| 1. |
- Kallas, M, et al.
(författare)
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Frequency and distribution pattern of melanocytic naevi in Estonian children and the influence of atopic dermatitis
- 2006
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Ingår i: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 0926-9959 .- 1468-3083. ; 20:2, s. 143-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a strong correlation between naevus number and prospective melanoma risk. Melanoma is one of the most rapidly increasing cancers in Estonia and primary prevention programmes for melanoma that target risk behaviour in the sun have so far not been launched. Methods: The naevus profile was examined in 549/700 9-year-old Estonian children (282 boys and 267 girls) and the presence of active atopic dermatitis (AD) was registered. Results: There was a wide range of naevi (4-121) and a median total body count of 26. There was no difference in naevus count between boys and girls. No dysplastic naevi were found. Thirty-nine of 549 children (7%) had at least one lesion clinically diagnosed as a congenital naevus. Boys had more naevi on the face (median 4) and trunk (median 12) than girls (median 3 and 9, respectively, P < 0.001). Girls had more naevi on the legs compared with boys (median 4 and 3, respectively, P < 0.01). Fifty-four out of 549 (9.8%) had naevi on the palms and 18/549 (3.3%) on the soles. Children with fair skin, freckles and light hair and eye colours had significantly more naevi than those with darker colours. Thirty-one of 549 (6%) children had AD diagnosed on the examination day and they had a lower total naevus count (median 20) compared with children with no AD (median 27,n = 518, P < 0.05). Conclusions: The naevus situation in Estonian children today might constitute a starting point for evaluating the efficiency of coming preventive measures as a change of naevus number in children might serve as an early marker for a change in melanoma incidence. © 2006 European Academy of Dermatology and Venereology.
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| 2. |
- Kertat, Khadija, et al.
(författare)
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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 population
- 2008
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 20:1, s. 179-183
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Mobacken, Håkan, et al.
(författare)
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Dags att minska användningen av antibiotika vid rosacea [Time to limit the use of antibiotics in rosacea!]
- 2018
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Ingår i: Läkartidningen. - : Läkartidningen förlag. - 0023-7205 .- 1652-7518. ; 115
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Forskningsöversikt (refereegranskat)abstract
- Rosacea is a chronic inflammatory disease with facial erythema and papulopustules. It is common in middle-aged/elderly persons and often affects self-perception and social well-being. It is generally classified into four subtypes. Improved understanding of pathophysiology has resulted in novel treatment approaches, but routine management in health care usually follows old trails. Most patients are managed in primary care. Greater attention to the reduced skin barrier, avoidance of exacerbating factors, better topicals and encouragement to topical maintenance treatment should reduce the use of oral tetracyclines. Low-dose isotretinoin is reserved for treatment-resistant patients, but relapses are frequent unlike its use in acne. In order to reduce antibiotic use, we propose that patients should be referred to a dermatologist for optimization of therapy including consideration of isotretinoin following tetracycline treatment of a maximum of 4-6 months.
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| 4. |
- Orfanidis, Kyriakos, 1983-
(författare)
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Identification and clinical evaluation of senescence-associated markers to distinguish melanocytic nevi from melanomas
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Melanoma is a form of cancer that develops in melanocytes. While it represents only 5% of skin malignancies, it is the most aggressive and lethal. Benign proliferation of these cells form the melanocytic nevi. The definitive diagnosis of melanocytic nevi or melanoma lesions is histopathologic. However, it is estimated that a correct diagnosis is established by means of standard skin biopsy in only 83% of the melanocytic lesions; of the remaining cases 8% and 9% are overinterpreted (false positives) and under-interpreted (false negatives), respectively. This underscores the importance of additional diagnostic tests. Since cellular senescence is considered to be a tumor suppressive mechanism, immuno-histochemistry using senescence markers has been suggested for the evaluation of difficult melanocytic lesions; however, the routinely used senescence markers lack the ability to distinguish nevi from melanoma. The general aim of this thesis is therefore to identify novel senescence markers that may aid in melanoma diagnosis.In study I, we established a cellular model with nevus-mimicking characteristics consisting in primary melanocytes that become senescent. Transcriptomic analysis allowed expanding the set of senescence-associated markers that could distinguish nevi from melanoma and identifying tubulin β-3 as a potential diagnostic marker. Depletion of tubulin β-3 and pretreatment with tubulin destabilizing drugs in melanocytes and melanoma cells induced a senescence-like phenotype in vitro. In particular, reduced migration capacity and induction of cell cycle arrest in G2/M phase of the cell cycle was demonstrated.In study II, a potential inter-cellular signaling pathway between melanoma cells and stromal fibroblasts, that might facilitate melanoma invasion, was investigated. Ultraviolet (UV) radiation was shown, both in melanoma cells and fibroblasts, to promote the release and activation of TGF-β1 and subsequent increase in expression of the serine protease FAP-α, a protein that plays role in extracellular matrix degradation and therefore facilitates the invasion of melanoma cells. Such mechanism was not functional in senescent melanocytes.In study III, it was shown that tubulin β-3 immunostaining aids in the diagnosis of nevi and melanomas. The diagnostic criterium was the tubulin β-3 gradient within the melanocytic nevi that was no longer apparent in melanoma. Different patterns of tubulin β-3 immunostaining in melanoma were described, dermoscopy-immunohistochemistry associations were found, specific dermoscopic features highlighted, and the prognostic value of this tubulin β-3 marker was examined. The progression rate in patients whose melanomas had areas with loss of tubulin β-3 was 4 times higher than in patients without this feature, although statistical significance could not be reached (p=0.06).In conclusion, transcriptomic analysis expanded the set of senescence-associated markers that could distinguish nevi from melanoma and identified tubulin β-3 as novel immunohistochemistry marker shown to have diagnostic and probably prognostic value. From a mechanistical point of view, ultraviolet radiation was shown to promote not only the formation of melanoma but also its progression by increasing a cathepsin-TGF-β1-FAP-α pathway resulting in extracellular matrix degradation.
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| 5. |
- Sandberg, Carin, 1969, et al.
(författare)
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Important factors for pain during photodynamic therapy for actinic keratosis
- 2006
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Ingår i: Acta dermato-venereologica. - : Medical Journals Sweden AB. - 1651-2057 .- 0001-5555. ; 86:5, s. 404-8
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Tidskriftsartikel (refereegranskat)abstract
- Photodynamic therapy (PDT) is an efficient treatment for actinic keratosis. A common problem, however, is pain. The aim of this study was to investigate pain during PDT for actinic keratosis. The possibility of using capsaicin cream for pain relief was also assessed. Pain was investigated during aminolaevulinic acid PDT in 91 patients. Size, redness, scaling and induration of the lesions were recorded. Maximum pain during treatment was registered, using a visual analogue scale (0-10). The pain-reducing efficacy of capsaicin was tested in a pilot study in six patients (10 lesions). These patients were pre-treated with capsaicin cream for one week before commencing PDT. Pain was found to be normally distributed around a mean value of visual analogue scale 4.6. Larger lesions gave more pain (p=0.001). The redness of the actinic lesions was found to be related to PDT-induced pain (p=0.01), the reduction of actinic area (p=0.007), and the cure rate (p=0.01). The redder the actinic area, the better the treatment outcome and the more pain experienced. Patients with the largest reduction in the actinic area experienced more pain (p=0.053). The most important factors for presence of pain seem to be the size and the redness of the lesion. No significant pain relief was experienced after pre-treatment with capsaicin.
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| 6. |
- Sigurdardottir, Gunnthorunn, 1975-
(författare)
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Studies of the Systemic Inflammation in Psoriasis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Psoriasis is a common immune-mediated disease, where an increased prevalence of extra cutaneous diseases and mortality is observed. Common inflammatory mechanisms are implicated. The general aim of this thesis was to investigate markers of inflammation and cardiovascular disease in psoriasis, now considered a systemic disease, assumed to reflect the systemic inflammation.In Study I, Th1-, Th2- and Th17-associated chemokines were elevated in the blood of psoriasis patients in comparison to controls and, in Study II, six markers of cardiovascular risk were demonstrated to be systemically elevated. After adjustment for body mass index and waist: hip ratio in Study II, only one marker, the total plasminogen activator inhibitor-1, showed sustained elevated levels. The levels of the chemokines and the cardiovascular markers were unaffected after treatment with narrowband UVB therapy (NB-UVB), despite a significant improvement in skin lesions, indicating more local than systemic effects of NBUVB. This was further strengthened by the fact that the response to in-vitro stimulation in the peripheral blood mononuclear cells (PBMCs) of psoriasis patients before and after NB-UVB treatment was unaffected. In Study I, CCL20 was shown to correlate to the psoriasis area severity index (PASI), but this correlation was lost after phototherapy, suggesting sources of CCL20 other than the skin. Conversely, systemic treatment with TNF-α inhibition in Study II alleviated the elevated systemic levels of the cardiovascular risk markers. In Study III, the levels of 17 potential biomarkers, with the emphasis on endothelial and adipocyte dysfunction, soluble receptors and the innate mechanisms were studied. Endocan-1, CXCL16, and sVEGFR1, were found to be systemically decreased in psoriasis patients at baseline. Endocan-1 showed a negative correlation to the PASI. In contrast to the results in Studies I and II, NB-UVB therapy affected the systemic levels of investigated markers; Endocan-1 and CXCL16 were restored to normal levels, while sVEGF1, FABP3, FABP4 and sIL-1R1 showed a significant reduction following NB-UVB. In Study IV, the focus was on the contribution of innate immune mechanisms and the effects of the cytokines IL-17 and TNF-α on systemic inflammation. In keratinocytes, the gene and protein expression of inflammasome components was increased upon exposure to IL-17 and TNF-α. Systemically, the constitutive expression of the inflammasome components NLRP1, NLRP3 and AIM2 was detected in neutrophils, classical monocytes, CD4+ lymphocytes and B-cell subsets from psoriasis patients. Upon exposure to IL-17 and TNF-α, increased systemic caspase-1 levels were detected, confirming systemic inflammasome activity.In conclusion, these studies support the hypothesis that there is a systemic inflammation in psoriasis to which both innate and adaptive immune mechanisms contribute. The systemic inflammation may be explained, to some extent, but not completely, by body weight and fat distribution. The different effects of NB-UVB therapy on the systemic levels of the investigated markers may reflect their different roles in psoriasis, but the ameliorating effects of the TNF-α inhibitor on the elevated cardiovascular markers suggests that systemic treatment should be evaluated in psoriasis patients with signs of a systemic inflammatory burden.
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| 7. |
- Synnerstad, Ingrid, 1968-, et al.
(författare)
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Fewer melanocytic nevi found in children with active atopic dermatitis than in children without dermatitis
- 2004
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Ingår i: Archives of Dermatology. - : American Medical Association (AMA). - 0003-987X. ; 140:12, s. 1471-1475
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the effects of atopic diseases on nevus development during childhood. Design: A descriptive survey of nevi in a cohort of 8- and 9-year-old children combining a skin examination and a validated questionnaire regarding atopic dermatitis, allergic rhinoconjunctivitis, and bronchial asthma. Setting: Fifty-one primary schools in Sweden. Participants: A total of 788 children born in 1992 participated in 1999 in a prevalence study of allergic diseases. The present study was restricted to the 545 children from that study who were still living in the community, and 515 (94%) of them participated. The cumulative incidence of atopic dermatitis, allergic rhino-conjunctivitis, and bronchial asthma was 24%, 12%, and 13%, respectively, from birth to age 7 years as reported by questionnaire, 3% reported all 3 diagnoses. Results: Children with reported atopic dermatitis and findings of active dermatitis on examination had fewer nevi (median, 4, mean, 7.4) than children with no reported atopic disease and no active dermatitis found on examination (median, 9, mean, 11.2) (P<.001). Children who developed active atopic dermatitis after the questionnaire was filled out (ie, during the last 2 years) had fewer nevi than children with no atopic disease (median, 3, mean, 5.3) (P<.001). There was no difference in nevus number between the children with bronchial asthma or allergic rhinoconjunctivitis and children with no atopic disease. Conclusion: Children with atopic dermatitis had few melanocytic nevi, which suggests that the proinflammatory cytokine network in the atopic skin might inhibit melanocyte growth and/or progression to nevi.
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| 8. |
- Synnerstad, Ingrid, 1968-, et al.
(författare)
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Frequency and distribution pattern of melanocytic naevi in Swedish 8-9-year-old children
- 2004
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Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 84:4, s. 271-276
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Tidskriftsartikel (refereegranskat)abstract
- The naevus profile was examined in a Swedish cohort of 8-9-year-old children, 524/545 individuals (96%) were examined (279 boys and 245 girls). There was a wide variation in the total number of naevi (0-79) and boys had more naevi than girls (median 9 and 7, respectively, p<0.01). No dysplastic naevi were found. Overall, 15/524 (3%) had at least one lesion clinically diagnosed as a congenital melanocytic naevus. Boys had more naevi on the face (median 1) and trunk (median 5) than girls (median 0 and 3, respectively, p<0.001). There was no difference in the number of naevi on the legs between the two sexes. The highest counts per unit surface area for both sexes were found on the back, chest and the lateral aspect of the arms, areas intermittently sun-exposed. Children with fair skin and light eye colours had significantly more naevi than those with darker colours but children with red hair had very few naevi. Children with one or more naevi on the buttocks (25%), dorsal surfaces of the feet (11%) or on the scalp (7%) had twice as many naevi in total compared with those without naevi in these regions. Children with naevi in all three regions (0.8%) had four times as many naevi in total. A relationship between total counts and counts on the back or lateral aspect of the arms was found (r2=0.59). Either of these two areas might be suitable for predicting total naevus counts.
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| 9. |
- Tinghög, Gustav, 1979-, et al.
(författare)
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Samhällskostnader för hudcancer samt en jämförelse med kostnaderna för vägtrafikolyckor
- 2007
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Skin cancer is one of the most rapidly increasing cancers among the Swedish population and a significant cause of illness and death. The aim of this study was to from a societal perspective estimate the total cost of skin cancer in Sweden in 2005, using a combined top-down and bottom- up, prevalence based cost of illness approach. The total cost of skin cancer was estimated to 1,25 billion SEK (1 €= 9,3 SEK). The direct costs were estimated to 665 million SEK and constituted 53 percent of the total cost. Indirect costs were estimated to 583 million SEK and constituted 47 percent of the total cost. The main cost driver was production lost caused by premature death, amounting to 39 percent of the total cost.In addition, this study compares the cost of skin cancer with the costs arising from road traffic accidents. Focusing on the methodological differences that arise when comparing economic cost founded on similar but yet different methods when conducting cost analysis. We demonstrate that the seemingly large difference between the cost of skin cancer and the cost arising from road traffic accident, in reality is not as large as it first appear.
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| 10. |
- Wyon, Yvonne, 1960-, et al.
(författare)
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Spectrophotometric analysis of melanocytic naevi during pregnancy
- 2007
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Ingår i: Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 87:3, s. 231-237
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Tidskriftsartikel (refereegranskat)abstract
- Malignant melanoma is the most common cancer during pregnancy, but it is unknown whether melanocytic naevi in general are activated. A total of 381 melanocytic naevi in 34 Caucasian primigravidae were examined using spectrophotometric intracutaneous analysis (SIAscopy) technology in early pregnancy and prior to delivery. The Siagraphs of each naevus were then compared in order to evaluate changes over time. A total of 163 melanocytic naevi in 21 nulliparous women served as an additional control group. At the first visit none of the Siagraphs examined for the case or control groups aroused suspicion of dysplastic naevus or melanoma and no significant structural changes were noted during the observation period. However, 2.1% of the melanocytic naevi in the pregnant group increased and 1.3% decreased in size. Corresponding figures in the non-pregnant group were 1.8% and 0%, respectively. Only one naevus in a pregnant woman increased slightly in epidermal pigmentation, and a decrease in pigmentation was noted in 3.7% of the melanocytic naevi in the cases and 1.8% in the controls. None of the differences within or between the groups was statistically significant. We conclude that pregnancy does not influence the appearance of pigmented naevi. A changing naevus during pregnancy should be examined carefully and considered for excision and histopathology. © 2007 Acta Dermato-Venereologica.
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