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  • 1.
    Anderson, K S
    et al.
    Harvard Medical School, Boston, MA 02115, USA.
    Wong, J
    Harvard Medical School, Boston, MA 02115, USA.
    Polyak, K
    Harvard Medical School, Boston, MA 02115, USA.
    Aronzon, D
    Harvard Medical School, Boston, MA 02115, USA.
    Enerbäck, Charlotta
    Sahlgrenska University Hospital.
    Detection of psoriasin/S100A7 in the sera of patients with psoriasis2009In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 160, no 2, p. 325-332Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Psoriasis is a disease of dysregulated inflammation and epithelial hyperproliferation in the skin, involving both the innate and adaptive immune system. Psoriatic keratinocytes express high levels of psoriasin (S100A7), a small calcium-binding protein. OBJECTIVES: To determine if patients with active psoriasis have elevated serum levels of psoriasin and psoriasin-specific autoantibodies. METHODS: Blood was collected from 14 patients with psoriasis vulgaris at the start of narrowband ultraviolet (UV) B therapy and from 11 of these patients every 2 weeks during the course of the UVB treatment. Patient and control sera were tested for psoriasin antigen levels by sandwich enzyme-linked immunosorbent assay, and for psoriasin autoantibody titres using recombinant purified psoriasin and overlapping peptides. RESULTS: We confirmed strong and specific expression of psoriasin in psoriatic epidermis by immunohistochemistry. Systemic psoriasin antigen levels tended to be lower in patients (mean 213 ng mL(-1)) than in controls (mean 331 ng mL(-1), P = 0.308) and decreased with increasing disease severity. Psoriasin-specific autoantibodies were detected in a subset of patients with psoriasis and healthy normal donors (mean 0.347 vs. 0.255 units, P = 0.246). The epitopes recognized by the autoantibodies were mapped to an external loop domain of the molecule but did not show corresponding T-cell immunogenicity. CONCLUSIONS: Although psoriasin is overexpressed in psoriatic skin lesions, systemic levels of psoriasin tended to be lower with increasing disease severity, which may be due to the presence of psoriasin-specific autoantibodies. Neither psoriasin nor psoriasin-specific autoantibodies appear to be promising serum biomarkers for clinical psoriasis.

  • 2. Basset-Seguin, N
    et al.
    Ibbotson, S
    Emtestam, L
    Tarstedt, M
    Morton, C
    Maroti, M
    Cazavara-Pinton, P
    Varma, S
    Roelandts, R
    Wolf, P
    Saksela, O
    Rosdahl, Inger
    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.
    Photodynamic therapy using methyl aminolaevulinate is as efficacious as cryotherapy in basal cell carcinoma, with better cosmetic results2003In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 149, p. 46-46Conference paper (Other academic)
  • 3.
    Carlsson, Annica
    et al.
    Department of Dermatology, Institute of Clinical Research in Malmö, Skåne University Hospital, Lund University, Malmö.
    Gånemo, Agneta
    Department of Dermatology, Institute of Clinical Research in Malmö, Skåne University Hospital, Lund University, Malmö.
    Anderson, Chris
    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.
    Meding, Birgitta
    Unit of Occupational and Environmental Dermatology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm.
    Stenberg, Berndt
    Department of Public Health and Clinical Medicine, Umeå University, Umeå.
    Svensson, Åke
    Department of Dermatology, Institute of Clinical Research in Malmö, Skåne University Hospital, Lund University, Malmö.
    Scoring of hand eczema: good agreement between patients and dermatological staff2011In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 165, no 1, p. 123-128Article in journal (Refereed)
    Abstract [en]

    Background Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand. Objectives To investigate whether the same scoring system could be used by patients to communicate current status of hand eczema. Methods In a study of 62 patients (36 women and 26 men, age range 1975 years), the patients own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patients visit to the clinic. Individual area scores were summed to a total score. Results The overall agreement was good, with an interclass correlation (ICC) of 0.61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0.78. Differences between observers were more pronounced for the more severe cases - those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand. Conclusions Patients are able to report the extent of hand eczema with good accuracy. Self-assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.

  • 4.
    Ekman, Anna-Karin
    et al.
    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. Ingrid Asp Psoriasis Research Center.
    Enerbäck, Charlotta
    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. Ingrid Asp Psoriasis Research Center.
    Lack of preclinical support for the efficacy of histone deacetylase inhibitors in the treatment of psoriasis.2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 2, p. 424-426Article in journal (Refereed)
  • 5.
    Ekman, Anna-Karin
    et al.
    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.
    Verma, Deepti
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Bivik, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Enerbäck, Charlotta
    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.
    Genetic variations of NLRP1: susceptibility in psoriasis2014In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1517-1520Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1β and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions.

    OBJECTIVES: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility.

    MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls.

    RESULTS: Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele.

    CONCLUSIONS: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.

  • 6. Ericson, MB
    et al.
    Sandberg, C
    Stenquist, B
    Gudmundson, F
    Karlsson, M
    Ros, A-M
    Rosén, A
    Larkö, O
    Wennberg, A-M
    Rosdahl, Inger
    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.
    Photodynamic therapy of actinic keratosis at varying fluence rates: Assessment of photobleaching, pain and primary clinical outcome2004In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 151, no 6, p. 1204-1212Article in journal (Refereed)
    Abstract [en]

    Background: Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. Objectives: The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. Patients/methods Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580-650 nm) and fluence rates of 30 or 45 mW cm-2, and two groups with broad filter (580-690 nm) and fluence rates of 50 or 75 mW cm-2. The total cumulative light dose was 100 J cm-2 in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. Results: Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photo-bleaching dose (1/e) was found to be related to fluence rate, ranging from 4.5 ± 1.0 J cm -2 at 30 mW cm-2, to 7.3 ± 0.7 J cm-2 at 75 mW cm-2, indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm-2 no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm-2. However, the pain was found to be most intense up to a cumulative light dose of 20 J cm-2. Conclusions: Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm-2) seems preferable when performing PDT of AK using noncoherent light sources.

  • 7.
    Geale, K.
    et al.
    Umeå University, Sweden; PAREXEL Int, Sweden.
    Henriksson, Martin
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Schmitt-Egenolf, M.
    Umeå University, Sweden.
    Evaluating equality in psoriasis healthcare: a cohort study of the impact of age on prescription of biologics2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 3, p. 579-587Article in journal (Refereed)
    Abstract [en]

    Background Inequality in healthcare has been identified in many contexts. To the best of our knowledge, this is the first study investigating age inequality in the form of prescription patterns of biologics in psoriasis care. Objectives To determine whether patients with psoriasis have equal opportunities to receive biological medications as they age. If patients did not receive equal treatment, a subsequent objective was to determine the magnitude of the disparity. Methods A cohort of biologic-naive patients with psoriasis was analysed using Cox proportional hazards models to measure the impact of each additional year of life on the likelihood of initiating biological treatment, after controlling for sex, body mass index, comorbidities, disease activity and educational level. A supporting analysis used a nonparametric graphical method to study the proportion of patients initiating biological treatment as age increased, after controlling for the same covariates. Results The Cox proportional hazards model resulted in hazard ratios of a 1-year increase in age of 0.96-0.97 depending on calendar-year stratification, which implies that an increase in age of 30 years corresponds to a reduced likelihood of initiating biological treatment by 61.3-67.6%. The estimated proportion of patients initiating biological medication always decreased as age increased, at a statistically significant level. Conclusions Patients with psoriasis have fewer opportunities to access biological medications as they age. This result was shown to be applicable at all stages in a patients life course and was not only restricted to the elderly, although it implies greater disparities as the age difference between patients increases. These results show that inequality in access to biological treatments due to age is prevalent in clinical practice today. Further research is needed to investigate the extent to which this result is influenced by patient preferences.

  • 8.
    Krynitz, B.
    et al.
    Karolinska University of Labs, Sweden; Karolinska Institute, Sweden.
    Olsson, H.
    Karolinska Institute, Sweden.
    Lundh Rozell, Barbro
    Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lindelof, B.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Edgren, G.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Smedby, K. E.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 174, no 1, p. 95-103Article in journal (Refereed)
    Abstract [en]

    Background Risk of basal cell carcinoma (BCC) has been reported to be several-fold increased among organ transplant recipients (OTRs). However, due to lack of reliable BCC registration, population-based risk estimates are scarce. Objectives To characterize risk of BCC among OTRs compared with the general population, and contrast with risk of cutaneous squamous cell carcinoma (SCC). Subjects and methods OTRs transplanted during 2004-2011 were identified through national healthcare registers and linked with the nationwide Swedish BCC Register initialized in 2004. Relative risk of BCC was expressed as standardized incidence ratios (SIR) with 95% confidence intervals (CI). Results Altogether, 4023 transplanted patients developed 341 BCCs during follow-up. Compared with the general population, the relative risk of BCC was increased sixfold (SIR 6.1, 95% CI 5.4-6.9). The risk was higher in kidney and heart/lung than in liver recipients (SIRkidney 7.2, 6.3-8.3; SIRheart/lung 5.8, 4.0-8.2; SIRliver 2.6, 1.7-4.0), and risk increased with time since transplantation (P-trend < 0.01). The SCC to BCC ratio was 1 : 1.7 and BCC developed earlier after transplantation than SCC. Distribution of anatomical sites and histological types did not differ substantially between OTR- and population-BCCs. Conclusions Risk of BCC was strikingly elevated in OTRs compared with the general population. Risk was higher in kidney recipients and increased with follow-up time. These findings support a tumour-promoting effect of immunosuppressive drugs in BCC development. The low SCC to BCC ratio was possibly attributed to short follow-up time.

  • 9. Lindelöf, B
    et al.
    Sigurgeirsson, B
    Tegner, E
    Johannesson, A
    Berne, B
    Christensen, OB
    Andersson, T
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Törngren, M
    Molin, M
    Nylander-Lundqvist, E
    Emtestam, L
    PUVA and cancer risk: the Swedish follow-up study.1999In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 141, p. 108-112Article in journal (Refereed)
  • 10.
    Lyth, Johan
    et al.
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, H.
    Department of Oncology-Pathology, Karolinska Institute, Stockholm.
    Hansson, J.
    Department of Oncology-Pathology, Karolinska Institute, Stockholm.
    Ingvar, C.
    Department of Surgery, Lund University Hospital, Lund.
    Jansson, M.
    Department of Surgery, Umeå University, Umeå.
    Lapins, J.
    Department of Dermatology, Karolinska University Hospital, Stockholm.
    Månsson-Brahme, E.
    Department of Oncology-Pathology, Karolinska Institute, Stockholm.
    Naredi, P.
    Department of Surgery, University of Gothenburg, Sahlgrenska University Hospital, Göteborg.
    Stierner, U.
    Department of Oncology, Sahlgrenska University Hospital, Göteborg.
    Ullenhag, G.
    Department of Radiology, Oncology and Radiation Science, Section of Oncology, Uppsala University, Uppsala.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Lindholm, C.
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men2015In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, no 3, p. 700-706Article in journal (Refereed)
    Abstract [en]

    Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most western countries, though the rate of improvement in survival appears to have declined in Sweden at the end of last millennium.

    Objectives: To analyse the most recent trends in the distribution of tumour thickness (T-category) as well as CMM-specific survival in Swedish patients diagnosed 1997-2011.

    Methods: This nationwide population-based study included 30 590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM 1997-2011. The patients were followed through 2012 in the national Cause-of-Death Register.

    Results: Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site, and health care region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P = 0·0008) and the CMM-specific survival significantly improved in men diagnosed 2007-2011 compared to men diagnosed 1997-2001 (hazard ratio=0·81; 95% CI 0·72-0·91, P = 0·0009) while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared to those diagnosed earlier 1997-2001 and later 2007-2011.

    Conclusion: In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.

  • 11.
    Lyth, Johan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Hansson, J.
    Department of Oncology–Pathology, Karolinska Institute, Stockholm, Sweden.
    Ingvar, C.
    Department of Surgery, Lund University Hospital, Lund, Sweden.
    Mansson-Brahme, E.
    Department of Oncology–Pathology, Karolinska Institute, Stockholm, Sweden.
    Naredi, P.
    Department of Surgery, Umeå University, Umeå, Sweden.
    Stierner, U.
    Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Wagenius, G.
    Department of Oncology, Akademiska University Hospital, Uppsala, Sweden.
    Lindholm, C.
    Östergötlands Läns Landsting, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
    Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion: results of a population-based study from the Swedish Melanoma Register2013In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 168, no 4, p. 779-786Article in journal (Refereed)
    Abstract [en]

    Background  Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed.

    Objectives  The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark’s level of invasion for risk stratification of T1 cutaneous melanoma.

    Methods  From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data.

    Results  Ulceration, tumour thickness and Clark’s level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2–1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0–7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2–21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1.

    Conclusions  Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark’s level of invasion, three distinct prognostic subgroups were identified.

  • 12. Scarisbrick, J.J.
    et al.
    Taylor, P.
    Holtick, U.
    Makar, Y.
    Douglas, K.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Juvonen, E.
    Marshall, S.
    U.K. consensus statement on the use of extracorporeal photopheresis for treatment of cutaneous T-cell lymphoma and chronic graft-versus-host disease2008In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 158, no 4, p. 659-678Article in journal (Refereed)
    Abstract [en]

    Extracorporeal photopheresis (ECP) has been used for over 30 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic graft-versus-host disease (cGVHD). The lack of prospective randomized trials has led to different centres having different patient selection criteria, treatment schedules, monitoring protocols and patient assessment criteria. ECP for CTCL and cGVHD is available only at six specialized centres across the U.K. In the recent Improving Outcomes Guidance the National Institute for Health and Clinical Excellence endorsed the use of ECP for CTCL and because of the complexity of treatment supported its use in specialized centres and also suggested the need for expansion of this service. In 2005 consultants and senior nurses from all U.K. sites and from Scandinavia formed a Photopheresis Expert Group. This group's first aim was to produce a consensus statement on the treatment of CTCL and cGVHD with ECP using evidence-based medicine and best medical practice, in order to standardize ECP eligibility, assessment and treatment strategies across the U.K.

  • 13.
    Schön, Thomas
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Hernández-Pando, R.
    Experimental Pathology Laboratory, Department of Pathology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
    Baquera-Heredia, J.
    Experimental Pathology Laboratory, Department of Pathology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
    Negesse, Y.
    Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Becerril-Villanueva, L. E.
    Experimental Pathology Laboratory, Department of Pathology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
    Leon-Contreras, J. C.
    Experimental Pathology Laboratory, Department of Pathology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Britton, Sven
    Department of Infectious Diseases, Karolinska Institute, Stockholm, Sweden.
    Nitrotyrosine localization to dermal nerves in borderline leprosy2004In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 150, no 3, p. 570-574Article in journal (Refereed)
    Abstract [en]

    Background  Nerve damage is a common and disabling feature of leprosy, with unclear aetiology. It has been reported that the peroxidizing agents of myelin lipids—nitric oxide (NO) and peroxynitrite—are produced in leprosy skin lesions.

    Objectives  To investigate the localization of nitrotyrosine (NT)—a local end-product of peroxynitrite—in leprosy lesions where dermal nerves are affected by a granulomatous reaction.

    Methods  We investigated by immunohistochemistry and immunoelectron microscopy the localization of the inducible NO synthase (iNOS) and NT in biopsies exhibiting dermal nerves from patients with untreated leprosy.

    Results  There were abundant NT-positive and iNOS-positive macrophages in the borderline leprosy granulomas infiltrating peripheral nerves identified by light microscopy, S-100 and neurofilament immunostaining. Immunoelectron microscopy showed NT reactivity in neurofilament aggregates and in the cell wall of Mycobacterium leprae.

    Conclusions  Our results suggest that NO and peroxynitrite could be involved in the nerve damage following borderline leprosy.

  • 14.
    Schön, Thomas
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Pando, R. H.
    Experimental Pathology Laboratory, Dept of Pathology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City.
    Negesse, Y.
    AHRI, Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
    Leekassa, R.
    ALERT, All Africa Leprosy Relief and Training Hospital, Addis Ababa, Ethiopia.
    Sundqvist, Tommy
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Britton, Sven
    AHRI, Armauer Hansen Research Institute, Addis Ababa, Ethiopia and Department of Infectious Diseases, Karolinska Hospital, Stockholm, Sweden.
    Expression of inducible nitric oxide synthase and nitrotyrosine in borderline leprosy lesions2001In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 145, no 5, p. 809-815Article in journal (Refereed)
    Abstract [en]

    Background In the response to T-helper cell (Th1)-type cytokines and interactions with pathogens, high levels of nitric oxide (NO) are produced by activated macrophages expressing the inducible NO synthase (iNOS). The role and importance of reactive nitrogen intermediates (RNIs) such as NO and peroxynitrite in the host response to diseases caused by intracellular pathogens such as Mycobacterium leprae and M. tuberculosis is unclear.

    Objectives The aim of this study was to investigate the presence of local production of NO and peroxynitrite in borderline leprosy by using antibodies against iNOS and the product of peroxynitrite, nitrotyrosine (NT).

    Methods We detected the presence of iNOS and NT in skin biopsies from borderline leprosy patients, with and without reversal reaction (RR), by immunohistochemistry (n = 26).

    Results In general, the granulomas from borderline leprosy lesions with and without RR showed high and specific expression of iNOS and NT. Moreover, strong immunoreactivity to iNOS and NT was observed in granulomas surrounding and infiltrating dermal nerves. The expression of iNOS and NT was also strong in keratinocytes, fibroblasts and endothelial cells in close relation to the granulomatous reaction. In contrast, normal human skin showed no expression of iNOS and NT in these cells.

    Conclusions We conclude that iNOS and NT are expressed in granulomas from borderline leprosy patients with and without RR and propose that RNIs might be involved in the nerve damage following RR in leprosy.

  • 15.
    Sjögren, Florence
    et al.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Svensson, C.
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences.
    Anderson, Chris
    Department of Dermatology, Liverpool Health Service, Australia.
    Technical prerequisites for in vivo microdialysis determination of interleukin-6 in human dermis2002In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 146, no 3, p. 375-382Article in journal (Refereed)
    Abstract [en]

    Background  Cutaneous microdialysis in vivoin human skin is demonstrably of use in the study of skin metabolism, percutaneous absorption and skin inflammation. A promising area for cutaneous microdialysis is the measurement of cytokines. This requires catheters equipped with membranes permeable to molecules of high molecular weight.

    Objectives  To address technical problems of poor sample volume retrieval and analysis sensitivity in the simplest model of provocation, namely the insertion of the catheter itself in vivo into human dermis.

    Methods  Use of a polyethylenesulphone membrane, with a cut-off value of 100 000 Da, allowed measurement of target molecules of large molecular weight. Using an adaptation of a commercially available high sensitivity enzyme-linked immunosorbent assay, the ubiquitous proinflammatory cytokine interleukin (IL)-6 was measured in the normal skin of six healthy volunteers after insertion of the microdialysis catheter.

    Results  Reliable sample volumes and high analyte recovery were achieved either by push–pull pumping or by standard pumping using a perfusate consisting of Ringers Dextran 60 Braun. No IL-6 was detected in 25 of 26 samples taken during the first 100 min after catheter insertion. The IL-6 concentration then increased and remained elevated for the duration of the experiments.

    Conclusions  Technical and analytical modifications in the microdialysis technique have allowed the measurement of IL-6 in vivo in human dermis. It is suggested that the cytokine production is the result of the dermal trauma caused by catheter insertion, but the cellular source of the IL-6 is at present unknown.

  • 16. Thomsen, JS
    et al.
    Sonne, M
    Benfeldt, E
    Jensen, SB
    Serup, Jörgen
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Dermatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Menné, T
    Experimental itch in sodium lauryl sulphate-inflamed and normal skin in humans: A randomized, double-blind, placebo-controlled study of histamine and other inducers of itch2002In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 146, no 5, p. 792-800Article in journal (Refereed)
    Abstract [en]

    Background: Investigations of pruritogenic substances in humans have involved intradermal injections in normal skin, itching of inflamed skin has been little studied. Objectives: To develop an itch model with provocation of itch in experimentally inflamed skin as well as in normal skin, using subjects as self-controls. Methods: In 32 non-atopic volunteers aged 21-30 years, the skin of five selected test sites on one volar forearm was pretreated for 24 h with large Finn chambers containing 1% sodium lauryl sulphate (SLS) used as a standard contact irritant to induce inflammation. Twenty microlitres of different pruritogenic substances [histamine, substance P, neurokinin A, neurokinin B, trypsin, platelet-activating factor (PAF) and serotonin] and saline as control were injected intradermally into the inflamed test sites and in corresponding non-treated sites on the opposite forearm. The test individuals scored itch intensity on a visual analogue scale for 20 min, and weal area was then measured. Results: Histamine and substance P induced itch in both normal and inflamed skin compared with a saline reference. Neurokinin A, trypsin, PAF and serotonin only elicited itch in normal skin, and neurokinin B neither elicited itch in normal skin nor in inflamed skin. Itch was induced in normal and SLS-inflamed skin to a similar magnitude. However, weal area after histamine was significantly (P<0.001) larger in inflamed skin when compared with normal skin. Conclusions: Histamine and substance P elicited itch to the same degree in normal skin and inflamed skin pretreated with SLS despite a stronger weal response in inflamed skin. Mediators present in inflamed skin did not potentiate itch, a c-fibre-mediated neuronal response. The weal reaction is based on enhanced vascular permeability (protein extravasation). A greater skin perfusion in inflamed skin may therefore have increased the weal size. We propose an experimental model in humans for testing of itch involving both normal and inflamed skin. The model has the potential for use in evaluating new topical and systemic treatments of itch.

  • 17.
    Tufvesson Stiller, Helena
    et al.
    Region Östergötland, Center for Business support and Development, Regional Cancer Center. Dermatology, Department of Public Health and Clincal Medicine, Umeå University, Sweden.
    Mikiver, R.
    Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Uppugunduri, Srinivas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Lindholm, C.
    Region Östergötland, Center for Business support and Development, Regional Cancer Center.
    Mansson Brahme, Eva
    Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
    Schmitt-Egenolf, Marcus
    Department of Public Health and Clinical Medicine, Umeå University, Sweden.
    Health-related quality of life in patients with melanoma - characterization of a Swedish cohort2019In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133Article in journal (Other academic)
    Abstract [en]

    Abstract not available.

  • 18.
    Ulff, E.
    et al.
    Ryhov Hospital, Jönköping, Sweden.
    Maroti, M.
    Ryhov Hospital, Jönköping, Sweden.
    Kettis-Lindblad, A.
    Uppsala University, Sweden.
    Kjellgren, Karin
    Sahlgrenska Academy, Göteborg University, Sweden.
    Ahlner, Johan
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
    Ring, L.
    Uppsala University, Sweden.
    Serup, Jörgen
    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.
    Single application of a fluorescent test cream by healthy volunteers: assessment of treated and neglected body sites2007In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 156, no 5, p. 974-978Article in journal (Refereed)
    Abstract [en]

    Background: Management of dermatological self-treatment is demanding. Imperfect application of creams and ointments and poor adherence to topical treatment are common, resulting in unsatisfactory treatment outcome. Objectives: To assess the technique and precision of test subjects' self-application of a test cream. Treated and neglected skin sites were measured after intended widespread single application of a fluorescent test cream. Methods: Twenty healthy volunteers (10 women, 10 men) were included. They were asked to treat their whole skin surface with the fluorescent test cream, except the head and neck and skin covered by underwear. Treated and untreated sites were subsequently measured under Wood's ultraviolet radiation. Results: Thirty-one per cent of the skin surface that was a target for application did not show any fluorescence and thus was assumed to have been untreated. Typical neglected sites included the central back, the upper breast, the axilla with surrounding skin, the legs and the feet, particularly the sole. The posterior aspect of both trunk and extremities, not easily inspected, was more often neglected. In the treated sites the fluorescence was typically uneven. Conclusions: Qualified and motivated persons with no obvious physical limitations practised imperfect self-application of a test cream mimicking a therapeutic cream product. As much as 31% of the skin surface was neglected. Sites especially prone to nonapplication were identified. This might imply that dermatological patients on long-term self-treatment may practise local application very poorly, a problem of major therapeutic and economic importance. A fluorescent test cream can be used for research, and as an educational tool in the training of dermatological patients on how to apply local treatment.

  • 19.
    Vegfors, Jenny
    et al.
    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.
    Ekman, Anna-Karin
    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.
    Stoll, S W
    University of Michigan, Ann Arbor, MI, U.S.A.
    Bivik Eding, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Enerbäck, Charlotta
    Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Psoriasin (S100A7) promotes stress-induced angiogenesis.2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 175, no 6, p. 1263-1273Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Vascular modifications occur early in the development of psoriasis, and angiogenesis is one of the key features in the pathogenesis of the disease.

    OBJECTIVES: To identify the role of the S100 protein psoriasin in psoriasis-associated angiogenesis.

    METHODS: The role of psoriasin in mediating angiogenesis was investigated by silencing psoriasin with small interfering RNA (siRNA) and measuring psoriasis-associated angiogenic factors in human epidermal keratinocytes. The secretion of psoriasin and the effect of psoriasin on general regulators of angiogenesis in keratinocytes, and on endothelial cell migration, proliferation, tube formation and production of angiogenic mediators, was evaluated.

    RESULTS: Reactive oxygen species (ROS) and hypoxia induced the expression of psoriasin. Downregulation of psoriasin in keratinocytes using siRNA altered the ROS-induced expression of the psoriasis-associated angiogenic factors vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor, matrix metalloproteinase 1 and thrombospondin 1. Overexpression of psoriasin altered several regulators of angiogenesis and led to the secretion of psoriasin. Treatment with extracellular psoriasin induced proliferation, migration and tube formation in dermal-derived endothelial cells to a similar extent as VEGF and interleukin-17, and induced the expression and release of proangiogenic mediators. These effects were suggested to be mediated by the PI3K and nuclear factor kappa B pathways.

    CONCLUSIONS: These findings suggest that psoriasin expression is promoted by oxidative stress in keratinocytes and amplifies the ROS-induced expression of angiogenic factors relevant to psoriasis. Moreover, extracellularly secreted psoriasin may act on dermal endothelial cells to contribute to key features angiogenesis.

  • 20.
    Wang, L.
    et al.
    Lund University.
    Andersson-Engel, Stefan
    Department of Physics, Lund University.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Svanberg, K.
    Lund University.
    Superficial Blood flow Following Photodynamic Therapy of Malignant Skin Tumours Measured by Laser Doppler Perfusion Imaging1997In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 136, no 2, p. 184-189Article in journal (Refereed)
    Abstract [en]

    Laser Doppler perfusion imaging offers a new modality for in vivo monitoring of the superficial blood perfusion in biological tissue. In this study, the superficial blood perfusion of malignant nonmelanoma skin tumours and the surrounding normal skin was measured in conjunction with photodynamic therapy (PDT) using topical ò–aminolaevulinic acid (ALA)–induced protoporphyrin IX as a photosensitizer. The results clearly show that, in contradiction to PDT with the intravenously administered photosensitizer photofrin. no direct vascular damage can be seen. With the topical sensitization the blood perfusion is increased immediately after the treatment irradiation. The increased blood flow is seen up to a week after treatment, in a similiar way as for an inflammatory reaction. Despite this, all basal cell carcinoma and squamous cell carcinoma in situ lesions in this study healed without any sign of residual tumour after the treatment, suggesting an efficient direct tumour cell destruction induced by PDT.

  • 21.
    Willis, C. M.
    et al.
    Buckinghamshire Healthcare NHS Trust, England.
    Britton, L. E.
    Buckinghamshire Healthcare NHS Trust, England.
    Swindells, M. A.
    Search Dogs UK, England.
    Jones, E. M.
    UCL, England.
    Kemp, A. E.
    Buckinghamshire Healthcare NHS Trust, England.
    Muirhead, N. L.
    Buckinghamshire Healthcare NHS Trust, England.
    Gul, A.
    Buckinghamshire Healthcare NHS Trust, England.
    Matin, R. N.
    Oxford University Hospital NHS Fdn Trust, England.
    Knutsson, L.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ali, M.
    Buckinghamshire Healthcare NHS Trust, England.
    Invasive melanoma in vivo can be distinguished from basal cell carcinoma, benign naevi and healthy skin by canine olfaction: a proof-of-principle study of differential volatile organic compound emission2016In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 175, no 5, p. 1020-1029Article in journal (Refereed)
    Abstract [en]

    Background Volatile organic compounds (VOCs) are continuously released by the body during normal metabolic processes, but their profiles change in the presence of cancer. Robust evidence that invasive melanoma in vivo emits a characteristic VOC signature is lacking. Objectives To conduct a canine olfactory, proof-of-principle study to investigate whether VOCs from invasive melanoma are distinguishable from those of basal cell carcinoma (BCC), benign naevi and healthy skin in vivo. Methods After a 13-month training period, the dogs ability to discriminate melanoma was evaluated in 20 double-blind tests, each requiring selection of one melanoma sample from nine controls (three each of BCC, naevi and healthy skin; all samples new to the dog). Results The dog correctly selected the melanoma sample on nine (45%) occasions (95% confidence interval 0.23-0.68) vs. 10% expected by chance alone. A one-sided exact binomial test gave a P-value of amp;lt;0.01, supporting the hypothesis that samples were not chosen at random but that some degree of VOC signal from the melanoma samples significantly increased the probability of their detection. Use of a discrete-choice model confirmed melanoma as the most influential of the recorded medical/personal covariates in determining the dogs choice of sample. Accuracy rates based on familiar samples during training were not a reliable indicator of the dogs ability to distinguish melanoma, when confronted with new, unknown samples. Conclusions Invasive melanoma in vivo releases odorous VOCs distinct from those of BCC, benign naevi and healthy skin, adding to the evidence that the volatile metabolome of melanoma contains diagnostically useful biomarkers.

  • 22.
    Wäster, Petra
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Rosdahl, Inger
    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.
    Öllinger, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.2014In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 171, no 6, p. 1336-1346Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation.

    OBJECTIVES: To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes.

    METHODS: Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied.

    RESULTS: UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis.

    CONCLUSIONS: We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression.

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