High risk of ischemic heart disease in patients with lupus nephritis

Objective.To investigate the occurrence of ischemic heart disease (IHD) in a cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN).Methods.Information on all hospitalizations in Denmark for IHD between 1977 and 2006 was obtained from the Danish National Hospital Register. Occurrence of IHD after date of first renal biopsy in the LN cohort was compared to the occurrence of IHD in the general population by calculation of standardized ratios of observed to expected events (O:E ratios) for different manifestations of IHD registered during inpatient and outpatient hospital visits.Results.The median duration of followup was 14.7 (range 0.1–30.0) years. Thirty-one first-time hospitalizations for IHD occurred in the cohort, yielding an overall O:E ratio for IHD of 6.8 (95% CI 4.6–9.7). Increased risks were found for angina pectoris (O:E ratio 6.0, 95% CI 3.0–11), myocardial infarction (O:E ratio 7.9, 95% CI 3.8–15), and other IHD-related diagnoses combined (O:E ratio 6.9, 95% CI 3.3–13). A high IHD risk was observed for patients aged &lt; 31 years at time of first renal biopsy (O:E ratio 17.1, 95% CI 9.1–29) and for patients aged 30–39 years during followup (O:E ratio 42.3, 95% CI 21–76). Patients undergoing chronic renal replacement therapy also had a pronounced risk of IHD (O:E ratio 19.4, 95% CI 7.8–40).Conclusion.LN is associated with markedly increased morbidity from IHD. Our findings indicate that patients with early-onset LN have a disturbingly high risk of IHD compared to the general population.</jats:sec

Implementing the European quality assurance in vocational education and training (EQAVET) at national level: some insights from the PEN Leonardo project

EQAVET, the quality assurance tool in vocational and educational training, was developed in response to the need for a supply of a trained workforce for labour market needs. Implementation of EQAVET at national level, however, remains a challenge. The research reported here focused on the implementation of QA processes by VET providers in 4 countries: Malta, Italy, Turkey, and Sweden. Data was collected through a questionnaire with 62 VET providers. Responses showed that there is an overall commitment to quality. There is, however, little knowledge of EQAVET across the countries, with the exception of Malta. None the less, all VET providers have implemented some aspects of EQAVET, even if not always intentionally. The situation is, however, far from EQAVET being fully implemented. Reflections are made on whether the EQAVET model specifically or qualification assurance principles assurances should be promoted across Europe. (author's abstract

Assessment of health‐related quality of life as an outcome measure in granulomatosis with polyangiitis (Wegener's)

Objective To assess a generic measure of health‐related quality of life (HRQOL) as an outcome measure in granulomatosis with polyangiitis (Wegener's) (GPA). Methods Subjects were participants in the Wegener's Granulomatosis Etanercept Trial (WGET) or the Vasculitis Clinical Research Consortium Longitudinal Study (VCRC‐LS). HRQOL was assessed with the Short Form 36 (SF‐36) health survey that includes physical and mental component summary scores (PCS and MCS, respectively). Disease activity was assessed with the Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG). Results The data from 180 subjects in the WGET (median followup 2.3 years, mean number of visits 10) and 237 subjects in the VCRC‐LS (median followup 2.0 years, mean number of visits 8) were analyzed. A 1 unit increase in the BVAS/WG corresponded to a 1.15 unit (95% confidence interval [95% CI] 1.02, 1.29) decrease for the PCS and a 0.93 (95% CI 0.78, 1.07) decrease for the MCS in the WGET, and to a 1.16 unit decrease for the PCS (95% CI 0.94, 1.39) and a 0.79 unit decrease for the MCS (95% CI 0.51, 1.39) in the VCRC‐LS. In both arms of the WGET study, SF‐36 measures improved rapidly during the first 6 weeks of treatment followed by gradual improvement among patients achieving sustained remission (0.5 improvement in PCS per 3 months), but worsened slightly (0.03 decrease in PCS every 3 months) among patients not achieving sustained remission ( P = 0.005). Conclusion HRQOL, as measured by the SF‐36, is reduced among patients with GPA. SF‐36 measures are modestly associated with other disease outcomes and discriminate between disease states of importance in GPA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90377/1/20649_ftp.pd

ANCA-associated vasculitis – Should we change the standard of care?

Collaborative clinical trials over the last 25 years have revolutionised the care of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This has led to production of management recommendations and standards of care. This paper reviews the existing standards and the recent evidence that has fed further evolution of standards of care. Pattern recognition remains vital to early diagnosis and therefore initiation treatment. While cyclophosphamide remains the treatment of choice, the advent of rituximab has been shown to be beneficial to patients with relapsing disease. It may be safer in young females and those with a risk of urothelial cancers. Methotrexate and mycophenolate mofetil may not be as good as previously thought for inducing remission. Azathioprine and rituximab are the standards for remission maintenance. There have been recent changes to the nomenclature of vasculitides. It is possible that these will continue to evolve over time to make them more meaningful and inform treatment and prognosis. In the absence of gold-standard biomarkers, we discuss the role of ANCA and histopathology, especially in the Indian setting. Follow-up and monitoring of these patients should include structured evaluation using validated clinical tools, assessing cardiovascular risk, vigilance for infections and other co-morbidities due to exposure to glucocorticoids and immunosuppression

Two cases of lymphoepithelial cyst of the pancreas

A 35-year-old man was found to have a cystic mass in the pancreatic body on a routine health examination ; high serum CA19-9 was also detected. The enucleated cyst was diagnosed as a lymphoepithelial cyst (LEC). A 74-year-old man found to have a cystic mass in the pancreatic head by computer tomography as well as high serum CA19-9 was suspected of a cystic neoplasm of the pancreas (IPMN), and pylorus-preserving pancreaticoduodenectomy (PPPD) was performed. Pathologically, the cyst was found to be LEC. It is often difficult to diagnose pancreatic cyst as LEC preoperatively. Care should be taken not to do over-surgery for benign disease LEC

Early clinical features in Systemic Lupus Erythematosus: can they be used to achieve earlier diagnosis?: a risk prediction model

OBJECTIVES: 1) To compare the primary care consulting behaviour prior to diagnosis of people with Systemic Lupus Erythematosus (SLE) with controls, 2) to develop and validate a risk prediction model to aid earlier SLE diagnosis. METHODS: 1,739 incident SLE cases practice-matched to 6,956 controls from the UK Clinical Practice Research Datalink. Odds ratios were calculated for age, gender, consultation rates, selected presenting clinical features and previous diagnoses in the 5 years preceding diagnosis date using logistic regression. A risk prediction model was developed from pre-selected variables using backward stepwise logistic regression. Model discrimination and calibration were tested in an independent validation cohort of 1,831,747 patients. RESULTS: People with SLE had a significantly higher consultation rate than controls (median 9.2 vs 3.8/year) which was in part attributable to clinical features that occur in SLE. The final risk prediction model included the variables age, gender, consultation rate, arthralgia or arthritis, rash, alopecia, sicca, Raynaud's, serositis and fatigue. The model discrimination and calibration in the validation sample was good (Receiver operator characteristic curve: 0.75, 95% CI 0.73-0.78). However, absolute risk predictions for SLE were typically less than 1% due to the rare nature of SLE. CONCLUSIONS: People with SLE consult their GP more frequently and with clinical features attributable to SLE in the five years preceding diagnosis, suggesting that there are potential opportunities to reduce diagnostic delay in primary care. A risk prediction model was developed and validated which may be used to identify people at risk of SLE in future clinical practice. This article is protected by copyright. All rights reserved

Vivienne Westwood and the ethics of consuming fashion

Our paper examines ethical consumption using the case study of Vivienne Westwood, the fashion designer, and her eponymous firm, and shows how consumers of fashion might be considered ethical. The fashion industry has figured prominently in ethical debates, notably its role in encouraging overconsumption of resources and promoting an idealised lifestyle that is often neither materially nor psychically sustainable for consumers (Buchholz, 1998). We acknowledge this, yet suggest the purchase and use of clothing carries with it the potential to be ethical insofar as customers find themselves personally implicated with and caring for a designers' work

The renal metallothionein expression profile is altered in human lupus nephritis

Udgivelsesdato: 2008-nullINTRODUCTION: Metallothionein (MT) isoforms I + II are polypeptides with potent antioxidative and anti-inflammatory properties. In healthy kidneys, MT-I+II have been described as intracellular proteins of proximal tubular cells. The aim of the present study was to investigate whether the renal MT-I+II expression profile is altered during lupus nephritis. METHODS: Immunohistochemistry was performed on renal biopsies from 37 patients with lupus nephritis. Four specimens of healthy renal tissue served as controls. Clinicopathological correlation studies and renal survival analyses were performed by means of standard statistical methods. RESULTS: Proximal tubules displaying epithelial cell MT-I+II depletion in combination with luminal MT-I+II expression were observed in 31 out of 37 of the lupus nephritis specimens, but not in any of the control sections (P = 0.006). The tubular MT score, defined as the median number of proximal tubules displaying this MT expression pattern per high-power microscope field (40x magnification), was positively correlated to the creatinine clearance in the lupus nephritis cohort (P = 0.01). Furthermore, a tubular MT score below the median value of the cohort emerged as a significant predictor of a poor renal outcome in renal survival analyses. Thus, patients with a tubular MT score &lt; 1.0 had a 6.2-times higher risk of developing end-stage renal disease than patients with a tubular MT score &gt;or= 1.0 (P = 0.03). CONCLUSION: Lupus nephritis is associated with significant alterations in renal MT-I+II expression. Our data indicate that important prognostic information can be deduced from the renal MT-I+II expression profile in systemic lupus erythematosus patients with nephritis

The Aminopeptidase CD13 Induces Homotypic Aggregation in Neutrophils and Impairs Collagen Invasion.

Aminopeptidase N (CD13) is a widely expressed cell surface metallopeptidase involved in the migration of cancer and endothelial cells. Apart from our demonstration that CD13 modulates the efficacy of tumor necrosis factor-α-induced apoptosis in neutrophils, no other function for CD13 has been ascribed in this cell. We hypothesized that CD13 may be involved in neutrophil migration and/or homotypic aggregation. Using purified human blood neutrophils we confirmed the expression of CD13 on neutrophils and its up-regulation by pro-inflammatory agonists. However, using the anti-CD13 monoclonal antibody WM-15 and the aminopeptidase enzymatic inhibitor bestatin we were unable to demonstrate any direct involvement of CD13 in neutrophil polarisation or chemotaxis. In contrast, IL-8-mediated neutrophil migration in type I collagen gels was significantly impaired by the anti-CD13 monoclonal antibodies WM-15 and MY7. Notably, these antibodies also induced significant homotypic aggregation of neutrophils, which was dependent on CD13 cross-linking and was attenuated by phosphoinositide 3-kinase and extracellular signal-related kinase 1/2 inhibition. Live imaging demonstrated that in WM-15-treated neutrophils, where homotypic aggregation was evident, the number of cells entering IL-8 impregnated collagen I gels was significantly reduced. These data reveal a novel role for CD13 in inducing homotypic aggregation in neutrophils, which results in a transmigration deficiency; this mechanism may be relevant to neutrophil micro-aggregation in vivo.This work was funded by a Medical Research Council Research Training Fellowship to CAF (G0900329), Addenbrooke’s Charitable Trust (ACT), CUHNHSFT, Papworth Hospital NHS Foundation Trust and the NIHR Cambridge Biomedical Research Centre. CAF received a Raymond and Beverly Sackler Studentship.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pone.016010