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Biomedical subjects

Andrew Pearson

Publications and source records attributed to Andrew Pearson.

10 recordsLinked to original sources
PubMed2006

Bilateral canaliculitis following SmartPLUG insertion for dry eye syndrome post LASIK surgery.

BACKGROUND: Dry eyes are a common symptom following LASIK corneal refractive surgery. Treatments include topical lubricants to supplement the tear film, and punctal occlusion to reduce tear outflow. Canaliculitis is a recognised complication of punctal plugs, but has not previously been described following insertion of newer generation semi-permanent intra-canalicular plugs, such as the SmartPLUG. METHODS: Case report. RESULTS: We describe a 60-year-old female who underwent bilateral LASIK surgery leading to aggravation of her dry eye syndrome. She was managed with the insertion of semi-permanent intra-canalicular moldable silicone SmartPLUGs. She subsequently developed bilateral canaliculitis requiring bilateral canaliculotomy. CONCLUSIONS: To the best of our knowledge, this is the first report of bilateral canaliculitis following intra-canalicular SmartPLUG insertion. This case illustrates that punctal occlusion with the newer generation intra-canalicular plugs carries a risk of canaliculitis and that irrigation is not always effective in removing these devices.

Dacryocystitis↗
PubMed2005

Surveillance and epidemiology of MRSA bacteraemia in the UK.

Surveillance of bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA) in the UK has involved collection of data from hospital microbiology laboratories via several mechanisms, including a voluntary reporting scheme that has been operational in England and Wales since 1989 and mandatory reporting schemes that have been running independently in England, Wales, Scotland and Northern Ireland since 2001. In addition, surveillance schemes involving panels of participating sentinel laboratories that submit isolates for centralized susceptibility testing, such as the Bacteraemia Resistance Surveillance Programme run by the BSAC, have also been established. Each of these data sources have particular advantages, but they also have their individual limitations, with the result that they each give an incomplete picture if considered in isolation. However, by pooling the findings from these different but complementary surveillance programmes, a much more comprehensive and credible picture of the problem posed by MRSA is produced. These schemes have shown both a dramatic rise in the total numbers of cases of S. aureus bacteraemia reported annually and an increase in the proportion of such cases that involve MRSA (from 2% in 1990 to >40% in the early 2000s), although the most recent data indicate a slight reversal of these trends. Characterization of isolates of MRSA shows a marked temporal relationship between the rise in MRSA bacteraemias and the emergence and spread of two strains of epidemic MRSA, EMRSA-15 and EMRSA-16. Surveillance and control of MRSA infection continue to be high profile and further developments to the mandatory surveillance system in England are likely in the near future.

Bacteremia↗
PubMed2005

The safety profile of long-term, high-dose intraocular corticosteroid delivery.

PURPOSE: To report the feasibility and safety profile of 2-mg and 6-mg fluocinolone acetonide implants after long-term follow-up in eyes with choroidal neovascularization (CNV). DESIGN: Prospective, noncomparative, interventional case series of patients with non-age-related subfoveal choroidal neovascularization enrolled in a compassionate use protocol. METHODS: Sustained drug delivery devices containing either 2 mg (eight eyes) or 6 mg (six eyes) of fluocinolone acetonide were implanted through the pars plana into the vitreous cavity of 14 patients with predominantly classic, subfoveal CNV. The main outcome measures were complications related to the device. Secondary outcome measures were involution of established CNV, inhibition of recurrent CNV, and visual acuity. RESULTS: Patients had a diagnosis of ocular histoplasmosis (seven), myopic degeneration (four), angioid streaks (two), and punctate inner choroidopathy (one). Patients were followed for an average of 33 months (range, 16 to 40 months). All 14 eyes developed elevated intraocular pressure and cataract. Four eyes developed nonischemic central retinal vein occlusion. Complications required implant removal in 8 eyes. Ten of 14 eyes demonstrated involution of CNV or inhibition of recurrent CNV. Ten eyes had stable or improved visual acuity. Median initial visual acuity was 20/64. Median final visual acuity was 20/40. CONCLUSIONS: Long-term follow-up demonstrates a significant complication rate with the sustained release of high-dose intraocular corticosteroids. The complications are treatable, and eyes can retain good vision. This therapeutic approach warrants further study to identify if lower doses of corticosteroids may reduce the complication rate yet still be effective in treating ocular disease.

Adult↗
PubMed2004

Metastatic mesothelioma presenting with proptosis.

PURPOSE: To describe the clinical presentation and histologic findings in a patient with metastatic mesothelioma presenting to the ophthalmologist with nonaxial proptosis. DESIGN: Case report. METHODS: A 55-year-old man presented with a short history of progressive ocular discomfort and vertical diplopia. Clinical examination identified nonaxial proptosis. Subsequent computed tomography showed a large extraconal mass consistent with a malignant process. Three months earlier the patient had been diagnosed with pleural mesothelioma. Unfortunately, he died 3 months after his ophthalmic presentation. Postmortem examination confirmed metastatic mesothelioma in the orbital roof that was histologically identical to the primary pleural malignancy. CONCLUSION: Pleural mesothelioma can metastasize to the orbit, causing proptosis.

Biomarkers, Tumor↗
PubMed2004

Assessment of arginine 97 and lysine 72 as determinants of substrate specificity in cytochrome P450 2C9 (CYP2C9).

CYP2C9 is distinguished by a preference for substrates bearing a negative charge at physiological pH. Previous studies have suggested that CYP2C9 residues R97 and K72 may play roles in determining preference for anionic substrates by interaction at the active site or in the access channel. The aim of the present study was to assess the role of these two residues in determining substrate selectivity. R97 and K72 were substituted with negative, uncharged polar and hydrophobic residues using a degenerate polymerase chain reaction-directed strategy. Wild-type and mutant enzymes were expressed in bicistronic format with human cytochrome P450 reductase in Escherichia coli. Mutation of R97 led to a loss of holoenzyme expression for R97A, R97V, R97L, R97T, and R97E mutants. Low levels of hemoprotein were detected for R97Q, R97K, R97I, and R97P mutants. Significant apoenzyme was observed, suggesting that heme insertion or protein stability was compromised in R97 mutants. These observations are consistent with a structural role for R97 in addition to any role in substrate binding. By contrast, all K72 mutants examined (K72E, K72Q, K72V, and K72L) could be expressed as hemoprotein at levels comparable to wild-type. Type I binding spectra were obtained with wild-type and K72 mutants using diclofenac and ibuprofen. Mutation of K72 had little or no effect on the interaction with these substrates, arguing against a critical role in determining substrate specificity. Thus, neither residue appears to play a role in determining substrate specificity, but a structural role for R97 can be proposed consistent with recently published crystallographic data for CYP2C9 and CYP2C5.

Animals↗
PubMed2003

Genes co-amplified with MYCN in neuroblastoma: silent passengers or co-determinants of phenotype?

Amplification of the MYCN oncogene in neuroblastoma is associated with poor prognosis. The amplified unit of DNA can be up to 1 Mb in size and so could contain additional genes that affect tumour phenotype. Identification of such genes may assist in optimising the determination of prognosis, and could provide new targets for treatment. Three genes have so far been identified, which are frequently co-amplified with MYCN in neuroblastoma, DDX1, NAG and N-cym. In this review, the known or putative properties of the protein products of the genes are discussed, and their possible roles in determining tumour behaviour are assessed.

DEAD-box RNA Helicases↗
PubMed2003

The MYCN oncoprotein as a drug development target.

The transcription factor and proto-oncogene MYCN is reviewed as a potential specific target for cancer therapy. Amplification of MYCN is frequently found in a number of advanced-stage tumours, including neuroblastoma (25%), small cell lung cancers (7%), alveolar rhabdomyosarcoma and retinoblastoma. It is associated with rapid tumour progression and poor outcome in human neuroblastoma. MYCN is a member of the myc family of proto-oncogenes which encode nuclear proteins that form heterodimers with MAX protein through their conserved HLHZip domains. The MYC/MAX complexes transactivate a number of MYC-target genes in a sequence-specific manner. MYC-MAX interaction is essential for MYC-induced cell cycle progression, cellular transformation, and transcriptional activation. A causal link between the transformed phenotype and MYCN has been established by a range of in vitro and in vivo studies, including a transgenic model of neuroblastoma in which MYCN overexpression is targeted to neuronal tissue by the use of a tyrosine hydroxylase promoter. Downregulation of MYCN expression either by antisense treatment targeted against MYCN mRNA or by retinoids has been shown to decrease proliferation and/or induce neuronal differentiation of neuroblastoma cells. Inhibition of MYC-MAX dimerisation by small-molecule antagonists has recently been shown to interfere with MYC-induced transformation of chick embryo fibroblasts, indicating that functional inhibitors of the MYC family of oncoproteins have potential as therapeutic agents. Finally, we describe the development and validation of a functional MYCN reporter gene assay using neuroblastoma cells (NGP) which have been stably transfected with a luciferase gene construct under control of the ornithine decarboxylase gene promoter. This assay has been used for a pilot screen of 2800 compounds from the Cancer Research-UK collection, identifying five compounds showing a consistent significant reduction of MYCN-dependent luciferase activity (>50%) in repeated screens. This cell-based, MYCN reporter gene assay will be scaled up for high throughput screens of compound libraries and will aid in the future development of specific therapeutic strategies in neuroblastoma and other tumours in which MYCN amplification has been implicated.

Antineoplastic Agents↗
PubMed2003

Research topics.

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Animals↗