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  • 1. Arildsson, Mikael
    et al.
    Asker, Claes
    Salerud, E. Göran
    Strömberg, Tomas
    Skin capillary appearance and skin microvascular perfusion due to topical application of analgesia cream2000In: Microvascular Research. 2000 Jan;59(1):14-23Article in journal (Refereed)
    Abstract [en]

    Local topical analgesia changes basal skin perfusion and its regulation. In particular, the response induced by local heating, which in nontreated skin comprises a rapidly increased perfusion followed by a normalization within 30 s, is altered to a delayed and persistent perfusion increase. The response dependency to the analgesia cream application time, that is, the intradermal penetration of the analgesics and in which vascular plexa the response occurs, is not known. The aim of this study was to assess changes in the appearance of superficial skin capillaries and skin microvascular perfusion changes due to different application periods of topical analgesia cream (EMLA). Twelve subjects were treated with EMLA and placebo applied to the volar side of each forearm, respectively. The treatment areas were assigned different application times (20 min, 40 min, 1 h, 2 h, and 3 h). The areas were cleared from the creams and shortly thereafter provoked during 9 s with a probe heated to 45 degrees C. To assess capillary number density and skin perfusion, capillary microscopy, and Laser Doppler perfusion imaging (LDPI), respectively, were used. The number density of physiologically active capillary was significantly decreased with longer application times of EMLA (P < 0.005). The LDPI-signal showed a persistent perfusion increase after provocation associated with increasing application time of the cream. This perfusion pattern was not seen after 20 min of treatment, but was present in 9 of 12 subjects after 3 h of treatment. No significant relationship between changes in the capillary number density and the LDF measurement was found. In conclusion, a longer application time and therefore a higher intradermal concentration and a deeper penetration of the analgesics was associated with a delayed and persistent perfusion increase after local heating. There was a discrepancy between changes in capillary number density and skin perfusion, indicating that the perfusion increase does not occur in the capillaries but in the deeper lying vessels. Hence, the contribution of the capillary perfusion to the LDF-signal is smaller than previously anticipated. Capillary number density and presumably their perfusion were decreased with longer application times

  • 2. Asker, Claes
    Computer Assisted Video Microscopy: in Characterization of Capillary Ensembles2000Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis focuses on evaluation and analysis of capillary microcirculatory changes in the skin, that can be improved and extended by computer assisted video microscopy. Capillary microscopy has been used extensively, both in clinical practice and research, to study different phenomena in the microvasculature of the skin, mainly in the nailfold of fingers and toes where a large portion of the capillary loop can be observed.



    In the majority of the different skin regions, the nutritive capillary network approaches the skin surface perpendicularly and capillary microscopy in these sites reveals the apex of the capillary loop as a dark spot. The main approach in this work has been to study a large ensemble of capillary loops, in order to apply statistical and planar models whilst, at the same time, obtaining spatial parameters related to the capillary localization.



    The statistical models of proximity are based on nearest neighbour methods and triangulation techniques. The main reason for introducing these models is because of their capability to characterize the heterogeneity of the capillary ensemble.



    A computer assisted video microscopy system, that enables both capturing and evaluating of capillary bed images, was assembled and was, thereafter, successfully used in laboratory and clinical studies

  • 3. Asker, Claes
    et al.
    Arildsson, M.
    Salerud, E.G.
    Strömberg, T.
    Compartmental skin perfusion responses affected by analgesia1999Conference paper (Refereed)
  • 4. Asker, Claes
    et al.
    Mørk, C.
    Kvernebo, K.
    Salerud, E.G.
    Skin Capillary Ensemble Analysis in Erythromelagia2000Conference paper (Refereed)
  • 5. Asker, Claes
    et al.
    Salerud, E.G.
    Capillary density, distribution and homogeneity in erythromelalgic subjects evaluated using computer-assisted video-microscopy1996Conference paper (Refereed)
  • 6. Asker, Claes
    et al.
    Salerud, E.G.
    Computer assisted capillary microscopy: Theory and clinical applications1995Conference paper (Refereed)
  • 7. Asker, Claes
    et al.
    Salerud, E.G.
    Datorbaserad kapillärmikroskopi1994Conference paper (Refereed)
  • 8. Asker, Claes
    et al.
    Salerud, E.G.
    Estimation of Spatial Heterogeneity of the Capillary Bed Using Mathematical Triangulation and Distance Models1996Conference paper (Refereed)
  • 9. Asker, Claes
    et al.
    Salerud, E.G.
    Technical aspects of image analysis in evaluating spatial heterogeneity of skin capillary bed ensembles1998Conference paper (Refereed)
  • 10. Asker, Claes
    et al.
    Salerud, E.G.
    The changes in capillary detection accuracy in video microscopy images depending on the choice of the image grayscale transform1997Conference paper (Refereed)
  • 11. Mørk, C.
    et al.
    Asker, Claes
    Salerud, E.G.
    Kvernebo, K.
    Eryhtromelalgia: A Syndrome of Dysfunctional Vascular Dynamics2001Conference paper (Refereed)
  • 12. Mørk, C.
    et al.
    Asker, Claes
    Salerud, E.G.
    Kvernebo, K.
    Erythromelagia: A Condition with Increased Arteriovenous Shunting2000Conference paper (Refereed)
  • 13. Mørk, Cato
    et al.
    Asker, Claes
    Göran Salerud, E.
    Kvernebo, Knut
    Microvascular Arteriovenous Shunting is a Probable Pathogenetic Mechanism in Erythromelalgia2000In: Journal of Investigative DermatologyArticle in journal (Refereed)
    Abstract [en]

    Erythromelalgia is a condition consisting of red, warm, and burning painful extremities. Symptoms are relieved by cold and aggravated by heat. A wide variety of etiologic conditions can cause erythromelalgia, but one common pathogenetic mechanism, microvascular arteriovenous shunting, has been hypothesized. The aim of this study was to test this hypothesis. Quantification of skin microvascular perfusion using laser Doppler perfusion imaging and skin temperature at rest and after central body heating was performed in 14 patients with erythromelalgia and 11 controls. Attacks of erythromelalgia were induced in eight patients after heat provocation. In the plantar region of the foot, the location of numerous anatomical arteriovenous shunts, these patients significantly increased the skin perfusion as compared with asymptomatic patients with erythromelalgia and controls. In the dorsal region with few arteriovenous shunts no significant differences between the groups were demonstrated. The results show a relation between clinical symptoms and increased perfusion in the region of numerous anatomical arteriovenous shunts, and support the hypothesis of increased thermoregulatory arteriovenous shunt flow during attacks in primary erythromelalgia

  • 14. Mørk, Cato
    et al.
    Kvernebo, Knut
    Asker, Claes
    Salerud, E. Göran
    Reduced Skin Capillary Density During Attacks of Erythromelalgia Implies Arteriovenous Shunting as Pathogenetic Mechanism2002In: Journal of Investigative DermatologyArticle in journal (Refereed)
    Abstract [en]

    Erythromelalgia is characterized by burning pain, erythema, and increased temperature in acral skin. The pain is aggravated by warming and relieved by cooling. Increased microvascular arteriovenous shunting in deep dermal plexa has been hypothesized as the pathogenetic mechanism of pain in affected skin, inducing hypoxia during pain attacks. The aim of this study was to quantify skin capillary density in erythromelalgic patients before and after heat provocation, as increased skin temperature should increase the need for nutritive blood supply by the capillaries. Fourteen patients and 10 healthy control subjects were studied using an enhanced technique of computer-assisted analysis of capillary bed morphology and temperature measurements before and after central body heating. The increase in acral skin temperature was significantly higher (p < 0.05) in the eight patients where symptoms were induced after heat provocation, compared to asymptomatic patients and healthy control subjects. The number of visible capillaries in a field of view (1.7Êmm 2) decreased significantly (p = 0.01) in erythromelalgia patients from 105 (62-137) (median with total range) to 89 (49-118) after warming in areas with numerous arteriovenous anastomoses (nail bed region). In symptomatic patients an even more significant reduction was observed (p = 0.01). The capillary size was also significantly reduced (p < 0.05) from 41.0 (31.5-50.5) (arbitrary units) to 37.3 (33.0-46.0) in symptomatic patients. The change in capillary density in the nail bed area was significantly larger in erythromelalgia patients 17 ( 49 to 39) compared to controls 0 ( 47 to 13) (p < 0.05), and in symptomatic patients 19 ( 49 to 12) compared to asymptomatic patients 8 ( 48 to 39) (p < 0.05) and controls (p < 0.01). The reduced skin capillary density after heating is compatible with increased microvascular arteriovenous shunting of blood and a corresponding relative deficit in nutritive perfusion (steal phenomenon) with skin hypoxia, causing the symptoms in erythromelalgia

  • 15. Mørk, Cato
    et al.
    Salerud, E. Göran
    Asker, Claes
    Kvernebo, Knut
    The Prostaglandin E1 Analog Misoprostol Reduces Symptoms and Microvascular Arteriovenous Shunting in Erythromelalgia - A Double-Blind, Crossover, Placebo-Compared Study2004In: Journal of Investigative Dermatology Volume 122, Issue 3, Page 587-593, Mar 2004Article in journal (Refereed)
    Abstract [en]

    Based on previous experience with parenteral prostanoids, we studied the effect of misoprostol treatment, an orally administered prostaglandin E1 analog, in patients with erythromelalgia. Treatment with placebo was followed by treatment with misoprostol (0.40.8 mg per d), both for 6 wk. The patients (n=21) and a study nurse who administered the trial were blinded. The endpoints were change in pain and need for cooling and global assessment of the treatment. Following central body heat provocation, global skin perfusion, capillary morphology, and change in pain were also recorded before and after each treatment period. Results were compared with data from healthy control subjects (n=11) that did not undergo treatment. Clinical safety and tolerability evaluation included physical examinations, clinical laboratory tests, and monitoring of adverse events. All clinical outcome measures were signifcantly better after treatment with misoprostol (p<0.01) as compared with placebo treatment and after a 3- mo follow-up without treatment. The heat-induced increase in global perfusion after misoprostol treatment was similar to the control group and signiÞcantly lower when compared with baseline (p<0.01) and placebo treatment (p<0.05), respectively. This study demonstrates that misoprostol is clinically superior to placebo in patients with erythromelalgia. The results of the perfusion studies may imply that the mechanism of action of the beneÞcial effect of misoprostol is reduced microvascular arteriovenous shunting in affected skin

  • 16.
    Mørk, Cato
    et al.
    Department of Dermatology, Rikshospitalet University Hospital, Norway.
    Salerud, E Göran
    Department of Biomedical Engineering, Linköping University.
    Asker, Claes L
    Karlstad University, Division for Chemistry.
    Kvernebo, Knut
    Department of Cardiothoracic Surgery, Ullevaal University Hospital, Norway.
    The Prostaglandin E1 Analog Misoprostol Reduces Symptoms and Microvascular Arteriovenous Shunting in Erythromelalgia: A Double-Blind, Crossover, Placebo-Compared Study2004In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 122, no 3, p. 587-593Article in journal (Refereed)
    Abstract [en]

    Based on previous experience with parenteral prostanoids, we studied the effect of misoprostol treatment, an orally administered prostaglandin E1 analog, in patients with erythromelalgia. Treatment with placebo was followed by treatment with misoprostol (0.4–0.8 mg per d), both for 6 wk. The patients (n=21) and a study nurse who administered the trial were blinded. The endpoints were change in pain and need for cooling and global assessment of the treatment. Following central body heat provocation, global skin perfusion, capillary morphology, and change in pain were also recorded before and after each treatment period. Results were compared with data from healthy control subjects (n=11) that did not undergo treatment. Clinical safety and tolerability evaluation included physical examinations, clinical laboratory tests, and monitoring of adverse events. All clinical outcome measures were significantly better after treatment with misoprostol (p<0.01) as compared with placebo treatment and after a 3-mo follow-up without treatment. The heat-induced increase in global perfusion after misoprostol treatment was similar to the control group and significantly lower when compared with baseline (p<0.01) and placebo treatment (p<0.05), respectively. This study demonstrates that misoprostol is clinically superior to placebo in patients with erythromelalgia. The results of the perfusion studies may imply that the mechanism of action of the beneficial effect of misoprostol is reduced microvascular arteriovenous shunting in affected skin.

  • 17.
    Mørk, Cato
    et al.
    Rikshospitalet University Hospital.
    Salerud, E Göran
    Linköpings universitet.
    Asker, Claes L
    Karlstad University.
    Kvernebo, Knut
    Ulleval University Hospital.
    The prostaglandin E1 analog misoprostol reduces symptoms and microvascular arteriovenous shunting in erythromelalgia-a double-blind, crossover, placebo-compared study.2004In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 122, no 3, p. 587-93Article in journal (Refereed)
    Abstract [en]

    Based on previous experience with parenteral prostanoids, we studied the effect of misoprostol treatment, an orally administered prostaglandin E1 analog, in patients with erythromelalgia. Treatment with placebo was followed by treatment with misoprostol (0.4-0.8 mg per d), both for 6 wk. The patients (n=21) and a study nurse who administered the trial were blinded. The endpoints were change in pain and need for cooling and global assessment of the treatment. Following central body heat provocation, global skin perfusion, capillary morphology, and change in pain were also recorded before and after each treatment period. Results were compared with data from healthy control subjects (n=11) that did not undergo treatment. Clinical safety and tolerability evaluation included physical examinations, clinical laboratory tests, and monitoring of adverse events. All clinical outcome measures were significantly better after treatment with misoprostol (p<0.01) as compared with placebo treatment and after a 3- mo follow-up without treatment. The heat-induced increase in global perfusion after misoprostol treatment was similar to the control group and significantly lower when compared with baseline (p<0.01) and placebo treatment (p<0.05), respectively. This study demonstrates that misoprostol is clinically superior to placebo in patients with erythromelalgia. The results of the perfusion studies may imply that the mechanism of action of the beneficial effect of misoprostol is reduced microvascular arteriovenous shunting in affected skin.

  • 18. Salerud, E.G.
    et al.
    Asker, Claes
    Datorstödd kapillärmikroskopi1996Conference paper (Refereed)
  • 19. Zhong, Jicun
    et al.
    Asker, Claes
    Salerud, E. Göran
    Imaging, image processing and pattern analysis of skin capillary ensembles2000In: Skin Research and TechnologyArticle in journal (Refereed)
    Abstract [en]

    Background/aims: The capillary bed is recognized as the site where metabolic and nutrient processes occur for living tissues at all levels. The evaluation of this vital process is a major concern in microcirculation. Unlike traditional approaches that concentrated on the extreme local properties of this process, a more global analysis toward capillary ensembles is employed here, since capillaries work as a cooperative entirety. As a first step toward ensemble analysis, the static and planar geometric parameters are investigated. Parameters such as the capillary adjacency and size information are very important in predicting and analysing certain malfunctions in the microvascular bed.



    Methods/results: In order to achieve an objective and accurate analysis of these vital parameters, a computerized imaging system is proposed. Not only the number of capillaries and the capillary cross-sectional areas are important in describing the microvascular bed but the planar distribution pattern of the capillaries also carries valid information. This information, unique to the ensemble analysis, can be used to reveal, visualise and quantify the clustering of capillaries; and this information, according to the Krogh model, is fundamental in estimating the tissue oxygen supply. Two spatial models, the closest neighbor and triangulation methods, have been applied to the captured images of capillary ensembles. The closest neighbor technique generates a minimal distance map or displays a distribution, which depicts the local clustering of capillaries. The triangulation technique, on the other hand, generates a mutual distance map, which is a global description of the capillary positions. Triangulation methods have been evaluated but all except the Greedy triangulation method have been rejected due to lack of robustness and model weakness. Therefore, the capillaries are triangulated by the Greedy triangulation method, and the capillary distribution uniformity is defined as one minus the coefficient of variance of the edge lengths of the mutual distance map.



    Conclusions: A series of advanced image processing methods have been developed that efficiently extract the capillary position, size and distribution information from the images. These results facilitate the automatic counting of capillaries and the capillary size-related pathological analysis

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