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  • 1.
    Jonsson, Thomas B.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Larzon, Thomas
    Department of Surgery, University Hospital, Örebro, Sweden.
    Arfvidsson, B.
    Department of Surgery, University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Medicine, University Hospital, Örebro, Sweden.
    Axelsson, C.-G.
    Department of Transfusion Medicine, University Hospital, Örebro, Sweden.
    Jurstrand, M.
    Clinical Research Centre, University Hospital, Örebro, Sweden.
    Norgren, Lars
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Surgery, University Hospital, Örebro, Sweden.
    Adverse events during treatment limb ischemia with autologous peripheral blood mononuclear cell implant2012In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 31, no 1, p. 77-84Article in journal (Refereed)
    Abstract [en]

    Aim: Trials have reported clinical improvement and reduced need for amputation in critical limb ischemia (CLI) patients receiving therapeutic angiogenesis with stem cells. Our objective was to test peripheral stem cell therapy efficacy and safety to gain experiences for further work.

    Methods: We included nine CLI patients (mean age 76.7 ±9.7). Stem cells were mobilized to the peripheral blood by administration of G-CSF (Filgrastim) for 4 days, and were collected on day five, when 30 mL of a stem cell suspension was injected into 40 points of the limb. The clinical efficacy was evaluated by assessing pain relief, wound healing and changes in ankle-brachial pressure index (ABI). Local metabolic and inflammatory changes were measured with microdialysis, growth factors and cytokine level determination. Patients were followed for 24 weeks.

    Results: Four patients experienced some degree of improvement with pain relief and/or improved wound healing and ABI increase. One patient was lost to follow up due to chronic psychiatric illness; one was amputated after two weeks. Two patients had a myocardial infarction (MI), one died. One patient died from a massive mesenteric thrombosis after two weeks and one died from heart failure at week 11. Improved patients showed variable effects in cytokine-, growth factor- and local metabolic response.

    Conclusion: Even with some improvement in four patients, severe complications in four out of nine patients, and two in relation to the bone marrow stimulation, made us terminate the study prematurely. We conclude that with the increased risk and the reduced potential of the treatment, peripheral blood stem cell treatment in the older age group is less appropriate. Metabolic and inflammatory response may be of value to gain insight into mechanisms and possibly to evaluate effects of therapeutic angiogenesis.

  • 2.
    Jonsson, Thomas Björn
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsson, T. K.
    Dept Med Biosci Clin Chem, Umeå Univ, Umeå, Sweden.
    Breimer, Lars H.
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Schneede, J.
    Dept Clin Pharmacol, Umeå Univ, Umeå, Sweden.
    Arfvidsson, B.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Norgren, Lars
    Örebro University, School of Health and Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Cloxacillin concentrations in serum, subcutaneous fat, and muscle in patients with chronic critical limb ischemia2014In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 70, no 8, p. 957-963Article in journal (Refereed)
    Abstract [en]

    Patients suffering from critical limb ischemia (CLI) have poor wound healing in the ankle and foot areas. Secondary wound infections are frequent and often treated with prolonged courses of antibiotics.

    This study set out to investigate to what extent the unbound fraction of 4 g of cloxacillin i.v. reaches its target organ in poorly vascularized tissues, i.e., the calf and foot of patients suffering from CLI.

    Cloxacillin concentrations were measured by HPLC in serum and in microdialysis samples from skin and muscle of the lower part of the calf and as reference subcutaneously at the pectoral level in eight patients suffering from CLI (four males, four females, mean age 78 years, range 66-85 years) and in three healthy controls (two females, one male, mean age 67, range 66-68 years).

    In patients suffering from CLI, the tissue penetration of cloxacillin after a single 4 g dose was comparable to that of healthy controls, despite impaired blood circulation.

    The reduced blood flow in the peripheral vessels of the CLI patients presented here apparently is not the rate-limiting factor for delivery or tissue penetration of cloxacillin.

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