Left ventricular mass regression following aortic valve replacement with mechanical valves

Objective The degree of Left Ventricular Mass Index (LVMI) regression following aortic valve replacement correlates with long-term survival. This study aims to assess the extent of LVMI regression at 3 months following aortic valve replacement (AVR) with different types and sizes of mechanical valves in rheumatic aortic valve disease. Methods The LVMI regression was studied in 34 consecutive patients, undergoing elective AVR for rheumatic aortic stenosis and/or regurgitation. They were grouped in A and B, matched in age, body surface area and pre-operative LVMI, receiving respectively a tilting disc and a bileaflet mechanical valve. The LVMI was calculated by M-mode echocardiography using the Devereux' formula pre-operatively and three months post-operatively. The trend of LVMI reduction was compared between the two groups and amongst the patients with stenotic, regurgitant and mixed aortic valve, pathologies; and receiving different sizes of valves. Results The mean preoperative LVMI was 199g±79.5 g/m². At three months post aortic valve replacement, the mean LVMI was 130g±49.0 g/m². There was a significant reduction of LVMI post-operatively (p=0.001) at three months follow-up. The extent of LVMI regression following surgery amongst the groups A and B did not vary significantly (p=0.92). The extent of LVMI regression did not vary significantly in patients with different aortic valve pathology nor with different sizes of the valves implanted. Conclusions There is a significant early LVMI regression following aortic valve replacement in rheumatic aortic valve disease. The type and the size of the mechanical prosthesis or the rheumatic pathology do not appear to influence this regression.     

New areas for therapeutic intervention in the treatment of rheumatic disease.

Anti-rheumatic therapy has been targeted against the symptoms arising from chronic inflammation of the joint. This has resulted in the extensive use of non-steroidal anti-inflammatory drugs. It is now becoming apparent that these agents have no beneficial effect on disease progression. This mini review concentrates on the formation and maintenance of pannus, the granulomatous tissue responsible for cartilage and bone erosion. This reveals a number of possible therapeutic targets. Protease inhibitors could be used to interfere with the degradatory processes. The diverse functions of endothelial cells suggest oedema formation, cell accumulation and supply of nutrients to the granulomatous tissue could all be targeted by appropriate therapy. Alternatively the immune processes that control pannus formation and state of activation could be regulated by interfering with antigen presentation and the cytokine network.     

Characterization of bortezomib-adapted I-45 mesothelioma cells

Background  

Bortezomib, a proteasome-specific inhibitor, has emerged as a promising cancer therapeutic agent. However, development of resistance to bortezomib may pose a challenge to effective anticancer therapy. Therefore, characterization of cellular mechanisms involved in bortezomib resistance and development of effective strategies to overcome this resistance represent important steps in the advancement of bortezomib-mediated cancer therapy.     

Secondary pharyngeal tuberculosis

Secondary tuberculosis of pharynx is a rare condition as pharynx is not a common site for clinically manifest tuberculosis. A rare and unusual case of secondary oropharyngeal tuberculosis in a 40 years male patient, who presented with an ulceroproliferative lesion of oropharynx extending to nasopharynx and laryngopharynx is being reported.     

Candidaemia: a 10-year study in an Indian teaching hospital

Retrospective evaluation of candidaemia patients was performed in an Indian teaching hospital over a 10-year period. The incidence of patients with candidaemia increased eleven-fold in the second half of the study period (55 patients) compared with the first half (5 patients). Haematological malignancies (11 patients), neonatal septicaemia (9), cardiac abnormalities and cardiac surgery (9) were the commonest underlying diseases in these patients. Candida albicans (50%), C. guilliermondii (17%), C. tropicalis (15%) and C. parapsilosis (8%) were the most common fungal pathogens isolated from blood culture. Therapy with two or more antibiotics (92%), corticosteroid administration (25%), intravascular catheter use for over 24 h (78%) and neutropenia (48%) were the accountable predisposing factors. Prolonged hospitalization (mean average 22.2 days as compared with 11.2 days in other patients) was an added risk factor in these patients.     

Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas(lpr) mice from autoimmune disease

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LFA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas(lpr) mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(lpr) mice, suggesting a lack of redundancy among the beta(2) integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE.     

Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.