensic science and legal medicine journals. This database was used to determine the most highly cited articles, authors, journals and the most prolific authors of articles in the forensic sciences. The forensic science and legal medicine journals evaluated were: Journal of Forensic Sciences (JFS), Forensic Science International (FSI), International Journal of Legal Medicine (IJLM), Medicine, Science and the Law (MSL), American Journal of Forensic Medicine and Pathology (AJFMP), and Science and Justice (S&J). The resulting forensics database contained 14,210 papers published between 1981 and 2003. This in-depth bibliometric analysis has identified the crème de la crème in forensic science and legal medicine in a quantitative and objective way by citation analysis with focus on articles, authors and journals. © Springer-Verlag 2005.

  • 41.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Driving under the influence of chlormethiazole2005In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 153, no 2-3, p. 213-217Article in journal (Refereed)
    Abstract [en]

    This article describes a case of driving under the influence of the sedative-hypnotic-anticonvulsant drug chlormethiazole. The suspect, who was a physician, was driving dangerously on a busy highway and caused a traffic collision. When apprehended by the police, the man had bloodshot and glazed eyes and pupil size was enlarged. He could not answer the questions properly and his gait was unsteady. A roadside breath-alcohol screening test was positive but an evidential breath-alcohol test conducted about one hour later was below the legal limit for driving of 0.10 mg/L (10 μg/100 mL or 0.021 g/210 L). Because of the special circumstances of the traffic crash and the man's appearance and behaviour, the police suspected that drugs other than alcohol were involved and obtained a venous blood sample for toxicological analysis. The blood contained 0.23 mg/g alcohol, which is above the legal limit for driving in Sweden 0.20 mg/g (20 mg/100 mL or 0.020 g/100 mL), and codeine was also present at a therapeutic concentration of 0.02 mg/L. The conflict between the clinical signs of impairment and the toxicology report prompted a reanalysis of the blood sample with major focus on sedative-hypnotic drugs. Analysis by capillary GC-NPD identified chlormethiazole at a concentration of 5 mg/L, the highest so far encountered in traffic cases in Sweden. In 13 other impaired driving cases over 10 years the mean (median) and range of concentrations of chlormethiazole were 1.6 mg/L (1.6 mg/L) and 0.3-3.3 mg/L. This case report underscores the need to consider clinical observations and the person's behaviour in relation to the toxicology report when interpreting and testifying in drug-impaired driving cases. © 2005 Elsevier Ireland Ltd. All rights reserved.

  • 42.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances2005In: Traffic Injury Prevention, ISSN 1538-9588, E-ISSN 1538-957X, Vol. 6, no 4, p. 317-322Article in journal (Refereed)
    Abstract [en]

    Objective. This article describes the background and implementation in Sweden of zero-concentration limits for controlled drugs in the blood of drivers. Eliminating the need to prove that a person's ability to drive safely was impaired by drugs has greatly simplified the prosecution case, which now rests primarily on the forensic toxicology report. Driving under the influence of a prescription drug listed as a controlled substance is exempt from the zero-limit law provided the medication was being used in accordance with a physician's direction and the person was not considered unfit to drive. Methods. The prevalence of driving under the influence of drugs (DUID) in Sweden was evaluated from police reports with the main focus on the toxicological findings. A large case series of DUID suspects was compared before and after introducing zero concentration limits in blood for controlled substances on July 1, 1999. The spectrum of drugs used by typical offenders and the concentrations of various licit and illicit substances in blood were evaluated and compared. Results. Immediately after the zero-limit law came into force, the number of cases of DUID submitted by the police for toxicological analysis increased sharply and is currently ten-fold higher than before the new legislation. Statistics show that about 85% of all blood samples sent for toxicological analysis have one or more banned substances present. Amphetamine is by far the leading drug of abuse in Sweden and was identified in about 50-60% of all DUID suspects either alone or together with other controlled substances. The next most frequently encountered illicit drug was tetrahydrocannabinol (THC), with positive findings in about 20-25% of cases. Various prescription drugs, mainly sedative-hypnotics like diazepam and flunitrazepam, were also highly prevalent and these occurred mostly together with illicit substances. Opiates, such as 6-acetyl morphine and morphine, the metabolites of heroin, were high on the list of substances identified. Most DUID suspects in Sweden were men (85%) who were poly-drug users combining illicit substances, like amphetamine and/or cannabis, with a prescription medication such as various benzodiazepines. Conclusions. Sweden's zero-concentration limit has done nothing to reduce DUID or deter the typical offender because recidivism is high in this population of individuals (40-50%). Indeed, many traffic delinquents in Sweden are criminal elements in society with previous convictions for drunk and/or drugged driving as well as other offenses. The spectrum of drugs identified in blood samples from DUID suspects has not changed much since the zero-limit law was introduced. Copyright © 2005 Taylor & Francis Inc.

  • 43.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Impact of JAT publications 1981-2003: The most prolific authors and the most highly cited articles2004In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 28, no 7, p. 541-545Article in journal (Refereed)
    Abstract [en]

    The Journal of Analytical Toxicology (JAT) recently celebrated its 25th anniversary as an international periodical devoted to publishing scholarly articles in the field of analytical and forensic toxicology. Over the years many important papers spanning the entire field of chemical toxicology have appeared in JAT. One way to assess the usefulness of these papers is by looking at the number of times they subsequently become cited in the reference lists of papers published in other peer-reviewed journals including JAT itself (self-citations). The Thomson Institute for Scientific Information (ISI), headquartered in Philadelphia, PA, has produced a citation database containing all JAT articles published between 1981 through 2003 (N = 2254). This database was used to gather information about the most prolific authors of articles appearing in JAT, the most highly cited articles, the inter-relationships between co-authors, and the countries where the work originated. The person listed most frequently as an author was E.J. Cone, who authored or co-authored 69 papers that attracted a total of 1432 citations, giving a citation impact of 20.76. However, the most highly cited article in JAT was a solo-author work from 1981 by M.E. Jolley describing a fluorescence polarization immunoassay for the analysis of therapeutic drugs in plasma, which was cited 184 times. Working and writing in teams can boost the output of scientific articles as exemplified by the Institut de Médecine Légale in Strasbourg with P. Kintz as the driving force. Kintz and his associates produced the most collaborative work published in JAT. Citation analysis is being increasingly used to evaluate the importance of scientific articles and the journals where these works are published (e.g., impact factors). This article has identified JAT's scientific elite as evidenced by the most prolific authors and the most highly cited papers.

  • 44.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Letter: Mode of classification of source material as citable items skews journal impact factor calculations2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 7, p. 623-625Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 45.
    Jones, A Wayne
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences.
    Letter to the editor: Body mass index and blood-alcohol calculations2007In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 31, no 3, p. 177-178Article in journal (Other academic)
    Abstract [en]

    Alcohol tops the list of psychoactive substances encountered in police investigations of crimes such as mugging, murder, sexual assault, and especially impaired driving. Accordingly, the need often arises to interpret a person`s blood-alcohol concentration (BAC) in relation to the degree of alcohol influence and the amount of alcohol consumed. Such calculations are usually done with the aid of so-called “know your limit” or blood-alcohol charts, and more recently, several computer programs have been developed for this purpose.

  • 46.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    The distribution of forensic journals, reflections on authorship practices, peer-review and role of the impact factor2007In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 165, no 2-3, p. 115-128Article in journal (Refereed)
    Abstract [en]

    This article presents information about journals specializing in the forensic sciences and legal medicine, their development and distribution and their current status as reflected in the journal impact factor. The first scientific journal devoted to spreading information and reporting new developments in social and legal medicine seemingly originated in Germany about 150 years ago. The official journal of the American Academy of Forensic Sciences (Journal of Forensic Sciences, JFS) was founded in 1956 and has enjoyed 50 years of scholarly publishing. The two leading European journals specializing in forensics are Forensic Science International (FSI) and International Journal of Legal Medicine (IJLM). Besides the size of the circulation, the readership numbers, the quality of the editorial staff and the peer-reviewers, the number of submitted and accepted manuscripts, considerable interest has focused on the journal's impact factor as a measure of prestige. The 2006 impact factor of a certain journal is derived by counting the number of citations in 2006 to all material published in the journal in the previous 2 years (2004 and 2005) and dividing this total by the number of citable items (articles and reviews) published in the same 2 years. Impact factors for several thousand scientific journals are compiled and published by a company called Thomson Institute for Scientific Information (Thomson ISI) and are available on-line via the database Journal Citation Reports. Forensic journals are grouped within the subject category Medicine, Legal, which currently comprises nine journals a few of which are seemingly unrelated to mainstream forensics. The top-ranked forensic journal in terms of its impact factor was IJLM with a score of just over 2.0 in 2004. This means that the average article published in 2003 and 2002 was cited twice per year in the 2-year window after publication. Impact factors of forensic journals are fairly low in comparison with many other disciplines, probably because of the small size of the field, fewer active researchers and less pressure to publish. The relatively low impact factors of forensic journals should be less of a concern than ensuring that manuscripts receive a rigorous and preferably an open peer-review prior to acceptance for publication. The information, conclusions and opinions published in forensic science journals might one day be proffered as evidence in criminal or civil litigation. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 47.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Urine as a biological specimen for forensic analysis of alcohol and variability in the urine-to-blood relationship2006In: Toxicological Reviews, ISSN 1176-2551, Vol. 25, no 1, p. 15-35Article in journal (Refereed)
    Abstract [en]

    This article concerns the use of urine as a biological specimen for determination of alcohol in clinical and forensic toxicology and discusses factors that might influence variability in the urine/blood concentration ratio of alcohol. A large number of human drinking experiments were conducted to determine the time course of urine-alcohol concentrations (UAC) in relation to blood-alcohol concentrations (BAC). The UAC and BAC curves were shifted in time and the BAC curve always began to decrease before the UAC started to decline. During the early absorption phase the UAC/BAC ratio was less than unity, whereas in the late absorption/ distribution period the ratio was between 1.0-1.2. On reaching the post-absorptive phase, the UAC always exceeded BAC and UAC/BAC ratios averaged 1.3-1.4, increasing appreciably as BAC decreased towards zero. Alcohol-induced diuresis was most pronounced during the rising portion of the BAC curve and near to the peak value. After about 2 hours post-drinking, the production rate of urine diminished to the pre-drinking rate of about 0.5-1 mL/min. Drinking water during the post-absorptive phase of the alcohol curve produced dilute urine, as reflected in lower creatinine content and osmolality, although the concentration of ethanol remained unchanged. After subjects drank a moderate dose of ethanol (0.54-0.85 g/kg) about 2% of the dose was recoverable in the urine after 7 hours. Ethyl glucuronide, a minor metabolite of ethanol, was measured in urine samples from drunk drivers. The UAC/BAC ratio of ethanol in drunk drivers did not depend on the creatinine content of the urine and therefore the relative dilution of the specimens. When alcohol-free urine was spiked with glucose and infected with the yeast species Candida albicans, ethanol was produced by fermentation after approximately 24 hours storage at room temperature. This post-sampling synthesis of ethanol was prevented by sodium fluoride (1% weight by volume) in the urine tubes or by keeping the specimens in the cold (4°C). The UAC and BAC were highly correlated (r > 0.95) in drunk drivers and in autopsy cases, although the residual standard deviations were appreciable. This speaks against attempting to estimate BAC indirectly from UAC in any individual case. The UAC/BAC ratio and the change in UAC between two successive voids can help to resolve whether a large amount of alcohol had recently been consumed. This information is useful to support or challenge allegations of drinking alcohol after driving, which has become known as the hip-flask defence.

  • 48.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Which articles and which topics in the forensic sciences are most highly cited?2005In: Science & justice, ISSN 1355-0306, E-ISSN 1876-4452, Vol. 45, no 4, p. 175-182Article in journal (Other academic)
    Abstract [en]

    Forensic science is a multidisciplinary field, which covers many branches of the pure, the applied and the biomedical sciences. Writing-up and publishing research findings helps to enhance the reputation of the investigators and the laboratories where the work was done. The number of times an article is cited in the reference lists of other articles is generally accepted as a mark of distinction. Indeed, citation analysis has become widely used in research assessment of individual scientists, university departments and entire nations. This article concerns the most highly cited papers published in the Journal of Forensic Sciences (JFS) between 1956 and 2005. These were identified with the help of Web-of-Science, which is the on-line version of Science Citation Index, produced by Thomson Institute for Scientific Information (Thomson ISI) with head offices in Philadelphia, USA. This database tracks, among other things, the annual citation records of articles published in several thousand scientific journals worldwide. Those JFS articles accumulating 50 or more citations were identified and rank-ordered according to the total number of citations. These articles were also evaluated according to the name of first author, the subject category of the article, the country of origin and the pattern of co-authorship. This search strategy located 46 articles cited between 50 and 292 times since they first appeared in print. The most highly cited paper by far was by Kasai, Nakamura and White (USA and Japan) concerning DNA profiling and the application of the polymerase chain reaction (PCR) in forensic science. Some forensic scientists appeared as first author on two to three highly cited articles, namely Wetli (USA), Budowle (USA) and Comey (USA). When the highly cited articles were sub-divided into subject category, 15 were identified as coming from toxicology, closely followed by criminalistics (14 articles), pathology (nine articles), physical anthropology (five articles), forensic psychiatry (two articles) and one from odontology. The number of co-authors on these highly cited articles ranged from one to nine and the names of some investigators appeared on as many as four highly cited papers. The vast majority of papers originated from US laboratories although five came from Japan, two each from Sweden and Canada and there was also a joint USA-Swiss collaboration. The Thompson ISI citation databases provide unique tools for tracking citations to individual articles and impact and citation records of scholarly journals.

  • 49.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Fransson, Monika
    Maldonado-Holmertz, Elisa
    Does consumption of ethanol distort measurements of exhaled nitric oxide?2005In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 99, no 2, p. 196-199Article in journal (Refereed)
    Abstract [en]

    Background: Measuring FENO is a novel and non-invasive way to monitor airway inflammation (e.g. asthma). This clinical study was designed to investigate whether drinking ethanol might distort FENO measurements. Methods: Twenty healthy subjects drank 0.40 g ethanol/kg body weight in 15 min. Measurement of FENO started ∼ 30 min before drinking and at various times afterwards for 4 h post-dosing. Ethanol concentrations were determined in venous blood by gas chromatography and in end-exhaled breath by infra-red spectrometry. Results: The within subject standard deviation for determination of FENO was 1.3 ppb, corresponding to a CV of 7.7%. The mean change in FENO from pre-drinking levels during the 4 h testing was statistically significant (P

  • 50.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Holmgren, A
    Abnormally high concentrations of amphetamine in blood of impaired drivers2005In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 50, no 5, p. 1215-1220Article in journal (Refereed)
    Abstract [en]

    We present a case series (N = 46) of individuals apprehended in Sweden for driving under the influence of drugs (DUID). These cases were selected because the concentrations of amphetamine in blood were abnormally high (> 5.0 mg/L), the highest being 17 mg/L. In comparison, the median blood-amphetamine concentration in a population of DUID offenders (N = 6,613) was 0.70 mg/L. Among the DUID suspects with extremely high blood-amphetamine concentrations there were 38 men (83%) with mean age of 37.8 y (SD 6.8 y) and 8 women (17%) with a mean age of 34.1 y (SD 4.3 y). All had previously been registered in our database (mean 12 times, median 9 times) for drug-related offences, including DUID. The concentration of amphetamine in blood of female offenders was slightly higher than the concentration in male offenders (6.6 mg/L vs. 5.8 mg/L), although this difference was not statistically significant (p > 0.05). The drugs other than amphetamine most frequently encountered in the blood samples were tetrahydrocannabinol and benzodiazepines (diazepam and nordiazepam). The commonest signs of drug use reported by the arresting police officers were bloodshot and glazed (watery) eyes, restlessness, talkativeness, exaggerated reflexes and slurred speech. Unsteady gait and dilated pupils were observed in some but not all individuals. These very high concentrations of amphetamine were tolerated without any fatalities indicating a pronounced adaptation to the pharmacologic effects of this central stimulant. Anecdotal information indicated that those with the very highest concentrations of amphetamine in blood had swallowed the drug to prevent being apprehended in possession of an illicit substance. Copyright © 2005 by ASTM International.

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