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  • 51.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Holmgren, A
    Holmgren, P
    High concentrations of diazepam and nordiazepam in blood of impaired drivers: Association with age, gender and spectrum of other drugs present2004In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 146, no 1Article in journal (Refereed)
    Abstract [en]

    A zero-concentration limit for controlled scheduled drugs in the blood of motorists was introduced in Sweden in 1999 and the annual number of arrests for driving under the influence of drugs (DUID) has since increased eight-fold. However, for prescription drugs that might cause impairment (e.g. benzodiazepines) additional proof is needed to justify prosecution, such as whether the medication was being misused. Over a 2-year period, we found 94 cases of DUID in which the concentrations of diazepam in blood was 1.1 μg/g or more. Diazepam (D) and nordiazepam (ND) were determined in whole blood by capillary gas chromatography with a limit of quantitation of 0.05 μg/g for each compound. The mean (median) and maximum concentrations of D were 2.0 μg/g (1.7 μg/g) and 7.8 μg/g and the corresponding ND concentrations were 1.5 μg/g (1.0 μg/g) and 7.6 μg/g, respectively. The concentration of D in blood exceeded 2 μg/g in 21% of cases and was over 3.0 μg/g in 11% of cases. D and ND were the only drugs present in eight cases (seven men and one women) and in another five cases ethanol was present at concentrations ranging from 0.81 to 1.98 mg/g. Polydrug use was very common in these DUID suspects and D and ND coexisted with amphetamine in 20% of cases, tetrahydrocannabinol in 18% of cases and with both these illicit drugs in 12% of cases. The next most prevalent drug combination was D, ND and morphine (mostly derived from heroin), seen in 13% of cases. Other psychoactive prescription drugs were identified in blood including alprazolam, flunitrazepam, oxazepam, zolpidem and zopiclone. This case series of DUID suspects demonstrate the high frequency of polydrug use showing preference for illicit drugs like amphetamine, cannabis and heroin, in that order. Furthermore, Swedish traffic delinquents frequently overdose with prescription drugs as exemplified here by unusually high concentrations of D and its active metabolite ND.

  • 52.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Holmgren, A
    Kugelberg, FC
    Gamma-hydroxybutyrate concentrations in the blood of impaired drivers, users of illicit drugs, and medical examiner cases2007In: Journal of Analytical Toxicology, ISSN 0146-4760, E-ISSN 1945-2403, Vol. 31, no 9, p. 566-572Article in journal (Refereed)
    Abstract [en]

    Gamma-hydroxybutyrate (GHB) was determined in blood samples from impaired drivers, people arrested for petty drug offenses (non-traffic cases), and GHB-related deaths. The method of analysis involved conversion of GHB into gamma-butyrolactone and determination of the latter by gas chromatography with a flame ionization detector, and with gamma-valerolactone as the internal standard. The mean and median concentrations of GHB in blood from impaired drivers (N = 473) were 90 and 84 mg/L, respectively, and offenders were predominantly men (96%) with an average age of 26 year (range 15-50 year). In 185 cases, GHB was the only drug present in blood at mean and median concentrations of 92 and 86 mg/L, respectively. People arrested for petty drug offenses (N = 1061) had slightly higher GHB concentrations in their blood: median 118 mg/L for men and 111 mg/L for women. In GHB-related deaths (N = 33), the mean and median concentrations were considerably higher: 307 mg/L and 190 mg/L, respectively, and the highest was 2200 mg/L. The typical signs of drug influence noted by the arresting police officers included sedation, agitation, slurred speech, irrational behaviour, jerky movements, and spitting. The short elimination half-life of GHB means that the concentrations in blood decrease rapidly and are probably a lot lower than at the time of driving, which was 30-90 min earlier.

  • 53.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Holmgren, A
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Concentrations of scheduled prescription drugs in blood of impaired drivers: Considerations for interpreting the results2007In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 29, no 2, p. 248-260Article in journal (Refereed)
    Abstract [en]

    We report the concentrations of scheduled prescription drugs in blood samples from people arrested in Sweden for driving under the influence of drugs (DUID). The investigation covered a 2 year period 2004 (N = 7052 cases) and 2005 (N = 7759 cases) and was prompted by recent legislation stipulating zero-concentration limits in blood for controlled substances. However, prescription drugs are exempt from the zero-limit law provided that the medication was being used in accordance with a doctor's prescription. The blood concentrations of various psychoactive substances were compared with the limits of quantitation of the analytic method used and the so-called therapeutic concentration range according to various reference books and tabulations. Diazepam [N = 1950 (26%)] and nordazepam [N = 2168 (28%)] were the therapeutic agents most frequently identified in these forensic blood samples along with other benzodiazepines such as alprazolam [N = 430 (5.6%)], flunitrazepam [N = 308 (4.0%)], and nitrazepam [N = 222 (2.9%)]. The newer hypnotics, exemplified by zolpidem [N = 148 (1.9%)] and zopiclone [N = 111 (1.5%)], were also high on the list of psychoactive substances identified. Interpreting the concentration of a prescription drug in blood in relation to whether the person had taken an overdose or was abusing the substance in question is not always easy. The age, gender, degree of obesity, and ethnicity of the person concerned, the pharmacokinetic profile of the drug, polymorphism of drug-metabolizing enzymes as well as liver and kidney function and blood hematocrit need to be considered. Among preanalytic factors, stability of the drug in blood after sampling, the type of tubes and preservatives used, the dosage form and route of administration deserve consideration. When therapeutic drug monitoring concentrations are compared with forensic toxicology results, then the plasma-to-whole blood distribution ratio of the drug also needs to be considered. In blood samples from DUID suspects, the concentrations of many commonly used sedatives and hypnotics exceeded the accepted therapeutic limits, which gives an indication of the abuse potential of these types of medications. © 2007 Lippincott Williams & Wilkins, Inc.

  • 54.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Hård, L
    How good are clinical chemistry laboratories at analysing ethylene glycol?2004In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 64, no 7, p. 629-634Article in journal (Refereed)
    Abstract [en]

    The results of an external proficiency test of clinical chemistry laboratories in Sweden when the target analyte was ethylene glycol (EG) are presented. Specimens of plasma were spiked with EG (10% w/v) to give assigned concentrations ranging from 5 to 50 mmol/L. Over a period of 6 years, two control specimens of plasma were sent for analysis on 21 occasions to between 14 and 20 participating laboratories as a declared proficiency trial. The analytical precision between and within laboratories was determined by spiking the plasma specimens with the same concentration of EG so that the results reported back could be considered a duplicate determination. On one occasion propylene glycol (PG) was substituted for EG without informing the participants. The standard deviation (SD) within laboratories expressed as the coefficient of variation (CV) was 4.5% compared with 11.4% between laboratories. Results reported by laboratories using gas chromatography (GC) were in good agreement with those when an enzymatic method was used. The between-laboratory SD increased with concentration of EG in the specimen and at a mean concentration of 18 mmol/L, the pooled SD was 4.11 mmol/L (CV = 23%). Four laboratories reported finding EG in plasma when PG was the diol present, three laboratories used an enzymatic method and one used GC. Clinical laboratories that provide a toxicology service should regularly participate in external quality assurance schemes that include low-molecular-weight alcohols such as EG. Efforts should be made to standardize the analytical methods used for toxicological analysis.

  • 55.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Karlsson, L
    Relation between blood- and urine-amphetamine concentrations in impaired drivers as influenced by urinary pH and creatinine2005In: Human and Experimental Toxicology, ISSN 0960-3271, E-ISSN 1477-0903, Vol. 24, no 12, p. 615-622Article in journal (Refereed)
    Abstract [en]

    Amphetamine undergoes extensive renal excretion and significant amounts are present in urine as the unchanged parent drug. This prompted us to investigate whether a quantitative relationship existed between blood and urine concentrations of amphetamine in the body fluids of drug-impaired drivers apprehended in Sweden, where this stimulant is the major drug of abuse. The relationship between blood and urine concentrations of amphetamine was determined by multivariate analysis with urinary pH and creatinine as predictor variables. Amphetamine was determined in blood and urine by gas chromatography-mass spectrometry with deuterium-labelled internal standards. The concentration of amphetamine in urine was about 200 times greater than the concentration in blood, the mean and median urine/blood ratios were 214 and 160, respectively, with large individual variations. The Pearson correlation coefficient between urine (y) and blood (x) amphetamine was r= 0.53, n=48, which was statistically highly significant (P < 0.001), although the residual standard deviation (SD) was large (±181 mg/L). The correlation coefficient increased (r=0.60) when the concentration of amphetamine in urine was normalized for dilution by dividing with the creatinine content. When urinary pH and creatinine were both included as predictor variables, the correlation coefficient was even higher (r=0.69), now explaining 48% (r 2=0.48) of the variation in urine-amphetamine concentration. However, the partial regression coefficient for creatinine (53±28.7) was not statistically significant (t=1.85, P >0.05), whereas the corresponding regression coefficient for pH was highly significant and had a negative sign (-102±32.6, t= -3.12, P

  • 56.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Kugelberg, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Letter to the Editor - Alcohol concentrations in post-mortem body fluids2006In: Human Exp Toxical, ISSN 0144-5952, Vol. 25, p. 623-624Article in journal (Other academic)
  • 57.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Larsson, H
    Distribution of diazepam and nordiazepam between plasma and whole blood and the influence of hematocrit2004In: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 26, no 4, p. 380-385Article in journal (Refereed)
    Abstract [en]

    The binding of drugs to plasma proteins is important to consider when concentrations in whole blood (eg, in forensic toxicology) are compared with therapeutic and toxic concentrations based on the analysis of plasma or serum. The plasma to whole blood distribution of diazepam (D) and its major metabolite nordiazepam (ND) was investigated under in vitro and ex vivo conditions. Studies in vitro were done by spiking whole blood with D and ND to give concentrations ranging from 0.1 to 1.0 μg/g. Venous blood was also obtained from hospital blood donors (n = 66) after informed consent. The hematocrit, hemoglobin, and water content of blood specimens were determined by routine procedures before D and ND were added to produce target concentrations of ∼0.5 μg/g for each substance. The ex vivo work was done with blood specimens from hospital outpatients who were being medicated with D. Concentrations of D and ND were determined in body fluids by capillary column gas chromatography after adding prazepam as internal standard and solvent extraction with butyl acetate. The method limit of quantitation was 0.03 μg/g for both D and ND. The concentrations of D and ND were highest in plasma and lowest in erythrocytes. The plasma/blood (P/B) distribution ratios did not depend on drug concentration between 0.1 and 1.0 μg/g. The mean P/B ratios were 1.79:1 for D and 1.69:1 for ND when hematocrit was 45%. Furthermore, the P/B ratio for D (y) was positively correlated with blood hematocrit (x) and the regression equation was y = 0.636 + 0.025x (r = 0.86, P < 0.001). A similar strong association was found between the P/B ratio and hematocrit for ND (r = 0.79). P/B ratios of D and ND, blood hematocrit, hemoglobin, and the water content differed between sexes (P < 0.001). The overall mean P/B ratios for D and ND were 1.69 ± 0.097 (± SD) and 1.62 ± 0.08 (P < 0.001, n = 66) respectively when the mean hematocrit was 42.9 ± 3.4 (± SD). For forensic purposes, it would be better to forgo making any conversion of a drug concentration measured in whole blood to that expected in plasma or serum, instead, therapeutic and toxic concentrations should be established for the actual specimens received.

  • 58.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Rössner, Stephan
    Helnykterist nobbad av alkolåset2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, no 35, p. 2487-2488Article in journal (Other academic)
  • 59.
    Jones, A Wayne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Wigmore, J G
    House, C J
    The course of the blood-alcohol curve after consumption of large amounts of alcohol under realistic conditions2006In: Journal of the Canadian Society of Forensic Science, ISSN 0008-5030, Vol. 39, no 3, p. 125-140Article in journal (Refereed)
    Abstract [en]

    This article presents a review and appreciation of an article by Zink and Reinhardt (Z & R) dealing with the time-course of blood-alcohol curves and pharmacokinetic Parameters in healthy men after they drank large amounts of alcohol under controlled real-world conditions. Here we present a reappraisal of this published study to highlight certain aspects of interest for forensic casework, such as when expert testimony is presented on the pharmacokinetics of ethanok Healthy men, all regular drinkers, consumed large doses of alcohol (3.0-5.7 g/kg body weight) in a social setting for 5 to 10 hours. According to preference, the men drank beer, stomach bitters, or spirits in the company of a girlfriend or spouse. Food was available during the drinking session and the men were allowed to watch video films or play cards. Specimens of venous blood were taken from indwelling catheters every 15 to 30 minutes during and after the end of drinking and the concentrations of ethanol were determined in duplicate by both gas chromatography and enzymatic oxidation. The mean of the four measurements was used to plot concentration-time profiles of alcohol for each rubject. The average Cmax was 2.65 g/kg (range 1.92-3.80 g/kg) and tmax occurred at 425 min (range 250-608 min) after the start of drinking. In five of the 14 drinking studies, Cmax occurred before the subjects finished their last drink, mean time to peak after the end of drinking was 2 min (range - 56 to 50 min). The rate of alcohol elimination from blood was 0.167 g/kg/h on average (range 0.11 to 0.26 g/kg/h) and only one subject exceeded 0.20 g/kg/h. The average volume of distribution of alcohol (Widmark's rho factor) was 1.05 (range 0.77-1.32), being considerably higher than expected from knowledge of the water content of the blood and the whole body. The abnormally high rho-factors suggest an appreciable presystemic metabolism of alcohol, either in the gut or the liver or both organs, when drinking continues for 5-10 hours. The rate of alcohol elimination from blood was not much different from many bolus dose drinking experiments (mean 0.15 g/kg/h). It seems that continuous heavy drinking for days or weeks is necessary to increase the activity of microsomal enzymes (CYP2E1) and cause a faster elimination rate of alcohol from blood. There were no unexpected irregularities in the concentrations of alcohol between successive blood samples, which does not support the notion of a so-called steepling effect in the post-absorptive state.

  • 60.
    Järemo, Petter
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Local Health Care Services in the East of Östergötland, Department of Internal Medicine VHN.
    Starkhammar, C
    Östergötlands Läns Landsting, Public Dental Service.
    Lundström, Å
    Östergötlands Läns Landsting, Public Dental Service.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Richter, Arina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Cardiology. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Inverse relationship between the severity of gingivitis and platelet reactivity in stable angina pectoris [6]2007In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 5, no 2, p. 422-423Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 61.
    Kallner, Anders
    et al.
    Karolinska Universitetssjukhuset.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Mätosäkerhet inom Laboratoriemedicin2005Report (Other academic)
  • 62.
    Kugelberg, Fredrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Pharmacology.
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Interpreting results of ethanol analysis in postmortem specimens: A review of the literature2007In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 165, no 1, p. 10-29Article in journal (Refereed)
    Abstract [en]

    We searched the scientific literature for articles dealing with postmortem aspects of ethanol and problems associated with making a correct interpretation of the results. A person's blood-alcohol concentration (BAC) and state of inebriation at the time of death is not always easy to establish owing to various postmortem artifacts. The possibility of alcohol being produced in the body after death, e.g. via microbial contamination and fermentation is a recurring issue in routine casework. If ethanol remains unabsorbed in the stomach at the time of death, this raises the possibility of continued local diffusion into surrounding tissues and central blood after death. Skull trauma often renders a person unconscious for several hours before death, during which time the BAC continues to decrease owing to metabolism in the liver. Under these circumstances blood from an intracerebral or subdural clot is a useful specimen for determination of ethanol. Bodies recovered from water are particular problematic to deal with owing to possible dilution of body fluids, decomposition, and enhanced risk of microbial synthesis of ethanol. The relationship between blood and urine-ethanol concentrations has been extensively investigated in autopsy specimens and the urine/blood concentration ratio might give a clue about the stage of alcohol absorption and distribution at the time of death. Owing to extensive abdominal trauma in aviation disasters (e.g. rupture of the viscera), interpretation of BAC in autopsy specimens from the pilot and crew is highly contentious and great care is needed to reach valid conclusions. Vitreous humor is strongly recommended as a body fluid for determination of ethanol in postmortem toxicology to help establish whether the deceased had consumed ethanol before death. Less common autopsy specimens submitted for analysis include bile, bone marrow, brain, testicle, muscle tissue, liver, synovial and cerebrospinal fluids. Some investigators recommend measuring the water content of autopsy blood and if necessary correcting the concentration of ethanol to a mean value of 80% w/w, which corresponds to fresh whole blood. Alcoholics often die at home with zero or low BAC and nothing more remarkable at autopsy than a fatty liver. Increasing evidence suggests that such deaths might be caused by a pronounced ketoacidosis. Recent research has focused on developing various biochemical tests or markers of postmortem synthesis of ethanol. These include the urinary metabolites of serotonin and non-oxidative metabolites of ethanol, such as ethyl glucuronide, phosphatidylethanol and fatty acid ethyl esters. This literature review will hopefully be a good starting point for those who are contemplating a fresh investigation into some aspect of postmortem alcohol analysis and toxicology. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 63.
    Kuteeva, Eugenia
    et al.
    Department of Neuroscience Karolinska Institutet.
    Calza, Laura
    DIMORFIPA University of Bologna.
    Holmberg, Kristina
    Department of Neuroscience Karolinska Institute.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Ögren, Sven Ove
    Department of Neuroscience Karolinska Institute.
    Hökfelt, Tomas
    Department of Neuroscience Karolinska Institutet.
    Distribution of galanin and galanin transcript in the brain of a galanin-overexpressing transgenic mouse2004In: Journal of Chemical Neuroanatomy, ISSN 0891-0618, E-ISSN 1873-6300, Vol. 28, no 4, p. 185-216Article in journal (Refereed)
    Abstract [en]

    The distribution of galanin mRNA-expressing cells and galanin-immunoreactive (IR) cell bodies and processes was studied in the brain of mice overexpressing galanin under the PDGF-B promoter (GalOE mice) and of wild type (WT) mice, both in colchicine-treated and non-treated animals. In this abstract, we only describe the results in GalOE mouse. A widespread ectopic expression of galanin (both mRNA and peptide) was found, that is a situation when neither transcript nor peptide could be seen in WT mice, not even after colchicine treatment. However, in some regions, such as claustrum, basolateral amygdala, thalamus, CA1 pyramidal cells, and Purkinje cells only galanin mRNA could be detected. In the forebrain galanin was seen in the mitral cells of the olfactory bulb, throughout the cortex, in the basolateral amygdaloid nucleus, claustrum, granular and pyramidal cell layers of the hippocampus, subiculum and presubiculum. In the thalamus, the anterodorsal, mediodorsal, intermediodorsal and mediodorsal lateral nuclei, the reuniens and reticular nuclei showed ectopic expression of galanin. Within the hypothalamus, neurons of the suprachiasmatic nucleus contained galanin. In the mesencephalon, the geniculate nucleus, nucleus ruber, the mesencephalic trigeminal and reticulotegmental nuclei ectopically expressed galanin. In the cerebellum, galanin was observed in the Purkinje cells and in the lateral and interposed cerebellar nuclei. In the pons, sensory and motor nuclei of the trigeminal nerve, the laterodorsal and dorsal tegmental nuclei, the pontine, reticulotegmental and gigantocellular reticular nuclei expressed galanin. Within the medulla oblongata, labeled cells were detected in the facial, ambiguus, prepositus, lateral paragigantocellular and lateral reticular nuclei, and spinal trigeminal nucleus. High densities of galanin-IR fibers were found in the axonal terminals of the lateral olfactory tract, the hippocampal and presumably the cerebellar mossy fibers system, in several thalamic and hypothalamic regions and the lower brain stem. Possible functional consequences of galanin overexpression are discussed.

  • 64.
    Kågedal, Bertil
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Kullman, Anita
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Lenner, Liselotte
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Träger, Catarina
    Kogner, Per
    Farnebäck, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Pterin-dependent tyrosine hydroxylase mRNA is not expressed in human melanocytes or melanoma cells2004In: Pigment Cell Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 17, no 4, p. 346-351Article in journal (Refereed)
    Abstract [en]

    Pterin-dependent tyrosine hydroxylase has been described to occur occasionally in melanocytes. It is therefore important to quantify the mRNA of this enzyme in pigment cells to understand whether this enzyme can take an active part in pigment formation. A real-time reverse transcription-polymerase chain reaction method was used to quantify tyrosine hydroxylase mRNA in melanocytes and melanoma cells. The calibrator was obtained by amplification of a segment of cDNA from tyrosine hydroxylase mRNA, which included the target thus allowing enumeration of the number of transcripts per cell. In melanocytes (n = 3), tyrosine hydroxylase mRNA ranged from non-detectable to 0.000492 transcripts/cell and in melanoma cells from non-detectable to 0.005340 transcripts/cell. In neuroblastoma cells, the median tyrosine hydroxylase mRNA number was 0.4 transcripts/cell (range 0.02-25 transcripts/cell). The amount of tyrosine hydroxylase mRNA in the pigment cells was far less than the mRNA concentrations of four melanocyte-specific proteins measured in the same melanocytes and melanoma cells. We conclude that on the average less than 1 of 1000 melanocytes and melanoma cells contains at least one tyrosine hydroxylase mRNA molecule. Consequently, in 999 of 1000 cells translation into the corresponding enzyme protein cannot occur because of the lack of an mRNA template. Thus, in these cells there is no pterin-dependent tyrosine hydroxylase that can contribute to pigment formation by producing priming amounts of L-dopa for proper function of tyrosinase.

  • 65.
    Kågedal, Bertil
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lindblad, Eva
    Bjuremark, Anna
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Behavioural Sciences, Studies in Adult, Popular and Higher Education.
    Kompetensutveckling i forskargrupper. Ett av arbetslivsfonden stött projekt1995Report (Other academic)
  • 66.
    Larsson, Lasse
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Joniserat kalcium ger bättre beslutsunderlag än albuminkorrigerat kalcium2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, p. 2289-2290Article in journal (Other academic)
  • 67.
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    D-dimeranalys av djup ventrombos kräver skicklighet hos avläsaren och dialog mellan laboratorium och klinik2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 9, p. 757-757Article in journal (Other academic)
  • 68.
    Lindahl, Tomas
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lundahl, T. H.
    Östergötlands Läns Landsting. Västervik Hospital, Sweden.
    Ranby, M
    Östergötlands Läns Landsting.
    Fransson, Sven-Göran
    Östergötlands Läns Landsting, Heart Centre, Department of Cardiology Thoracic Radiology.
    Clinical evaluation of a diagnostic strategy for deep venous thrombosis with exclusion by low plasma levels of fibrin degradation product D-dimer1998In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 58, no 4, p. 307-316Article in journal (Refereed)
    Abstract [en]

    Clinical research studies have indicated the possibility of diagnostic strategies for deep venous thrombosis (DVT), strategies which include a step where the diagnosis is excluded by low or undetectable plasma levels of fibrin degradation product D-dimer. In collaboration with two local hospitals in Sweden, three implementations of such a strategy are evaluated in this study. Procedures 1, 2 and 3 differed in the method for D-dimer determination, i.e. latex agglutination, immunofiltration and both, respectively. The evaluated procedures were performed in parallel and compared with the current procedure in the different hospitals. At both hospitals, the current procedure stipulated mandatory phlebography and laboratory analysis of acute coagulation status and routine haematology with report-back time of 2 h. Within the 2 h the hospitals clinical chemistry laboratories also determined plasma D-dimer by the two methods. Of 180 patients enrolled in the study, phlebography was successful in 155 and unsuccessful in 25. The phlebographies revealed 47 proximal DVT, 13 distal DVT and 95 no DVT. With Procedure 1, 53 patients (29%) were excluded in the D-dimer step. For these patients, 47 successful phlebographies revealed one proximal DVT and two distal DVT. With Procedure 2, 71 patients (39%) were excluded. For these patients, 65 successful phlebographies revealed two proximal DVT and four distal DVT. With Procedure 3,44 patients (24%) were excluded. For these patients, 41 successful phlebographies revealed two distal DVT. The negative predictive values of the D-dimer exclusion step, with 95% confidence intervals given within parentheses, were 96% (88-100%), 91% (84-98%) and 95% (89-100%) for Procedures 1, 2 and 3, respectively. The evaluation demonstrated that the diagnostic potential of D-dimer revealed in research studies can be achieved in clinical practice. The study also indicated that the positive diagnostic value of high levels of D-dimer may be of use in finalizing the diagnosis in the 14% of patients for whom phlebography is unsuccessful.

  • 69. Lindberg, L
    et al.
    Brauer, S
    Wollmer, P
    Goldberg, L
    Jones, A Wayne
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Olsson, SG
    Breath alcohol concentration determined with a new analyzer using free exhalation predicts almost precisely the arterial blood alcohol concentration2007In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 168, no 2-3, p. 200-207Article in journal (Refereed)
    Abstract [en]

    A new breath alcohol (ethanol) analyzer has been developed, which allows free exhalation, standardizes measured exhaled alcohol concentration to fully saturated water vapor at a body temperature of 37 °C (43.95 mg/L) and includes a built-in self-calibration system. We evaluated the performance of this instrument by comparing standardized alcohol concentration in freely expired breath (BrAC) with arterial (ABAC) and venous (VBAC) blood alcohol concentrations in fifteen healthy volunteers who drank 0.6 g of alcohol per kg body weight. The precision (coefficient of variation, CV) of the analyzer based on in vivo duplicate measurements in all phases of the alcohol metabolism was 1.7%. The ABAC/BrAC ratio was 2251 ± 46 (mean ± S.D.) in the post-absorptive phase and the mean bias between ABAC and BrAC × 2251 was 0.0035 g/L with 95% limits of agreement of 0.033 and -0.026. The ABAC and BrAC × 2251 were highly correlated (r = 0.998, p < 0.001) and the regression relationship was ABAC = 0.00045 + 1.0069 × (BrAC × 2251) indicating excellent agreement and no fixed or proportional bias. In the absorption phase, ABAC exceeded BrAC × 2251 by at most 0.04 ± 0.03 g/L when tests were made at 10 min post-dosing (p < 0.05). The VBAC/BrAC ratio never stabilized and varied continuously between 1834 and 3259. There was a proportional bias between VBAC and BrAC × 2251 (ABAC) in the post-absorptive phase (p < 0.001). The pharmacokinetic analysis of the elimination rates of alcohol and times to zero BAC confirmed that BrAC × 2251 and ABAC agreed very well with each other, but not with VBAC (p < 0.001). We conclude that this new breath analyzer using free exhalation has a high precision for in vivo testing. The BrAC reflects very accurately ABAC in the post-absorption phase and substantially well in the absorption phase and thereby reflects the concentration of alcohol reaching the brain. Our findings highlight the magnitude of arterio-venous differences in alcohol concentration and support the use of breath alcohol analyzers as a stand-alone test for medical and legal purposes. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 70.
    Ljungdahl, Nina
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences.
    Haarhaus, Mathias
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences.
    Linder, Cecilia
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Magnusson, Per
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Comparison of 3 Third-Generation Assays for Bio-intact Parathyroid Hormone2006In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 52, no 5, p. 903-904Article in journal (Refereed)
  • 71.
    Löfman, Owe
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Hallberg, Inger
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Berglund, Kenneth
    Community Medicine, County Council of Uppsala, Uppsala, Sweden.
    Wahlström, Ola
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Orthopaedics and Sports Medicine. Östergötlands Läns Landsting, Orthopaedic Centre, Department of Orthopaedics Linköping.
    Kartous, Lisa
    Department of Geriatrics, Ryhov Hospital, Jönköping, Sweden.
    Rosenqvist, Anna-Maria
    Department of Geriatrics, Ryhov Hospital, Jönköping, Sweden.
    Larsson, Lasse
    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.
    Toss, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Women with low-energy fracture should be investigated for osteoporosis2007In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 78, no 6, p. 813-821Article in journal (Refereed)
    Abstract [en]

    Introduction: Treatment of osteoporosis is becoming more effective, but methods to identify patients who are most suitable for investigation and treatment are still being debated. Should any type of fracture have higher priority for investigation of osteoporosis than any other? Is the number of previous fractures useful information? Material and methods: We investigated 303 consecutive women patients between 55 and 75 years of age who had a newly diagnosed low-energy fracture. They answered a questionnaire on previous fractures which also dealt with risk factors. Bone mineral density (BMD) was measured at the hip, lumbar spine, and forearm. Results: The distribution of fracture location was: distal forearm 56%, proximal humerus 12%, vertebra 18%, and hip 13%, all with similar age. Half of the subjects had had at least one previous fracture before the index fracture, 19% had had two previous fractures, and 6% had had three or more previous fractures. Patients with vertebral or hip fracture had lower BMD and had had more previous fractures than patients with forearm or humerus fractures. There was an inverse correlation between number of fractures and BMD. Osteoporosis was present in one-third of patients with forearm fracture, in one-half of those with hip or humerus fracture, and in two-thirds of those with vertebral fracture. Interpretation: Vertebral fractures were the strongest marker of low BMD and forearm fractures the weakest. The number of previous fractures is helpful information for finding the most osteoporotic patient in terms of severity. Investigation of osteoporosis therefore seems warranted in every woman between the ages of 55 and 75 with a recent low-energy fracture, with highest priority being given to those with vertebral, hip, or multiple fractures. Copyright© Taylor & Francis 2007. all rights reserved.

  • 72.
    Nezirevic Dernroth, Dzeneta
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Årstrand, Kerstin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Kågedal, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Hydrophilic interaction liquid chromatographic analysis of aminohydroxyphenylalanines from melanin pigments2007In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1163, no 1-2, p. 70-79Article in journal (Refereed)
    Abstract [en]

    Malignant melanomas are more often seen in subjects with light colored skin who tan poorly than in persons who tan more rapidly. This has been attributed to the structure of their pigment, pheomelanin, which differs markedly from the eumelanin of persons with darker skin. To study the hydrolysis products of pheomelanin pigments a new method was developed for analysis of 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-amino-4-hydroxyphenylalanine (3-AHP). Pheomelanin samples were hydrolyzed and extracted with solid-phase extraction columns using strong cation-exchange (SCX) cartridges. Separation of 4-AHP and 3-AHP was achieved on a ZIC-HILIC column (150 mm × 2.1 mm I.D.) with a mobile phase consisting of acetonitrile:0.1 M ammonium acetate buffer, pH 4.5 (82:18, v/v). Detection was performed with an electrochemical detector at +400 mV. Run time was 30 min. The limits of detection were 73 pg and 51 pg for 4-AHP and 3-AHP respectively, using 2 μl injections. Good linearity was found within the range 0.05-5.0 μg/ml. Absolute recovery was 70% and relative recovery was 100%. The AHPs were stable for 1 year in the hydrolyzed samples, for 4 days in the eluates from solid-phase sorbents stored in the refrigerator, and for 2 days diluted with mobile phase and stored in the autosampler at 10 °C. The within-day imprecision was <5% and the between-day imprecision was <7% for the two analytes. The method, applied to the analysis of pheomelanin in urine from human melanoma patients, allows the analysis of 30 samples in one set and is suitable for routine work with human hair and melanoma cells. By using the ZIC-HILIC stationary phase, ion-pairing reagents could be avoided, which makes the method suitable to further analysis of degradation products from pheomelanins using mass spectrometric detection. © 2007 Elsevier B.V. All rights reserved.

  • 73.
    Olhager, Elisabeth
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Flinke, Eva
    Linköping University, Department of Medicine and Care, Medical Radiology. Linköping University, Faculty of Health Sciences.
    Hannerstad, Ulf
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Linköping University, Faculty of Health Sciences.
    Forsum, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Nutrition. Linköping University, Faculty of Health Sciences.
    Studies on human body composition during the first 4 months of life using magnetic resonance imaging and isotope dilution2003In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 54, no 6, p. 906-912Article in journal (Refereed)
    Abstract [en]

    Assessing body composition during infancy requires data for the so-called reference infant. Currently available data for this purpose need to be updated and extended using methods based on principles different from those used previously to define the reference infant. Thus, magnetic resonance imaging was applied to full-term healthy boys (n = 25) and girls (n = 21), 4-131 d old, to estimate adipose tissue volume (ATV) and the amounts of s.c. and non-s.c. adipose tissue (AT). Total body water was estimated using isotope dilution. Total body fat (TBF), fat free weight (FFW) and the degree of hydration in FFW were calculated. Increases in weight, TBF, and FFW with age agreed with current reference data, although when compared with the reference, a slightly more rapid increase in % TBF was observed for boys. The degree of hydration in FFW was 78.9 ± 4.5% (n = 45). Both sexes showed significant increases with age in s.c. ATV (14.7 and 13.0 mL/d for boys and girls, respectively) and in non-s.c. ATV (1.58 and 1.26 mL/d, respectively). Subcutaneous ATV was 90.5 ± 1.8% (boys) and 91.1 ± 1,9% (girls) of total ATV. In conclusion, a pronounced increase with age in the amount of AT was demonstrated involving a considerable gain in s.c. fat during early life. Except for % TBF in boys, changes in body composition with age agreed with current reference data.

  • 74.
    Ramström, Sofia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Clotting time analysis of citrated blood samples is strongly affected by the tube used for blood sampling2005In: Blood Coagulation and Fibrinolysis, ISSN 0957-5235, E-ISSN 1473-5733, Vol. 16, no 6, p. 447-452Article in journal (Refereed)
    Abstract [en]

    Our aim was to establish whether differences in clotting times for recalcified blood and plasma samples might be explained by the use of different blood collection tubes. Samples obtained from different plastic vacuum tubes were recalcified and clotting times determined by free oscillation rheometry. The clotting times for blood collected in Vacutainer (Becton Dickinson, Rutherford, New Jersey, USA) or Vacuette (Greiner Bio-One, Kremsmünster, Austria) tubes decreased with time, with maximal effect after 30 min. Blood from Monovette (Sarstedt, Nümbrecht, Germany) tubes displayed longer clotting times, which did not decrease with time. Clotting times for plasma prepared after 1 h storage in Vacutainer or Vacuette tubes were unaffected by subsequent addition of corn trypsin inhibitor to inhibit factor XIIa, although an antibody against factor XI prolonged the clotting time markedly. In Monovette plasma, both corn trypsin inhibitor and anti-factor XI effectively prolonged the clotting time. When corn trypsin inhibitor or anti-factor XI was added to the tubes before blood collection, but both additions clearly prolonged the clotting times in all types of tubes, even though corn trypsin inhibitor was less effective in whole blood. Antibodies against human tissue factor did not affect the clotting times. The amounts of platelet or leukocyte microparticles in plasma were low and similar in all tubes. This indicates that blood collection in Vacutainer or Vacuette tubes induces a rapid activation of factor XII and factor XI.

  • 75. Ronquist, G
    et al.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Inherited, non-spherocytic haemolysis due to deficiency of glucose-6-phosphate dehydrogenase2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 1, p. 105-111Article in journal (Refereed)
    Abstract [en]

    The about 400 million individuals worldwide suffering from a hereditary deficiency of the enzyme glucose-6-phosphate dehydrogenase (G6PD) may experience different degrees of haemolytic anaemia. Haemoglobin is present in very high concentrations in the erythrocyte cytoplasm, at risk of falling out of solution if the internal environment or the haemoglobin itself is changed. G6PD is a crucial enzyme producing reduced glutathione in the erythrocyte cytoplasm for the purpose of protecting haemoglobin against oxidative damage. The presence of unopposed oxidizing agents leading to oxidation of the sulfhydryl bridges between parts of the haemoglobin molecule decrease the solubility of haemoglobin, leading to precipitations called Heinz bodies. The laboratory investigation of G6PD deficiency is commonly done by a quantitative spectrophotometric analysis or by a rapid fluorescent spot test detecting the generation of NADPH from NADP. Genetic tests based on polymerase chain reaction detect specific mutations and may be used for population screening, family studies, or prenatal diagnosis. © 2007 Taylor & Francis.

  • 76.
    Schmid, Eduard
    et al.
    Department of Opthalmology Insbruch Medical University.
    Leisterer, Johannes
    Department of Pharmacology Insbruch Medical University.
    Doblinger, Alfred
    Department of Pharmacology Medical University of Insbruch.
    Laslop, Andrea
    Department of Pharmacology Medical University of Insbruch.
    Fischer-Colibrie, Reiner
    Department of Pharmacology Medical University of Insbruch.
    Humpel, Christian
    Laboratory of Psychiatry Medical University of Insbruch.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Teuchner, Barbara
    Department of Opthalmology Medical University of Insbruch.
    Lalehabbasi, Djavad
    Department of Opthalmology Medical Uiversity of Insbruch.
    Dragosits, Ernst
    Department of Opthalmology Medical University of Insbruch.
    Kunze, Christian
    Department of Opthalmology Medical University of Insbruch.
    Philipp, Wolfgang
    Department of Opthalmology Medical University of Insbruch.
    Göttinger, Wolfgang
    Department of Opthalmology Medical University of Insbruch.
    Troger, Josef
    Department of Opthalmology Medical University of Insbruch.
    Neurokinin A is a main constituent of sensory neurons innervating the anterior segment of the eye2005In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 46, no 1, p. 268-274Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To study the innervation pattern of the anterior segment of the eye by neurokinin (NK)-A-immunoreactive nerves and to determine their sensory origin. METHODS. The presence and distribution of NKA was examined in human eyes by radioimmunoassay and immunofluorescence. The source of nerves was determined by measuring the concentration of NKA in the trigeminal ganglion (TG) in comparison with that of the classic sensory peptides substance P (SP) and calcitonin gene-related peptide (CGRP) and in eye tissues in capsaicin-pretreated rats versus control subjects. The NKA-like immunoreactivities were further characterized by reversed phase HPLC in the rat TG and the human iris- ciliary body complex. The presence of γ-PPT-A mRNA was studied in the rat TG by in situ hybridization. RESULTS. The levels of NKA in human eye tissues were approximately 10 times higher than those of SP but lower than those of CGRP. Nerve fibers were visualized in the cornea, the trabecular meshwork, the iridial stroma, and, prominently, in the sphincter muscle, the ciliary body stroma and muscle and processes, and the choroidal stroma and surrounding blood vessels. In the rat TG, the concentration of NKA was approximately five times higher than that of SP. Capsaicin led to a >60% decrease of the concentration of the peptide in the rat TG and rat eye tissues except for the retina. NKA-like immunoreactivities were present in a single peak corresponding to synthetic NKA, both in the rat TG and in the human iris- ciliary body complex, and numerous ganglion cells of small size were labeled by a γ-PPT-A probe in the rat TG. CONCLUSIONS. The present results clearly demonstrate that NKA is a main constituent of sensory neurons innervating the anterior segment of the eye. The presence of the peptide in C fibers in ocular tissues indicates a participation in sensory transmission and an involvement in the irritative response in the eye, a model for neurogenic inflammation in lower mammals.

  • 77. Schmidt, PT
    et al.
    Degerblad, M
    Lindström, E
    Sundqvist, M
    Näslund, E
    Gillberg, PG
    Husebye, E
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hellström, PM
    Circulating ghrelin levels after food intake during different phases of the migrating motor complex in man2006In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 36, no 7, p. 503-508Article in journal (Refereed)
    Abstract [en]

    Background: The timing of the migrating motor complexes (MMC) at food intake may influence gastric emptying and release of regulatory hormones. This report studies the relationships between phases I (motor quiescence) and II (intermediate frequency contractions) of MMC and prandial gut hormone response. Materials and methods: Seven fasting volunteers ingested a meal during phase I or II of MMC verified by manometry, using paracetamol as a marker for gastric emptying. Blood was sampled before, during and 210 min after food intake for analysis of ghrelin, motilin, insulin and paracetamol. Results: The basal level of ghrelin during phase I was 127.5 ± 25.4 pmol L-1 and during phase II was 132.4 ± 24.8 pmol L-1. After food intake during phase I, ghrelin fell to 77.2 ± 10 pmol L-1, in phase II it fell to 82.7 ± 17.8 pmol L-1 within 60 min and returned to baseline levels after 120 min. Baseline levels of motilin were 16 ± 2 pmol L-1 and 18 ± 3 pmol L-1 during phases I and II, respectively. After food, motilin decreased to 8.5 ± 0.7 pmol L-1 and 8.7 ± 1.0 pmol L-1 within 60 min and returned to baseline after 90 min. Insulin levels in phases I and II were 8.1 ± 1.2 mU L-1 and 8.6 ± 0.7 mU L-1, respectively, reaching 138.9 ± 35.6 mU L-1 and 167.4 ± 30.0 mU L-1 at 45 min postprandially. Conclusions: The nutritional status of the gastrointestinal tract at food intake had only a limited impact on plasma ghrelin. After food intake, plasma ghrelin drops, similar to motilin, and resumes preprandial levels within 120 min. © 2006 Blackwell Publishing Ltd.

  • 78. Sharp, CA
    et al.
    Brown, SJ
    Davie, MWJ
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Mohan, S
    Increased matrix concentrations of IGFBP-5 in cancellous bone in osteoarthritis2004In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 63, no 9, p. 1162-1165Article in journal (Refereed)
    Abstract [en]

    Background: In osteoarthritis cancellous bone adapts to meet altered mechanical loading. These changes may be mediated by insulin-like growth factors (IGF-I and IGF-II), but the matrix bound binding protein, IGFBP-5 has not been investigated. Objectives: To measure IGF-I, IGF-II, and IGFBP-5 in femoral head bone from non-OA controls and patients with OA, and to relate these to apparent density (PA) and elastic modulus (Ec). Methods: ρA, Ec, and IGF system components were measured in cancellous bone from superior and inferior regions of femoral heads from 31 patients with OA and 11 age selected controls. Results: Ec and ρA were greater (p<0.05) in the superior region of all femoral heads. In primary OA, ρA was increased in the inferior region (p<0.05). IGFBP-5 was increased, about twofold, at superior and inferior regions in primary OA (1.60 and 1.54 ng/mg bone, respectively, both p<0.05) and in Paget's disease (2.44 and 1.75 ng/mg bone, both p<0.05) compared with controls (0.73 and 0.95 ng/mg bone). In controls, inverse correlations between IGFBP-5 and both ρA and Ec at superior (rs = -0.64 and -0.73, both p<0.05) and inferior regions (rs = -0.72, p<0.05 and -0.24 (NS)) were seen, but these were lost in OA. Conclusions: IGFBP-5 may modulate cancellous bone formation by negative feedback. In end stage OA this is disrupted, but has little influence on material properties.

  • 79. Sharp, Christopher A
    et al.
    Linder, Cecilia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Analysis of human bone alkaline phosphatase isoforms: Comparison of isoelectric focusing and ion-exchange high-performance liquid chromatography2007In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 379, no 1-2, p. 105-112Article in journal (Refereed)
    Abstract [en]

    Background: Several isoforms of alkaline phosphatase (ALP) can be identified in human tissues and serum after separation by anion-exchange HPLC and isoelectric focusing (IEF). Methods: We purified four soluble bone ALP (BALP) isoforms (B/I, B1x, B1 and B2) from human SaOS-2 cells, determined their specific pI values by broad range IEF (pH 3.5-9.5), compared these with commercial preparations of bone, intestinal and liver ALPs and established the effects of neuraminidase and wheat germ lectin (WGA) on enzyme activity. Results: Whilst the isoforms B1x (pI = 4.48), B1 (pI = 4.32) and B2 (pI = 4.12) resolved as well-defined bands, B/I resolved as a complex (pI = 4.85-6.84). Neuraminidase altered the migration of all BALP isoforms to pI = 6.84 and abolished their binding to the anion-exchange matrix, but increased their enzymatic activities by 11-20%. WGA precipitated the BALP isoforms in IEF gels and the HPLC column and attenuated their enzymatic activities by 54-73%. IEF resolved the commercial BALP into 2 major bands (pI = 4.41 and 4.55). Conclusions: Migration of BALP isoforms is similar in IEF and anion-exchange HPLC and dependent on sialic acid content. HPLC is preferable in smaller scale research applications where samples containing mixtures of BALP isoforms are analysed. Circulating liver ALP (pI = 3.85) can be resolved from BALP by either method. IEF represents a simpler approach for routine purposes even though some overlapping of the isoforms may occur. © 2007 Elsevier B.V. All rights reserved.

  • 80. Shi, T-J S
    et al.
    Dahlström, A
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Ceccatelli, S
    Decosterd, I
    Pedrazzini, T
    Hökfelt, T
    Deletion of the neuropeptide Y Y1 receptor affects pain sensitivity, neuropeptide transport and expression, and dorsal root ganglion neuron numbers2006In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 140, no 1, p. 293-304Article in journal (Refereed)
    Abstract [en]

    Neuropeptide Y has been implicated in pain modulation and is substantially up-regulated in dorsal root ganglia after peripheral nerve injury. To identify the role of neuropeptide Y after axotomy, we investigated the behavioral and neurochemical phenotype of neuropeptide Y Y1 receptor knockout mice with focus on dorsal root ganglion neurons and spinal cord. Using a specific antibody Y1 receptor immunoreactivity was found in dorsal root ganglia and in dorsal horn neurons of wild-type, but not knockout mice. The Y1 receptor knockout mice exhibited a pronounced mechanical hypersensitivity. After sciatic nerve axotomy, the deletion of Y1 receptor protected knockout mice from the axotomy-induced loss of dorsal root ganglion neurons seen in wild-type mice. Lower levels of calcitonin gene-related peptide and substance P were identified by immunohistochemistry in dorsal root ganglia and dorsal horn of knockout mice, and the axotomy-induced down-regulation of both calcitonin gene-related peptide and substance P was accentuated in Y1 receptor knockout. However, the transcript levels for calcitonin gene-related peptide and substance P were significantly higher in knockout than in wild-type dorsal root ganglia ipsilateral to the axotomy, while more calcitonin gene-related peptide- and substance P-like immunoreactivity accumulated proximal and distal to a crush of the sciatic nerve. These results indicate that the deletion of the Y1 receptor causes increased release and compensatory increased synthesis of calcitonin gene-related peptide and substance P in dorsal root ganglion neurons. Together, these findings suggest that, after peripheral nerve injury, neuropeptide Y, via its Y1 receptor receptor, plays a key role in cell survival as well as in transport and synthesis of the excitatory dorsal horn messengers calcitonin gene-related peptide and substance P and thus may contribute to pain hypersensitivity. © 2006 IBRO.

  • 81.
    Sjöstedt, Camilla
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Hannestad, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Franzén, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Söderholm, Johan D
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Borch, Kurt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Atrophic gastritis is associated with increased sucrose permeability related to chronic inflammation2005In: Digestion, ISSN 0012-2823, E-ISSN 1421-9867, Vol. 72, no 4, p. 201-206Article in journal (Refereed)
    Abstract [en]

    Background: Different theories have been presented to explain how atrophic gastritis may lead to gastric cancer development. One contributing factor could be impaired function of the gastric mucosal barrier. The aim of this study was to investigate if there are changes in gastric mucosal permeability to sucrose in atrophic gastritis. Methods: The study comprised 22 patients with atrophic gastritis and 21 normal controls. Gastritis was classified according to the Sydney system from endoscopic biopsies of the gastric corpus and antrum. All subjects were exposed to oral sucrose load (100 g), and the fraction of sucrose excreted in urine was measured by gas chromatography-mass spectrometry. Results: The fraction of sucrose excreted in urine after oral load was significantly increased in atrophic gastritis compared with controls (median 0.08 vs. 0.04%, p = 0.003). Sucrose excretion was positively related to the degree of chronic inflammation (median fraction excreted: mild inflammation 0.06%, moderate inflammation 0.08%, severe inflammation 0.18%, p = 0.04) rather than to the degree of atrophy in the gastric mucosa. Occurrence of intestinal metaplasia was also associated with significantly higher sucrose excretion. However, in multivariate analysis, including intestinal metaplasia, only the degree of inflammation was positively related to sucrose excretion. Conclusion: Atrophic gastritis is associated with increased sucrose permeability, suggesting paracellular leakage of the gastric mucosa. This leakage seems to be related to the degree of inflammation rather than the degree of atrophy. The findings may have implications for the diseases and complications associated with atrophic gastritis. Copyright © 2005 S. Karger AG.

  • 82.
    Spetz, Anna-Clara
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Ellefsen, Katrine
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Lassvik, Claes
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Calcitonin gene-related peptide during sweating in young healthy women2005In: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 60, no 3, p. 149-153Article in journal (Refereed)
    Abstract [en]

    Calcitonin gene-related peptide (CGRP) concentrations are increased in postmenopausal women and castrated men with symptomatic flushing. We wanted to determine if a CGRP increase exists in the plasma of healthy fertile-age women during sweating. Plasma concentrations of CGRP were measured by radioimmunoassay at maximal sweating during a sauna session and during bicycle exercise both at maximal and 70% of maximal work capacity in 8 healthy women of fertile age. Plasma concentrations of CGRP were unaffected (>90% statistical power) during both experimental sessions. We suggest that sweating itself does not expiai n the rise in CGRP concentrations observed in flushing postmenopausal women. Copyright © 2005 S. Karger AG.

  • 83.
    Spetz, Anna-Clara
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Palmefors, Lennart
    Skobe, Staffan
    Strömstedt, Martin
    Fredriksson, Mats
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hammar, Mats
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping.
    Testosterone correlated to symptoms of partial androgen deficiency in aging men (PADAM) in an elderly Swedish population2007In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 14, no 6, p. 999-1005Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate the prevalence of different symptoms of partial androgen deficiency in aging men (PADAM) and to correlate them with blood concentrations of testosterone and bioavailable testosterone. DESIGN: A total of 370 men, aged 55 to 75 years, were invited to one of three primary healthcare centers in Sweden. They were asked to complete a questionnaire regarding demographic data, medical history, mood status, medication, castration therapy and smoking, exercise and alcohol habits, as well as different symptoms of PADAM. The 10 questions from a previously used questionnaire (the ADAM questionnaire) were included. The men were offered blood tests for analyses of testosterone, follicle stimulating hormone, luteinizing hormone, steroid hormone-binding globulin, and albumin. From these test results, we calculated the bioavailable testosterone. RESULTS: Of the questionnaires sent out, 81.6% were returned and eligible for evaluation. Blood samples were obtained from 85.8% of men answering the questionnaire. Many of the symptoms, including five from the ADAM questionnaire, were more common in older age groups (P < 0.05). Three symptoms, deterioration in work performance, decreased strength and/or endurance, and bothersome hot flushes, were associated with low bioavailable testosterone and/or testosterone (P < 0.05). Testosterone and bioavailable testosterone did not differ between age groups, but bioavailable testosterone was higher in men with three or fewer symptoms on the ADAM questionnaire. CONCLUSIONS: Symptoms associated with PADAM often occur in an elderly population, but we could only find an association between three symptoms and blood testosterone concentrations, one being bothersome hot flushes. It is likely that these symptoms have a more complex background than only PADAM. ©2007The North American Menopause Society.

  • 84.
    Sturnegk, Patrik
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Mellergård, Pekka
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Yonas, H
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Potential use of quantitative bedside CBF monitoring (Xe-CT) for decision making in neurosurgical intensive care2007In: British Journal of Neurosurgery, ISSN 0268-8697, E-ISSN 1360-046X, Vol. 21, no 4, p. 332-339Article in journal (Refereed)
    Abstract [en]

    During a 3-year period, mobile xenon-computerized tomography (Xe-CT) for bedside quantitative assessment of cerebral blood flow was used as an integrated tool for decision making during the care of complicated patients in our neurosurgical intensive care units (NSICU), in an attempt to make a preliminary evaluation regarding the usefulness of this method in routine work in the neurosurgical intensive care. With approximately 200 studies involving 75 patients, we identified six different categories where the use of bedside Xe-CT significantly influenced (or, with more experience, could have influenced) the decision making, or facilitated the handling of patients. These categories included identification of problems not apparent from other types of monitoring, avoidance of adverse effects from treatment, titration of standard treatments, evaluation of the vascular resistance reserve, assessment of adequate perfusion pressure and better utilization of resources from access to the bedside cerebral blood flow (CBF) technology. We conclude that quantitative bedside measurements of CBF could be an important addition to the diagnostic and monitoring arsenal of NSICU-tools. © The Neurosurgical Foundation.

  • 85.
    Sundell, I.B.
    et al.
    Department of Haematology, University of Liverpool, Liverpool L69 3GA, United Kingdom, Puget Sound Blood Center, 921 Terry Avenue, Seattle, WA 98104, United States.
    Ranby, M.
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Zuzel, M.
    Department of Haematology, University of Liverpool, Liverpool L69 3GA, United Kingdom.
    Robinson, K.A.
    Amer. Cardiovasc. Research Institute, 3155 Northwoods Place, Norcross, GA 30071, United States.
    Theakston, R.D.G.
    Alistair Reid Venom Research Unit, Liverpool Sch. of Tropical Medicine, Liverpool L3 5QA, United Kingdom.
    In vitro procoagulant and anticoagulant properties of Naja naja naja venom2003In: Toxicon, ISSN 0041-0101, E-ISSN 1879-3150, Vol. 42, no 3, p. 239-247Article in journal (Refereed)
    Abstract [en]

    Bites by the Indian cobra (Naja naja naja) are common in India and Sri Lanka because of its close association with humans. Cobra venoms are complex and contain several toxic components, including neurotoxins that cause post-synaptic neuromuscular blockade with respiratory paralysis and even death. Bites may also cause extensive local necrosis by mechanisms not fully elucidated. Although no significant coagulopathy has been reported, N.n. naja venom can form blood clots in vitro by activating prothrombin as demonstrated by thrombin-specific chromogenic substrate. Scanning electron microscopy demonstrates that the clots formed by venom lack the thin fibrin strands of normal blood clots formed by thromboplastin or glass contact. Rheometry shows that clots formed by venom have abnormally low elasticity over an extended period and then, as the platelets contract, a retarded and more feeble increase in elasticity. Purified N.n. naja venom PLA2 inhibits platelet aggregation in PRP and explains the decreased clot retraction and retarded and compromised elasticity build up. The present study shows that the PLA 2 and the prothrombin activator from N.n. naja venom have effects on haemostasis and blood clotting, although such effects are not observed systemically in envenomed humans. © 2003 Elsevier Ltd. All rights reserved.

  • 86. Swolin-Eide, Diana
    et al.
    Hansson, Sverker
    Larsson, Lasse
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    The novel bone alkaline phosphatase B1x isoform in children with kidney disease2006In: Pediatric nephrology (Berlin, West), ISSN 0931-041X, E-ISSN 1432-198X, Vol. 21, no 11, p. 1723-1729Article in journal (Refereed)
    Abstract [en]

    The bone alkaline phosphatase (BALP) B1x isoform has previously only been identified in some adults with chronic kidney disease on dialysis and in human bone tissue. Twenty-nine patients, 3-20 years of age, with reduced renal function due to a variety of kidney diseases were examined. We measured parathyroid hormone (PTH), biointact (whole 1-84) PTH, osteoprotegerin (OPG), CrossLaps (CTX), tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) type I procollagen intact amino-terminal propeptide (PINP), osteocalcin, total alkaline phosphatase (ALP), and BALP isoforms B/I, B1x, B1, and B2. Fifty percent higher levels were detected of PTH vs. biointact PTH, demonstrating non-(1-84) PTH fragments detected by the PTH assay. Increased activities were found in five, four, and three patients for total ALP, B1, and B2, respectively. Sixteen (55%) patients had increased B/I levels. B1x was identified in two (7%) patients, who had OPG levels in the higher range independently of age, glomerular filtration rate (GFR), and biointact PTH. B1x was identified prior to and after 9 days of growth hormone (GH) therapy in one patient but not after 1, 3, 6, and 12 months, however. In conclusion, our study demonstrates that the novel BALP B1x isoform is occasionally found to be present in children with kidney disease but to a lesser degree in comparison with adults with chronic kidney disease on dialysis. It is essential to perform bone histomorphometry for future investigations in order to elucidate the exact nature of circulating B1x in patients with kidney disease for accurate classification of type of renal bone disease. © IPNA 2006.

  • 87. Swolin-Eide, Diana
    et al.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Hansson, Sverker
    Bone mass, biochemical markers and growth in children with chronic kidney disease: A 1-year prospective study2007In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 96, no 5, p. 720-725Article in journal (Refereed)
    Abstract [en]

    Aim: This study was designed to investigate bone mineral density (BMD), growth parameters and biochemical markers in children with chronic kidney disease (CKD). Methods: Sixteen patients, 4-18 years, with CKD were prospectively followed for 1 year. Auxological data, body composition, BMD by dual-energy X-ray absorptiometry, bone age, bone turnover markers, vitamin D, parathyroid hormone (PTH), leptin, osteoprotegerin, insulin-like growth factor-I (IGF-I) and IGF binding protein-3 were measured. A questionnaire regarding bone health and diet was also performed. Results: Delayed bone age was observed (n = 11) and the BMD Z-scores for total body were below zero in seven patients. However, total body BMD (TBBMD) increased in 12 patients. Most patients had increased osteocalcin and carboxy-terminal telopeptide of type I collagen, but normal alkaline phosphatase, type I procollagen intact amino-terminal propeptide and tartrate-resistant acid phosphatase 5b. Ten patients had increased PTH. Most children had normal levels of leptin, osteoprotegerin, IGF-I and IGFBP-3. Leptin, at baseline, correlated with differences in TBBMD over 1 year. Conclusions: Only seven (44%) had negative Z-scores and TBBMD increased over 1 year. Bone markers at baseline did not predict the longitudinal changes in BMD. © 2007 The Author(s).

  • 88.
    Söderlind, Kristina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Anaesthesiology. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Theodorsson, Annette
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Hälsoekonomi på liv och död2006In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, p. 901-901Article in journal (Other academic)
    Abstract [sv]

      

  • 89. Söderpalm, Ann-Charlott
    et al.
    Magnusson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Åhlander, Anne-Christine
    Karlsson, Jón
    Kroksmark, Anna-Karin
    Tulinius, Már
    Swolin-Eide, Diana
    Low bone mineral density and decreased bone turnover in Duchenne muscular dystrophy2007In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 17, no 11-12, p. 919-928Article in journal (Refereed)
    Abstract [en]

    This cross-sectional study examined bone mineral density, bone turnover, body composition and calciotropic hormones in 24 boys with Duchenne muscular dystrophy (DMD) (2.3-19.7 years), most of whom were being treated with prednisolone, and 24 age-matched healthy boys. Our study demonstrated lower bone mineral density in the DMD group for total body, spine, hip, heel and forearm measurements. These differences between DMD patients and controls increased with increasing age. Biochemical markers of both bone formation and resorption revealed reduced bone turnover in DMD patients. The fracture rate was not higher in DMD patients. The DMD group had low vitamin D levels but high leptin levels in comparison with the control group. Muscle strength correlated with bone mineral density assessed at the hip and heel in the DMD group. Interventions that increase bone formation should be considered, as DMD patients have reduced bone turnover in addition to their low bone mineral density. © 2007 Elsevier B.V. All rights reserved.

  • 90.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Babels torn ... eller systematiska begrepp, termer och koder2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 17, p. 1297-1298Article in journal (Other academic)
  • 91.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Digestionsorganen2003In: Laurells Klinisk kemi i Praktisk Medicin / [ed] Peter Nilsson-Ehle, Maria Berggren Söderlund, Elvar Theodorsson, Charlotte Becker, Kjell Grankvist, Lund: Studentlitteratur , 2003, 9, p. 535-548Chapter 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.

  • 92.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Haemochromatosis, hepcidin and disorders of iron metabolism: Fields of substantial clinical relevance and current advances2006In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 66, no 2, p. 79-82Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 93.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Norden - åter internationellt lokomotiv inom laboratoriemedicinen? Nygammalt samarbete ger enhetliga referensintervall2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 10, p. 870-871Article in journal (Other academic)
  • 94.
    Theodorsson, Elvar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Regulatory Peptides as Disease Markers2004In: Journal of The International Federation of Clinical Chemistry And Laboratory Medicine, ISSN 1051-2292, Vol. 15, no 3Article in journal (Other academic)
    Abstract [en]

    Measurement of regulatory peptides has an established role in the diagnosis and monitoring of heart failure, severe infections and of several peptide-producing tumours, including endocrine pancreatic tumours, carcinoid tumours, medullary thyroid carcinomas; pheochromocytomas and neuroblastomas. Proper sample handling (rapid cooling and freezing) is important since most regulatory peptides (except brain natriuretic peptides (BNP, N-BNP), procalcitonin, gastrin and pancreatic polypeptide) are labile in plasma. High assay specificity is generally an advantage but when diagnosing peptide-producing tumours the immunoassay used should preferably have broad specificity for the peptide family to be analysed since endocrine tumours may result in elevated concentrations of different spectra of the peptides in individual patients. Peptide- producing endocrine tumours co-secrete chromogranin A together with their respective characteristic hormones/regulatory peptides. Chromogranin A is therefore the most valuable general marker for neuroendocrine tumours. Analyses of several regulatory peptides during diagnosis and follow-up in patients in endocrine oncology units are well established. However, very few studies have as yet addressed the specificity and predictive value of analyses of regulatory peptides. The predictive value of any laboratory test is dependent not only on quality of test and the reference limits used, but also on the prevalence of disease in the population under study. In the case of endocrine tumours the prevalence of the disease in the population is extremely low, and results from analyses of regulatory peptides in patients not known to have peptide producing tumours should be interpreted with utmost care so that further unnecessary investigations are avoided.

  • 95.
    Theodorsson, Elvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Birgens, H
    Hagve, TA
    Haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in a Scandinavian perspective2007In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 67, no 1Article in journal (Refereed)
    Abstract [en]

    Haemoglobinopathies (mainly thalassaemia and sickle-cell anaemia syndromes) and glucose-6-phosphate dehydrogenase deficiency (G6PD) are globally among the most prevalent single-genomic diseases. About 3 % of the world's population are heterozygotic for β-thalassaemia and about 1-2 % for sickle-cell anaemia, and it is estimated that more than 400 million people are affected by G6PD deficiency worldwide. The disorders are most prevalent in the Mediterranean area, in Asia and Africa. The Scandinavian countries, among others, have seen a boom in immigration during the past 20 years, and therefore migration makes haemoglobinopathies as well as G6PD deficiency increasingly more important from a differential diagnostic perspective in most countries. The purpose of the present special issue of the Journal is to summarize current epidemiological data and elucidate trends and practices in the laboratory diagnosis of these disorders. © 2007 Taylor & Francis.

  • 96.
    Theodorsson, Elvar
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Malm, Johan
    Syra-basbalans, Blodgaser2003In: Laurells Klinisk kemi i Praktisk Medicin / [ed] Peter Nilsson-Ehle, Maria Berggren Söderlund, Elvar Theodorsson, Charlotte Becker, Kjell Grankvist, Lund: Studentlitteratur , 2003, 9, p. 71-96Chapter 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.

  • 97.
    Theodorsson, Elvar
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Näntö, Veikko
    Postgraduate education in clinical biochemistry: Nothern European co-operation. Joint European project.1999In: Joint European project : development of academic laboratory medicine : an international collaborative programme to develop laboratory medicine in Estonia / [ed] Marek H. Dominiczak and Veikko Näntö, Glasgow: University of Glasgow Computer Publishing Unit , 1999, p. 16-22Chapter in book (Other academic)
  • 98. Viprey, Virginie F
    et al.
    Corrias, Maria V
    Kågedal, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Oltra, Silvestre
    Swerts, Katrien
    Vicha, Ales
    Ladenstein, Ruth
    Burchill, Susan A
    Standardisation of operating procedures for the detection of minimal disease by QRT-PCR in children with neuroblastoma: Quality assurance on behalf of SIOPEN-R-NET2007In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 43, no 2, p. 341-350Article in journal (Refereed)
    Abstract [en]

    The clinical utility of detecting minimal residual disease (MRD) in children with neuroblastoma (NB) by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) is not clear. This in part reflects the lack of uniform methodology for analysis and reporting. Reference laboratories across Europe have therefore established standard operating procedures (SOPs) for the detection of NB cells by QRT-PCR. Haemopoietic samples are collected into PAXgene™ blood RNA tubes, which stabilise mRNA for 48 h at room temperature and more than 6 months at -80 °C. Tyrosine hydroxylase (TH) was selected as the target for NB cell detection, expression is normalised to β2-microglobulin and reported using the ΔΔCt method. The sensitivity of QRT-PCR increased from 58% to 90% following the development of SOPs. A robust, transferable, objective method for the detection of NB cells by QRT-PCR has been defined to improve the power and consistency of studies on MRD in children with NB. © 2006 Elsevier Ltd. All rights reserved.

  • 99.
    Vretenbrant, Karin
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Ramström, Sofia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry.
    Bjerke, Maria
    Lindahl, Tomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Platelet activation via PAR4 is involved in the initiation of thrombin generation and in clot elasticity development2007In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 97, no 3, p. 417-424Article in journal (Refereed)
    Abstract [en]

    Thrombin is a pivotal enzyme formed in the coagulation cascade and an important and potent platelet activator. The two protease-activated thrombin receptors on human platelets are denoted PARI and PAR4. The physiological relevance of PAR4 is still unclear, as both aggregation and secretion can be accomplished by PAR1 activation alone. In the present study we have investigated the role of PARS in platelet activation, blood coagulation, clot elasticity and fibrinolysis. Flow cytometry, free oscillation rheometry and thrombin generation measurements were used to analyze blood or platelet-rich plasma from healthy individuals. Maximum PAR1 activation with the peptide SFLLRN gave fewer fibrinogen-binding platelets with lower mean fluorescent intensity than maximum PAR4 activation with AYPGKF. Inhibition of any of the receptors prolonged clotting times. However, PAR1 is more important for fibrinolysis, inhibition of this receptor prolonged all the steps in the fibrinolytic process. Clot elasticity decreased significantly when the PAR4 receptor was inhibited. In the thrombin generation measurements, PAR4 inhibition delayed the thrombin generation start and peak, but did not affect the total amount of thrombin generated. PAR1 inhibition had no significant impact on thrombin generation. We found that PAR4 is most likely activated by low concentrations of thrombin during the initial phase of thrombin generation and is of importance to the clotting time. Furthermore, we suggest that the PAR4 receptor may have a physiological role in the stabilisation of the coagulum.

  • 100. Wakamatsu, Kazumasa
    et al.
    Takasaki, Akihiko
    Kågedal, Bertil
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of clinical chemistry. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Kageshita, Toshiro
    Ito, Shosuke
    Determination of eumelanin in human urine2006In: Pigment Cell Research, ISSN 1755-1471, E-ISSN 1755-148X, Vol. 19, no 2, p. 163-169Article in journal (Refereed)
    Abstract [en]

    Normal and malignant melanocytes produce melanins and melanin-related metabolites, most of which are retained in the cells but some are secreted into the blood and then excreted in the urine. In this study, we developed a method to measure levels of eumelanin in urine samples and evaluated its clinical significance in comparison with the melanin-related metabolites 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) and 5-S-cysteinyldopa (5-S-CD), and with pheomelanin, measured after degradation as 4-amino-3-hydroxyphenylalanine (4-AHP). The method is based on the production of pyrrole-2,3,5-tricarboxylic acid (PTCA) on permanganate oxidation of eumelanin, followed by quantification by liquid chromatography. For 118 urine samples from 10 control subjects, mean urinary excretions of PTCA, 6H5MI2C, 5-S-CD and 4-AHP were 19, 67, 37 and 59 μmol/mol creatinine respectively. In melanoma patients (n = 45), the mean urinary excretions of PTCA, 6H5MI2C, 5-S-CD, and 4-AHP were 91, 926, 4070 and 3530 μmol/mol creatinine respectively. Median level of PTCA in melanoma patients was elevated 2.1-fold compared with control subjects. The degrees of elevation for 6H5MI2C, 5-S-CD, and 4-AHP were 1.8-, 22- and 6.2-fold respectively. Thus, although urinary PTCA is of little clinical value in following the progression of melanoma, urinary 4-AHP appears to be of considerable value in this respect. © 2006 Blackwell Munksgaard.

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