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  • 1.
    Alaish, Ram
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundgren, David
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Safety of azathioprine and 6-mercaptopurine in patients with inflammatory bowel disease naive to thiopurine treatment2017In: International journal of clinical pharmacology and therapeutics, ISSN 0946-1965, Vol. 55, no 7, p. 594-600Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine if 6-mercaptopurine (MP) is better tolerated than azathioprine (AZA) as the initial thiopurine treatment in patients suffering from inflammatory bowel disease (IBD). Switching patients with IBD from AZA to MP is advocated in patients intolerant to AZA. However, no study has determined if MP is more suited than AZA as a first-line treatment for patients who are naive to thiopurine treatment. Study: The tolerance of AZA and MP treatments in clinical practice was retrospectively evaluated from start to 12 months after initiating treatment in 113 patients with IBD who were all naive to thiopurines (82 patients treated with AZA and 31 patients with MP). Results: 65% of the patients treated with AZA and 61% of the patients treated with MP tolerated their treatment during 12 months (i.e., no group difference, p = 0.742). No difference in reported side effects between the two treatments was observed. The mean equivalent initial dose (0.92 vs. 0.61 mg/kg; p < 0.001) and the mean equivalent dose at 12 months (1.98 vs. 1.65 mg/kg; p = 0.014) was significantly higher in the MP group vs. the AZA group. The proportion of patients with.MCV = 7 at 12 months was numerically higher in the MP group than in the AZA group (53% vs. 31%; p = 0.090). Conclusions: In this retrospective observational study, no differences in tolerance or adherence between AZA and MP were observed in patients naive to thiopurines. However, MP treatment was at a higher equivalent thiopurine dose than AZA treatment, which tended to be associated with better treatment response.

  • 2.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bacterial landscape of human skin: seeing the forest for the trees2013In: Experimental dermatology, ISSN 0906-6705, E-ISSN 1600-0625, Vol. 22, no 7, p. 443-446Article in journal (Refereed)
    Abstract [en]

    Skin harbours large communities of colonizing bacteria. The same bacterial species can exist in different physiological states: viable, dormant, non-viable. Each physiological state can have a different impact on skin health and disease. Various analytical methodologies target different physiological states of bacteria, and this must be borne in mind while interpreting microbiological tests and drawing conclusions about possible cause-effect relationships.

  • 3.
    Alexeyev, Oleg A
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lundskog, Bertil
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Ganceviciene, Ruta
    Palmer, Ruth H
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    McDowell, Andrew
    Patrick, Sheila
    Zouboulis, Christos
    Golovleva, Irina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Pattern of tissue invasion by Propionibacterium acnes in acne vulgaris2012In: Journal of dermatological science (Amsterdam), ISSN 0923-1811, E-ISSN 1873-569X, Vol. 67, no 1, p. 63-66Article in journal (Refereed)
  • 4.
    Alexeyev, Oleg A
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Zouboulis, Christos C
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Shooting at skin propionibacterium acnes: to be or not to be on target2013In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 133, no 9, p. 2292-2294Article in journal (Refereed)
  • 5.
    Andersson, Chris D
    et al.
    Linköpings universitetssjukhus, Dermatologi.
    Meding, Birgitta
    Karolinska Institutet, Inst för miljömedicin.
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Svensson, Åke
    Malmö Allmänna Sjukhus.
    Working with Population to Treat Individuals: A Report from the Swedish Dermato-Epidemiological Network (SweDEN)2012In: Forum for Nordic Dermato-Venereology, ISSN 1402-2915, Vol. 17, no 2, p. 44-46Article in journal (Refereed)
  • 6.
    Andersson, Nirina
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Rectal chlamydia - should screening be recommended in women?2017In: International Journal of STD and AIDS (London), ISSN 0956-4624, E-ISSN 1758-1052, Vol. 28, no 5, p. 476-479Article in journal (Refereed)
    Abstract [en]

    Chlamydia trachomatis is the most common bacterial sexually transmitted infection in Europe and has large impacts on patients' physical and emotional health. Unidentified asymptomatic rectal Chlamydia trachomatis could be a partial explanation for the high Chlamydia trachomatis prevalence. In this study, we evaluated rectal Chlamydia trachomatis testing in relation to symptoms and sexual habits in women and men who have sex with men. Rectal Chlamydia trachomatis prevalence was 9.1% in women and 0.9% in men who have sex with men. None of the patients reported any rectal symptoms; 59.0% of the women with a rectal Chlamydia trachomatis infection denied anal intercourse and 18.8% did not have a urogenital infection; 9.4% did neither have a urogenital infection nor reported anal sex. We suggest that rectal sampling should be considered in women visiting sexually transmitted infection clinics regardless of rectal symptoms and irrespective of anal intercourse, since our data suggest that several cases of rectal Chlamydia trachomatis otherwise would be missed, thus enabling further disease transmission.

  • 7.
    Berglin, Ewa
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Predictors of disease onset and progression in early rheumatoid arthritis: A clinical, laboratory and radiological study2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    To diagnose rheumatoid arthritis (RA) during the early stages of the disease is often difficult. The disease course shows great inter-individual variation from mild, self-limiting to very severe destruc-tive disease with extra-articular manifestations. Early aggressive treatment with potentially toxic drugs has been shown to improve the long-term outcome. Thus, it is desirable to make an early reliable di-agnosis and to identify those patients who would benefit from being treated most aggressively.

    The aim of this thesis was to evaluate laboratory and clinically markers of inflammation as predic-tors of disease course, to compare dual-energy X-ray absorptiometry (DXA) and conventional radiog-raphy (CR) as measures of joint destruction and to investigate the significance of antibodies against cyclic citrullinated peptide (anti-CCP antibodies), rheumatoid factors (RFs) and HLA shared epitope (SE) alleles for the relative risk of future development of RA and as predictors of disease severity in patients with early RA.

    Patients with RA of recent onset are included in the early RA programme at the Department of Rheumatology, University Hospital, Umeå and are followed longitudinally. The prediction of markers of inflammation for bone loss and radiological outcome was analyzed in the first 43 patients recruited. Radiographs of hands and feet (Larsen score) and bone mineral density (BMD) in hands (DXA), were assessed at baseline, after 1 and 2 years. The disease activity was evaluated clinically and by labora-tory tests. Radiological damage increased significantly during the study and was particularly corre-lated with Larsen score at baseline. BMD in hands decreased significantly in postmenopausal women and the decrease was greater than in healthy matched controls. Radiological progression and bone loss in hands was retarded by an early response to therapy.

    In a case-control study within the Medical Biobank and the Maternity cohort of Northern Sweden, patients from the early RA programme were identified among blood donors from whom samples had been collected years before onset of symptoms. The prevalence of anti-CCP antibodies and RFs (IgA-RF, IgG-RF and IgM-RF) was investigated in samples from 83 individuals (pre-patients) and com-pared with matched controls. SE alleles were assessed in a sub-group of 59 individuals. Anti-CCP antibodies and RFs preceded onset of RA by several years and increased in prevalence closer to dis-ease onset. Anti-CCP antibodies and IgA-RF significantly predicted the onset of RA. The combination of anti-CCP antibodies and SE alleles was associated with a high relative risk for future development of RA.

    In a later co-analysis between the register of patients in the early RA programme (n=138) and the Medical Biobank and the Maternity cohort, 93 pre-patient samples were identified. The significance of SE alleles and of the presence of anti-CCP antibodies and RFs before and at disease onset for disease activity and severity was studied. Radiographs of hands and feet were assessed at baseline and after 2 years (Larsen score). The presence of anti-CCP antibodies in pre-patient samples and at baseline was associated with radiological damage, as was presence of all RFs at baseline. A higher titre of anti-CCP antibodies was associated with greater radiological progression. The titre was lowered by a therapeutic response. In multiple logistic regression analyses anti-CCP antibodies, IgA-RF, ESR and swollen joint count predicted greater radiological progression, whilst a therapeutic response predicted a lesser pro-gression.

    In conclusion, anti-CCP antibodies and IgA-RF are predictors for future onset of RA and for radio-logical destruction and progression. The combination of anti-CCP antibodies and SE alleles is associ-ated with a high relative risk for future RA. Therapeutic response decreases the radiological progres-sion and the bone loss in hands and lowers the titre of anti-CCP antibodies. Conventional radiography is a better measure of joint destruction than DXA.

  • 8.
    Björklund, Martin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Effects of repetitive work on proprioception and of stretching on sensory mechanisms: implications for work-related neuromuscular disorders2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aims of the thesis were (i) to investigate the impact of repetitive low-intensity work exposure on proprioception and (ii) to examine effects of muscle stretching (especially sensory effects and effects on muscle nociception) and to relate its application to the prevention, alleviation and/or treatment of work-related neuromuscular disorders.

    The effects of low-intensity repetitive work on the shoulder proprioception were tested in healthy subjects. The effect of working time on the retention of subjective fatigue and their relation to changes in proprioception, and the immediate effect of stretching on shoulder proprioception were investigated. A new method to test the stretchability of the rectus femoris muscle was investigated for reliability and validity and used to assess the effects of a two-week stretching regimen on range of motion and on subjective stretch sensation. Finally, the interactions between innocuous muscle stretch and nociceptive chemical stimulation on discharge behavior of nociceptive dorsal horn neurons in the feline spinal cord were explored.

    The main findings were as follows: 1) The repetitive low-intensity work to fatigue diminished the shoulder proprioception; the working time as well as the retention of subjective fatigue were partly related to the extent of changed proprioception. 2) There was no effect of acute muscle stretching on the proprioception. 3) The new method for testing muscle stretchability proved valid and reliable. A two-week stretching regimen increased the tolerance to stretch torque, but the range of motion remained unchanged. 4) Half of the nociceptive dorsal horn neurons that responded to close arterial injections of bradykinin were modulated by muscle stretching applied directly after the injections.

    Altogether, the results give credence to the hypothesis of an involvement of sensory information distortion due to repetitive low-intensity work exposure in the development of work-related neuromuscular disorders. Increased tolerance to stretch torque may be an important mechanism in explaining improvements following stretch treatment. The spinal interactions between innocuous stretch and nociceptive muscle afferent inputs indicate a possible mechanism involved in stretching-induced pain alleviation.

  • 9.
    Bodén, Ida
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Larsson, William
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nilsson, David
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Forssell, Erik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindholm-Sethson, Britta
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    In vivo skin measurements with a novel probe head for simultaneous skin impedance and near-infrared spectroscopy2011In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 17, no 4, p. 494-504Article in journal (Refereed)
    Abstract [en]

    Background/purpose: Near-infrared (NIR) spectroscopy and skin impedance (IMP) measurements are useful techniques for objective diagnostics of various skin diseases. Here, we present a combined probe head for simultaneous, time-saving NIR spectroscopy and skin impedance measurements. The probe also ensures that both measurements are performed under equal conditions and at the same skin location.

    Methods: Finite element method simulations were performed for evaluation of the impedance. In vivo skin measurements were performed and combined NIR and impedance spectra were analysed by means of multivariate methods with respect to body location, age and gender. The classification rate was determined by a planar discriminant analysis. Reproducibility was investigated by calculation of scatter values and statistical significance between overlapping groups was assessed by the calculation of intra-model distances, q.

    Results: The novel probe yielded rapid reproducible results and was easy to manage. Significant differences between skin locations and to a lesser extent age groups and gender were demonstrated.

    Conclusion: With the novel probe, statistically significant differences between overlapping classes in score plots can be confirmed by calculating intra-model distances. The influence of molecular differences in the skin at different body locations is larger than the influence of gender or age and therefore relevant reference measurements are discussed.

  • 10.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Prevention of Chlamydia trachomatis infections2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Urogenital chlamydia infection, caused by the bacterium Chlamydia trachomatis (CT), is the most common sexually transmitted bacterial infection in Sweden. In 2008 it was estimated by WHO that there were 105.7 million new cases of CT worldwide, an increase by 4.2 million cases (4.1%) compared to 2005. If untreated, CT infections can progress to serious reproductive health problems, especially in women. These complications include subfertility/infertility, ectopic pregnancy and chronic pain. The CT infection is often asymptomatic and reliable diagnostic methods and contact tracing are important tools for identifying infected individuals. CT infection is classified in the Swedish Communicable Diseases Act as a serious disease; consequently, written reporting and contact tracing are compulsory. Previous or ongoing CT infection is not uncommon in infertile couples, especially in women with tubal factor infertility (TFI). We have tested 244 infertile couples for CT antibodies, and CT IgG positive couples were tested for CT DNA in urine. The prevalence of CT antibodies was higher in infertile men and women, and ongoing CT infection was common. Our results support a role of CT in infertility and underscore the importance of prevention of CT infection. Contact tracing was studied during using questionnaires. A total of 544 questionnaires was sent to tracers in a Swedish county and 534 (98%) were completed. Centralized contact tracing performed by experienced tracers is effective; on average 65% of sexual contacts found by contact tracing are CT-infected. Our data show that it is worthwhile to extend the tracing period beyond 6 months as 30% of reported sexual contacts between months 7-12 were CT-infected. Contact tracing may be performed face-to-face at the clinic or by telephone. Because of the severe consequences of CT infection there is a need for useful methods for both primary and secondary prevention of CT and other sexually transmitted infections (STIs). An important sub-population for CT/STI-prevention is the “core group”, i.e. a subpopulation with high incidence of STIs combined with risky sexual behaviours. This subpopulation contributes particularly to the spread of STIs in the population. Therefore, we have developed and evaluated a brief standardised but flexible manual-based single-session intervention based on motivational interviewing (MI) for the reduction of high risk sexual behaviour. Women (n=105) and men (n=119) at high risk of contracting CT infection were randomly eighter offered brief MI counselling or standard care. Our findings support the effectiveness of brief MI-based counselling in reducing high-risk sexual behaviour and incident CT infection in women (p<0.01) but not in men. Our results suggest that gender aspects need to be considered and that men and women should be treated differently for achieving maximal risk-reduction. Whereas it might be sufficient to include information and motivation when performing risk-reducing counselling on women, counsellors may also add other components, such as behavioural skills and booster sessions, when counselling is performed on men.

  • 11.
    Boman, Jens
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Gaydos, Charlotte
    Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
    Juto, Per
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Quinn, Thomas C
    Department of Medicine, The Johns Hopkins University, Baltimore, Maryland.
    Failure to detect Chlamydia trachomatis in cell culture by using a monoclonal antibody directed against the major outer membrane protein1997In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 35, no 10, p. 2679-2680Article in journal (Refereed)
    Abstract [en]

    Two commercially available monoclonal antibodies for cell culture confirmation of Chlamydia trachomatis were compared in two prospective studies and one large retrospective study. In total, more than 33,000 genital specimens were cultured in parallel and stained with both antibodies, one of which was directed against the major outer membrane protein (MOMP) and one uf which was directed against the lipopolysaccharide (LPS). We found the anti-LPS-based assay to be more sensitive and as specific as the anti-MOMP-based assay for C. trachomatis cell culture confirmation of genital specimens.

  • 12.
    Boman, Jens
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Lindqvist, Helena
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Janlert, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Brandell Eklund, Astri
    Department of Knowledge Development, Swedish National Institute of Public Health, Östersund, Sweden.
    Forsberg, Lars
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Development and evaluation of brief manual-based single-session motivational interviewing for reducing Chlamydia trachomatis infection rates in women with high-risk sexual behaviorManuscript (preprint) (Other academic)
  • 13.
    Boman, Jens
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Lindqvist, Helena
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Janlert, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Brandell Eklund, Astri
    Swedish National Institute of Public Health, Östersund, Sweden.
    Forsberg, Lars
    Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Is single-session motivational interviewing effective to reduce high risk sexual behavior in men?Manuscript (preprint) (Other academic)
  • 14.
    Boman, Jens
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    [Chlamydia decreasing mostly in Västerbotten: why?]2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 13-14, p. 920-921Article in journal (Refereed)
  • 15.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Kallikrein-related peptidases and inhibitors of the skin2012In: Kallikrein-related peptidases: characterization, regulation, and interactions within the protease web / [ed] Viktor Magdolen, Christian P. Sommerhoff, Hans Fritz and Manfred Schmitt, Berlin: Walter de Gruyter, 2012, p. 329-347Chapter in book (Refereed)
  • 16.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Missing factors in human skin equivalent models?2017In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 176, no 1, p. 11-12Article in journal (Refereed)
  • 17.
    Brattsand, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Stefansson, Kristina
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Hubiche, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Nilsson, Stefan K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Egelrud, Torbjörn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor.2009In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 129, no 7, p. 1656-1665Article in journal (Refereed)
    Abstract [en]

    A previously unreported Kazal-type serine protease inhibitor, serine protease inhibitor Kazal type 9 (SPINK9), was identified in human skin. SPINK9 expression was strong in palmar epidermis, but not detectable or very low in non palmoplantar skin. Analysis of a human cDNA panel showed intermediate expression in thymus, pancreas, liver, and brain, and low or undetectable expression in other tissues. Using kallikrein-related peptidases (KLKs) 5, 7, 8, and 14, thrombin, trypsin, and chymotrypsin, inhibition with recombinant SPINK9 was seen only for KLK5 using low molecular weight substrates, with an apparent K(i) of 65 nM. Also KLK5 degradation of fibrinogen was totally inhibited by SPINK9. Slight inhibition of KLK8 using fibrinogen substrate could be observed using high concentrations of SPINK9. Analyses by surface plasmon resonance showed heterogeneous binding to SPINK9 of KLK5 and KLK8, but no binding of KLK7 or KLK14. KLK5 has been suggested to play a central role in skin desquamation as an initiating activating enzyme in proteolytic cascades formed by KLKs. An apparently KLK5-specific inhibitor, such as SPINK9, may play a significant regulatory role in such cascades. We suggest a possible role for SPINK9 in the site-specific epidermal differentiation of palms and soles.

  • 18.
    Bukachi, Frederick
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Ventricular Long Axis Function: Amplitudes and Timings: Echocardiographic Studies in Health and Disease2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: The ageing process not only increases the risk of coronary artery disease (CAD) but also complicates its diagnosis and treatment. It is therefore important to understand the newer concepts of cardiovascular ageing physiology as well as methods of predicting the outcomes of therapeutic options available for the elderly with severe CAD. Studies of atrioventricular (AV) ring or plane motion have attracted considerable interest in the last few years as a means of assessing ventricular and atrial function. As the displacement of AV rings towards the ventricular apex is a direct reflection of longitudinal fibre contraction, its measurement by echocardiography provides additional information regarding global and regional systolic and diastolic function. Left ventricular (LV) long axis amplitude of motion, referred to as mitral valve annular (MA) motion, is reduced in CAD and to some extent in the elderly as part of the normal ageing process. Objectives & Methods: The aim of the present study was two-fold. First, to investigate the relationship between the timing of MA motion and transmitral and pulmonary venous flow in healthy subjects, and to define the physiological significance of that relationship including its potential diagnostic utility. Second, to investigate the relationship between the clinical outcome and the behaviour of long axis function in patients with severe ischaemic LV dysfunction (SLVD) after percutaneous coronary angioplasty (PTCA). Transmitral early (E) and late (A) filling, and pulmonary venous flow reversal (Ar) were studied by Doppler echocardiography, while at the left lateral AV ring, the MA motion in early (Em) and late (Am) diastole were recorded by Doppler tissue imaging (DTI) and M-mode echocardiography. Results: Healthy subjects – In early diastole the onsets of LV filling (E) and relaxation (Em) were simultaneous, and peak Em preceded peak E by 26 msec in all age groups, constituting a time interval referred to as early diastolic temporal discordance (EDTD). Similarly, the onsets of Am, A and Ar were simultaneous at onset and began approximately 84 msec after the electrocardiographic P wave. Peak Am preceded peak A by 23 msec in the young and by 13 msec in the elderly, a time interval referred to as late diastolic temporal discordance (LDTD). Peak Ar, on the other hand, coincided with peak Am in all age groups. With increasing age and sequential prolongation of isovolumic relaxation time, the peaks of Am, Ar and A converged. This point of convergence is described as atrial mechanical alignment (AMA). Patients – MA total amplitude of motion, rates of shortening and lengthening were all reduced in patients with SLVD. At mid-term, 3-6 months after PTCA, there was improvement in all these variables. A pre-procedure long axis cut off value of ≥5 mm was associated with favourable symptomatic outcome. Overall angiographic success was 95.2%, and event-free survival was 78.4% at one month and declined steadily to 62.3% at one year with 2.5% mortality. Conclusions: EDTD, which reflects ventricular restoring forces (suction) is age independent while the narrowing of LDTD leading to AMA provides a novel method to identify healthy subjects at increased dependency on left atrial contraction for late diastolic filling. Peak atrial contraction (Am) coincides with peak Ar, thus the timing of regional atrial contraction by DTI can be used to estimate corresponding measurements of Ar, which is often difficult to image by transthoracic echocardiography. In patients with SLVD long axis total amplitude of at least 5 mm at the left MA suggests a significant potential for segmental function recovery after PTCA.

    Keywords: Echocardiography, Doppler tissue imaging, ageing, coronary disease, left ventricular dysfunction, atrial contraction, electromechanical function, coronary angioplasty.

  • 19.
    Bäckman, Assar
    et al.
    Astra Hässle AB, Umeå, Sweden.
    Strandén, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Brattsand, Maria
    Hansson, Lennart
    Astra Hässle AB, Umeå, Sweden.
    Egelrud, Torbjörn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Molecular cloning and tissue expression of the murine analog to human stratum corneum chymotryptic enzyme1999In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 113, no 2, p. 152-5Article in journal (Refereed)
    Abstract [en]

    Human stratum corneum chymotryptic enzyme (SCCE) may play a central part in epidermal homeostasis. Its proposed function is to catalyze the degradation of intercellular structures, including desmosomes, in the stratum corneum as part of the desquamation process. In order to facilitate physiologic and pathophysiologic studies on SCCE we have looked for the corresponding murine enzyme. A cDNA obtained by reverse transcription-polymerase chain reaction with total RNA prepared from mouse tails as starting material was cloned, and the expression of the corresponding mRNA studied. The murine cDNA showed 77% homology to human SCCE cDNA. It had an open-reading frame encoding a protein comprising 249 amino acids with 82% amino acid sequence homology to human SCCE including the conserved sequences of the catalytic traid of mammalian serine proteases. The murine protein was deduced to have a 21 amino acid signal peptide and a four amino acid propeptide ending with a tryptic cleavage site, followed by a sequence motif identical to the N-terminal amino acid sequence of native active human SCCE. As in human SCCE the P2 position of the propeptide was occupied by an acidic amino acid residue, and the position corresponding to the suggested bottom of the primary substrate specificity pouch occupied by an asparagine residue. Analyses of mouse tissues by reverse transcriptase-polymerase chain reaction showed high expression in the skin, low expression in lung, kidney, brain, heart, and spleen, and no expression in liver or skeletal muscle. In situ hybridization of mouse skin showed expression in high suprabasal keratinocytes and in the luminal parts of hair follicles. Our results strongly suggest that we have cloned the murine analog of human SCCE cDNA.

  • 20. Calara, Paul S
    et al.
    Althin, Rikard
    Carlsson, Katarina Steen
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Regional Differences in the Prescription of Biologics for Psoriasis in Sweden: a Register-Based Study of 4168 Patients2017In: BioDrugs, ISSN 1173-8804, E-ISSN 1179-190X, Vol. 31, no 1, p. 75-82Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Observational studies suggest an inequitable prescription of biologics in psoriasis care, which may be attributed to geographical differences in treatment access. Sweden regularly ranks high in international comparisons of equitable healthcare, and is, in connection with established national registries, an ideal country to investigate potential inequitable access.

    OBJECTIVE: The aim was to determine whether the opportunity for patients to receive biologics depends on where they receive care.

    METHODS: Biologic-naïve patients enrolled in the Swedish National Register for Systemic Treatment of Psoriasis (PsoReg) from 2008 to 2015 (n = 4168) were included. The association between the likelihood of initiating a biologic and the region where patients received care was analyzed. The strength of the association was adjusted for patient and clinical characteristics, as well as disease severity using logistic regression analysis. The proportion of patients that switched to a biologic (switch rate) and the probability of switch to a biologic was calculated in 2-year periods.

    RESULTS: The national switch rate increased marginally over time from 9.7 to 11.0%, though the uptake varied across regions. Adjusted odds ratios for at least one region were significantly different from the reference region in every 2-year period. During the latest period (2014-2015), the average patient in the lowest prescribing region was nearly 2.5 times less likely to switch as a similar patient in the highest prescribing region.

    CONCLUSIONS: Geographical differences in biologics prescription persist after adjusting for patient characteristics and disease severity. The Swedish example calls for further improvements in delivering equitable psoriasis care.

  • 21. Calara, Paul S.
    et al.
    Norlin, Jenny M.
    Althin, Rikard
    Steen Carlsson, Katarina
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Healthcare Provider Type and Switch to Biologics in Psoriasis: Evidence from Real-World Practice2016In: BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, ISSN 1173-8804, Vol. 30, no 2, p. 145-151Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Previous research indicates an uneven uptake of biologics in patients with moderate-to-severe psoriasis in Sweden. Therefore, it is essential to scrutinise variations in treatment patterns.

    OBJECTIVE: The aim of this study was to evaluate the extent to which the uptake of biologics for psoriasis differs between types of healthcare provider.

    METHODS: Three types of provider were identified within 52 units participating in the Swedish National Registry for Systemic Psoriasis Treatment (PsoReg): university hospitals, non-university hospitals and individual practices. Biologics-naïve patients (n = 3165) were included in analyses to investigate the probability of switch to biologics. The numbers of patients fulfilling the criteria for moderate-to-severe psoriasis [Psoriasis Area and Severity Index (PASI) ≥10 and Dermatology Life Quality Index (DLQI) ≥10] among patients who switched to biologics and patients who did not switch were reported. A logistic regression model was used to calculate how healthcare provider type influenced the probability of switch to biologics whilst adjusting for patient characteristics and disease severity.

    RESULTS: During registration, 16 % of patients switched to biologics while 84 % remained on conventional systemic treatment. In 7 % of patients, the criteria PASI ≥10 and DLQI ≥10 was fulfilled at their last visit without switching to biologics, whereas in 10 % of patients the criteria was not fulfilled prior to switch. After controlling for patient characteristics and disease severity, small or no difference in the probability of switch was observed between provider types.

    CONCLUSIONS: Disease severity does not explain the decision to switch or not to switch to biologics for a disproportionate number of patients. There seems to be an uneven uptake of biologics in Swedish clinical practice, but the type of healthcare provider cannot explain this variation. More research is needed on what factors influence the prescription of biologics.

  • 22. Carlsson, A
    et al.
    Gånemo, A
    Anderson, C D
    Meding, Birgitta
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Svensson, Åke
    Scoring of hand eczema: good agreement between patients and dermatological staff2011In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, ISSN 0007-0963, Vol. 165, no 1, p. 123-128Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Assessment of hand eczema in a clinical study has been achieved using a scoring system which documents extent of eczema on different areas of the hand.

    OBJECTIVES: To investigate whether the same scoring system could be used by patients to communicate current status of hand eczema.

    METHODS: In a study of 62 patients (36 women and 26 men, age range 19-75 years), the patient's own assessment was compared with the assessment by a dermatologist and a dermatological nurse. Standardized information was given to the patient and the form was filled in independently by the patient, the nurse and the dermatologist, during the patient's visit to the clinic. Individual area scores were summed to a total score.

    RESULTS: The overall agreement was good, with an interclass correlation (ICC) of 0·61 between patient and dermatologist for the total score. The ICC between nurse and dermatologist was 0·78. Differences between observers were more pronounced for the more severe cases - those with higher numerical scores as assessed by the dermatologist. There was a tendency for women and for patients over the median age of 44 years to set a lower point score than the dermatologist. The concordance of observations from individual anatomical areas was higher for fingertips and nails and lower for the palm and dorsum of the hand.

    CONCLUSIONS: Patients are able to report the extent of hand eczema with good accuracy. Self-assessment protocols for hand eczema may well have a place in the monitoring of hand eczema extent over time.

  • 23. Carlsson, Annica
    et al.
    Svensson, Åke
    Anderson, Chris D
    Baranovskaya, Irina
    Hindsén-Stenström, Monica
    Holt, Ingebjörg
    Meding, Birgitta
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Gånemo, Agneta
    Scoring of hand eczema: good reliability of hand eczema extent score2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 2, p. 193-197Article in journal (Refereed)
    Abstract [en]

    There is good agreement between dermatological staff and patients using the Hand Eczema Extent Score (HEES). The aim of this study was to assess inter- and intra-observer reliability of the HEES in dermatologists and intra-observer reliability of the HEES in patients with hand eczema. Six dermatologists assessed 18 patients twice. Only the hands of the patients were visible to the assessors. Patients performed a self-assessment twice. Inter- and intra-observer reliability was tested with intraclass correlation coefficient (ICC). The mean HEES score for all dermatologists' assessments was 21.0 (range 3.6-46.3). The corresponding mean scores for all patients' own assessments were 24.9 (range 4.0-54.0). Inter-observer reliability in the dermatologists' observations ICC classification was very good, median value 0.82 (range 0.56-0.92). The overall intra-observer reliability for the 6 dermatologists' ICC classification was very good (range 0.88-0.94). Intra-observer reliability in the patients' 2 self-assessments ICC classification was very good (ICC 0.95). In conclusion, HEES is a reliable tool for both dermatologists and patients to grade the extent of hand eczema.

  • 24.
    Carré, Helena
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Who's at risk of catching Chlamydia trachomatis? Identifying factors associated with increased risk of infection to enable individualized care and intervention2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    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. 

  • 25.
    Carré, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Gärdén, Bodil
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    [Contact tracing a year back is worthwhile. Follow the Vasterbottens example to prevent Chlamydia transmission in Sweden!]2005In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 102, no 7, p. 468-71Article in journal (Refereed)
    Abstract [sv]

    Contact tracing is proved to be a good way to prevent asymptomatic sexually transmitted infections, such as Chlamydia trachomatis, from spreading. According to the Swedish law a physician has to report all cases of genital C. trachomatis to the County Medical Officer of Health and to the National institute for Infectious Disease Control and perform contact tracing. An evaluation of the sexual history 6 months back in time is recommended and standard in most of the country. The county of Västerbotten has one of the lowest incidenses of C. trachomatis in Sweden though the population is younger than the Swedish average. During year 2002 the contact tracing in Västerbotten was evaluated by sending a questionnaire to everyone who reported a case of genital C. trachomatis. We recived 534 (98%) out of 544 questionnaires. The patients reported 1360 partners, 2.5 on average, 1129 were identified. 761 had a known test result and 497 of them were positive, 0.9 on average. 72% of the contact tracers evaluated the sexual history > or = 12 months back in time. 78% of the contact tracings were performed by four social workers. Their patients reported 2.5 partners on average and 80% evaluated > or = 12 months back in time. 14 persons did only one contact tracing, 1.3 partners/index on average, 40% evaluated > or = 12 months back in time. 82% of the partners had sex with the infected patient 0-6 months before the patients was diagnosed with C. trachomatis, 75% out of those with a known test result were infected, 16% had sex 7-12 months before diagnosis, 30% infected. (The C. trachomatis prevalence in Sweden is estimated to be 2.7-4.9% among young women.) Conclusion: A few experienced persons tracing for at least 12 month back in time is probably two important reasons why Västerbotten has such a small C. trachomatis incidence.

  • 26.
    Carré, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Österlund, A
    Communicable Disease Prevention and Control, Sunderby Hospital, Luleå, Sweden.
    Gärdén, B
    The School of Life Sciences, University of Skövde, Skövde, Sweden.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Improved contact tracing for Chlamydia trachomatis with experienced tracers, tracing for one year back in time and interviewing by phone in remote areas2008In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 84, no 3, p. 239-242Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the Swedish model for contact tracing and especially the "Västerbotten model" with centralised, extended contact interview periods, sometimes by telephone.

    METHODS: Using questionnaires, the contact tracing and interview procedure was evaluated during 2002, followed by an evaluation of contact interviewing by phone in 2005-6.

    RESULTS: Patients with diagnosed Chlamydia trachomatis infection reported on average 2.5 sexual contacts, 3.0 contacts when contact interviewing was performed at the clinic, and 2.3 contacts when performed by phone. 65% of the sexual contacts with a known test result were infected.

    CONCLUSION: Centralised contact tracing, exploring the sexual history for at least 12 months back in time, shows good results. Combined with screening of certain risk groups it is probably one effective way of preventing C trachomatis infections. Preventing C trachomatis by primary prevention such as information and counselling is, however, still of great importance.

  • 27.
    Carré, Helena
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Lindström, Richard
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Nordström, Annika
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Janlert, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    High prevalence of anxiety and hazardous alcohol consumption among patients attending an STI-clinic in northern SwedenManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: Depression and hazardous alcohol consumption is associated to high-risk sexual behaviours among adolescents and young adults. Is the same true among grownups? The impact of anxiety on sexual risk behaviour is not thoroughly investigated. Our aim was to evaluate the correlation between hazardous alcohol consumption, depression and anxiety to sexual risk taking including Chlamydia infections, among patients attending an STI reception.

     Method: Patients attending an urban STI reception in Sweden were consecutively included and received questionnaires; screening- and demographic information, Alcohol Use Disorder Identification Test (AUDIT) and Hospital Anxiety and Depression scale (HAD). All patients also had a test for Chlamydia trachomatis taken.

    Results: 539 patients were included in the study, mean age 28 years. 152 (30%) had signs of anxiety and 37 (7%) of depression, of which 30 had also anxiety. Neither anxiety nor depression was correlated to sexual risk behaviour. >50% had hazardous alcohol consumption and it was independently linked to sexual risk behaviours and anxiety.

    Conclusion: Depression is not associated to sexual risk behaviours among adult STI-patients. Health care staff and must consider the high frequency of anxiety and hazardous alcohol consumption at their treatment of STI-clinic patients and in the preventive work. The society must work with lowering the stigmatization that still seems to be connected to STIs.

  • 28.
    Christianson, Monica
    et al.
    Umeå University, Faculty of Medicine, Department of Nursing.
    Boman, Jens
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Essén, Birgitta
    'Let men into the pregnancy': men's perceptions about being tested for Chlamydia and HIV during pregnancy2013In: Midwifery, ISSN 0266-6138, E-ISSN 1532-3099, Vol. 29, no 4, p. 351-358Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate how to prevent transmission of HIV and Chlamydia trachomatis (CT) by exploring whether screening of men during pregnancy may be an innovative way to reach men, to increase detection, and to avoid the present gendered responsibility.

    DESIGN: An explorative research strategy with in-depth interviews and an analysis informed by grounded theory principles was used.

    SETTING: The northern part of Sweden.

    PARTICIPANTS: Twenty men/becoming fathers in their twenties and early thirties were offered CT and HIV testing and were interviewed about their perceptions about being tested during pregnancy.

    FINDINGS: Six categories emerged that concerned the men's risk perceptions, reasons for not testing men, benefits and negative consequences associated with being tested, incentive measures for reaching men and the optional time for testing men during pregnancy. The majority of the men perceived their own risk for having CT or HIV to be close to zero, trusted their stable partner, and did not see men as transmitters. They did not understand how men could play a role in CT or HIV transmission or how these infections could negatively affect the child. However, few informants could see any logical reasons for excluding men from testing and the majority was positive towards screening men during the pregnancy.

    KEY CONCLUSIONS: Men's sexual health and behaviour on social and biological grounds will affect the health of women and their children during pregnancy and childbirth. As long as expectant fathers do not count in this 'triad', there is a risk that CT and HIV infections in adults and infants will continue to be an unsolved problem.

    IMPLICATIONS FOR PRACTICE: Knowledge from this research can contribute to influencing the attitudes among health-care providers positively, and inspiring policy changes.

  • 29.
    Claesson, Maria
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine.
    Women's hearts: ischaemic heart disease and stress management in women2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Acute myocardial infarction (AMI), caused by ischaemic heart disease (IHD), is a leading cause of death in both men and women in the western society. Hypertension, diabetes, and smoking are examples of well-known risk factors of IHD, but also there are psychosocial factors, such as stress, vital exhaustion (unusual fatigue, irritability, and demoralization) and depression that have been associated with an increased risk in both genders. After an AMI, however, women are more likely than men to be psychosocially impaired resulting in suffering and a presumed increase in the risk of recurrent cardiac events.

    Psychosocial factors may be targeted in secondary prevention, complementary to drug treatment and conventional lifestyle advice. There is some evidence of beneficial effects on both psychosocial well-being and cardiac outcomes by psychosocial interventions in men. Far fewer women have been studied and the results have been inconsistent. It is not clear how psychosocial factors convey the increased risk of cardiac events, but many possible psychopathological mechanisms, including biochemical and physiological links, have been suggested.

    In the Women’s Hearts study we have, in a randomised controlled trial, evaluated a one-year cognitive-behavioural stress management programme designed specifically for women with IHD. We included 198 women with IHD, with a mean age of 61 years and from the county of Västerbotten in Northern Sweden, who were randomised to either conventional treatment and follow-up, or to stress management in addition to conventional care. Extensive questionnaires, blood samplings, and biomedical and physiologic data were obtained before randomisation, as well as at follow-ups approximately one and two years after randomisation. Two groups of healthy controls were included for comparisons with women with IHD.

    Compared to women without IHD, women with IHD reported more stress behaviour and vital exhaustion. Women with IHD also had a lower heart rate variability (HRV) than the healthy controls, possibly reflecting a dysfunctional autonomic nervous regulation of the heart. Reduced HRV has been shown to increase the risk of cardiac arrhythmias and sudden death.

    At the first follow-up, performed at the end of the one-year stress management programme, women who had participated in the programme had reduced the stress behaviour and vital exhaustion, compared to the women in the conventional care group. We could not find any evidence of a direct cause-effect relationship between stress management and biological cardiovascular risk indicators, or HRV; the intervention and control groups did not differ in insulin resistance, inflammatory, haemostatic and fibrinolytic factors, or HRV.

    At second follow-up one year later, several additional psychosocial domains were studied. The stress management programme had accelerated psychosocial recovery at the first follow-up over and above that observed in the control group. At the second follow-up, there was further marked improvement in the control group, so the differences in psychosocial variables between the intervention and control groups were no longer significant.

    In conclusion, a cognitive-behavioural stress management programme could accelerate psychosocial improvement in women with IHD, and thus reduce the amount of psychological and psychosocial suffering. We could not find any evidence that the stress management programme was associated with a concomitant improvement in biological cardiovascular risk indicators, or HRV. Our results suggest that the women with the greatest psychosocial burden should be identified and targeted in new clinical trials of cognitive-behavioural interventions in women with IHD. Future studies within the Women’s Hearts project will evaluate the psychosocial effects at a five-year follow-up, as well as investigations of other possible pathways by which psychosocial interventions might mediate beneficial effects on cardiac events.

  • 30.
    Dahmoun, Marju
    Umeå University, Faculty of Medicine, Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Radiation Sciences, Oncology. Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Apoptosis, proliferation, and sex steroid receptors in endometrium and endometrial carcinoma2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focuses on the involvement of apoptosis and proliferation in the mechanisms of menstruation and hormonal replacement therapy, HRT, as well as in the mechanisms of progesterone therapy in endometrial carcinoma.

    The aim of the first study was to investigate endometrium for 4 days before and for 2 days during menstruation. In the epithelium, rapid increase in the apoptotic index, decreasing expression of estrogen receptor α (ER) and progesterone receptor (PR), and minimal proliferation were observed prior to menstruation. In the stroma, an increase in the expression of ER and PR and proliferation was seen before the final decrease, and increased apoptosis was seen during menstruation. Thus, apoptosis is involved in the remodeling of the endometrium during menstruation.

    Postmenopausal endometrium showed unaffected homeostasis, i.e. unchanged ratio between apoptotic index and Ki-67 index during substitution therapy. ER expression was decreased both in the epithelium and stroma, while PR showed some increase in receptor expression. The unchanged homeostasis contributes to endometrial safety during combined continuous HRT.

    Unchanged apoptosis and increasing proliferation were observed with increasing tumor grade in 29 patients with endometrioid endometrial carcinoma, which may contribute to greater aggression as tumor grade increases. Decreased proliferation was observed after medroxy-progesterone at 20 mg per day particularly in the foci of maximal proliferation in G1 and G2 tumors. The expression of ER was unchanged, while PR was decreased in the foci of maximal expression for PR in G1 and G2 tumors. Since high proliferation and PR expression also coexisted in the same foci, evaluated in G1 and G2 tumors, the effect of progesterone could be facilitated in these tumor groups. High expression of sex steroid receptors was also a predicting factor for good response to progesterone (= decrease in proliferation), while the amount of stroma could not predict that effect.

  • 31.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Rentoft, Matilda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Coates, Philip
    Tayside Tissue Bank/Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Autoantibodies and decreased expression of the transcription factor ELF-3 together with increased chemokine pathways support an autoimmune phenotype and altered differentiation in lichen planus located in oral mucosa2013In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 27, no 11, p. 1410-1416Article in journal (Refereed)
    Abstract [en]

    Background  The pathogenesis of oral lichen planus (OLP), a chronic inflammatory disease, is not fully understood. It is known that OLP has autoimmune features, and it is suggested to be an autoimmune disease. ELF-3 is involved in differentiation of keratinocytes and deregulated in different tumours and inflammatory diseases. CXCR-3 and its ligands CXCL-10 and CXCL-11 are increased in autoimmune diseases and linked to Th-1 immune response. Objectives  To analyse and compare expression of ELF-3, CXCR-3, CXCL-10 and CXCL-11 in OLP lesions and controls in whole and microdissected epithelium. Methods  Tissue biopsies from 20 patients clinically and histologically diagnosed with OLP and 20 healthy controls were studied using whole tissues or microdissected epithelium. By the use of qRT-PCR, mRNA levels of ELF-3, CXCR-3, CXCL-10 and CXCL-11 were studied. Western blot was used for analysis of ELF-3 protein expression. Sera from 19 OLP patients and 20 controls were analysed with ELISA in search for autoantibodies. Results  The upregulation of CXCR-3, CXCL-10 and CXCL-11 found in OLP is similar to previous findings showing an autoimmune phenotype in lichen planus (LP) and lichen sclerosus. Decreased expression of the differentiation-related transcription factor ELF-3 was also seen in OLP lesions, and we further demonstrate presence of circulating autoantibodies against the ELF-3 protein in sera from 3 of 19 (16%) LP patients tested. Conclusions  On the basis of these findings, we confirm that OLP shows features of an autoimmune disease and suggest deregulated differentiation of keratinocytes to be one of the causes of the disease phenotype.

  • 32.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ebrahimi, Maijd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Increased levels of COX-2 in oral lichen planus supports an autoimmune cause of the disease2012In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 26, no 11, p. 1415-1419Article in journal (Refereed)
    Abstract [en]

    Background: Oral lichen planus (OLP) is a chronic inflammatory disease for which the pathogenesis is not fully understood. OLP has autoimmune features and auto immunity has been suggested as a potential cause, whereas WHO has classified OLP as a premalignant condition. Association between chronic inflammation and cancer is known and chronic inflammation is one of the characteristics of OLP. A protein connected to inflammation and suggested to be involved in cancer development is cyclooxygenase-2 (COX-2) which can be inhibited by microRNA-26b (miR-26b).

    Objective: The aim was to map levels of COX-2 and miR-26b in OLP lesions to see if there was any correlation between expression of COX-2 and its regulator miR-26b in OLP.

    Methods: In biopsies from 20 OLP patients and 20 age and gender-matched controls laser- micro dissection of epithelium was performed. Quantitative RT-PCR, immunohistochemistry and Western blot were used in the analysis.

    Results: Levels of COX-2 mRNA were significantly higher while levels of miR-26b were significantly lower in OLP lesions compared to controls. Using immunohistochemistry normal oral mucosa samples did not show any expression of COX-2 while OLP samples expressed the protein. No COX-2 protein was detectable with Western blot.

    Conclusion: Increased expression of COX-2 and decreased expression of miR-26b in OLP suggests both to play a role in OLP. COX-2 has been connected to both malignant development and autoimmunity but as malignant development of OLP is quite rare we suggest that the increased levels of COX-2 seen here support an autoimmune cause of the disease.

  • 33.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Alterations in factors involved in differentiation and barrier function in the epithelium in oral and genital lichen planus2017In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 97, no 2, p. 214-218Article in journal (Refereed)
    Abstract [en]

    Lichen planus is a chronic recurrent inflammatory disease affecting both skin and mucosa, mainly in oral and/or genital regions. Keratinocytes go through a well-regulated process of proliferation and differentiation, alterations in which may result in defects in the protective epithelial barrier. Long-term barrier impairment might lead to chronic inflammation. In order to broaden our understanding of the differentiation process in mucosal lichen planus, we mapped the expression of 4 factors known to be involved in differentiation. Biopsies were collected from oral and genital lichen planus lesions and normal controls. Altered expression of all 4 factors in epithelium from lichen planus lesions was found, clearly indicating disturbed epithelial differentiation in lichen planus lesions.

  • 34.
    Danielsson, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics.
    Ebrahimi, Majid
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics. Umeå University, Faculty of Medicine, Department of Odontology, Endodontics.
    Wahlin, Ylva-Britt
    Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics. Umeå University, Faculty of Medicine, Department of Odontology, Prosthetic Dentistry.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Reply to increased levels of COX-2 and oral lichen planus by P.D. Pigatto, F. Spaderi, G.P. Bombeccari, G. Guzzi by Danielsson et al2013In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 27, no 3, p. 395-396Article in journal (Refereed)
  • 35. Dans, Antonio
    et al.
    Ng, Nawi
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Varghese, Cherian
    Tai, E. Shyong
    Firestone, Rebecca
    Bonita, Ruth
    Non-communicable diseases in southeast Asia Reply2011In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 377, no 9782, p. 2005-2005Article in journal (Refereed)
  • 36.
    Davila-Seijo, P.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Academia Espanola de Dermatologıa Venereolog Fundacion Piel Sana, Madrid, Spain.
    Descalzo, M. A.
    Registries as real-world cohort studies that are useful and necessary in the pyramid of evidence2018In: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 178, no 1, p. 300-301Article in journal (Refereed)
  • 37. de Veer, Simon J.
    et al.
    Furio, Laetitia
    Swedberg, Joakim E.
    Munro, Christopher A.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Clements, Judith A.
    Hovnanian, Alain
    Harris, Jonathan M.
    Selective Substrates and Inhibitors for Kallikrein-Related Peptidase 7 (KLK7) Shed Light on KLK Proteolytic Activity in the Stratum Corneum2017In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 137, no 2, p. 430-439Article in journal (Refereed)
    Abstract [en]

    Proteases have pivotal roles in the skin's outermost layer, the epidermis. In the stratum corneum, serine proteases from the kallikrein-related peptidase (KLK) family have been implicated in several key homeostatic processes, including desquamation. However, the precise contribution of specific KLKs to each process remains unclear. To address this, we used a chemical biology approach and designed selective substrates and inhibitors for KLK7, the most abundant KLK protease in the stratum corneum. The resulting KLK7 inhibitor is the most potent inhibitor of this protease reported to date (K-i = 140 pM), and displays at least 1,000-fold selectivity over several proteases that are related by function (KLK5 and KLK14) or specificity (chymotrypsin). We then used substrates and inhibitors for KLK5, KLK7, and KLK14 to explore the activity of each protease in the stratum corneum using casein zymography and an ex vivo desquamation assay. These experiments provide the most detailed assessment of each KLK's contribution to corneocyte shedding in the plantar stratum corneum, revealing that inhibition of KLK7 alone is sufficient to block shedding, whereas KLK5 is also a major contributor. Collectively, these findings unveil chemical tools for studying KLK activity and demonstrate their potential for characterizing KLK biological functions in epidermal homeostasis.

  • 38.
    Ebrahimi, Majid
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology, Endodontics. Umeå University, Faculty of Medicine, Department of Odontology, Oral Diagnostics.
    Lundqvist, Lotta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Wahlin, Ylva Britt
    Umeå University, Faculty of Medicine, Department of Odontology.
    Nylander, Elisabet
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Mucosal lichen planus, a systemic disease requiring multidisciplinary care: a cross-sectional clinical review from a multidisciplinary perspective2012In: Journal of Lower Genital Tract Disease, ISSN 1089-2591, E-ISSN 1526-0976, Vol. 16, no 4, p. 377-380Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study aimed to emphasize the importance of seeing mucosal lichen planus (LP) as a systemic disease and not an isolated oral or genital disease and to analyze the proportion of thyroid antibodies among patients with multimucosal LP.

    MATERIALS AND METHODS: All patients examined by the authors and diagnosed with mucosal LP within 1 year were consecutively included. Full medical histories were collected with special emphasis on autoimmune and thyroid diseases. Sera were analyzed for thyroid antibodies and underwent serologic test for herpes virus. The control group comprised 83 healthy volunteers matched regarding sex and age.

    RESULTS: Of the patients, 120 were included, 89 (74%) of whom were women and 31 (26%) were men. The vast majority of the patients had multifocal lesions, whereas oral lesions solely were found in 28% of women and 36% of men. Of the patients, 28% had at least 1 additional autoimmune disease. Approximately half of the women were treated with levothyroxine owing to thyroid disease. Antibodies against herpes simplex virus were found in 60% of the patients and 44% of the controls (p < .03).

    CONCLUSIONS: Lichen planus with mucosal involvement should be considered and taken care of as a systemic disease and not as an isolated oral and/or genital lichen. Contradictory to many former reports, most of our patients have a multimucosal disease that emphasizes the need for a multidisciplinary clinic to get optimal care and treatment.

  • 39.
    Eilers, Hinnerk
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Alexeyev, Oleg A.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Effect of GT-Peptide 10 and Triethyl Citrate on P. acnes Biofilm Formation, Viability, and Dispersion2016In: Journal of drugs in dermatology, ISSN 1545-9616, Vol. 15, no 6, p. 778-781Article in journal (Refereed)
    Abstract [en]

    Background: P. acnes biofilms are emerging topics in acne vulgaris pathogenesis and may be responsible for antibiotic tolerance. Objective: To investigate the efficacy of GT peptide 10 either alone or in combination with triethyl citrate (TEC) in in vitro model of P acnes biofilm. Methods: Six-day-old P acnes biofilms were treated with various concentrations of these substances and biofilm dispersion and cell viability were monitored. Results: A 24-hour exposure of preformed biofilms to a combination of GT peptide 10/TEC led to killing of up to 92% of bacterial cells inside the biofilm. Neither the single substance nor the combination of both substances affected the biofilm integrity or resulted in biofilm dispersal. Conclusions: A combination of GT peptide 10/TEC shows antibacterial effects in in vitro model of P. acnes biofilm.

  • 40. Ekelund, Mats
    et al.
    Mallbris, Lotus
    Qvitzau, Susanne
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    A Higher Score on the Dermatology Life Quality Index, Being on Systemic Treatment and Having a Diagnosis of Psoriatic Arthritis is Associated with Increased Costs in Patients with Plaque Psoriasis2013In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 93, no 6, p. 684-688Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to examine the relationship between measures of disease severity and costs from a socie-tal perspective in patients with plaque psoriasis. Dermatologists in Sweden recruited 443 consecutive patients who had had no biological treatment during the past 12 months. Following a Psoriasis Area and Severity Index (PASI) assessment, subjects completed self-assessments on health status/quality of life and a healthcare resource utilization/work status questionnaire. The costs of healthcare resources and sick-leave due to plaque psoriasis were estimated and related to the subject's health status. A patient's Dermatology Life Quality Index (DLQI) and being on systemic therapy, or having diagnosis of psoriatic arthritis, appeared to be more strongly associated with direct and indirect costs than did their PASI. The cost of biological therapy should be considered from the perspective of the already high costs of patients with high DLQI undergoing traditional systemic treatment.

  • 41.
    Ekholm, Elisabeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Sondell, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Strandén, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Egelrud, Torbjörn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Expression of stratum corneum chymotryptic enzyme in human sebaceous follicles1998In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 78, no 5, p. 343-347Article in journal (Refereed)
    Abstract [en]

    Stratum corneum chymotryptic enzyme (SCCE) may be involved in desquamation, a process necessary for maintaining a normal anatomy at all sites where there is continuous turnover of cornified epithelia. Using immunohistochemistry and in situ hybridization, we have, in this work, analysed SCCE expression in the sebaceous follicle. We found expression of SCCE in luminal parts of the pilary canal, common sebaceous ducts and proximal sebaceous ducts. In addition, SCCE was seen in cells apparently situated within the distal parts of the glandular lobules. Co-expression of SCCE and keratin 10 was seen only in the pilary canal and the common sebaceous ducts. The results give further support for SCCE being involved in desquamation-like processes. The association with cornification seems to be more general for SCCE than for keratin 10. The possible role of SCCE in diseases involving disturbances in the turnover of cornified cells in the sebaceous follicle, such as acne vulgaris, is a question for future studies.

  • 42.
    Ekholm, I Elisabeth
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Brattsand, Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Egelrud, Torbjörn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Stratum corneum tryptic enzyme in normal epidermis: a missing link in the desquamation process?2000In: Journal of Investigative Dermatology, ISSN 0022-202X, E-ISSN 1523-1747, Vol. 114, no 1, p. 56-63Article in journal (Refereed)
    Abstract [en]

    Stratum corneum chymotryptic enzyme may be important in desquamation. It has also been suggested that other proteases, especially stratum corneum tryptic enzyme, may be involved. Stratum corneum tryptic enzyme has been purified and its cDNA has been cloned. Results from expression analyses indicate that stratum corneum tryptic enzyme is as skin specific as stratum corneum chymotryptic enzyme. In this work we have produced and characterized antibodies specific for stratum corneum tryptic enzyme. We have also by means of biochemical, immunochemical, and immunohistochemical methods performed studies on stratum corneum tryptic enzyme in normal human epidermis. Antibodies against bacterial recombinant stratum corneum tryptic enzyme were produced and purified by affinity chromatography. Two types of antibodies were obtained: one reacting only with pro-stratum corneum tryptic enzyme and one specific for the catalytically active part of stratum corneum tryptic enzyme. Immunohistochemistry with the antibodies reacting with pro-stratum corneum tryptic enzyme showed a staining pattern similar to stratum corneum chymotryptic enzyme-specific antibodies, i.e., the expression was confined to cornifying epithelia with a need of desquamation-like processes. Extracts of tape strips with superficial human stratum corneum were found to contain precursors as well as active forms of stratum corneum tryptic enzyme and stratum corneum chymotryptic enzyme. The enzymes had maximal activity at pH 8, but both had considerable activity also at pH 5.5. The results were compatible for a role of stratum corneum tryptic enzyme in desquamation. Stratum corneum tryptic enzyme may act in concert with stratum corneum chymotryptic enzyme and/or function as a stratum corneum chymotryptic enzyme-activating enzyme. The presence in normal superficial stratum corneum of precursors as well as of active forms of stratum corneum chymotryptic enzyme and stratum corneum tryptic enzyme, and the activity of both enzymes over a broad range of pH-values, suggest some possible ways by which the desquamation may be regulated.

  • 43.
    Emgård, Per
    Umeå University, Faculty of Medicine, Clinical Sciences, Otorhinolaryngology. Umeå University, Faculty of Medicine, Clinical Microbiology, Clinical Bacteriology.
    External otitis and its treatment: is a group III steroid without antibiotics sufficent therapy? Experimental and clinical studies2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    ABSTRACT

    External otitis and its treatment. Is a group III steroid without antibiotics sufficient therapy? – Experimental and clinical studies

    Per Emgård, Department of Otorhinolaryngology, University of Umeå and Ystad Hospital, Umeå and Ystad, Sweden

    External otitis is one of the most common ear, nose and throat (ENT) diagnoses in out-patient clinics. The clinical course of external otitis includes itching, pain, redness, swelling and effusion of the external auditory canal (EAC) with normal tympanic membrane status. The inflammatory condition is often associated with infection by bacteria, e.g. Pseudomonas aeruginosa, or skin bacteria such as Staphylococcus species. Fungi are present only in a low percentage of cases and if present Candida albicans infection is the most frequent in northern countries such as Sweden and the UK. Topical therapy is recommended in most countries and dominates the therapy in most studies. Topical drugs used are usually a combination of antibiotics and a steroid. However, external otitis is treated with surprisingly many strategies – eleven different ones in Sweden, for example, and 18 in the UK.

    The aims of the present studies were to –

    -establish an animal model, infected and uninfected, suitable for testing various treatment strategies of external otitis; and

    -perform a clinical study in patients to elucidate whether a group III steroid alone is as efficient for treatment of external otitis as is the commonly used topical drug containing a combination of a steroid and antibiotics.

    The animal model was established through mechanical irritation of the external ear canal skin of Sprague-Dawley rats. An evaluation scale for characterization of the clinical status of the ear canal was introduced, recording redness, swelling and occurrence of effusion in a standardized way. Specimens of the ear canal skin were analysed by histological techniques. A topical solution of 0.05% bethametasone dipropionate (BD) was compared with a 1% hydrocortisone solution with antibiotics oxytetracycline and polymyxin B added (HCPB), administered in the external otitis model infected or non-infected with bacteria (P. aeruginosa) and a fungus (C. albicans).

    The same drugs were tested in a randomized parallel-group multi-centre study in 51 patients. The clinical status of the external otitis patients was evaluated on a similar scale as used in the animal model. Early normalization of the ear canal skin status and frequency of relapses during the 6-month follow-up period were used as end-points of the study.

    The studies showed the following:

    -An animal model for external otitis, infected or uninfected, could be established.

    -A new scale for evaluation of the external ear canal status with regard to redness, swelling and occurrence of effusion was introduced for the animal model as well as for the investigations in patients.

    -Treatment with a group III steroid topical solution without antibiotics was superior to treatment with a group I steroid with antibiotics added in achieving resolution of external otitis.

    -The effectiveness of the topical drugs in the clinical studies in external otitis patients was similar to that in animal external otitis models.

    We conclude that a group III steroid solution cures external otitis more effectively than does a solution containing a group I steroid combined with antibiotics, whether infected by bacteria or by fungi. No difference was evident regarding adverse effects. Furthermore, costs favour a solution without any antibiotic components. In view of these observations a group III steroid solution is preferred for remedy of external otitis in the clinical situation.

    Key words: external otitis, external auditory canal (EAC), animal model, treatment, betamethasone, hydrocortisone, antibiotics, human study, Pseudomonas aeruginosa, Candida albicans.

  • 44. Engfeldt, Malin
    et al.
    Bråred-Christensson, Johanna
    Isaksson, Marlene
    Matura, Mihály
    Ryberg, Kristina
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Svedman, Cecilia
    Bruze, Magnus
    Swedish Experiences From Patch-testing Methylisothiazolinone Separately2015In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 95, no 6, p. 717-719Article in journal (Refereed)
    Abstract [en]

    The preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) is a well-known sensitiser and present in the Swedish baseline series since the 1980s. The proportions of MCI/MI are 3:1. MI alone has been used as a preservative since less than 10 years. This study was conducted on behalf of the Swedish Contact Dermatitis Research Group to evaluate inclusion of MI in the Swedish baseline series since the preparation of MCI/MI might fail to detect contact-allergic reactions to MI alone. Patients with suspected allergic contact dermatitis at 5 Swedish dermatology departments were consecutively patch-tested with MI 2,000 ppm aq and MCI/MI 200 ppm aq. The number of cases with exclusive contact allergy to MI varied between 0.8-4.2%. In total, 1.9% reacted exclusively to MI and not to MCI/MI. Due to the considerable frequency of contact allergy to MI not traced by MCI/MI, MI 2,000 ppm aq is included in the Swedish baseline series from January 2014. This corresponds to a dose of 60 mu g/cm(2).

  • 45. Engfeldt, Malin
    et al.
    Hagvall, Lina
    Isaksson, Marlene
    Matura, Mihaly
    Mowitz, Martin
    Ryberg, Kristina
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Svedman, Cecilia
    Bruze, Magnus
    Patch testing with hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) - a multicentre study of the Swedish Contact Dermatitis Research Group2017In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 76, no 1, p. 34-39Article in journal (Refereed)
    Abstract [en]

    Background. In 2014, the fragrance hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) was excluded from the Swedish baseline series. Objectives. To study (i) whether fragrance mix (FM) II with 5% HICC detects more positive reactions than usual FM II with 2.5% HICC, and (ii) the reproducibility of patch testing with HICC. Methods. Two thousand one hundred and eighteen dermatitis patients at five Swedish dermatology departments were consecutively tested with FM II 14% pet., FM II 16.5% pet., and duplicate preparations of HICC 5% pet. Results. Of the patients, 3.2% reacted to FMII 14%, and 1.5% reacted to HICC. Separate testing with HICC detected 0.3% reactions without concomitant reactivity to FM II. FM II with 5% HICC did not give rise to more irritant reactions or signs of active sensitization than FM II with 2.5% HICC. Patch testing with duplicate applications of HICC increased the overall prevalence of HICC contact allergy to 1.9%. Conclusion. FMII with5% HICC does not detect more positive reactions than FMII with 2.5% HICC. Separate testing with HICC does not detect a sufficient proportion of patients who react only to HICC, without concomitant reactions to FMII, to warrant its inclusion in a baseline series.

  • 46. Fakler, JW
    et al.
    Schmitt-Egenolf, Marcus
    Department of Dermatology, University of Ulm, Ulm, Germany.
    Vejbaesya, S
    Boehncke, WH
    Sterry, W
    Eiermann, TH
    Analysis of TAP2 and HLA-DP gene polymorphism in psoriasis1994In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 40, no 4, p. 299-302Article in journal (Refereed)
    Abstract [en]

    TAP2 is a gene, located between HLA-DP and HLA-DQ, whose products form a transporter molecule involved in endogenous antigen processing. Polymorphic residues have been described in this gene. TAP2 is of particular interest because its involvement in antigen presentation makes it a candidate for a disease susceptibility gene. In psoriasis, two clinical subtypes analogous to the situation in diabetes type I with early onset and family history and type II with later onset and without family history have been described. We have previously shown that type I but not type II psoriasis is associated with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 haplotype. To investigate whether this haplotype extends to include particular TAP2 and/or DP alleles, we tested the TAP2 and HLA-DP alleles of a control group (n = 199), patients with psoriasis type I (n = 66), and patients with psoriasis type II (n = 35) by hybridization with SSOs. Our data show that there is no significant correlation between TAP2 and/or HLA-DP gene polymorphism and psoriasis type I and/or type II. We conclude that disease association in type I psoriasis is associated with the extended haplotype HLA-B57, -Cw6, -DRB1*0701/2, -DQA1*0201, -DQB1*0303.

  • 47.
    Falk Kieri, Catarina
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Bergendal, Birgitta
    Lind, Lisbet K
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Schmitt-Egenolf, Marcus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Stecksén-Blicks, Christina
    Umeå University, Faculty of Medicine, Department of Odontology.
    EDAR-induced hypohidrotic ectodermal dysplasia: a clinical study on signs and symptoms in individuals with a heterozygous c.1072C > T mutation2014In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 15, p. 57-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mutations in the EDAR-gene cause hypohidrotic ectodermal dysplasia, however, the oral phenotype has been described in a limited number of cases. The aim of the present study was to clinically describe individuals with the c.1072C > T mutation (p. Arg358X) in the EDAR gene with respect to dental signs and saliva secretion, symptoms from other ectodermal structures and to assess orofacial function.

    METHODS: Individuals in three families living in Sweden, where some members had a known c.1072C > T mutation in the EDAR gene with an autosomal dominant inheritance (AD), were included in a clinical investigation on oral signs and symptoms and self-reported symptoms from other ectodermal structures (n = 37). Confirmation of the c.1072C > T mutation in the EDAR gene were performed by genomic sequencing. Orofacial function was evaluated with NOT-S.

    RESULTS: The mutation was identified in 17 of 37 family members. The mean number of missing teeth due to agenesis was 10.3 ± 4.1, (range 4-17) in the mutation group and 0.1 ± 0.3, (range 0-1) in the non-mutation group (p < 0.01). All individuals with the mutation were missing the maxillary lateral incisors and one or more of the mandibular incisors; and 81.3% were missing all four. Stimulated saliva secretion was 0.9 ± 0.5 ml/min in the mutation group vs 1.7 ± 0.6 ml/min in the non-mutation group (p < 0.01). Reduced ability to sweat was reported by 82% in the mutation group and by 20% in the non-mutation group (p < 0.01). The mean NOT-S score was 3.0 ± 1.9 (range 0-6) in the mutation group and 1.5 ± 1.1 (range 0-5) in the non-mutation group (p < 0.01). Lisping was present in 56% of individuals in the mutation group.

    CONCLUSIONS: Individuals with a c.1072C > T mutation in the EDAR-gene displayed a typical pattern of congenitally missing teeth in the frontal area with functional consequences. They therefore have a need for special attention in dental care, both with reference to tooth agenesis and low salivary secretion with an increased risk for caries. Sweating problems were the most frequently reported symptom from other ectodermal structures.

  • 48. Fall, Sofia
    et al.
    Bruze, Magnus
    Isaksson, Marlene
    Liden, Carola
    Matura, Mihaly
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Lindberg, Magnus
    Contact allergy trends in Sweden - a retrospective comparison of patch test data from 1992, 2000, and 20092015In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 72, no 5, p. 297-304Article in journal (Refereed)
    Abstract [en]

    Background. Contact allergy prevalence rates change over time as a result of variations in allergen exposure. Data from patch test clinics are often used as markers for allergy trends.

    Objectives. The aim of the present retrospective study was to describe trends in rates of sensitization to allergens in the Swedish baseline series. Patients/materials/methods. Prevalence rates are described by comparing consecutive patch test data from 1992, 2000 and 2009 in Swedish patch test clinics. In total, 3680 patients were included in 1992, 3825 in 2000, and 3112 in 2009.

    Results. Among test substances with a sensitization rate above 2% in 2009, significant decreases were noted for nickel sulfate, cobalt chloride, colophonium, and methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI), and a significant increase for p-phenylenediamine, as compared with 1992. Potassium dichromate reactions had increased among younger women, whereas reactions to nickel and cobalt had decreased in this group. Sensitization to chromium, cobalt and fragrance mix I had decreased among older men, and sensitization to nickel had decreased among younger men.

    Conclusions. It is probable that these changes in 1992-2009 reflect both changes in regulations for nickel, lower levels of chromium in cement and of MCI/MI in cosmetics, and increasing use of hair dyes.

  • 49. Flytström, Ingela
    et al.
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Svensson, Åke
    Bergbrant, Ing-Marie
    Patients' visual analogue scale: a useful method for assessing psoriasis severity2012In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 92, no 4, p. 347-348Article in journal (Refereed)
  • 50.
    Fors, Ronny
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Persson, Maurits
    Umeå University, Faculty of Medicine, Department of Odontology.
    Bergström, Erik
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Stymne, Birgitta
    Stenberg, Berndt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Dermatology and Venerology.
    Lifestyle and nickel allergy in a Swedish adolescent population: effects of piercing, tattooing and orthodontic appliances2012In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 92, no 6, p. 664-668Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to estimate the prevalence of life-style practices in adolescents and their association with nickel allergy. Upper secondary school pupils (n = 4,376; 15-23 years) were patch-tested for nickel aller-gy, follow-ing completion of a questionnaire (answered by 6,095). Almost 86% girls and 21% of boys reported piercing. More girls (6%) than boys (3%) had a tattoo. Twenty-six percent of the girls and 18% of the boys were regular smokers. Vegetarian/vegan diets were reported by 20% of girls and by 6% of boys. Piercing, female gender, and vocational programme increased the risk of nickel allergy, whereas orthodontic appliance treat-ment prior to piercing reduced the risk of nickel allergy. Pupils in vocational programmes had the highest prevalence of nickel allergy. Lifestyle behaviours are interconnected and cluster in subgroups of adolescents. Female sex, piercing and choice of educational programme are prominent lifestyle markers. A trend shift is observed, where more girls than boys report tattooing.

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