Elastin modulation and modification by homocysteine: a key factor in the pathogenesis of Pseudoexfoliation syndrome?
BRITISH JOURNAL OF OPHTHALMOLOGY
Authors: Rebecca, Manohar; Gayathri, Ramakrishnan; Bhuvanasundar, Renganathan; Sripriya, Krishnamoorthy; Shantha, Balekudaru; Angayarkanni, Narayanasamy
Abstract
Background Pseudoexfoliation syndrome (PXF) is an idiopathic, elastogenesis-associated systemic disease characterised by amyloid-like material aggregates in the eye. Elevated plasma and aqueous humour (aqH) homocysteine (Hcy) is reportedly associated with PXF. This study is aimed to probe Hcy-mediated alterations in elastin expression. Methodology Lens level of Hcy (total Hcy (tHcy)), mRNA expression of Eln, CBS and MTR in lens capsule, protein expression of elastin in aqH were estimated by enzyme immunoassay, quantitative PCR and western blot, respectively in PXF, PXF with glaucoma (PXF-G) cases, in comparison with cataract-alone disease controls. Human lens epithelial cells (hLECs) were exposed to Hcy and homocysteine thiolactone (HCTL) to evaluate elastin expression in vitro. Furthermore, elastin recombinant protein was incubated with Hcy and HCTL to assess secondary and tertiary structural modifications based on circular dichroism spectroscopy, spectrophotometric and SEM studies. Results The lens tHcy was significantly high in PXF (p=0.02) and PXF-G (p=0.009). Eln expression was elevated in PXF and PXF-G (p=0.0007). Elastin level in aqH was elevated in PXF (p=0.01) and PXF-G (p=0.002). Hcy (200 mu M) and HCTL (1 mu M) promoted elastin expression at mRNA level by 36-fold (p=0.02) and 10-fold (p=0.05), respectively, and at protein level by nearly two-fold in cultured hLECs. Secondary structure changes in elastin protein caused by Hcy were evident from 34.11% drop in alpha-helix and 6.17% gain in beta-sheet. Fluorescence, spectral assays and SEM analyses showed aggregation and amyloid formation of elastin with homocysteinylation. Conclusion The study reveals that lens accumulation of Hcy associated with hyperhomocysteinaemia is characteristic of PXF that augments elastin expression. Hcy causes structural changes promoting elastin aggregation, thereby contributing to defective elastin in PXF and PXF-G.
A critical review of thyroidectomy consent in the UK
INTERNATIONAL JOURNAL OF SURGERY
Authors: McIntyre, C.; Tolley, N.
Abstract
Background: In 2015-16, the National Health Service (NHS) Litigation Authority received 10,965 claims for clinical negligence, with surgery having the highest number of claims. Currently a sum amounting to 25% of the annual NHS budget has been ring-fenced to meet extant claims. Claims made on a basis of inadequate informed consent are increasingly seen with many achieving a successful plaintiff outcome. There are presently no UK guidelines for thyroidectomy consent. Method: A prospective study was performed to investigate current consent practice among the British Association of Endocrine and Thyroid Surgeons (BAETS) membership and patients having previously undergone thyroidectomy. For surgeons, the Bolam legal test applied where surgeons declared what risks and complications they routinely consented for during their practice. A study was also undertaken in patients who had previously undergone thyroidectomy for cancer applying the rule of Montgomery. Results: Consent practice from 193 surgeons and data from 415 patients was analysed. In total thyroidectomy for cancer, 95% of surgeons consent for Recurrent Laryngeal Nerve (RLN) injury and temporary or permanent voice change. 70% specifically consent for External Laryngeal Nerve (ELN) injury, 50% for tracheostomy and 55% for general anaesthetic associated complications. Analysis of patient data showed they would like to be consented for far more risks than they are presently informed about in general medical practice. There was significant variation in the consenting practice in BAETS surgeons. Conclusion: A BAETS approved consensus guideline to standardise UK consent practice would be appropriate. This may reduce complaints, litigation claims and guide expert witnesses.