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  • 1
    Keywords: CELLS ; IN-VITRO ; BLOOD ; CELL ; COMBINATION ; Germany ; MODEL ; THERAPY ; VITRO ; DRUG ; METABOLISM ; PATIENT ; MACROPHAGES ; murine ; CONTRAST ; treatment ; antibody ; TARGET ; NUMBER ; DELIVERY ; PHARMACOKINETICS ; DOUBLE-BLIND ; PERIPHERAL-BLOOD ; T lymphocytes ; MONONUCLEAR-CELLS ; METHOTREXATE ; COLLAGEN-INDUCED ARTHRITIS ; albumin ; DRUG-DELIVERY ; rheumatoid arthritis ; RHEUMATOID-ARTHRITIS ; II COLLAGEN ; LOW-DOSE METHOTREXATE ; PLACEBO-CONTROLLED TRIAL ; RHEUMATOID-ARTHRITIS PATIENTS
    Abstract: Objective. To evaluate the anti-arthritic effects of the new inflammation-targeted drug MTX-HSA and to investigate whether peripheral blood mononuclear cells (PBMC) are potential target cells for albumin-mediated drug delivery. Methods. The murine model of collagen-induced arthritis (CIA) was used to measure the anti-arthritic effect of MTX, MTX-HSA or a combination of both (n = 30 to 35 per group). In addition, the uptake of fluorescence-labelled albumin (AFLc-HSA) in PBMC of 14 patients with RA was measured by fluorescence-activated cell sorting (FACS). Results. In equivalent doses of 7.5 mg/kg intravenously (IV) twice a week, MTX-HSA is significantly (P〈0.02) superior to MTX in inhibiting the development of CIA and reducing the joint count as well as the number of affected paws. When given in lower doses as combination therapy, both drugs act synergistically (P〈0.03). A mean of 96, 72 and 64% of the CD14-, CD16- and CD20-positive cells from peripheral blood of rheumatoid arthritis (RA) patients showed an uptake of albumin after incubation with AFLc-HSA in vitro. This finding was not significantly different in comparison to healthy controls. In contrast, the number of CD3-positive cells taking up albumin is increased significantly in RA patients in comparison to controls (26.3 +/- 12.9% s.d. vs 11.6 +/- 7.3% s.d.; P = 0.005). Conclusion. The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically. In addition, albumin appears to be taken up by peripheral blood cells, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approach
    Type of Publication: Journal article published
    PubMed ID: 15199219
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  • 2
    Keywords: CELLS ; EXPRESSION ; IRRADIATION ; tumor ; CELL ; COMBINATION ; Germany ; DISEASE ; EXPOSURE ; TISSUE ; PATIENT ; NITRIC-OXIDE SYNTHASE ; NITRIC-OXIDE ; MECHANISM ; IMPACT ; mechanisms ; SKIN ; T cell ; T cells ; T-CELL ; T-CELLS ; FIELD ; LESIONS ; UP-REGULATION ; DAMAGE ; RECRUITMENT ; CLEARANCE ; FUTURE ; inflammation ; PROGRAM ; RE ; SYNTHASE ; chemokines ; REGULATORY T-CELLS ; SUBTYPES ; APOPTOTIC CELLS ; TESTS ; EVENTS ; SLE ; function ; nitric oxide ; regulatory T cells ; regulatory T cell ; PROTECTS ; CD4(+)CD25(+) ; ENVIRONMENTAL-FACTORS ; SKIN-LESIONS ; LUPUS-ERYTHEMATOSUS
    Abstract: The pathophysiology of cutaneous lupus erythematosus (CLE) has been investigated in numerous studies demonstrating that the combination of specific cellular and molecular events is leading to inflammation and tissue damage in this disease. However, a complete understanding of the diverse pathophysiological mechanisms and interactions does not exist. Various environmental factors influence the clinical expression of CLE and a striking relationship has emerged between sunlight exposure and the various subtypes of this disease. In the past years, photoprovocation tests with different ultraviolet (UV) wavelengths have been approved to be an optimal way to evaluate photosensitivity in patients with CLE. Furthermore, research on the pathogenetic mechanisms of UV-induced skin lesions has become an increasingly dynamic field and several new aspects of this disease could be identified. In this review, the impact of UV exposure that contributes to the manifestations of CLE is discussed and recently reported mechanisms in the pathophysiology of this disease are considered including the clearance of apoptotic cells, expression of inducible nitric oxide synthase, function of CD4(+)CD25(+) regulatory T cells, and the role of chemokines for lymphocyte recruitment. Elucidation of the relevant factors might lead to future development of effective strategies to prevent abnormal reactivity in patients with CLE
    Type of Publication: Journal article published
    PubMed ID: 16987823
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  • 3
    Keywords: SPECTRA ; EXPRESSION ; IN-VITRO ; IRRADIATION ; Germany ; THERAPY ; VITRO ; DISEASE ; DISEASES ; MECHANISM ; REDUCTION ; mechanisms ; SKIN ; treatment ; EXPERIENCE ; SYSTEMIC-SCLEROSIS ; fibrosis ; INHIBIT ; ACROSCLEROSIS ; DOSE UVA1 PHOTOTHERAPY ; LOCALIZED SCLERODERMA
    Abstract: In systemic sclerosis (SSc; scleroderma) fibrosis of the skin can lead to considerable morbidity. No significant improvement has been reported from studies investigating antifibrotic therapies so far. In dermatology, phototherapy with ultraviolet (UV) irradiation is successfully used for treatment of several diseases because of its anti-inflammatory as well as immunosuppressive mechanisms, and its low-risk profile. In addition, the UVA spectrum in particular exerts antifibrotic effects as it leads to reduction of procollagen synthesis and expression of collagenase-1 in vitro. Accordingly, treatment with long-wavelength UVA-1 irradiation or photochemotherapy with UVA plus the photosensitizer psoralen (PUVA) have been successfully used to reduce skin fibrosis in localized scleroderma (morphea). There are only in particular few reports on treatment of skin sclerosis in SSc, but the results are in concordance with the good experience that have been observed at our and other dermatological centres. Phototherapy is able to stop or inhibit the fibrotic processes and to induce softening of sclerotic skin, especially in limited SSc. Phototherapy thus represents a therapeutic alternative for antifibrotic treatment with a low rate of adverse effects, which should be applied before the sclerotic process has proceeded too far
    Type of Publication: Journal article published
    PubMed ID: 16987838
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  • 4
    Keywords: CANCER ; Germany ; RISK ; PATIENT ; RISK-FACTORS ; SUSCEPTIBILITY ; risk factors ; DATABASE ; familial risk ; RE ; RHEUMATOID-ARTHRITIS ; RISK-FACTOR ; ENGLAND
    Type of Publication: Journal article published
    PubMed ID: 18308735
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  • 5
  • 6
    Keywords: CANCER ; CELL ; Germany ; FOLLOW-UP ; COHORT ; DISEASE ; incidence ; POPULATION ; RISK ; RISKS ; TIME ; PATIENT ; TRANSPLANTATION ; colon ; SKIN ; ASSOCIATION ; SUSCEPTIBILITY ; LYMPHOMA ; MELANOMA ; SWEDEN ; cancer risk ; DATABASE ; SKIN-CANCER ; RE ; INCREASE ; RHEUMATOID-ARTHRITIS ; non-Hodgkin lymphoma ; methods ; CANCERS ; CANCER-RISK ; ENGLAND ; INCREASES ; NORDIC COUNTRIES ; non Hodgkin lymphoma ; EXCESS ; AERODIGESTIVE TRACT CANCERS ; age at onset ; AUTOIMMUNE ; changing risk ; national databases ; subsequent cancer
    Abstract: Objectives. Patients diagnosed with RA have been at an increased risk of many cancers and at a decreased risk of some cancers. We planned to revisit the theme by using a nation-wide population of RA patients. Methods. An RA research database was constructed by identifying hospitalized RA patients from the Hospital Discharge Register and cancer patients from the Cancer Registry. Earlier studies from Sweden have shown that some 75 of RA patients have been hospitalized at some time point. Follow-up of 42 262 RA patients was carried out from year 1980 to 2004 including separate follow-ups for shorter intervals. Standardized incidence ratios (SIRs) were calculated for cancer in RA patients by comparing with subjects without RA. Results. Many cancers were in excess in RA patients, especially Hodgkin disease, non-Hodgkin lymphoma and squamous cell skin cancer; a novel association was found for non-thyroid endocrine tumours. Colon, rectal and endometrial cancers were decreased in RA patients. When RA patients were first hospitalized after 1999, the SIRs for melanoma, squamous cell skin and upper aerodigestive tract cancers and for leukaemia were increased compared with previous periods. Conclusions. This study, the largest so far published, quantified the increased and decreased site-specific risks of cancer in RA patients. The recent increases in the risks of squamous cell skin and upper aerodigestive tract cancers, melanoma and leukaemia call for continuous vigilance and recording of changes in treatment
    Type of Publication: Journal article published
    PubMed ID: 18378514
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  • 7
    Keywords: ENVIRONMENT ; FOLLOW-UP ; DISEASE ; DISEASES ; incidence ; MORTALITY ; POPULATION ; RISK ; RISKS ; GENE ; GENES ; ARTHRITIS ; FAMILY ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY ; antibodies ; SWEDEN ; PREVALENCE ; SYSTEMIC-LUPUS-ERYTHEMATOSUS ; sibling risk ; SIBLINGS ; FAMILIES ; rheumatoid arthritis ; RHEUMATOID-ARTHRITIS ; AUTOIMMUNE-DISEASES ; QUALITY-OF-LIFE ; analysis ; methods ; follow-up study ; COMMUNITY ; ENGLAND ; systemic ; GENETIC-BASIS ; SWEDISH ; systemic lupus erythematosus ; ANKYLOSING-SPONDYLITIS ; ankylosing spondylitis ; NEUROPSYCHIATRIC SYNDROMES
    Abstract: Objectives. To quantify the sibling risk of RA, SLE and AS. To analyse the concordant and discordant associations between RA, SLE and AS. Methods. Follow-up study of all individuals and their siblings born in or after 1932 and hospitalized for RA, SLE or AS between 1973 and 2004 (32 yrs). Data were retrieved from a comprehensive dataconstructed by using several national Swedish data registers, including the Total Population Register, the Swedish Hospital Discharge Register and the Multigeneration Register. Standardized incidence ratios (SIRs) were used to estimate sibling risks. Results. For males, the overall significant SIRs were 4.72, 4.35 and 4.14 for RA, SLE and AS, respectively, if a sibling was affected by any inflammatory disease. The corresponding significant SIRs for females were 4.12, 3.73 and 4.73. The concordant significant SIRs in siblings were 5.12, 17.02 and 17.14 for RA, SLE and AS, respectively. There were also discordant associations between RA and SLE, whereas AS was only associated with AS. Conclusions. This study was able objectively to quantify the sibling risk of RA, SLE and AS, which represents useful knowledge for clinicians and geneticists. The analysis of concordant and discordant associations may be useful in future studies aimed at finding specific genes associated with these diseases
    Type of Publication: Journal article published
    PubMed ID: 18524808
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  • 8
    Keywords: CANCER ; carcinoma ; CELL ; LUNG ; PROSTATE ; FOLLOW-UP ; SYSTEM ; DISEASE ; EPIDEMIOLOGY ; incidence ; RISK ; kidney ; MECHANISM ; mechanisms ; SKIN ; ASSOCIATION ; LYMPHOMA ; AGE ; skin cancer ; MELANOMA ; SWEDEN ; STOMACH ; ENDOMETRIAL CANCER ; CELL CARCINOMA ; REGISTRY ; ASSOCIATIONS ; methods ; INCREASED RISK ; CANCERS ; CANCER-RISK ; tumours ; national databases ; REGISTER ; Follow up ; Giant cell arteritis ; Polymyalgia rheumatica ; TEMPORAL ARTERITIS
    Abstract: Objectives. Studies reporting cancer risk after PMR and GCA are few, but it remains an issue of both concern and controversy. We examined the overall and specific cancer risks among Swedish subjects following hospitalization for these diseases. Methods. PMR and GCA patients were identified from the Swedish Hospital Discharge Register and by linking them with the Cancer Registry. Follow-up of patients was carried out from the last hospitalization through year 2006. Standardized incidence ratios (SIRs) were calculated in these patients compared with subjects without the diseases. Results. A total of 35 918 patients were hospitalized for PMR and GCA during the years 1965-2006; the hospitalization rate increased towards late age. A total of 3941 patients developed subsequent cancer, giving an overall SIR of 1.19; and for cancer diagnosed later than 1 year of follow-up, the SIR was 1.06. A significant excess was noted for skin (squamous cell carcinoma and melanoma), stomach, lung, prostate, kidney, nervous system and endocrine gland tumours, and additionally for non-Hodgkin's lymphoma, myeloma and leukaemia. Decreased risk was noted for endometrial cancer. Conclusions. Patients hospitalized for PMR and GCA had a marginally increased risk of cancer, with the highest risk noted for the first year after hospitalization. However, for specific cancers, such as skin cancer and leukaemia, the increases were still significant for patients diagnosed later than 1 year after hospitalization, suggesting that these could be true associations, but the mechanisms remain to be established
    Type of Publication: Journal article published
    PubMed ID: 20299378
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