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  • 1. Danielsson, P.
    et al.
    Truedsson, L.
    Norgren, Lars
    Örebro University, Department of Clinical Medicine.
    Systemic white blood and endothelial cell response after revascularization of critical limb ischemia is only influenced in case of ischemic ulcers2006In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 25, no 3, p. 310-315Article in journal (Refereed)
    Abstract [en]

    AIM: The aim of this study was to study the inflammatory response to open revascularization of an ischemic leg in terms of activation of white blood cells (WBC), platelets and endothelial cells. DESIGN: prospective study. METHODS: Venous samples from 21 patients suffering critical limb ischemia (CLI) were drawn before, and 4 weeks after (20 patients) revascularization. Total WBC, differentiated WBC, and platelets were counted. Expression of CD11b/CD18 on granulocytes and monocytes and CD41 on platelets was measured by flow cytometry. Soluble endothelial markers (sICAM-1, sVCAM-1, sE-selectin and sP-selectin) were analysed with ELISA. RESULTS: WBC and granulocyte count decreased in the subgroup of patients with ulcer and gangrene but no change in activation of WBC was recorded. The endothelial marker sICAM-1 decreased while VCAM-1 increased following surgery, most evident in the subgroup with ulcers and gangrene. CONCLUSIONS: This study shows that revascularization of CLI does not significantly influence the inflammatory response in patients with rest pain only, but a limited response of down regulation was found in the ulcer/gangrene patients probably as an effect of healing ulcers.

  • 2.
    El Marghani, Ahmed M.
    et al.
    Örebro University, School of Science and Technology.
    Abuabaid, Hanan M.
    Örebro University, School of Health and Medical Sciences.
    Hurtig-Wennlöf, Anita
    Örebro University, School of Health and Medical Sciences.
    Sirsjö, Allan
    Örebro University, School of Health and Medical Sciences.
    Norgren, Lars
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Kjellén, Peter
    Örebro University, School of Science and Technology.
    High MAPK p38 activity and low level of IL-10 in intermittent claudication as opposed to stable angina2010In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 29, no 4, p. 331-337Article in journal (Refereed)
    Abstract [en]

    AIM:

    The aim of the present pilot study was to relate the activity of MAPK p38 with the levels of pro- and anti-inflammatory cytokines in a small cohort of patients with either stable angina (N=5) or intermittent claudication (N=5) compared to healthy controls (N=10).

    METHODS:

    The activity of MAPK p38 was determined in peripheral blood mononuclear cells, isolated from whole blood by western blot using phospho-specific anti-MAPK p38 antibodies. Cytokine levels of 11 pro- and anti-inflammatory cytokines were determined from the serum using flow cytometry.

    RESULTS:

    We found a significant elevation of the MAPK p38 activity in the intermittent claudication group (P=0.0027) compared with the healthy control group whereas the stable angina group showed similar MAPK p38 activity as the healthy control group. The IL-10 level in serum found in the stable angina group was significantly higher compared with both the healthy control group (P=0.0116) and the intermittent claudication group (P=0.0317).

    CONCLUSION:

    Our results imply that there is a casual relationship between increased levels of the anti-inflammatory cytokines IL-10 and IL-4 and the activity of the MAPK p38. Possibly has IL-10 a protective role that down-regulates the activity of MAPK p38 and thereby further inflammatory processes in stable angina patients.

  • 3.
    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.

  • 4.
    Lee, Byung B.
    et al.
    Division of Vascular Surgery, Department of Surgery, George Washington University, Washington DC, WA, USA.
    Blomgren, Lena
    of Vascular Surgery Karolinska University Hospital Stockholm, Sweden.
    Ezpeleta, Santiago Z.
    Interventional Vascular Radiology Unit, Ruber International Hospital, Madrid, Spain.
    Venous hemodynamic changes in lower limb venous disease: the UIP consensus according to scientific evidence2016In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 35, no 3, p. 236-352Article in journal (Refereed)
    Abstract [en]

    There are excellent guidelines for clinicians to manage venous diseases but few reviews to assess their hemodynamic background. Hemodynamic concepts that evolved in the past have largely remained unchallenged in recent decades, perhaps due to their often complicated nature and in part due to emergence of new diagnostic techniques. Duplex ultrasound scanning and other imaging techniques which evolved in the latter part of the 20th century have dominated investigation. They have greatly improved our understanding of the anatomical patterns of venous reflux and obstruction. However, they do not provide the physiological basis for understanding the hemodynamics of flow, pressure, compliance and resistance. Hemodynamic investigations appear to provide a better correlation with post-treatment clinical outcome and quality of life than ultrasound findings. There is a far better prospect for understanding the complete picture of the patient's disability and response to management by combining ultrasound with hemodynamic studies. Accordingly, at the instigation of Dr Angelo Scuderi, the Union Internationale de Phlebologie (UIP) executive board commissioned a large number of experts to assess all aspects of management for venous disease by evidence-based principles. These included experts from various member societies including the European Venous Forum (EVF), American Venous Forum (AVF), American College of Phlebology (ACP) and Cardiovascular Disease Educational and Research Trust (CDERT). Their aim was to confirm or dispel long-held hemodynamic principles and to provide a comprehensive review of venous hemodynamic concepts underlying the pathophysiology of lower limb venous disorders, their usefulness for investigating patients and the relevant hemodynamic changes associated with various forms of treatment. Chapter 1 is devoted to basic hemodynamic concepts and normal venous physiology. Chapter 2 presents the mechanism and magnitude of hemodynamic changes in acute deep vein thrombosis indicating their pathophysiological and clinical significance. Chapter 3 describes the hemodynamic changes that occur in different classes of chronic venous disease and their relation to the anatomic extent of disease in the macrocirculation and microcirculation. The next four chapters (Chapters 4-7) describe the hemodynamic changes resulting from treatmen by compression using different materials, intermittent compression devices, pharmacological agents and finally surgical or endovenous ablation. Chapter 8 discusses the unique hemodynamic features associated with alternative treatment techniques used by the CHIVA and ASVAL. Chapter 9 describes the hemodynamic effects following treatment to relieve pelvic reflux and obstruction. Finally, Chapter 10 demonstrates that contrary to general belief there is a moderate to good correlation between certain hemodynamic measurements and clinical severity of chronic venous disease. The authors believe that this document will be a timely asset to both clinicians and researchers alike. It is directed towards surgeons and physicians who are anxious to incorporate the conclusions of research into their daily practice. It is also directed to postgraduate trainees, vascular technologists and bioengineers, particularly to help them understand the hemodynamic background to pathophysiology, investigations and treatment of patients with venous disorders. Hopefully it will be a platform for those who would like to embark on new research in the field of venous disease.

  • 5.
    Norgren, Lars
    et al.
    Örebro University, School of Health and Medical Sciences.
    Hiatt, W. R.
    Dormandy, J. A.
    Nehler, M. R.
    Harris, K. A.
    Fowkes, F. G. R.
    Rutherford, R. B.
    Inter-society consensus for the management of peripheral arterial disease2007In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 26, no 2, p. 81-157Article in journal (Refereed)
  • 6. Novo, S.
    et al.
    Balbarini, A.
    Belch, J. J.
    Bonura, F.
    Clement, D. L.
    Diamantopoulos, E.
    Fareed, J.
    Norgren, Lars
    Örebro University, School of Health and Medical Sciences.
    Poredos, P.
    Rotzocil, K.
    The metabolic syndrome: definition, diagnosis and management2008In: International Journal of Angiology, ISSN 0392-9590, E-ISSN 1827-1839, Vol. 27, no 3, p. 220-31Article in journal (Refereed)
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