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  • 1.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10-year study in primary care2009In: EUROPEAN JOURNAL OF HEART FAILURE, ISSN 1388-9842, Vol. 11, no 4, p. 354-360Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) is common among the elderly patients. It is essential to identify those at high risk in order to optimize the use of resources. We aimed to evaluate whether a combination of two biomarkers might give better prognostic information about the risk of cardiovascular (CV) mortality in patients with symptoms associated with HF, compared with only one biomarker. Four hundred and sixty-four primary health-care patients (mean age 73 years, range 65-87) with symptoms of HF were examined. All patients were evaluated using Doppler echocardiography and blood samples, including measurement of cystatin C and NT-proBNP. The patients were followed over a 10-year period. Patients with serum cystatin C levels within the highest quartile had almost three times the risk (HR: 2.92; 95% CI: 1.23-4.90) of CV mortality compared with those patients who had levels within the first, second, or third quartiles. If, at the same time, the patient had a plasma concentration of NT-proBNP within the highest quartile, the risk increased to andgt; 13 times (HR: 13.61; 95% CI: 2.56-72.24) during 10 years of follow-up or andgt; 17 times (HR: 17.04; 95% CI: 1.80-163.39) after 5 years of follow-up. Combined analysis of cystatin C and NT-proBNP could provide important prognostic information among elderly patients in the community with symptoms of HF.

  • 2.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.2010In: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, ISSN 1473-5733, Vol. 21, no 1, p. 62-9Article in journal (Refereed)
    Abstract [en]

    Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

  • 3.
    Amatya, B
    et al.
    Karolinska University Hospital.
    El-Nour, H
    Karolinska University Hospital.
    Holst, M
    Astrid Lindgren Childrens Hospital.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Nordlind, K
    Karolinska University Hospital.
    Expression of tachykinins and their receptors in plaque psoriasis with pruritus2011In: BRITISH JOURNAL OF DERMATOLOGY, ISSN 0007-0963, Vol. 164, no 5, p. 1023-1029Article in journal (Refereed)
    Abstract [en]

    Pandgt;Background Cutaneous melanoma is rapidly increasing in incidence worldwide and approximately 5% of melanomas are hereditary. Deletions in chromosome 1p36 have been detected in melanoma but no candidate melanoma tumour suppressor gene has yet been found in this area. Recently, strong evidence has been reported that CHD5 is a tumour suppressor gene in this region. Objectives To investigate CHD5 involvement in familial melanoma. Methods Peripheral blood DNA from 47 melanoma families who do not carry mutations in any of the three currently recognized melanoma genes, 398 patients with sporadic melanoma and 398 geographically matched nonmelanoma-bearing controls were studied. Linkage investigation, single nucleotide polymorphism (SNP) genotyping and mutation screening studies were carried out on the CHD5 locus. Results The CHD5 gene was not excluded by linkage analysis in any of the families. On SNP genotyping, the CHD5 rs7513548 SNP was found to be significantly associated with sporadic melanoma (odds ratio 1 center dot 53, 95% confidence interval 1 center dot 13-2 center dot 06). The AG genotype was found in 208 cases and 169 controls (cf. 141 and 175 cases and controls, respectively, for the AA genotype). On CHD5 mutation screening, a total of 50 single-base substitutions were detected. Of these, 39 were intronic and 11 were exonic. While 32 were previously recognized variants, 18 were newly identified. Three, in exons 4, 31 and 32, led to nonsynonymous substitutions. A p.Met1576Ile substitution was identified in a mother and daughter, both with invasive cutaneous melanoma. Conclusions This study appears to be the first report of CHD5 variants in familial cutaneous melanoma. Such CHD5 variants could block or alter the ability of CHD5 to regulate the cell cycle pathway and to effect cellular control. As only one of the 47 families studied has this variant, it appears to be a rare event and further screening of melanoma families is required to confirm whether or not CHD5 is involved in melanoma pathogenesis.

  • 4.
    Andersson, Henrik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Monitoring of troponin release from cardiomyocytes during exposure to toxic substances using surface plasmon resonance biosensing2010In: ANALYTICAL AND BIOANALYTICAL CHEMISTRY, ISSN 1618-2642, Vol. 398, no 3, p. 1395-1402Article in journal (Refereed)
    Abstract [en]

    Troponin T (TnT) is a useful biomarker for studying drug-induced toxicity effects on cardiac cells. We describe how a surface plasmon resonance (SPR) biosensor was applied to monitor the release of TnT from active HL-1 cardiomyocytes in vitro when exposed to cardiotoxic substances. Two monoclonal human TnT antibodies were compared in the SPR immunosensor to analyse the TnT release. The detection limit of TnT was determined to be 30 ng/ml in a direct assay set-up and to be 10 ng/ml in a sandwich assay format. Exposure of the cardiomyocytes to doxorubicin, troglitazone, quinidine and cobalt chloride for periods of 6 and 24 h gave significant SPR responses, whereas substances with low toxicity showed insignificant effects (ascorbic acid, methotrexate). The SPR results were verified with a validated immunochemiluminescence method which showed a correlation of r(2)=0.790.

  • 5.
    Andersson, Henrik
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.
    Steel, Daniella
    Cellartis AB, Gothenburg, Sweden .
    Asp, Julia
    University of Gothenburg.
    Dahlenborg, Kerstin
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Jonsson, Marianne
    University of Gothenburg.
    Jeppsson, Anders
    Sahlgrens University Hospital.
    Lindahl, Anders
    University of Gothenburg.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Sartipy, Peter
    Cellartis AB, Gothenburg, Sweden .
    Mandenius, Carl-Fredrik
    Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, The Institute of Technology.
    Assaying cardiac biomarkers for toxicity testing using biosensing and cardiomyocytes derived from human embryonic stem cells2010In: JOURNAL OF BIOTECHNOLOGY, ISSN 0168-1656, Vol. 150, no 1, p. 175-181Article in journal (Refereed)
    Abstract [en]

    Human embryonic stem cell (hESC) derived cardiomyocytes are in the present study being used for testing drug-induced cardiotoxicity in a biosensor set-up. The design of an in vitro testing alternative provides a novel opportunity to surpass previous methods based on rodent cells or cell lines due to its significantly higher toxicological relevance. In this report we demonstrate how hESC-derived cardiomyocytes release detectable levels of two clinically decisive cardiac biomarkers, cardiac troponin T and fatty acid binding protein 3, when the cardiac cells are exposed to the well-known cardioactive drug compound. doxorubicin. The release is monitored by the immuno-biosensor technique surface plasmon resonance, particularly appropriate due to its capacity for parallel and high-throughput analysis in complex media.

  • 6.
    Appelgren, A
    et al.
    St Eriks Hosp, Orofacial Pain & TMD Ctr, Stockholm, Sweden Karolinska Inst, S-10401 Stockholm, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Appelgren, BH
    St Eriks Hosp, Orofacial Pain & TMD Ctr, Stockholm, Sweden Karolinska Inst, S-10401 Stockholm, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Carleson, J
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lundberg, T
    St Eriks Hosp, Orofacial Pain & TMD Ctr, Stockholm, Sweden Karolinska Inst, S-10401 Stockholm, Sweden Linkoping Univ Hosp, S-58185 Linkoping, Sweden.
    Central and peripheral changes in neuropeptide Y-like immunoreactivity following adjuvant monoarthritis in the rat temporomandibular joint.2002In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 81, p. 3190-Conference paper (Other academic)
  • 7.
    Arbring, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Chaireti, Roza
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    First experience of structured introduction of new oral anticoagulants in a Swedish health care district: dabigatran as an alternative to warfarin in atrial fibrillation2013Conference paper (Refereed)
  • 8.
    Arbring, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Comparison of prothrombin time (INR) results and main characteristics of patients on warfarin treatment in primary health care centers and anticoagulation clinics2013In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 13Article in journal (Refereed)
    Abstract [en]

    Background

    Oral anticoagulant therapy is used to prevent thrombosis in patients with atrial fibrillation (AF), venous thrombosis and prosthetic heart valves. The introduction of new therapies emphasizes the need to discern the best practice for the patients remaining on warfarin treatment. This study compares patient characteristics and therapeutic control in two settings managing warfarin treatment: Swedish primary health care centers (PHCC) and specialized anticoagulation clinics (ACC).

    Methods

    Prothrombin time (PT) test results reported as International Normalized Ratio (INR) were collected for five consecutive days from patients on warfarin treatment; 564 PHCC and 927 ACC patients. Therapeutic control was calculated as PT test results in relation to intended therapeutic range (TR). Mann–Whitney Rank Sum Test and Chi2 test were used for statistical comparisons.

    Results

    The PHCC patients were older than the ACC patients, 76 v. 70 years (p<0.01) with a predominance of men in both groups. The reasons for treating differed between the groups. Seventy-two percent of PHCC patients and 66% of ACC patients had a PT-INR within the intended TR (p<0.05). Men generally had better results than women (72% v. 63%, p<0.001) and particularly in the PHCC group v. the ACC group (78% v. 69%, p<0.01).

    PT-INR above intended TR was significantly more common in the ACC setting, (p<0.05), for women overall (p<0.01), for women in the PHCC setting, and for ACC men (p<0.05).

    Conclusions

    In this study both settings achieved good therapeutic control of warfarin treatment with a minor advantage for PHCC over ACC, and better results for men, especially in the PHCC setting. As patient characteristics differ between the PHCC and ACC, it is important to conduct further randomized studies to discern the best practice locally for warfarin management also after the introduction of new drugs.

  • 9.
    Arvidsson, Sara
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Applied Physics .
    Askendal, Agneta
    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 Clinical and Experimental Medicine, 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 .
    Detection of surface bound complement at increasing serum anticoagulant concentrations2008In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 62, p. 214-219Article in journal (Refereed)
    Abstract [en]

      

  • 10.
    Aspenberg, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Agholme, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics and Sports Medicine. Linköping University, Faculty of Health Sciences.
    Fahlgren, Anna
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Targeting RANKL for reduction of bone loss around unstable implants: OPG-Fc compared to alendronate in a model for mechanically induced loosening2011In: BONE, ISSN 8756-3282, Vol. 48, no 2, p. 225-230Article in journal (Refereed)
    Abstract [en]

    Orthopedic joint prostheses may loosen because of localized bone resorption. Despite initial optimism, there are no reports showing that bisphosphonates can stop the progression of prosthetic loosening once it has begun. This might be due to the strong resorptive stimulus, which continuously recruits new osteoclasts. Therefore, we hypothesized that a treatment targeting osteoclast recruitment would be more efficacious than a treatment reducing osteoclast activity. We used a previously described rat model for instability-induced bone resorption, and compared OPG-Fc with alendronate at a clinically relevant or an extreme dose. A titanium plate was osseointegrated at the rat tibial surface. Instability was simulated by a piston, moving perpendicularly to the bone surface. Piston movement induced bone loss via hydrostatic pressure or fluid flow. Rats were randomized to 5 groups (total n = 56), of which 4 were subjected to instability and one was stable. The unstable groups were injected with either high-dose OPG-Fc (10 mg/kg, twice weekly), a high dose of alendronate (20 mu g /kg/day), an extreme dose of alendronate (200 mu g/kg/day) or saline. Significant protection against resorption could only be shown for OPG-Fc and the extreme alendronate dose. Both alendronate doses reduced serum levels of tartrate-resistant acid phosphatase isoform 5b to a similar extent, demonstrating that the lower dose was able to reduce resorption in the normally remodeling skeleton, although not in the osteolytic lesions caused by instability. Osteoclast numbers in the lesion were increased by the lower bisphosphonate dose and reduced by OPG-Fc. The results suggest the possibility of targeting osteoclast recruitment via the RANKL system in patients with impending prosthetic loosening.

  • 11.
    Astrom, E
    et al.
    Karolinska Institute.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Eksborg, S
    Karolinska University Hospital.
    Soderhall, S
    Karolinska Institute.
    Biochemical bone markers in the assessment and pamidronate treatment of children and adolescents with osteogenesis imperfecta2010In: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 99, no 12, p. 1834-1840Article in journal (Refereed)
    Abstract [en]

    Aim: To assess the role of biochemical bone markers in classification of children with osteogenesis imperfecta (OI), their possible association with vertebral compression fractures in milder forms of OI and their role in monitoring of intravenous pamidronate (APD) treatment. Methods: Serum total alkaline phosphatase (ALP), bone ALP isoforms (in a subgroup), osteocalcin, type I procollagen carboxy-terminal propeptide, carboxy-terminal telopeptide of type I collagen, and urine deoxypyridinoline (DPD) were measured in a cross-sectional study of 130 untreated individuals, 0.25-20.9 years (median 6.7), with OI types I, III and IV. Of those, sixty-nine were also assessed longitudinally during monthly APD treatment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: Significant differences in bone markers, however not sufficient for individual clinical use, were found in the larger untreated group but not between subgroups with or without vertebral compressions. All bone markers decreased during treatment for 1.0-12.5 years, but with different relative amounts. Changes were not correlated to the improvement in BMD, mobility or pain. Conclusion: Bone markers are, despite significant differences, not useful for the classification of OI type in the individual child and are not associated with vertebral compressions. Serum ALP and urinary DPD are sensitive in monitoring bisphosphonate treatment.

  • 12.
    Barklin, A.
    et al.
    Aarhus University Hospital.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Larsson, A.
    Aarhus University Hospital.
    Tyvold, S.
    Norwegian University of Science & Technology.
    Granfeldt, A.
    Aarhus University Hospital.
    Tonnesen, E.
    Aarhus University Hospital.
    Neuropeptides in brain death-induced neurogenic pulmonary edema2009In: in ACTA ANAESTHESIOLOGICA SCANDINAVICA, vol 53, 2009, Vol. 53, p. 45-45Conference paper (Refereed)
    Abstract [en]

    n/a

  • 13.
    Barklin, Anne
    et al.
    Aarhus University Hospital.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Tyvold, Stig S
    Norwegian Univ Science & Technology.
    Larsson, Anders
    Aarhus University Hospital.
    Granfeldt, Asger
    Aarhus University Hospital.
    Sloth, Erik
    Aarhus University Hospital.
    Tonnesen, Else
    Aarhus University Hospital.
    Alteration of Neuropeptides in the Lung Tissue Correlates Brain Death-Induced Neurogenic Edema2009In: JOURNAL OF HEART AND LUNG TRANSPLANTATION, ISSN 1053-2498, Vol. 28, no 7, p. 725-732Article in journal (Refereed)
    Abstract [en]

    Background: increased intracranial pressure induces neurogenic pulmonary edema (NPE), potentially explaining why only lungs from less than 20% of brain dead organ donors can be used for transplantation. This study investigated the underlying mechanisms of NPE, focusing on neuropeptides, which potently induce vasoconstriction, vasodilatation, and neurogenic inflammation. Methods: Brain death was induced in 10 pigs by increasing the intracranial pressure. Eight additional pigs served as controls. Neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and substance P were analyzed in plasma, bronchoalveolar lavage (BAL) fluid, and homogenized lung tissue 6 hours after brain death. Pulmonary oxygen exchange was estimated using partial pressure of arterial oxygen (Pao(2))/fraction of inspired oxygen (FIO2), and pulmonary edema by wet/dry weight ratio. Results: Brain death induced a decrease in PaO2/FIO2 (P less than 0.001) and increased the wet/dry weight of both apical (p = 0.01) and basal lobes (p = 0.03). NPY and CGRP concentrations were higher in the BAL fluid of brain-dead animals compared with controls (p = 0.02 and p = 0.02) and were positively correlated with the wet/dry weight ratio. NPY content in lung tissue was lower in brain-dead animals compared with controls (p = 0.04) and was negatively correlated with the wet/dry weight ratio. There were no differences in substance P concentrations between the groups. Conclusion: NPY was released from the lung tissue of brain-dead pigs, and its concentration was related to the extent of pulmonary edema. NPY may be one of several crucial mediators of neurogenic pulmonary edema, raising the possibility of treatment with NPY-antagonists to increase the number of available lung donors.

  • 14.
    Bastami, Salumeh
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Frödin, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Topical morphine gel in the treatment of painful leg ulcers, a double-blind, placebo-controlled clinical trial: a pilot study2012In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 9, no 4, p. 419-427Article in journal (Refereed)
    Abstract [en]

    Chronic painful wounds, a major health problem, have a detrimental impact on the quality of life due to associated pain. Some clinical reports have suggested that local administration of morphine could be beneficial. The aim of this study was to evaluate the analgesic effect of topically applied morphine on chronic painful leg ulcers. Twenty-one patients were randomly assigned to receive either morphine or placebo in a randomised, placebo-controlled, crossover pilot study. Each patient was treated four times in total. Pain was measured by the visual analogue score (VAS) before application of gel, directly after and after 2, 6, 12 and 24 hours. Although an overall, clinically relevant, reduction of pain was observed upon treatment with morphine, the difference was not statistically significant. Morphine reduced pain scores more than placebo on treatment occasions 1 and 2. The difference was statistically significant only 2 hours after dressing on the first treatment occasion. Thus, our study did not demonstrate a consistent and globally significant difference in nociception in patients treated with morphine. However, the relatively small number of patients included in our study and other methodological limitations makes it difficult for us to draw general conclusions regarding efficacy of topically applied morphine as an effective treatment for some painful ulcers. Further studies are warranted to evaluate the value of topically applied morphine in the treatment of patients with chronic painful leg ulcers.

  • 15.
    Bastami, Salumeh
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Haage, Pernilla
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Kronstrand, Robert
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Kugelberg, Fredrik C.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Zackrisson, Anna Lena
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Influence of genetic polymorphism on tramadol pharmacokinetics and pharmacodynamicsManuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: There is a significant interindividual variation in the response to tramadol (TRA), which can partly be explained by genetic variation. The main purpose of this study was to determine if there is a correlation between the metabolic ratio of O-desmethyltramadol (ODT) to TRA (MR) and time after drug administration. We also studied the association between genetic polymorphisms in CYP2D6, OPRM1 and ABCB1 and pharmacokinetic and pharmacodynamic properties of TRA.

    Methods: Nineteen healthy volunteers were randomized into two groups receiving a single dose of either 50 or 100 mg of orally administrated TRA. Blood samples were collected prior to dosing and up to 72 h after drug intake. The subjects were asked to report drug related symptoms (DRS) during the experimental day.

    Results: We found a positive correlation between MR and the time after drug intake for both intermediate metabolizers (IMs) and extensive metabolizers (EMs). For the only poor metabolizer (PM) with detectable ODT levels the MR was almost constant. The AUC MR and Cmax MR were associated with CYP2D6 genotype, showing the highest mean values for EMs. Multiple regression analysis showed that 56% of the  variation in AUC MR could be explained by CYP2D6 alone and 78% by investigated SNPs altogether. There was great interindividual variation in DRS, but no associations could be found between DRS and investigated polymorphisms.

    Conclusions: MR can be used for estimation of the time of drug intake when the CYP2D6 genotype is known and taken into consideration. The influence of genetic polymorphisms in ABCB1 and OPRM1 requires further study. We propose that pharmacogenetics should be taken into consideration when interpreting clinical pharmacology and forensic toxicology results, more specifically CYP2D6 genotypes when interpreting the pharmacokinetics of TRA.

  • 16.
    Bastami, Salumeh
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Norling, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Trinks, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Holmlund, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology UHL.
    Walz, Thomas M
    Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Inhibitory effect of opiates on LPS mediated release of TNF and IL-82013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 1022-1033Article in journal (Refereed)
    Abstract [en]

    Most patients with advanced cancer experience severe pain and are often treated with opiates. Cancer patients are especially susceptible to opportunistic infections due to treatment with immunosuppressive and cytostatic drugs. Since opiates have been demonstrated to have immunomodulatory effects, it is of clinical importance to evaluate potential differences between commonly used opiates with regard to their effect on the immune system. The aim of this study was to evaluate the effect of morphine, tramadol, fentanyl and ketobemidone on the functioning of the immune system with special reference to TNF and IL-8 release. Method. U-937 cells were preincubated with different concentrations of opioids followed by stimulation with LPS 100 μg/ml for three hours. The effect of opioids on the levels of cytokine mRNA was studied using RT-PCR. Erk and Akt phosphorylation was also measured by Western blot. Results. All opioids with the exception of fentanyl were capable of inhibiting TNF release from U-937 cells. Morphine had no effect on IL-8 release but the effect of other opiates was almost the same as the effect on TNF. All opioids with the exception of fentanyl were capable of inhibiting production of mRNA for TNF and IL-8. The observed effects of opiates were not always reversible by naloxone, suggesting that the effects might be mediated by other receptors or through a non-receptor mediated direct effect. Although preliminary evidence suggests the involvement of Erk and Akt pathways, further studies are needed to unravel the intracellular pathways involved in mediating the effects of opiates. Our data suggests that the order of potency with regard to inhibition of cytokine release is as follows: tramadol > ketobemidone > morphine > fentanyl. Conclusion. Further studies are needed to understand the clinical implications of the observed immunosuppressive effects of tramadol and ketobemidone and to improve opioid treatment strategies in patients with cancer.

  • 17.
    Bellanti, Francesco
    et al.
    Division of Pharmacology, Leiden/Amsterdam Centre Drug Research, Leiden, The Netherlands.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Della Pasqua, Oscar
    Division of Pharmacology, Leiden/Amsterdam Centre Drug Research, Leiden, The Netherlands.
    Do pharmacokinetic polymorphisms explain treatment failure in high-risk patients with neuroblastoma?2011In: EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, ISSN 0031-6970, Vol. 67, p. S87-S107Article, review/survey (Refereed)
    Abstract [en]

    Purpose Neuroblastoma is the most common extracranial solid tumour in childhood. It accounts for 15% of all paediatric oncology deaths. In the last few decades, improvement in treatment outcome for high-risk patients has not occurred, with an overall survival rate andlt;30-40%. Many reasons may account for such a low survival rate. The aim of this review is to evaluate whether pharmacogenetic factors can explain treatment failure in neuroblastoma. Methods A literature search based on PubMeds database Medical Subject Headings (MeSH) was performed to retrieve all pertinent publications on current treatment options and new classes of drugs under investigation. One hundred and fifty-eight articles wer reviewed, and relevant data were extracted and summarised. Results and conclusions Few of the large number of polymorphisms identified thus far showed an effect on pharmacokinetics that could be considered clinically relevant. Despite their clinical relevance, none of the single nucleotide polymorphisms (SNPs) investigated can explain treatment failure. These findings seem to reflect the clinical context in which anti-tumour drugs are used, i.e. in combination with multi-modal therapy. In addition, many pharmacogenetic studies did not assess (differences in) drug exposure, which could contribute to explaining pharmacogenctic associations. Furthermore, it remains unclear whether the significant activity of new drugs on different neuroblastoma cell lines translates into clinical efficacy, irrespective of resistance or myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification. Elucidation of the clinical role of pharmacogenetic factors in the treatment of neuroblastoma demands an integrated pharmacokinetic pharmacodynamic approach to the analysis of treatment response data.

  • 18.
    Ben, Rayana M.C.
    et al.
    Ben Rayana, M.C., Laboratory of Clinical Chemistry, National Institute of Nutrition, Bab Saadoun, Tunis, Tunisia.
    Burnett, R.W.
    Department of Pathology, Hartford Hospital, Hartford, CT, United States.
    Covington, A.K.
    Department of Chemistry, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
    D'Orazio, P.
    Instrumentation Laboratory, Lexington, MA, United States.
    Fogh-Andersen, N.
    Laboratory of Clinical Chemistry, Herlev Hospital, Herlev, Denmark.
    Jacobs, E.
    Clinical Laboratory Program, Wadsworth Center, NY State Deparmtent of Health, Albany, NY, United States.
    Kulpmann, W.R.
    Külpmann, W.R., Klinische Chemie, Medizinische Hochschule, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
    Kuwa, K.
    Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lewenstam, A.
    Center ProSens, Åbo Akademi University, Åbo-Turku, Finland.
    Maas, A.H.J.
    Eurotrol bv, Wageningen, Netherlands.
    Mager, G.
    Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany.
    Naskalski, J.H.J.
    Department of Clinical Biochemistry, Colleguim Medicum, Jagiellonian University, Krakow, Poland.
    Okorodudu, A.O.
    Department of Pathology, John Sealy Hospital, Galveston, TX, United States.
    Ritter, C.
    Roche Diagnostics GmbH, Graz, Austria.
    St, John A.
    St John, A., ARC Consulting, MT Lawley, WA, Australia.
    Guidelines for sampling, measuring and reporting ionized magnesium in undiluted serum, plasma or blood: International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)2005In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 43, no 5, p. 564-569Article in journal (Refereed)
    Abstract [en]

    All analyzers with ion-selective electrodes for ionized magnesium (iMg) should yield comparable and unbiased results. The prerequisite to achieve this goal is to reach consensus on sampling, measurement and reporting. The recommended guidelines for sampling, measurement and reporting iMg in plasma ("plasma" refers to circulating plasma and the forms in which it is sampled: the plasma phase of anticoagulated whole blood, plasma separated from blood cells, or serum) or blood, referring to the substance concentration of iMg in the calibrants, will provide results for iMg that are approximately 3% greater than its true concentration, and 4% less than its true molality. Binding of magnesium to proteins and ligands in plasma and blood is pH-dependent. Therefore, pH should be simultaneously measured to allow adjustment of iMg concentration to pH 7.4. The substance concentration of iMg may be physiologically and consequently clinically more relevant than the substance concentration of total magnesium. © 2005 by Walter de Gruyter.

  • 19.
    Ben Rayana, Mohammed C.
    et al.
    Natl Inst Nutr, Clin Chem Lab, Tunis, Tunisia.
    Burnett, Robert W.
    Hartford Hosp, Dept Pathol, Hartford, CT 06115 USA.
    Covington, Arthur K.
    Univ Newcastle Upon Tyne, Dept Chem, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
    D'Orazio, Paul
    Instrumentat Lab, Lexington, MA USA.
    Fogh-Andersen, Niels
    Herlev Hosp, Dept Clin Biochem, Clin Chem Lab, DK-2730 Herlev, Denmark.
    Jacobs, Ellis
    NY State Dept Hlth, Wadsworth Ctr, Clin Lab Program, Albany, NY USA.
    Kulpmann, Wolf R.
    Med Hochschule, Klin Chem, Hannover, Germany.
    Kuwa, Katsuhiko
    Univ Tsukuba, Inst Clin Med, Tsukuba, Ibaraki 305, Japan.
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lewenstam, Andrzej
    Abo Akad Univ, Ctr ProSens, Turku, Finland.
    Maas, Anton H. J.
    Eurotrol Bv, Ede, Netherlands.
    Mager, Gerhard
    Fresenius Med Care, Bad Homburg, Germany.
    Naskalski, Jerzy W.
    Jagiellonian Univ, Coll Med, Clin Biochem, Krakow, Poland.
    IFCC guideline for sampling, measuring and reporting ionized magnesium in plasma2008In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 46, no 1, p. 21-26Article in journal (Refereed)
    Abstract [en]

    Analyzers with ion-selective electrodes (ISEs) for ionized magnesium (iMg) should yield comparable and unbiased results for iMg. This IFCC guideline on sampling, measuring and reporting iMg in plasma provides a prerequisite to achieve this goal [in this document, "plasma" refers to circulating plasma and the forms in which it is sampled, namely the plasma phase of anticoagulated whole blood (or "blood"), plasma separated from blood cells, or serum]. The guideline recommends measuring and reporting ionized magnesium as a substance concentration relative to the substance concentration of magnesium in primary aqueous calibrants with magnesium, sodium, and calcium chloride of physiological ionic strength. The recommended name is "the concentration of ionized magnesium in plasma". Based on this guideline, results will be approximately 3% higher than the true substance concentration and 4% lower than the true molality in plasma. Calcium ions interfere with all current magnesium ion-selective electrodes (Mg-ISEs), and thus it is necessary to determine both ions simultaneously in each sample and correct the result for Ca2+ interference. Binding of Mg in plasma is pH-dependent. Therefore, pH should be measured simultaneously with iMg to allow adjustment of the result to pH 7.4. The concentration of iMg in plasma may be physiologically and clinically more relevant than the concentration of total magnesium. Furthermore, blood-gas analyzers or instruments for point-of-care testing are able to measure plasma iMg using whole blood (with intact blood cells) as the sample, minimizing turnaround time compared to serum and plasma, which require removal of blood cells.

  • 20.
    Bengtson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Larson, Cecilia
    Institute of Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Lundblad, Arne
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Larson, Göran
    Institute of Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Påhlsson, Peter
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Identification of a Missense Mutation (G329A; Arg110→ Gln) in the Human FUT7 Gene2001In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 276, no 34, p. 31575-31582Article in journal (Refereed)
    Abstract [en]

    The human FUT7 gene codes for the α1,3-fucosyltransferase VII (Fuc-TVII), which is involved in the biosynthesis of the sialyl Lewis x (SLex) epitope on human leukocytes. The FUT7 gene has so far been considered to be monomorphic. Neutrophils isolated from patients with ulcerative colitis were examined for apparent alterations in protein glycosylation patterns by Western blot analysis using monoclonal antibodies directed against SLex and SLex-related epitopes. One individual showed lower levels of SLex expression and an elevated expression of CD65s compared to controls. The coding regions of the FUT7 gene from this individual were cloned, and a G329A point mutation (Arg110 → Gln) was found in one allele, whereas the other FUT7 allele was wild type. No Fuc-TVII enzyme activity was detected in COS-7 cells transiently transfected with the mutated FUT7 construct. TheFUT7 Arg110 is conserved in all previously cloned vertebrate α1,3-fucosyltransferases. Polymerase chain reaction followed by restriction enzyme cleavage was used to screen 364 unselected Caucasians for the G329A mutation, and a frequency of ≤1% for this mutation was found (3 heterozygotes). Genetic characterization of the family members of one of the additional heterozygotes identified one individual carrying the G329A mutation in both FUT7alleles. Peripheral blood neutrophils of this homozygously mutated individual showed a lowered expression of SLex and an elevated expression of CD65s when analyzed by Western blot and flow cytometry. The homozygous individual was diagnosed with ulcer disease, non-insulin-dependent diabetes, osteoporosis, spondyloarthrosis, and Sjögren's syndrome but had no history of recurrent bacterial infections or leukocytosis.

  • 21.
    Bengtson, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Zetterberg, H
    Påhlsson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Larson, G
    EBV transformed B cells from an individual homozygously mutated (G329A) in the FUT7 gene do not roll on E- or P-selectins2003In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 17, no 5, p. A989-A989Conference paper (Other academic)
  • 22.
    Bjerner, Johan
    et al.
    University of Oslo.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hovig, Eivind
    Norwegian Radium Hospital.
    Kallner, Anders
    Karolinska University Hospital.
    Non-parametric estimation of reference intervals in small non-Gaussian sample sets2009In: ACCREDITATION AND QUALITY ASSURANCE, ISSN 0949-1775, Vol. 14, no 4, p. 185-192Article in journal (Refereed)
    Abstract [en]

    This study aimed at validating common bootstrap algorithms for reference interval calculation.We simulated 1500 random sets of 50-120 results originating from eight different statistical distributions. In total, 97.5 percentile reference limits were estimated from bootstrapping 5000 replicates, with confidence limits obtained by: (a) normal, (b) from standard error, (c) bootstrap percentile (as in RefVal) (d) BCa, (e) basic, or (f) student methods. Reference interval estimates obtained with ordinary bootstrapping and confidence intervals by percentile method were accurate for distributions close to normality and devoid of outliers, but not for log-normal distributions with outliers. Outlier removal and transformation to normality improved reference interval estimation, and the basic method was superior in such cases. In conclusions, if the neighborhood of the relevant percentile contains non-normally distributed results, bootstrapping fails. The distribution of bootstrap estimates should be plotted, and a non-normal distribution should warrant transformation or outlier removal.

  • 23.
    Bjorses, Katarina
    et al.
    Lund University.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Montan, Carl
    Lund University.
    Wildt-Persson, Katarina
    Magle Life Science.
    Fyhr, Peter
    Magle Life Science.
    Holst, Jan
    Lund University.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    In vitro and in vivo evaluation of chemically modified degradable starch microspheres for topical haemostasis2011In: ACTA BIOMATERIALIA, ISSN 1742-7061, Vol. 7, no 6, p. 2558-2565Article in journal (Refereed)
    Abstract [en]

    Degradable starch microspheres (DSMs) are starch chains cross-linked with epichlorhydrin, forming glycerol-ether links. DSMs have been used for many years for temporary vascular occlusion and drug delivery in treatment of malignancies. They are also approved and used for topical haemostasis by absorbing excess fluid from the blood and concentrating endogenous coagulation factors, thereby facilitating haemostasis. This mechanism of action is not sufficient for larger bleedings in current chemical formulations of DSMs, and modification of DSMs to trigger activation of platelets or coagulation would be required for use in such applications. Chemical modifications of DSMs with N-octenyl succinic anhydride, chloroacetic acid, acetic anhydride, diethylaminoethyl chloride and ellagic acid were performed and evaluated in vitro with thrombin generation and platelet adhesion tests, and in vivo using an experimental renal bleeding model in rat. DSMs modified to activate platelets in vitro were superior in haemostatic capacity in vivo. Further studies with non-toxic substances are warranted to confirm these results and develop the DSM as a more effective topical haemostatic agent.

  • 24.
    Björk, Per
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry. Linköping University, The Institute of Technology.
    Lenner, Liselotte
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Persson, Birgitta
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Inganäs, Olle
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Jonasson, Jon
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Conjugated polythiophene probes target lysosome-related acidic vacuoles in cultured primary cells2007In: Molecular and Cellular Probes, ISSN 0890-8508, Vol. 21, no 5-6, p. 329-337Article in journal (Refereed)
    Abstract [en]

    Conformation-sensitive optical probes for studying biological processes and structures are of great interest. The present work shows for the first time that conjugated polyelectrolyte (CPE) probes can be used for specific targeting of chromatin, nuclear and cytoplasmatic vesicles, and cytoskeletal components in a complex system of cultured cells. One of the probes could also be used for vital staining of live cells. When bound to different entities, the polythiophene derivative probes emitted light with different colors due to the unique spectral properties of these conformation sensitive probes. The physical pre-requisites for binding could also be exploited for characterization of the target. Unexpectedly, lysosome-related acidic vacuoles were targeted in cultured primary cells by both anionic, cationic, and zwitter-ionic polythiophene derivatives. Pre-treatment with Bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase, caused redistribution of the staining. The targeting of lysosome-related acidic vesicles could not be demonstrated in transformed cells (melanoma, neuroblastoma, and prostate cancer cell lines), indicating a difference in the localization, structure, accessibility, or quantity of the target in cultured normal cells as compared with the malignant cell lines. The chemical nature of the conjugated polyelectrolyte complex in the cytoplasmatic vacuoles remains elusive.

  • 25. Blomquist, L.
    et al.
    Dizdar, N.
    Linköping University, Department of Biomedicine and Surgery.
    Karlsson, M.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemestry. Linköping University, Faculty of Health Sciences.
    Ossowicki, H.
    Pettersson, A.
    Smeds, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Microdialysis of 5-S-cysteinyldopa from interstitial fluid in cutaneous human melanoma transplanted to athymic mice1991In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, p. 23-32Article in journal (Refereed)
    Abstract [en]

    Microdialysis was investigated as a tool for the determination of the extracellular concentration of the pigment metabolite 5-S-cysteinyldopa in human melanoma transplanted to athymic mice. Histology of the tumour with the microdialysis probes in situ showed no tissue damage. With probes equipped with polycarbonate membranes (20 kD) extraction (relative recovery) was approximately 50% at pH 4.0 and flow rates of 1 microliter/min, but at pH 7.0 recoveries were markedly lower, particularly from serum. In a first series of human melanomas transplanted to athymic mice low concentrations of 5-S-cysteinyldopa were detected in only two out of ten dialysates and were not detected in the other eight. Utilizing devices constructed for comparison of membrane characteristics in vitro we found about 4-fold higher recoveries with cuprophane and polyamide membranes than with polycarbonate membranes. Therefore newly constructed microdialysis probes (CMA/11) with cuprophane membranes were tested in vitro and gave recoveries of 38-48% from Ringer-Acetate solutions and 22-31% from serum, and the pH effects were low. When these probes were utilized in a second series of melanomas transplanted to athymic mice, 5-S-cysteinyldopa could easily be quantified in 10/10 experiments. A steady-state level of the dialysate 5-S-cysteinyldopa concentration was reached after 45 min.

  • 26.
    Boij, R
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Nilsson-Ekdahl, K
    Uppsala University.
    Svensson, J
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sandholm, K
    Linneus University.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Chemistry.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Palonek, E
    Karolinska University.
    Jarle, M
    Karolinska University.
    Biomarkers of coagulation, inflammation and angiogenesis are independently associated with preeclampsia in JOURNAL OF REPRODUCTIVE IMMUNOLOGY, vol 94, issue 1, pp 109-1092012In: JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Elsevier , 2012, Vol. 94, no 1, p. 109-109Conference paper (Refereed)
    Abstract [en]

    n/a

  • 27.
    Boij, Roland
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences.
    Svensson, Judit
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Nilsson-Ekdahl, Kristina
    Uppsala University, Sweden Linneaus University, Sweden .
    Sandholm, Kerstin
    Linneaus University, Sweden .
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Palonek, Elzbieta
    Karolinska University Hospital, Sweden Doping Control Lab, Sweden .
    Garle, Mats
    Karolinska University Hospital, Sweden Doping Control Lab, Sweden .
    Berg, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Jenmalm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Matthiesen, Leif
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Biomarkers of Coagulation, Inflammation, and Angiogenesis are Independently Associated with Preeclampsia2012In: AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, ISSN 1046-7408, Vol. 68, no 3, p. 258-270Article in journal (Refereed)
    Abstract [en]

    Problem Although preeclampsia has been associated with inflammation, coagulation, and angiogenesis, their correlation and relative contribution are unknown. Method of Study About 114 women with preeclampsia, 31 with early onset (EOP) and 83 with late onset preeclampsia (LOP), and 100 normal pregnant controls were included. A broad panel of 32 biomarkers reflecting coagulation, inflammation, and angiogenesis was analyzed. Results Preeclampsia was associated with decreased antithrombin, IL-4 and placental growth factor levels and with increased C3a, pentraxin-3, and sFlt-1 levels, with more marked differences in the EOP group. The Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in the preeclampsia and EOP group than in controls, respectively. No correlations between the biomarkers were found in preeclampsia. Multivariate logistic regression tests confirmed the results. Conclusions Cytokines, chemokines and complement activation seem to be part of a Th1-like inflammatory reaction in preeclampsia, most pronounced in EOP, where chemokines may be more useful than cytokines as biomarkers. Biomarkers were not correlated suggesting partly independent or in time separated mechanisms.

  • 28.
    Bolin, Maria
    et al.
    Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Faxälv, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Jager, Edwin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Berggren, Magnus
    Linköping University, Department of Science and Technology, Physics and Electronics. Linköping University, The Institute of Technology.
    Electroactive Control of Platelet Adhesion to Conducting Polymer MicropatternsManuscript (preprint) (Other academic)
    Abstract [en]

    In this work, we report a method to fabricate addressable micropatterns of electroactive surfaces based on the conducting polymer poly-(3, 4-ethylenedioxytiophene) (PEDOT:Tos) to gain dynamic control over the spatial distribution of platelets, in vitro. Utilizing thin film processing and microfabrication techniques desired patterns down to the scale of  individual cells, were achieved to enable active regulation of cell  populations and their extracellular environment at high spatial resolution.Upon electronic addressing, both reduced and oxidized surfaces were created within the same device. The changes of the electrochemical state of PEDOT results in a reversible modification of the surface properties of the material. This surface modulation dictates the conformation and/or orientation, rather than the concentration, of surface proteins, thus indirectly regulating cell adhesion. The chemistry, texture, charge, and softness of fiacrtiial cell-hosting surfaces are parameters known to affect the binding characteristics and orientation of the extracellular proteins, thus dictating adhesion, spreading, migration, and proliferation of cells.

  • 29.
    Borud, Einar Kristian
    et al.
    University of Tromso.
    Alraek, Terje
    University of Tromso.
    White, Adrian
    University of Exeter.
    Fonnebo, Vinjar
    University of Tromso.
    Eggen, Anne Elise
    University of Tromso.
    Hammar, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Lindh-Åstrand, Lotta
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Grimsgaard, Sameline
    University of Tromso.
    The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial2009In: MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY, ISSN 1072-3714, Vol. 16, no 3, p. 484-493Article in journal (Refereed)
    Abstract [en]

    Objective: This study compared the effectiveness of individualized acupuncture plus self-care versus self-care alone on hot flashes and health-related quality of life in postmenopausal women.

    Methods: This study involved a multicenter, pragmatic, randomized, controlled trial with two parallel arms. Participants were postmenopausal women experiencing, on average, seven or more hot flashes per 24 hours during seven consecutive days. The acupuncture group received 10 acupuncture treatment sessions and advice on self-care, and the control group received advice on self-care only. The frequency and severity (0-10 scale) of hot flashes were registered in a diary. Urine excretion of calcitonin gene-related peptide was assessed at baseline and after 12 weeks. The primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. The secondary endpoint was change in health-related quality of life measured by the Womens Health Questionnaire.

    Results: Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per 24 hours in the control group (n = 133), a difference of 2.1 (P &lt; 0.001). Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group, a difference of 1.4 (P &lt; 0.001). The acupuncture group experienced statistically significant improvements in the vasomotor, sleep, and somatic symptoms dimensions of the Womens Health Questionnaire compared with the control group. Urine calcitonin gene-related peptide excretion remained unchanged from baseline to week 12.

    Conclusions: Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women.

  • 30.
    Boström, Sverre
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Bobinski, L
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Improved brain protection at decompressive craniectomy - a new method using Palacoso (R) R-40 (methylmethacrylate)2005In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 147, no 3, p. 279-281Article in journal (Refereed)
    Abstract [en]

    A new method is described for protecting the brain after decompressive craniectomy in which a temporary methylmethacrylate flap is formed, somewhat larger than the original bone flap, thus gaining "extra" volume for the oedematous brain in which to expand. The present procedure was developed as a pan of ordinary clinical practice particularly in response to demands from the NICU staff and our colleagues at other clinics who were responsible for the care of the patient in the post NICU period. They made us keenly aware that these patients frequently lack optimal co-ordination and balance and therefore run an increased risk of trauma to the unprotected brain when failing. This prompted us to develop a method for brain protection after decompressive craniectomy aiding in the care and rehabilitation until the final installation of the patient's own bone flap can be performed.

  • 31.
    Boström, Sverre
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Theodorsson, Annette
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Bobinski, Lukas
    Department of Neurosurgery, Umeå University Hospital, Umeå.
    A new microsurgical instrument - a suction tube combined with a microdissector2011In: BRITISH JOURNAL OF NEUROSURGERY, ISSN 0268-8697, Vol. 25, no 3, p. 320-321Article in journal (Refereed)
    Abstract [en]

    A microsurgical suction tube with an attached ball probe has been developed. It functions as a microdissector when the ball probe is in its extended position, creating a larger working field than an ordinary sucker. When the ball probe is in the repose position, it does not interfere with the suction capacity, and the suction tube serves as a regular sucker. By adding the properties of the microdissector to the suction tube, dissection of exquisitely fine and subtle structures, including arachnoidal membranes, is facilitated. The ball probe is easily dismantled from the suction tube and the whole instrument conveniently cleaned.

  • 32.
    Brynhildsen, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Claesson, Ing-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Sydsjö, Adam
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Leptin and adiponectin in cord blood from children of normal weight, overweight and obese mothers2013In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 102, no 6, p. 620-624Article in journal (Refereed)
    Abstract [en]

    Aim To study cord blood concentrations of adiponectin and leptin in children born by normal weight, overweight and obese mothers and to study these parameters in relation to a weight gain intervention programme for obese mothers. Methods Ten millilitre cord blood was collected and analysed for leptin and adiponectin concentrations in children with gestational age andgt;37weeks born by 60 normal weight, 45 overweight and 145 obese mothers. 82 obese mothers took part in a weight gain intervention programme. Results Concentrations of leptin and adiponectin were higher in cord blood from children of overweight and obese mothers compared with children of normal weight mothers (leptin: Md 13.2, 30, 3 and 90.2ng/mL respectively, pandlt;0.001; adiponectin 35.9, 205.4, 213.8ng/L pandlt;0.001). No differences were found between overweight and obese mothers. The weight gain intervention programme for obese pregnant women had significant effects on the weight gain during pregnancy but had no effects on cord blood serum concentrations of leptin and adiponectin. Conclusion Cord blood leptin and adiponectin concentrations were higher in children born by overweight or obese women compared with children of normal weight mothers. A weight gain intervention programme for obese pregnant women did not affect these results. Intrauterine exposition to high concentrations of leptin and adiponectin may play a role in weight development later in life.

  • 33.
    Börgeson, Emma
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lönn, Johanna
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Bergström, Ida
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Brodin Patcha, Veronika
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Sarndahl, Eva
    University Orebro.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lipoxin A(4) Inhibits Porphyromonas gingivalis-Induced Aggregation and Reactive Oxygen Species Production by Modulating Neutrophil-Platelet Interaction and CD11b Expression2011In: INFECTION AND IMMUNITY, ISSN 0019-9567, Vol. 79, no 4, p. 1489-1497Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. Lipoxin A(4) (LXA(4)) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA(4) on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 and upregulates CD11b/CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA(4). Furthermore, we found that LXA(4) significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA(4) was unable to inhibit either aggregation or ROS production, respectively. In conclusion, this study suggests that LXA(4) antagonizes P. gingivalis-induced cell activation in a manner that is dependent on leukocyte-platelet interaction, likely via the inhibition of Rho GTPase signaling and the downregulation of CD11b/CD18. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis.

  • 34.
    Carlson, Joyce
    et al.
    Lunds universitet.
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Lindstedt, Göran
    Sahlgrenska akademin, Göteborgs universitet.
    Digestionsorganens sjukdomar2012In: Laurells Klinisk kemi i praktisk medicin / [ed] Peter Nilsson-Ehle, Maria Berggren Söderlund, Elvar Theodorsson, Lund: Studentlitteratur, 2012, 9, p. 441-496Chapter in book (Other academic)
    Abstract [sv]

    Klinisk kemi i praktisk medicin används som kurslitteratur för läkare, biomedicinska analytiker och biomedicinare sedan 40 år tillbaka. Den finns på avdelningar, mottagningar och vårdcentraler - överallt där man behöver ta prover för kliniskt kemiska analyser och tolka deras resultat. Nu föreligger den i sin nionde upplaga efter omfattande revision och med nyskrivna kapitel. I denna upplaga har innehållet organiserats med tydlig anknytning till kliniska problemområden. Alla kapitel har grundligt reviderats. Avsnitten om tolkning av analysresultat, allergi och autoimmunitet, hjärtinfarkt och hjärtskademarkörer, digestionsorganens sjukdomar, graviditet, infertilitet och prenataldiagnostik samt läkemedel, förgiftningar och missbruk är helt nyskrivna. Boken kan användas både för att slå upp fakta om specifika analyser och för att förstå de sjukdomsmekanismer som är av betydelse för tolkningen av laboratorieresultat. Modern medicinsk praxis är patientcentrerad och har sitt fundament i ett nära samspel mellan klinik, laboratorier och patienter. Kunskapsfragment inom klinisk kemi är lättillgängliga för alla och envar på nätet, men ger sällan den helhetsbild som behövs för grundlig förståelse och därmed optimal användning av laboratorieanalyser. Denna bok ger sådan helhetsbild.

  • 35.
    Chaireti, Roza
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Jennersjö, Cecilia
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Is thrombin generation at the time of an acute thromboembolic episode a predictor of recurrence? The LInkoping Study on Thrombosis (LIST) - A 7-year follow-up2013In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 131, no 2, p. 135-139Article in journal (Refereed)
    Abstract [en]

    Introduction: Venous thromboembolism(VTE) is considered a chronic disease, since a high percentage of patients experience recurrences. Oral anticoagulants are effective in preventing recurrences at a price of potential bleeding complications, which underlines the importance of finding reliable markers for estimating the individual recurrence risk. In this report we evaluate thrombin generation markers at the time of an acute VTE as predictive markers for recurrence risk. Gender, presence of factor V Leiden and acquired provocative factors were taken into consideration. Additionally, we study the correlation between thrombin generation at the time of an acute VTE and thrombin generation measured four to eight weeks after discontinuation of anticoagulants. less thanbrgreater than less thanbrgreater thanMaterials and Methods: Themain cohort consisted of 115 patients with a confirmed thromboembolic event at inclusion. The follow-up period was seven years. less thanbrgreater than less thanbrgreater thanResults: Patients with an initial unprovoked VTE and at least one recurrence had significantly prolonged thrombin generation, whereas those without recurrences had higher maximum and total thrombin concentration. In contrast, when thrombin generation was measured one to two months after discontinuation of anticoagulant treatment, it was shown that the patients who experienced recurrences had higher maximum thrombin concentration. less thanbrgreater than less thanbrgreater thanConclusions: Our study shows that thrombin generation profiles at the time of a VTE correlate to the clinical course after the acute episode. The great over-lap in thrombin generation between patients with and without recurrences though, makes the use of thrombin generation profiles for advice on length of oral anticoagulation for an individual patient doubtful at the present stage of knowledge.

  • 36. Chaireti, Roza
    et al.
    Jennersjö, Cecilia
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Thrombin generation and D-dimer concentrations in a patient cohort investigated for venous thromboembolism. Relations to venous thrombosis, factor V Leiden and prothrombin G20210A. The LIST study.2009In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 124, no 2, p. 178-84Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The present study evaluated possible relations between various markers of thrombin generation, D-dimer and venous thromboembolism in outpatients with and without the FV Leiden and the protrombin mutations. PATIENTS AND METHODS: Our cohort consisted of 98 patients with the FV Leiden and 15 with the prothrombin mutation and an equal number of age- and gender-matched controls. All subjects were investigated due to suspicion of venous thromboembolism and the diagnosis was objectively confirmed or refuted. RESULTS: We compared the D-dimer values and the thrombin generation markers among different patient groups (with/without thromboembolism, with/without genetic factors, gender-linked). The only statistically significant difference noted was prolonged time both for the initiation and termination of thrombin generation in patients with thrombosis. This applied to controls and to patients heterozygous for the FV Leiden. Additionally, the D-dimer values were elevated in patients with the FV Leiden. No difference was found among the patients with prothrombin mutation and their controls. DISCUSSION: Multi-variant analysis indicated that the difference in D-dimer between FV Leiden patients and controls was due to the greater number of patients with confirmed thrombosis in the former group, a finding supported by an independent prospective study on postoperative thrombosis. Neither D-dimer concentration nor thrombin generation depend on FV Leiden. The total amount of thrombin generated was not related to diagnosis. The prolonged thrombin generation noted in controls and FV Leiden heterozygotes with thrombosis may point out different thrombin generation profiles in different patient populations and requires further studies.

  • 37.
    Dawidson, I
    et al.
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Blom, M
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Angmar-Mansson, B
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lundeberg, T
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden.
    Sensory stimulation (acupuncture) increases the release of CGRP and VIP in the saliva of xerostomic patients1999In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 848, no 1-2, p. P62-Conference paper (Other academic)
  • 38.
    Dawidson, I
    et al.
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Blom, M
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Angmar-Mansson, B
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lundeberg, T
    Karolinska Inst, Dept Cariol, Stockholm, Sweden Linkoping Univ Hosp, Dept Clin Chem, S-58185 Linkoping, Sweden Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Sensory stimulation increases salivary CGRP and VIP in xerostomic patients.2001In: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 80, no 4, p. 1302-1302Conference paper (Other academic)
  • 39.
    Diczfalusy, Elin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Didzar, Nil
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Biochemical monitoring and simulation of the electric field during deep brain stimulation (oral)2010Conference paper (Other academic)
  • 40.
    Diczfalusy, Elin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Simulations and visualizations for interpretation of brain microdialysis data during deep brain stimulation2012In: IEEE Engineering in Medicine and Biology Society (EMBC), 2012, IEEE , 2012, p. 6438-6441Conference paper (Refereed)
    Abstract [en]

    Microdialysis of the basal ganglia was used in parallel to deep brain stimulation (DBS) for patients with Parkinson’s disease. The aim of this study was to patientspecifically simulate and visualize the maximum tissue volume of influence (TVImax) for each microdialysis catheter and the electric field generated around each DBS electrode. The finite element method (FEM) was used for the simulations. The method allowed mapping of the anatomical origin of the microdialysis data and the electric stimulation for each patient. It  was seen that the sampling and stimulation targets differed among the patients, and the results will therefore be used in the future interpretation of the biochemical data.

  • 41.
    Diczfalusy, Elin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Loyd, Dan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    A model for simulation and patient-specific visualization of the tissue volume of influence during brain microdialysis2011In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, Vol. 49, no 12, p. 1459-1469Article in journal (Refereed)
    Abstract [en]

    Microdialysis can be used in parallel to deep brain stimulation (DBS) to relate biochemical changes to the clinical outcome. The aim of the study was to use the finite element method to predict the tissue volume of influence (TVI(max)) and its cross-sectional radius (r (TVImax)) when using brain microdialysis, and visualize the TVI(max) in relation to patient anatomy. An equation based on Fick's law was used to simulate the TVI(max). Factorial design and regression analysis were used to investigate the impact of the diffusion coefficient, tortuosity and loss rate on the r (TVImax). A calf brain tissue experiment was performed to further evaluate these parameters. The model was implemented with pre-(MRI) and post-(CT) operative patient images for simulation of the TVI(max) for four patients undergoing microdialysis in parallel to DBS. Using physiologically relevant parameter values, the r (TVImax) for analytes with a diffusion coefficient D = 7.5 × 10(-6) cm(2)/s was estimated to 0.85 ± 0.25 mm. The simulations showed agreement with experimental data. Due to an implanted gold thread, the catheter positions were visible in the post-operative images. The TVI(max) was visualized for each catheter. The biochemical changes could thereby be related to their anatomical origin, facilitating interpretation of results.

  • 42.
    Diczfalusy, Elin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Didzar, Nil
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    A finite element model for biochemical monitoring in the brain during deep brain stimulation (poster)2010Conference paper (Refereed)
  • 43.
    Diczfalusy, Elin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Dizdar, Nil
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    A Finite Model for Biochemical Monitoring in the Brain during Deep Brain Stimulation (oral)2010Conference paper (Refereed)
  • 44.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Granerus, Ann-Kathrine
    Linköping University, Department of Clinical and Experimental Medicine, Geriatric. Linköping University, Faculty of Health Sciences.
    Hannestad, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Ljungdahl, Å.
    Department of Neurology, Huddinge Hospital, Stockholm.
    Olsson, Jan-Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    L-dopa pharmacokinetics studied with microdialysis in patients with Parkinson's disease and a history of malignant melanoma1999In: Acta neurologica Scandinavica, ISSN 0001-6314, Vol. 100, no 4, p. 231-237Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The pharmacokinetics of free L-dopa in blood and tissue of five parkinsonian patients with malignant melanoma was studied with microdialysis. In one case the effect of L-dopa treatment on 5-S-cysteinyldopa and the melanoma was studied. Gastric emptying and its effects on free L-dopa in blood were also investigated in one of the patients.

    METHODS: Five patients were given 100 mg L-dopa with 25 mg benserazide. Blood and dialysates from the circulation and fatty tissue were collected for analysis. [13C]-Octanoic breath test was used for analyzing gastric half-emptying time.

    RESULTS: Four of the patients had similar pharmacokinetic patterns for L-dopa and a significant (P < 0.05) increase of serum 5-S-cysteinyldopa occurring 30 min after L-dopa intake. Delayed L-dopa peaks and slow gastric half-emptying time were found in 1 patient. A dose-dependent increase of 5-S-cysteinyldopa occurred but no melanoma metastases were seen during long-term L-dopa therapy.

    CONCLUSION: L-dopa therapy increases 5-S-cysteinyldopa levels but does not seem to cause progress of melanomas. Gastric emptying impacts L-dopa pharmacokinetics.

  • 45.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Comparison of N-acetylcysteine and l-2-oxothiazolidine-4-carboxylate as cysteine deliverers and glutathione precursors in human malignant melanoma transplants in mice2000In: Cancer chemotherapy and pharmacology, ISSN 0344-5704, Vol. 45, no 3, p. 192-198Article in journal (Refereed)
    Abstract [en]

    Purpose: Glutathione is an important cellular compound which affects detoxification of electrophiles and may have direct or indirect effects on pigment formation. It is therefore of importance to study interstitial concentrations in melanoma tissue while decreasing its formation with an enzyme inhibitor and increasing its amount with cysteine deliverers. Method: Glutathione formation was inhibited by intraperitoneal (i.p.) injection of BSO. N-Acetylcysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) were then given i.p. to subgroups of the animals. Intratumoral microdialysis was performed during BSO treatment, during BSO treatment combined with NAC or OTC and after discontinuation of BSO but ongoing NAC or OTC treatment. Results: Glutathione formation was inhibited during BSO treatment. The dialysate concentrations of both glutathione and cysteine decreased during concomitant treatment with BSO and NAC or OTC. Recovery of the amounts of the two compounds was seen in both groups after discontinuation of BSO treatment. In the NAC group we also observed an acute increase in dialysate concentrations of cysteine after NAC injection. The 5-S-cysteinyldopa concentrations were unaffected by variations in glutathione and cysteine concentrations. Conclusions: 5-S-Cysteinyldopa in melanoma is not formed from glutathione in vivo to any appreciable extent. The intracellular amount of cysteine is probably not a limiting factor for cysteinyldopa formation. It seems that both NAC and OTC can be used as cysteine deliverers to melanoma cells in vivo to produce recovery of glutathione levels after synthesis inhibition by BSO treatment.

  • 46.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Årstrand, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Effects on interstitial glutathione, cysteine and 5-S-cysteinyldopa of buthionine sulphoximine in human melanoma transplants1997In: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 7, no 4, p. 322.-328Article in journal (Refereed)
    Abstract [en]

    Using microdialysis of human melanoma transplants in athymic mice we have shown that interstitial glutathione levels decreased during treatment with buthionine sulphoximine (BSO) and recovered after cessation of treatment. The cysteine concentrations also decreased, while 5-S-cysteinyldopa tended to increase during BSO treatment. Restoration of the glutathione levels was not seen after either N-acetylcysteine (NAC) or L-2-oxothiazolidine-4-carboxylate (OTC) injections, given on the third day of BSO treatment. These results were to be expected since NAC and OTC were given during the BSO treatment, and BSO is a specific and potent inhibitor of glutathione synthesis. Cysteine levels, however, increased after the NAC injection but remained unaltered after the OTC injection, while 5-S-cysteinyldopa remained unaltered after both the NAC and the OTC injections.

  • 47.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Norlander, Björn
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Olsson, Jan-Edvin
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Human pharmacokinetics of L-3,4-dihydroxyphenylalanine studied with microdialysis1999In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 45, no 10, p. 1813-1820Article in journal (Refereed)
    Abstract [en]

    Background: Intravenous and subcutaneous microdialysis was performedto compare the free concentrations and pharmacokinetics of L-3,4-dihyroxyphenylalanine(L-dopa) in blood and tissue in healthy subjects and in patientswith Parkinson disease.

    Methods: Nine healthy volunteers and 10 patients with Parkinson disease, stage 1.5–2 according to the Hoehn-Yahr rating scale, took part of the study. In the patient group subcutaneous microdialysis and ordinary blood sampling were performed, whereas in the control group intravenous microdialysis was also performed. Microdialysis samples were collected in fractions of 15 min. The first two fractions were collected for analysis of basal concentrations. A blood sample was also taken. The patients were then given one tablet of Madopar® (100 mg of L-dopa and 25 mg of benserazide),and the microdialysis was continued for another 210 min. Bloodsamples were obtained at 30-min intervals.

    Results: The serum samples gave a significantly higher meanarea under the curve (AUC; 491 ± 139 µmol ·min/L) than that for intravenous dialysates (235 ± 55.3µmol · min/L), suggesting a protein binding of50%. The L-dopa concentrations from the subcutaneous dialysatesmatched those from the intravenous dialysates, indicating rapiddistribution of L-dopa to the tissues.

    Conclusions: Parkinsonian patients in early stages of the disease have a pharmacokinetic pattern of free L-dopa similar to that of healthy subjects. Comparison of AUCs from microdialysis with ordinary serum analysis revealed data indicating significant protein binding. Microdialysis is a suitable and easily applied tool in pharmacokinetic studies.

  • 48.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences.
    Kågedal, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Smeds, Staffan
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Årstrand, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    A high-sensitivity fluorometric high-performance liquid chromatographic method for determination of glutathione and other thiols in cultured melanoma cells, microdialysis samples from melanoma tissue, and blood plasma.1991In: Melanoma Research, ISSN 0960-8931, Vol. 1, no 1, p. 33-42Article in journal (Refereed)
    Abstract [en]

    A high-performance liquid chromatographic method with fluorometric detection is described which is suitable for determination of glutathione in small samples. Reduced glutathione (GSH) and total glutathione obtained as GSH after reduction with glutathione reductase is derivatized with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM) and subjected to chromatography. The detection limit for the GSH-DACM derivative was 5-10 fmol/injection, and analytical recovery was quantitative. The method is suitable for determination of both reduced and total glutathione in samples from microdialysis of melanoma tumours, and cysteine can be quantified in the same chromatogram. Application is shown also for glutathione determinations in cultured melanoma cells, melanoma homogenates and plasma.

  • 49.
    Dizdar (Dizdar Segrell), Nil
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Kullman, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Nezirevic, Dzeneta
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Letter: Untitled2013In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 212, no 2, p. 363-363Article in journal (Refereed)
    Abstract [en]

    n/a

  • 50.
    D'Orazio, P.
    et al.
    Instrumentation Laboratory, Lexington, MA, United States.
    Burnett, R.W.
    Hartford Hospital, Hartford, CT, United States.
    Fogh-Andersen, N.
    Herlev Hospital, Herlev, Denmark, Department of Clinical Biochemistry, Herlev Hospital, 2730 Herlev, Denmark.
    Jacobs, E.
    Wadsworth Center, Albany, NY, United States.
    Kuwa, K.
    University of Tsukuba, Tsukuba, Japan.
    Kulpmann, W.R.
    Külpmann, W.R., Medizinizche Hochschule Hannover, Hannover, Germany.
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lewenstam, A.
    Åbo Akademi University, Åbo-Turku, Finland.
    Maas, A.H.J.
    Eurotrol bv, Ede, Netherlands.
    Mager, G.
    Fresenius, Bad Homburg, Germany.
    Naskalski, J.W.
    Jagiellonian University, Krakow, Poland.
    Okorodudu, A.O.
    Department of Pathology, University of Texas Medical Branch, Galveston, TX, United States.
    Approved IFCC recommendation on reporting results for blood glucose2006In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 44, no 12, p. 1486-1490Article 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 is distributed, like water, between erythrocytes and plasma. The molality of glucose (amount of glucose per unit 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 the calibrator, plasma, and erythrocyte fluid can explain some of the differences. Results for glucose measurements depend on the sample type and on whether the method requires sample dilution or uses biosensors in undiluted samples. If the results are mixed up or used indiscriminately, the differences may exceed the maximum allowable error for glucose determinations for diagnosing and monitoring diabetes mellitus, thus complicating patient treatment. The goal of the International Federation of Clinical Chemistry and Laboratory Medicine, 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 (in 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 plasma. The conversion will provide harmonized results, facilitating the classification and care of patients and leading to fewer therapeutic misjudgments. © 2006 by Walter de Gruyter.

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