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Träfflista för sökning "AMNE:(MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Dermatologi och venereologi) srt2:(2010-2014)"

Sökning: AMNE:(MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Dermatologi och venereologi) > (2010-2014)

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2.
  • Josefson, Anna (författare)
  • Nickel allergy and hand eczema : epidemiological aspects
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Nickel allergy is the most prevalent contact allergy and has been discussed as a possible riskfactor for hand eczema. However, hand eczema is one of the most frequently occurring skindiseases and has multifactorial origin. The aim of this thesis was to study the association between nickel allergy and hand eczema in the general population. There are only a fewpopulation-based studies previously published, that include patch testing. In addition, this thesis aimed to evaluate methods to follow the prevalence of nickel allergy.The study cohort consisted of 908 women who had been patch tested for the occurrence of nickel allergy as schoolgirls. Twenty years later, they were invited to participate in a follow-up questionnaire study. The response rate was 81%. In total, 17.6% of respondents reported handeczema after the age of 15 years and there was no statistically significant difference in the occurrence of hand eczema between those who were nickel-positive and those who were nickel negativeas schoolgirls. To further investigate possible links, another study was performed,which included a second questionnaire, a clinical investigation and patch testing. All schoolgirls from the baseline study who were still living in the area as adults were invited to participate and the participation rate was 77%. Patch test showed 30.1% nickel-positive individuals.When all participants were included in the analysis, there was no statistically significant difference between nickel-positive and nickel-negative women regarding occurrence of hand eczema. The most important risk factor for hand eczema was childhood eczema. Adjusted prevalence proportion ratio (PPR) for hand eczema after age 15 in relation to nickel patch testresults was 1.03 (95% CI 0.71--1.50) and in relation to childhood eczema 3.68 (95% CI 2.45--5.54). When women with and without history of childhood eczema were analyzed separately, the hand eczema risk was doubled in nickel-positive women without history of childhood eczema. In conclusion, the risk of hand eczema in nickel-positive women may previously havebeen overestimated. Next, the validity of self-reported nickel allergy was investigated. In the established cohort; two questions regarding nickel allergy were compared with patch test results. The validity of self-reported nickel allergy was low, and the questions regarding nickel allergy overestimated the true prevalence of nickel allergy. The positive predictive values were 59% and 60%. Another method for estimating the prevalence of nickel allergy, namely self-patch testing, was validated in the last study. In total, 191 patients from three different dermatology departments participated. The validity of self-testing for nickel allergy was adequate, with sensitivity 72%and proportion of agreement 86%.
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3.
  • Josefson, Anna, et al. (författare)
  • Validation of self-testing as a method to estimate the prevalence of nickel allergy
  • 2011
  • Ingår i: Acta Dermato-Venereologica. - : Society for Publication of Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 91:5, s. 526-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Valid epidemiological tools are required for surveillance of the prevalence of contact allergy. Population based studies including patch testing is the most reliable method, but implies heavy expenses and logistical problems. Clinical data are not representative for the general population and questionnaires concerning contact allergy have a low validity. Self-testing might be a useful method but it has to be validated and evaluated.Objectives: To investigate the validity of self-patch testing for nickel allergy. Methods: Patients from three dermatology clinics were included consecutively when referred to patch testing. In total, 191 patients participated and they were provided with a self-test package including written instructions. The self-test was applied on the arm by the patient, on the same day as the patch test was applied on the back, in the clinic. The patient evaluated the self-test before the patch test reading at the clinic.Results: Patch test at dermatology clinic (‘gold standard’) gave 46/191 (24%) nickel-positive individuals. The sensitivity of the self-test was 72% (95% CI 57–84), the specificity was 91% (95% CI 85–95) and the proportion of agreement was 86% (95% CI 81–91).Conclusions: The validity of self-testing for nickel allergy was adequate in the studied population. To determine whether self-testing is a useful tool for measuring the prevalence of nickel allergy in the general population further studies will be needed.
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4.
  • Josefson, Anna, et al. (författare)
  • Validity of self-reported nickel allergy
  • 2010
  • Ingår i: Contact Dermatitis. - Oxford : Wiley. - 0105-1873 .- 1600-0536. ; 62:5, s. 289-293
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: To estimate the prevalence of nickel allergy, self-reports are sometimes used in epidemiological studies. Self-reports are practical and may facilitate estimation of prevalence provided that the questions are validated.Objectives: To investigate the validity of self-reported nickel allergy.Methods: Three hundred and sixty-nine women, aged 30–40 years, from the general population participated in the study. The participants answered a questionnaire before a clinical examination and patch testing. The two questions being validated were ‘Are you sensitive/hypersensitive/allergic to nickel?’ and ‘Do you get a rash from metal buttons, jewellery or other metal items that come in direct contact with your skin?’Results: Patch test showed nickel-positive reaction in 30% of the subjects. Self-reported prevalence of nickel allergy as indicated by the two respective questions was 40% and 35%. Positive predictive values for the two questions were 59% (95% CI 50–67) and 60% (95% CI 51–69). History of childhood eczema was over-represented among women with ‘false-positive’ self-reported nickel allergy (P = 0.008). Self-reported hand eczema or ‘high wet exposure’ did not influence the validity.Conclusions: The validity of self-reported nickel allergy is low. The questions regarding nickel allergy overestimate the true prevalence of nickel allergy.
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5.
  • Franck, Niclas, et al. (författare)
  • Identification of adipocyte genes regulated by caloric intake
  • 2011
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine society. - 0021-972X .- 1945-7197. ; 96:2, s. E413-E418
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Changes in energy intake have marked and rapid effects on metabolic functions and some of the effects may be due to changes in adipose tissue gene expression that precede alterations in body weight. OBJECTIVE: To identify genes in adipose tissue regulated by changes in caloric intake independent of changes in body weight. RESEARCH DESIGN AND METHODS: Obese subjects were given a very-low calorie diet (VLCD; 450 kcal/day) for 16 weeks. After the diet, ordinary food was gradually reintroduced during 2 weeks while there were minimal changes in body weight. Adipose tissue gene expression was measured by microarray analysis. First, genes regulated during caloric restriction and in the opposite direction during the weight stable re-feeding phase were identified. To verify opposite regulation to that observed during caloric restriction, identified genes were further analyzed using adipocyte expression profiles from healthy subjects before and after overfeeding. Results were confirmed using real time PCR or immunoassay. RESULTS: Using a significance level of p<0.05 for all comparisons, 52 genes were downregulated and 50 were up-regulated by caloric restriction and regulated in the opposite direction by re-feeding and overfeeding. Among these were genes that affect lipogenesis (ACLY, ACACA, FASN, SCD), protein synthesis (4EBP1, 4EBP2), beta-oxidation (CPT1B), liberation of fatty acids (CIDEA) and glyceroneogenesis (PCK2). Interestingly, several of these are under control of the master regulator mTOR. CONCLUSIONS: The observed transcriptional changes indicate that mTOR plays a central role in the control of diet-regulated adipocyte genes involved in lipogenesis and protein synthesis.
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6.
  • Johansson, Joakim, et al. (författare)
  • Dynamics of leukocyte receptors after severe burns: An exploratory study
  • 2011
  • Ingår i: BURNS. - Oxford : Elsevier Science B.V., Amsterdam.. - 0305-4179 .- 1879-1409. ; 37:2, s. 227-233
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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7.
  • Lyth, Johan, et al. (författare)
  • Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion : results of a population-based study from the Swedish Melanoma Register
  • 2013
  • Ingår i: British Journal of Dermatology. - : Wiley-Blackwell. - 0007-0963 .- 1365-2133. ; 168:4, s. 779-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Background  Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed.Objectives  The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark’s level of invasion for risk stratification of T1 cutaneous melanoma.Methods  From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data.Results  Ulceration, tumour thickness and Clark’s level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2–1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0–7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2–21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1.Conclusions  Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark’s level of invasion, three distinct prognostic subgroups were identified.
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8.
  • Walser, Marion, 1961, et al. (författare)
  • Peripheral administration of bovine GH regulates the expression of cerebrocortical beta-globin, GABAB receptor 1, and the Lissencephaly-1 protein (LIS-1) in adult hypophysectomized rats.
  • 2011
  • Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1532-2238. ; 21:1, s. 16-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth hormone (GH) therapy substantially improves several cognitive functions in hypopituitary experimental animals and in humans. Although a number of biochemical correlates to these effects have been characterized, there are no comprehensive analysis available examining effects of GH on the brain. Hypophysectomized female rats were given replacement therapy with cortisol and thyroxine (=hx). Subcutaneous infusions of bovine GH (bGH, henceforth designated GH) were supplied in osmotic minipumps for 6 days (=hx+GH). To evaluate whether GH normalized specific transcript expression levels in cerebral cortex, pituitary-intact rats were used as normal controls. DNA microarrays (Affymetrix) of cerebrocortical samples showed that 24 transcripts were changed by more than 1.5-fold by GH treatment in addition to being normalized by GH treatment. The expression of three selected highly regulated transcripts was confirmed by quantitative real-time polymerase chain reaction analysis. These were the GABAB receptor 1, Lissencephaly-1 protein (LIS-1), and hemoglobin b or beta-globin. A similar regulation was found for hemoglobin b also in the hippocampus. Both the GABAB receptor 1 and hemoglobin b may have importance for the previously described neuroprotective and perhaps cognitive potential of GH treatment. Altogether, these results show that short term GH treatment affects a number of transcripts in cerebral cortex with various biological functions. These transcripts represent potential novel mechanisms by which GH can interact with the brain.
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  • Albertsson, Daniel M, 1957, et al. (författare)
  • Hip and fragility fracture prediction by 4-item clinical risk score and mobile heel BMD: a women cohort study
  • 2010
  • Ingår i: BMC Musculosceletal disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background One in four Swedish women suffers a hip fracture yielding high morbidity and mortality. We wanted to revalidate a 4-item clinical risk score and evaluate a portable heel bone mineral density (BMD) technique regarding hip and fragility fracture risk among elderly women. Methods In a population-based prospective cohort study we used clinical risk factors from a baseline questionnaire and heel BMD to predict a two-year hip and fragility fracture outcome for women, in a fracture preventive program. Calcaneal heel BMD was measured by portable dual X-ray laser absorptiometry (DXL) and compared to hip BMD, measured with stationary dual X-ray absorptiometry (DXA) technique. Results Seven women suffered hip fracture and 14 women fragility fracture/s (at hip, radius, humerus and pelvis) among 285 women; 60% having heel BMD ≤ -2.5 SD. The 4-item FRAMO (Fracture and Mortality) Index combined the clinical risk factors age ≥80 years, weight <60 kg, prior fragility fracture, and impaired rise-up ability. Women having 2-4 risk factors showed odds ratio (OR) for hip fracture of 5.9 and fragility fracture of 4.4. High risk group hip fracture risk was 2.8% annually compared to 0.5% for the low risk majority (69%). Heel BMD showed hip fracture OR of 3.1 and fragility fracture OR of 2.6 per SD decrease. For 30 DXA assessed participants mean hip BMD at -2.5 SD level corresponded to a lower BMD at the heel. Five of seven hip fractures occurred within a small risk group of 32 women, identified by high FRAMO Index + prior fragility fracture + heel T-score ≤-3.5 SD. Conclusions In a follow-up study we identified high risk groups for hip and fragility fracture with our plain 4-item risk model. Increased fracture risk was also related to decreasing heel BMD in calcaneal bone, measured with a mobile DXL technique. A combination of high FRAMO Index, prior fragility fracture, and very low BMD restricted the high risk group to 11%, among whom most hip fractures occurred (71%). These practical screening methods could eventually reduce hip fracture incidence by concentrating preventive resources to high fracture risk women.
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10.
  • Eldh, Maria, 1980, et al. (författare)
  • MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma
  • 2014
  • Ingår i: BMC Cancer. - London : Springer Science and Business Media LLC. - 1471-2407. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Uveal melanoma is a tumour arising from melanocytes of the eye, and 30 per cent of these patients develop liver metastases. Exosomes are small RNA containing nano-vesicles released by most cells, including malignant melanoma cells. This clinical translational study included patients undergoing isolated hepatic perfusion (IHP) for metastatic uveal melanoma, from whom exosomes were isolated directly from liver perfusates. The objective was to determine whether exosomes are present in the liver circulation, and to ascertain whether these may originate from melanoma cells.
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11.
  • Dahl, Anna K., et al. (författare)
  • Agreement between self-reported and measured height, weight and body mass index in old age : a longitudinal study with 20 years of follow-up
  • 2010
  • Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 39:4, s. 445-451
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: self-reported body mass index (BMI) based on self-reported height and weight is a widely used measure of adiposity in epidemiological research. Knowledge about the accuracy of these measures in late life is scarce.Objective: the study aimed to evaluate the accuracy and changes in accuracy of self-reported height, weight and BMI calculated from self-reported height and weight in late life.Design: a longitudinal population-based study with five times of follow-up was conducted.Participants: seven hundred seventy-four community-living men and women, aged 40–88 at baseline (mean age 63.9), included in The Swedish Adoption/Twin Study of Aging.Methods: participants self-reported their height and weight in a questionnaire, and height and weight were measured by experienced research nurses at an in-person testing five times during a 20-year period. BMI was calculated as weight (kilogramme)/height (metre)2.Results: latent growth curve modelling showed an increase in the mean difference between self-reported and measured values over time for height (0.038 cm/year) and BMI (0.016 kg/m2/year), but not for weight.Conclusions: there is a very small increase in the mean difference between self-reported and measured BMI with ageing, which probably would not affect the results when self-reported BMI is used as a continuous variable in longitudinal studies.
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12.
  • Sonkoly, Enikö, et al. (författare)
  • Protein kinase C-dependent upregulation of miR-203 induces the differentiation of human keratinocytes
  • 2010
  • Ingår i: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 130:1, s. 124-134
  • Tidskriftsartikel (refereegranskat)abstract
    • Terminal differentiation of keratinocytes is a multistep process that requires a coordinated program of gene expression. We aimed to explore the possible involvement of a previously unreported class of non-coding RNA genes, microRNAs (miRNAs) in keratinocyte differentiation by using miRNA expression profiling. Out of 365 miRNAs tested, 7 showed significant change between keratinocytes cultured in low or high calcium concentration. The highest-ranked upregulated gene was miR-203, whose expression was significantly upregulated in response to calcium and other inducers of keratinocyte differentiation such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and vitamin D(3). Differentiation-induced upregulation of miR-203 expression was blocked by treatment with specific inhibitors of protein kinase C (PKC), GF109203X, and Ro31-8220. Moreover, our results showed that the activator protein-1 (AP-1) proteins c-Jun and JunB regulate miR-203 expression in keratinocytes. In contrast to inducers of keratinocyte differentiation, epidermal growth factor and keratinocyte growth factor suppressed miR-203 expression in keratinocytes below the basal level. Overexpression of miR-203 in keratinocytes resulted in enhanced differentiation, whereas inhibition of miR-203 suppressed calcium-induced terminal differentiation as judged by involucrin expression. These results suggest that upregulation of miR-203 in human keratinocytes is required for their differentiation and is dependent on the activation of the PKC/AP-1 pathway.
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  • Bingefors, Kristina, et al. (författare)
  • Self-reported lifetime prevalence of atopic dermatitis and co-morbidity with asthma and eczema in adulthood : a population-based cross-sectional survey
  • 2013
  • Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 93:4, s. 438-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Atopic dermatitis and its co-morbidity with asthma and allergy is well described in younger age groups. However, population-based studies on adults with atopic dermatitis in childhood are sparse. The aims of this study were to determine: (i) the prevalence of self-reported childhood atopic dermatitis in the population; and (ii) its association with present self-reported hand eczema, eczema, allergy, urticaria and asthma. A questionnaire was sent to a cross-sectional random sample of the Swedish population (n = 7,985), age range 18–84 years (response rate 61.1%). The questionnaire included the question “Have you had childhood eczema?” and questions on 5 other medical problems (hand eczema, other eczema, asthma, urticaria and allergy). Persons reporting eczema in childhood reported increased odds ratios (OR) for hand eczema (4.01), other eczema (3.88), urticaria (2.50), allergy (2.98), and asthma (2.06) as adults. The combination of eczema, allergy and asthma had an OR of 14.10 (95% confidence interval 8.44–23.54). Adults in the age range 18–84 years reporting childhood atopic dermatitis still have high co-morbidity with eczema, asthma, urticaria and allergy.
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15.
  • Falk, Lars, 1954-, et al. (författare)
  • Sampling for Chlamydia trachomatis infection : a comparison of vaginal, first-catch urine, combined vaginal and first-catch urine and endocervical sampling
  • 2010
  • Ingår i: International Journal of STD and AIDS (London). - : SAGE Publications. - 0956-4624 .- 1758-1052. ; 21:4, s. 283-287
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study was to evaluate the sensitivity of patients' self-sampled vaginal specimens, first-catch urine (FCU), combined vaginal/FCU specimens and endocervical specimens for detecting chlamydial infection in women. Women attending sexually transmitted disease clinics, youth clinics and a women's health clinic were enrolled. They self-collected a vaginal specimen with two swabs, which were placed into a sterile tube and into a tube containing a buffer medium, respectively. An FCU sample was collected and aliquoted into both an empty tube and the tube containing the vaginal swab. A clinician collected an endocervical swab. The samples were sent to laboratories for analysis using polymerase chain reaction testing and strand displacement amplification testing, respectively. The sensitivities calculated in all 171 Chlamydia trachomatis-infected women were equal for endocervical specimens (97.1%), vaginal specimens (96.5%) and combined vaginal/FCU specimens (95.3%), whereas the sensitivity for FCU was significantly lower (87.7%). The sensitivity of vaginal specimens for the detection of C. trachomatis is as high as that of combined vaginal/FCU specimens.
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  • Svensson, Sara L, et al. (författare)
  • Midkine and Pleiotrophin have bactericidal properties : preserved antibacterial activity in a family of Heparin-binding growth factors during evolution
  • 2010
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:21, s. 16105-16115
  • Tidskriftsartikel (refereegranskat)abstract
    • Antibacterial peptides of the innate immune system combat pathogenic microbes, but often have additional roles in promoting inflammation and as growth factors during tissue repair. Midkine (MK) and pleiotrophin (PTN) are the only two members of a family of heparin-binding growth factors. They show restricted expression during embryogenesis and are up-regulated in neoplasia. In addition, MK shows constitutive and inflammation-dependent expression in some non-transformed tissues of the adult. In the present study, we show that both MK and PTN display strong antibacterial activity, present at physiological salt concentrations. Electron microscopy of bacteria and experiments using artificial lipid bilayers suggest that MK and PTN exert their antibacterial action via a membrane disruption mechanism. The predicted structure of PTN, employing the previously solved MK structure as a template, indicates that both molecules consist of two domains, each containing three antiparallel beta-sheets. The antibacterial activity was mapped to the unordered C-terminal tails of both molecules and the last beta-sheets of the N-terminals. Analysis of the highly conserved MK and PTN orthologues from the amphibian Xenopus laevis and the fish Danio rerio suggests that they also harbor antibacterial activity in the corresponding domains. In support of an evolutionary conserved function it was found that the more distant orthologue, insect Miple2 from Drosophila melanogaster, also displays strong antibacterial activity. Taken together, the findings suggest that MK and PTN, in addition to their earlier described activities, may have previously unrealized important roles as innate antibiotics.
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19.
  • Krynitz, Britta, et al. (författare)
  • Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008 : A Swedish population-based study
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:6, s. 1429-1438
  • Tidskriftsartikel (refereegranskat)abstract
    • Organ transplant recipients are at increased risk of a wide range of malignancies, especially cutaneous squamous cell carcinomas (SCC). Few previous population-based studies have quantified and compared cancer risks according to graft type and with long-term follow-up. Using nationwide Swedish registers, we identified 10,476 recipients transplanted from 1970 to 2008 and followed them for cancer occurrence. Relative risks of cancer in comparison with the general population were expressed as standardized incidence ratios (SIR) and within the transplanted cohort as incidence rate ratios (IRR). During a total follow-up of 93,432 person-years, patients were diagnosed with 1,175 cancers excluding SCC, and with 2,231 SCC, SIRcancer excl SCC 2.4 (95% CI, 2.2–2.5); SIRSCC 121 (95% CI, 116–127). Cancer risks were most increased among heart and/or lung recipients SIRcancer excl SCC 3.3 (95% CI, 2.8–4.0); SIRSCC 198 (95% CI, 174–224), followed by kidney SIRcancer excl SCC 2.3 (95% CI, 2.1–2.4); SIRSCC 121 (95% CI, 116–127) and liver recipients SIRcancer excl SCC 2.3 (95% CI, 1.9–2.8); SIRSCC 32 (95% CI, 24–42). During follow-up, risk of cancer excluding SCC remained stable while risk of SCC tripled over 20 years irrespective of graft type, partly due to a subgroup of patients developing new SCCs at a rapidly increasing rate. In summary, post-transplant cancer risk varied by transplanted organ and by cancer site, with the bulk of the excess risk driven by an exceptionally high and accelerating risk of SCC. These findings underscore the importance of regular skin screening in organ transplant recipients.
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21.
  • Hjelmevoll, Stig Ove, et al. (författare)
  • Appropriate Time for Test-of-Cure when Diagnosing Gonorrhoea with a Nucleic Acid Amplification Test
  • 2012
  • Ingår i: Acta Dermato-Venereologica. - Uppsala : Acta Dermato-Venereologica. - 0001-5555 .- 1651-2057. ; 92:3, s. 316-319
  • Tidskriftsartikel (refereegranskat)abstract
    • Culture is commonly regarded as the gold standard for diagnosis of Neisseria gonorrhoeae. However, nucleic acid amplification tests (NAATs) have rapidly replaced culture for diagnostics in many settings. The aim of the present study was to investigate the appropriate time for test-of-cure (TOC) when NAATs are used for diagnosis of gonorrhoea. In total, 30 patients (28 men and 2 women) provided urethral, cervical, rectal or pharyngeal specimens for TOC. All included patients, except one who did not return for second TOC before day 19, tested negative within 2 weeks after treatment with cefixime 400 mg x 1. Antimicrobial susceptibility testing showed that 68% of the culture-positive strains were resistant to ciprofloxacin. Thus, the recommended empirical treatment with ciprofloxacin in Norway should be changed immediately. TOC can be performed 2 weeks after treatment when NAATs are used for diagnosis of gonorrhoea.
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22.
  • Kasetty, Gopinath, et al. (författare)
  • Structure-Activity Studies and Therapeutic Potential of Host Defense Peptides of Human Thrombin
  • 2011
  • Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 55:6, s. 2880-2890
  • Tidskriftsartikel (refereegranskat)abstract
    • Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length-and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (> 12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.
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23.
  • Trimpou, Penelope, 1973, et al. (författare)
  • Male risk factors for hip fracture-a 30-year follow-up study in 7,495 men.
  • 2010
  • Ingår i: Osteoporosis international. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 21:3, s. 409-416
  • Tidskriftsartikel (refereegranskat)abstract
    • Risk factors for hip fracture were studied in 7,495 randomly selected men during 30 years; 451 men had a hip fracture. High degree of leisure-time, but not work-related, physical activity, high occupational class, and high body mass index (BMI) protected against hip fracture. Smoking, tall stature, interim stroke, and dementia increased the risk. PURPOSE: The purpose was to prospectively study risk factors for hip fracture in men. METHODS: We studied midlife determinants of future hip fractures in 7,495 randomly selected men aged 46-56 years in Gothenburg, Sweden. The subjects were investigated in 1970-1973 and followed for over 30 years. Questionnaires were used regarding lifestyle factors, psychological stress, occupational class, and previous myocardial infarction, stroke, and diabetes mellitus. Alcohol problems were assessed with the aid of registers. Using the Swedish hospital discharge register, data were collected on intercurrent stroke and dementia diagnoses and on first hip fractures (X-ray-verified). RESULTS: Four hundred fifty-one men (6%) had a hip fracture. Age, tall stature, low occupational class, tobacco smoking, alcoholic intemperance, and interim stroke or dementia were independently associated with the risk of hip fracture. There were inverse associations with leisure-time physical activity, BMI, and coffee consumption. The gradient of risk for one standard deviation of multivariable risk decreased with time since measurement yet was a good alternative to dual energy X-ray absorptiometry measurements. CONCLUSIONS: High degree of leisure-time physical activity, high occupational class, and high BMI protected against hip fracture. However, work-related physical activity was not protective. Smoking, tall stature, and interim stroke or dementia increased the risk.
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24.
  • Shen, Yue, 1981- (författare)
  • Plasminogen : a novel inflammatory regulator that promotes wound healing
  • 2013
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The plasminogen activator (PA) system has been shown to be intimately involved in wound healing. However, the role of this system in the initiation and resolution of inflammation during healing process remained to be determined. The aims of this thesis were to investigate the molecular mechanism underlying the interaction between the PA system and the inflammatory system during wound healing and to explore the therapeutic potential of plasminogen in various wound-healing models.The role of plasminogen in the inflammatory phase of the healing process of acute and diabetic wounds was studied first. Our data showed that administration of additional plasminogen to wild-type mice accelerates the healing of acute wounds. After injury, both endogenous and exogenous plasminogen are bound to inflammatory cells and are transported to the wound site, which leads to activation of inflammatory cells. In diabetic db/db mice, wound-specific accumulation of plasminogen does not take place and the inflammatory response is impaired. However, when additional plasminogen is injected, plasminogen accumulates in the wound, the inflammatory response is enhanced, the signal transduction cascade is activated and the healing rate is significantly increased. These results indicate that administration of plasminogen may be a novel therapeutic strategy to treat different types of wounds, especially chronic wounds in diabetes.The role of plasminogen at the later stage of wound healing was also studied in plasminogen-deficient mice. Our data showed that even if re-epithelialization is achieved in these mice, a prolonged inflammatory phase with abundant neutrophil accumulation and persistent fibrin deposition is observed at the wound site. These results indicate that plasminogen is also essential for the later phases of wound healing by clearing fibrin and resolving inflammation.The functional role of two physiological PAs during wound healing was further studied in a tympanic membrane (TM) wound-healing model. Our data showed that the healing process was clearly delayed in urokinase-type PA (uPA)-deficient mice but not in tissue-type PA (tPA)-deficient mice. Less pronounced keratinocyte migration, abundant neutrophil accumulation and persistent fibrin deposition were observed in uPA-deficient mice. These results indicate that uPA plays a central role in the generation of plasmin during the healing of TM perforations.Finally the therapeutic potential of plasminogen in the TM wound-healing model was studied. Our data showed that local injection of plasminogen restores the ability to heal TM perforations in plasminogen-deficient mice in a dose-dependent manner. Plasminogen supplementation also potentiates healing of acute TM perforations in wild-type mice, independent of the administration method used. A single local injection of plasminogen in plasminogen-deficient mice can initiate healing of chronic TM perforations resulting in a closed TM with a continuous but rather thick outer keratinocyte layer. Three plasminogen injections lead to a completely healed TM with a thin keratinizing squamous epithelium covering a connective tissue layer that can start to reorganize and further mature to its normal appearance. In conclusion, our results suggest that plasminogen is a promising drug candidate for the treatment of chronic TM perforations in humans. Taken together, our data indicate that plasminogen is a novel inflammatory regulator that promotes wound healing.
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25.
  • Carré, Helena, 1979- (författare)
  • Who's at risk of catching Chlamydia trachomatis? Identifying factors associated with increased risk of infection to enable individualized care and intervention
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Chlamydia trachomatis (CT) can cause infertility and is the most common sexually transmitted infection (STI) of bacterial origin in Europe. Surveys in seven countries estimated a population prevalence of 1.4-3.0 % in people 18 to 44 years. Approximately 87% of those diagnosed in Sweden are 15-29 years. Since 1997, with the exception of 2009-2010, despite all efforts, CT has increased steadily in many European countries including Sweden. That made us investigate risk factors associated with catching STIs, especially CT. In Sweden partner notification is mandatory by law when a patient is diagnosed with CT. Centralised partner notification, performed by a few experienced counsellors, and evaluation of the sexual history for at least 12 months back in time, shows superior results compared to other studies. Phone-interviews are a good option in remote areas. “The Västerbotten model” for partner notification fulfils these criteria and our evaluation has functioned as a model for changing recommendations of partner notification in Sweden. Preventing CT by primary prevention such as information and counselling is, however, still of great importance. We investigated whether it was necessary to test for CT in the throat. We found that patients testing positive for pharyngeal CT neither had more symptoms or signs nor a sexual history that differed from others. We therefore believe that we will find most or all of these patients by conventional testing of urine and cervical/vaginal samples. We wanted to further identify risk factors among patients attending a clinic for sexually transmitted infections to enable individualized care depending on risk. None or inconsistent use of condoms with new/temporary partners in combination with having at least one new/temporary partner within the past 6 months could identify persons with risk behaviour and at increased risk of CT (re)infection. Additional information about whether the condom was used during the whole intercourse did not add any risk of infection. A drop-in reception is a good contribution to an opportunistic screening approach. The rate of CT infected is high and the clinic attracts men and individuals ≥25 years old at risk of infection, groups which usually have a reduced test rate. The mean age was 28 years and 58% of the patients were men. The figure of correct condom usage is very low indicating the need for risk reducing counselling also in this grown-population. Among adult STI patients anxiety was common and depression uncommon. Neither was linked to high risk sexual behaviour nor ongoing CT infection. Hazardous alcohol consumption, however, was common and linked to anxiety and high risk sex. We conclude that preventive work can not only focus on STI prevention, but must consider the high frequency of hazardous alcohol consumption, which probably is contributing to sexual risk behaviour. 
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26.
  • Chamcheu, Jean Christopher (författare)
  • Disease-causing Keratin Mutations and Cytoskeletal Dysfunction in Human Skin : In vitro Models and new Pharmacologic Strategies for Treating Epidermolytic Genodermatoses
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Epidermolysis bullosa simplex (EBS) and epidermolytic ichthyosis (EI) are rare skin fragility diseases characterized by intra-epidermal blistering due to autosomal dominant-negative mutations in basal (KRT5 or KRT14) and suprabasal (KRT1 or KRT10) keratin genes,  respectively. Despite vast knowledge in the disease pathogenesis, the pathomechanisms are not fully understood, and no effective remedies exist. The purpose of this work was to search for keratin gene mutations in EBS patients, to develop in vitro models for studying EBS and EI, and to investigate novel pharmacological approaches for both diseases. We identified both novel and recurrent KRT5 mutations in all studied EBS patients but one which did not show any pathogenic keratin mutations. Using cultured primary keratinocytes from EBS patients, we reproduced a correlation between clinical severity and cytoskeletal instability in vitro. Immortalized keratinocyte cell lines were established from three EBS and three EI patients with different phenotypes using HPV16-E6E7. Only cell lines derived from severely affected patients exhibited spontaneous keratin aggregates under normal culture conditions. However, heat stress significantly induced keratin aggregates in all patient cell lines. This effect was more dramatic in cells from patients with a severe phenotype. In organotypic cultures, the immortalized cells were able to differentiate and form a multilayered epidermis reminiscent of those observed in vivo. Addition of two molecular chaperones, trimethylamine N-oxide dihydrate (TMAO) and sodium 4-phenylbutyrate (4-PBA), reduced the keratin aggregates in both stressed and unstressed EBS and EI keratinocytes, respectively. The mechanism of action of TMAO and 4-PBA was shown to involve the endogenous chaperone system (Heat shock proteins e.g. Hsp70). Besides, MAPK signaling pathways also seemed to be incriminated in the pathogenesis of EBS. Furthermore, depending on which type of keratin is mutated, 4-PBA up-regulated Hsp70 and KRT4 (possibly compensating for mutated KRT1/5), and down-regulated KRT1 and KRT10, which could further assist in protecting EBS and EI cells against stress. In conclusion, novel and recurrent pathogenic keratin mutations have been identified in EBS. Immortalized EBS and EI cell lines that functionally reflect the disease phenotype were established. Two pharmacologic agents, TMAO and 4-PBA, were shown to be promising candidates as novel treatment of heritable keratinopathies in this in vitro model.
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27.
  • Ekbäck, Maria Palmetun, et al. (författare)
  • Health-Related Quality of Life, Depression and Anxiety Correlate with the Degree of Hirsutism
  • 2013
  • Ingår i: Dermatology. - : Karger. - 1018-8665 .- 1421-9832. ; 227:3, s. 278-284
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hirsutism has a negative impact on womens quality of life. The relation between quality of life, anxiety, depression and the level of hairiness has not been described. Aims: To investigate the correlations between the levels of hairiness, quality of life, anxiety and depression. Methods: 200 patients from Malmo, Orebro and Uppsala, who had been in contact with the clinics for problems with excessive hair growth, were invited to answer a self-administered questionnaire including sociodemographic questions, EQ-5D index score, Dermatology Life Quality Index (DLOI), Hospital Anxiety and Depression Scale (HADS) and Ferriman-Gallwey scale (F-G); of these, 127 women participated in the study. Results: The mean values were: EQ-5D index 0.73 (SD = 0.27), EQ visual analogue scale 61.0 (SD = 22.6), HADS-anxiety 9.5 +/- 5.3 and HADS-depression 6.5 +/- 4.6. The mean DLQI was 11.8 +/- 8.4, indicating a very large effect on patients lives. All were significantly correlated with the amount of hairiness. Conclusions: Higher levels of hair growth were significantly correlated with a lower level of quality of life and symptoms of both anxiety and depression.
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28.
  • Ericson, Lisa, et al. (författare)
  • Atrial fibrillation : the cost of illness in Sweden
  • 2011
  • Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7598 .- 1618-7601. ; 12:5, s. 479-87
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To provide an estimate of the annual cost of atrial fibrillation (AF) in Sweden.METHODS: Prevalence-based cost analysis of AF in Sweden for 2007. Direct medical (hospitalizations, hospital outpatient care, primary health care, non-pharmacological interventions, pharmaceuticals, and anticoagulation monitoring) and non-medical (transportation associated with health care visits) costs of AF, direct costs of AF complications (stroke and heart failure), and indirect costs (production loss), were included. Data were based on Swedish registries, reports and databases, published literature, and an expert panel.RESULTS: There were 100,557 individuals with AF as primary or secondary diagnosis that were either hospitalized or treated in hospital outpatient care in 2007. The total cost of AF was estimated at 708 million. The major cost driver was the direct cost of complications (54%), followed by hospitalization due to AF including AF as secondary diagnosis (18%), and production loss (12%).CONCLUSION: This is a comprehensive, nation-based cost analysis of AF where relevant data were derived from national registries covering the entire Swedish population. The results showed that the annual cost of AF was high in comparison with other diseases, but likely to be underestimated as a conservative approach was applied in the analysis.
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29.
  • Falk, Magnus (författare)
  • Self-estimation or Phototest Measurement of Skin UV Sensitivity and its Association with Peoples Attitudes Towards Sun Exposure
  • 2014
  • Ingår i: Anticancer Research. - : International Institute of Anticancer Research (IIAR). - 0250-7005 .- 1791-7530. ; 34:2, s. 797-803
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Fitzpatrick's classification is the most common way of assessing skin UV sensitivity. The study aim was to investigate how self-estimated and actual UV sensitivity, as measured by phototest, are associated with attitudes towards sunbathing and the propensity to increase sun protection, as well as the correlation between self-estimated and actual UV sensitivity.PATIENTS AND METHODS:A total of 166 primary healthcare patients filled-out a questionnaire investigating attitudes towards sunbathing and the propensity to increase sun protection. They reported their skin type according to Fitzpatrick, and a UV sensitivity phototest was performed.RESULTS:Self-rated low UV sensitivity (skin type III-VI) was associated with a more positive attitude towards sunbathing and a lower propensity to increase sun protection, compared to high UV sensitivity. The correlation between the two methods was weak.CONCLUSION:The findings might indicate that individuals with a perceived low but in reality high UV sensitivity do not seek adequate sun protection with regard to skin cancer risk. Furthermore, the poor correlation between self-reported and actual UV sensitivity, measured by phototest, makes the clinical use of Fitzpatrick's classification questionable.
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30.
  • Hagforsen, Eva, et al. (författare)
  • Normal and PPP-affected palmoplantar sweat gland express neuroendocrine markers chromogranins and synaptophysin differently
  • 2010
  • Ingår i: Archives of Dermatological Research. - : Springer Science and Business Media LLC. - 0340-3696 .- 1432-069X. ; 302:9, s. 685-693
  • Tidskriftsartikel (refereegranskat)abstract
    • Earlier findings indicate the acrosyringium as the target for the inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat gland apparatus seems to be an immune-competent structure that probably contributes to the defence of the skin. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ because it expresses cholineacetyl-transferase and acetylcholinesterase, nicotinic receptors, beta-adrenergic and angiotensin receptors.The aim of this study was to obtain further information about neuroendocrine properties of the sweat gland apparatus by examining the expression of common neuroendocrine markers synaptophysin and chromogranins A and B in healthy palmar skin and in PPP skin.Synaptophysin and chromogranins were expressed in the sweat glands and ducts with some variation in the pattern and intensity of the expression. In PPP skin the expression differed, being higher and lower, depending on the part of the sweat duct. Chromogranins were further expressed in the epidermis, endothelium and inflammatory cells, but its intensity was weaker in epidermis than in the sweat gland apparatus. In most cases, chromogranins in epidermis in involved PPP were weakly expressed compared to healthy controls. The presence of synaptophysin and chromogranins in palmoplantar skin may have marked neuroendocrine effects, and the palmoplantar skin is likely to have important neuroimmuno-endocrine properties. Moreover, the altered chromogranin expression in PPP skin might influence both the neuroendocrine and neuroimmunologic properties of palmoplantar skin in these patients. These results indicate important neuroendocrine properties of the palmoplantar skin.
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31.
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32.
  • Kalle, Martina, et al. (författare)
  • A Peptide of Heparin Cofactor II Inhibits Endotoxin-Mediated Shock and Invasive Pseudomonas aeruginosa Infection.
  • 2014
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII) has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.
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33.
  • Koutouzis, Michael, 1973, et al. (författare)
  • Radial vs. femoral approach for primary percutaneous coronary intervention in octogenarians.
  • 2010
  • Ingår i: Cardiovascular revascularization medicine : including molecular interventions. - : Elsevier BV. - 1878-0938 .- 1553-8389. ; 11:2, s. 79-83
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The transradial approach is associated with fewer bleeding complications during percutaneous coronary interventions (PCIs) but is more technically challenging and associated with prolonged times during intervention. The aim of this study is to retrospectively compare the results of radial vs. femoral approach in patients >or=80 years old undergoing primary or rescue PCI. METHODS: Between January 2002 and December 2007, 354 interventions were performed in our institution with the indication of primary or rescue PCI in patients over 80 years old, without history of previous bypass operation or cardiogenic shock on presentation. Thirteen patients required a change of the approach during the procedure and were not enrolled in the final analysis. Forty (12%) interventions were performed through the transradial approach and 301 (88%) through the femoral approach. In-hospital major adverse cerebral and cardiac events and access site bleeding complications as well as 30- and 365-day mortality, procedural times, and contrast volume were evaluated. RESULTS: The two groups had similar clinical characteristics, with the exception of serum creatinine that was higher in the transfemoral approach group. There were no differences in procedural times and clinical outcomes, although the transfemoral group had numerically more access site bleeding complications (12/301 vs. 0/40, P=.41). The transradial approach had a higher conversion rate compared with the transfemoral approach (18.3% vs. 1.3%, P<.001). CONCLUSION: The transradial approach is feasible and safe in the octogenarians undergoing primary and rescue PCI, but it is associated with a high conversion rate to another approach.
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34.
  • Nielsen, Kari, et al. (författare)
  • Swedish CDKN2A mutation carriers do not present the atypical mole syndrome phenotype.
  • 2010
  • Ingår i: Melanoma Research. - 0960-8931. ; Jul 1, s. 266-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Phenotypic characteristics were examined in melanoma-prone southern Swedish CDKN2A (p16-113insArg/p14ARF-128insSer) mutation families, in relation to the CDKN2A genotype, nevi, clinically atypical nevi (CAN) and melanoma. Individuals from eight melanoma-prone families, with index patients carrying the CDKN2A mutation, were offered skin examinations and genotyping (CDKN2A and MC1R). Ninety-three individuals above 18 years of age participated; 29 invasive melanomas in 16 patients were recorded, all in the 38 verified CDKN2A mutation carriers. Median age at diagnosis was 36 years. Several MC1R variants were observed. A significant correlation to CAN (P=0.01) and red hair colour (P=0.02) could be confirmed in melanoma patients. A positive mutation status (CDKN2A) was correlated to one or more CAN (P=0.007) but neither to blue eyes, red hair colour, heavy freckling nor high number of nevi. For mutation carriers, median total naevus count was 24 and interquartile range was 12-47 (mean 31); whereas for the whole cohort, median total naevus count was 12 and interquartile range was 5-25 (mean 22). No participant fulfilled the atypical mole syndrome phenotype criteria. Melanomas were diagnosed only in mutation carriers, and melanoma diagnosis was statistically correlated to the presence of one or more CAN and red hair colour, supporting the possible synergistic effect of a MC1R mutation on increased risk of melanoma in patients with a CDKN2A mutation. Family history, with verified tumour diagnoses, remains an important clinical tool for finding mutation carriers for referral to clinical geneticists and simultaneous presence of CAN in probable mutation carriers might strengthen this indication. The atypical mole syndrome phenotype was, however, not verified in the studied families and total naevus counts were low.
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35.
  • Papareddy, Praveen, et al. (författare)
  • Antimicrobial Effects of Helix D-derived Peptides of Human Antithrombin III
  • 2014
  • Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 289:43, s. 29790-29800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Antithrombin III (ATIII), an antiproteinase-inhibiting coagulation, was investigated for roles in host defense. Results: Extensive proteolysis of ATIII by endogenous and bacterial enzymes generated antimicrobial activity, mapped to helix D of the molecule. Conclusion: ATIII harbor cryptic host defense epitopes released during proteolysis. Significance: The results explain previously observed antimicrobial and anti-inflammatory effects of ATIII supplementation during infection. Antithrombin III (ATIII) is a key antiproteinase involved in blood coagulation. Previous investigations have shown that ATIII is degraded by Staphylococcus aureus V8 protease, leading to release of heparin binding fragments derived from its D helix. As heparin binding and antimicrobial activity of peptides frequently overlap, we here set out to explore possible antibacterial effects of intact and degraded ATIII. In contrast to intact ATIII, the results showed that extensive degradation of the molecule yielded fragments with antimicrobial activity. Correspondingly, the heparin-binding, helix d-derived, peptide FFFAKLNCRLYRKANKSSKLV (FFF21) of human ATIII, was found to be antimicrobial against particularly the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Fluorescence microscopy and electron microscopy studies demonstrated that FFF21 binds to and permeabilizes bacterial membranes. Analogously, FFF21 was found to induce membrane leakage of model anionic liposomes. In vivo, FFF21 significantly reduced P. aeruginosa infection in mice. Additionally, FFF21 displayed anti-endotoxic effects in vitro. Taken together, our results suggest novel roles for ATIII-derived peptide fragments in host defense.
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36.
  • Jaenson, Thomas G. T., 1948-, et al. (författare)
  • "Fågelloppor" kan ha varit fågelkvalster
  • 2010
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:29-31, s. 1791-1792
  • Tidskriftsartikel (populärvet., debatt m.m.)
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37.
  • Bergfors, Elisabet, et al. (författare)
  • A child with a long-standing, intensely itching subcutaneous nodule on a thigh : an uncommon (?) reaction to commonly used vaccines
  • 2013
  • Ingår i: BMJ Case Reports. - : BMJ Publishing Group. - 1757-790X.
  • Tidskriftsartikel (refereegranskat)abstract
    • A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.
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38.
  • Bergfors, Elisabet, et al. (författare)
  • How common are long-lasting, intensely itching vaccination granulomas and contact allergy to aluminium induced by currently used pediatric vaccines? A prospective cohort study
  • 2014
  • Ingår i: European Journal of Pediatrics. - : Springer Berlin/Heidelberg. - 0340-6199 .- 1432-1076. ; 173:10, s. 1297-1307
  • Tidskriftsartikel (refereegranskat)abstract
    • The frequency of long-lasting, intensely itching subcutaneous nodules at the injection site for aluminium (Al)-adsorbed vaccines (vaccination granulomas) was investigated in a prospective cohort study comprising 4,758 children who received either a diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (Infanrix®, Pentavac®) alone or concomitant with a pneumococcal conjugate (Prevenar). Both vaccines were adsorbed to an Al adjuvant. Altogether 38 children (0.83 %) with itching granulomas were identified, epicutaneously tested for Al sensitisation and followed yearly. Contact allergy to Al was verified in 85 %. The median duration of symptoms was 22 months in those hitherto recovered. The frequency of granulomas induced by Infanrix® was >0.66 % and by Prevenar >0.35 %. The risk for granulomas increased from 0.63 to 1.18 % when a second Al-adsorbed vaccine was added to the schedule. Conclusion: Long-lasting itching vaccination granulomas are poorly understood but more frequent than previously known after infant vaccination with commonly used diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b and pneumococcal conjugate vaccines. The risk increases with the number of vaccines given. Most children with itching granulomas become contact allergic to aluminium. Itching vaccination granulomas are benign but may be troublesome and should be recognised early in primary health care to avoid unnecessary investigations, anxiety and mistrust.
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39.
  • Khmaladze, Ia, et al. (författare)
  • Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice
  • 2014
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - Washington, DC : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:35, s. E3669-E3678
  • Tidskriftsartikel (refereegranskat)abstract
    • Psoriasis (Ps) and psoriasis arthritis (PsA) are poorly understood common diseases, induced by unknown environmental factors, affecting skin and articular joints. A single i.p. exposure to mannan from Saccharomyces cerevisiae induced an acute inflammation in inbred mouse strains resembling human Ps and PsA-like disease, whereas multiple injections induced a relapsing disease. Exacerbation of disease severity was observed in mice deficient for generation of reactive oxygen species (ROS). Interestingly, restoration of ROS production, specifically in macrophages, ameliorated both skin and joint disease. Neutralization of IL-17A, mainly produced by gammadelta T cells, completely blocked disease symptoms. Furthermore, mice depleted of granulocytes were resistant to disease development. In contrast, certain acute inflammatory mediators (C5, Fcgamma receptor III, mast cells, and histamine) and adaptive immune players (alphabeta T and B cells) were redundant in disease induction. Hence, we propose that mannan-induced activation of macrophages leads to TNF-alpha secretion and stimulation of local gammadelta T cells secreting IL-17A. The combined action of activated macrophages and IL-17A produced in situ drives neutrophil infiltration in the epidermis and dermis of the skin, leading to disease manifestations. Thus, our finding suggests a new mechanism triggered by exposure to exogenous microbial components, such as mannan, that can induce and exacerbate Ps and PsA.
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40.
  • Dalemo, Sofia, et al. (författare)
  • Variation in plasma calcium analysis in primary care in Sweden--a multilevel analysis.
  • 2010
  • Ingår i: BMC family practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Primary hyperparathyroidism (pHPT) is a common disease that often remains undetected and causes severe disturbance especially in postmenopausal women. Therefore, national recommendations promoting early pHPT detection by plasma calcium (P-Ca) have been issued in Sweden. In this study we aimed to investigate variation of P-Ca analysis between physicians and health care centres (HCCs) in primary care in county of Skaraborg, Sweden.
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41.
  • Herlitz, Johan, 1949, et al. (författare)
  • Symptoms of chest pain and dyspnoea during a period of 15 years after coronary artery bypass grafting.
  • 2010
  • Ingår i: European journal of cardio-thoracic surgery. - : Elsevier. - 1873-734X .- 1010-7940. ; 37:1, s. 112-118
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: To describe changes in chest pain and dyspnoea during a period of 15 years after coronary artery bypass grafting (CABG) and to define factors at the time of operation that were associated with the occurrence of these symptoms after 15 years. DESIGN: Prospective observational study in western Sweden. SUBJECTS: All patients who underwent first-time CABG, without simultaneous valve surgery, between 1 June 1988 and 1 June 1991. There were no exclusion criteria. FOLLOW-UP: All patients were followed up prospectively for 15 years. The evaluation of symptoms took place through postal questionnaires prior to and 5, 10 and 15 years after the operation. RESULTS: Totally, 2000 patients were included in the survey and 904 (45%) of them survived to 15 years. Among these 904 survivors, the percentage of patients with chest pain increased from 44% to 50% between the 5- and 15-year follow-up (p=0.004). The percentage of patients who reported symptoms of dyspnoea increased from 60% after 5 years to 74% after 15 years (p<0.001). Factors at the time of surgery that independently tended to predict chest pain after 15 years were higher age (p=0.04) and prolonged duration of symptoms prior to surgery (p=0.04). Predictors of dyspnoea after 15 years were higher age (p<0.0001), the use of inotropic drugs at the time of surgery (p=0.001), a history of diabetes (p=0.01) and obesity (p=0.01). CONCLUSION: After CABG, relief from chest pain and dyspnoea is generally maintained over a long period of time. Eventually, however, functional-limiting symptoms tend to recur and about half the patients report symptoms of chest pain, while three-quarters report dyspnoea after 15 years. Even if no clear predictor of chest pain was found at the time of surgery, age, the use of inotropic drugs, diabetes and obesity predicted dyspnoea.
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42.
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43.
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44.
  • von Kobyletzki, Laura, et al. (författare)
  • Validation of a parental questionnaire to identify atopic dermatitis in a population-based sample of children up to 2 years of age
  • 2013
  • Ingår i: Dermatology. - Basel, Switzerland : S. Karger. - 1018-8665 .- 1421-9832. ; 226:3, s. 222-226
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Validated eczema questionnaires have been available for schoolchildren only, but the incidence of atopic dermatitis (AD) is highest during infancy. Objective: To validate a parental questionnaire to identify AD in children up to 2 years of age.Methods: Parents of 476 children answered a written questionnaire prior to an examination by a physician. Sensitivity, specificity, predictive values and test-retest reliability of the questionnaire were assessed.Results: A total of 245 (51%) girls and 231 (49%) boys, aged 1-24 months, with and without physician-diagnosed AD participated. Seventy-one children (15%) had physician-diagnosed AD. Validation of the questionnaire by comparisons with physicians' diagnoses showed a sensitivity of 0.87 (95% confidence interval, CI, 0.77-0.94) and a specificity of 0.98 (95% CI, 0.96-0.99). The positive predictive value was 0.90 (95% CI, 0.80-0.96) and the negative predictive value was 0.98 (95% CI, 0.96-0.99). Conclusion: The questionnaire identified AD in children aged 0-2 years with high accuracy.
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45.
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46.
  • Gastaldi, Cécile, et al. (författare)
  • miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma.
  • 2014
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1110-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Incidence of cutaneous squamous cell carcinomas (cSCCs) constantly increases in the Caucasian population. Developing preferentially on precancerous lesions such as actinic keratoses due to chronic sunlight exposure, cSCCs result from the malignant transformation of keratinocytes. Although a resection of the primary tumor is usually curative, a subset of aggressive cSCCs shows a high risk of recurrence and metastases. The characterization of the molecular dysfunctions involved in cSCC development should help to identify new relevant targets against these aggressive cSCCs. In that context, we have used small RNA sequencing to identify 100 microRNAs (miRNAs) whose expression was altered during chemically induced mouse skin tumorigenesis. The decreased expression of the miR-193b/365a cluster during tumor progression suggests a tumor suppressor role. Ectopic expression of these miRNAs in tumor cells indeed inhibited their proliferation, clonogenic potential and migration, which were stimulated in normal keratinocytes when these miRNAs were blocked with antisense oligonucleotides. A combination of in silico predictions and transcriptome analyses identified several target genes of interest. We validated KRAS and MAX as direct targets of miR-193b and miR-365a. Repression of these targets using siRNAs mimicked the effects of miR-193b and miR-365a, suggesting that these genes might mediate, at least in part, the tumor-suppressive action of these miRNAs.
  •  
47.
  • Lindqvist, P. G., et al. (författare)
  • Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort
  • 2014
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 276:1, s. 77-86
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels. Methods. We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data. Results. There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%. Conclusion. The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.
  •  
48.
  • Sonkoly, E, et al. (författare)
  • MicroRNA-203 functions as a tumor suppressor in basal cell carcinoma.
  • 2012
  • Ingår i: Oncogenesis. - : Springer Science and Business Media LLC. - 2157-9024. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Basal cell carcinoma (BCC) of the skin represents the most common malignancy in humans. MicroRNAs (miRNAs), small regulatory RNAs with pleiotropic function, are commonly misregulated in cancer. Here we identify miR-203, a miRNA abundantly and preferentially expressed in skin, to be downregulated in BCCs. We show that activation of the Hedgehog (HH) pathway, critically involved in the pathogenesis of BCCs, as well as the EGFR/MEK/ERK/c-JUN signaling pathway suppresses miR-203. We identify c-JUN, a key effector of the HH pathway, as a novel direct target for miR-203 in vivo. Further supporting the role of miR-203 as a tumor suppressor, in vivo delivery of miR-203 mimics in a BCC mouse model results in the reduction of tumor growth. Our results identify a regulatory circuit involving miR-203 and c-JUN, which provides functional control over basal cell proliferation and differentiation. We propose that miR-203 functions as a 'bona fide' tumor suppressor in BCC, whose suppressed expression contributes to oncogenic transformation via derepression of multiple stemness- and proliferation-related genes, and its overexpression could be of therapeutic value.
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