Bronchial Smooth Muscle Cells of Asthmatics Promote Angiogenesis through Elevated Secretion of CXC-Chemokines (ENA-78, GRO-alpha, and IL-8)

<p>Background: Airway wall remodelling is a key pathology of asthma. It includes thickening of the airway wall, hypertrophy and hyperplasia of bronchial smooth muscle cells (BSMC), as well as an increased vascularity of the sub-epithelial cell layer. BSMC are known to be the effector cells of bronchoconstriction, but they are increasingly recognized as an important source of inflammatory mediators and angiogenic factors.</p><p>Objective: To compare the angiogenic potential of BSMC of asthmatic and non-asthmatic patients and to identify asthma-specific angiogenic factors.</p><p>Methods: Primary BSMC were isolated from human airway tissue of asthmatic and non-asthmatic patients. Conditioned medium (CM) collected from BSMC isolates was tested for angiogenic capacity using the endothelial cell (EC)-spheroid in vitro angiogenesis assay. Angiogenic factors in CM were quantified using a human angiogenesis antibody array and enzyme linked immunosorbent assay.</p><p>Results: Induction of sprout outgrowth from EC-spheroids by CM of BSMC obtained from asthma patients was increased compared with CM of control BSMC (twofold, p <0.001). Levels of ENA-78, GRO-alpha and IL-8 were significantly elevated in CM of BSMC from asthma patients (p <0.05 vs. non-asthmatic patients). SB 265610, a competitive antagonist of chemokine (CXC-motif) receptor 2 (CXCR2), attenuated the increased sprout outgrowth induced by CM of asthma patient-derived BSMC.</p><p>Conclusions: BSMC isolated from asthma patients exhibit increased angiogenic potential. This effect is mediated through the CXCR2 ligands (ENA78, GRO-alpha and IL-8) produced by BSMC. Implications: CXCR2 ligands may play a decisive role in directing the neovascularization in the sub-epithelial cell layers of the lungs of asthma patients. Counteracting the CXCR2-mediated neovascularization by pharmaceutical compounds may represent a novel strategy to reduce airway remodelling in asthma.</p>

Outcomes of macular hole surgery:implications for surgical management and clinical governance

PURPOSE: The optimal method and timing of the surgical treatment for idiopathic macular holes remains unknown. The aim of this retrospective study was to identify factors associated with anatomical and visual success in macular hole surgery.METHODS: Case records of 55 patients undergoing macular hole surgery at three units in the 2-year period up to July 2002 were reviewed to identify factors associated with anatomical and visual success. The following potential prognosticators were evaluated: patient age, hole stage, hole latency prior to surgery, preoperative acuity, simultaneous phacoemulsification, and intraocular lens implantation, internal limiting membrane peeling with and/or without indocyanine green, and postoperative posturing.RESULTS: The duration of preoperative symptoms, indocyanine green-assisted internal limiting membrane peeling, hole stage, and better preoperative visual acuity were associated with both anatomical success and regaining a postoperative visual acuity of 6/12 or better.DISCUSSION: The closure rate in patients undergoing surgery within 1 year of onset was 94.0%, and in those waiting 1 year or more it was 47.4%. Clinical governance and quality issues should dictate that NHS macular hole surgery is available to all within 1 year of onset. This study showed no adverse effect of ICG dye retinal staining. The results support the use of a 'patient-friendly' approach of simultaneous cataract surgery with no prone postoperative posturing.</p

External ocular infections due to methicillin-resistant Staphylococcus aureus (MRSA)

Purpose: To determine the prevalence and clinical characteristics of external ocular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in an ophthalmic hospital in the UK. Methods: A retrospective analysis of the case notes of patients who had culture proven external ocular Staphylococcal infections during a 44-month period was undertaken. Results: There were a total of 548 external eye infections caused by Staphylococcus aureus. Of these, 17 (3%) were MRSA positive. The most common presentation was conjunctivitis seen in six patients. All MRSA isolates were sensitive to chloramphenicol. Ofloxacin resistance was observed in all isolates from patients over the age of 50 years. All patients had an underlying history of either an ocular surface disease, malignancy, or a debilitating medical illness. Conclusions: MRSA is as yet an infrequent cause of external ocular infections. Patients typically have underlying ocular risk factors and/or are medically debilitated. Different strains infect young and old age groups with characteristic antimicrobial sensitivity. This study highlights the need for more work to establish the role of MRSA commensals and ocular infections. © 2005 Nature Publishing Group All rights reserved