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  • 1.
    Carlsson, Eva
    et al.
    Örebro University, School of Health Sciences.
    Anderzén Carlsson, Agneta
    Örebro University, School of Health Sciences.
    Prenkert, Malin
    Örebro University, School of Health Sciences.
    Svantesson, Mia
    Örebro University, School of Health Sciences.
    Ways of understanding being a healthcare professional in the role of family member of a patient admitted to hospital: A phenomenographic study2016In: International Journal of Nursing Studies, ISSN 0020-7489, E-ISSN 1873-491X, Vol. 53, p. 50-60Article in journal (Refereed)
    Abstract [en]

    Healthcare professionals' experience of being family member of a patient can contribute to knowledge development and organizational learning in further ways than the experiences of general family members. However, there is little research on healthcare professionals' experience being on 'the other side of the bed'.

    Objective: To describe how healthcare professionals understand the role of being a healthcare professional and a family member of a patient admitted to hospital.

    Design: Qualitative with a phenomenographic approach.

    Setting: Three Swedish hospitals.

    Participants: All healthcare professionals in three hospitals were invited. Twenty-one volunteered for the study and 18 met the inclusion criteria; to have one year of professional experience and to have visited the family member in hospital daily during hospitalization. Family members in maternity or psychiatric care were excluded.

    Methods: Semi-structured interviews were used for data collection. Transcripts were analyzed with a phenomenographic method to describe variation and commonality in the ways of understanding the phenomenon under study.

    Results: Four dominant ways of understanding the phenomenon were identified; the informed bystander, the supervisor, the advocate and the carer. The four ways of understanding were hierarchically related with "The informed bystander" being least involved in the care of the family member and "The carer" more or less taking over the patient's care because of inappropriate, unsafe or omitted care. Common for all ways of understanding the phenomenon, except "The informed bystander", was the difficult balance between their loyalty toward the family member and their colleagues among the staff. "The informed bystander" and "The supervisor" are ways of understanding the phenomenon under study that, to our knowledge, has not been described before.

    Conclusions: This study describes how being a family member of a patient can be understood in four different ways when the family member is a healthcare professional. The findings show similarities to previous studies on general family members as well as nurse-family members of patients in critical care. The need for professional communication, support and coordination will be substantially different if the family member understands his/her role as an informed bystander compared to if they perceive themselves as a carer. The role conflict and ambivalence toward building relationships described are aspects that need further exploration, as does the experience of being forced to care for a family member. Our findings contribute with new knowledge developing patient- and family-centered care.

  • 2.
    Franzén, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Johansson, Madelaine
    Örebro University.
    Prenkert, Malin
    Örebro University, School of Health Sciences.
    Doktoranders upplevelse av nyttan med den obligatoriska forskarutbildningskursen Allmänvetenskaplig forskningsmetodik i medicinsk vetenskap vid Örebro universitet2016Conference paper (Other academic)
  • 3.
    Möllgård, Lars
    et al.
    Karolinska Institutet.
    Prenkert, Malin
    Örebro University, Department of Nursing and Caring Sciences.
    Smolowicz, Adam
    Paul, Christer
    Karolinska Institutet.
    Tidefelt, Ulf
    Örebro University, Department of Clinical Medicine.
    In vitro chemosensitivity testing of selected myeloid cells in acute myeloid leukemia 2003In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 44, no 5, p. 783-789Article in journal (Refereed)
    Abstract [en]

    In several studies different chemosensitivity assays have been examined in acute myeloid leukemia (AML). Some have shown that in vitro chemosensitivity testing is an independent prognostic factor but so far no one has been able to show that the use of these methods can improve treatment outcome. In an attempt to improve in vitro chemosensitivity testing in AML we wanted to establish and evaluate a new flow cytometry chemosensitivity assay. After 4 days of incubation viable mononuclear myeloid cells were identified by the exclusion of propidium iodide in CD13 or CD33 positive cells. Sixty-eight samples from 64 AML patients were included. In this study, we showed that the flow cytometry method is feasible in AML and we also found some correlations to clinical data. The secondary AML at diagnosis showed an in vitro resistance to etoposide and amsacrine that was significantly higher compared to de novo AML at diagnosis (p = 0.04 and p = 0.02). When AML patients at diagnosis were compared to resistant disease/relapse patients there was a significantly higher effect of ara-C in the diagnosis group (p = 0.03). Responders and non-responders were compared in vitro but we found no significant differences. In vitro mitoxantrone was more effective in multidrug resistance (MDR) negative cells compared to MDR positive cells (p < 0.01). This new method is feasible and makes it possible to selectively evaluate the effect of cytotoxic drugs in myeloid cells. Further studies with a larger group of patients are needed to evaluate the predictive value of the assay.

  • 4.
    Prenkert, Malin
    Örebro University, School of Health and Medical Sciences.
    On mechanisms of drug resistance in acute myeloid leukemia2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis focus has been to increase the knowledge and understanding of some of the mechanisms responsible for drug resistance in acute myeloid leukemia, as well as identify possibilities to predict drug resistance at diagnosis.

    We have studied the intracellular behavior of cytostatic drugs and their main metabolites (paper I) and the cellular response to cytostatic drugs (paper III). A new flow cytometry in vitro chemosensitivity assay was developed, to enable identification of viable myeloid cells and determination of drug sensitivity (paper II). Finally, possible new markers involved in drug resistance were investigated (paper IV).

    In conclusion we found that idarubicin and daunorubicin are equally toxic at the same intracellular concentrations. The contribution of the main metabolites to the cytotoxic effects of idarubicin and daunorubicin, in both drug sensitive and drug resistant human myeloid leukemia cells, is low. It is most likely the pharmacokinetic properties of idarubicin and daunorubicin that confer their main cytotoxic effect. With the new flow cytometry chemosensitivity assay we selectively identified viable CD13/CD33 expressing myeloid cells and found that the cytotoxicity results correlated to clinical parameters, such as secondary AML and resistant disease. Short-term exposure of leukemia cell lines with different levels of drug resistance to ara-C revealed that Pgp mRNA and protein ex-pression levels, as well as GSTπ mRNA levels, were rapidly up-regulated. Clinically, this up-regulation may be of importance for the sequential scheduling of daunorubicin and ara-C during the induction treatment of AML. CRIM1 has

    never been studied in the context of drug resistance before. We show for the first time that baseline expression of CRIM1 mRNA is much higher in drug resistant leukemia cells compared to drug sensitive cells. We also found a co-variance between CRIM1 and Pgp mRNA expression levels in leukemia cell lines with different levels of drug resistance, suggesting that CRIM1 may be useful as a marker of drug resistance.

    List of papers
    1. Comparison of idarubicin and daunorubicin and their main metabolites regarding intracellular uptake and effect on sensitive and multidrug-resistant HL60 cells
    Open this publication in new window or tab >>Comparison of idarubicin and daunorubicin and their main metabolites regarding intracellular uptake and effect on sensitive and multidrug-resistant HL60 cells
    1996 (English)In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 38, no 5, p. 87p. 476-480Article in journal (Refereed) Published
    Abstract [en]

    To study the effect of the main metabolites on the cytotoxic effect of daunorubicin and idarubicin in human HL-60 cells, drug-sensitive and multidrug-resistant HL60 cells were incubated with idarubicin and daunorubicin and their metabolites idarubicinol and daunorubicinol over a wide range of concentrations. The intracellular uptake of the drugs was determined by photofluorometry, and the cytotoxic effect in vitro was determined by a bioluminescence assay of intracellular adenosine triphosphate (ATP) after 4 days of culture in liquid medium. The effect of intracellular drugs was calculated from the incubation-concentration versus intracellular-uptake and cytotoxic-effect curves. The intracellular uptake of idarubicin was 6 times that of daunorubicin in drug-sensitive cells and 25 times higher in resistant cells. For idarubicinol as compared with daunorubicinol the corresponding factors were 25 and 7, respectively. As compared with the parent substances, the uptake of idarubicinol and daunorubicinol was 16% and 4%, respectively, in sensitive cells and 40% and >100%, respectively, in resistant cells. An intracellular concentration of 0.5 nmol/mg protein of both parent substances caused a 50% growth inhibition in drug-sensitive cells as compared with 10 nmol/mg protein for drug-resistant cells. For the metabolites an intracellular concentration of 0.4 nmol/mg protein of idarubicinol and 2.0 nmol/mg protein of daunorubicinol was required to inhibit cells’ growth by 50% in drug-sensitive HL60 cells. In the resistant HL60 cells the corresponding values were 30 nmol/mg protein for idarubicinol and 40 nmol/mg protein for daunorubicinol. These results confirm that idarubicinol may significantly contribute to the clinical effect of idarubicin. However, in combination with previous results that have shown low intracellular concentrations of the metabolites in vivo, it appears that the pharmacokinetic properties of the mother substances provide the major explanation for the clinical effect of idarubicin.

    Place, publisher, year, edition, pages
    Berlin: Springer, 1996. p. 87
    Keywords
    Idarubicin, idarubicinol, daunorubicin, daunorubicinol, intracellular uptake, in vitro effect.
    National Category
    Medical and Health Sciences
    Research subject
    biomedicin
    Identifiers
    urn:nbn:se:oru:diva-10451 (URN)10.1007/s002800050514 (DOI)978-91-7668-729-1 (ISBN)
    Available from: 2010-05-03 Created: 2010-04-22 Last updated: 2017-12-12Bibliographically approved
    2. In vitro chemosensitivity testing of selected myeloid cells in acute myeloid leukemia 
    Open this publication in new window or tab >>In vitro chemosensitivity testing of selected myeloid cells in acute myeloid leukemia 
    Show others...
    2003 (English)In: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 44, no 5, p. 783-789Article in journal (Refereed) Published
    Abstract [en]

    In several studies different chemosensitivity assays have been examined in acute myeloid leukemia (AML). Some have shown that in vitro chemosensitivity testing is an independent prognostic factor but so far no one has been able to show that the use of these methods can improve treatment outcome. In an attempt to improve in vitro chemosensitivity testing in AML we wanted to establish and evaluate a new flow cytometry chemosensitivity assay. After 4 days of incubation viable mononuclear myeloid cells were identified by the exclusion of propidium iodide in CD13 or CD33 positive cells. Sixty-eight samples from 64 AML patients were included. In this study, we showed that the flow cytometry method is feasible in AML and we also found some correlations to clinical data. The secondary AML at diagnosis showed an in vitro resistance to etoposide and amsacrine that was significantly higher compared to de novo AML at diagnosis (p = 0.04 and p = 0.02). When AML patients at diagnosis were compared to resistant disease/relapse patients there was a significantly higher effect of ara-C in the diagnosis group (p = 0.03). Responders and non-responders were compared in vitro but we found no significant differences. In vitro mitoxantrone was more effective in multidrug resistance (MDR) negative cells compared to MDR positive cells (p < 0.01). This new method is feasible and makes it possible to selectively evaluate the effect of cytotoxic drugs in myeloid cells. Further studies with a larger group of patients are needed to evaluate the predictive value of the assay.

    Place, publisher, year, edition, pages
    Taylor & Frances healthsciences, 2003
    Keywords
    Chemosensitivity, cytotoxicity, drug resistance, flow cytometry, acute myeloid leukemia
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10578 (URN)10.1080/1042819031000067594 (DOI)12802914 (PubMedID)
    Available from: 2010-05-03 Created: 2010-05-03 Last updated: 2017-12-12Bibliographically approved
    3. Rapid Induction of P-Glycoprotein mRNA and Protein Expression by Cytarabine in HL-60 Cells
    Open this publication in new window or tab >>Rapid Induction of P-Glycoprotein mRNA and Protein Expression by Cytarabine in HL-60 Cells
    Show others...
    2009 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 10, p. 4071-4076Article in journal (Refereed) Published
    Abstract [en]

    Background: Overexpression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and glutathione-S-transferase π (GSTπ) is associated with drug resistance in acute myeloid leukemia (AML). The short-term effects of drug exposure on their expression levels were investigated.

    Materials and Methods: HL-60 cells and drug-resistant sublines were cultured with or without daunorubicin (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P-gp, BCRP and GSTπ were determined.

    Results: After exposure to Ara-C, P-gp mRNA rapidly increased in all the cell lines. P-gp protein was detected in the sensitive cells after 8 h exposure to Ara-C. GSTπ mRNA increased in the resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR revealed rapidly increased P-gp and GSTπ mRNA in the resistant cells.

    Conclusion: Ara-C rapidly increases P-gp mRNA and protein expression in sensitive and resistant cells, and GSTπ mRNA in resistant cells, in vitro. This may be of clinical importance during AML induction chemotherapy.

    Place, publisher, year, edition, pages
    Athens: International Institute of Anticancer Research, 2009
    Keywords
    Drug resistance, P-glycoprotein, daunorubicin, cytarabine, HL-60 cells, glutathione-S-transferase pi
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10580 (URN)000271487400051 ()19846953 (PubMedID)2-s2.0-71949122848 (Scopus ID)
    Available from: 2010-05-03 Created: 2010-05-03 Last updated: 2017-12-12Bibliographically approved
    4. CRIM1 is expressed at higher levels in drug resistant than in drug sensitive myeloid leukemia HL60 cells
    Open this publication in new window or tab >>CRIM1 is expressed at higher levels in drug resistant than in drug sensitive myeloid leukemia HL60 cells
    (English)Manuscript (preprint) (Other academic)
    Keywords
    CRIM1, cytarabine, daunorubicin, drug resistance, HL60 cells
    National Category
    Medical and Health Sciences
    Research subject
    Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-10582 (URN)
    Available from: 2010-05-03 Created: 2010-05-03 Last updated: 2017-10-18Bibliographically approved
  • 5.
    Prenkert, Malin
    et al.
    Örebro University, School of Health Sciences.
    Carlsson, Eva
    Örebro University, School of Health Sciences.
    Svantesson, Mia
    Örebro University, School of Health Sciences.
    Anderzén-Carlsson, Agneta
    Örebro University, School of Health Sciences.
    Healthcare-professional patients’ conceptions of being ill and hospitalised: a phenomenographic study2017In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 26, no 11-12, p. 1725-1736Article in journal (Refereed)
    Abstract [en]

    Aims and Objectives: To describe the variation of conceptions of being ill and hospitalised, from the perspective of health-care-professional-patients.

    Background: Previous literature focuses on either physicians' or nurses' experiences of being a patient, without aiming at determining a variation of ways of understanding that phenomena. Nor have we been able to identify any study reporting other health-care-professionals' experiences.

    Design: This study has an inductive descriptive design.

    Methods: Qualitative interviews with health care professionals (n=16), who had been hospitalised for at least two days. Phenomenographic data analysis was conducted.

    Results: The feelings of security were based on knowledge, insight and trust, and acceptance of the health care system. Being exposed and totally dependent due to illness provoked feelings of vulnerability and insecurity. The patients used their knowledge to achieve participation in the care. The more severe they perceived their illness to be, the less they wanted to participate and the more they expressed a need for being allowed to surrender control. The patients' ideal picture of care was sometimes disrupted and based on their experience they criticised care and made suggestions that could contribute to general care improvements.

    Conclusions: Health-care-professional patients' have various conceptions of being ill and hospitalised. Based on the general nature of the many needs expressed, we believe that the some insights provided in this study can be transferred so as to also be valid for lay patients. Possibly, an overhaul of routines for discharge planning and follow-up, and adopting a person-centred approach to care, can resolve some of the identified shortcomings. Finally, the results can be used for the purpose of developing knowledge for health-care professions and for educational purposes.

    Relevance to clinical practice: The results can be used for the purpose of develop-ing knowledge for healthcare professions and for educational purposes.

  • 6.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ehnfors, Margareta
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Growth data of underprivileged children living in rural areas of Chin State, Burma/Myanmar, compared to the WHO reference growth standards: an observational study2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1, article id e009119Article in journal (Refereed)
    Abstract [en]

    Objectives: To explore growth data (height-for-age, weight-for-age and BMI-for-age) of children living in poor socioeconomic conditions in rural areas of Chin State, Burma/Myanmar; and to compare these data with the growth and development z-score (GDZ) values for school-aged children and adolescents, provided by the WHO.

    Setting: A support and educational programme, run by the Swedish association Chin Development and Research Society (CDRS), was carried out among underprivileged school-aged children, unable to attend school without economic and practical support, living in villages and remote areas in Chin State.

    Participants: Community leaders who were well familiar with the citizens in the community identified children in need of this support. Other community members could also suggest or apply for this. The sample includes all participating children in the CDRS programme at the time of the data collection in six townships. The children were placed in host families, close to a suitable school. Two samples with a total of 639 children from 144 villages and remote areas were obtained:

    1. Children in the CDRS Chin Programme (CCP) (20072010) comprised 558 children: 50% girls and boys.

    2. Children in the Chin Society (CCS) (2010) comprised 81 children: 44% girls and 56% boys.

    Primary outcome measures: Growth data.

    Results: All growth data from both groups deviated significantly from the WHO standard references (p=0.001). The prevalence of stunting (height-for-age <=-2SD) was 52% among girls and 68% among boys. High levels of wasting (weight-for-age <=-2SD) were found among girls 29% and boys 36% aged 5-10 years. In addition, severe thinness (BMI-for-age <=-2SD) was found among girls 31% and boys 44%, all results to be compared to the expected 2.27%.

    Conclusions: Many more than expected-according to the WHO reference values-in CCP and CCS suffered from stunting, wasting and thinness.

  • 7.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Uggla, Bertil
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Strid, Hilja
    CRIM1 is expressed at higher levels in drug resistant than in drug sensitive myeloid leukemia HL60 cellsManuscript (preprint) (Other academic)
  • 8.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Research Center, Örebro University Hospital, Örebro; Sweden.
    Uggla, Bertil
    Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    CRIM1 is expressed at higher levels in drug-resistant than in drug-sensitive myeloid leukemia HL60 cells2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 10, p. 4157-61Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to explore possible differences in the mRNA expression levels of CRIM1, SMAD5, BMP4 and BMP7 in sensitive (S) and multidrug-resistant (R0.5) myeloid leukemia HL60 cells.

    Materials and Methods: HL60S and HL60R0.5 cells were exposed to daunorubicin (DNR) or cytarabine (Ara-C).

    Results: Baseline levels of CRIM1 were found to be 15-fold higher in HL60R0.5 than in HL60S. Sixteen hours of exposure to DNR resulted in a 5.6-fold increase in CRIM1 levels in HL60S. Exposure to either DNR or Ara-C resulted in modest increases in CRIM1 levels in HL60R0.5. Similarly, baseline levels of SMAD5 and BMP4 were higher in HL60R0.5 than in HL60S cells. Analysis of the drug SMAD5-resistance marker permeability-glycoprotein (Pgp) revealed that CRIM1 and Pgp exhibit a covariance pattern of expression.

    Conclusion: This study demonstrated that CRIM1 is expressed at high levels in resistant leukemia cells, indicating that CRIM1 may play a role in drug-resistance.

  • 9.
    Prenkert, Malin
    et al.
    Örebro University, School of Health and Medical Sciences.
    Uggla, Bertil
    Karolinska Institutet.
    Tina, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences.
    Rapid Induction of P-Glycoprotein mRNA and Protein Expression by Cytarabine in HL-60 Cells2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 10, p. 4071-4076Article in journal (Refereed)
    Abstract [en]

    Background: Overexpression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and glutathione-S-transferase π (GSTπ) is associated with drug resistance in acute myeloid leukemia (AML). The short-term effects of drug exposure on their expression levels were investigated.

    Materials and Methods: HL-60 cells and drug-resistant sublines were cultured with or without daunorubicin (DNR) and cytarabine (Ara-C). At several time-points the expression levels of P-gp, BCRP and GSTπ were determined.

    Results: After exposure to Ara-C, P-gp mRNA rapidly increased in all the cell lines. P-gp protein was detected in the sensitive cells after 8 h exposure to Ara-C. GSTπ mRNA increased in the resistant cells, but no change in BCRP mRNA was observed. Exposure to DNR revealed rapidly increased P-gp and GSTπ mRNA in the resistant cells.

    Conclusion: Ara-C rapidly increases P-gp mRNA and protein expression in sensitive and resistant cells, and GSTπ mRNA in resistant cells, in vitro. This may be of clinical importance during AML induction chemotherapy.

  • 10.
    Svantesson, Mia
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Carlsson, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Prenkert, Malin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Anderzen-Carlsson, Agneta
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    'Just so you know, the patient is staff': healthcare professionals' perceptions of caring for healthcare professional-patients2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 1, article id e008507Article in journal (Refereed)
    Abstract [en]

    Objective: To explore healthcare professionals' conceptions of the care of patients who are also healthcare professionals.

    Design: Explorative, with a qualitative, phenomenographic approach.

    Participants and setting: 16 healthcare personnel within different professions (doctors, nurses, assistant nurses, physiotherapists, occupational therapists) were interviewed about the care of 32 patients who were themselves members of different healthcare professions, in one healthcare organisation in Sweden.

    Results: The care of patients who are healthcare professionals was conceived in five different ways, as: usual, dutiful, prioritised and secure, insecure and responsive. An initial conception was that their care was usual, just as for any other patient, and also a perceived duty to treat them and to protect their right to be a patient-as any other patient. Exploring further, informants described that these patients did receive secure and prioritised care, as the informants experienced making a greater commitment, especially doctors giving privileges to doctor-patients. A conception of insecure care infused the informants' descriptions. This comprised of them feeling intimidated in their professional role, feeling affected by colleagues' stressful behaviour and ambiguity whether the healthcare professional-patient could be regarded as a competent professional. The deepest way of understanding care seemed to be responsive care, such as acknowledging and respecting the patient's identity and responding to their wishes of how treatment was to be met.

    Conclusions: Caring for healthcare professionals seems to trigger different ethical approaches, such as deontology and ethics of care. According to ethics of care, the findings may indeed suggest that these patients should be cared for just as any other patients would be, but only if this means that they are cared for as persons, that is, they are given 'person-centred care'. This would imply balancing between acknowledging the vulnerable patient in the colleague and acknowledging the identity of the colleague in the patient.

  • 11.
    Tidefelt, Ulf
    et al.
    Örebro University, School of Health and Medical Sciences.
    Prenkert, Malin
    Örebro University, School of Health and Medical Sciences.
    Paul, Christer
    Karolinska Institutet.
    Comparison of idarubicin and daunorubicin and their main metabolites regarding intracellular uptake and effect on sensitive and multidrug-resistant HL60 cells1996In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 38, no 5, p. 87p. 476-480Article in journal (Refereed)
    Abstract [en]

    To study the effect of the main metabolites on the cytotoxic effect of daunorubicin and idarubicin in human HL-60 cells, drug-sensitive and multidrug-resistant HL60 cells were incubated with idarubicin and daunorubicin and their metabolites idarubicinol and daunorubicinol over a wide range of concentrations. The intracellular uptake of the drugs was determined by photofluorometry, and the cytotoxic effect in vitro was determined by a bioluminescence assay of intracellular adenosine triphosphate (ATP) after 4 days of culture in liquid medium. The effect of intracellular drugs was calculated from the incubation-concentration versus intracellular-uptake and cytotoxic-effect curves. The intracellular uptake of idarubicin was 6 times that of daunorubicin in drug-sensitive cells and 25 times higher in resistant cells. For idarubicinol as compared with daunorubicinol the corresponding factors were 25 and 7, respectively. As compared with the parent substances, the uptake of idarubicinol and daunorubicinol was 16% and 4%, respectively, in sensitive cells and 40% and >100%, respectively, in resistant cells. An intracellular concentration of 0.5 nmol/mg protein of both parent substances caused a 50% growth inhibition in drug-sensitive cells as compared with 10 nmol/mg protein for drug-resistant cells. For the metabolites an intracellular concentration of 0.4 nmol/mg protein of idarubicinol and 2.0 nmol/mg protein of daunorubicinol was required to inhibit cells’ growth by 50% in drug-sensitive HL60 cells. In the resistant HL60 cells the corresponding values were 30 nmol/mg protein for idarubicinol and 40 nmol/mg protein for daunorubicinol. These results confirm that idarubicinol may significantly contribute to the clinical effect of idarubicin. However, in combination with previous results that have shown low intracellular concentrations of the metabolites in vivo, it appears that the pharmacokinetic properties of the mother substances provide the major explanation for the clinical effect of idarubicin.

  • 12.
    Tina, Elisabet
    et al.
    Örebro University, School of Health and Medical Sciences.
    Prenkert, Malin
    Örebro University, School of Health and Medical Sciences.
    Höglund, Martin
    Paul, Christer
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences.
    Topoisomerase IIalpha expression in acute myeloid leukaemia cells that survive after exposure to daunorubicin or ara-C2009In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 22, no 6, p. 1527-1531Article in journal (Refereed)
    Abstract [en]

    Patients diagnosed with acute myeloid leukaemia are often treated with a combination of daunorubicin and 1-β-D-arabinofuranosylcytosine (ara-C). Both daunorubicin and ara-C exert their effects in the cell nucleus but by different mechanisms, i.e. daunorubicin causes double stranded DNA breaks by inhibition of the nuclear enzyme, topoisomerase (topo) IIα, whereas ara-C is an anti-metabolite that integrates with DNA during DNA synthesis and causes cell cycle arrest. Despite the initial efficacy of these drugs, resistance often develops in the clinical setting. The mechanisms underlying clinical resistance to these drugs are poorly understood, but may be associated with an increase in the proportion of topo IIα negative cells. Therefore, the aim of this study was to determine whether daunorubicin treatment results in increased numbers of topo IIα negative subpopulations in vitro. Acute myeloid leukaemia cells isolated from 12 consenting patients were treated for 24 h with increasing concentrations of daunorubicin or ara-C and the proportion of topo IIα-negative cells in surviving cell populations determined by flow cytometry. Treatment with daunorubicin, but not ara-C, resulted in a significant increase in the proportion of topo IIα negative cells (p=0.0023). These results suggest that daunorubicin may act by cell cycle arrest and/or by selection of pre-existing topo IIα negative subpopulations. Both of these mechanisms can theoretically contribute to a reduced efficacy of a second dose of daunorubicin. The clinical relevance of these interactions should be further elucidated in experimental and clinical studies.

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