| 11. |
- Kucinskiene, Vesta, et al.
(författare)
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Home sampling and pooling of vaginal samples are effective tools for genetic screening of Chlamydia trachomatis among high school female students in Lithuania
- 2008
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Ingår i: Scandinavian Journal of Infectious Diseases. - London : Taylor & Francis. - 0036-5548 .- 1651-1980. ; 40:2, s. 88-93
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Tidskriftsartikel (refereegranskat)abstract
- The aims were 1) to estimate the prevalence of C. trachomatis infection among sexually active female students in Kaunas, Lithuania; 2) to investigate the usefulness of personal invitation, self-sampling, and pooling of samples for screening; and 3) to evaluate the costs of the approaches used. A cross-sectional study inviting 795 female students (18–31 y of age) from 7 high schools and 1 college in Kaunas was performed. The response rate was 67% (533/795). Self-obtained vaginal samples were analysed, individually and pooled (n=3), using Digene Hybrid Capture II CT/NG Test. The overall prevalence of C. trachomatis infection was 5.6%. Among the sexually active female students 20–24 y of age (n=424), the prevalence was 7.1%; however, the prevalence varied from 0% to 14.2% at the different schools. For estimation of the population prevalence based solely on identification of C. trachomatis positive pools, the pooling strategy reduced the costs by 85%. For estimation of population prevalence and for diagnosis of each individual sample, pooling reduced the costs by 70%. Targeted screening, using pooling to reduce the expenses, mainly of 3rd and 4th y Lithuanian female students could be recommended. By extended personal contact and internet-based communication, increased participation rates may be attained.
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| 12. |
- Lan, P. T., et al.
(författare)
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Reproductive tract infections including sexually transmitted infections : a population-based study of women of reproductive age in a rural district of Vietnam.
- 2008
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Ingår i: Sexually Transmitted Infections. - London : BMJ Publishing Group. - 1368-4973 .- 1472-3263. ; 84:2, s. 126-132
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the prevalences of reproductive tract infections (RTI)/sexually transmitted infections (STI) among married women in a rural district of Vietnam, and analyse the influence of socioeconomic, sociodemographic, and other determinants possibly related to RTI/STI. Methods: A community-based cross-sectional study. Married women aged 18–49 years (n = 1012) were interviewed and underwent a gynaecological examination. Specimens were collected for laboratory diagnosis of chlamydia, gonorrhoea, trichomonas, bacterial vaginosis (BV), candidiasis, hepatitis B, HIV, and syphilis. Results: In total, 37% of the women were clinically diagnosed with an RTI/STI. Aetiologically confirmed RTI/STI was identified in 39% of the women (including 6% with STI). Endogenous infections were most prevalent (candidiasis 26%, BV 11%) followed by hepatitis B 8.3%, Chlamydia trachomatis 4.3%, Trichomonas vaginalis 1%, Neisseria gonorrhoeae 0.7%, genital warts 0.2%, and HIV and syphilis 0%. Fifty per cent of the STI cases were asymptomatic. Younger age and intrauterine devices were significantly associated with an increased risk of BV. Determinants of candidiasis were vaginal douching, high education level and low economic status, whereas a determinant of chlamydia was high economic status. Outmigration of the husband was associated with an increased risk of hepatitis B surface antigen seroposivity among women. Conclusions: RTI/STI were prevalent among married women in a rural population of Vietnam. Syndromic algorithms should be consistently supplemented by risk assessment in order to reduce under and overtreatment. Microscopic diagnosis could be applied in primary care settings to achieve more accurate diagnoses. The promotion of health education aimed at reducing RTI/STI prevalences is an important tool in STI/HIV control programmes. Vaccination to prevent hepatitis B for migrants should be considered.
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| 13. |
- Lundbäck, David, et al.
(författare)
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Molecular epidemiology of Neisseria gonorrhoeae- identification of the first presumed Swedish transmission chain of an azithromycin-resistant strain
- 2006
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 114:1, s. 67-71
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, 10 azithromycin-resistant Neisseria gonorrhoeae isolates from 6 Swedish male patients in 2004, 3 sporadic Swedish azithromycin-resistant N. gonorrhoeae isolates from recent years and one Swedish N. gonorrhoeae isolate from 2003 that was susceptible to azithromycin but assigned the same serological variant (serovar), i.e. IB-37, as the isolates from 2004 were included. The isolates were characterized phenotypically using antibiograms and serovar determination and genetically with pulsed-field gel electrophoresis (PFGE), entire porB gene sequencing and N. gonorrhoeae multiantigen sequence typing (NG-MAST). The epidemiological information and the results of the thorough phenotypic characterisation and genetic characterisation identified the first presumed domestic transmission of one azithromycin-resistant N. gonorrhoeae strain in Sweden in 2004. This stresses the need for continuous surveillance of the antibiotic susceptibility of N. gonorrhoeae in order to identify emergence of new resistance, monitor the changing patterns of the susceptibility, and be able to update treatment recommendations on a regular basis.
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| 14. |
- Berglin, Ewa, 1955-
(författare)
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Predictors of disease onset and progression in early rheumatoid arthritis : A clinical, laboratory and radiological study
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 15. |
- Claesson, Maria, 1971-
(författare)
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Women's hearts : ischaemic heart disease and stress management in women
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 16. |
- Nilsson, Mats, 1954-
(författare)
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Cobalamin communication in Sweden 1990 – 2000 : views, knowledge and practice among Swedish physicians
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cobalamin (vitamin B12) is one of several essential micronutrients needed by the human organism. Other important micronutritients, which interplay with vitamin B12, are folate and iron. During the last ten years, the attention has been drawn to different forms of neurological disorders supposed to be caused by vitamin B12 deficiency. Vitamin B12 deficiency states are common among elderly patients in primary health care and sometimes in hospital care, especially in geriatric practice. This is a study to define the cobalamin treatment traditions, among Swedish physicians in the period 1990 – 2000. The period was distinguished by an intense debate on the issue by the physicians, an increase of cobalamin consumption, and a shift from parenteral therapy towards oral high-dose therapy. It had been known that symptoms of cobalamin deficiency could start in the nervous system. This knowledge was reinforced by the application of homocysteine and methyl-malonic acid (MMA) in deficiency diagnosis. Introduction of homocysteine and MMA in deficiency diagnosis changed the view on deficiency prevalence, by identifying persons at risk to develop B12 deficiency prior to established symptoms. In this study, Swedish physicians are regarded mainly as receivers of communication about the markers homocysteine and MMA, and deficiency states of cobalamin and folate. The main senders were scientists from North America, Norway, Denmark, and Sweden. This study sets the senders and the receivers of cobalamin communication on a collegial level and quantifies and evaluates the feed-back from the receivers. The receivers, gen¬eral practitioners and geriatricians, appeared to be familiar with old knowledge and frontier concepts in the field. Thus, it is suggested that the increase of B12 prescriptions in Sweden 1990 – 2000 reflected an increased awareness of B12-associated clinical problems among the physicians managing the majority of deficiency patients, although a possible overconsumption of pharmaceutical drugs must be kept in mind.
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| 17. |
- Rydengård, Victoria
(författare)
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ANTIMICROBIAL ACTIVITIES OF HISTIDINE-RICH GLYCOPROTEIN AND CATIONIC PEPTIDES
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In an environment full of potential pathogens it is of importance for organisms to mount a fast and effective defence. Antimicrobial peptides are ancient and integral effector molecules of the innate immune system. They are found in all kinds of species from bacteria to plants and animals, indicating their importance during evolution. They possess a broad-spectrum antimicrobial activity and some peptides can also participate in wound healing and connect the innate and adaptive immune systems. Results presented in this thesis show that structural motifs connected with heparin-binding may confer antimicrobial activity to a given peptide. Peptides from various heparin-binding endogenous proteins exerted antimicrobial activity against Gram-positive and Gram-negative bacteria and similar results were obtained with consensus sequences for heparin-binding. Furthermore, we demonstrated that replacement of lysine and arginine by histidine in the consensus motifs abrogated the antibacterial effects of these peptides. Antibacterial effects of the histidine-rich consensus peptides were restored by the addition of Zn2+ or low pH. Similar results were obtained with histidine-rich peptides derived from domain 5 of kininogen and histidine-rich glycoprotein (HRGP). HRGP, an abundant heparin-binding plasma protein, exerted antimicrobial effects against Gram-positive and Gram-negative bacteria and fungi. The antibacterial activity of HRGP was dependent on Zn2+-ions or low pH, and the antifungal activity was increased under low pH conditions. Electron microscopy demonstrated that HRGP induced lysis of bacteria and fungi. Truncated HRGP, devoid of the heparin-binding and histidine-rich domain, was not antimicrobial. In addition, HRGP was found to have antifungal effects ex vivo when bound to fibrin clots.
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| 18. |
- Wågsäter, Dick, 1976-
(författare)
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CXCL16 and CD137 in atherosclerosis
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis is a progressive inflammatory disease that is characterized by the accumulation of lipids, infiltrated cells and fibrous elements in large arteries. This thesis focuses on the molecular mechanisms behind foam cell formation and inflammation, two central processes in the development of atherosclerosis. More specific, we studied the effects of proinflammatory cytokines on CXCL16 expression and its role as scavenger receptor on macrophages and smooth muscle cells in atherogenesis. CXCL16 is defined as a chemokine and a scavenger receptor, regulating adhesion and chemoattraction of CXCR6 expressing cells and uptake of oxLDL. We show that the expression of CXCL16 and its receptor CXCR6 are more pronounced in human atherosclerotic lesions compared with non-atherosclerotic vessels. Increased expression of CXCL16 was also seen in atherosclerotic aortas of apoE-/- mice compared with aortas of non-atherosclerotic, age-matched C57BL/6 mice. In vitro, IFN gamma induced CXCL16 expression in primary human monocytes and smooth muscle cells which resulted in an increased uptake of oxLDL. Treatment of mice with IFN gamma also induced CXCL16 expression in atherosclerotic lesions. Thus, we have demonstrated a role for IFN gamma in foam cell formation through upregulation of CXCL16. The expression of CXCR6 was defined to the same regions as for CXCL16 in the lesion, indicating the presence of cells able to respond to CXCL16. Consequently, CXCL16 could serve as a molecular link between lipid metabolism and immune activity in atherosclerotic lesion. CD137 belongs to the TNF family and mediates several important processes in inflammation. CD137 is involved in the activation of T cells, NK cells, B cells and monocytes and regulate cytokine production, proliferation and apoptosis in these cells. A limited number of studies have demonstrated CD137 expression on smooth muscle cells and endothelial cells. Our results show that CD137 mRNA is higher expressed in human atherosclerotic lesions compared with unaffected vessels. We found that endothelial cells express CD137 in atherosclerotic lesions and that cultured endothelial cells and smooth muscle cells express CD137 and CD137 ligand in vitro. CD137 was regulated differentially by proinflammatory cytokines (i.e. IFN gamma, TNF alpha, IL-1 beta) and bacterial lipopolysaccharide depending on cell type. Furthermore, we investigated the effects of CD137 signalling, demonstrating that binding of the CD137 ligand to its receptor increases proliferation and migration of smooth muscle cells. In summary, this thesis has focused on the expression, regulation and role of CXCL16 and CD137, two genes that have not been described earlier in the concept of atherosclerosis. The findings demonstrate some of the molecular mechanisms involved in vascular inflammation and may increase our knowledge about the development of atherosclerosis.
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| 19. |
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| 20. |
- Cedervall, Jessica, et al.
(författare)
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Species-specific in vivo engraftment of the human BL melanoma cell line results in an invasive dedifferentiated phenotype not present in xenografts
- 2009
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 69:9, s. 3746-3754
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Tidskriftsartikel (refereegranskat)abstract
- For clinically relevant studies on melanoma progression and invasiveness, in vivo experimental systems with a human cellular microenvironment would be advantageous. We have compared tumor formation from a human cutaneous malignant melanoma cell line (BL), after injection as conventional xenografts in the mouse, or when injected into a predominantly species-specific environment of human embryonic stem cell-derived teratoma induced in the mouse (the hEST model). The resulting melanoma histology was generally analogous, both systems showing delimited densely packed areas with pleomorphic cells of malignant appearance. A specificity of the integration process into the human embryonic teratoma tissues was indicated by the melanoma exclusively being found in areas compatible with condensed mesenchyme, similar to neural crest development. Here, also enhanced neovascularization was seen within the human mesenchymal tissues facing the BL melanoma growth. Furthermore, in the hEST model an additional melanoma cell phenotype occurred, located at the border of, or infiltrating into, the surrounding human loose mesenchymal fibrous stroma. This BL population had a desmoplastic spindle-like appearance, with markers indicative of dedifferentiation and migration. The appearance of this apparently more aggressive phenotype, as well as the induction of human angiogenesis, shows specific interactions with the human embryonic microenvironment in the hEST model. In conclusion, these data provide exciting options for using the hEST model in molecular in vivo studies on differentiation, invasiveness, and malignancy of human melanoma, while analyzing species-specific reactions in vivo.
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