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  • 1.
    Bergkvist, Max
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Bergstrand, Sara
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Droog Tesselaar, Erik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Medical radiation physics.
    Farnebo, Simon
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Assessment of oxygenation with polarized light spectroscopy enables new means for detecting vascular events in the skin2020In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 130, article id 104000Article in journal (Refereed)
    Abstract [en]

    Introduction: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. Materials and methods: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (C-RBC,(TiVi)), oxygenation (Delta C-OH,(TiVi)) and deoxygenation (Delta C-DOH,(TiVi)) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). Results: During arterial occlusion, C-RBC,(TiVi) remained unchanged while Delta C-OH,(TiVi) decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, C-RBC,C-TiVi increased to 39.2 (18.8) AU (p < 0.001), Delta C-OH,C-TiVi increased to 38.5. During venous occlusion, C-RBC,C-TiVi increased to 28.9 (11.2) AU (p < 0.001), Delta C-OH,C-TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. Conclusion: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.

  • 2.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Assessment of microcirculation of the skin using Tissue Viability Imaging: A promising technique for detecting venous stasis in the skin2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 101, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Background: : Venous occlusion in the skin is difficult to detect by existing measurement techniques. Our aim was to find out whether Tissue Viability Imaging (TiVi) was better at detecting venous occlusion by comparing it with results of laser Doppler flowmetry (LDF) during graded arterial and venous stasis in human forearm skin. Methods: : Arterial and venous occlusions were simulated in 10 healthy volunteers by inflating a blood pressure cuff around the upper right arm. Changes in the concentration of red blood cells (RBC) were measured using TiVi, while skin perfusion and concentration of moving red blood cells (CMBC) were measured using static indices of LDF during exsanguination and subsequent arterial occlusion, postocclusive reactive hyperaemia, and graded increasing and decreasing venous stasis. Results: : During arterial occlusion there was a significant reduction in the mean concentration of RBC from baseline, as well as in perfusion and CMBC (p less than 0.008). Venous occlusion resulted in a significant 28% increase in the concentration of RBC (p = 0.002), but no significant change in perfusion (mean change -14%) while CMBC decreased significantly by 24% (p = 0.02). With stepwise increasing occlusion pressures there was a significant rise in the TiVi index and reduction in perfusion (p = 0.008), while the reverse was seen when venous flow was gradually restored. Conclusion: : The concentration of RBC measured with TiVi changes rapidly and consistently during both total and partial arterial and venous occlusions, while the changes in perfusion, measured by LDF, were less consistent This suggests that TiVi could be a more useful, non-invasive clinical monitoring tool for detecting venous stasis in the skin than LDF.

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  • 3.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Zötterman, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation.2017In: Plastic and Reconstructive Surgery - Global Open, E-ISSN 2169-7574, Vol. 5, no 11, article id e1531Article in journal (Refereed)
    Abstract [en]

    Background: Venous congestion in skin flaps is difficult to detect. This study evaluated the ability of tissue viability imaging (TiVi) to measure changes in the concentration of red blood cells (CRBC), oxygenation, and heterogeneity during vascular provocations in a porcine fasciocutaneous flap model.

    Methods: In 5 pigs, cranial gluteal artery perforator flaps were raised (8 flaps in 5 pigs). The arterial and venous blood flow was monitored with ultrasonic flow probes. CRBC, tissue oxygenation, and heterogeneity in the skin were monitored with TiVi during baseline, 50% and 100% venous occlusion, recovery, 100% arterial occlusion and final recovery, thereby simulating venous and arterial occlusion of a free fasciocutaneous flap. A laser Doppler probe was used as a reference for microvascular perfusion in the flap.

    Results: During partial and complete venous occlusion, increases in CRBC were seen in different regions of the flap. They were more pronounced in the distal part. During complete arterial occlusion, CRBC decreased in all but the most distal parts of the flap. There were also increases in tissue oxygenation and heterogeneity during venous occlusion.

    Conclusions: TiVi measures regional changes in CRBC in the skin of the flap during arterial and venous occlusion, as well as an increase in oxygenated hemoglobin during venous occlusion that may be the result of reduced metabolism and impaired delivery of oxygen to the tissue. TiVi may provide a promising method for measuring flap viability because it is hand-held, easy to-use, and provides spatial information on venous congestion.

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  • 4.
    Droog Tesselaar, Erik
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert E.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects2004In: Microvascular research, ISSN 0026-2862, Vol. 67, no 2, p. 197-202Article in journal (Refereed)
    Abstract [en]

    Iontophoresis of vasoactive substances is a promising tool for studying pharmacological aspects of the (patho)physiology of the microvasculature. However, nonspecific microvascular responses are a common problem in most protocols used. We studied the effect of current density (mA/cm2), charge density (mC/cm2), drug concentration (mass %) and vehicle concentration (M) on the nonspecific vasodilatation during iontophoresis of sodium chloride, acetylcholine (ACh) and sodium nitroprusside (SNP).

    We found that nonspecific vasodilatation depended on current density and charge density in both anodal and cathodal iontophoresis. The responses to ACh and SNP were dependent on current density, charge density and drug concentration. We found that by limiting current density (<0.01 mA/cm2) and charge density (<7.8 mC/cm2) and with adjusted concentrations for drugs and vehicles, it is possible to prevent nonspecific effects during iontophoresis of ACh and SNP, while maximum drug effects (plateaus in the dose–response curves) are still obtained. These new findings are important for future iontophoresis studies in which vasoactive drugs are used to assess microvascular function because the presented approach has advantages compared to older techniques, which mainly have attempted to suppress or compensate for the nonspecific responses during iontophoresis by the use of local anaesthetics or the measurement of drug-minus-vehicle responses, both of which present well-known experimental shortcomings.

  • 5.
    Farnebo, Simon
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Thorfinn, Johan
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times2010In: MICROVASCULAR RESEARCH, ISSN 0026-2862, Vol. 80, no 3, p. 412-416Article in journal (Refereed)
    Abstract [en]

    Tissue occlusion and the hyperaemic response upon reperfusion can be used as a tool to assess microvascular function in various vascular diseases. Currently, laser Doppler flowmetry (LDF) is applied most often to measure hyperaemic responses. In this study, we have applied tissue viability imaging (TiVi) and LDF to measure the change in red blood cell concentration and perfusion in the skin after occlusions of the forearm with increasing duration. We have found that there is a strong correlation between the changes in perfusion and red blood cell (RBC) concentration during post-occlusive hyperaemia (perfusion: r = 0.80; RBC concentration: r = 0.94). This correlation increases with longer occlusion durations (1, 5 and 10 min). Furthermore, for both perfusion and RBC concentration, the maximum responses (perfusion: r(2) = 0.59; RBC concentration: r(2) = 0.78) and the recovery times (perfusion: r(2) = 0.62; RBC concentration: r(2) = 0.91) increase linearly with the duration of the occlusion. Maximum responses and recovery times were more reproducible for RBC concentration (as measured with TiVi) than for perfusion (as measured with LDF). These results show that perfusion and RBC concentration are related during post-occlusive hyperaemia and that TiVi can be used as a tool in the assessment of hyperaemic responses that has advantages in terms of reproducibility, sensitivity and ease of use.

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  • 6.
    Glasin, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Wireless vitals: Proof of concept for wireless patient monitoring in an emergency department setting2019In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 12, no 4, article id e201800275Article in journal (Refereed)
    Abstract [en]

    Vital sign assessment is a common task in emergency medicine, but resources for continuous monitoring are restricted, data is often recorded manually, and entangled wires cause frustration. Therefore, we designed a small, wireless photoplethysmographic device capable of continuously assessing pulse, respiratory frequency and oxygen saturation on the sternum and tested the performance and feasibility in an emergency department setting. Fifty (56.3 20.2 years), consenting emergency patients (29 male) were recruited. Heart rate, respiratory rate and oxygen saturation were recorded simultaneously using the device and standard monitoring equipment. Data was compared using Bland-Altman plotting (heart rate, respiratory rate) and mean difference (oxygen saturation). The bias for heart- and respiratory rate was 0.4 (limits of agreements -11.3, 12.2 and -6.1, 7.0). Mean difference for oxygen saturation was -0.21 +/- 2.35%. This may be the first wireless device to use photoplethysmography on the sternum for vital sign assessment. We noted good agreement with standard monitors, but lack of standardization in data processing between monitoring systems may limit the generalizability of these findings. Although further improvements are needed, the feasibility of this approach provides proof of concept for a new paradigm of large scale, wireless patient monitoring.

  • 7.
    Hackethal, Johannes
    et al.
    Ludwig Boltzmann Inst Expt & Clin Traumatol, Austria; Austrian Cluster Tissue Regenerat, Austria.
    Iredahl, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Anderson, Chris
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Tesselaar, Erik
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Microvascular effects of microneedle applicationIn: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846Article in journal (Refereed)
    Abstract [en]

    Background The efficiency of transdermal drug delivery may be increased by pretreating the skin with microneedles, but distinct effects of microneedles and the microneedle-enhanced delivery of vasoactive drugs on the skin microvasculature are still not well investigated. Materials and Methods In eight healthy human subjects, we measured the microvascular response to microneedle-induced microtraumas in the skin microvasculature using polarized light spectroscopy imaging (Tissue Viability imaging, TiVi). The microvascular response was assessed for up to 48 hours for three microneedle sizes (300 mu m, 500 mu m, and 750 mu m) and for different pressures and application times. Results In our results, microneedle application increased the local red blood cell (RBC) concentration for up to 24 hours dependent on the needle lengths, applied time, and force. Conclusion Optimization of microneedles size, pressure, and application time should be taken into account for future protocols for drug delivery and experimental provocations.

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  • 8.
    Haridass, Isha N.
    et al.
    Curtin Univ, Australia; Univ Queensland, Australia.
    Wei, Jonathan C. J.
    Univ Queensland, Australia; Delft Univ Technol, Netherlands.
    Mohammed, Yousuf H.
    Univ Queensland, Australia.
    Crichton, Michael L.
    Heriot Watt Univ, Scotland.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Sanchez, Washington Y.
    Univ Queensland, Australia.
    Meliga, Stefano C.
    Univ Queensland, Australia.
    Grice, Jeffrey E.
    Univ Queensland, Australia.
    Benson, Heather A. E.
    Curtin Univ, Australia.
    Kendall, Mark A. F.
    Australian Natl Univ, Australia; Univ Queensland, Australia.
    Roberts, Michael S.
    Univ Queensland, Australia; Univ South Australia, Australia.
    Cellular metabolism and pore lifetime of human skin following microprojection array mediation2019In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 306, p. 59-68Article in journal (Refereed)
    Abstract [en]

    Skin-targeting microscale medical devices are becoming popular for therapeutic delivery and diagnosis. We used cryo-SEM, fluorescence lifetime imaging microscopy (FLIM), autofluorescence imaging microscopy and inflammatory response to study the puncturing and recovery of human skin ex vivo and in vivo after discretised puncturing by a microneedle array (Nanopatch (R)). Pores induced by the microprojections were found to close by similar to 25% in diameter within the first 30 min, and almost completely close by similar to 6 h. FLIM images of ex vivo viable epidermis showed a stable fluorescence lifetime for unpatched areas of similar to 1000 ps up to 24 h. Only the cells in the immediate puncture zones (in direct contact with projections) showed a reduction in the observed fluorescence lifetimes to between similar to 518-583 ps. The ratio of free-bound NAD(P)H (alpha 1/alpha 2) in unaffected areas of the viable epidermis was similar to 2.5-3.0, whereas the ratio at puncture holes was almost double at similar to 4.2-4.6. An exploratory pilot in vivo study also suggested similar closure rate with histamine administration to the forearms of human volunteers after Nanopatch (R) treatment, although a prolonged inflammation was observed with Tissue Viability Imaging. Overall, this work shows that the pores created by the microneedle-type medical device, Nanopatch (R), are transient, with the skin recovering rapidly within 1-2 days in the epidermis after application.

  • 9. Order onlineBuy this publication >>
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Assessment of microvascular effects of vasoactive drugs: Methodological in vivo studies in humansbased on iontophoresis2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cardiovascular disease is the leading cause of death in western societies and endothelial dysfunction is one of the earliest signs seen in the development of such conditions. Thedevelopment of prognostic tools to aid in the prediction of micro- and macrovascular diseasebased on assessment of vascular reactivity is therefore of paramount importance.

    Transdermal iontophoresis offers a quick, non-invasive and relatively straightforward way todeliver vasoactive substances in order to provoke a vascular response in man. When combined with either laser Doppler flowmetry (LDF) or tissue viability imaging (TiVi) for quantification of these responses the methodology offers a potentially powerful tool forvascular investigations. The technique has, however, not been established in clinical practice yet and is mostly used in experimental settings. The lack of consensus in what data analysistechnique to use, uncertainty concerning the actual drug dose applied, and the difficulties associated with the assessment of responses to vasoconstrictors may have contributed to thisfact. The aim of this thesis is therefore to address these issues and thus facilitate the use and improve the applicability of transdermal iontophoresis for assessment of cutaneous microvascular function.

    More specifically, a non-linear dose-response model (Emax-model) that is commonly used in in vitro investigations of vascular function was applied to the iontophoresis data. The resultsshow that the Emax-model accurately describes the cutaneous vascular responses totransdermally iontophoresed acetylcholine (ACh) and, sodium nitroprusside (SNP). The Emaxmodelgenerates variables that can be used for quantitative statistical analysis of data andenables a more powerful analysis compared to the methods presently used. It is furtherdemonstrated that the maximal dose effect and vascular responses vary between differentprotocols with the same total iontophoretic charge but with different current strengths anddurations. This finding implies that the assumption that the local drug dose is linearlyproportional to the iontophoretic charge (used for estimation of delivered drug dose to themicrovascular bed) may be inaccurate in in vivo investigations and that there is need for amore refined model.

    It is also demonstrated that in a vasoconstrictive setting (iontophoresis of noradrenaline andphenylephrine) TiVi is the favourable technique for measuring vascular responses as it issensitive enough to generate data that can be fitted to the Emax-model even without predilatationof the vessels.

    List of papers
    1. Assessment of microvascular function by study of the dose‐response effects of iontophoretically applied drugs (acetylcholine and sodium nitroprusside): Methods and comparison with in vitro studies
    Open this publication in new window or tab >>Assessment of microvascular function by study of the dose‐response effects of iontophoretically applied drugs (acetylcholine and sodium nitroprusside): Methods and comparison with in vitro studies
    Show others...
    2007 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 73, no 2, p. 143-149Article in journal (Refereed) Published
    Abstract [en]

    Current knowledge about vascular function stems mainly from pharmacological in vitro studies using mounted vascular strips on a strain gauge. We know of no paper that has systematically examined the possibility of assessing the conventional dose–response effects of iontophoresis and laser Doppler investigation of vasoactive substances and compared those relations to data obtained from strips mounted on a strain gauge.

    We used the vasoactive substances acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) and an antagonist (atropine) to enable further investigations in the receptor physiology of iontophoresis.

    Dose–response curves from the iontophoresis experiments showed close similarity to those obtained by vascular strips mounted on a strain gauge. The coefficient of variation (CV) of the dose–response factors found in iontophoresis (both inter and intra experimental variability) was low. The iontophoretic effective dose of 50% (ED50) for acetylcholine and nitroprusside had only CVs of 25% and 26%, respectively, compared with 71% and 77% for the vascular strips. Acetylcholine-induced response was antagonized by iontophoresis of atropine. Contrary to expectations, this antagonism was not competitive.

    The results show that iontophoresis in combination with laser Doppler technology produces reproducible and reliable dose–response curves that picture the vascular effects of vasoactive drugs.

    Keywords
    Microvascular circulation, Endothelium, Dose–response, Iontophoresis, Laser doppler
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14459 (URN)10.1016/j.mvr.2006.10.004 (DOI)
    Available from: 2007-05-04 Created: 2007-05-04 Last updated: 2017-12-13Bibliographically approved
    2. Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation
    Open this publication in new window or tab >>Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation
    Show others...
    2007 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 13, no 4, p. 472-484Article in journal (Refereed) Published
    Abstract [en]

    Background/aims: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non-invasive, more user-independent and objective methods are available today. Limited portability, high cost, lack of robustness and non-specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy-to-use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology.

    Methods: The use of orthogonal linear polarization filters over both the flash source and the detector array removes the polarization-retaining light reflected from the epidermal layer. Only the depolarized light backscattered from the papillary dermal matrix reaches the detector array. By separating the RGB color planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the chromophores in the dermal tissue can be attained. If the algorithm is based on a differential principle in which the normalized differences between the individual values of the red and green color plane are calculated, tissue components with similar spectral signature in both planes are suppressed, while components with different spectral signatures such as RBCs are enhanced.

    Results: In vitro fluid models compare well with theory and computer simulations in describing a linear relationship between the imager output signal termed the tissue viability index (TiVi index) and RBC concentration in the physiological range of 0-4% RBC fraction of tissue volume (cc=0.997, n=20). The influence of oxygen saturation on the calculated RBC concentration is limited to within -3.9% for values within the physiological range (70-100% oxygen saturation). Monte Carlo simulations provide information about the sampling depth (about 0.5mm on the average) of the imaging system. In vivo system evaluation based on iontophoresis of acetylcholine displays a heterogeneous pattern of vasodilatation appearing inside the electrode area after about 10min. Topical application of methyl nicotinate and clobetasol propionate further demonstrates the capacity to document the extent and intensity of both an increase (erythema) and a decrease (blanching) in the skin RBC concentration without movement artifact and with compensation for irregularity in pigmentation.

    Conclusions: Polarization light spectroscopy imaging for assessment of RBC concentration in the skin microvasculature is a robust and accessible technique for the clinical setting. Additionally, the technique has pre-clinical research applications for investigation of the spatial and temporal aspects of skin erythema and blanching as well as a potential role in drug development, skin care product development and skin toxicological assessment.

    Keywords
    Biomedical optics, Blanching, Erythema, Microcirculation, Polarizationspectroscopy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-48066 (URN)10.1111/j.1600-0846.2007.00253.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    3. Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetry
    Open this publication in new window or tab >>Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetry
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Laser-Doppler flowmetry (LDF) is an attractive method to assess blood flow responses butlacks sensitivity to accurately measure low perfusion values during iontophoresis of vasoconstricting drugs without predilatation of the microvascular bed.

    The aim of this study was to develop a protocol for iontophoresis of noradrenaline (NA) andphenylephrine (Phe) in the skin, using local heating to predilate the microvascular bed andLDF to measure blood flow responses. Three protocols with the same electrical charge (12mC) but different durations and current strengths (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x0.04 mA) were used to study the effect of pulse duration and current strength on the responses.

    Skin perfusion decreased to 68-78% of the predilatated state with both NA and Phe. Doseresponse plateaus were not obtained with any protocol. The extent of the vasoconstriction depended on the protocol used.

    These results suggest that predilatation by local heating appears less suitable duringiontophoresis of NA and Phe, due to limited vascular responses and especially absence of response plateaus, even at high current strengths. The latter leads to difficulties in performing proper dose response analyses. Another interesting finding was that the actual dose of NA and Phe given to the tissue was affected not only by the size of the electrical charge, but local blood flow as well.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-50639 (URN)
    Available from: 2009-10-13 Created: 2009-10-13 Last updated: 2010-01-14Bibliographically approved
    4. Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis
    Open this publication in new window or tab >>Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis
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    2009 (English)In: Microvascular Research, ISSN 0026-2862, Vol. 78, no 2, p. 199-205Article in journal (Refereed) Published
    Abstract [en]

    When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging.

    Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED50-values with narrow confidence intervals and acceptable r2 values. Mean ED50-values for the TiVi did not differ significantly from similar values obtained using laser Doppler.

    Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.

    Keywords
    Cutaneous microcirculation; Iontophoresis; Laser Doppler; Tissue viability imager
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-21238 (URN)10.1016/j.mvr.2009.04.008 (DOI)
    Note
    Original Publication: Joakim Henricson, Anders Nilsson, Erik Tesselaar, Gert Nilsson and Folke Sjöberg, Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis, 2009, Microvascular Research, (78), 2, 199-205. http://dx.doi.org/10.1016/j.mvr.2009.04.008 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2009-10-30Bibliographically approved
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    Assessment of microvascular effects of vasoactive drugs : Methodological in vivo studies in humans based on iontophoresis
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  • 10.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Baiat, Yashma
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Surgery.
    Local Heating as a Predilatation Method for Measurement of Vasoconstrictor Responses with Laser-Doppler Flowmetry2011In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 18, no 3, p. 214-220Article in journal (Refereed)
    Abstract [en]

    Studying microvascular responses to iontophoresis of vasoconstricting drugs contributes to a better understanding of the regulatory mechanisms of cutaneous vessels, but measuring these responses with laser-Doppler flowmetry at basal blood flow conditions is technically challenging. This study aimed to investigate whether the measurement of cutaneous vasoconstrictor responses to noradrenaline (NA) and phenylephrine (PE), delivered by iontophoresis, is facilitated by predilatation of the microvascular bed using local heating. We used different drug delivery rates (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x 0.04 mA) to investigate whether predilatation affects the local drug dynamics by an increased removal of drugs from the skin. In a predilatated vascular bed, iontophoresis of NA and PE resulted in a significant decrease in perfusion from the thermal plateau (p andlt; 0.001). The decrease was 25-33%, depending on drug delivery rate. In unheated skin, a significant vasoconstriction was observed (p andlt; 0.001), with 17% and 14% decrease from baseline for NA and PE, respectively. These results indicate that predilatating the cutaneous vascular bed by local heating facilitates measurement of vasoconstriction with laser-Doppler flowmetry and does not seem to significantly affect the result by an increased removal of drugs from the skin.

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  • 11.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Droog Tesselaar, Erik
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Baiat, Y
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery and Burns.
    Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetryManuscript (preprint) (Other academic)
    Abstract [en]

    Laser-Doppler flowmetry (LDF) is an attractive method to assess blood flow responses butlacks sensitivity to accurately measure low perfusion values during iontophoresis of vasoconstricting drugs without predilatation of the microvascular bed.

    The aim of this study was to develop a protocol for iontophoresis of noradrenaline (NA) andphenylephrine (Phe) in the skin, using local heating to predilate the microvascular bed andLDF to measure blood flow responses. Three protocols with the same electrical charge (12mC) but different durations and current strengths (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x0.04 mA) were used to study the effect of pulse duration and current strength on the responses.

    Skin perfusion decreased to 68-78% of the predilatated state with both NA and Phe. Doseresponse plateaus were not obtained with any protocol. The extent of the vasoconstriction depended on the protocol used.

    These results suggest that predilatation by local heating appears less suitable duringiontophoresis of NA and Phe, due to limited vascular responses and especially absence of response plateaus, even at high current strengths. The latter leads to difficulties in performing proper dose response analyses. Another interesting finding was that the actual dose of NA and Phe given to the tissue was affected not only by the size of the electrical charge, but local blood flow as well.

  • 12.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Droog Tesselaar, Erik
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Persson, Karin
    Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Assessment of microvascular function by study of the dose‐response effects of iontophoretically applied drugs (acetylcholine and sodium nitroprusside): Methods and comparison with in vitro studies2007In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 73, no 2, p. 143-149Article in journal (Refereed)
    Abstract [en]

    Current knowledge about vascular function stems mainly from pharmacological in vitro studies using mounted vascular strips on a strain gauge. We know of no paper that has systematically examined the possibility of assessing the conventional dose–response effects of iontophoresis and laser Doppler investigation of vasoactive substances and compared those relations to data obtained from strips mounted on a strain gauge.

    We used the vasoactive substances acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) and an antagonist (atropine) to enable further investigations in the receptor physiology of iontophoresis.

    Dose–response curves from the iontophoresis experiments showed close similarity to those obtained by vascular strips mounted on a strain gauge. The coefficient of variation (CV) of the dose–response factors found in iontophoresis (both inter and intra experimental variability) was low. The iontophoretic effective dose of 50% (ED50) for acetylcholine and nitroprusside had only CVs of 25% and 26%, respectively, compared with 71% and 77% for the vascular strips. Acetylcholine-induced response was antagonized by iontophoresis of atropine. Contrary to expectations, this antagonism was not competitive.

    The results show that iontophoresis in combination with laser Doppler technology produces reproducible and reliable dose–response curves that picture the vascular effects of vasoactive drugs.

  • 13.
    Henricson, Joakim
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Ekelund, Ulf
    Lund Univ, Sweden.
    Hartman, Jens
    Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.
    Ziegler, Bruno
    Orebro Univ, Sweden.
    Kurland, Lisa
    Orebro Univ, Sweden.
    Wilhelms, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Pathways to the emergency department - a national, cross-sectional study in Sweden2022In: BMC Emergency Medicine, ISSN 1471-227X, E-ISSN 1471-227X, Vol. 22, no 1, article id 58Article in journal (Refereed)
    Abstract [en]

    Background Swedish Emergency Departments (EDs) see 2.6 million visits annually. Sweden has a strong tradition of health care databases, but information on patients pathways to the ED is not documented in any registry. The aim of this study was to provide a national overview of pathways, degree of medical acuteness according to triage, chief complaints, and hospital admission rates for adult patients (&gt;= 18 years) visiting Swedish EDs during 24 h. Methods A national cross-sectional study including all patients at 43 of Swedens 72 EDs during 24 h on April 25th, 2018. Pathway to the ED, medical acuteness at triage, admission and basic demographics were registered by dedicated assessors present at every ED for the duration of the study. Descriptive data are reported. Results A total of 3875 adult patients (median age 59; range 18 to 107; 50% men) were included in the study. Complete data for pathway to the ED was reported for 3693 patients (98%). The most common pathway was self-referred walk-in (n = 1310; 34%), followed by ambulance (n = 920; 24%), referral from a general practitioner (n = 497; 1 3%), and telephone referral by the national medical helpline "1177" (n = 409; 10%). In patients 18 to 64 years, self-referred walk-in was most common, whereas transport by ambulance dominated in patients > 64 years. Of the 3365 patients who received a medical acuteness level at triage, 4% were classified as Red (Immediate), 18% as Orange (very urgent), 47% as Yellow (Urgent), 26% as Green (Standard), and 5% as Blue (Non-Urgent). Abdominal or chest pain were the most common chief complaints representing approximately 1/3 of all presentations. Overall, the admission rate was 27%. Arrival by ambulance was associated with the highest rate of admission (53%), whereas walk-in patients and telephone referrals were less often admitted. Conclusion Self-referred walk-in was the overall most common pathway followed by ambulance. Patients arriving by ambulance were often elderly, critically ill and often admitted to in-patient care, whereas arrival by self-referred walk-in was more common in younger patients.

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  • 14.
    Henricson, Joakim
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Glasin, Joakim
    Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Rindebratt, Sandra
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Björk Wilhelms, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Respiratory rate monitoring in healthy volunteers by central photoplethysmography compared to capnography2022In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 15, no 4, article id e202100270Article in journal (Refereed)
    Abstract [en]

    Monitoring of respiration is a central task in clinical medicine, crucial to patient safety. Despite the uncontroversial role of altered respiratory frequency as an important sign of impending or manifest deterioration, reliable measurement methods are mostly lacking outside of intensive care units and operating theaters. Photoplethysmography targeting the central blood circulation in the sternum could offer accurate and inexpensive monitoring of respiration. Changes in blood flow related to the different parts of the respiratory cycle are used to identify the respiratory pattern. The aim of this observational study was to compare photoplethysmography at the sternum to standard capnography in healthy volunteers. Bland Altman analysis showed good agreement (bias -0.21, SD 1.6, 95% limits of agreement -3.4 to 2.9) in respiratory rate values. Photoplethysmography provided high-quality measurements of respiratory rate comparable to capnographic measurements. This suggests that photoplethysmography may become a precise, cost-effective alternative for respiratory monitoring.

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  • 15.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lassus, J.
    Sterisol AB, Vadstena, Sweden.
    Eklund, J.
    Sterisol AB, Vadstena, Sweden.
    Lassus, S.
    Cosmetox AB, Linkoping, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Avoidance of dermal exposure to preservatives by packaging2010In: JOURNAL OF PHARMACY AND PHARMACOLOGY, vol 62, issue 6, pp 802-802, Pharmaceutical Press , 2010, Vol. 62, no 6, p. 802-802Conference paper (Refereed)
    Abstract [en]

    Dermal exposure to chemicals in cosmetics and hygiene products (e.g. moisturising creams, soaps, shampoos) is increasingly recognized as an important area for risk assessment and regulation. The contents of such products is regulated by classification of exposure types (e.g. stay on/wash off) and regulatory concepts based on toxicological studies and manufacturing or market experience. Positive lists, negative lists or establishment of recommendations on concentration and exposure form a basis for consumer safety. Common problem areas are perfumes, preservatives and the formation of oxidation products after manufacture.

    A new patented system, suitable for packages from 100 ml to 5 l, with collapsible plastic bags and unique dosage valves prevents bacteria and air from entering the packaging. Thus the use of preservatives can be avoided.

    This may lead to a reduced risk of individual reactions to specific preservatives as well as cross-allergy reactions. The consumer no longer needs to hunt for strange names on small ingredient labels. Also, it could prevent the prospective development of allergy. The avoidance of oxidation products is another advantage.

  • 16.
    Henricson, Joakim
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Muller, David A.
    Univ Queensland, Australia.
    Ben Baker, S.
    Vaxxas Pty Ltd, Australia.
    Iredahl, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Togö, Totte
    Region Östergötland, Medicine Center, Allergy Center.
    Anderson, Chris D
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Micropuncture closure following high density microarray patch application in healthy subjects2022In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 28, no 2, p. 305-310Article in journal (Refereed)
    Abstract [en]

    Background The high-density microarray patch (HD-MAP) promises to be a robust vaccination platform with clear advantages for future global societal demands for health care management. The method of action has its base not only in efficient delivery of vaccine but also in the reliable induction of a local innate physical inflammatory response to adjuvant the vaccination process. The application process needs to induce levels of reactivity, which are acceptable to the vaccine, and from which the skin promptly recovers. Materials and methods 1 x 1 cm HD-MAP patches containing 5000, 250-mu m long microprojections were applied to the skin in 12 healthy volunteers. The return of skin barrier function was assessed by transepidermal water loss (TEWL) and reaction to topical histamine challenge. Results Skin barrier recovery by 48 h was confirmed for all HD-MAP sites by recovered resistance to the effects of topical histamine application. Conclusions Our previous observation, that the barrier disruption indicator TEWL returns to normal by 48 h, is supported by this papers demonstration of return of skin resistance to topical histamine challenge in twelve healthy subjects.

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  • 17.
    Henricson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Nilsson, A.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Sub-epidermal imaging using polarized light spectroscopy for assessment of cutaneous microvascular function during iontophoresis of nor-adrenaline and phenylephrine2007In: 8th World Congress for microcirculation,2007, 2007Conference paper (Refereed)
  • 18.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Anders
    Berzelius Clinical Research Center AB.
    Tesselaar, Erik
    Berzelius Clinical Research Center AB.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis2009In: Microvascular Research, ISSN 0026-2862, Vol. 78, no 2, p. 199-205Article in journal (Refereed)
    Abstract [en]

    When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging.

    Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED50-values with narrow confidence intervals and acceptable r2 values. Mean ED50-values for the TiVi did not differ significantly from similar values obtained using laser Doppler.

    Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.

    Download full text (pdf)
    FULLTEXT01
  • 19.
    Henricson, Joakim
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Microvascular response to iontophoretically applied acetylcholine investigated by Tissue Viability Imaging2006Conference paper (Other academic)
  • 20.
    Henricson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    The polarization scectroscopic camera allows assessment of vasoconstriction after topical application of clobetasol2007In: 16th congress of the European Academy of Dermatology and Venerology,2007, 2007Conference paper (Refereed)
  • 21.
    Henricson, Joakim
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Sandh, Jenny
    Absorbest AB, Sweden.
    Iredahl, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Moisture sensor for exudative wounds: A pilot study2021In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 27, no 5, p. 918-924Article in journal (Refereed)
    Abstract [en]

    Background Exudative wounds cause discomfort for patients. Introduction of a moisture sensor to dressings could facilitate change of dressings only when needed. The aim of this pilot study was to evaluate the ability of a newly developed moisture sensor to detect moisture in relation to the absorbing capacity of the dressing. Materials and Methods In five patients, with one leg ulcer each, three dressing changes per patient were observed. Interval of dressing change was according to clinical need and healthcare professionals decision. Sensor activation, dressing weight and complications were registered. To investigate the effect of dressing on sensor activation, half of the observations were made without an extra layer of non-woven between the dressing and sensor (Variant A), and half with (Variant B). Results The sensor indicated time for dressing change in six out of fifteen observations. Variants A and B did not differ regarding activation or the timing of the activation. Conclusions The addition of a moisture sensor for facilitating management of exudative wounds is promising. We recommend future larger studies evaluating the potential clinical benefits and risks of the addition of a moisture sensor. We also recommend evaluation of potential home monitoring of wounds by a moisture sensor.

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  • 22.
    Henricson, Joakim
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Sjöberg, Folke
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, ANOPIVA US. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Iredahl, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Björk Wilhelms, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    In vivo dose-response analysis to acetylcholine: pharmacodynamic assessment by polarized reflectance spectroscopy2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 6594Article in journal (Refereed)
    Abstract [en]

    Transdermal iontophoresis offers an in vivo alternative to the strain-gauge model for measurement of vascular function but is limited due to lack of technical solutions for outcome assessment. The aims of this study were to, after measurement by polarized reflectance spectroscopy (PRS), use pharmacodynamic dose-response analysis on responses to different concentrations of acetylcholine (ACh); and to examine the effect of three consecutively administered iontophoretic current pulses. The vascular responses in 15 healthy volunteers to iontophorised ACh (5 concentrations, range 0.0001% to 1%, three consecutive pulses of 0.02 mA for 10 min each) were recorded using PRS. Data were fitted to a four-parameter logistic dose response model and compared. Vascular responses were quantifiable by PRS. Similar pharmacodynamic dose response curves could be generated irrespectively of the ACh concentration. Linearly increasing maximum vasodilatory responses were registered with increasing concentration of ACh. A limited linear dose effect of the concentration of ACh was seen between pulses. Polarized reflectance spectroscopy is well suited for measuring vascular responses to iontophoretically administrated ACh. The results of this study support further development of iontophoresis as a method to study vascular function and pharmacological responses in vivo.

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  • 23.
    Henricson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Toll John, Rani
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Diffuse Reflectance Spectroscopy: Getting the Capillary Refill Test Under Ones Thumb2017In: Journal of Visualized Experiments, E-ISSN 1940-087X, no 130, article id e56737Article in journal (Refereed)
    Abstract [en]

    The capillary refill test was introduced in 1947 to help estimate circulatory status in critically ill patients. Guidelines commonly state that refill should occur within 2 s after releasing 5 s of firm pressure (e.g., by the physicians finger) in the normal healthy supine patient. A slower refill time indicates poor skin perfusion, which can be caused by conditions including sepsis, blood loss, hypoperfusion, and hypothermia. Since its introduction, the clinical usefulness of the test has been debated. Advocates point out its feasibility and simplicity and claim that it can indicate changes in vascular status earlier than changes in vital signs such as heart rate. Critics, on the other hand, stress that the lack of standardization in how the test is performed and the highly subjective nature of the naked eye assessment, as well as the tests susceptibility to ambient factors, markedly lowers the clinical value. The aim of the present work is to describe in detail the course of the refill event and to suggest potentially more objective and exact endpoint values for the capillary refill test using diffuse polarization spectroscopy.

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  • 24.
    Horiuchi, Yoshihito
    et al.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Droog Tesselaar, Erik
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Wikström, Thore
    Linköping University, Department of Clinical and Experimental Medicine, Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
    Lennquist, Sten
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis2004In: Microvascular research, ISSN 0026-2862, Vol. 67, no 2, p. 192-196Article in journal (Refereed)
    Abstract [en]

    Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60–65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.

  • 25.
    Hultman, Martin
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Iredahl, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Flowmotion imaging analysis of spatiotemporal variations in skin microcirculatory perfusion2023In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 146, article id 104456Article in journal (Refereed)
    Abstract [en]

    Background: Flowmotion is the rhythmical variations in measured skin blood flow that arise due to global and local regulation of the vessels and can be studied using frequency analysis of time-resolved blood flow signals. It has the potential to reveal clinically useful information about microvascular diseases, but the spatial heteroge-neous nature of the microvasculature makes interpretation difficult. However, recent technological advances in multi-exposure laser speckle contrast imaging (MELSCI) enable new possibilities for simultaneously studying spatial and temporal variations in flowmotion.Aim: To develop a method for flowmotion analysis of MELSCI perfusion images. Furthermore, to investigate the spatial and temporal variations in flowmotion in forearm baseline skin perfusion.Method: In four healthy subjects, forearm skin perfusion was imaged at 15.6 fps for 10 min in baseline. The time -trace signal in each pixel was analyzed using the wavelet transform and summarized in five physiologically relevant frequency intervals, resulting in images of flowmotion. Furthermore, a method for reducing the effect of motion artifacts in the flowmotion analysis was developed.Results: The flowmotion images displayed patterns of high spatial heterogeneity that differed between the fre-quency intervals. The spatial variations in flowmotion, quantified as the coefficient of variation, was between 11 % and 31 % in four subjects. Furthermore, significant temporal variations in flowmotion were also observed, indicating the importance of a spatiotemporal analysis.Conclusion: The new imaging technique reveals significant spatial differences in flowmotion that cannot be ob-tained with single-point measurements. The results indicate that global statistics of flowmotion, such as the mean value in a large region of interest, is more representative of the microcirculation than data measured only in a single point. Therefore, imaging techniques have potential to increase the clinical usefulness of flowmotion analysis.

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  • 26.
    Hörlin, Erika
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Munir Ehrlington, Samia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Toll, Rani
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Björk Wilhelms, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Inter-rater reliability of the Clinical Frailty Scale by staff members in a Swedish emergency department setting2022In: Academic Emergency Medicine, ISSN 1069-6563, E-ISSN 1553-2712, Vol. 29, no 12, p. 1431-1437Article in journal (Refereed)
    Abstract [en]

    Introduction As frailty among the elderly is receiving increasing attention in emergency departments (EDs) around the world, the use of frailty assessment tools is growing. An often used such tool is the Clinical Frailty Scale (CFS), whose inter-rater reliability has been sparingly investigated in ED settings. No inter-rater reliability study regarding CFS has previously been performed within the Scandinavian ED context. The primary aim of this study was to evaluate the inter-rater reliability of the CFS in a Swedish ED setting. Methods This was a prospective observational study conducted at three Swedish EDs. Patients &gt;= 65 years were independently assessed with CFS by their responsible physician, registered nurse, and assistant nurse. Demographic information for each assessor was collected, along with frailty status (frail/not frail) on the basis of clinical judgment. Inter-rater reliability was calculated using intraclass correlation coefficient (ICC), whereas agreement of frailty assessed by CFS (dichotomized between frail/not frail, cutoff at &gt;= 5 points) versus solely by clinical judgment was calculated by using cross-tabulation. Results One-hundred patients were included. We found inter-rater reliability to be moderate to good (ICC 0.78, 95% confidence interval [CI] 0.72-0.84), regardless of whether the care team included an emergency physician (ICC 0.74, 95% CI 0.62-0.83) or an intern/resident from another specialty (ICC 0.83, 95% CI 0.74-0.89). The agreement of clinically judged frailty compared to frailty according to CFS was 84%. In the opposing cases, staff tended to assess patients as frail to a higher extent using clinical judgment than by applying CFS on the same patient. Conclusions The CFS appears to have a moderate to good inter-rater reliability when used in a clinical ED setting. When guiding clinical decisions, we advise that the CFS score should be discussed within the team. Further research needs to be performed on the accuracy of clinical judgment to identify frailty in ED patients.

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  • 27.
    Hörlin, Erika
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Munir Ehrlington, Samia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Toll, Rani
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Wilhelms, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Is the clinical frailty scale feasible to use in an emergency department setting? A mixed methods study2023In: BMC Emergency Medicine, ISSN 1471-227X, E-ISSN 1471-227X, Vol. 23, no 1, article id 124Article in journal (Refereed)
    Abstract [en]

    Background: The Clinical Frailty Scale (CFS) is a frailty assessment tool used to identify frailty in older patients visitingthe emergency department (ED). However, the current understanding of how it is used and accepted in ED clinicalpractice is limited. This study aimed to assess the feasibility of CFS in an ED setting.

    Methods :This was a prospective, mixed methods study conducted in three Swedish EDs where CFS had recentlybeen introduced. We examined the completion rate of CFS assessments in relation to patient- and organisationalfactors. A survey on staff experience of using CFS was also conducted. All quantitative data were analyseddescriptively, while free text comments underwent a qualitative content analysis.

    Results: A total of 4235 visits were analysed, and CFS assessments were performed in 47%. The completion rate exceeded 50% for patients over the age of 80. Patients with low triage priority were assessed to a low degree (24%). There was a diurnal variation with the highest completion rates seen for arrivals between 6 and 12 a.m. (58%). The survey response rate was 48%. The respondents rated the perceived relevance and the ease of use of the CFS with a median of 5 (IQR 2) on a scale with 7 being the highest. High workload, forgetfulness and critical illness were rankedas the top three barriers to assessment. The qualitative analysis showed that CFS assessments benefit from a clearroutine and a sense of apparent relevance to emergency care.

    Conclusion: Most emergency staff perceived CFS as relevant and easy to use, yet far from all older ED patientswere assessed. The most common barrier to assessment was high workload. Measures to facilitate use may includeclarifying the purpose of the assessment with explicit follow-up actions, as well as formulating a clear routine for the assessment.

    Registration: The study was registered on ClinicalTrials.gov 2021-06-18 (identifier: NCT04931472).

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  • 28.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Högstedt, Alexandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load2016In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 23, no 7, p. 597-605Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load.

    METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI).

    RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load.

    CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

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  • 29.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Muller, David A.
    Univ Queensland, Australia.
    Togö, Totte
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Jonasson, Hanna
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Baker, Ben
    Vaxxas Pty Ltd, Australia.
    Anderson, Chris
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Local Response and Barrier Recovery in Elderly Skin Following the Application of High-Density Microarray Patches2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 4, article id 583Article in journal (Refereed)
    Abstract [en]

    The high-density microneedle array patch (HD-MAP) is a promising alternative vaccine delivery system device with broad application in disease, including SARS-CoV-2. Skin reactivity to HD-MAP applications has been extensively studied in young individuals, but not in the &gt;65 years population, a risk group often requiring higher dose vaccines to produce protective immune responses. The primary aims of the present study were to characterise local inflammatory responses and barrier recovery to HD-MAPs in elderly skin. In twelve volunteers aged 69-84 years, HD-MAPs were applied to the forearm and deltoid regions. Measurements of transepidermal water loss (TEWL), dielectric permittivity and erythema were performed before and after HD-MAP application at t = 10 min, 30 min, 48 h, and 7 days. At all sites, TEWL (barrier damage), dielectric permittivity (superficial water);, and erythema measurements rapidly increased after HD-MAP application. After 7 days, the mean measures had recovered toward pre-application values. The fact that the degree and chronology of skin reactivity and recovery after HD-MAP was similar in elderly skin to that previously reported in younger adults suggests that the reactivity basis for physical immune enhancement observed in younger adults will also be achievable in the older population.

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  • 30.
    Jonsson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Saager, Rolf
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Wilhelms, Daniel
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Microcirculatory response to lower body negative pressure and the association to large vessel function2023In: PHOTONICS IN DERMATOLOGY AND PLASTIC SURGERY 2023, SPIE-INT SOC OPTICAL ENGINEERING , 2023, Vol. 12352, article id 123520AConference paper (Refereed)
    Abstract [en]

    Vital signs reflect circulatory function and hence hemodynamics on a macroscopic scale and are often unreliable or late indicators of hemodynamic instability. Previous studies support that alterations in the microcirculation may provide early indicators of deterioration and impending shock. Microcirculation is also restored late in the recovery process. Hence, monitoring microcirculation is important since treatments based on normalizing classical vital signs will not always restore microvascular hemodynamics and the microcirculation may remain in shock although e.g., blood pressure seems normal. The aim of this study was to investigate alterations in skin microcirculation dynamics during lower body negative pressure as a model of shock and central hypovolemia. By using spatial frequency domain imaging (SFDI) and polarized reflectance imaging, we investigated the association between micro- and macrovascular function during these conditions. Furthermore, we evaluated microvascular reactivity using the capillary refill test. A cohort of 9 subjects were subjected to a progressive lower body negative pressure (LBNP) protocol. At baseline and at LBNP = -20mmHg, -30mmHg and -40mmHg, SFDI images were acquired and analyzed for tissue hemoglobin content and oxygenation. Superficial hemoglobin content was estimated by polarized reflectance imaging. We found that microcirculatory reactivity was prolonged during LBNP, but recovered after end of the protocol. These results indicate a correlation between negative pressure and microcirculatory function and that may provide a basis for early detection of shock in emergency care settings.

  • 31.
    Junker, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Jonson, Carl-Oscar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Standardized Measurement of Capillary Refill Time using Novel Technology2019In: Prehospital and Disaster Medicine, ISSN 1049-023X, E-ISSN 1945-1938, Vol. 34, no s1, p. 167-168Article in journal (Other academic)
    Abstract [en]

    Introduction: In a patient going into shock, blood is redistributed from the periphery to the central circulation, making an assessment of skin perfusion useful in a prehospital setting. Capillary refill time (CRT) is the time required for a pressure blanched skin site to reperfuse. Currently, CRT is tested by manually applying pressure for 5s to the skin and observing the time before reperfusion. Guidelines state that CRT should be 2-3s in a healthy patient. Shortcomings in this procedure include lack of standardization of pressure, subjective assessment of the time for reperfusion, and not accounting for the patient’s skin temperature.

    Aim: To develop a standardized objective procedure for testing CRT in the prehospital setting.

    Method: The study protocol was approved by the Ethics Committee at Linköping University (M200-07, 2015-99-31). An electro-pneumatic device exerting constant force (9N) over 5s was developed. CRT was measured using the Tissue Viability Imager (Wheelsbridge AB, Sweden) which relies on polarization spectroscopy. To simulate hypothermic conditions, healthy volunteers were subjected to low ambient temperature (8°C). Blood loss was simulated using a custom-built lower body negative pressure (LBNP) chamber. In both scenarios, the CRT test was carried out on three test sites (finger pulp, forehead, and sternum).

    Results: CRT on the finger pulp and sternum was shown to be increased following the hypothermic conditions, but not on the forehead. Skin temperature on the three sites followed the same pattern, with the forehead being virtually unchanged. Tests performed during LBNP revealed an apparent effect on CRT following the simulated blood loss, with prolonged CRT for all sites tested.

    Discussion: A successful methodology for objective assessment of CRT was developed, which was validated on healthy volunteers following hypothermia or simulated blood loss. Ongoing work will investigate a combination of hypothermia and blood loss to more accurately simulate the prehospital setting.

  • 32. Leahy, M.
    et al.
    ODoherty, J.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Tissue Viability Imaging: A new modality for microcirculation imaging2006In: Imaging Technology in Drug Discovery Development,2006, 2006Conference paper (Refereed)
  • 33.
    Leahy, Martin J.
    et al.
    Department of Physics, University of Limerick Limerick, Ireland.
    O'Doherty, Jim
    Department of Physics, University of Limerick Limerick, Ireland.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology UHL.
    A new method for visualizing red blood cell content in the microcirculation2007In: Progress in Biomedical Optics and Imaging, ISSN 1605-7422, E-ISSN 1042-4687Article in journal (Other academic)
    Abstract [en]

    n/a

  • 34.
    Leahy, MJ.
    et al.
    Department of Physics, University of Limerick, National Technological Park, Ireland.
    ODoherty, J.
    Department of Physics, University of Limerick, National Technological Park, Ireland.
    McNamara, P.
    Department of Physics, University of Limerick, National Technological Park, Ireland.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Diffuse reflection imaging of sub-epidermal tissue haematocrit using a simple RGB camera2007In: Optical Technologies in Biophysics and Medicine VIII / [ed] Valery V. Tuchin, SPIE - International Society for Optical Engineering, 2007, Vol. 6535, p. 653503-1-653503-17Conference paper (Other academic)
    Abstract [en]

    This paper describes the design and evaluation of a novel easy to use, tissue viability imaging system (TiVi). The system is based on the methods of diffuse reflectance spectroscopy and polarization spectroscopy. The technique has been developed as an alternative to current imaging technology in the area of microcirculation imaging, most notably optical coherence tomography (OCT) and laser Doppler perfusion imaging (LDPI). The system is based on standard digital camera technology, and is sensitive to red blood cells (RBCs) in the microcirculation. Lack of clinical acceptance of both OCT and LDPI fuels the need for an objective, simple, reproducible and portable imaging method that can provide accurate measurements related to stimulus vasoactivity in the microvasculature. The limitations of these technologies are discussed in this paper. Uses of the Tissue Viability system include skin care products, drug development, and assessment spatial and temporal aspects of vasodilation (erythema) and vasoconstriction (blanching).

  • 35. Leahy, MJ.
    et al.
    ODoherty, J.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    A new method for visualizing red blood cell content in the microcirculation. SPIE newsroom2006In: The International Society for Optical Engineering,2006, 2006Conference paper (Refereed)
  • 36.
    Magnusson, B.M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Intra- and inter-individual variability in the development of erythema after application of methyl nicotinate evaluated by polarization spectroscopy imaging2010In: JOURNAL OF PHARMACY AND PHARMACOLOGY, vol 62, issue 6, pp 801-801, ISSN: 002-3573, Pharmaceutical Press , 2010, Vol. 62, no 6, p. 801-801Conference paper (Refereed)
    Abstract [en]

    The concept that the time to onset of erythema after the application of the rubefacient and urticant substance methyl nicotinate (MN) indicates skin barrier competence was introduced 30 years ago. MN produces a dose-dependent erythema on topical application to intact skin, the nature of which is known to be fast moving (in the order of minutes) and variable. Using tissue viability imaging (TiVi) the time course and degree of the reaction can be conveniently followed and analysed. Inter-individual variability can be quite marked but intra-individual variability is less pronounced. At the upper end of provocation (higher doses, more sensitive individuals) urtication can occur, which decreases blood flow by increasing pressure on and thus emptying capillaries. The TiVi system can quantitate urtication and inherent (blanched) skin colour. The utility of MN application in the study of individual barrier function and microvascular reactivity is increased by the use of the TiVi system for collection and analysis of data.

  • 37.
    Mernelius, S.
    et al.
    Ryhov County Hospital, Jönköping, Sweden.
    Carlsson, E.
    Ryhov County Hospital, Jönköping, Sweden.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Löfgren, S.
    Ryhov County Hospital, Jönköping, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping, Sweden.
    Ehricht, R.
    Alere Technology GmbH, Germany; InfectoGnostics, Germany.
    Monecke, S.
    Alere Technology GmbH, Germany; InfectoGnostics, Germany.
    Matussek, A.
    Ryhov County Hospital, Jönköping, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Staphylococcus aureus colonization related to severity of hand eczema2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 8, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

    Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p amp;lt; 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES a parts per thousand yen 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare.

  • 38.
    Morin, Maxim
    et al.
    Malmo Univ, Sweden; Malmo Univ, Sweden.
    Jankovskaja, Skaidre
    Malmo Univ, Sweden; Malmo Univ, Sweden.
    Ruzgas, Tautgirdas
    Malmo Univ, Sweden; Malmo Univ, Sweden.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Anderson, Chris
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Brinte, Anders
    ImaGene iT, Sweden.
    Engblom, Johan
    Malmo Univ, Sweden; Malmo Univ, Sweden.
    Björklund, Sebastian
    Malmo Univ, Sweden; Malmo Univ, Sweden.
    Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers - An Explorative In Vivo Study2022In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 14, no 2, article id 313Article in journal (Refereed)
    Abstract [en]

    The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.

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  • 39.
    Muller, David A.
    et al.
    Univ Queensland, Australia.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Ben Baker, S.
    Vaxxas Pty Ltd, Australia.
    Togoe, Totte
    Region Östergötland, Medicine Center, Allergy Center.
    Jayashi Flores, Cesar M.
    Vaxxas Pty Ltd, Australia.
    Lemaire, Pierre A.
    Vaxxas Pty Ltd, Australia.
    Forster, Angus
    Vaxxas Pty Ltd, Australia.
    Anderson, Chris
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Innate local response and tissue recovery following application of high density microarray patches to human skin2020In: Scientific Reports, E-ISSN 2045-2322, Vol. 10, no 1, article id 18468Article in journal (Refereed)
    Abstract [en]

    The development of microarray patches for vaccine application has the potential to revolutionise vaccine delivery. Microarray patches (MAP) reduce risks of needle stick injury, do not require reconstitution and have the potential to enhance immune responses using a fractional vaccine dose. To date, the majority of research has focused on vaccine delivery with little characterisation of local skin response and recovery. Here we study in detail the immediate local skin response and recovery of the skin post high density MAP application in 12 individuals receiving 3 MAPs randomly assigned to the forearm and upper arm. Responses were characterised by clinical scoring, dermatoscopy, evaporimetry and tissue viability imaging (TiVi). MAP application resulted in punctures in the epidermis, a significant transepidermal water loss (TEWL), the peak TEWL being concomitant with peak erythema responses visualised by TiVi. TEWL and TiVi responses reduced over time, with TEWL returning to baseline by 48 h and erythema fading over the course of a 7 day period. As MAPs for vaccination move into larger clinical studies more variation of individual subject phenotypic or disease propensity will be encountered which will require consideration both in regard to reliability of dose delivery and degree of inherent skin response.

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  • 40.
    Nilsson, Gert
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Leahy, J.
    ODoherty, J.
    Polarization Spectroscopy camera: a new technique for mapping redness2007In: 16th congress of the European Academy of Dermatology and Venerology,2007, 2007Conference paper (Refereed)
  • 41.
    Nilsson, Gert
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Leahy, J.
    ODoherty, J.
    Tissue Viability Imaging in Dermatology2007In: 21th World congress of Dermatology,2007, 2007Conference paper (Refereed)
  • 42.
    Nilsson, Gert
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Leahy, M.
    Department of Physics University of Limeric, Ireland.
    O´Doherty, J.
    Department of Physics University of Limerick, Ireland.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Assessment of tissue viability by polarization spectroscopy2008In: Opto-Electronics Review, ISSN 1230-3402, E-ISSN 1896-3757, Vol. 16, no 3, p. 309-313Article in journal (Refereed)
    Abstract [en]

    A new and versatile method for tissue viability imaging based on polarization spectroscopy of blood in superficial tissue structures such as the skin is presented in this paper. Linearly polarized light in the visible wavelength region is partly reflected directly by the skin surface and partly diffusely backscattered from the dermal tissue matrix. Most of the directly reflected light preserves its polarization state while the light returning from the deeper tissue layers is depolarized. By the use of a polarization filter positioned in front of a sensitive CCD-array, the light directly reflected from the tissue surface is blocked, while the depolarized light returning from the deeper tissue layers reaches the detector array. By separating the colour planes of the detected image, spectroscopic information about the amount of red blood cells (RBCs) in the microvascular network of the tissue under investigation can be derived. A theory that utilizes the differences in light absorption of RBCs and bloodless tissue in the red and green wavelength region forms the basis of an algorithm for displaying a colour coded map of the RBC distribution in a tissue. Using a fluid model, a linear relationship (cc. = 0.99) between RBC concentration and the output signal was demonstrated within the physiological range 0–4%. In-vivo evaluation using transepidermal application of acetylcholine by the way of iontophoresis displayed the heterogeneity pattern of the vasodilatation produced by the vasoactive agent. Applications of this novel technology are likely to be found in drug and skin care product development as well as in the assessment of skin irritation and tissue repair processes and even ultimately in a clinic case situation.

  • 43.
    Nyman, Erika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris D.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Hyaluronic Acid Accelerates Re-epithelialization and Alters Protein Expression in a Human Wound Model2019In: Plastic and Reconstructive Surgery - Global Open, E-ISSN 2169-7574, Vol. 7, no 5, article id e2221Article in journal (Refereed)
    Abstract [en]

    Background: Hyaluronic acid (HA), a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to be an important factor for keratinocyte activation and re-epithelialization. The experimental hypothesis of this study was that HA accelerates re-epithelialization, and we aimed to investigate the effect of exogenous intradermal HA during deep dermal, incisional wound healing in vivo in humans, the primary endpoint being re-epithelialization. Methods: A total of 8 standardized deep dermal incisional wounds (depth 1.6mm, width 1.8mm) per subject were induced in 10 healthy volunteers. Two of the wound sites per subject were pretreated with injections of HA and 2 with saline solution. At 2 time points (24 hours and 14 days), 2 biopsies for each treatment group (one for histology and one for proteomics) were taken. Skin erythema was measured at 24-hour intervals for 14 days as a surrogate measurement of inflammation. Results: At 24 hours, 8 of 9 wounds pretreated with HA showed complete re-epithelization, whereas none of the wounds pretreated with saline had re-epithelized. Wounds pretreated with HA also showed a 10-fold regulation of 8 identified proteins involved in wound healing compared to wounds treated with saline solution. No difference in inflammation, as measured as erythema, could be seen between any of the groups. Conclusions: We conclude that HA accelerates re-epithelialization and stimulates an altered protein expression in vivo in human deep dermal incisional skin wounds, but has no effect on the inflammation process as measured by erythema.

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  • 44.
    Nyman, Erika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Rakar, Jonathan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Exogenous hyaluronic acid induces accelerated re-epithelialization and altered protein expression in adult human skin wounds in vivoManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Hyaluronic acid, a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to play an important role in ideal scarless fetal wound healing. This study aimed to investigate the effect of exogenous hyaluronic acid intradermal during deep dermal wound healing. Study parameters were erythema, re-epithelialization, and protein expression examined by using a previously described, minimally invasive in vivo human wound model in combination with tissue viability imaging, histology, and proteomics.

    Methods

    Standardized deep dermal wounds were created in the ventral forearm in ten healthy volunteers using blood collection lancets. The wound sites were injected with hyaluronic acid or saline solution, prior to wounding, or were left untreated. To quantify changes in red blood cell concentration as a measurement of inflammation, the study sites were photographed daily for two weeks using a tissue viability imaging system. At 24 hours and after 14 days, biopsy specimens were taken for histology and proteomics analysis.

    Results

    The inflammatory response was not affected by the injection of hyaluronic acid, as measured by tissue viability imaging. Hyaluronic acid significantly induced (p < 0.05) accelerated reepithelialization at 24 hours, and wounds treated with hyaluronic acid showed an altered protein expression.

    Conclusion

    The results from the present study are in concordance with  previous in vitro findings and suggest that exogenous hyaluronic acid has a  positive effect on the healing process of cutaneous wounds. We conclude that hyaluronic acid injected intradermally induces accelerated re-epithelialization and alters protein expression in vivo in human deep dermal skin wounds.

  • 45. ODoherty, J.
    et al.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Leahy, MJ.
    O'Doherty Investigation of Microvascular Red Blood Cell Proliferation in Dermal Tissue2006In: Institute of Physics IOP Ireland Annual Spring Meeting,2006, 2006Conference paper (Refereed)
  • 46.
    O'doherty, Jim
    et al.
    Department of Physics, University of Limerick, Plassey Technological Park, Limerick, Ireland.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Leahy, Martin J.
    Department of Physics, University of Limerick, Plassey Technological Park, Limerick, Ireland.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation2007In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 13, no 4, p. 472-484Article in journal (Refereed)
    Abstract [en]

    Background/aims: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non-invasive, more user-independent and objective methods are available today. Limited portability, high cost, lack of robustness and non-specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy-to-use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology.

    Methods: The use of orthogonal linear polarization filters over both the flash source and the detector array removes the polarization-retaining light reflected from the epidermal layer. Only the depolarized light backscattered from the papillary dermal matrix reaches the detector array. By separating the RGB color planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the chromophores in the dermal tissue can be attained. If the algorithm is based on a differential principle in which the normalized differences between the individual values of the red and green color plane are calculated, tissue components with similar spectral signature in both planes are suppressed, while components with different spectral signatures such as RBCs are enhanced.

    Results: In vitro fluid models compare well with theory and computer simulations in describing a linear relationship between the imager output signal termed the tissue viability index (TiVi index) and RBC concentration in the physiological range of 0-4% RBC fraction of tissue volume (cc=0.997, n=20). The influence of oxygen saturation on the calculated RBC concentration is limited to within -3.9% for values within the physiological range (70-100% oxygen saturation). Monte Carlo simulations provide information about the sampling depth (about 0.5mm on the average) of the imaging system. In vivo system evaluation based on iontophoresis of acetylcholine displays a heterogeneous pattern of vasodilatation appearing inside the electrode area after about 10min. Topical application of methyl nicotinate and clobetasol propionate further demonstrates the capacity to document the extent and intensity of both an increase (erythema) and a decrease (blanching) in the skin RBC concentration without movement artifact and with compensation for irregularity in pigmentation.

    Conclusions: Polarization light spectroscopy imaging for assessment of RBC concentration in the skin microvasculature is a robust and accessible technique for the clinical setting. Additionally, the technique has pre-clinical research applications for investigation of the spatial and temporal aspects of skin erythema and blanching as well as a potential role in drug development, skin care product development and skin toxicological assessment.

  • 47.
    O'Doherty, Jim
    et al.
    Royal Surrey County Hospital, Guildford, United Kingdom.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Enfield, Joey
    University of Limerick, Ireland.
    Nilsson, Gert E
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Leahy, Martin J.
    University of Limerick, Ireland.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Tissue viability imaging (TiVi) in the assessment of divergent beam UV-B provocation2011In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 303, no 2, p. 79-87Article in journal (Refereed)
    Abstract [en]

    In routine clinical phototesting and in basic research, naked eye dermatological assessment is the "gold standard" for determining the patient's minimal erythemal dose (MED). In UV-B testing with a divergent, radially attenuating beam of characterised dosimetry, laser Doppler perfusion imaging has been previously used to give quantitative description of reactivity to doses above the MED in addition to a "single-dose" objective determination of the MED itself. In the present paper, the recently developed tissue viability imaging (TiVi) technology is presented for the first time as a reliable, easily applicable, high-resolution alternative to LDPI in the divergent beam testing concept. Data obtained after provocation with a range of doses was analysed in order to determine the reaction diameter, which can be related to the MED using field dosimetry. The dose-response features of exposure above the MED and the relationship between naked eye readings and the diameter were determined from the image data. TiVi data were obtained faster than LDPI data and at a higher spatial resolution of 100 μm instead of 1 mm. A tool was developed to centre over the erythema area of the acquired image. Response data could be plotted continuously against dose. Thresholding of processed images compared to naked eye "gold standard" readings showed that the normal skin value +4 standard deviations produced a good fit between both methods. A linear fitting method for the dose-response data provided a further method of determination of the reaction diameter (MED). Erythemal "volume under the surface (VUS)" for the reaction provided a new concept for visualising information. TiVi offers advantages over LDPI in the acquisition and analysis of data collected during divergent beam testing. An increased amount of data compared to traditional phototesting is easily and more objectively obtained which increases applicability in the clinical and research environment.

  • 48.
    ODoherty, Jim
    et al.
    St Thomas Hospital, England .
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Correcting for possible tissue distortion between provocation and assessment in skin testing: The divergent beam UVB photo-test2013In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 19, no 4, p. 368-374Article in journal (Refereed)
    Abstract [en]

    BackgroundIn tissue viability imaging (TiVi), an assessment method for skin erythema, correct orientation of skin position from provocation to assessment optimizes data interpretation. Image processing algorithms could compensate for the effects of skin translation, torsion and rotation realigning assessment images to the position of the skin at provocation. less thanbrgreater than less thanbrgreater thanMethodsA reference image of a divergent, UVB phototest was acquired, as well as test images at varying levels of translation, rotation and torsion. Using 12 skin markers, an algorithm was applied to restore the distorted test images to the reference image. less thanbrgreater than less thanbrgreater thanResultsThe algorithm corrected torsion and rotation up to approximately 35 degrees. The radius of the erythemal reaction and average value of the input image closely matched that of the reference images true value. less thanbrgreater than less thanbrgreater thanConclusionThe image de-warping procedure improves the robustness of the response image evaluation in a clinical research setting and opens the possibility of the correction of possibly flawed images performed away from the laboratory setting by the subject/patient themselves. This opportunity may increase the use of photo-testing and, by extension, other late response skin testing where the necessity of a return assessment visit is a disincentive to performance of the test.

  • 49.
    O'Doherty, Jim
    et al.
    Physics Department, University of Limerick, National Technological Park, Limerick, Ireland.
    Henricson, Joakim
    Östergötlands Läns Landsting.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Östergötlands Läns Landsting.
    Leahy, Martin J.
    Physics Department, University of Limerick, National Technological Park, Limerick, Ireland.
    Real time diffuse reflectance polarisation spectroscopy imaging to evaluate skin microcirculation2007In: Novel Optical Instrumentationfor Biomedical Applications III / [ed] Christian D. Depeursinge, SPIE - International Society for Optical Engineering, 2007, p. 66310O-1-66310O-10Conference paper (Refereed)
    Abstract [en]

    This article describes the theoretical development and design of a real-time microcirculation imaging system, an extension from a previously technology developed by our group. The technology utilises polarisation spectroscopy, a technique used in order to selectively gate photons returning from various compartments of human skin tissue, namely from the superficial layers of the epidermis, and the deeper backscattered light from the dermal matrix. A consumer-end digital camcorder captures colour data with three individual CCDs, and a custom designed light source consisting of a 24 LED ring light provides broadband illumination over the 400 nm - 700 nm wavelength region. Theory developed leads to an image processing algorithm, the output of which scales linearly with increasing red blood cell (RBC) concentration. Processed images are displayed online in real-time at a rate of 25 frames s(-1), at a frame size of 256 x 256 pixels, and is limited only by computer RAM memory and processing speed. General demonstrations of the technique in vivo display several advantages over similar technology.

  • 50. O'Doherty, Jim
    et al.
    Leahy, Martin J.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Polarized Light Spectroscopy for the Non-Invasive Investigation of Microvascular Red Blood Cell Proliferation in Dermal Tissue2006In: Biomedical Topical Meeting (BIO), Optical Society of America, 2006Conference paper (Other academic)
    Abstract [en]

    This paper describes the construction and testing of a novel non-invasive imaging system based on the method of polarization spectroscopy. Computer simulations of the algorithm, Monte Carlo studies and in vivo testing have been performed.

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