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ID PMID Title PublicationDate abstract
24149013 Psoriatic arthritis classification criteria: Moll and Wright, ESSG and CASPAR -- a compara 2013 Jul OBJECTIVES: to evaluate and compare Moll and Wright, ESSG and CASPAR criteria for psoriatic arthritis (PsA) classification. PATIENTS AND METHODS: Study comprised 356 patients (pts): 120 PsA pts in the investigated group, 123 pts with rheumatoid arthritis (RA) and 113 pts with non-inflammatory musculoskeletal symptoms (NIMS) in two control groups. Clinical diagnosis was the gold standard. Moll and Wright, ESSG and CASPAR criteria were applied to all pts. Sensitivity was calculated for each of the classification criteria sets; specificity was assessed in relation to RA and to NIMS groups, separately. Concordance between the investigated criteria sets was determined. RESULTS: Sensitivity was 91.7% for CASPAR, 85.8% for Moll and Wright and 63.3% for ESSG criteria. Specificity for Moll and Wright criteria was 100%, with relation to both RA and to NIMS group. Specificity of CASPAR criteria was 99.2% and 99.1%; specificity of ESSG criteria was 94.3% and 67%, with regard to RA and to NIMS groups, respectively. Significant fair concordance was found only between CASPAR and Moll and Wright criteria (k=0.379 p<0.001). CONCLUSIONS: The highest sensitivity had the CASPAR criteria, followed by Moll and Wright and ESSG. The highest specificity showed Moll and Wright criteria, followed by CASPAR and ESSG. CASPAR criteria demonstrated high specificity when applied to both NIMS and RA group. The lowest specificity was found for the ESSG criteria in relation to NIMS group. The only significant concordance was shown between CASPAR and Moll and Wright criteria.
22447330 Rheumatic disease presenting as septic arthritis: a report of 10 cases. 2013 Aug To determine the forms and characteristics of rheumatic diseases whose initial presentation mimics septic arthritis. Retrospective study of 398 patients hospitalized between 1979 and 2005 for arthritis diagnosed and treated as septic. In 10 cases, initial presentation of a rheumatic disease was highly suggestive of septic arthritis, and the patient was treated as such. Three had rheumatoid arthritis, 3 spondyloarthropathies, 2 unclassified rheumatic diseases, 1 Wegener granulomatosis and 1 cytosteatonecrosis. Mean time to diagnosis of rheumatic arthritis was 6 months. There were 7 males and 3 females aged from 15 to 77 years. Six had fever, and 3 had leucocytosis. Average ESR was 68 mm/1 h, and C-reactive protein was above 100 mg/l in 6 patients. Five patients had radiological signs suggestive of septic arthritis. Joint fluid count was above 100,000 WBCs/mm(3) in 2/5. Synovial biopsy suggested septic arthritis in 5 out of 6. These cases of pseudoseptic arthritis were indistinguishable from true septic arthritis. Follow-up is required in septic arthritis with negative culture findings to exclude rheumatic disease.
24962873 Early predictors of prognosis in juvenile idiopathic arthritis: a systematic literature re 2015 Nov OBJECTIVES: Juvenile idiopathic arthritis (JIA) is subdivided into seven categories. Even within these categories, the prognosis varies markedly. To start appropriate treatment in patients with JIA and to inform patients and their parents correctly, it is essential to know the individual prognosis, preferably at the time of diagnosis. The aim of this study was to identify variables that predict disease activity, joint damage, functional ability and quality of life (QoL) early in the disease course. METHODS: A systematic literature review was performed, and 3679 articles were identified. The results were screened and critically appraised using predefined criteria. Articles that described validated outcomes, such as the Wallace criteria, the childhood health assessment questionnaire (CHAQ) and the juvenile arthritis damage index (JADI), and that determined predictors in the first 6 months of disease were selected. RESULTS: Forty mostly retrospective articles were selected. Polyarticular onset predicted a worse prognosis for all outcomes, except QoL. A diagnostic delay and the systemic category predicted continuation of active disease. Notably, antinuclear antibodies (ANA) did not predict disease activity. Symmetric involvement and rheumatoid factor positivity predicted less damage. More disease activity was mainly associated with worse functional outcome. However, most predictors were not validated. CONCLUSIONS: Few predictors for the selected outcomes were found. Prospective, longitudinal studies using standardised outcome measurements, and evaluating a broader range of predictors, such as genetics, immunological and imaging data, should be performed. For the outcomes joint assessment and quality of life, standardised and validated outcomes should be developed.
22886618 Elevated serum resistin in juvenile idiopathic arthritis: relation to categories and disea 2013 Jan BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is one of the more common chronic diseases of childhood that often persists into adulthood and can result in significant long-term morbidity, including physical disability. The aim of the present study was to assess the serum level of resistin in JIA patients and compare its levels according to the categories, clinical manifestations and disease activity. METHODS: Sixty-eight JIA patients and 33 age and sex matched control children were included in the present study. All patients included in this study were subjected to full history taking, clinical examination. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated and Childhood Health Assessment Questionnaire (CHAQ) was used to measure the functional status. Serum resistin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum resistin was significantly higher in the JIA patients (4.01 ± 2.46 ng/ml) compared to the control (2.08 ± 1.23 ng/ml) (p<0.001) especially those with systemic-onset. Its level was significantly higher in those receiving steroids and those with a positive antinuclear antibody. Resistin significantly correlated with the JADAS27 (r 0.26, p 0.035) and CHAQ (r 0.4, p 0.001). The JIA patients were 50 females and 18 males; however, the level of resistin was insignificantly different according to the gender although there was a tendency to be higher in females. CONCLUSION: Our results reinforce the proposition of an important role for resistin in JIA and may be considered an interesting biomarker for disease activity especially those with systemic onset.
25220583 Reciprocal effects of Schistosoma mansoni infection on spontaneous autoimmune arthritis in 2015 Feb Schistosome infections have been shown to prevent inflammation in induced-type arthritis models. However, its effects on spontaneous arthritis remain unknown. We here investigated the effects of Schistosoma mansoni (Sm) infection on spontaneous autoimmune arthritis in IL-1 receptor antagonist (IL-1Ra)-deficient mice. Sm infection partially reduced the severity of arthritis in male IL-1Ra-deficient mice. The splenic responses of IL-17 and TNF-α were reduced, while those of IL-4 and IL-10 were enhanced by the infection. However, Sm infection increased IgG rheumatoid factor and anti-dsDNA IgG serum levels. These results suggest that Sm infection has both ameliorating and exacerbating effects on autoimmunity in IL-1Ra-deficient mice.
24150746 Prevalence of psoriatic arthritis in psoriasis patients according to newer classification 2014 Feb The aim of this study is to determine the prevalence of psoriatic arthritis (PsA) according to CASPAR criteria, ASAS peripheral and axial SpA criteria, and New York criteria for AS. The first 100 patients consecutively attending a psoriasis dermatology clinic were assessed. Demographic and clinical data were collected; all patients were questioned and examined for joint manifestations. Rheumatoid factor and radiographies of hands, feet, cervical spine, and pelvis for sacroiliac joints were obtained. X-rays were read independently by two experienced observers in blind fashion. Patients with objective joint manifestations, both axial and peripheral, were evaluated for fulfillment of CASPAR, ASAS peripheral and axial, and New York criteria. Median age 48 years; 93 % of patients had psoriasis vulgaris and 56 % nail involvement. Seventeen patients had peripheral arthritis as follows: nine mono/oligoarticular and eight polyarthritis. Median arthritis duration was 8 years. Seventeen percent of patients fulfilled CASPAR and ASAS peripheral criteria, 6 % New York, and 5 % ASAS axial criteria. Patients who met CASPAR criteria showed a significantly higher psoriasis duration compared to those without arthritis (M 16 vs. 10 years, p = 0.02), and a higher frequency of nail involvement (88.2 vs. 49.4 %, p = 0.003). Five patients (29.4 %) fulfilled ASAS axial criteria; all of them had peripheral involvement as follows: mono/oligoarticular in three patients and polyarticular in two. Patients with peripheral and axial involvement presented a significantly higher frequency of erythrodermic psoriasis compared to the other patients (35.3 vs. 1.2 %, p = 0.0006 and 80 vs. 16.7 %, p = 0.02). Prevalence of PsA, for CASPAR and ASAS peripheral criteria, was of 17 %. Five percent of patients met ASAS axial criteria, while 6 % met New York criteria. Worth noting, few patients without signs or symptoms of arthritis had radiological changes, both axial and peripheral, precluding a proper classification.
25242730 Suppression of experimental arthritis with self-assembling glycol-split heparin nanopartic 2014 Nov 28 It has been recently shown that Toll-like receptor4 mediated nuclear factor κB (TLR4-NF-κB) signaling plays a critical role in the pathogenesis of rheumatoid arthritis mediated by pro-inflammatory cytokines in arthritic synovium. Here we evaluate the therapeutic potential of glycol-split non-anticoagulant heparin/d-erythro-sphingosine nanoparticles (NAHNPs), which have shown strong inhibitory effect against TLR4 induced inflammation, in an experimental arthritis model. NAHNP significantly inhibited the production of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β in lipopolysaccharide (LPS)-induced primary mouse macrophages and DC2.4 dendritic cell line. The nanoparticles were administered to type II collagen-induced arthritis (CIA) mice by intraarticular injections once per day starting from onset of the disease symptoms. Treatment with NAHNP had a potent suppressive effect in CIA mice, observed with a decrease in arthritis score and footpad swelling. The animals treated with NAHNP significantly reduced levels of IgG1 and IgG2a antibodies against bovine type II collagen. Levels of proinflammatory cytokines--e.g., TNF-α, IL-6 and IL-1β in knee joints and sera were significantly inhibited compared to control mice. Moreover, nuclear localization of RelA in knee joints was significantly inhibited in NAHNP treatment, indicating down-regulation of the NF-κB signaling pathway. In addition, histological examination revealed significant suppression of inflammatory cell infiltration, joint destruction and synovial proliferation in synovium compared with control mice. These results suggest that selective inhibition of TLR4-NF-κB signaling with lipid modified heparin derivatives composited to nanostructures provides an effective therapeutic approach to inhibit chronic inflammation in an animal model of rheumatoid arthritis.
24618287 HLA-DR typing in polyarticular juvenile idiopathic arthritis: a study from a tertiary care 2014 Mar INTRODUCTION: Many studies of human leukocyte antigen (HLA) association with juvenile idiopathic arthritis (JIA) have reported conflicting results, which were probably related to ethnic differences. Moreover, in India, studies on HLA-DR typing on JIA, particularly polyarticular JIA, is lacking. OBJECTIVE: The aim of our study was to reveal the frequency of HLA DR types in a cohort of polyarticular JIA in northern India. METHODS: Fifty-two polyarticular JIA patients were included as per the recent International League of Associations for Rheumatology classification, 2001. HLA-DR typing was performed in 21 patients (18 rheumatoid factor [RF]+ and three RF-) by a DNA-based polymerase chain reaction method for the determination of HLA alleles using sequence specific primers (SSP). The results were compared with that of 23 healthy controls of the same age and sex. RESULTS: HLA-DR4 was present in five cases (23%) in the diseased group while only in one case (4.3%) in the control group with a relative risk of 5.47, but when compared with only RF+ polyarticular JIA, HLA-DR4 was found to be significantly high (27.7% vs. 4.43%; P < 0.05) with a relative risk of 6.3. Further, DR4, DR1, DR2, DR9, DR10 were also non-significantly high in these patients with relative risk of 3.2 for DR9 and 1.8 for DR10. In contrast, HLA-DR6 was seen only in 5.5% of polyarticular JIA cases, whereas it was present in 39% of controls (P < 0.05), a showing negative association. CONCLUSION: HLA-DR4 codes for susceptibility to RF+ polyarticular JIA with a six-fold risk, whereas HLA-DR6 offers protection.
23237458 Anti-inflammatory activity of lycopene isolated from Chlorella marina on type II collagen 2013 Apr The role of commercially available lycopene (all-trans) from tomato in controlling arthritis has been reported. Even though many reports are available that the cis form of lycopene is more biologically active, no report seems to be available on lycopene (cis and trans) isolated from an easily available and culturable sources. In the present study, the anti-arthritic effect of lycopene (cis and trans) from the algae Chlorella marina (AL) has been compared with lycopene (all-trans) from tomato (TL) and indomethacin (Indo). Arthritis (CIA) was developed in male Sprague dawley rats by collagen and the following parameters were studied. The activities of inflammatory marker enzymes like cyclooxygenase (COX), lipoxygenase (LOX) and myeloperoxidase (MPO) were found to be decreased on treatment with AL when compared to TL and Indo. Changes in Erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, red blood cells (RBC) count, hemoglobin (Hb), C-reactive protein (CRP), rheumatoid factor (RF), and ceruloplasmin levels observed in the blood of arthritic animals were brought back to normal by AL when compared to TL and Indo. Histopathology of paw and joint tissues showed marked reduction in edema on supplementation of AL. Thus these results indicate the potential beneficiary effect of algal lycopene on collagen induced arthritis in rats when compared to TL and even to the commonly used anti-inflammatory drug indomethacin. Therefore lycopene from C. marina would be recommended as a better natural source with increased activity and without side effects in the treatment of anti-inflammatory diseases.
22784433 The importance for daily occupations of perceiving good health: Perceptions among women wi 2013 Mar OBJECTIVE: The purpose was to describe and characterize what women with rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) perceive as important in considering the performance of daily occupations to perceive good health. METHODS: By using a phenomenographic research approach with semi-structured interviews with nine women between the ages of 42 and 65 the core category "Being able to be as active as possible in daily occupations" emerged. RESULTS: The women's repertoire of daily occupations had changed as the years had passed. To perceive good health the women expressed the importance of continuing to be active and to perform occupations as independently as possible despite their chronic rheumatic diseases. CONCLUSIONS: By adapting to their level of physical function and strength and by compensation with assistive devices, selecting adjusted environment, and by getting support from others, the women perceived good health. The results also suggested that training in different ways, medical treatment, and rheumatologic team care were related to increased performance of daily occupations and the perceptions of good health.
25610674 Primary hepatic lymphoma in a patient with rheumatoid arthritis treated with methotrexate. 2014 Primary hepatic lymphoma (PHL) has rarely been reported in patients with immunosuppression. We herein describe a case of Epstein-Barr virus- (EBV-) positive PHL in a 67-year-old Japanese woman receiving methotrexate (MTX) treatment for rheumatoid arthritis (RA). The patient, who had been receiving MTX therapy for more than 6 years, presented with low-grade fever and abdominal pain. Initial laboratory tests showed mildly elevated liver enzymes with normal levels of alpha-fetoprotein and carcinoembryonic antigen, and computed tomography scans revealed multiple hepatic tumors with no lymph-node swelling. Examination of liver specimens obtained via ultrasonography-guided needle biopsy indicated EBV-positive diffuse large B cell lymphoma; therefore, she was diagnosed with PHL. MTX was discontinued, and she was carefully monitored thereafter owing to the prolonged history of MTX administration for RA. Rapid progression of PHL was observed; therefore 10 days after the PHL diagnosis, she received 6 cycles of R-THP-COP (rituximab, cyclophosphamide, pirarubicin, vincristine, and prednisolone) therapy and achieved complete remission for more than 1 year. Although MTX-associated lymphoproliferative disorders often show remission after withdrawal of MTX, early diagnosis and treatment are essential for PHL in patients with RA treated with MTX, because of the aggressive nature of the disease.
24738934 Systemic disease sequelae in chronic inflammatory diseases and chronic psychological stres 2014 May In chronic inflammatory diseases (CIDs), the neuroendocrine-immune crosstalk is important to allocate energy-rich substrates to the activated immune system. Since the immune system can request energy-rich substrates independent of the rest of the body, I refer to it as the "selfish immune system," an expression that was taken from the theory of the "selfish brain," giving the brain a similar position. In CIDs, the theory predicts the appearance of long-term disease sequelae, such as metabolic syndrome. Since long-standing energy requirements of the immune system determine disease sequelae, the question arose as to whether chronic psychological stress due to chronic activation of the brain causes similar sequelae. Indeed, there are many similarities; however, there are also differences. A major difference is the behavior of body weight (constant in CIDs versus loss or gain in stress). To explain this discrepancy, a new pathophysiological theory is presented that places inflammation and stress axes in the middle.
23690848 A systems biology-based investigation into the pharmacological mechanisms of wu tou tang a 2013 Aim. To investigate pharmacological mechanisms of Wu Tou Tang acting on rheumatoid arthritis (RA) by integrating network analysis at a system level. Methods and Results. Drug similarity search tool in Therapeutic Targets Database was used to screen 153 drugs with similar structures to compositive compounds of each ingredient in Wu Tou Tang and to identify 56 known targets of these similar drugs as predicted molecules which Wu Tou Tang affects. The recall, precision, accuracy, and F1-score, which were calculated to evaluate the performance of this method, were, respectively, 0.98, 0.61, 59.67%, and 0.76. Then, the predicted effector molecules of Wu Tou Tang were significantly enriched in neuroactive ligand-receptor interaction and calcium signaling pathway. Next, the importance of these predicted effector molecules was evaluated by analyzing their network topological features, such as degree, betweenness, and k-coreness. We further elucidated the biological significance of nine major candidate effector molecules of Wu Tou Tang for RA therapy and validated their associations with compositive compounds in Wu Tou Tang by the molecular docking simulation. Conclusion. Our data suggest the potential pharmacological mechanisms of Wu Tou Tang acting on RA by combining the strategies of systems biology and network pharmacology.
23609371 Late spontaneous rupture of the extensor pollicis longus tendon after corticosteroid injec 2013 Mar INTRODUCTION: Spontaneous rupture of the extensor pollicis longus (EPL) tendon has been reported after trauma, rheumatoid arthritis and sports. Rupture may also occur as a consequence of the use of anabolic steroids for recreational purposes, or systemic steroids for the treatment of a variety of medical conditions. CASE REPORT: We present a case report of a woman affected with a spontaneous EPL tendon rupture resulted 14 months after a corticosteroid injection for flexor tenosynovitis, "trigger finger," of the thumb. The edges of the tendon were debrided and sutured using figure of eight stitch and a running locked stitch. In addition multiple specimens were sent to Pathology. DISCUSSION: Duplay in 1876 described spontaneous rupture as a problem of mechanical and pressure phenomena. Another cause of EPL rupture is related to the development and persistence of inflammatory processes seen in patients with medical illnesses such as rheumatoid arthritis. There have been no reports in the literature to date of spontaneous EPL tendon rupture in the late period after steroid injection. Tendon ruptures in the hand usually occur one or two weeks after a corticosteroid injection, and the affected tendons are usually in neighbouring areas.
23504875 Exposure-Exposure Relationship of Tocilizumab, an Anti-IL-6 Receptor Monoclonal Antibody, 2013 Jan 24 Relationships between tocilizumab exposure and response were evaluated using data from 4 phase III studies. Increased tocilizumab exposure was associated with improvements in Disease Activity Score using 28 joints (DAS28) and American College of Rheumatology (ACR) criteria and with a decrease in inflammation markers. A population pharmacokinetic/pharmacodynamic (PKPD) model was developed to describe data from 2 studies. An indirect-response model with a sigmoid E(max) (maximal drug effect) inhibitory drug effect on DAS28 "production" rate adequately described the relationship between tocilizumab concentration and DAS28. Mean minimum serum tocilizumab concentration at steady state was greater than the EC(50) (concentration at which 50% of E(max) on DAS28 is reached) with the 8-mg/kg dose but not with the 4-mg/kgdose. Simulations within a large rheumatoid arthritis (RA) population showed that DAS remission rates were 38% for 8 mg/kg and 24% for 4 mg/kg. Tocilizumab was more potent in RA patients with higher baseline interleukin-6 levels, but this effect was not clinically significant. Other covariates (eg, presence of neutralizing antitocilizumab antibodies) did not demonstrate a clinically meaningful effect on tocilizumab DAS28 dose-response relationships. These data support clinical observations that tocilizumab 8 mg/kg is more effective than 4 mg/kg in reducing disease activity.
25530272 A novel histone deacetylase 6-selective inhibitor suppresses synovial inflammation and joi 2015 Jun AIM: To investigate the effects of Tubastatin A, a selective histone deacetylase-6 inhibitor, on synovial inflammation and joint destruction in a collagen antibody-induced arthritis (CAIA) mouse model. METHODS: Collagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100 mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 in the serum were analyzed using enyme-linked immunosorbent assay (ELISA). Two pathologists independently measured the synovitis score. Micro-computed tomography (CT) scans of the joints were performed to quantify joint destruction. The expression of IL-6 from human fibroblast-like synoviocytes (FLSs) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3 μmol/L) was measured using ELISA. RESULTS: The clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100 mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100 mg/kg Tubastatin A-treated group compared with the control group. Micro-CT showed that quantitative measures of joint destruction were significantly attenuated in the 100 mg/kg Tubastatin A-treated group compared with the control. The expression of IL-6 in the sera was lower in the mice treated with Tubastatin A compared with the control. The expression of IL-6 in human FLSs decreased dose-dependently after incubation with Tubastatin A without affecting cell viability. CONCLUSIONS: Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression.
25387054 AA amyloidosis: pathogenesis and targeted therapy. 2015 The understanding of why and how proteins misfold and aggregate into amyloid fibrils has increased considerably during recent years. Central to amyloid formation is an increase in the frequency of the β-sheet structure, leading to hydrogen bonding between misfolded monomers and creating a fibril that is comparably resistant to degradation. Generation of amyloid fibrils is nucleation dependent, and once formed, fibrils recruit and catalyze the conversion of native molecules. In AA amyloidosis, the expression of cytokines, particularly interleukin 6, leads to overproduction of serum amyloid A (SAA) by the liver. A chronically high plasma concentration of SAA results in the aggregation of amyloid into cross-β-sheet fibrillar deposits by mechanisms not fully understood. Therefore, AA amyloidosis can be thought of as a consequence of long-standing inflammatory disease. This review summarizes current knowledge about AA amyloidosis. The systemic amyloidoses have been regarded as intractable conditions, but improvements in the understanding of fibril composition and pathogenesis over the past decade have led to the development of a number of different therapeutic approaches with promising results.
24757559 Gender and ocular manifestations of connective tissue diseases and systemic vasculitides. 2014 Ocular manifestations are present in many connective tissue diseases which are characterized by an immune system that is directed against self. In this paper, we review the ocular findings in various connective tissue diseases and systemic vasculitides and highlight gender differences in each disease. In rheumatoid arthritis, we find that dry eyes affect women nine times more than men. The other extra-articular manifestations of rheumatoid arthritis affect women three times more commonly than men. Systemic lupus erythematosus can involve all ocular structures and women are nine times more affected than men. Systemic sclerosis is a rare disease but, again, it is more common in women with a female to male ratio of 8 : 1. Polymyositis and dermatomyositis also affect women more commonly than men but no gender differences have been found in the incidence or disease course in the systemic vasculitides associated with antineutrophil cytoplasmic antibody such as granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis). Finally, Behcet's disease is more common in males, and male gender is a risk factor for Behcet's disease. There is a slight female preponderance in sarcoidosis with female gender carrying a worse prognosis in the outcome of ocular disease.
25295562 Nurse-led clinics for patients with chronic diseases in hospital and transmural care organ 2014 Nov OBJECTIVES: The objectives of this study were to elucidate the purpose, content, and organization of nurse-led clinics for patients with chronic diseases and to explore whether there are differences in the content and context of the nurse-led clinics and attention for the home situation between a transmural and a hospital setting. SETTINGS: Transmural setting by which nurses work in both primary and secondary care and hospital setting where nurses are employed by a local hospital. Within the transmural setting, 4 nurse-led clinics were studied: heart failure, rheumatoid arthritis, Parkinson disease, and multiple sclerosis. Within the hospital setting, 3 nurse-led clinics were studied: heart failure, rheumatoid arthritis, and Parkinson disease. METHODS: A multiple-case embedded design was used to investigate the content and context of the nurse-led clinics for patients with heart failure, rheumatoid arthritis, Parkinson disease, and multiple sclerosis in the transmural and hospital setting. SAMPLE: One hundred twenty-one patient records, bimonthly telephone interviews with 218 patients, and face-to-face interviews with 7 nurses. RESULTS: Nurses focus on disease itself, treatment, and the everyday life of the patient. In addition, nurses maintain contacts with colleagues and other disciplines both inside and outside the hospital. No influence of setting was found on the execution of nurse-led clinics. CONCLUSIONS: Nurse-led clinics for chronically ill patients focus on all aspects of living with a chronic disease. The organizational context does not seem to contribute to the execution of the nurse-led clinics. Instead, this seems to be driven by patient needs, the definition of nursing and nursing competencies, and general developments in the nursing profession. IMPLICATIONS: To improve nursing care for patients with chronic illnesses, changing the organizational context might not be useful.
25228904 Effects of Interleukin-17A on Osteogenic Differentiation of Isolated Human Mesenchymal Ste 2014 OBJECTIVES: Rheumatoid arthritis (RA) is characterized by defective bone repair and excessive destruction and ankylosing spondylitis (AS) by increased ectopic bone formation with syndesmophytes. Since TNF-α and IL-17A are involved in both diseases, this study investigated their effects on the osteogenic differentiation of isolated human bone marrow-derived mesenchymal stem cells (hMSCs). METHODS: Differentiation of hMSCs into osteoblasts was induced in the presence or absence of IL-17A and/or TNF-α. Matrix mineralization (MM) was evaluated by alizarin red staining and alkaline phosphatase (ALP) activity. mRNA expression was measured by qRT-PCR for bone morphogenetic protein (BMP)-2 and Runx2, genes associated with osteogenesis, DKK-1, a negative regulator of osteogenesis, Schnurri-3 and receptor activator of nuclear factor kappa B ligand (RANKL), associated with the cross talk with osteoclasts, and TNF-α receptor type I and TNF-α receptor type II (TNFRII). RESULTS: TNF-α alone increased both MM and ALP activity. IL-17A alone increased ALP but not MM. Their combination was more potent. TNF-α alone increased BMP2 mRNA expression at 6 and 12 h. These levels decreased in combination with IL-17A at 6 h only. DKK-1 mRNA expression was inhibited by TNF-α and IL-17A either alone or combined. Supporting an imbalance toward osteoblastogenesis, RANKL expression was inhibited by TNF-α and IL-17A. However, TNF-α but not IL-17 alone decreased Runx2 mRNA expression at 6 h. In parallel, TNF-α but not IL-17 alone increased Schnurri-3 expression with a synergistic effect with their combination. This may be related to an increase of TNFRII overexpression. CONCLUSION: IL-17 increased the effects of TNF-α on bone matrix formation by hMSCs. However, IL-17 decreased the TNF-α-induced BMP2 inhibition. Synergistic interactions between TNF-α and IL-17 were seen for RANKL inhibition and Schnurri-3 induction. Such increase of Schnurri-3 may in turn activate osteoclasts leading to bone destruction as in RA. Conversely, in the absence of osteoclasts, this could promote ectopic bone formation as in AS.