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  • 1.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Dermato-Venereological Research at Linköping University2011Ingår i: Forum for Nordic Dermato-Venereology, ISSN 1402-2915, Vol. 16, nr 1, s. 16-17Artikel, forskningsöversikt (Övrigt vetenskapligt)
  • 2.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    JUST A LITTLE PRICK WITH A NEEDLE in WOUND REPAIR AND REGENERATION, vol 18, issue 4, pp 65-2010Ingår i: WOUND REPAIR AND REGENERATION, Blackwell Publishing Ltd , 2010, Vol. 18, nr 4, s. 65-Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 3.
    Andersson, Rolf
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Quirk, Chris
    Royal Perth Hospital, WA Australien.
    Sullivan, John
    Liverpool Hospital, NSW Australien.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Cutaneous manifestations of internal disease2008Ingår i: Drug Discovery Today : Disease Mechanisms, ISSN 1740-6765, E-ISSN 1740-6765, Vol. 5, nr 1, s. e113-e123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The skin mirrors the individual's well being. Visible for both the patient and the attending physician, it can be a source of information for the diagnosis of multi-system diseases and diseases of internal organs. Therapy is usually directed at the primary disease. Pharmaco-therapeutic options for internal diseases are at present not always optimal and specific management of side effects of drugs with vital indication may be necessary. Better understanding of the mechanisms of the cutaneous manifestations may help develop more efficacious, better tolerated therapy and improve the patient's situation.

  • 4.
    Andersson, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Cutaneous microdialysis: a technique for human in vivo sampling1995Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Microdialysis enables in vivo sampling of endogenous and exogenous substances in the interstitial fluid. A probe equipped with a tubular semi-permeable dialysis membrane is inserted into the skin, and perfused with a physiological solution. Diffusion of molecules from the extracellular space to the perfusate takes place, and the perfusate is collected for analysis. In this thesis, experimental and clinical applications of human cutaneous microdialysis in the fields of skin inflammation and percutaneous absorption are presented.

    The in vivo absorption kinetics of the model solvents ethanol and isopropanol, applied in excess to the skin over the dialysis probe, could be demonstrated in all subjects. Ethanol levels increased in a linear fashion to reach a peak at about 100 min, then establishing a plateau level. Isopropanol absorption showed similar kinetics. The absolute levels detected were lower for isopropanol than for ethanol.

    Laser Doppler perfusion imaging visualized the skin circulatory response to the microdialysis probe insertion. An immediate increase in skin blood perfusion was observed. The response began to subside after 15 min and returned to near normal within 60 min after probe insertion.

    Histamine, a ubiquitous inflammatory mediator, was studied as a model. Following the skin trauma caused by probe insertion, peak histamine levels were observed in the first 10-min sample, then falling successively to reach baseline within 40-60 min. Multiple regression analysis did not reveal any correlation between probe depth, as measured by ultrasoundtechnique, and obtained histamine levels during the equilibration period following probe insertion. Provocation with compound 48/80 as a positive control for skin histamine release, resulted in increased histamine levels in the perfusate. Histamine release was followed in reactions provoked in the skin of patients with cold urticaria. An up to 80-fold increase of histamine levels was observed, with peak levels 20-30 min after start of ice provocation, returning to baseline within 50-60 min.

    Human, in vivo, cutaneous microdialysis has the potential to be an important sampling method in studies of skin inflammation and percutaneous absorption of noxious chemicals as well as in dennal and transdermal drug delivery studies.

  • 5. 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
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Photodynamic therapy using methyl aminolaevulinate is as efficacious as cryotherapy in basal cell carcinoma, with better cosmetic results2003Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 149, s. 46-46Konferensbidrag (Övrigt vetenskapligt)
  • 6.
    Bastami, Salumeh
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Frödin, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Ahlner, Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet.
    Uppugunduri, Srinivas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Topical morphine gel in the treatment of painful leg ulcers, a double-blind, placebo-controlled clinical trial: a pilot study2012Ingår i: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 9, nr 4, s. 419-427Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic painful wounds, a major health problem, have a detrimental impact on the quality of life due to associated pain. Some clinical reports have suggested that local administration of morphine could be beneficial. The aim of this study was to evaluate the analgesic effect of topically applied morphine on chronic painful leg ulcers. Twenty-one patients were randomly assigned to receive either morphine or placebo in a randomised, placebo-controlled, crossover pilot study. Each patient was treated four times in total. Pain was measured by the visual analogue score (VAS) before application of gel, directly after and after 2, 6, 12 and 24 hours. Although an overall, clinically relevant, reduction of pain was observed upon treatment with morphine, the difference was not statistically significant. Morphine reduced pain scores more than placebo on treatment occasions 1 and 2. The difference was statistically significant only 2 hours after dressing on the first treatment occasion. Thus, our study did not demonstrate a consistent and globally significant difference in nociception in patients treated with morphine. However, the relatively small number of patients included in our study and other methodological limitations makes it difficult for us to draw general conclusions regarding efficacy of topically applied morphine as an effective treatment for some painful ulcers. Further studies are warranted to evaluate the value of topically applied morphine in the treatment of patients with chronic painful leg ulcers.

  • 7.
    Bivik, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Regulation of UV induced apoptosis in human melanocytes2007Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Malignant melanoma arises from the pigment producing melanocytes in epidermis and is the most aggressive type of skin cancer. The incidence of malignant melanoma is increasing faster than any other type of cancer in white population worldwide, with a doubling rate every 10-20 years. So far, the only identified external risk factor for malignant melanoma is UV exposure. Elimination of photodamaged cells by apoptosis (programmed cell death) is essential to prevent tumor formation. Melanocytes are considered relatively resistant to apoptosis, however, the regulation of apoptosis in melanocytes is still unknown.

    The aim of this thesis was to investigate the apoptotic process following ultraviolet (UV) irradiation in primary cultures of human melanocytes. Focus was on regulation of mitochondrial stability by Bcl-2 family proteins and the possible participation of lysosomal proteases, cathepsins. UV irradiation activated the mitochondrial pathway of apoptosis, leading to cytochrome c release, caspase activation, and nuclear fragmentation. No change in protein expression of Bax and Bcl-2 was observed in response to UV. Instead, translocation of the Bcl-2 family proteins from cytosol to mitochondia was important in the regulation of survival and death of melanocytes. The findings further demonstrated permeabilization of the lysosomal membrane to occur early in the apoptotic process, resulting in cathepsin release into the cytosol. The cathepsins were potent pro-apoptotic mediators and triggered apoptosis upstream of Bax translocation and mitochondrial membrane permeabilization. In response to both heat and UV irradiation, there was a marked increase in expression of stress-induced heat shock protein 70 (Hsp70), which inhibited apoptosis by binding lysosomal and mitochondrial membranes and counteracting the release of cathepsins and cytochrome c. Furthermore, UV irradiation activated c-jun N-terminal kinase (JNK), which triggered apoptosis upstream of cathepsins release from the lysosomes. In addition, JNK mediated apoptosis through phosphorylation of pro-apoptotic Bim, which was released from anti-apoptotic Mcl-1, by UV induced Mcl-1 depletion.

    This thesis illustrates that permeabilization of mitochondria and lysosomes and release of their constituents to the cytosol participates in UV induced apoptosis signaling in human melanocytes in vitro. The process is regulated by a complex network of pro- and anti-apoptotic proteins, exerting their effects through intracellular translocation and alteration of protein expression.

    Delarbeten
    1. Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects
    Öppna denna publikation i ny flik eller fönster >>Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects
    2005 (Engelska)Ingår i: Melanoma Research, ISSN 0960-8931, Vol. 15, nr 1, s. 7-13Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Apoptosis and alterations in Bcl-2 and Bax messenger RNA (mRNA) and protein expression were examined in cultured human epidermal melanocytes following UVB irradiation (50 mJ/cm2). The effects of various spectral ranges within UVB were investigated. A co-culture system was set up to study the interplay between melanocytes and keratinocytes in response to UVB. Melanocytes expressed high basal levels of the anti-apoptotic protein Bcl-2 compared with keratinocytes. Different wavelengths within the UVB spectrum induced diverse response patterns of Bcl-2 and Bax mRNA and had different apoptotic power. Both Bcl-2 and Bax mRNA were upregulated to preserve protein levels and only a slight increase in apoptosis was noted 24 h after UVB ([lambda]>305 nm). Increasing UVB between 280 and 305 nm enhanced apoptosis and upregulated Bcl-2, whilst Bax mRNA was unaltered. However, no change in protein levels was detected. A redistribution of Bax protein from different compartments within the cell may be more important than direct upregulation for the acceleration of apoptosis, but it cannot be excluded that other apoptotic pathways may be induced by shorter UVB wavelengths. The increase in apoptosis was significantly lower in melanocytes co-cultured with irradiated matched keratinocytes than in melanocytes from pure cultures, indicating that melanocytes are protected from UVB-induced apoptosis by the release of substance(s) from keratinocytes. This rescue response concurred with a fast and significant increase in Bcl-2 mRNA level in melanocytes.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14399 (URN)10.1097/00008390-200502000-00003 (DOI)
    Tillgänglig från: 2008-11-13 Skapad: 2008-11-13 Senast uppdaterad: 2009-04-28
    2. UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Öppna denna publikation i ny flik eller fönster >>UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members
    Visa övriga...
    2006 (Engelska)Ingår i: Journal of Investigative Dermatology, ISSN 0022-202X, Vol. 126, nr 5, s. 1119-1127Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    We demonstrate UVA/B to induce apoptosis in human melanocytes through the mitochondrial pathway, displaying cytochrome c release, caspase-3 activation, and fragmentation of nuclei. The outcome of a death signal depends on the balance between positive and negative apoptotic regulators, such as members of the Bcl-2 protein family. Apoptotic melanocytes, containing fragmented nucleus, show translocation of the proapoptotic proteins Bax and Bid from the cytosol to punctate mitochondrial-like structures. Bcl-2, generally thought to be attached only to membranes, was in melanocytes localized in the cytosol as well. In the fraction of surviving melanocytes, that is, cells with morphologically unchanged nucleus, the antiapoptotic proteins Bcl-2 and Bcl-XL were translocated to mitochondria following UVA/B. The lysosomal proteases, cathepsin B and D, which may act as proapoptotic mediators, were released from lysosomes to the cytosol after UVA/B exposure. Proapoptotic action of the cytosolic cathepsins was confirmed by microinjection of cathepsin B, which induced nuclear fragmentation. Bax translocation and apoptosis were markedly reduced in melanocytes after pretreatment with either cysteine or aspartic cathepsin inhibitors. No initial caspase-8 activity was detected, excluding involvement of the death receptor pathway. Altogether, our results emphasize translocation of Bcl-2 family proteins to have central regulatory functions of UV-induced apoptosis in melanocytes and suggest cathepsins to be proapoptotic mediators operating upstream of Bax.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14400 (URN)10.1038/sj.jid.5700124 (DOI)
    Tillgänglig från: 2008-11-13 Skapad: 2008-11-13 Senast uppdaterad: 2017-08-30
    3. Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes
    Öppna denna publikation i ny flik eller fönster >>Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes
    2007 (Engelska)Ingår i: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 28, nr 3, s. 537-544Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Stress-induced heat shock protein 70 (Hsp70) effectively protects cells against apoptosis, although the anti-apoptotic mechanism is still undefined. Exposure of human melanocytes to heat and subsequent UVB irradiation increased the level of Hsp70 and pre-heating reduced UVB induced apoptosis. Immunofluorescence staining of Hsp70 in combination with staining of lysosomes (Lamp2) or mitochondria (Mitotracker®) in pre-heated UVB exposed cells showed co-localization of Hsp70 with both lysosomes and mitochondria in the surviving cell population. Furthermore, UVB induced apoptosis was accompanied by lysosomal and mitochondrial membrane permeabilization, detected as release of cathepsin D and cytochrome c, respectively, which were prevented by heat pre-treatment. In purified fractions of lysosomes and mitochondria, recombinant Hsp70 attached to both lysosomal and mitochondrial membranes. Moreover, in apoptotic cells Bax was translocated from a diffuse cytosolic location into punctate mitochondrial-like structures, which was inhibited by Hsp70 induction. Such inhibition of Bax translocation was abolished by transfection with Hsp70 siRNA. Furthermore, Hsp70 siRNA eliminated the apoptosis preventive effect observed after pre-heating. These findings show Hsp70 to rescue melanocytes from UVB induced apoptosis by preventing release of cathepsins from lysosomes, Bax translocation and cytochrome c release from mitochondria.

     

    Abbreviations: AIF, apoptosis-inducing factor; Hsp, heat shock protein; NAG, ß-N-acetylglucosaminidase; tBid, truncated Bid; UV, ultraviolet

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14401 (URN)10.1093/carcin/bgl152 (DOI)
    Tillgänglig från: 2007-05-14 Skapad: 2007-05-14 Senast uppdaterad: 2017-12-13
    4. JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins
    Öppna denna publikation i ny flik eller fönster >>JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins
    2008 (Engelska)Ingår i: Apoptosis (London), ISSN 1360-8185, E-ISSN 1573-675X, Vol. 13, nr 9, s. 1111-1120Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    UVB irradiation induced phosphorylation of JNK and subsequent apoptosis in human melanocytes. Depletion of both JNK1 and JNK2 expression using siRNA transfection, protected against apoptosis, as detected by decreased nuclear fragmentation and caspase-3 activity, as well as reduced translocation of Bax to mitochondria. Moreover, release of cathepsin B and D from lysosomes to the cytosol was reduced when JNK expression was suppressed by siRNA, demonstrating a JNK dependent regulation of lysosomal membrane permeabilization. In unirradiated control melanocytes, coimmunoprecipitation showed that Bim was sequestered by Mcl-1, which had a pro-survival function. After UVB irradiation, a significant decrease in Mcl-1 protein level was found, which was prevented by addition of a proteasome inhibitor. The interaction between Bim and Mcl-1 was reduced in response to UVB irradiation and Bim was phosphorylated in a JNK dependent manner. In conclusion, these findings Suggest JNK to have an important pro-apoptotic function following UVB irradiation in human melanocytes, by acting upstream of lysosomal membrane permeabilization and Bim phosphorylation.

    Nyckelord
    UV, Cathepsin, JNK, Mcl-1, Bim
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-16886 (URN)10.1007/s10495-008-0240-7 (DOI)
    Anmärkning
    The original publication is available at www.springerlink.com: Cecilia Bivik and Karin Öllinger, JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins, 2008, Apoptosis (London), (13), 9, 1111-1120. http://dx.doi.org/10.1007/s10495-008-0240-7 Copyright: Springer Science Business Media http://www.springerlink.com/ Tillgänglig från: 2009-04-29 Skapad: 2009-02-20 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
  • 8.
    Bivik, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Regulation of UV-induced apoptosis in human melanocytes2009Ingår i: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, nr 1, s. 25-26Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    [No abstract available]

  • 9.
    Bivik, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Andersson, Eva
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Wavelength specific effects on UVB induced apoptosis in melanocytes. A study of the Bcl-2/Bax expression and keratinocyte rescue effects2005Ingår i: Melanoma Research, ISSN 0960-8931, Vol. 15, nr 1, s. 7-13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Apoptosis and alterations in Bcl-2 and Bax messenger RNA (mRNA) and protein expression were examined in cultured human epidermal melanocytes following UVB irradiation (50 mJ/cm2). The effects of various spectral ranges within UVB were investigated. A co-culture system was set up to study the interplay between melanocytes and keratinocytes in response to UVB. Melanocytes expressed high basal levels of the anti-apoptotic protein Bcl-2 compared with keratinocytes. Different wavelengths within the UVB spectrum induced diverse response patterns of Bcl-2 and Bax mRNA and had different apoptotic power. Both Bcl-2 and Bax mRNA were upregulated to preserve protein levels and only a slight increase in apoptosis was noted 24 h after UVB ([lambda]>305 nm). Increasing UVB between 280 and 305 nm enhanced apoptosis and upregulated Bcl-2, whilst Bax mRNA was unaltered. However, no change in protein levels was detected. A redistribution of Bax protein from different compartments within the cell may be more important than direct upregulation for the acceleration of apoptosis, but it cannot be excluded that other apoptotic pathways may be induced by shorter UVB wavelengths. The increase in apoptosis was significantly lower in melanocytes co-cultured with irradiated matched keratinocytes than in melanocytes from pure cultures, indicating that melanocytes are protected from UVB-induced apoptosis by the release of substance(s) from keratinocytes. This rescue response concurred with a fast and significant increase in Bcl-2 mRNA level in melanocytes.

  • 10.
    Bivik, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Carlström, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Enerbäck, Charlotta
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi.
    Apoptosis has a role in the disturbed homeostasis of epidermal keratinocytes in psoriasis in JOURNAL OF INVESTIGATIVE DERMATOLOGY, vol 132, issue , pp S79-S792012Ingår i: JOURNAL OF INVESTIGATIVE DERMATOLOGY, Nature Publishing Group , 2012, Vol. 132, s. S79-S79Konferensbidrag (Refereegranskat)
    Abstract [en]

    n/a

  • 11.
    Bivik, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Hsp70 protects against UVB induced apoptosis by preventing release of cathepsins and cytochrome c in human melanocytes2007Ingår i: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 28, nr 3, s. 537-544Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Stress-induced heat shock protein 70 (Hsp70) effectively protects cells against apoptosis, although the anti-apoptotic mechanism is still undefined. Exposure of human melanocytes to heat and subsequent UVB irradiation increased the level of Hsp70 and pre-heating reduced UVB induced apoptosis. Immunofluorescence staining of Hsp70 in combination with staining of lysosomes (Lamp2) or mitochondria (Mitotracker®) in pre-heated UVB exposed cells showed co-localization of Hsp70 with both lysosomes and mitochondria in the surviving cell population. Furthermore, UVB induced apoptosis was accompanied by lysosomal and mitochondrial membrane permeabilization, detected as release of cathepsin D and cytochrome c, respectively, which were prevented by heat pre-treatment. In purified fractions of lysosomes and mitochondria, recombinant Hsp70 attached to both lysosomal and mitochondrial membranes. Moreover, in apoptotic cells Bax was translocated from a diffuse cytosolic location into punctate mitochondrial-like structures, which was inhibited by Hsp70 induction. Such inhibition of Bax translocation was abolished by transfection with Hsp70 siRNA. Furthermore, Hsp70 siRNA eliminated the apoptosis preventive effect observed after pre-heating. These findings show Hsp70 to rescue melanocytes from UVB induced apoptosis by preventing release of cathepsins from lysosomes, Bax translocation and cytochrome c release from mitochondria.

     

    Abbreviations: AIF, apoptosis-inducing factor; Hsp, heat shock protein; NAG, ß-N-acetylglucosaminidase; tBid, truncated Bid; UV, ultraviolet

  • 12.
    Bivik, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Wäster, Petra
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    UVA/B induced apoptosis in human melanocytes involves translocation of cathepsins and Bcl-2 family members2006Ingår i: Journal of Investigative Dermatology, ISSN 0022-202X, Vol. 126, nr 5, s. 1119-1127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We demonstrate UVA/B to induce apoptosis in human melanocytes through the mitochondrial pathway, displaying cytochrome c release, caspase-3 activation, and fragmentation of nuclei. The outcome of a death signal depends on the balance between positive and negative apoptotic regulators, such as members of the Bcl-2 protein family. Apoptotic melanocytes, containing fragmented nucleus, show translocation of the proapoptotic proteins Bax and Bid from the cytosol to punctate mitochondrial-like structures. Bcl-2, generally thought to be attached only to membranes, was in melanocytes localized in the cytosol as well. In the fraction of surviving melanocytes, that is, cells with morphologically unchanged nucleus, the antiapoptotic proteins Bcl-2 and Bcl-XL were translocated to mitochondria following UVA/B. The lysosomal proteases, cathepsin B and D, which may act as proapoptotic mediators, were released from lysosomes to the cytosol after UVA/B exposure. Proapoptotic action of the cytosolic cathepsins was confirmed by microinjection of cathepsin B, which induced nuclear fragmentation. Bax translocation and apoptosis were markedly reduced in melanocytes after pretreatment with either cysteine or aspartic cathepsin inhibitors. No initial caspase-8 activity was detected, excluding involvement of the death receptor pathway. Altogether, our results emphasize translocation of Bcl-2 family proteins to have central regulatory functions of UV-induced apoptosis in melanocytes and suggest cathepsins to be proapoptotic mediators operating upstream of Bax.

  • 13.
    Bivik, Cecilia
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Öllinger, Karin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    JNK mediates UVB-induced apoptosis upstream lysosomal membrane permeabilization and Bcl-2 family proteins2008Ingår i: Apoptosis (London), ISSN 1360-8185, E-ISSN 1573-675X, Vol. 13, nr 9, s. 1111-1120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    UVB irradiation induced phosphorylation of JNK and subsequent apoptosis in human melanocytes. Depletion of both JNK1 and JNK2 expression using siRNA transfection, protected against apoptosis, as detected by decreased nuclear fragmentation and caspase-3 activity, as well as reduced translocation of Bax to mitochondria. Moreover, release of cathepsin B and D from lysosomes to the cytosol was reduced when JNK expression was suppressed by siRNA, demonstrating a JNK dependent regulation of lysosomal membrane permeabilization. In unirradiated control melanocytes, coimmunoprecipitation showed that Bim was sequestered by Mcl-1, which had a pro-survival function. After UVB irradiation, a significant decrease in Mcl-1 protein level was found, which was prevented by addition of a proteasome inhibitor. The interaction between Bim and Mcl-1 was reduced in response to UVB irradiation and Bim was phosphorylated in a JNK dependent manner. In conclusion, these findings Suggest JNK to have an important pro-apoptotic function following UVB irradiation in human melanocytes, by acting upstream of lysosomal membrane permeabilization and Bim phosphorylation.

  • 14.
    Bu, Huajie
    et al.
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Holmdahl-Källenand, Katarina
    Zhang, Hong
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Importance of polymorphisms at NF-κB1 and NF-κBIα genes in melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients2007Ingår i: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 133, nr 11, s. 859-866Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, functional polymorphisms of NF-κB1 and NF-κBIα genes were examined in 185 melanoma patients and 438 tumor-free individuals. Associations of the polymorphisms with melanoma risk, age and pigment phenotypes of the patients and clinico-pathological tumor characteristics were analyzed. DNAs were isolated from mononuclear cells of venous blood. Polymorphisms of the genes were genotyped by a PCR-RFLP technique, and transcription level of NF-κBIα was examined by a quantitative real-time reverse transcription PCR. Results showed that both ATTG insertion polymorphism of NF-κB1 and A to G polymorphism of NF-κBIα genes were correlated with melanoma risk, especially, in a combination of ATTG2/ATTGT2 and GG. NF-κB1 ATTG2/ATTG2 and NF-κBIα GG genotypes were associated with male gender and age > 65 years (at diagnosis). Patients with ATTG1/ATTG1 genotype had thinner tumors and lower Clark levels at diagnosis. Frequency of ATTG1/ATTG1 genotype was higher in patients with melanomas on intermittently sun-exposed pattern of the body and NF-κBIα GG was more frequent in the patients with melanomas at rarely exposed sites. There were no differences in the gene transcription level between patients with different NF-κBIα genotypes. These data suggest that NF-κB1 and NF-κBIα genes might be susceptible genes for melanoma risk and functional polymorphisms of these genes might be biological predictors for melanoma progression.

  • 15.
    Bu, Huajie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Zhang, Hong
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Genotype < 21CAs/>= 21CAs and allele < 21CAs of the MANBA gene in melanoma risk and progression in a Swedish population2009Ingår i: Molecular medicine reports, ISSN 1791-2997, Vol. 2, nr 2, s. 259-263Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cutaneous melanoma is characterized by poor patient outcome in its later stages. The search for genetic markers is therefore crucial for the identification of populations at risk for melanoma. Highly polymorphic CA repeats in 3 proximity in the MANBA gene were examined by PCR-capillary electrophoresis in 185 Swedish melanoma patients and 441 tumor-free age- and gender-matched individuals. The associations of the polymorphisms with melanoma risk, the pigment phenotypes of the patients and tumor characteristics were analyzed. A significant difference in allelic distribution between melanoma patients and tumor-free individuals was observed. The frequency of the MANBA genotype <21CAs/>= 21CAs was significantly higher in melanoma patients than in the controls. When comparing allele distribution in patients and their matched controls, the allele <21 CAs was found to be associated with the female gender (39.8 vs. 31.2%, P=0.041, OR=1.46, 95% Cl 1.02-2.10), but not with male gender (34.4 vs. 30.9%, P=0.39). Within the melanoma group, there were no differences in the distribution of the MANBA alleles associated with patient gender or age before or after 55 years at diagnosis, nor was there any association between the MANBA genotype and pigment phenotype or tumor sites. The MANBA allele <21CAs was, however, associated with thin melanomas at diagnosis (Breslow thickness <= 1.5 mm and Clark levels I and II). In conclusion, these data suggest that MANBA polymorphisms might be an indicator of tumor growth and progression and, together with other markers, could be used to identify individuals at increased risk of melanoma.

  • 16.
    Carlsen, K H
    et al.
    University of Copenhagen.
    Carlsen, K M
    University of Copenhagen.
    Serup, Jörgen
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Non-attendance rate in a Danish University Clinic of Dermatology2011Ingår i: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 25, nr 11, s. 1269-1274Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim To clarify the rate of non-attendance (NA) in an out-patient clinic. less thanbrgreater than less thanbrgreater thanMethods Attendance lists of 3592 patients were collected daily from 21 July-21 August and 21 October-21 November, 2009. NA patients were contacted to determine extenuations. To study NA in relation to diagnosis and age, a control group of patients who attended before or after a NA was established. Furthermore, two time periods from 8:00-11:30 AM and 11:30 AM-3:00 PM were compared. less thanbrgreater than less thanbrgreater thanResults In total, 13% NA gave no cancellation (54.2% females and 45.8% males). Divided into age groups, 496 patients 0-25 years old had appointments, but 87 (18.6%) showed NA. In the 26-65 years old, 2188 patients were planned, but 313 (14.1%) showed NA. Over 65 years old, 878 patients were planned, but 69 patients (7.9%) showed NA. NA was higher (P andlt; 0.05) in patients 0-25 years old in comparison with the other age groups. Diagnoses had no influence on the rate of NA (P andgt; 0.05), neither had seasons nor time of the day. The main explanations reported by the NA were: forgetfulness (34.3%), erroneous scheduling (27.7%) and various reasons (38.0%). However, 18.5% had shown NA before while 17.1% were NA first timers. less thanbrgreater than less thanbrgreater thanConclusion The NA rate 13% of 3592 patients was mostly patient-related. Erroneous scheduling was estimated to be 3.6%. NA was more frequent among young patients. NA rate is small in comparison with non-adherence to medicines, however, of major practical and economic consequence for the health system. SMS or e-mail notification and improved scheduling are potential actions to improve NA in the routine.

  • 17.
    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
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i 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 staff2011Ingår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 165, nr 1, s. 123-128Artikel i tidskrift (Refereegranskat)
    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.

  • 18.
    Christiansen Clifford, Jenny
    et al.
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Färm, Gunilla
    Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
    Eid-Forest, Ruth
    Department of Dermatology, University Hospital, 701 85 Örebro, Sweden.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Hudkliniken US.
    Cederbrant, Karin
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och cytologi.
    Interferon-gamma secreted from peripheral blood mononuclear cells as a possible diagnostic marker for allergic contact dermatitis to gold2006Ingår i: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 55, nr 2, s. 101-112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    10% of patch-tested patients have a positive reaction to gold. Most lack clinical symptoms, but allergic contact dermatitis (ACD) to gold is increasing. In this study, 77 dermatological outpatients were divided into 3 groups depending on epicutaneous patch test outcomes: a group positive to gold (EPI+), a group negative to gold (EPI-), and a group with irritant reactions to gold (EPI-IR). Lymphocytes were stimulated in vitro with gold sodium thiosulfate. Proliferation was assessed using the lymphocyte transformation test (LTT), and cytokine secretion was assessed using a multibead array (Luminex; Linco Research Inc., St. Charles, MO, USA), in order to evaluate whether an in vitro method with high diagnostic accuracy could be devised. The EPI+ group showed a significantly increased secretion of interferon (IFN)-gamma, interleukin (IL)-2, and IL-13 and also showed a significantly higher stimulation indexes for LTT, compared to the other 2 subject groups. Sensitivity and specificity were calculated for all methods individually and combined, but IFN-gamma assessment alone was the most accurate method for identifying ACD to gold, with sensitivity and specificity of 81.8% and 82.1%, respectively. This method also identified 87.5% of the EPI-IR subjects as non-allergic. Therefore, assessment of secretion of IFN-gamma should be a valuable complement to patch test for diagnosing gold allergy.

  • 19.
    Clancy, Neil T
    et al.
    University of London Imperial College of Science, Technology and Medicine.
    Nilsson, Gert
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Leahy, Martin J
    University of Limerick.
    A new device for assessing changes in skin viscoelasticity using indentation and optical measurement2010Ingår i: SKIN RESEARCH AND TECHNOLOGY, ISSN 0909-752X, Vol. 16, nr 2, s. 210-228Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/aims Skin is a viscoelastic material, comprised of fluidic and fibrous components. Changes in viscoelasticity can arise due to a number of conditions including dehydration, swelling (associated with injury or disease), impaired heart function, rehydration therapy, ageing, scarring, sun exposure and genetic conditions affecting connective tissue. Quantification of changes in skin viscoelasticity due to these processes is of great clinical interest in the fields of therapy monitoring, wound healing and disease screening. However, devices currently available to measure aspects of the mechanical properties of skin have limitations in ease-of-use, accessibility, and depth of measurement. This paper describes a new technique to follow changes in the viscoelasticity of the skin, using a novel approach to an indentation manoeuvre. The device is portable, low-cost and easy to use while at the same time providing rich information on the mechanical response of the skin. Methods The method proposed optically tracks the skins recovery from an initial strain, made with a novel linear indentor, using diffuse side-lighting and a CCD video camera. Upon indentation, the skins elastin fibres are stretched and fluid is displaced from the compressed region. When the indentor is removed, the rate of recovery of the skin from this imprint is therefore principally dependent on its hydration and elasticity. Using the blue colour plane of the image and polarisation filtering, it is possible to examine the surface topography only, and track the decay of the imprint over time. Results The decrease in size of the imprint over time (decay curve) recorded by the device is shown to agree with the theoretical predictions of an appropriate viscoelastic model of skin mechanical behaviour. The contributors to the response measured using the indentation device are fully characterised and evaluated using separate measurement techniques including high-frequency ultrasound, polarisation spectroscopy and optical coherence tomography. Conclusion The device developed is capable of tracking the viscoelastic response of skin to minimal indentation. The high precision achieved using low-cost materials means that the device could be a viable alternative to current technologies.

  • 20.
    Clifford, Jenny
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Hudkliniken US.
    Karin, Cederbrant
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet.
    T-cells expressing CD4, CD45RO and CLA from gold-allergic but not healthy subjects react to gold sodium thiosufate in vitroManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Patch test positivity to gold is common in western societies, but in contrast to nickel (Ni) allergy it is uncommon that the patch test positive patient shows any clinical symptoms. In this study we investigated cytotoxic effects of gold sodium thiosulphate (GSTS) on peripheral blood mononuclear cells (PBMC), including different T-cell subsets. We also separated lymphocytes from allergic and non-allergic subjects into CD45RA and CD45R0 cell fractions. We also expressed CLA. The fraction of analyzed the effects of GSTS using lymphocyte transformation test, propidium iodide staining and flow cytometry to determine lymphocyte memory status, expression of chemokine receptors and cutaneous lymphocyte-associated antigen (CLA), and compared the results to what has previously been reported on Ni allergy. We found that only the cells from the allergic subjects proliferated in the lymphocyte transformation test (LTT), and in the CD45R0 fraction there was a dose-dependent increase in the fraction of CD3/CD4 cells. Similar to Ni-allergy, these CD3/CD4/CD45R0 cells also expressed CLA. The fraction of CD3/CD8 in the CD45R0 enriched fraction decreased with GSTS exposure. In contrast to Ni allergy, however, we found no differences between the allergic and non-allergic subjects regarding the chemokine receptors CCR4, CXCR3 and CCR10.

  • 21. Corrie, S R
    et al.
    Fernando, G J P
    Crichton, M L
    Brunck, M E G
    Anderson, Chris D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Kendall, M A F
    Surface-modified microprojection arrays for intradermal biomarker capture, with low non-specific protein binding2010Ingår i: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 10, s. 2655-2658Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Minimally invasive biosensors are of great interest for rapid detection of disease biomarkers for diagnostic screening at the point-of-care. Here we introduce a device which extracts disease-specific biomarkers directly from the upper dermis, without the needle and syringe or resource-intensive blood processing. Using antigen-specific antibodies raised in mice as a model system, we confirm the analytical specificity and sensitivity of the antibody capture and extraction in comparison to the conventional methods based on needle/syringe blood draw followed by processing and antigen-specific ELISAs.

  • 22.
    Dahlen Gyllencreutz, J.
    et al.
    Skaraborg Hospital, Sweden.
    Paoli, J.
    University of Gothenburg, Sweden.
    Bjellerup, M.
    Lund University, Sweden.
    Bucharbajeva, Z.
    Umeå University, Sweden.
    Gonzalez, H.
    University of Gothenburg, Sweden.
    Nielsen, K.
    Lund University, Sweden.
    Sandberg, C.
    University of Gothenburg, Sweden.
    Synnerstad, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Region Östergötland, Hjärt- och Medicincentrum, Hudkliniken i Östergötland. Linköpings universitet, Medicinska fakulteten.
    Terstappen, K.
    Skaraborg Hospital, Sweden.
    Wennberg Larko, A. -M.
    University of Gothenburg, Sweden.
    Diagnostic agreement and interobserver concordance with teledermoscopy referrals2017Ingår i: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 31, nr 5, s. 898-903Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

  • 23.
    Falk, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Anogenital Chlamydia trachomatis Infection Including Lympho­granuloma Venereum: Clinical Guidelines, Sweden2009Ingår i: Forum for Nordic Dermato-Venerology, ISSN 1402-2915, Vol. 14, nr 4, s. 101-103Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    [No abstract available]

  • 24.
    Falk, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Challenges of treatment for urethritis and cervicitis, (SY06:5)2012Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    Challenges of treatment for urethritis and cervicitis

     

    Urethritis in men caused by gonorrhoea is symptomatic. Non-gonorrhoic-urethritis (NGU) i.e. caused by Chlamydia trachomatis, Mycoplasma genitalium and occasionally other bacteria is in most cases an asymptomatic infection. Swartz’ definition of microscopic urethritis > 4 polymorphonucleated leucocytes (PML) per high power field (HPF) in > 4 HPF is the general accepted, but has limitations and is dependant on the sampling, microscope, the physician and the patient as well. Cervicitis is even more cumbersome since it is even more often asymptomatic. Other factors such as which contraception method is used, concurrent infections (bacterial vaginosis, candidosis), the microscope and the physician, may have a great impact. Brunham proposed as definition observed mucopurulent discharge from the cervix orifice combined with > 10 PML per HPF in stained endocervical smear. Lindner proposed sign of friability of the portio cervicis. Weström found a correlation of more PML than vaginal epithelial cells in wet mount. The variety of definitions causes problem in comparing scientific studies and at the clinic as well. The intention to treat also means testing and treatment of a current sexual partner as well.

     

    The ever emerging decreased susceptibility of various antibiotics especially against Neisseria gonorrhoeae and M. genitalium makes it even more important to choose whether to treat immediately without having positive tests or to miss a treatment of a potential serious infection. N. gonorrhoeae is visible microscopically in urethral stains from men, but can be missed in smears from endocervix and urethra in women. Cefixim 400 mg stat is the recommended first line antibiotic treatment. Ceftriaxone 500 mg is under consideration to become the first treatment of choice due to emerging decreased susceptibility. M.genitalium will be discussed in another speech by Jørgen Skov Jensen. There are some few reports of antibiotic resistance of Chlamydia trachomatis but this infection is generally still eradicated by tetracycline and macrolide treatment. In an NGU and or unspecific cervicitis doxycycline 100 mg bid for one week is the first treatment of choice. Azithromycin 1 g stat should be used with precaution. If there are persisting signs and or symptoms after doxycycline treatment, azithromycin 500 mg day 1 and 250 mg following four days should be prescribed. Bacterial vaginosis may give symptoms and signs of cervicitis and is also a very common concurrent infection in women with C. trachomatis and M.genitalium as well and treatment with metronidazole or clindamycin should be considered. The fast ways of communication via the Internet and the easy accessible and legal way of an individual to buy antibiotics just for safe or to avoid attending a clinic is a big threat now and even more in the future because of the potential rapid increasing antibiotic resistance of many bacterial infections including STIs

  • 25.
    Falk, Lars
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Urethritis and cervicitis with special reference to Chlamydia trachomatis and Mycoplasma genitalium: diagnostic and epidemiological aspects2004Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Denna avhandling vill belysa urethrit och cervicit orsakad av sexuellt överrörd sjukdom med speciellt fokus på Chlamydia trachomatis och Mycoplasma genitalium. Trots skyldighet, enligt Smittskyddslagen, att vid klamydia spåra sexuella partners till dem med infektion har antalet rapporterade klamydiafall till Smittskyddsinstitutet (SMI), efter en markant nedgång åren 1989 till 1994, ökat med cirka 10 % årligen sedan 1997. Urethrit och cervicit som orsakas av andra mikroorganismer än C traehomalis och Neisseria gonorrhoeae utgör mer än hälften av alla fall med urethrit och cervicit på en STD-mottagning. Mycoplasma genitalium, en bakterie som upptäcktes 1980, är troligen en viktig orsak.

    I arbete I och II studerades män och kvinnor som sökt STD-mottagningen vid Universitetssjukhuset Örebro (1999-2000) och som hade en genital klamydiainfektion. En metod för att sekvensera den gen (omp 1) som kodar för ett protein i bakteriens yttermembran (MOMP) utvecklades. Metoden var framgångsrik på både invasiva prover från cervix och urethra liksom urinprov och 237 prover kunde sekvenseras från 231 personer (96 kvinnor och 135 män). Alla kända genotyper för genital klamydiainfektion fanns representerade, med en uttalad ökad förekomst av genotyp E (47%), följt av F (17%). Den genetiska stabiliteten var mycket hög. I 7 av 47 (15%) sexuella nätverk (kontaktspårningskedjor) förekom diskrepanta genotyper. 90% (n=204) av de 226 som primärt sökt STD-mottagningen (93 kvinnor och 133 män) kom på återbesök och 2% (5/204) var klamydiapositiva, varav två med annan klamydiagenotyp än vid första besöket. Sanmmanlagt 161 nätverk med 688 personer hittades. Lyckad kontaktspårning, där alla individer i ett nätverk undersökts, förekom endast i 19% (30/161) av nätverken. Orsaker till misslyckande var bristfälliga uppgifter om partners från indexpatienter och att partners sökt till annan mottagning där testresultatet förblev okänt för partnerspåraren, pga sekretesslagen.

    I arbete III och IV jämfördes, mikroskopiska tecken på infektion, symptom och forekorost mellan C trachomatis och Mycoplasma genitalium infektion bland män (III) och kvinnor (IV) som sökte STD-mottagningen (2000). En undersökning av 59 unga kvinnor, kallade för cellprovskontroll (screening), där prover för C trachomatis, M genitalium och mikroskopi togs genomfordes 2002 (IV). Det fanns ingen signifikant skillnad av mikroskopiska tecken på infektion mellan dem infekterade med C trachomatis eller med M genitalium. Däremot hade kvinnor med C trachomatis eller M genitalium infektion signifikant oftare mikroskopiska tecken på infektion än kvinnor (n=58) utan någon av dessa infektioner i jämförelsegruppen. Män med M genitalium infektion hade signifikant oftare symptom än män infekterade med klamydia. Någon signifikant skillnad fanns inte i motsvarande grupper hos kvinnor. Prevalensen av M genitalium och C trachomatis infektion bland män var 7% respektive 12% (III). Av kvinnorna som sökte på STD-mottagningen hade 10% C trachomatis och 6% M genitalium infektion, medan endast en respektive ingen av de 59 kvinnorna i jämförelsegruppen var C trachomatis eller M genitalium positiva (IV). Partners till män respektive kvinnor med C trachomatis eller M genitalium infektion var signifikant oftare infekterade med motsvarande bakterie (67% respektive 63% (=kvinnliga partners) och 59%, respektive 56% (manliga partners)) än partners till patienter med urethrit eller cervicit, men med negativt test för M genitalium och C trachomatis (p<0.001). Dessa arbeten visar att M genitalium är vanligt förekommande, på STD-mottagningar, men att den inte förekommer allmänt och att den som klamydia ofta ger infektionstecken.

    I en öppen pilotbehandlingsstudie (arbete V) av M genitalium infektion, där sedvanlig tetracyklinbehandling jämfördes med azithromycin i fem dygn, visades att tetracyklin har en otillräcklig effekt, medan azithromycin tycks fungera. Randomiserade kontrollerade behandlingsstudier (RCT) behövs.

    Delarbeten
    1. Characterization of Chlamydia trachomatis omp1 genotypes among sexually transmitted sisease patients in Sweden
    Öppna denna publikation i ny flik eller fönster >>Characterization of Chlamydia trachomatis omp1 genotypes among sexually transmitted sisease patients in Sweden
    Visa övriga...
    2001 (Engelska)Ingår i: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 39, nr 11, s. 3915-3919Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A method for detection and genotyping of genital Chlamydia trachomatis infections based on omp1 gene amplification and sequencing was developed. DNA was extracted from urogenital or urine samples using a Chelex-based method, and an approximately 1,100-bp-long fragment from the omp1 gene was directly amplified and sequenced. Genotyping was performed by BLAST similarity search, and phylogenetic tree analysis was used to illustrate the evolutionary relationships between clinical isolates and reference strains. The method was used to determine the genotypes ofC. trachomatis in 237 positive urogenital and/or urine specimens collected at a Swedish sexually transmitted disease clinic during 1 year. The most common genotypes corresponded to serotypes E (47%) and F (17%). The omp1 gene was highly conserved for genotype E (106 of 112 samples without any mutation) and F (41 of 42 samples without any mutation) strains but appear slightly less conserved for genotypes G (n = 6) and H (n = 6), where the sequences displayed one to four nucleotide substitutions relative to the reference sequence. Genotyping of samples collected at the follow-up visit indicated that two patients had become reinfected, while three other patients suffered treatment failure or reinfection. One woman appeared to have a mixed infection with two different C. trachomatis strains. Thisomp1 genotyping method had a high reproducibility and could be used for epidemiological characterization of sexually transmitted Chlamydia infections.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-25864 (URN)10.1128/​JCM.39.11.3915-3919.2001 (DOI)10301 (Lokalt ID)10301 (Arkivnummer)10301 (OAI)
    Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2017-12-13
    2. Genotyping of Chlamydia trachomatis would improve contact tracing
    Öppna denna publikation i ny flik eller fönster >>Genotyping of Chlamydia trachomatis would improve contact tracing
    Visa övriga...
    2003 (Engelska)Ingår i: Sexually Transmitted Diseases, ISSN 0148-5717, E-ISSN 1537-4521, Vol. 30, nr 3, s. 205-210Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: The reported number of genital Chlamydia trachomatis infections has increased 15% annually since 1997 in Sweden. Inaccurate partner notification might be one reason.

    Goal: The goals were to determine if genotyping of C trachomatis would improve partner notification and to study the duration of infection.

    Study Design: Sexual networks were constructed. C trachomatis isolates from 231 individuals attending the Örebro STD clinic during 1 year were typed by sequencing of the omp1 gene.

    Results: All individuals were traced and diagnoses were established in 30 of 161 networks. More than one genotype was seen in seven networks. The mean duration of C trachomatis infection in each network was calculated to be 23 weeks.

    Conclusion: Genotyping could be a useful tool in partner notification when there are discrepant or uncommon genotypes. Limited clinic catchment areas create information difficulties that obstruct accurate contact tracing.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-26459 (URN)10.1097/00007435-200303000-00005 (DOI)11007 (Lokalt ID)11007 (Arkivnummer)11007 (OAI)
    Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2017-12-13
    3. Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis
    Öppna denna publikation i ny flik eller fönster >>Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis
    2004 (Engelska)Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 80, nr 4, s. 289-293Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives: To study the prevalence, symptoms, and signs of Mycoplasma genitalium and Chlamydia trachomatis infections in men attending a Swedish STD clinic and to study the criteria for urethritis.

    Methods: A cross sectional study among STD clinic attendees in Örebro, Sweden. Attendees were examined for microscopic urethritis and first void urine (FVU) was tested for M genitalium and C trachomatis.

    Results: The prevalence of M genitalium and C trachomatis was 7% (34/512) and 12% (61/512), respectively. Dual infection was diagnosed in four men. In both infections 90% of the patients had signs of microscopic urethritis. M genitalium positive men had symptomatic urethritis significantly more often than those infected with C trachomatis (73% v 40%, RR 1.8; 95% CI 1.2 to 2.7). 63% of female partners of men infected with M genitalium were infected with M genitalium compared with chlamydial infection in 67% of female partners of men infected with C trachomatis. Non-chlamydial non-gonococcal urethritis without evidence of M genitalium infection was diagnosed in 180 men (35%). Symptoms and/or visible discharge were reported in 49% in this group.

    Conclusions:M genitalium is a common infection associated with symptomatic urethritis and with a high prevalence of infected sexual partners supporting its role as a sexually transmitted infection.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-85062 (URN)10.1136/sti.2003.006817 (DOI)
    Tillgänglig från: 2012-11-01 Skapad: 2012-11-01 Senast uppdaterad: 2017-12-07
    4. Signs and symptoms of urethritis and cervicitis among women with or without Mycoplasma genitalium or Chlamydia trachomatis infection
    Öppna denna publikation i ny flik eller fönster >>Signs and symptoms of urethritis and cervicitis among women with or without Mycoplasma genitalium or Chlamydia trachomatis infection
    2005 (Engelska)Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 81, nr 1, s. 73-78Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives: To study the prevalence, symptoms, and signs of Mycoplasma genitalium and Chlamydia trachomatis infections in women attending a Swedish STD clinic, accessible for both sexes, and in a group of young women called in the cervical cancer screening programme.

    Methods: A cross sectional study among female STD clinic attendees in Örebro and a study among women called for Papanicolaou smear screening. Attendees were examined for urethritis and cervicitis. First void urine and endocervical samples were tested for M genitalium and C trachomatis.

    Results: The prevalence of C trachomatis and M genitalium in the STD clinic population was 10% (45/465) and 6% (26/461), respectively. Dual infection was diagnosed in four women. In the cancer screening group of women the corresponding prevalence was 2% (1/59) and 0%, respectively. Among the STD clinic attendees there were no significant differences in symptoms (32% v 23%, RR 1.4, 95% CI 0.6 to 3.4) or signs (71% v 50%, RR 1.4, 95% CI 0.9 to 2.3) between C trachomatis and M genitalium infections. Microscopic signs of cervicitis were significantly more common among M genitalium and C trachomatis infected women than in the cancer screening group of women. 56% (15/27) of male partners of M genitalium infected women were infected with M genitalium compared to 59% of male partners of C trachomatis infected women who were infected with C trachomatis (p = 0.80).

    Conclusions:M genitalium is a common infection associated with cervicitis and with a high prevalence of infected sexual partners supporting its role as a cause of sexually transmitted infection.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-32379 (URN)10.1136/sti.2004.010439 (DOI)18278 (Lokalt ID)18278 (Arkivnummer)18278 (OAI)
    Tillgänglig från: 2009-10-09 Skapad: 2009-10-09 Senast uppdaterad: 2017-12-13
    5. Tetracycline treatment does not eradicate Mycoplasma genitalium
    Öppna denna publikation i ny flik eller fönster >>Tetracycline treatment does not eradicate Mycoplasma genitalium
    2003 (Engelska)Ingår i: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 79, nr 4, s. 318-319Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives: To study the treatment efficacy of tetracyclines and azithromycin in Mycoplasma genitalium positive patients attending an STD clinic.

    Methods: All M genitalium positive patients (34 men and 26 women) attending an STD clinic during a 6 month period were treated with antibiotics. All patients known to be partners of M genitalium positive patients and those who were M genitalium positive, but not initially treated, were treated with azithromycin. Patients with urethritis and/or cervicitis were treated with tetracyclines before their M genitalium status was known.

    Results: 10 of 14 women (71%) and 10 of 16 men (63%) treated with tetracyclines were M genitalium positive at follow up, whereas all patients treated with azithromycin (16 men and 20 women) were M genitalium negative, at the 4 week follow up visit.

    Conclusions: These results suggest that tetracyclines are not sufficient to eradicate M genitalium. Randomised controlled treatment trials are urgently needed.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-85063 (URN)10.1136/sti.79.4.318 (DOI)
    Tillgänglig från: 2012-11-01 Skapad: 2012-11-01 Senast uppdaterad: 2017-12-07
  • 26.
    Falk, Lars
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Hegic, Sabina
    Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Wilson, Daniel
    Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Primärvården i centrala länsdelen.
    Wiréhn, Ann-Britt
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Home-sampling as a Tool in the Context of Chlamydia trachomatis Partner Notification: A Randomized Controlled Trial2014Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 94, nr 1, s. 72-74Artikel i tidskrift (Övrigt vetenskapligt)
  • 27.
    Falk, M
    et al.
    Cty Ostergotland, Res and Dev Unit Local Hlth Care, S-58185 Linkoping, Sweden .
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Influence of age, gender, educational level and self-estimation of skin type on sun exposure habits and readiness to increase sun protection2013Ingår i: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 37, nr 2, s. 127-132Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Sun exposure habits and the propensity to undertake sun protection differ between individuals. Not least in primary prevention of skin cancer, aiming at reducing ultraviolet (UV) exposure, knowledge about these factors may be of importance. The aim of the present study was to investigate, in a primary health care (PHC) population, the relationship between sun exposure habits/sun protection behaviour/readiness to increase sun protection and gender, age, educational level and skin UV-sensitivity. Methods: The baseline data from a previously performed RCT on skin cancer prevention was used. 415 patients, aged andgt;18 years, visiting a PHC centre in southern Sweden, filled-out a questionnaire mapping sun exposure, readiness to increase sun protection according to the Transtheoretical Model of Behaviour Change (TTM), and the above mentioned factors. Results: Female gender was associated with more frequent suntanning (p andlt; 0.001) and sunbed use (p andlt; 0.05), but also with more extensive sunscreen use (p andlt; 0.001). High age was in general associated with low level of sun exposure and high level of protection. Subjects with low educational level reported less frequent sunscreen use than those with higher educational level, and also chose lower SPF (p andlt; 0.001). For almost all parameters, high skin UV-sensitivity was associated with markedly lower sun exposure (p andlt; 0.001) and more pronounced readiness to increase sun protection. Females and subjects with high educational level reported higher readiness to increase sunscreen use than males and subjects with lower educational level (p andlt; 0.001). Conclusions: Gender, age, educational level and skin type appear to be important factors affecting sun exposure habits and sun protection behaviour, which supports the idea of appropriate mapping of these factors in patients in order to individualise sun protection advice according to the individual patient situation and capabilities.

  • 28.
    Falk, Magnus
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Towards a broader use of phototesting: in research, clinical practice and skin cancer prevention2007Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Under de senaste årtiondena har insjuknandet i hudcancer ökat dramatiskt i västvärlden, detta till stor del beroende på förändrade solvanor. Exponering för solens ultravioletta strålning (UVstrålning) samt den individuella ljuskänsligheten i huden utgör två viktiga faktorer av betydelse för uppkomsten av hudcancer. Individer med ökad benägenhet att bli rödbrända i solen löper också ökad risk för hudcancer av solexponering, och behöver således vara extra noga med att skydda sig mot solen. Hur känslig man är mot solljuset kan bedömas antingen genom självskattning (klassificering enligt Fitzpatrick), eller genom att använda ett ljustest. Det sistnämnda är en betydligt mer objektiv metod, men används ändå relativt sparsamt, sannolikt ofta beroende på brist på resurser, tid eller klinisk rutin.

    Det övergripande syftet med avhandlingen var att utveckla och förbättra aspekter på ljustestningsförfarandet med inriktning på att kunna bredda användningen av ljustest inom forskning, klinisk verksamhet och hudcancerprevention. Som ett första steg undersöktes och utvärderades en ny ljustestteknik, baserad på en divergent (spridd) UV-stråle. Genom att belysa huden med ett cirkulärt UV-ljusfält framkallas en cirkulär rodnad (erytem), där diametern på rodnaden står i relation till den individuella ljuskänsligheten i huden. I jämförelse med traditionell ljustestningsmetodik visade sig metoden resultera i en noggrannare uppskattning av ljuskänslighet, samt möjligheten att beskriva ett dos-responsförhållande inom det rodnade hudområdet. Eftersom kanten på den framkallade rodnaden tenderade att bli ganska diffust avgränsad framkom dock, med undantag för speciellt tränade avläsare, svårigheter att läsa av testet med enbart ögats hjälp. Av den anledningen krävdes mer objektiv, hudfysiologisk mätmetodik. I de genomförda studierna användes så kallad Laser Doppler perfusion imaging (LDPI) för detta. Förutom uppskattning av ljuskänsligheten testades den divergenta UV-strålen också som modell för skattning av anti-inflammatorisk effekt av ämnen som appliceras på huden, exempelvis cortison, och visade sig användbar för detta.

    I syfte att öka förutsättningarna för bredare användning av ljustest, genomfördes en studie där försökspersonerna själva fick avläsa ett traditionellt ljustest och rapportera in testresultatet. Resultaten jämfördes med avläsningar utförda av en kunnig avläsare, och visade på god tillförlitlighet.

    Slutligen, med hjälp av den beskrivna självavläsningsproceduren, undersöktes i en primärvårdspopulation, om ljustestning kan vara användbart för att förebygga hudcancer, med inriktning på att påverka individers solvanor, solskyddsbeteende och attityder gentemot solning. I studien jämfördes även olika modeller för att presentera ett preventionsbudskap, och där ett muntligt sådant, förmedlat vid ett läkarbesök, hade ett betydligt bättre genomslag än motsvarande, enbart skriftlig, information. För individer med hög ljuskänslighet bidrog ljustestet till ökat solskyddsbeteende, vilket indikerar att ljustest skulle kunna vara ett användbart verktyg i eftersträvan att förebygga hudcancer speciellt i denna grupp av individer med förhöjd hudcancerrisk.

    Sammanfattningsvis utgör ljustestning med divergent UV-stråle, självavläsning av ljustest samt användning av ljustest vid hudcancerprevention tre nya, tidigare sparsamt undersökta aspekter på ljustestning, för vilka den här avhandlingen visar lovande resultat.

    Delarbeten
    1. Phototesting based on a divergent beam: a study on normal subjects
    Öppna denna publikation i ny flik eller fönster >>Phototesting based on a divergent beam: a study on normal subjects
    2001 (Engelska)Ingår i: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 17, nr 4, s. 189-196Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-12817 (URN)10.1034/j.1600-0781.2001.170409.x (DOI)
    Tillgänglig från: 2007-12-05 Skapad: 2007-12-05 Senast uppdaterad: 2017-12-14
    2. Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders
    Öppna denna publikation i ny flik eller fönster >>Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders
    2008 (Engelska)Ingår i: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 14, nr 4, s. 397-402Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: In both clinical and experimental phototesting, naked eye assessment of erythema has been the main assessment parameter. As with all subjective assessment, variability in recorded results due to variable circumstances around the performance and reading of tests influences reliability and utility of data whether they be interpreted for an individual patient or for a group of research subjects.

    Methods: In the present study, variability in the reporting of diameter of ultraviolet B (UVB) erythema has been studied. The erythematous reactions were assessed by the naked eye and with the help of a millimetre-graded ruler by a group of dermatologists and dermatological trainees. Reaction size, objectively quantified by means of laser Doppler perfusion imaging (LDPI) using thresholding of the reaction perfusion, and known size of UVB provocation were used as yardsticks in order to quantify this variability.

    Results: Agreement between observers, against known size, was excellent for reactions with a sharp border, but for reactions with a diffuse or indistinct border there was a substantial inter-observer variability. This was also true for the comparison between naked-eye reading and LDPI assessment of the reaction size.

    Conclusion: It is concluded that if naked-eye readings are to be the outcome measurement, then provocations/protocols producing distinct borders are an advantage. If borders between provoked and unprovoked skin can be expected to be diffuse, i.e. part of a continuum of response, the use of objective, bioengineering techniques such as LDPI is required. Quantitative methods are also the basis for more detailed presentation and interpretation of test results including information on dose response above the minimal erythema dose.

    Nyckelord
    erythema, phototesting, UVB, LDPI, observer variability
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-12818 (URN)10.1111/j.1600-0846.2008.00305.x (DOI)
    Tillgänglig från: 2007-12-05 Skapad: 2007-12-05 Senast uppdaterad: 2017-12-14
    3. Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
    Öppna denna publikation i ny flik eller fönster >>Phototesting with a divergent UVB beam in the investigation of anti-inflammatory effects of topically applied substances
    2003 (Engelska)Ingår i: Photodermatology, Photoimmunology & Photomedicine, ISSN 0905-4383, E-ISSN 1600-0781, Vol. 19, nr 4, s. 195-202Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Phototesting based on a single exposure to a divergent ultraviolet B (UVB) beam with radially decreasing UVB doses can be used to determine an individual's minimal erythema dose (MED). Laser Doppler perfusion imaging (LDPI) data can be combined with dosimetry data to produce objective dose–response plots in addition to the MED. The aim of this study was to investigate whether the divergent beam protocol could be used to demonstrate and quantify the anti-inflammatory effects of clobetasol diproprionate (Dermovate®), pharmaceutical-grade acetone and a gel vehicle, applied after skin provocation by UVB.

    Method: Sixteen Caucasian subjects were illuminated with the divergent beam on three areas close together on the left side of their upper backs. Two of the provoked areas on each subject were treated with acetone, gel vehicle or Dermovate®, and one area was left untreated as a control. Skin blood perfusion was assessed 6 and 24 h after UVB illumination using LDPI. The reaction diameter, the mean perfusion, and the average dose–response plots for each group and treatment were extracted from the LDPI data.

    Results: Application of the topical steroid clobetasol diproprionate after UVB provocation markedly decreased the inflammatory response. Acetone and the gel vehicle also showed mild anti-inflammmatory effects in two of the parameters but not for the mean perfusion response. The mean diameter differences between controls and treated reactions had predominantly positive 99% confidence intervals. Analysis of the dose–response data at doses higher than the MED showed a linear relationship (0.89≤R2≤0.98) for all reactions but with lower gradients in treated reactions, mostly marked for clobetasol diproprionate.

    Conclusions:  The divergent beam protocol can be used to demonstrate and quantify the effects of topical agents on the UVB reaction, in terms of reaction diameter, mean perfusion and changes in dose–response characteristics. The dose–response approach seems to be applicable even in diagnostic testing of an individual patient's response to UVB.

    Ort, förlag, år, upplaga, sidor
    Wiley-Blackwell Publishing Inc., 2003
    Nyckelord
    acetone, anti-inflammatory effects, clobetasol diproprionate, erythema, gel vehicle, laser Doppler perfusion imaging, phototesting.
    Nationell ämneskategori
    Mikrobiologi inom det medicinska området
    Identifikatorer
    urn:nbn:se:liu:diva-12819 (URN)10.1034/j.1600-0781.2003.00037.x (DOI)000184575000006 ()2-s2.0-0042925506 (Scopus ID)
    Tillgänglig från: 2007-12-05 Skapad: 2007-12-05 Senast uppdaterad: 2018-01-13Bibliografiskt granskad
    4. Can patients read their own UVB minimal erythema dose and irritant skin tests
    Öppna denna publikation i ny flik eller fönster >>Can patients read their own UVB minimal erythema dose and irritant skin tests
    2010 (Engelska)Artikel i tidskrift (Refereegranskat) Submitted
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-12820 (URN)
    Tillgänglig från: 2007-12-05 Skapad: 2007-12-05 Senast uppdaterad: 2012-03-27
    5. Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest
    Öppna denna publikation i ny flik eller fönster >>Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest
    2008 (Engelska)Ingår i: European Journal of General Practice, ISSN 1381-4788, E-ISSN 1751-1402, Vol. 14, nr 2, s. 68-75Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background/objective: The high skin cancer incidence in western society, and its known association with sun exposure habits, makes the area an important target for prevention. We investigated, in a primary healthcare setting, differentiated levels of prevention efforts directed at the propensity of the patient to change his/her sun habits, sun protection behaviour, and attitudes, after information intervention. Additionally, the impact of the performance of a phototest to determine individual sun sensitivity was evaluated. Methods: 308 patients visiting a primary healthcare centre in southern Sweden completed a questionnaire concerning sun habits, sun protection behaviour, and attitudes, and were randomized into one of three groups, representing increasing levels of prevention effort in terms of resources. Feedback on their questionnaire and general preventive sun protection advice was given, in the first group by means of a letter, and in the second and third groups by a doctor's consultation. Group 3 also underwent a phototest, with a self-reading assessment and a written follow-up of the phototest result. Change of sun habits, behaviour, and attitudes, based on the Transtheoretical Model of Behaviour Change and on Likert scale scorings, was evaluated after 6 months, by a repeated questionnaire. Results: Prevention mediated by a doctor's consultation had a clearly better impact on the subjects. The addition of a phototest did not further reinforce this effect in the group as a whole, but it did for a subgroup of individuals with high ultraviolet (UV) sensitivity, as determined by the phototest itself, suggesting that this might actually be a tool to improve outcome in this high-risk group. Conclusion: A personal doctor's consultation is a valuable tool in the effective delivery of preventive information in the general practice setting. In individuals with high UV-sensitivity and thus high risk for skin cancer the performance of a photo-test reinforces a positive outcome in habits, behaviour and attitudes.

    Ort, förlag, år, upplaga, sidor
    London, UK: Informa Healthcare, 2008
    Nyckelord
    Skin cancer prevention; phototesting; behavioural change; self-assessment; questionnaire
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-12821 (URN)10.1080/13814780802423430 (DOI)
    Tillgänglig från: 2007-12-05 Skapad: 2007-12-05 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
  • 29.
    Falk, Magnus
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Vårdcentraler. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Can patients read their own UVB minimal erythema dose and irritant skin tests2010Artikel i tidskrift (Refereegranskat)
  • 30.
    Falk, Magnus
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Vårdcentraler.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Measuring sun exposure habits and sun protection behaviour using a comprehensive scoring instrument: An illustration of a possible model based on Likert scale scorings and on estimation of readiness to increase sun protection2012Ingår i: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 36, nr 4, s. 265-269Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Few attempts to present a comprehensive scoring instrument for sun exposure and protection have been made. The present paper aims to describe a possible set of questions suitable for such an instrument, comprising the most important aspects of sun exposure and protection. Methods: The material from a previously performed intervention study, using a questionnaire based on Likert scales and on the Transtheoretical Model of Behaviour Change (TTM), was utilised. 213 primary healthcare patients filled in the questionnaire and were randomised into two groups receiving sun protection advice, in Group 1 in letter-form, and in Group 2 orally during a doctor's consultation. In the original study, increased sun protection/readiness to increase sun protection was demonstrated for several items in Group 2, at six months. To compose a comprehensive scoring instrument, five questions concerning sun exposure/protection (intentional tanning, sunscreen use, choice of SPF, number of occasions with sunburn, and time spent in the sun at midday), were selected to give a 20 point behavioural score. Similarly, four TTM-based questions (giving up sunbathing, using clothes for sun protection, using sunscreens, and staying in the shade) gave a 16 point "propensity-to-change"-score. Results: At follow-up, increased sun protection reflected in the behavioural score occurred only in Group 2 (p<0.001). For the propensity-to-change-score, increased readiness to increase sun protection occurred in both groups, but the change was significantly higher in Group 2 (p<0.05). Categorisation of the 20 point behavioural score, into three risk levels, revealed a significantly higher shift of subjects moving to a lower risk level in Group 2 compared to Group 1 (p<0.05). Conclusions: In conclusion, twinning of a summarised Likert scale behavioural score with a TTM-based propensity-to-change-score seems promising for the creation of a questionnaire-based, comprehensive scoring instrument for sun exposure and protection.

  • 31.
    Falk, Magnus
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Primärvården i centrala länsdelen. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Prevention of skin cancer in primary health care: an evaluation of three different prevention effort levels and the applicability of a phototest2008Ingår i: European Journal of General Practice, ISSN 1381-4788, E-ISSN 1751-1402, Vol. 14, nr 2, s. 68-75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/objective: The high skin cancer incidence in western society, and its known association with sun exposure habits, makes the area an important target for prevention. We investigated, in a primary healthcare setting, differentiated levels of prevention efforts directed at the propensity of the patient to change his/her sun habits, sun protection behaviour, and attitudes, after information intervention. Additionally, the impact of the performance of a phototest to determine individual sun sensitivity was evaluated. Methods: 308 patients visiting a primary healthcare centre in southern Sweden completed a questionnaire concerning sun habits, sun protection behaviour, and attitudes, and were randomized into one of three groups, representing increasing levels of prevention effort in terms of resources. Feedback on their questionnaire and general preventive sun protection advice was given, in the first group by means of a letter, and in the second and third groups by a doctor's consultation. Group 3 also underwent a phototest, with a self-reading assessment and a written follow-up of the phototest result. Change of sun habits, behaviour, and attitudes, based on the Transtheoretical Model of Behaviour Change and on Likert scale scorings, was evaluated after 6 months, by a repeated questionnaire. Results: Prevention mediated by a doctor's consultation had a clearly better impact on the subjects. The addition of a phototest did not further reinforce this effect in the group as a whole, but it did for a subgroup of individuals with high ultraviolet (UV) sensitivity, as determined by the phototest itself, suggesting that this might actually be a tool to improve outcome in this high-risk group. Conclusion: A personal doctor's consultation is a valuable tool in the effective delivery of preventive information in the general practice setting. In individuals with high UV-sensitivity and thus high risk for skin cancer the performance of a photo-test reinforces a positive outcome in habits, behaviour and attitudes.

  • 32.
    Falk, Magnus
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Vårdcentraler. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Reliability of self-assessed reading of skin tests: A possible approach in research and clinical practice?2010Ingår i: Dermatologi Online, ISSN 1087-2108, E-ISSN 1087-2108, Vol. 16, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the investigation and management of skin disease, various testing protocols are of importance. The extent to which clinical judgments and decisions on therapy are supported by the performance of such testing can be affected negatively by the lack of time and resources for the performance of tests. In the present study, the possibility of utilizing self-reporting by subjects is investigated. Determination of irritation threshold for sodium lauryl sulphate (SLS) and minimal erythema dose for ultraviolet B were chosen as suitable self-reading protocols. Test reading by 26 subjects instructed in "present" or "absent" reporting of test reactions were compared to trained observer reading. Absolute agreement was found in 76.9 percent of the SLS reactions and in 85 percent of the UVB reactions. Weighted Kappa for the agreement between observations showed values of 0.76 for the SLS reactions and 0.83 for UVB reactions. We conclude that use of the protocols here studied, and other test protocols modified to accommodate a binomial assessment outcome ("+" or "-"), could well lead to an increase in the performance of skin testing. This could be a qualitative advantage for diagnosis and management of skin diseases. Additionally, population studies and even prevention initiatives could be facilitated. © 2010 Dermatology Online Journal.

  • 33.
    Falk, Magnus
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Allmänmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Vårdcentraler. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland.
    Ilias, Michail
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Inter-observer variability in reading of phototest reactions with sharply or diffusely delineated borders2008Ingår i: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 14, nr 4, s. 397-402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In both clinical and experimental phototesting, naked eye assessment of erythema has been the main assessment parameter. As with all subjective assessment, variability in recorded results due to variable circumstances around the performance and reading of tests influences reliability and utility of data whether they be interpreted for an individual patient or for a group of research subjects.

    Methods: In the present study, variability in the reporting of diameter of ultraviolet B (UVB) erythema has been studied. The erythematous reactions were assessed by the naked eye and with the help of a millimetre-graded ruler by a group of dermatologists and dermatological trainees. Reaction size, objectively quantified by means of laser Doppler perfusion imaging (LDPI) using thresholding of the reaction perfusion, and known size of UVB provocation were used as yardsticks in order to quantify this variability.

    Results: Agreement between observers, against known size, was excellent for reactions with a sharp border, but for reactions with a diffuse or indistinct border there was a substantial inter-observer variability. This was also true for the comparison between naked-eye reading and LDPI assessment of the reaction size.

    Conclusion: It is concluded that if naked-eye readings are to be the outcome measurement, then provocations/protocols producing distinct borders are an advantage. If borders between provoked and unprovoked skin can be expected to be diffuse, i.e. part of a continuum of response, the use of objective, bioengineering techniques such as LDPI is required. Quantitative methods are also the basis for more detailed presentation and interpretation of test results including information on dose response above the minimal erythema dose.

  • 34.
    Farnebo, Simon
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Karlander, Lars-Erik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Steinwall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Sjögren, Florence
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Continuous assessment of concentrations of cytokines in experimental injuries of the extremity2009Ingår i: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, Vol. 2, nr 4, s. 354-362Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Inflammation plays an important part in the healing process. Little is known about the extent local inflammatory trauma response interacts with the central circulation and inflammation produced by central organs. The aim of the present study was to examine whether high cut-off microdialysis catheters offer potential to in real time assess interstitial cytokines variations in conjunction to markers of metabolism distal to a blunt vascular contusion. Methods. In a standardised contusion trauma model, microdialysis catheters (high MW (100kDa)) were inserted in the gracilis muscle distal to the trauma for the local assessment of IL-6, IL-8, TNF-a, total protein and the metabolic mediators (glycerol, puruvate and lactate). The contra lateral uninjured leg served as control of the centrally mediated inflammation propagated to the extremities. Results. The trauma led to a significant and quantitatively large (8-10 fold) increase in inflammatory cytokines (IL6 and 8) as measured both in the injured and control legs. There was only a minor, and not significant increase in concentrations of cytokines in the injured leg compared to the control leg.. There were no signs of ischemia in either leg. Conclusion. The new finding in this study is that both central, and local, inflammatory responses as well as metabolic mediators may be assessed continuously in skeletal muscle tissue distal to a major injury in an animal model. The findings suggest that the large trauma elicits a generalised inflammatory response to trauma rather than propagating a local one distal to the trauma.

  • 35.
    Farsi Razavi, Monireh
    et al.
    Östergötlands Läns Landsting, Katastrofmedicinskt centrum.
    Falk, Lars
    Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Bjorn, Ake
    Östergötlands Läns Landsting, Katastrofmedicinskt centrum.
    Wilhelmsson, Susan
    Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland. Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad.
    Experiences of the Swedish healthcare system: An interview study with refugees in need of long-term health care2011Ingår i: SCANDINAVIAN JOURNAL OF PUBLIC HEALTH, ISSN 1403-4948, Vol. 39, nr 3, s. 319-325Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Refugees needing long-term health care must adapt to new healthcare systems. The aim of this study was to examine the viewpoints of nine refugees in a county in Sweden, with a known chronic disease or functional impairment requiring long-term medical care, on their contacts with care providers regarding treatment and personal needs. Methods: Semi-structured interviews with nine individuals and/or their next of kin. Inductive content analysis was used to identify experiences. Results: "Care organisations/resources" and "professional competence" were the categories extracted. Participants felt cared for due to accessibility to and regular appointments with the same care provider. Visiting different clinics contributed to a negative experience and lack of trust. The staffs interest in participants lives and health contributed to a sense of professionalism. Most participants said the problems experienced were not related to their backgrounds as refugees. Many patients did not fully understand which clinic they were attending or the purpose of the care that the specific clinic provided. Some lacked knowledge of their disease. Conclusions: Health care was perceived as equal to other Swedish citizens and problems experienced were not explained by refugee backgrounds. Lack of information from care providers and being sent to various levels of care created feelings of a lack of overall medical responsibility.

  • 36.
    Fredriksson, Camilla
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Hand och plastikkirurgi. Linköpings universitet, Hälsouniversitetet.
    Ilias, Michail
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    New mechanical device for effective removal of skin tags in routine health care2009Ingår i: Dermatologi Online, ISSN 1087-2108, E-ISSN 1087-2108, Vol. 15, nr 2, artikel-id 9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Skin tags (acrochordons) are exceedingly common benign skin lesions. A novel medical device in the form of a flat adhesive patch applies pressure to the base of a skin tag, leading to its removal within 3-6 days. The device was used in a clinical trial to treat and remove skin tags of the neck, upper torso, and axillae in volunteers. In this study, a total of 177 skin tags were treated in 32 individuals. One hundred seventy-two lesions fulfilled intention to treat (ITT) criteria. A majority of ITT lesions (90%) reached final assessment. Successful outcome was highest (90%) for lesions up to 1 mm in base. For lesions up to 2 mm, the rate of successful outcome was 76 percent. The desired outcome was seen in 65 percent of all ITT lesions. The cosmetic outcome after removal was excellent. Discomfort was assessed as minimal during all stages of the procedure. Analysis of data on blood flow in the skin tags during the treatment showed that the outcome was influenced by whether a decrease in blood flow was achieved immediately after application and at 2-3 days, but that the degree of occlusion was not critical. The results of this study illustrate that the device presents a new option for the management of unmet needs in the treatment of skin tags.

  • 37.
    Gao, Jingfang
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Arbman, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Wadhra, Tabasum Imran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Zhang, Hong
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Relationships of tumor inflammatory infiltration and necrosis with microsatellite instability in colorectal cancers2005Ingår i: World Journal of Gastroenterology, ISSN 1007-9327, Vol. 11, nr 14, s. 2179-2183Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The relationships between microsatellite instability (MSI) and survival in colorectal cancer patients are not consistent. The favorable survival of patient with MSI has been suggested to be related to pronounced inflammatory infiltration; however, the reason for non-association of MSI with survival is unclear. Our aims were to investigate the associations of inflammatory infiltration and tumor necrosis (TN) with microsatellite status and clinicopathological factors in colorectal cancer patients in whom MSI was not related to survival.

    Methods: Three hundred and one colorectal adenocar-cinomas were evaluated for inflammatory infiltration and 300 for TN under light microscope.

    Results: Low infiltration at invasive margin (c2 = 3.94, P = 0.047) and in whole tumor stroma (c2 = 3.89, P = 0.049) was associated with MSI, but TN was not (c2 = 0.10, P = 0.75). Low infiltration was related to advanced stage (c2 = 8.67, P = 0.03), poorer differentiation (c2 = 8.84, P = 0.03), DNA non-diploid (c2 = 10.04, P = 0.002), higher S-phase fraction (c2 = 11.30, P = 0.004), positive p53 expression (c2 = 7.94, P = 0.01), and worse survival (P = 0.03 for both univariate and multivariate analyses). Abundant TN was related to advanced stage (c2 = 17.74, P = 0.001) and worse survival (P = 0.02 for univariate, and P = 0.05 for multivariate analysis).

    Conclusion: The result that high inflammatory infiltration was not related to MSI might help explain the non-association of MSI with survival in colorectal cancer patients.

  • 38.
    Gao, Jingfang
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Zhang, Hong
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Arbman, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet.
    Sun, Xiao-Feng
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    The different roles of hRAD50 in microsatellite stable and unstable colorectal cancers2008Ingår i: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, Vol. 24, nr 2, s. 127-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    RAD50 protein is essential for DNA double-strand break repair and maintaining genomic integrity. In this study, we investigated the clinicopathological significance of hRAD50 expression and mutation in microsatellite stable (MSS) and unstable (MSI) colorectal cancers (CRCs). hRAD50 expression was examined in primary CRC (n=268), the corresponding distant (n=69) and adjacent normal mucosa (n=138), and lymph node metastasis (n=44) by immunohistochemistry. hRAD50 mutation was analyzed in 87 primary CRCs by PCR-SSCP-DNA sequencing. hRAD50 expression was increased in MSS primary CRCs, but not MSI ones, compared with distant/adjacent normal mucosa (p<0.05). There was no difference in the hRAD50 expression between primary and metastatic CRCs. The increased hRAD50 expression in MSS primary CRCs was related (p<0.05) or tended to be related (p=0.05) to early tumor stage, better differentiation, high inflammatory infiltration, p53 overexpression. Frameshift mutations of (A)_{9} at coding region of hRAD50 were only found in MSI CRCs. Our results suggest that hRAD50 may play different roles in the development of MSS and MSI CRCs: increased hRAD50 expression in MSS CRCs {may be a cellular response against tumor from further progression}, while hRAD50 mutation may be involved in the development of MSI CRCs.

  • 39. Geusens, B
    et al.
    Mollet, I
    Anderson, Chris D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Terras, S
    Roberts, M S
    Lambert, J
    Changes in skin immunity with age and disease2010Ingår i: The Innate Immune System of Skin and Oral Mucosa: Properties and Impact in Pharmaceutics, Cosmetics and Personal Care Products / [ed] Nava Dayan and Philip Wertz, Wiley , 2010Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    An in-depth look at cutting-edge research on the body's innate immune system

    Innate immunity is the body's first line of protection against potential microbial, viral, and environmental attacks, and the skin and oral mucosa are two of the most powerful barriers that which we rely on to stay well. The definitive book on the subject, Innate Immune System of Skin and Oral Mucosa: Properties and Impact in Pharmaceutics, Cosmetics, and Personal Care Products provides a comprehensive overview of these systems, including coverage of antimicrobial peptides and lipids and microbial challenges and stressors that can influence innate immunity.

    Designed to help experts and newcomers alike in fields like dermatology, oral pathology, cosmetics, personal care, and pharmaceuticals, the book is filled with suggestions to assist research and development. Looking at the many challenges facing the innate immune system, including the impact of topically applied skin products and medications, Innate Immune System of Skin and Oral Mucosa paves the way for next generation treatment avenues, preventative approaches, and drug development.

  • 40. Hansson, Johan
    et al.
    Bergenmar, Mia
    Hofer, Per-Ake
    Lundell, Goeran
    Mansson-Brahme, Eva
    Ringborg, Ulrik
    Synnerstad, Ingrid
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Bratel, Annika Ternesten
    Wennberg, Ann-Marie
    Rosdahl, Inger
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Monitoring of kindreds with hereditary predisposition for cutaneous melanoma and dysplastic nevus syndrome: Results of a Swedish preventive program2007Ingår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 25, nr 19, s. 2819-2824Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. Patients and Methods Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. Results Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. Conclusion This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.

  • 41.
    Henricson, Joakim
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Lassus, J.
    Sterisol AB, Vadstena, Sweden.
    Eklund, J.
    Sterisol AB, Vadstena, Sweden.
    Lassus, S.
    Cosmetox AB, Linkoping, Sweden.
    Anderson, Chris
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Avoidance of dermal exposure to preservatives by packaging2010Ingår i: JOURNAL OF PHARMACY AND PHARMACOLOGY, vol 62, issue 6, pp 802-802, Pharmaceutical Press , 2010, Vol. 62, nr 6, s. 802-802Konferensbidrag (Refereegranskat)
    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.

  • 42.
    Häggblad, Erik
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Petersson, Henrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Tillämpad Fysik. Linköpings universitet, Tekniska högskolan.
    Ilias, Michail A.
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Anderson, Chris D
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Salerud, Göran
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    A diffuse reflectance spectroscopic study of UV-induced erythematous reaction across well-defined borders in human skin2010Ingår i: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 16, nr 3, s. 283-290Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction The colour of tissue is often of clinicaluse in the diagnosis of tissue homeostasis andphysiological responses to various stimuli.Determining tissue colour changes and borders,however, often poses an intricate problem and visualexamination, constituting clinical praxis, does notallow them to be objectively characterized orquantified. Demands for increased inter- and intraobserverreproducibility have been incentives for theintroduction of objective methods and techniques fortissue colour (e.g. erythema) evaluation. The aim ofthe present paper was to study the border zone of anUVB provoked erythematous response of humanskin in terms of blood volume and oxygenationmeasured by means of diffuse reflectancespectroscopy using a commercial probe.

    Material and Methods A provocation model, basedon partial masking of irradiated skin areas, definestwo erythema edges at every skin site responding tothe UV irradiation. In every subject, 5 test sites wereexposed with a constant UV light irradiance (14mW/cm2), but with different exposures times (0, 3,6, 9, 12 seconds). An analysis of the spectral datameasured across the two edges was performed for every scan line. The oxygenized and deoxygenizedhemoglobin contents were estimated in everymeasurement point, using a modified Beer-Lambertmodel.

    Results The fit of the experimental data to the model derived by the modified Beer-Lambert law was excellent (R2>0.95). Analyzing data for the chromophore content showed that the erythematous response in provoked areas is dominated by the increase in oxyhemoglobin. The width for the left and right border zone was estimated to 1.81±0.93 mm and 1.90±0.88 mm respectively (M±SD). The unprovoked area between the two edges was estimated to 0.77±0.68 mm.

    Conclusion While the chosen data analysis performed satisfactory, the ability of the probe design to differentiate spatial aspects of a reaction with abrupt borders was found to be suboptimal resulting in a probable overestimation of the erythematous edge slope. Probe modification or imaging are possible solutions.

  • 43. Ivens, U.
    et al.
    Serup, Jörgen
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    O'goshi, K.
    Allergy patch test reading from photographic images: Disagreement on ICDRG grading but agreement on simplified tripartite reading2007Ingår i: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 13, nr 1, s. 110-113Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/aims: The International Contact Dermatitis Research Group (ICDRG) system for clinical scoring of allergic patch test reactions is well established in clinical dermatology for detailed scoring of allergic reactions. The degree of redness and the presence of swelling, papules, vesicles and bullae are assessed based on visual examination and palpation of reactions. In photographic assessment used in research and tele-dermatology, the scoring is solely based on visual examination of photos. The aim of the study was to evaluate inter-expert variation in patch test reading using photographic images, with ICDRG reading as a reference. Material and methods: Five experienced senior dermatologists each scored 55 positive patch test reactions from 16 slides in an office environment. The slides showed pictures of patch tests with different allergens. The scoring system by ICDRG with six categories for scoring was used. Results: The five dermatologists performed the scoring very differently. When the scoring system was simplified to a tripartite scoring system, the scoring was performed almost similarly by the five clinicians. Conclusion: Based on the present results, it is proposed that the number of scoring categories should be minimized and simplified into negative (including doubtful) reactions, positive reactions and irritant reactions. Such simplified tripartite reading is proposed for research purposes and for tele-dermatology, when scoring is based on photographic images. © Blackwell Munksgaard 2007.

  • 44.
    Johansson, Joakim
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin.
    Sjögren, Florence
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland.
    Bodelsson, Mikael
    Lund University.
    Sjöberg, Folke
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Brännskadevård. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Östergötlands Läns Landsting, Sinnescentrum, Anestesi- och operationkliniken US.
    Dynamics of leukocyte receptors after severe burns: An exploratory study2011Ingår i: BURNS, ISSN 0305-4179, Vol. 37, nr 2, s. 227-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Patients with burns are susceptible to organ failure, and there is indirect evidence that leukocytes may contribute to this process. They may change the expression of cell-surface receptors after certain stimuli, for example, the burn. We therefore aimed to assess the changes induced by the burn in the expression of leukocyte cell-surface receptors CD11b, CD14, CD16, and CD62L on the surface of PMNs and monocytes. We also wanted to examine the dynamics of this activation during the first week after the burn, and to relate it to the size of the injury. Methods: Ten patients with burns of andgt;15% (TBSA) were included in the study. Blood samples were collected on arrival and every consecutive morning during the first week. Healthy volunteers acted as controls. Results: PMN CD11b expression was increased. The extent of PMN CD11b expression correlated negatively to the size of the full thickness burn. Monocyte CD14 expression increased initially but there was no relation to the size of the burn. PMN CD16 expression decreased initially during the first days and the decrease was related to burn size. CD62L did not vary depending on the burn in either PMN or monocytes during the first week after the burn. Conclusion: This study showed that specific receptors on the surface of leukocytes (PMN CD11b, monocyte CD14 and PMN CD16) are affected by the burn. Expression of PMN CD11b and CD16 are related to burn size. Burn-induced effects on the expression of PMN receptors, such as PMN CD11b and CD16, may contribute to burn-induced infection susceptibility.

  • 45.
    Karlsson, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Cutaneous melanoma in children and adolescents and aspects of naevus phenotype in melanoma risk assessment2006Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Cutaneous malignant melanoma (CMM) is one of the most rapidly increasing cancers in the Swedish population. The aetiology of melanoma is a complex interplay between genetics, host characteristics and environmental factors. The host characteristic with the strongest association with CMM is a phenotype with high numbers of common naevi and with dysplastic naevi. The principal environmental factor is sun exposure.

    Melanoma risk assessment (paper I)

    In a multi-national study including 986 subjects from Sweden, Denmark, the UK, Germany and the Netherlands, the ability of primary care physicians and nurses to identify individuals at increased melanoma risk was assessed. The atypical mole syndrome (AMS) scoring system for melanoma risk was used. The AMS scoring system consists of a five point check list incorporating total body naevus counts, clinically dysplastic naevi and body distribution of naevi. After brief training, the overall agreement in diagnosis between the trained personnel and experienced dermatologists was 94.5% (kappa value 0.70, p<0.05). The study showed that the scoring system successfully can be taught to personnel in primary care.

    The naevus phenotype in a population in northern Sweden (paper II)

    The naevus phenotype was investigated in a population living in the inland of northern Sweden with a low melanoma incidence. Two hundred and one participants from the community of Storuman were included. The median naevus count was15 common naevi/individual, and the prevalence of dysplastic naevi was 11%. The median naevus count and prevalence of dysplastic naevi were significantly lower than previously described in populations with higher melanoma incidence and higher ambient ultraviolet exposure in southern Sweden. This geographical variation in naevus phenotype might be explained by differences in levels of sun exposure and in genotype.

    Cutaneous malignant melanoma in children and adolescents (papers III–V)

    During the years 1973 to 2002, 250 cases of primary CMM in individuals aged 0-19 years were reported to the Swedish Cancer Registry. Histological material was available for review in 87% of the cases registered during the two first decades (1973–1992). The diagnostic accuracy in the reviewed material was 88%.

    The melanoma incidence doubled in teenagers between the first decade (1973–1982) and the second (1983–1992). During the third decade (1993–2002) the increasing trend was broken. A decrease in incidence was noted in boys during 1993–1997, and in girls during 1998–2002. In younger children the incidence remained extremely low, only 4 cases in children aged 0–9 years were reported during the studied 30-year period. The trunk was the most common melanoma site in boys, and legs and trunk were the most common sites in girls. Superficial spreading melanoma was the most frequent subtype, followed by nodular melanoma. During the two first decades (1973–1992), the median melanoma thickness decreased from 1.5 to 0.9 mm. The melanoma-specific 5-year survival rate was 93%. The most important prognostic factor was melanoma thickness. The prognosis for thin lesions was excellent, during a median follow up time of 12 years, no tumour less than 0.8 mm was lethal according to the Registry.

    The results indicate that CMM in teenagers has many features in common with adult onset melanoma. The tudy also underlines the importance of not neglecting lesions suspected for malignant change in children and adolescents, as early detection and removal is crucial for the prognosis also in this young age group.

    Delarbeten
    1. Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study
    Öppna denna publikation i ny flik eller fönster >>Teaching non-specialist health care professionals how to identify the atypical mole syndrome phenotype: a multinational study
    Visa övriga...
    2000 (Engelska)Ingår i: British Journal of Dermatology, ISSN 0007-0963, Vol. 142, nr 2, s. 331-337Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The atypical mole syndrome (AMS) phenotype is the strongest known risk factor for cutaneous melanoma but recognition of the phenotype has been claimed to be problematic and to require specialist assessment. This study determined the ability of previously unskilled doctors and nurses in five countries to recognize the phenotype after brief training. The system used was the AMS scoring system. This incorporates melanocytic naevus counts, clinical atypia of naevi and distribution of naevi. The agreement in scoring between the dermatologist and trained personnel was determined in 986 patients; overall agreement in diagnosis was 94·5% (kappa 0·70, P < 0·0001). The kappa scores in different countries ranged from 0·65 to 0·77 for individual naevus characteristics, indicative of good agreement. Accurate diagnosis of the atypical mole syndrome phenotype is possible by non-specialists. This has implications for collaborative studies of naevi, for screening and for both primary and secondary prevention of melanoma.

    Nyckelord
    AMS scoring system, atypical mole syndrome, melanoma, risk factor, teaching
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14135 (URN)10.1046/j.1365-2133.2000.03405.x (DOI)
    Tillgänglig från: 2008-11-14 Skapad: 2008-11-14 Senast uppdaterad: 2009-08-19
    2. Prevalence of pigmented naevi in a Swedish population living close to the Arctic Circle
    Öppna denna publikation i ny flik eller fönster >>Prevalence of pigmented naevi in a Swedish population living close to the Arctic Circle
    2000 (Engelska)Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, Vol. 80, nr 5, s. 335-339Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The prevalence of common naevi and dysplastic naevi was investigated in a Swedish population with a low incidence of melanoma. A total of 201 subjects aged 30-50 years living in northern Sweden participated. The median number of common naevi per individual was 15, and 11% had dysplastic naevi. Higher numbers of common naevi were found in individuals with dysplastic naevi (median 68) and in those who had spent their childhood in southern Sweden (median 44). The prevalence of common naevi and dysplastic naevi was significantly lower than reported from a previously studied population in southern Sweden, with a melanoma incidence 4 times higher than in the north. The strong variability in naevus phenotype, and in melanoma incidence, between different regions of Sweden seems to be due to different levels of sun exposure rather than to differences in constitutional factors.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14136 (URN)10.1080/000155500459259 (DOI)
    Tillgänglig från: 2008-11-14 Skapad: 2008-11-14 Senast uppdaterad: 2009-08-19
    3. Increasing incidence of cutaneous malignant melanoma in children and adolescents 12–19 years of age in Sweden 1973–92
    Öppna denna publikation i ny flik eller fönster >>Increasing incidence of cutaneous malignant melanoma in children and adolescents 12–19 years of age in Sweden 1973–92
    Visa övriga...
    1998 (Engelska)Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, Vol. 78, nr 4, s. 289-292Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    One-hundred-and-seventy-seven cases of cutaneous malignant melanoma were reported to the Swedish National Cancer Registry in subjects below the age of 20 during the period 1973-92. One-hundred-and-fifty-four (87%) were re-examined histologically, and the original diagnosis of primary cutaneous malignant melanoma was verified in 88%. The age-specific mean annual incidence rate increased to 0.5/100,000 in 1983-92 from 0.2/100,000 in 1973-82. Cutaneous malignant melanoma remained extremely rare in children below the age of 12, where only two cases were found. In subjects aged 12-19, the incidence doubled to 93 cases in the second 10-year period compared to 41 in the first. In boys, most of the melanomas occurred on the trunk, and, in girls, on the legs. Sixty-three percent of the melanomas were of the superficial spreading type, which also was the most rapidly increasing type of melanoma. These results emphasize the importance of surveillance and intensified preventive measures in protecting children and adolescents from the harmful effects of excessive exposure to the sun

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14137 (URN)10.1080/000155598441882 (DOI)
    Tillgänglig från: 2008-11-13 Skapad: 2008-11-13 Senast uppdaterad: 2009-08-19
    4. Cutaneous malignant melanoma in Swedish children and teenagers 1973–1992 clinicopathological: study of 130 cases
    Öppna denna publikation i ny flik eller fönster >>Cutaneous malignant melanoma in Swedish children and teenagers 1973–1992 clinicopathological: study of 130 cases
    Visa övriga...
    1999 (Engelska)Ingår i: International Journal of Cancer, ISSN 0020-7136, Vol. 80, nr 5, s. 646-651Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    To assess whether there has been a change in histological features and prognostic factors of primary cutaneous malignant melanoma (CMM) in young individuals in Sweden, an unselected, population-based study was undertaken; 177 cases of primary CMM in persons below 20 years of age were reported to the Swedish National Cancer Registry between 1973 and 1992. In 87% of the cases, original tumor tissue was available for histo-pathological review. The original diagnosis was verified in 88% (n = 126) of these cases. All tumors had histological features similar to adult CMM; 17% had an associated precursor lesion. Superficial spreading melanoma (SSM) was the most common sub-type, constituting 20/36 cases in the first decade and 59/90 in the second. Corresponding figures for nodular melanoma (NM) were 11/36 and 23/90. Only 5 melanomas in situ were diagnosed. In girls, the mean thickness of SSM decreased from 1.5 to 0.6 mm (p < 0.001). Overall mortality was 10%, 22% in the group with CMM diagnosed 0-15 years of age and 8% in individuals 15-19 years. Fatal CMM cases diagnosed below 15 years of age (n = 4) were NM >1.6 mm thick and in subjects 15-19 years (n = 9) 44% of fatal tumors were NM with a mean thickness of 2.2 mm. Breslow index was the single most important prognostic factor. However, when known prognostic factors were adjusted for in a Cox regression analysis, young age remained an independent risk factor, with a relative death rate of 0.21 for individuals aged 15-19 compared with children <15 years of age.

    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14138 (URN)10.1002/(SICI)1097-0215(19990301)80:5<646::AID-IJC2>3.0.CO;2-H (DOI)
    Tillgänglig från: 2008-11-14 Skapad: 2008-11-14 Senast uppdaterad: 2009-08-20
    5. Cutaneous malignant melanoma in children and adolescents in Sweden, 1993–2002: the increasing trend is broken
    Öppna denna publikation i ny flik eller fönster >>Cutaneous malignant melanoma in children and adolescents in Sweden, 1993–2002: the increasing trend is broken
    2007 (Engelska)Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 121, nr 2, s. 323-328Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The incidence of cutaneous malignant melanoma rose rapidly in teenagers in Sweden during 1973-1992, while it remained low in younger children. To study the further trends and characteristics of melanoma in this young population, data on all cases in individuals under 20 years of age reported to the Swedish Cancer Registry during 1993-2002, and the corresponding pathology reports were examined. Seventy-nine cases were reported to the Registry. There were 24 males and 55 females. Most melanomas occurred on the trunk followed by the legs in both genders. The median tumor thickness was 0.8 mm. Children under age 15 had thicker melanomas than individuals aged 15-19. Superficial spreading melanoma was the most common histological subtype (43/78, 55%). The melanoma-specific 5-year survival rate was 90%. During 1993-2002, the age-standardized incidence fell to 3.6/million from 5.0/million in 1983-1992 (RR 0.74, 95% CI 0.58-0.92). The most pronounced decrease was for melanomas on the trunk in boys and on the legs in girls. The incidence for 15-19-year-old boys peaked for the cohort born between 1968 and 1972 and for girls between 1973 and 1977. The decrease in incidence may be a result of public health campaigns aiming at reducing sun exposure in childhood. A contributing effect from an increased immigration of individuals with darker complexions and at a lower melanoma risk is probable.

    Nyckelord
    childhood, adolescence, melanoma, population-based, epidemiology
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-14139 (URN)10.1002/ijc.22692 (DOI)
    Tillgänglig från: 2006-11-09 Skapad: 2006-11-09 Senast uppdaterad: 2017-12-13
  • 46. Karlsson, Pia
    et al.
    Boeryd, Bernt
    Sander, Birgitta
    Westermark, Per
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Increasing incidence of cutaneous malignant melanoma in children and adolescents 12–19 years of age in Sweden 1973–921998Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, Vol. 78, nr 4, s. 289-292Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    One-hundred-and-seventy-seven cases of cutaneous malignant melanoma were reported to the Swedish National Cancer Registry in subjects below the age of 20 during the period 1973-92. One-hundred-and-fifty-four (87%) were re-examined histologically, and the original diagnosis of primary cutaneous malignant melanoma was verified in 88%. The age-specific mean annual incidence rate increased to 0.5/100,000 in 1983-92 from 0.2/100,000 in 1973-82. Cutaneous malignant melanoma remained extremely rare in children below the age of 12, where only two cases were found. In subjects aged 12-19, the incidence doubled to 93 cases in the second 10-year period compared to 41 in the first. In boys, most of the melanomas occurred on the trunk, and, in girls, on the legs. Sixty-three percent of the melanomas were of the superficial spreading type, which also was the most rapidly increasing type of melanoma. These results emphasize the importance of surveillance and intensified preventive measures in protecting children and adolescents from the harmful effects of excessive exposure to the sun

  • 47.
    Karlsson, Pia M.
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet.
    Fredrikson, Mats
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Yrkes- och miljömedicin. Linköpings universitet, Hälsouniversitetet.
    Cutaneous malignant melanoma in children and adolescents in Sweden, 1993–2002: the increasing trend is broken2007Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 121, nr 2, s. 323-328Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The incidence of cutaneous malignant melanoma rose rapidly in teenagers in Sweden during 1973-1992, while it remained low in younger children. To study the further trends and characteristics of melanoma in this young population, data on all cases in individuals under 20 years of age reported to the Swedish Cancer Registry during 1993-2002, and the corresponding pathology reports were examined. Seventy-nine cases were reported to the Registry. There were 24 males and 55 females. Most melanomas occurred on the trunk followed by the legs in both genders. The median tumor thickness was 0.8 mm. Children under age 15 had thicker melanomas than individuals aged 15-19. Superficial spreading melanoma was the most common histological subtype (43/78, 55%). The melanoma-specific 5-year survival rate was 90%. During 1993-2002, the age-standardized incidence fell to 3.6/million from 5.0/million in 1983-1992 (RR 0.74, 95% CI 0.58-0.92). The most pronounced decrease was for melanomas on the trunk in boys and on the legs in girls. The incidence for 15-19-year-old boys peaked for the cohort born between 1968 and 1972 and for girls between 1973 and 1977. The decrease in incidence may be a result of public health campaigns aiming at reducing sun exposure in childhood. A contributing effect from an increased immigration of individuals with darker complexions and at a lower melanoma risk is probable.

  • 48.
    Karlsson, Pia
    et al.
    Linköpings universitet, Institutionen för datavetenskap. Linköpings universitet, Tekniska högskolan.
    Stenberg, Berndt
    Rosdahl, Inger
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Prevalence of pigmented naevi in a Swedish population living close to the Arctic Circle2000Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, Vol. 80, nr 5, s. 335-339Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The prevalence of common naevi and dysplastic naevi was investigated in a Swedish population with a low incidence of melanoma. A total of 201 subjects aged 30-50 years living in northern Sweden participated. The median number of common naevi per individual was 15, and 11% had dysplastic naevi. Higher numbers of common naevi were found in individuals with dysplastic naevi (median 68) and in those who had spent their childhood in southern Sweden (median 44). The prevalence of common naevi and dysplastic naevi was significantly lower than reported from a previously studied population in southern Sweden, with a melanoma incidence 4 times higher than in the north. The strong variability in naevus phenotype, and in melanoma incidence, between different regions of Sweden seems to be due to different levels of sun exposure rather than to differences in constitutional factors.

  • 49.
    Kertat, Khadua
    et al.
    Department of Experimental and Clinical Medicine Linköping University.
    Rosdahl, Inger
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Sun, Xiao-Feng
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    Synnerstad, Ingrid
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Zhang, Hong
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi.
    The Gln/Gln genotype of XPD codon 751 as a genetic marker for melanoma risk and Lys/Gln as an important predictor for melanoma progression: A case control study in the Swedish population2008Ingår i: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 20, nr 1, s. 179-183Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Xeroderma pigmentosum complementation group D (XPD) is a critical protein in the nucleotide excision repair system for DNA damage. Genetic variations in XPD exert an important effect on the capacity of DNA repair. In this study, we examined Lys751Gln polymorphism at the XPD gene in 244 melanoma patients and 251 healthy individuals (as controls) from the south-eastern region of Sweden. The associations of polymorphism with melanoma risk, as well as with melanoma features and pigment phenotypes of the melanoma patients were analysed. DNA was extracted from the mononuclear cells of venous blood of the melanoma patients and controls. XPD codon 751 was genotyped by the PCR restriction fragment length polymorphism technique. Results showed that there was no difference in the distribution of the XPD codon 751 genotypes between the melanoma patients and healthy controls. However, the Gln/Gln genotype was found to be associated with melanoma risk in the male population. Furthermore, the frequency of the Gln/Gln genotype was significantly higher in the early stages of melanomas, whereas Lys/ Gln was more frequent in the later stages and in the patients with melanoma located on intermittently UV-exposed areas. No correlations between the polymorphisms and phenotypes of the patients were found. In conclusion, Gln/Gln was a useful genetic marker for melanoma risk in the males, while Lys/Gln was an important predictor for melanoma progression.

  • 50.
    Kristjansson, S.
    et al.
    Kristjánsson, S., Department of Cancer Prevention, Stockholm Center of Public Health, Karolinska Hospital, S-171 76 Stockholm, Sweden.
    Helgason, AR.
    Helgason, ÁR., Department of Tobacco Prevention, Stockholm Center of Public Health, Stockholm, Sweden.
    Rosdahl, Inger
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Dermatologi och venerologi. Östergötlands Läns Landsting, Medicincentrum, Hudkliniken i Östergötland.
    Holm, L.-E
    Swedish Radiation Protection Institute, Stockholm, Sweden.
    Ullen, H.
    Ullén, H., Department of Cancer Prevention, Stockholm Center of Public Health, Karolinska Hospital, S-171 76 Stockholm, Sweden.
    Readiness to change sun-protective behaviour2001Ingår i: European Journal of Cancer Prevention, ISSN 0959-8278, E-ISSN 1473-5709, Vol. 10, nr 3, s. 289-296Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The incidence of malignant melanoma and non-melanoma skin cancers has increased rapidly in Sweden during the last 20 years. The best-known way to revert this trend is primary prevention. Matching health messages to readiness to change in the population may enhance the effect of community-based prevention. The aims of this study were to investigate readiness to change sun-protective behaviour in two groups (visitors to mobile screening units and beach-goers) and to test a single-item algorithm in assessing the stage of change in sun-protective behaviour. Seven hundred and forty-two visitors to the mobile screening units and 202 individuals on nearby beaches answered a short questionnaire. The assessment of readiness to change was based on stages of change in sun-protective behaviour modified from the Transtheoretical Model of Behaviour Change. As expected, the visitors to the screening units were more often in action/maintenance stages than the beach group for most sun-protective behaviours. In conclusion, the single-item algorithm method appears to be sensitive to assess readiness to change sun-protective behaviour, based on the Transtheoretical Model of Behaviour Change. This method can be incorporated into population surveys and may aid in developing successful skin cancer prevention programmes. © 2001 Lippincott Williams & Wilkins.

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