Increased expression of HLA-DQ antigens by interstitial cells and endothelium in the synovial membrane of rheumatoid arthritis patients compared with reactive arthritis patients

We investigated cellular phenotypes and expression of class II major histocompatibility complex antigens on endothelium and cellular infiltrates in synovium from patients with rheumatoid arthritis (RA) or reactive arthritis, using an indirect immunoperoxidase technique. The RA specimens showed synovial lining layer hypertrophy and several focal accumulations of lymphocytes, both of which were absent in the reactive arthritis synovium. The percentage of cells expressing monocyte/macrophage markers was significantly higher in RA specimens. The percentages of cells expressing B and T cell markers were similar in both diseases. There was no significant difference in the expression of HLA-DR or DP by endothelium in the 2 diseases, but a marked increase in expression of HLA-DQ by endothelium was observed in the RA synovium versus that from patients with reactive arthritis. This overexpression of HLA-DQ was also seen in the interstitial cells of RA patients compared with reactive arthritis patients. In the reactive arthritis synovium, a significant population of cells (30%) was noted to be HLA-DR positive, and negative for macrophage and lymphocyte markers. Some of these cells had a dendritic morphology. The coexpression of HLA-DQ and HLA-DR may play an important role in antigen presentation and disease chronicity in RA.     

Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine–glycine–glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.     

Molecular and Biochemical Characterization of CTX-M-131, a Natural Asp240Gly Variant Derived from CTX-M-2, Produced by a Providencia rettgeri Clinical Strain in S?o Paulo,Brazil

CTX-M-131 is a natural Asp240Gly variant from the CTX-M-2 group detected in a Providencia rettgeri clinical strain from Brazil. Molecular analysis showed that bla_CTX-M-131 was inserted in a complex class 1 integron harbored by a 112-kb plasmid, which has not been previously described as a platform for CTX-M-encoding genes with the Asp240Gly mutation. Steady-state kinetic parameters showed that the enzyme has a typical cefotaximase catalytic profile and an enhanced activity against ceftazidime.     

Health Economic Modelling of Treatment Sequences for Rheumatoid Arthritis: A Systematic Review

The objective of the work reported in this paper was to critically assess how sequential disease-modifying anti-rheumatic drugs (DMARDs) have been modelled in the context of economic evaluation of the use of DMARDs for treatment of rheumatoid arthritis (RA). A secondary purpose was to identify the methodological challenges of modelling sequential therapies. Systematic searches of 10 databases were undertaken in February 2013. Studies were included if they were in the English language and a full comparative economic evaluation was reported. They were appraised by use of the Drummond checklist (Appendix to this paper). Data extracted included economic evaluation data, data relating to sequential treatment, and data on the modelling methods used. Fifty-seven studies were identified, with 25 (44 %) modelling a sequence of treatments. Forty-three (75 %) were cost–utility analyses. Eleven (19 %) were UK studies and 11 (19 %) were US. The remainder were mainly European (26 (46 %)). A distinction was made between studies of recent-onset RA (14 (25 %)) and those of established RA (42 (74 %)). One study (1 %) was unclear. Individual-level models were more likely to meet the Drummond criteria and evaluate sequences. No study identified an optimum sequence of multiple treatments given a set of treatment options. The level of reporting of the methods and evidence used to assess the effect of downstream treatments in the sequence was generally poor. When lifelong models and downstream treatment sequences were considered, evidence gaps were identified. The review discovered that methods have not been consistently applied, leading to varied estimates of cost-effectiveness. Treatment sequences have not been fully considered and modelled, potentially resulting in inaccurate estimates of cost-effectiveness.     

Coronary cardiac allograft vasculopathy versus native atherosclerosis: difficulties in classification

Cardiac allograft vasculopathy is regarded as a progressive and diffuse intimal hyperplastic lesion of arteries and veins that leads to insidious vessel narrowing and to allograft ischemic disease, such as acute myocardial infarction or sudden cardiac death. The coronary lesions in transplanted hearts are considered as a particular type of arteriosclerosis with many similarities but also significant differences compared to native coronary atherosclerosis. It is particularly difficult for pathologists to systematically classify the lesions and to elucidate their origins, since over time, the allograft immune responses cause vascular pathology characterized by not only the onset of de novo fibrocellular lesions but also remodeling of already-existing native atherosclerotic lesions in the donor heart. Intraplaque hemorrhages, which result from newly formed leaky microvessels, may cause rapid increase of stenosis and generate a substrate for plaque destabilization. Comparing cardiac allograft vasculopathy from explanted hearts at autopsy with native coronary atherosclerosis from hearts removed at transplantation has revealed that ongoing intraplaque hemorrhages are also an important feature of cardiac allograft vasculopathy and may be important factors in the rapid progression of cardiac allograft vasculopathy.     

How we manage the haematological aspects of major obstetric haemorrhage

Major obstetric haemorrhage (MOH) remains an important medical challenge worldwide, contributing to significant maternal morbidity and mortality. Prompt and appropriate management is essential if we are to improve outcomes and reduce substandard care that may result in adverse consequences. This review describes the current understanding of the pathophysiological aspects of MOH together with the principles of transfusion and haemostatic therapy, with emphasis on a coordinated multidisciplinary approach. We also highlight the current lack of evidence available from randomized controlled trials to inform best practice and the need to prioritize research in this key clinical area.