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  • 51.
    Gréen, Henrik
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Runnqvist, Cecilia
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Bak, Julia
    Söderqvist, Peter
    Rosenberg, Per
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Strategies for individualization of Taxol (paclitaxel) treatment of ovarian cancer2002Inngår i: Proceedings of the American Association for Cancer Research,2002, 2002, s. 275-276Konferansepaper (Fagfellevurdert)
  • 52.
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Evaluation of complementary care in breast cancer - a scientific challenge2001Inngår i: Eur J Cancer,2001, 2001, s. 407-407Konferansepaper (Fagfellevurdert)
  • 53.
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Stroke mitt i livet - ett aktionsprogram2005Inngår i: Incitament, ISSN 1103-503X, Vol. 1, s. 45-46Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 54.
    Hamrin, Elisabeth
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Baer-Dubowska, Wanda
    Dept of Pharmaceutical Biochemistry Faculty of Pharmacy.
    Cooperation between the Faculty of Health Sciences, University of Linköping, Sweden and the University of Medical Sciences in Poznan, Poland2006Inngår i: Seria: Farmacja I Analityka Medyczna W Poznaniu, Poznan: Wydawnictwo naukowe akademiimedycznej , 2006, s. 120-123Kapittel i bok, del av antologi (Annet (populærvitenskap, debatt, mm))
    Abstract [en]

      

  • 55.
    Hamrin, Elisabeth
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Lorensen, Margarethe
    Oslo.
    Östlinder, Gerthrud
    Stockholm.
    Teoriutveckling inom sykepleievitenskap/Omvårdnadsvetenskap/Vårdvetenskap i Norden. Nordisk workshop 12 november 1999, Stockholm, Sverige.2001Inngår i: Vårdalstiftelsens rapportserie,2001, 2001Konferansepaper (Fagfellevurdert)
  • 56. Hindorf, U
    et al.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Almer, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Assessment of Thiopurine Methyltransferase and Metabolite Formation During Thiopurine Therapy: Results from a Large Swedish Patient Population2004Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 26, s. 673-678Artikkel i tidsskrift (Fagfellevurdert)
  • 57.
    Hindorf, Ulf
    et al.
    Lund.
    Lindqvist Appell, Malin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Hildebrand, Hans
    Stockholm.
    Fagerberg, Ulrika
    Stockolm.
    Almer, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Adverse events leading to modification of therapy in a large cohort of patients with inflammatory bowel disease2006Inngår i: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 24, nr 2, s. 331-342Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Adverse events leading to discontinuation or dose reduction of thiopurine therapy occur in 9-28% of patients with inflammatory bowel disease. Aims: To evaluate the influence of thiopurine methyltransferase status and thiopurine metabolites in a large patient population for the risk of developing adverse event. Methods: Three hundred and sixty-four patients with inflammatory bowel disease and present or previous thiopurine therapy were identified from a local database. Results: The adverse event observed in 124 patients (34%) were more common in adults than children (40% vs. 15%, P < 0.001) and in low to intermediate (≤9.0 U/mL red blood cell) than normal thiopurine methyltransferase activity (P = 0.02). Myelotoxicity developed later than other types of adverse event. An increased frequency of adverse event was observed in patients with tioguanine (thioguanine) nucleotide above 400 or methylated thioinosine monophosphate above 11 450 pmol/ 8 × 108 red blood cell. A shift to mercaptopurine was successful in 48% of azathioprine-intolerant patients and in all cases of azathioprine-induced myalgia or arthralgia. Conclusions: A pre-treatment determination of thiopurine methyltransferase status might be appropriate as patients with low to intermediate thiopurine methyltransferase activity are more prone to develop an adverse event, determination of metabolite levels can be useful in the case of an adverse event. Mercaptopurine therapy should be considered in azathioprine-intolerant patients. © 2006 The Authors.

  • 58.
    Hindorf, Ulf
    et al.
    Lund .
    Lindqvist Appell, Malin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Söderkvist, Peter
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Ström, Magnus
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Hjortswang, Henrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Pousette, A
    Almer, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease2006Inngår i: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, nr 10, s. 1423-1431Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Firm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking. Aim: To evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. Patients: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study. Methods: Thiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored. Results: 27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)), 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio, p = 0.02). Patients with meTIMP concentrations > 11 450 pmol/8 × 108 red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0, p = 0.015). Conclusions: After initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

  • 59.
    Hindorf, Ulf
    et al.
    Lunds Universitet.
    Lindqvist Appell, Malin
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Söderkvist, Peter
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Ström, Magnus
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    Hjortswang, Henrik
    Linköpings universitet, Institutionen för molekylär och klinisk medicin.
    Pousette, Anneli
    Almer, Sven
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Östergötlands Läns Landsting, Medicincentrum, Endokrin- och magtarmmedicinska kliniken US.
    High methylthioinosine monophosphate levels as a cause of myelotoxicity when introducing thiopurine therapy in patients with inflammatory bowel disease2005Inngår i: 13th United European Gastroenterology week,2005, Stuttgart: Georg Thieme Verlag KG , 2005, s. A169-Konferansepaper (Fagfellevurdert)
  • 60.
    Hoffmann, Mikael
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Hammar, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Kjellgren, Karin I.
    Faculty of Health and Caring Sciences, Institute of Nursing, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
    Lindh-Åstrand, Lotta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Brynhildsen, Jan
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Changes in women’s attitudes towards and use of hormone therapy after HERS and WHI2005Inngår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 52, nr 1, s. 11-17Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives:

    To assess changes in women's attitudes towards risk and benefits of, and use of hormone treatment in the menopausal transition (HT) before and after Heart and Estrogen/Progestin Replacement Study (HERS) and the oestrogen and progestin trial of Women's Health Initiative (WHI).

    Methods:

    Postal questionnaires to all women 53 and 54 years of age in a Swedish community in 1999 (n = 1.760) and 2003 (n = 1.733). Data on sales of HT were collected from the database of the National Corporation of Swedish Pharmacies.

    Results:

    The fraction of women reporting current use of HT fell from 40.5 to 25.3% (p < 0.001, χ2-test) both by fewer women starting and more women discontinuing treatment. This corresponded to a decrease in dispensation of HT in Linköping and nationwide for the same age group. The fraction of women who had tried complementary treatment for climacteric discomfort, increased from 9.6 to 18.1% for natural remedies (p < 0.001, χ2-test).

    Women perceived HT as more risky and less beneficial in 2003 as compared with 1999 (both p < 0.001, χ2-test). The most frequent source of information about HT during the last year before the 2003 questionnaire were newspaper or magazines (43.8%) and television or radio (31.7%).

    Conclusions:

    The decreased use of HT in the community correlated with pronounced changes in the attitudes towards HT. Media were a more frequent source of information than health care personnel. This indicates that media reports about major clinical studies might have influenced the use of HT among women.

  • 61.
    Hoffmann, Mikael
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Hammar, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Kjellgren, Karin
    Linköpings universitet, Hälsouniversitetet. The Sahlgrenska Academy at Göteborg University, Sweden.
    Lindh-Åstrand, Lotta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Ahlner, Johan
    National Board of Forensic Medicine, Linköping, Sweden.
    Risk communication in consultations about hormone therapy in the menopause: concordance in risk assessment and framing due to the context2006Inngår i: Climacteric, ISSN 1369-7137, E-ISSN 1473-0804, Vol. 9, nr 5, s. 347-354Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    It is important for the physician and the patient to have a mutual understanding of the possible consequences of different treatment alternatives in order to achieve a partnership in decision-making.

    OBJECTIVE:

    The aim of this study was to explore to which degree first-time consultations for discussion of climacteric discomfort achieved shared understanding of the risks and benefits associated with hormone therapy in the menopausal transition.

    METHODS:

    Analysis of structure and content of transcribed consultations (n = 20), and follow-up interviews of the women (n = 19 pairs of consultations and interviews), from first-time visits for discussion of climacteric discomfort and/or HT with five physicians at three different outpatient clinics of gynecology in Sweden.

    RESULTS:

    Four distinctively different interpretations of risk, depending on whether or not benefits were discussed in the same context, emerged from the analysis. On average, five advantages (range 0-11) and two (0-3) disadvantages were mentioned during the consultations. In the interviews, the women expressed on average four advantages (0-7) and one disadvantage (0-3). There were major variations between advantages and disadvantages expressed in the consultation and the following interview.

    CONCLUSION:

    Even though the consultations scored high in patient involvement, the information in most consultations was not structured in a way that made it possible to achieve a shared or an informed decision-taking.

  • 62.
    Hoffmann, Mikael
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Lindh-Åstrand, Lotta
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Ahlner, Johan
    National Board of Forensic Medicine, Linköping, Sweden.
    Hammar, Mats
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Kjellgren, Karin I.
    Faculty of Health and Caring Sciences, Institute of Nursing, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
    Hormone replacement therapy in the menopause - structure and content of risk talk2005Inngår i: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 50, nr 1, s. 8-18Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To investigate how risks and benefits of hormone replacement therapy (HRT) are communicated to women in clinical practice. To evaluate the usefulness of a risk classification based on context framing, i.e. whether the risk is discussed for one or several alternative treatments, and/or in the same context as possible benefits.

    Design: Analysis of structure and content of transcribed consultations (n=20) from first-time visits for discussion of climacteric discomfort and/or HRT with five physicians at three different out-patient clinics of gynecology.

    Results: All women received a prescription of HRT. An alternative to HRT was discussed in seven of the consultations. No decision aids were used. Risk discussion was dominated by the physicians giving information about long-time risk and benefits. The decision to prescribe was made either before the risk discussion was initiated, or before it was finished, in 8 of the 18 consultations where risk discussion was present. Risk classification according to context framing was performed and indicated use of different communication strategies by the physicians.

    Conclusions: The perspective of the physicians was mainly on prevention while the women were more focused on symptom alleviation. Each physician had a strategy of his/her own for the risk discussion. Thus, the major differences found between the consultations were between physicians, and not between the women. Risk discussion seemed to be aimed at motivating the woman to follow the physician’s decision rather than to help her participate in the decision-making process.

  • 63. Holmgren, A
    et al.
    Holmgren, P
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Jones, A Wayne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Predominance of illicit drugs and poly-drug use among drug-impaired drivers in Sweden2007Inngår i: Traffic Injury Prevention, ISSN 1538-9588, E-ISSN 1538-957X, Vol. 8, nr 4, s. 361-367Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

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

  • 64.
    Holmgren, Anita
    et al.
    Department of Forensic Genetics and Forensic Toxicology National Board of Forensic Medicine, Linköping.
    Holmgren, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi.
    Jones, A Wayne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi.
    High re-arrest rates among drug-impaired drivers despite zero-tolerance legislation2008Inngår i: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 40, nr 2, s. 534-540Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A zero-tolerance law for driving under the influence of drugs (DUID) in Sweden led to a 10-fold increase in the number of cases submitted by the police for toxicological analysis. The statutory blood-alcohol concentration (BAC) limit for driving is 0.2 mg/g (∼0.02 g%). Methods: An in-house database (TOXBASE) was used to investigate re-arrests for impaired driving over 4 years (2001-2004), which comprised 36,799 cases. The age, gender, re-arrest rate of the offenders and the concentrations of ethanol and amphetamine in blood samples were evaluated. Results: We found that 44% of individuals (N = 16,277) re-offended 3.2 times on average (range 1-23 arrests). Between 85 and 89% of first-time offenders were men and there was also a male dominance among the recidivists (88-93%). The mean age of drunken drivers was ∼40 years compared with ∼35 years for driving under the influence of amphetamine, which was the drug identified in 50-60% of DUID cases, either alone or together with other licit or illicit drugs. The median BAC was 1.5 mg/g (∼0.15 g%), which suggests a dominance of heavy drinkers. The median BAC was even higher in recidivists (1.6-1.7 mg/g). The median concentration of amphetamine in blood was 1.0 mg/L in recidivists compared with 0.5 mg/L in the first-time offenders. About 14% of drunken drivers re-offended 1-10 times compared with 68% of DUID suspects, who were re-arrested 1-23 times. People with only a scheduled prescription drug in blood were re-arrested much less frequently (∼17%) compared with those taking illicit drugs (68%). Conclusions: The appreciable increase in number of arrests for DUID after a zero-tolerance law might reflect a heightened enthusiasm by the police authorities armed with knowledge that a prosecution is easier to obtain. Zero-tolerance laws do not deter people from impaired driving judging by the high re-arrest rates. During the sentencing of hardcore offenders, the courts should give more consideration to the underlying substance abuse problem. © 2007 Elsevier Ltd. All rights reserved.

  • 65.
    Holmgren, Per
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Jones, A Wayne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi.
    Coexistence and concentrations of ethanol and diazepam in postmortem blood samples; Risk for enhanced toxicity?2003Inngår i: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 48, s. 1416-1421Artikkel i tidsskrift (Fagfellevurdert)
  • 66.
    Hursti, Timo J
    et al.
    Uppsala Universitet.
    Börjeson, Sussanne
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Hellström, Per M
    Karolinska.
    Åvall-Lundqvist, Elisabeth
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Karolinska.
    Stock, Solveig
    Karolinska.
    Steineck, Gunnar
    Karolinska.
    Peterson, Curt
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Effect of chemotherapy on circulating gastrointestinal hormone levels in ovarian cancer patients: Relationship to nausea and vomiting2005Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 40, nr 6, s. 654-661Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. The introduction of 5-HT3 receptor antagonists greatly reduced the problems associated with nausea and vomiting immediately after cancer chemotherapy. However, delayed nausea and vomiting is still a major problem and the underlying mechanism is obscure. Material and methods. We studied the effect of cisplatin-containing combination chemotherapy in 14 ovarian cancer patients on the levels of gastrin and a panel of other hormones as well as glucose and prostaglandin F2α. Blood samples were obtained once daily in the morning before chemotherapy and for 4 days after chemotherapy. Results. Concentrations of many hormones including gastrin were generally high. A pronounced increase in plasma insulin levels occurred on the day after chemotherapy accompanied by a modest increase in plasma glucose concentrations. Minor increases were observed for gastrin, oxytocin and prostaglandin F2α. In contrast, a transient decrease after chemotherapy was observed for motilin. Plasma cortisol decreased markedly after chemotherapy as expected since betamethasone was given as an antiemetic prophylaxis. Certain trends concerning the relationship between some hormones and nausea and vomiting were noted. A high plasma gastrin concentration before chemotherapy was related to delayed vomiting. Relative day-to-day variability of cholecystokinin tended to correlate positively with delayed nausea, whereas an inverse relationship was observed for gastrin variability. Conclusions. Changes in hormone plasma levels were found but only few could be distinguished as possible mediators of delayed nausea and vomiting. © 2005 Taylor & Francis.

  • 67.
    Hägg, Staffan
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Lindblom, Y
    Umeå.
    Mjörndal, Tom
    Umeå.
    Adolfsson, R
    Umeå.
    High prevalence of the metabolic syndrome among a Swedish cohort of patients with schizophrenia2006Inngår i: International Clinical Psychopharmacology, ISSN 0268-1315, E-ISSN 1473-5857, Vol. 21, nr 2, s. 93-98Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several cardiovascular risk factors have been linked to antipsychotic treatment and cardiovascular mortality is increased in these patients compared to the general population. The full metabolic syndrome (or its components) is associated with an increased risk of cardiovascular disorders. The prevalence of the metabolic syndrome was investigated using a cross-sectional study design in a cohort of 269 patients, aged 20-69 years, with schizophrenia living in Northern Sweden, and was defined according to the criteria of the National Cholesterol Education program. The prevalence of the metabolic syndrome was 34.6% (95% CI = 28.8-40.3) and highest (43%, 95% CI = 32-53) for participants aged 40-49 years. Clozapine treated subjects reached the highest prevalence of the metabolic syndrome (48%, 95% CI = 34-62). The prevalence was similar for men (32.8%, 95% CI = 25.8-39.8) and women (38.0%, 95% CI = 27.9-48.2). Men had a high prevalence of hypertension (49.2%, 95% CI = 41.7-56.6) and women had high prevalence of low high-density lipoprotein cholesterol (40.2%, 95% CI = 30.0-50.4) and abdominal obesity (75.0%, 95% CI = 66.0-84.0). Subjects with the metabolic syndrome had significantly higher mean body mass index (BMI) (P < 0.001), HbA1c (P = 0.002), and fasting serum insulin (P < 0.001) compared to non-metabolic syndrome subject. Subjects with the metabolic syndrome had also significantly more often a positive history of cardiovascular diseases compared to non-metabolic syndrome subjects (25.8% versus 12.5%, P = 0.01). Of all study subjects 36.8% were obese (BMI > 30). These results clearly show that the metabolic syndrome and its components are highly prevalent in patients with schizophrenia. Physicians treating patients with schizophrenia are recommended to monitor the components included in the metabolic syndrome. © 2006 Lippincott Williams & Wilkins.

  • 68.
    Idvall, Ewa
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Rooke, Liselotte
    Malmö.
    Sjöström, Björn
    Göteborg.
    Kvalitetsindikatorer inom postoperativ smärtbehandling2001Inngår i: Hälso- och sjukvårsstämman,2001, 2001, s. 80-80Konferansepaper (Fagfellevurdert)
  • 69.
    Idvall, Ewa
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Sjöström, Björn
    Göteborg.
    Unosson, Mitra
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Patients and nurse assessment on quality of care in postoperative pain management2002Inngår i: 10th World congress on pain, San Diego, USA,2002, 2002, s. 563-563Konferansepaper (Fagfellevurdert)
  • 70.
    Idvall, Ewa
    et al.
    Linköpings universitet, Institutionen för medicin och vård.
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Unosson, Mitra
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Development of an instrument to measure the quality of postoperative pain management2004Inngår i: 12th Biennal Conference of the Workgroup of European Nurse Researchers,2004, 2004Konferansepaper (Annet vitenskapelig)
  • 71.
    Idvall, Ewa
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Unosson, Mitra
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Development of an instrument to measure the quality of postoperative pain management.2003Inngår i: The 4th congres of the european federation of IASP chapters - Pain in Europe IV Prag - Tjeckien,2003, 2003, s. 774-774Konferansepaper (Fagfellevurdert)
  • 72.
    Idvall, Ewa
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Unosson, Mitra
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Omvårdnad.
    Kvalitetsindikatorer inom postoperativ smärtbehandling: en valideringsstudie2002Inngår i: Vårdfacket, ISSN 0347-0911, Vol. 3, s. 49-49Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 73. Isaksson, Björn
    et al.
    Thorell, Lars-Håkan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Psykiatri. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Psykiatriska kliniken.
    Bengtsson, Finn
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Rosén, I
    Jeppsson, I
    Hepatic encephalopathy verified by psychometric testing and EEG in cirrhotic patients: Effects of mesocaval interposition shunt or sclerotherapy2005Inngår i: HPB, ISSN 1365-182X, Vol. 7, nr 1, s. 65-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background. The aim of this randomised prospective study was to evaluate hepatic encephalopathy after mesocaval interposition shunt operation and after repeated endoscopic sclerotherapy. Methods. Forty-five patients with bleeding oesophageal varices due to liver cirrhosis were randomised to the two treatment groups, 24 to the shunt group and 21 to the sclerotherapy group. The patients were evaluated preoperatively regarding blood tests, hepatic encephalopathy as measured by electroencephalogram with spectral analysis and by a battery of psychometric tests. The direction of portal flow in the shunt group was investigated by shunt phlebography and ultrasonography with Doppler. During follow-up the same investigations were performed twice at median 6.7 and 14.7 months after operation. Results. No statistically significant difference was found during follow-up regarding blood tests and electroencephalography with spectral analysis. Although the preoperative psychometric tests showed that the shunt group performed significantly better than the sclerotherapy group, the first follow-up showed that the shunt group performed statistically worse than the sclerotherapy group in seven of the tests: Synonyms (measuring verbal ability), Block Design Test (measuring visuo-spatial ability), Memory for Design Test, Error Score (measuring memory function), Revised Visual Retention Test, correct answers and the same test error answers (measuring visuo-spatial memory, ability and immediate memory), Digit Symbol Test (measuring perceptual ability) and Trial Making Test B (measuring cognitive motor abilities). Conclusions. Patients treated by mesocaval interposition shunt showed a progressive general reduction in psychometric performance compared with patients treated with repeated sclerotherapy, in whom a general intellectual improvement was observed. This finding corresponds to the reverse direction of the preoperative portal flow to a hepatofugal pattern at first follow-up and at 12 months among two-thirds of the patients. © 2005 Taylor & Francis Group Ltd.

  • 74. Jaracz, K
    et al.
    Gustafsson, G
    Hamrin, Elisabeth
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    The life situation and functional capacity of the elderly with locomotor disability in Sweden and Poland according to a model by Lawton2004Inngår i: International Journal of Nursing Practice, ISSN 1322-7114, E-ISSN 1440-172X, Vol. 10, s. 45-53Artikkel i tidsskrift (Fagfellevurdert)
  • 75.
    Jones, A Wayne
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Holmgren, A
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Concentrations of scheduled prescription drugs in blood of impaired drivers: Considerations for interpreting the results2007Inngår i: Therapeutic Drug Monitoring, ISSN 0163-4356, E-ISSN 1536-3694, Vol. 29, nr 2, s. 248-260Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 76.
    Jones, A Wayne
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi.
    Holmgren, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Comparison of blood-ethanol concentration in deaths attributed to acute alcohol poisoning and chronic alcoholism2003Inngår i: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 48, nr 4, s. 874-879Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ethanol concentrations were measured in femoral venous blood in deaths attributed to acute alcohol poisoning (N = 693) or chronic alcoholism (N = 825), according to the forensic pathology report. Among acute alcohol poisonings were 529 men (76%) with mean age 53 years and 164 women (24%) with mean age 53 years. In the chronic alcoholism deaths were 705 men (85%) with mean age 55 years and 120 women (15%) with mean age 57 years. The blood-ethanol concentrations were not related to the person's age (r = -0.17 in acute poisonings and r = -0.09 in chronic alcoholism). The distribution of blood-ethanol concentrations in acute poisoning cases agreed with a normal or Gaussian curve with mean, median, standard deviation, coefficient of variation, and spread of 0.36 g/100 mL, 0.36 g/100 mL, 0.086 g/100 mL, 24% and 0.074 to 0.68 g/100 mL, respectively. The corresponding concentrations of ethanol in chronic alcoholism deaths were not normally distributed and showed a mode between 0.01 and 0.05 g/100 mL and mean, median, and spread of 0.172 g/100 mL, 0.150 g/100 mL, and 0.01 to 0.56 g/100 mL, respectively. The 5th and 95th percentiles for blood-ethanol concentration in acute poisoning deaths were 0.22 and 0.50 g/100 mL, respectively. However, these values are probably conservative estimates of the highest blood-ethanol concentrations before death owing to metabolism of ethanol until the time of death. In 98 chronic alcoholism deaths (12%) there was an elevated concentration of acetone in the blood (> 0.01 g/100 mL), and 50 of these (6%) also had elevated isopropanol (>0.01 g/100 mL). This compares with 28 cases (4%) with elevated blood-acetone in the acute poisoning deaths and 22 (3%) with elevated blood-isopropanol. We offer various explanations for the differences in blood-ethanol and blood-acetone in acute poisoning and alcoholism deaths such as chronic tolerance, alcohol-related organ and tissue damage (cirrhosis, pancreatitis), positional asphyxia or suffocation by inhalation of vomit, exposure to cold coupled with alcohol-induced hypothermia, as well as various metabolic disturbances such as hypoglycemia and ketoacidosis.

  • 77.
    Jones, A Wayne
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi.
    Holmgren, Per
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Urine/blood ratios of ethanol in deaths attributed to acute alcohol poisoning and chronic alcoholism2003Inngår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 135, nr 3, s. 206-212Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The concentrations of ethanol were determined in femoral venous blood (BAC) and urine (UAC) and the UAC/BAC ratios were evaluated for a large case series of forensic autopsies in which the primary cause of death was either acute alcohol poisoning (N=628) or chronic alcoholism (N=647). In alcohol poisoning deaths both UAC and BAC were higher by about 2g/l compared with chronic alcoholism deaths. In acute alcohol poisoning deaths the minimum BAC was 0.74g/l and the distribution of UAC/BAC ratios agreed well with the shape of a Gaussian curve with mean-standard deviation (S.D.) and median (2.5th and 97.5th centiles) of 1.18-0.182 and 1.18 (0.87 and 1.53), respectively. In alcoholism deaths, when the BAC was above 0.74g/l (N=457) the mean-S.D. and median (2.5th and 97.5th centiles) UAC/BAC ratios were 1.30-0.29 and 1.26 (0.87 and 2.1), respectively. When the BAC was below 0.74g/l (N=190), the mean and median UAC/BAC ratios were considerably higher, being 2.24 and 1.58, respectively. BAC and UAC were highly correlated in acute alcohol poisoning deaths (r=0.84, residual S.D.=0.47g/l) and in chronic alcoholism deaths (r=0.95, residual S.D.=0.41g/l). For both causes of death (N=1275), the correlation between BAC and UAC was r=0.95 and the residual S.D. was 0.46g/l. The lower UAC/BAC ratio observed in acute alcohol poisoning deaths (mean and median 1.18:1) suggests that these individuals died before absorption and distribution of ethanol in all body fluids were complete. The higher UAC/BAC ratio in chronic alcoholism (median 1.30:1) is closer to the value expected for complete absorption and distribution of ethanol in all body fluids.

  • 78.
    Jones, A. Wayne
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, K. Å.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Institutionen för medicin och vård, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Effect of high-fat, high-protein, and high-carbohydrate meals on the pharmacokinetics of a small dose of ethanol1997Inngår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 44, nr 6, s. 521-526Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims To investigate whether the relative amounts of fat, carbohydrate (CHO), or protein in a meal influence the pharmacokinetics of a small dose of ethanol.

    Methods Nine healthy men received ethanol (0.30 g kg−1 body weight) on five occasions in a randomized cross-over fashion. On three occasions the dose of ethanol was consumed within 15 min of eating a standardized breakfast of similar volume and calorific value but containing different amounts of fat, CHO, and protein. On two other occasions the same dose of ethanol was ingested on an empty stomach (overnight fast) or administered by intravenous (i.v.) infusion over 30 min.

    Results The blood-ethanol profiles showed large inter and intraindividual variations, especially when ethanol was ingested after eating food. The peak blood-alcohol concentrations (BAC) were 16.6±4.0, 17.7±7.1, and 13.3±4.0 mg dl−1 (mean±s.d.) after fat, CHO, and protein-rich meals and 30.8±4.3 and 54.3±6.4 mg dl−1 after fasting and i.v. infusion, respectively. The corresponding areas under the concentration-time profiles (AUC) were 1767±549, 1619±760, 1270±406 mg dl−1 min after fat, CHO, and protein-rich meals compared with 3210±527 and 4786±446 mg dl−1  min after fasting and i.v. infusion, respectively. The time required to eliminate ethanol from the blood was shortened by 1–2 h in the fed-state.

    Conclusions Drinking ethanol after eating a meal, regardless of the nutritional composition, decreases the systemic availability of ethanol. Because gastric emptying is slow and more prolonged with food in the stomach, the delivery of ethanol to the duodenum and the liver will be highly variable as will the hepatic clearance of ethanol. Provided that portal venous BAC remains fairly low and ethanol metabolizing enzymes are not fully saturated then part of the dose of ethanol can be cleared by hepatic first-pass metabolism (FPM), as one consequence of Michaelis-Menten elimination kinetics.

  • 79.
    Jones, A Wayne
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för klinisk kemi.
    Kugelberg, Fredrik
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Letter to the Editor - Alcohol concentrations in post-mortem body fluids2006Inngår i: Human Exp Toxical, ISSN 0144-5952, Vol. 25, s. 623-624Artikkel i tidsskrift (Annet vitenskapelig)
  • 80.
    Jönsson, Anna
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Benzodiazepiner, bruk och missbruk2005Inngår i: Det förbisedda missbruket - läkemedlens del i beroendeproblematiken, Mobilisering mot narkotika,2005, 2005Konferansepaper (Annet vitenskapelig)
  • 81.
    Jönsson, Anna
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Andersson, Mats
    Neurologiska kliniken Neurocentrum.
    Jacobsson, Ingela
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Large underreporting of cerebral haemorrhage during warfarin treatment in Sweden2005Inngår i: 7th Congress of European association for clinical pharmacology,2005, 2005Konferansepaper (Annet vitenskapelig)
  • 82.
    Jönsson, Anna
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Andersson, Mats
    Neurologiska kliniken Neurocentrum.
    Jacobsson, Ingela
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Stor underrapportering av hjärnblödningar under warfarinbehandling2005Inngår i: Läkarsällskapets Riksstämma,2005, 2005Konferansepaper (Annet vitenskapelig)
  • 83.
    Jönsson, Anna
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Brundin, Lars
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Hedenmalm, Karin
    Eriksson, Anders
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Low-potency and atypical antipsychotics were associated with pulmonary embolism among Swedish autopsy cases2006Inngår i: International conference on Pharmacoepidemiology Therapeutic risk management,2006, 2006Konferansepaper (Annet vitenskapelig)
  • 84.
    Jönsson, Anna
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Druid, Henrik
    RMV KI, Stockholm.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Narkotikarelaterade dödsfall och missbruksmönster i Sverige 2002-20032005Inngår i: Mobilisering mot narkotika, Forskningsdagarna,2005, 2005Konferansepaper (Annet vitenskapelig)
  • 85.
    Jönsson, Anna
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi. National Board of Forensic Medicine, Linköping, Sweden.
    Holmgren, Per
    National Board of Forensic Medicine, Linköping, Sweden.
    Druid, Henrik
    KI, Stockholm.
    Ahlner, Johan
    National Board of Forensic Medicine, Linköping, Sweden.
    Cause of death and drug use pattern in deceased drug addicts in Sweden, 2002-20032007Inngår i: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 169, nr 2-3, s. 101-107Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Compared with their contemporaries, individuals abusing illicit drugs suffer a higher risk of premature death. In Sweden, a simple protocol for registration of fatalities among abusers of alcohol, pharmaceuticals, illicit drugs, or other substances, has been used by the forensic pathologists since 2001. This routine was introduced to allow for an evaluation of the cause and manner of death, and patterns of abuse among different groups of abusers. We explored the data on drug abusers (i.e. abusers of illicit drugs) subjected to a forensic autopsy 2002-2003. The Swedish forensic pathologists examined 10,273 dead victims during the study period and 7% (743/10,273) of the cases were classified as drug abusers. Toxicological analyses were carried out in 99% (736/743) and illicit drugs were detected in 70% (514/736) of these. On average, 3.8 substances (legal or illegal) were found per case. The most common substances were ethanol and morphine, detected in 43 and 35% of the cases, respectively. When exploring the importance of the different substances for the cause of death, we found that the detection of some substances, such as fentanyl and morphine, strongly indicated a poisoning, whereas certain other substances, such as benzodiazepines more often were incidental findings. In total, 50% (372/743) died of poisoning, whereas only 22% (161/743) died of natural causes. Death was considered to be directly or indirectly due to drug abuse in 47% (346/743), whereas evidence of drug abuse was an incidental finding in 21% (153/743) or based on case history alone in 33% (244/743). We believe that this strategy to prospectively categorize deaths among drug addicts constitutes a simple means of standardizing the surveillance of the death toll among drug addicts that could allow for comparisons over time and between countries. © 2006 Elsevier Ireland Ltd. All rights reserved.

  • 86.
    Jönsson, Anna
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Jacobsson, Ingela
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Andersson, Mats
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Hägg, Staffan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Stor underrapportering av hjärnblödning som läkemedelsbiverkning2006Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 103, s. 3456-3458Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

         

  • 87.
    Jönsson, Anna K.
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Spigset, Olav
    Department of Clinical Pharmacology, St. Olav University Hospital; and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway.
    Jacobsson, Ingela
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Hägg, Staffan
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk farmakologi.
    Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions2007Inngår i: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, ISSN 1, Vol. 16, nr 3, s. 309-315Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Östergötland, Sweden.

    Methods: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated.

    Results: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100 000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid.

    Conclusions: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.

  • 88. Jönsson, S
    et al.
    Bergström, I
    Li, Wei
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Nilsson,
    Jonasson, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Kardiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Kardiologiska kliniken.
    Neutrophils- a potential source for increased serum MMP-9 in coronary artery disease.2009Konferansepaper (Fagfellevurdert)
  • 89.
    Kalman, Sigga
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Linköpings universitet, Hälsouniversitetet.
    Österberg, Anders
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Sörensen, Jan
    Linköpings universitet, Institutionen för medicin och vård, Anestesiologi. Linköpings universitet, Hälsouniversitetet.
    Boivie, Jörgen
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Neurologi. Linköpings universitet, Hälsouniversitetet.
    Bertler, Åke
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Morphine responsiveness in a group of well-defined multiple sclerosis patients: a study with i.v. morphine2002Inngår i: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 6, nr 1, s. 69-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pain in multiple sclerosis (MS) is more common than has previously been believed. About 28% of all MS patients suffer from central pain (CP), a pain that is difficult to treat. In the present study we have investigated the responsiveness of this pain to morphine. Fourteen opioid-free patients (eight woman and six men) with constant, non-fluctuating, long-lasting CP caused by MS were investigated. Placebo (normal saline), morphine and naloxone were given intravenously in a standardized manner. The study design was non-randomized, single blind and placebo controlled. Ten patients experienced less than 50% pain reduction by placebo and less than 50% pain reduction by morphine. Four patients were opioid responders, i.e. had minimal or no effect on pain by placebo, >50% pain reduction after morphine and >25% pain increase after naloxone, given intravenously following morphine. However, this response was obtained after high doses of morphine (43 mg, 47 mg, 50 mg and 25 mg; mean 41 mg). Thus, compared with nociceptive pain, only a minority of the patients with CP due to MS responded to morphine and only at high doses. The present results are in accord with experimental studies indicating that neuropathic pain is poorly responsive but not totally unresponsive to opioids. The results do not support the routine use of strong opioids in MS patients with CP.

  • 90.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, K. Å.
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Akutkliniken. Linköpings universitet, Hälsouniversitetet.
    Franzén, Thomas
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Andersson, L.
    Jones, A. Wayne
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi.
    Reliability of breath-alcohol analysis in individuals with gastroesophageal reflux disease1999Inngår i: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 44, nr 4, s. 814-818Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gastroesophageal reflux disease (GERD) is widespread in the population among all age groups and in both sexes. The reliability of breath alcohol analysis in subjects suffering from GERD is unknown. We investigated the relationship between breath-alcohol concentration (BrAC) and blood-alcohol concentration (BAC) in 5 male and 5 female subjects all suffering from severe gastroesophageal reflux disease and scheduled for antireflux surgery. Each subject served in two experiments in random order about 1-2 weeks apart. Both times they drank the same dose of ethanol (~0.3 g/kg) as either beer, white wine, or vodka mixed with orange juice before venous blood and end-expired breath samples were obtained at 5-10 min intervals for 4 h. Ah attempt was made to provoke gastroesophageal reflux in one of the drinking experiments by applying an abdominal compression belt, Blood-ethanol concentration was determined by headspace gas chromatography and breath-ethanol was measured with an electrochemical instrument (Alcolmeter SD-400) of a quantitative infrared analyzer (Data-Master). During the absorption of alcohol, which occurred during the first 90 min after the start of drinking, BrAC (mg/210 L) tended to be the same of higher than venous BAC (mg/dL). In the post-peak phase, the BAC al ways exceeded BrAC. Four of the 10 subjects definitely experienced gastric reflux during the study although this did not result in widely deviant BrAC readings compared with BAC when sampling occurred at 5- min intervals. We conclude that the risk of alcohol erupting from the stomach into the mouth owing to gastric reflux and falsely increasing the result of an evidential breath-alcohol test is highly improbable.

  • 91.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, K. Å.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jones, A. Wayne
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Impact of gastric emptying on the pharmacokinetics of ethanol as influenced by cisapride1999Inngår i: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 48, nr 5, s. 728-732Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims To examine the influence of cisapride on the pharmacokinetics of ethanol and the impact of gastric emptying monitored by the paracetamol absorption test.

    Methods Ten healthy male volunteers took part in a cross-over design experiment. They drank a moderate dose of ethanol 0.30 g kg−1 body weight exactly 1 h after eating breakfast either without any prior drug treatment or after taking cisapride (10 mg three times daily) for 4 consecutive days. In a separate study, the same dose of ethanol was ingested on an empty stomach (overnight fast). Paracetamol (1.5 g) was administered before consumption of ethanol to monitor gastric emptying. Venous blood was obtained at 5–10 min intervals for determination of ethanol by headspace gas chromatography and paracetamol was analysed in serum by high performance liquid chromatography (h.p.l.c.).

    Results The maximum blood-ethanol concentration (Cmax ) increased from 3.8±1.7 to 5.6±2.3 mmol l−1 (±s.d.) after treatment with cisapride (95% confidence interval CI on mean difference 0.28–3.28 mmol l−1 ). The area under the blood-ethanol curve (AUC) increased from 6.3±3.5 to 7.9±2.6 mmol l−1 h after cisapride (95% CI −0.74–3.9 mmol l−1 h). The mean blood ethanol curves in the cisapride and no-drug sessions converged at ≈2 h after the start of drinking. Both Cmax and AUC were highest when the ethanol was ingested on an empty stomach (Cmax 9.5±1.7 mmol l−1 and AUC 14.6±1.9 mmol l−1 h), compared with drinking 1 h after a meal and regardless of pretreatment with cisapride.

    Conclusions A small but statistically significant increase in Cmax occurred after treatment with cisapride owing to faster gastric emptying rate as shown by the paracetamol absorption test. However, the rate of absorption of ethanol, as reflected in Cmax and AUC, was greatest after drinking the alcohol on an empty stomach. The cisapride–ethanol interaction probably lacks any clinical or forensic significance.

  • 92.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet.
    Jönsson, K. Å.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Norlander, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Carlsson, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Jones, A. Wayne
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Low-dose aspirin decreases blood alcohol concentrations by delaying gastric emptying1997Inngår i: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 53, nr 04-Mar, s. 241-246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective: To determine if treatment with low-dose aspirin (ASA) influences the bioavailability of orally administered alcohol and to assess whether this is caused by altered gastric emptying as measured by the paracetamol absorption test.

    Methods: In a single-center controlled crossover trial, ten healthy male medical students, aged 20–27 years, participated in two experiments in random order. Both times they took paracetamol (1.5 g together with a standardized breakfast) and drank ethanol (0.3 g/kg) 1 h after eating breakfast. On one drinking occasion, no previous medication was given. The other alcohol session was performed after the subjects had taken 75 mg ASA once daily for 7 days. On both occasions, venous blood samples were obtained at exactly timed intervals for a period of 3.5 h.

    Results: The blood-ethanol profiles showed large interindividual variations for both experiments. After treatment with ASA, the maximum blood-ethanol concentration was distinctly lower in seven subjects, almost unchanged in two subjects and increased in one subject. Overall, a statistically significant decrease in the peak blood-ethanol concentration was observed. The time required to reach peak blood-ethanol levels was somewhat longer after treatment with ASA. Although the areas under the concentration–time profiles were smaller after ASA treatment, these differences were not statistically significant. The concentrations of paracetamol in plasma were lower when ethanol was ingested after treatment with ASA and the areas under the concentration–time curves (0–170 min) were smaller.

    Conclusions: Intake of low-dose ASA (75 mg daily) tends to delay the absorption of a moderate dose of ethanol, which results in lower peak blood-ethanol concentrations and smaller areas under the concentration–time curves. The underlying mechanism seems to be delayed gastric emptying as indicated by the paracetamol absorption test.

  • 93.
    Kechagias, Stergios
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Gastroenterologi och hepatologi. Linköpings universitet, Hälsouniversitetet.
    Jönsson, Kjell-Åke
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Borch, Kurt
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Jones, A. Wayne
    Linköpings universitet, Institutionen för medicin och hälsa, Rättskemi. Linköpings universitet, Hälsouniversitetet.
    Influence of Age, Sex, and Helicobacter pylori Infection Before and After Eradication on Gastric Alcohol Dehydrogenase Activity2001Inngår i: Alcoholism: Clinical and Experimental Research, ISSN 0145-6008, E-ISSN 1530-0277, Vol. 25, nr 4, s. 508-512Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Gastric alcohol dehydrogenase may contribute to the metabolism of orally ingested ethanol and decrease the bioavailability of the drug. The aims of this study were to assess the impact of Helicobacter pylori infection and its eradication on gastric alcohol dehydrogenase activity and to relate the findings to gastric histology. Furthermore, the role of age- and sex-related differences in gastric alcohol dehydrogenase activity were studied.

    Methods: A total of 76 subjects (39 women and 37 men) underwent upper gastrointestinal endoscopy, and biopsies were obtained from the corpus and antrum. The specimens were used for determining gastric alcohol dehydrogenase activity, histological examination, and urease testing. Subjects with H. pylori infection (n= 36) received medication to eradicate the infection, and repeat biopsies were taken 2 and 12 months later.

    Results: No significant difference in gastric alcohol dehydrogenase activity was found between men and women (p > 0.05). Gastric alcohol dehydrogenase activity did not differ significantly between the subjects older than 50 years (n= 39) and those 50 years or younger (n= 37). In subjects with H. pylori infection, gastric alcohol dehydrogenase activity was significantly reduced in the antrum (p < 0.05). After eradication of H. pylori, alcohol dehydrogenase activity in the antrum increased significantly within 2 months (p < 0.01). Antral biopsies with the most pronounced inflammation and histological changes had significantly decreased alcohol dehydrogenase activity (p < 0.05). In contrast, no significant differences were found in corpus.

    Conclusions: H. pylori infection is associated with decreased antral alcohol dehydrogenase activity, which seems to be related to the severity of the inflammatory changes in the mucosa. Eradication of H. pylori normalizes antral alcohol dehydrogenase activity within 2 months.

  • 94.
    Kjellgren, Karin
    et al.
    Linköpings universitet, Hälsouniversitetet.
    Ahlner, JohanLinköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.Dahlgren, Lars-OveLinköpings universitet, Institutionen för beteendevetenskap, Avdelningen för studier av vuxenutbildning, folkbildning och högre utbildning, VUFo. Linköpings universitet, Utbildningsvetenskap.Haglund, LenaLinköpings universitet, Institutionen för nervsystem och rörelseorgan, Arbetsterapi. Linköpings universitet, Hälsouniversitetet.
    Problembaserad inlärning: Erfarenheter från Hälsouniversitetet1993Collection/Antologi (Annet vitenskapelig)
  • 95.
    Kjellgren, Karin
    et al.
    Hälsouniversitet Linköping.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Dahlöf, Björn
    Sahlgrenska sjukhuset Göteborg.
    Gill, Hans
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik.
    Patients' and physicians' assessment of risks associated with hypertension and benefits from treatment1998Inngår i: Journal of Cardiovascular Risk, ISSN 1350-6277, E-ISSN 1473-5652, Vol. 5, s. 161-166Artikkel i tidsskrift (Fagfellevurdert)
  • 96.
    Kjellgren, Karin
    et al.
    Hälsouniveristetet LInköping.
    Ahlner, Johan
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi.
    Dahlöf, Björn
    Sahlgrenska sjukhuset Göteborg.
    Gill, Hans
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för medicinsk teknik, Medicinsk informatik.
    Perceived symptoms amongst hypertensive patients in routine clinical practice - a population-based study1998Inngår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 244, s. 325-332Artikkel i tidsskrift (Fagfellevurdert)
  • 97.
    Kjellgren, Karin I.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Antihypertensive medication in clinical practice: Aspects of patient adherence in treatment1998Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Adherence to antihypertensive drug regimens is a well-documented determinant of blood pressure control. A review of the literature shows that little attention has been paid to how antihypertensive medication is managed in clinical practice.

    The aim of the empirical studies was to document and analyse the prerequisites of patient adherence to antihypertensive medication in routine clinical practice. The studies are based on two complementary sets of data, generated through intensive and extensive studies. In the intensive studies, audio-recordings (n=51) of follow-up appointments with hypertensive patients and their physicians were made in order to explore the nature of interaction ih routine clinical practice. Afterwards, patients (n=33) were interviewed to assess their knowledge of high blood pressure and antihypertensive medication. The extensive studies were population-based and carried out at Swedish primary health care centres (n=55) and clinics of internal medicine (n=ll). The intention of these studies was to assess perceived symptoms among hypertensive patients with (n=l 013) and without (n=l35) antihypertensive medication. Furthermore, concordance between the patients' and physicians' (n=212) views regarding risks of hypertension and benefits from antihypertensive medication was analysed.

    Most patients had a passive role and initiated few topics during the consultations. Little time was invested in discussing risks related to hypertension. The interviewed hypertensive patients had an unsatisfactory understanding of their condition and of the effects of the medication. The prevalence of perceived symptoms did not differ between patients with and without antihypertensive medication. Patients estimated the effects of medication to be more beneficial than did their physicians. Trade-offs between perceived benefits and side-effects of drug treatment showed that patients were generally unwilling to endure side-effects in return for long-term benefits of treatment. In routine clinical praxis, 14% of the antihypertensive medicated patients had reached a blood pressure o:;l40/90 mm Hg. Target values above 140/90 mm Hg were given for 63% of the patients by their physicians. Among patients who where aware of their target blood pressure, we found close agreement between the values given by patients and physicians. This implies that when the target blood pressure is communicated in clinical practice, the patients remember quite accurately.

    Better control of hypertension and coexisting risk factors is an essential objective in clinical practice. From the studies, two factors stood out as. important to improve adherence: more knowledge-sharing with the aim of increasing self-care competence and more effort to reduce side-effects of treatment.

  • 98.
    Knaust, Eva
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Experimental studies on multidrug resistance in human leukaemia: role of cellular heterogeneity for daunorubicin kinetics2005Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cellular resistance to chemotherapy is a major cause of treatment failure in acute myeloid leukaemia (AML) and still the majority of the patients die from their disease. Drug resistance 1s multifactorial, the most studied mechanism being multidrug resistance (MDR), mediated by the P-glycoprotein (Pgp). Pgp is an energy-dependent transport protein, encoded by the mdr1 gene, with the power to extrude the cytotoxic drugs out of the cells; thus causing reduced effect of the drug on the leukaemic cells. MDR is characterised by cross-resistance to a wide range of chemotherapeutics of natural origin. Other transport proteins, involved in drug resistance, are the multidrug resistance associated protein (MRP) and the lung resistance protein (Lrp).

    The aims of this thesis were to elucidate transport kinetics of the anthracycline, daunorubicin, (Dnr) and to investigate the effects of reversing agents on heterogeneity of drug accumulation in cells from patients with AML. The ultimate goal is to improve treatment based on each patient's individual resistance patterns.

    Density gradient isolated mononuclear cells from patients with AML were incubated with Dnr. Incubated cells were sorted with flow cytometry (FC) on the basis of accumulation levels of the autofluorescent Dnr. Gene expression of the Pgp and the MRP in sorted subpopulations were analysed with polymerase chain reaction (PCR). Apoptosis, expression of p53 and bcl-2 in the sorted subpopulations were determined with monoclonal antibodies and FC. Drug accumulation and efflux, with/without the resistance modifier Cyclosporin A (CyA) and energy-depleting metabolic inhibitors (MJ), were also determined in the leukaemic cell populations with FC.

    Gene expressions of mdr1 and mrp1 were shown to be heterogeneous in the leukaemic samples and drug accumulation correlated inversely to the gene expression. Cell populations with the higher drug accumulation entailed more apoptosis. The leukaemic cell lopulation, defined by immunopenotyping, differed in drug accumulation an efflux compared to the total mononuclear cell population that also contains normal lymphocytes and monocytes. In leukaemic samples with two blast cell populations, the more immature blast ceUs accumulated drug to a lesser extent and bad a higher efflux rate than the differentiating blast cells. CyA reduced Dnr efflux more efficiently than MI, but MJ increased drug accumulation in leukaemic cells more than CyA.

    In conclusion: analysis of the total mononuclear population does not give an accurate picture of the leukaemic cell population as concerns resistance mechanisms. Heterogeneity in the leukaemic cell population ought to be taken into account since two or more leukaemic cell populations often exist. The most immature blast cell population should be analysed as relapse usually derives from this population. Furthermore the role of Pgp in MDR is not conclusive as results with reversing agents differed from what was expected.

    Delarbeid
    1. Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation
    Åpne denne publikasjonen i ny fane eller vindu >>Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation
    Vise andre…
    1996 (engelsk)Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 92, nr 4, s. 847-854Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Multidrug resistance gene (mdr1) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML). Whether expression of the recently described multidrug resistance-associated gene (mrp) has any prognostic importance in AML is still unclear. The aim of the present study was to investigate the functional role of the mdr1 and mrp mRNA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubated with daunorubicin (DNR). Cellular DNR content was analysed with a fluorescence-activated cell sorter (FACS). From each cell population the 20–25% cells with the lowest and highest DNR content were sorted out, and mdr1 and mrp RNA were quantified in these subpopulations with competitive polymerase chain reaction. The ratio between the mean DNR content in the cell populations with high and low DNR content varied between 1.9 and 6.6. The cell fraction with low DNR content had higher (3.8–40 times) mdr1 mRNA levels in 10/10 patients and higher (1.4–26 times) mrp mRNA levels in 8/10, as compared to the cell fraction with high DNR accumulation.

    In conclusion, mdr1 and mrp mRNA expressions are heterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely correlated to DNR accumulation in vitro.

    Emneord
    acute myelocytic leukaemia; multidrug resistance; mRNA; cell sorting; PCR
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-84232 (URN)10.1046/j.1365-2141.1996.425963.x (DOI)8616077 (PubMedID)
    Tilgjengelig fra: 2012-10-02 Laget: 2012-10-02 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. Intraclonal heterogeneity in the in vitro daunorubicin-induced apoptosis in acute myeloid leukemia
    Åpne denne publikasjonen i ny fane eller vindu >>Intraclonal heterogeneity in the in vitro daunorubicin-induced apoptosis in acute myeloid leukemia
    Vise andre…
    1999 (engelsk)Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 32, nr 3-4, s. 309-316Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Leukemic cells from ten patients with acute myeloid leukemia (AML) were sorted on the basis of in vitro daunorubicin (DNR) uptake. The obtained subpopulations with high and low DNR accumulation were compared with regard to induction of apoptosis, expression of bcl-2 and p53. Heterogeneous induction of apoptosis, confined to subpopulations with high DNR uptake, was observed. The size of the DNR-induced apoptotic fraction (4% to 16%) within a given AML blast population was determined by intracellular drug accumulation and was not related to the level of bcl-2 expression. All tested leukemic samples displayed expression of p53 in a growth promoter orientation, i.e. PAb1620-/PAb240+. In two samples, however, sub-populations expressing a growth suppressor orientation of p53, i.e. PAb1620+/PAb240-, were also present. These subpopulations were confined to high-DNR-uptake fractions and associated with the induction of apoptosis. We conclude that intraclonal heterogeneity in the intracellular drug accumulation and subsequently in DNR-induced apoptosis might allow the selection of inherently drug-resistant AML clones thus contributing to relapse of leukemia.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26976 (URN)10.3109/10428199909167391 (DOI)11610 (Lokal ID)11610 (Arkivnummer)11610 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Heterogeneity of isolated mononuclear cells from patients with acute myeloid leukemia affects cellular accumulation and efflux of daunorubicin
    Åpne denne publikasjonen i ny fane eller vindu >>Heterogeneity of isolated mononuclear cells from patients with acute myeloid leukemia affects cellular accumulation and efflux of daunorubicin
    Vise andre…
    2000 (engelsk)Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 85, nr 2, s. 124-132Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Pharmacologic studies on blasts from patients with leukemia are generally performed on density gradient isolated blood or bone marrow cells. Thereby, cellular drug accumulation and efflux are determined as mean values of the entire cell population. The objective of the present study was to characterize the heterogeneity in the accumulation and efflux of daunorubicin in various subpopulations of mononuclear cells isolated from patients with acute myeloid leukemia (AML).

    DESIGN AND METHODS: Mononuclear cells from 33 patients with AML were isolated from peripheral blood by density gradient centrifugation on Lymphoprep (1. 077 g/mL). Cellular accumulation of fluorescent daunorubicin was determined by flow cytometry after incubation of the cells at +37C for 1 hour. Thereafter, the cells were washed and reincubated in drug-free medium. Kinetics of drug efflux were determined by frequent determination of cellular fluorescence during 30 min. Daunorubicin accumulation and efflux were compared in the total isolated mononuclear cell population and in the various blast cell populations gated on FSC/SSC according to the results of immunophenotyping.

    RESULTS: In 8 of these 33 (24%) patient samples, two distinct blast cell populations could be identified. In 7 out of 8 these cases the more immature blasts had a lower drug accumulation and in 6 out of the 8 cases also a higher efflux rate than the differentiating cell population. Cyclosporin A increased daunorubicin accumulation and reduced efflux in the immature blast population. In the differentiating cell population cyclosporin A increased both the accumulation and the efflux. In patients with a single blast cell population, the gated blast cells had a significantly lower drug accumulation but also a lower drug efflux rate than the total cell population.

    INTERPRETATION AND CONCLUSIONS: The results imply that drug transport studies on cells isolated from patients with AML give somewhat different results depending on the cell population studied. Some, but not all, of these differences in daunorubicin accumulation and efflux as well as in the effect of cyclo-sporin A can be explained by a heterogenous expression of the mdr1-gene. The observed heterogeneity may be of special relevance with regard to drug resistance. The presence of even a small resistant cell clone may jeopardize the effect of the chemotherapy due to expansion resulting in relapse of disease.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26978 (URN)11612 (Lokal ID)11612 (Arkivnummer)11612 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Different effects of metabolic inhibitors and cyclosporin A on daunorubicin transport in leukemia cells from patients with AML
    Åpne denne publikasjonen i ny fane eller vindu >>Different effects of metabolic inhibitors and cyclosporin A on daunorubicin transport in leukemia cells from patients with AML
    Vise andre…
    2003 (engelsk)Inngår i: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 27, nr 2, s. 183-191Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The objective of this study was to determine the role of transport proteins in daunorubicin (Dnr) accumulation and efflux in leukemia cells from 36 patients with acute myeloid leukemia (AML). Mononuclear cells were isolated and incubated with 1 μM Dnr with/without addition of 3 μM cyclosporin A (CyA) or metabolic inhibitors (MI). Cellular Dnr concentration in leukemia blast cells was measured with flow cytometry. After washing and reincubation of the cells in drug-free medium, Dnr efflux was followed with/without addition of CyA or MI. Levels of mRNA expression for mdr1, multidrug resistance associated protein (mrp) and lung resistance protein (lrp) were determined with reverse transcriptase-polymerase chain reaction (RT-PCR). MI enhanced cellular Dnr accumulation to a higher extent than CyA whereas CyA reduced Dnr efflux more efficiently than MI (P<0.001). There was a significant difference in Dnr accumulation between samples with low and high mdr1 mRNA levels but only in the presence of MI or CyA. Our results imply that other factors than P-glycoprotein (Pgp) are of major importance for in vitro Dnr accumulation in AML blasts and that the role of Pgp as a drug efflux pump is not conclusive.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26979 (URN)10.1016/S0145-2126(02)00093-0 (DOI)11613 (Lokal ID)11613 (Arkivnummer)11613 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
  • 99.
    Knaust, Eva
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Heterogeneity of leukemic cells with regard to daunorubicin accumulation and efflux: potential role in drug resistance2000Licentiatavhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Cellular resistance to chemotherapy is a major cause of treatment failure in acute myelocytic leukemia (AML) and other malignancies. Drug resistance is multifactorial; the most studied mechanism being multidrug resistance (MDR), mediated by the P-glycoprotein (PPG), a transmembrane transport protein with a pump function, encoded by the mdr 1 gene. MDR is characterised by cross resistance to a wide range of chemotherapeutics of natural origin e.g. anthracyclines, vinca alkaloids, epipodophyllotoxins and taxanes. The aim of the present study was to elucidate transport kinetics of the anthracycline daunorubicin (Dnr) and to study various forms of heterogeneity in cells from patients with AML. The ultimate goal is to improve treatment based on each patient's individual resistance patterns.

    Density gradient isolated mononuclear cells from patients with AML were incubated with Dnr. Incubated cells were sorted on the basis of accumulation of the autofluorescent Dnr with flow cytometry. Gene expression of the Pgp and the multidrug resistance-associated protein (MRP) in sorted subpopulations were analysed with polymerase chain reaction (PCR). Drug accumulation and efflux in leukemic cell populations, apoptosis, expression of p53 and bcl-2 in the sorted subpopulations were studied with flow cytometry.

    Gene expressions of mdrl and mrp were shown to be heterogeneous in the leukemic samples and drug accumulation correlated inversely to the gene expression. The blast cell population differed in drug accumulation and efflux compared to the total mononuclear cell population that contains also normal lymphocytes and monocytes. In leukemic samples with two blast cell populations the more immature blast cells accumulated less drug and had a higher efflux rate than the differentiating blast cells. Cell populations with higher drug accumulation entailed more apoptosis.

    The results suggest that, since several resistance factors can occur in the same patient heterogeneity in the leukemic cell population ought to be taken into account whenever resistance patterns are studied.

    Delarbeid
    1. Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation
    Åpne denne publikasjonen i ny fane eller vindu >>Levels of mdr1 and mrp mRNA in leukaemic cell populations from patients with acute myelocytic leukaemia are heterogenous and inversely correlated to cellular daunorubicin accumulation
    Vise andre…
    1996 (engelsk)Inngår i: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 92, nr 4, s. 847-854Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Multidrug resistance gene (mdr1) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML). Whether expression of the recently described multidrug resistance-associated gene (mrp) has any prognostic importance in AML is still unclear. The aim of the present study was to investigate the functional role of the mdr1 and mrp mRNA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubated with daunorubicin (DNR). Cellular DNR content was analysed with a fluorescence-activated cell sorter (FACS). From each cell population the 20–25% cells with the lowest and highest DNR content were sorted out, and mdr1 and mrp RNA were quantified in these subpopulations with competitive polymerase chain reaction. The ratio between the mean DNR content in the cell populations with high and low DNR content varied between 1.9 and 6.6. The cell fraction with low DNR content had higher (3.8–40 times) mdr1 mRNA levels in 10/10 patients and higher (1.4–26 times) mrp mRNA levels in 8/10, as compared to the cell fraction with high DNR accumulation.

    In conclusion, mdr1 and mrp mRNA expressions are heterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely correlated to DNR accumulation in vitro.

    Emneord
    acute myelocytic leukaemia; multidrug resistance; mRNA; cell sorting; PCR
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-84232 (URN)10.1046/j.1365-2141.1996.425963.x (DOI)8616077 (PubMedID)
    Tilgjengelig fra: 2012-10-02 Laget: 2012-10-02 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. Heterogeneity of isolated mononuclear cells from patients with acute myeloid leukemia affects cellular accumulation and efflux of daunorubicin
    Åpne denne publikasjonen i ny fane eller vindu >>Heterogeneity of isolated mononuclear cells from patients with acute myeloid leukemia affects cellular accumulation and efflux of daunorubicin
    Vise andre…
    2000 (engelsk)Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 85, nr 2, s. 124-132Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Pharmacologic studies on blasts from patients with leukemia are generally performed on density gradient isolated blood or bone marrow cells. Thereby, cellular drug accumulation and efflux are determined as mean values of the entire cell population. The objective of the present study was to characterize the heterogeneity in the accumulation and efflux of daunorubicin in various subpopulations of mononuclear cells isolated from patients with acute myeloid leukemia (AML).

    DESIGN AND METHODS: Mononuclear cells from 33 patients with AML were isolated from peripheral blood by density gradient centrifugation on Lymphoprep (1. 077 g/mL). Cellular accumulation of fluorescent daunorubicin was determined by flow cytometry after incubation of the cells at +37C for 1 hour. Thereafter, the cells were washed and reincubated in drug-free medium. Kinetics of drug efflux were determined by frequent determination of cellular fluorescence during 30 min. Daunorubicin accumulation and efflux were compared in the total isolated mononuclear cell population and in the various blast cell populations gated on FSC/SSC according to the results of immunophenotyping.

    RESULTS: In 8 of these 33 (24%) patient samples, two distinct blast cell populations could be identified. In 7 out of 8 these cases the more immature blasts had a lower drug accumulation and in 6 out of the 8 cases also a higher efflux rate than the differentiating cell population. Cyclosporin A increased daunorubicin accumulation and reduced efflux in the immature blast population. In the differentiating cell population cyclosporin A increased both the accumulation and the efflux. In patients with a single blast cell population, the gated blast cells had a significantly lower drug accumulation but also a lower drug efflux rate than the total cell population.

    INTERPRETATION AND CONCLUSIONS: The results imply that drug transport studies on cells isolated from patients with AML give somewhat different results depending on the cell population studied. Some, but not all, of these differences in daunorubicin accumulation and efflux as well as in the effect of cyclo-sporin A can be explained by a heterogenous expression of the mdr1-gene. The observed heterogeneity may be of special relevance with regard to drug resistance. The presence of even a small resistant cell clone may jeopardize the effect of the chemotherapy due to expansion resulting in relapse of disease.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26978 (URN)11612 (Lokal ID)11612 (Arkivnummer)11612 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Intraclonal heterogeneity in the in vitro daunorubicin-induced apoptosis in acute myeloid leukemia
    Åpne denne publikasjonen i ny fane eller vindu >>Intraclonal heterogeneity in the in vitro daunorubicin-induced apoptosis in acute myeloid leukemia
    Vise andre…
    1999 (engelsk)Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 32, nr 3-4, s. 309-316Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Leukemic cells from ten patients with acute myeloid leukemia (AML) were sorted on the basis of in vitro daunorubicin (DNR) uptake. The obtained subpopulations with high and low DNR accumulation were compared with regard to induction of apoptosis, expression of bcl-2 and p53. Heterogeneous induction of apoptosis, confined to subpopulations with high DNR uptake, was observed. The size of the DNR-induced apoptotic fraction (4% to 16%) within a given AML blast population was determined by intracellular drug accumulation and was not related to the level of bcl-2 expression. All tested leukemic samples displayed expression of p53 in a growth promoter orientation, i.e. PAb1620-/PAb240+. In two samples, however, sub-populations expressing a growth suppressor orientation of p53, i.e. PAb1620+/PAb240-, were also present. These subpopulations were confined to high-DNR-uptake fractions and associated with the induction of apoptosis. We conclude that intraclonal heterogeneity in the intracellular drug accumulation and subsequently in DNR-induced apoptosis might allow the selection of inherently drug-resistant AML clones thus contributing to relapse of leukemia.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-26976 (URN)10.3109/10428199909167391 (DOI)11610 (Lokal ID)11610 (Arkivnummer)11610 (OAI)
    Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2017-12-13bibliografisk kontrollert
  • 100.
    Knaust, Eva
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Porwit-MacDonald, Anna
    Department of Pathology, Division of Hematology, Karolinska Hospital and Institutet, Stockholm, Sweden.
    Gruber, Astrid
    Departments of Medicine, Division of Hematology, Karolinska Hospital and Institutet, Stockholm, Sweden.
    Xu, Dawei
    Departments of Medicine, Division of Hematology, Karolinska Hospital and Institutet, Stockholm, Sweden.
    Peterson, Curt
    Linköpings universitet, Institutionen för medicin och vård, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Different effects of metabolic inhibitors and cyclosporin A on daunorubicin transport in leukemia cells from patients with AML2003Inngår i: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 27, nr 2, s. 183-191Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The objective of this study was to determine the role of transport proteins in daunorubicin (Dnr) accumulation and efflux in leukemia cells from 36 patients with acute myeloid leukemia (AML). Mononuclear cells were isolated and incubated with 1 μM Dnr with/without addition of 3 μM cyclosporin A (CyA) or metabolic inhibitors (MI). Cellular Dnr concentration in leukemia blast cells was measured with flow cytometry. After washing and reincubation of the cells in drug-free medium, Dnr efflux was followed with/without addition of CyA or MI. Levels of mRNA expression for mdr1, multidrug resistance associated protein (mrp) and lung resistance protein (lrp) were determined with reverse transcriptase-polymerase chain reaction (RT-PCR). MI enhanced cellular Dnr accumulation to a higher extent than CyA whereas CyA reduced Dnr efflux more efficiently than MI (P<0.001). There was a significant difference in Dnr accumulation between samples with low and high mdr1 mRNA levels but only in the presence of MI or CyA. Our results imply that other factors than P-glycoprotein (Pgp) are of major importance for in vitro Dnr accumulation in AML blasts and that the role of Pgp as a drug efflux pump is not conclusive.

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