Publications by authors named "Eugene P Halligan"

7 Publications

  • Page 1 of 1

Patient characteristics and severity of human rhinovirus infections in children.

J Clin Virol 2013 Sep 22;58(1):216-20. Epub 2013 Jul 22.

Department of Infectious Diseases, King's College London School of Medicine, London, UK.

Background: It is increasingly recognized that human rhinoviruses (HRV) can be associated with severe infections. However, conflicting results have been reported on the relative prevalence and severity of the three HRV species.

Objectives: The relative prevalence and clinical characteristics of HRV-A, B and C, in children attending a South London teaching hospital were investigated retrospectively.

Study Design: Children aged<16 years with episodes of respiratory tract infections and detectable entero/rhinovirus RNA in respiratory samples between November 2009 and December 2010 were investigated. Retrospective case review was performed and patients' characteristics recorded.

Results: Entero/rhinoviruses were the commonest viral pathogens (498/2316; 21.5%). Amongst 204 infection episodes associated with entero/rhinovirus, 167 were typed HRV, HRV-C was the most prevalent (99/167, 59.3%) followed by HRV-A (60/167; 35.9%) and HRV-B (8/167, 4.8%). The severity spectrum of HRV-A and HRV-C infections were similar and affected all parts of the respiratory tract. Co-pathogens were observed in 54 (26.5%) episodes. Severity was increased in patients with non-viral co-pathogens and those with an underlying respiratory condition. Univariate and multiple regression analyses of potential prognostic variables including age, co-pathogens and underlying respiratory illnesses showed that mono-infection with HRV-C, as compared with other HRV species, was associated with more severe disease in young children<3 years.

Conclusions: HRV-C was the most prevalent species and on its own was associated with severe disease in children<3 years. The association between infection with HRV species and clinical presentation is complex and affected by many confounding factors.
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http://dx.doi.org/10.1016/j.jcv.2013.06.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108361PMC
September 2013

Selection for qacA carriage in CC22, but not CC30, methicillin-resistant Staphylococcus aureus bloodstream infection isolates during a successful institutional infection control programme.

J Antimicrob Chemother 2013 May 3;68(5):992-9. Epub 2013 Jan 3.

Centre for Clinical Infection and Diagnostics Research (CIDR), Department of Infectious Diseases, King's College London & Guy's and St Thomas' NHS Foundation Trust, London, UK.

Objectives: The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization raises concerns about reduced susceptibility. We evaluated the carriage of chlorhexidine resistance genes and chlorhexidine susceptibility in MRSA before and after introduction of an institutional MRSA control programme incorporating chlorhexidine-based decolonization in 2004.

Methods: MRSA bloodstream infection (BSI) isolates identified between 2001 and 2009 were tested for spa and staphylococcal cassette chromosome mec type and carriage of qacA, qacB and smr. Selected isolates were tested for chlorhexidine susceptibility. Logistic regression was used to evaluate associations between clone type, carriage of resistance genes and chlorhexidine susceptibility. Temporal trends in qacA or smr carriage were analysed using separate binomial generalized linear models.

Results: Typing identified two dominant clones: CC22 (n = 224) and CC30 (n = 197). Annual MRSA BSI rates declined from 2004, although the rate of decline for CC22 was slower than for CC30. Carriage of qacA and smr and having a chlorhexidine MIC ≥2 mg/L did not increase overall amongst MRSA BSI isolates; however, qacA carriage increased in CC22 compared with in CC30 (OR, 7.21; 95% CI, 1.32-39.17). Furthermore, qacA+ CC22 isolates were more likely to have a chlorhexidine MIC ≥2 mg/L than qacA+ CC30 isolates (OR, 21.67; CI, 2.54-185.20).

Conclusions: A successful infection control programme was associated with the selection of qacA linked with a higher chlorhexidine MIC in one dominant endemic MRSA clone (CC22), but not another (CC30). The slower reduction in the CC22 MRSA BSI rate suggests that carriage of qacA confers a selective advantage, with implications for the sustainability of decolonization practice.
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http://dx.doi.org/10.1093/jac/dks500DOI Listing
May 2013

Lineages, sub-lineages and variants of enterovirus 68 in recent outbreaks.

PLoS One 2012 20;7(4):e36005. Epub 2012 Apr 20.

Department of Infectious Diseases, School of Medicine, King's College London, London, United Kingdom.

Enterovirus 68 (EV68) was first isolated in 1962. Very few cases of EV68 infection were described over the ensuing 40 years. However, in the past few years, an increase in severe respiratory tract infections associated with EV68 has been reported. We identified two clusters of EV68 infection in South London, UK, one each in the autumn/winters of 2009 and 2010. Sequence comparison showed significant homology of the UK strains with those from other countries including the Netherlands, Japan and the Philippines, which reported EV68 outbreaks between 2008 and 2010. Phylogenetic analysis of all available VP1 sequences indicated the presence of two modern EV68 lineages. The 2010 UK strains belonged to lineage 2. Lineage 1 could be further divided into two sub-lineages: some Japanese and Dutch strains collected between 2004 and 2010 form a distinct sub-lineages (sub-lineage 1.1), whereas other strains from the UK, Japan, Netherlands and Philippines collected between 2008 and 2010 represent sub-lineage 1.2. The UK 2009 strains together with several Dutch and Japanese strains from 2009/2010 represents one variant (1.2.1), whereas those from the Philippines a second variant (1.2.2). Based on specific deletions and substitutions, we suggest rules for the assignment of lineages and sub-lineages. Molecular epidemiological analysis indicates rapid recent evolution of EV68 and this may explain the recent findings of a global resurgence of EV68. Continuous global monitoring of the clinical and molecular epidemiology of EV68 is recommended.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036005PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335014PMC
August 2012

Comparative gene expression profiling of human umbilical vein endothelial cells and ocular vascular endothelial cells.

Br J Ophthalmol 2012 Jan 25;96(1):128-32. Epub 2011 Oct 25.

Division of Ophthalmology and Visual Sciences, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, UK.

Background/aims: To investigate the difference between human umbilical vein endothelial cells (HUVEC) and human ocular microvascular endothelial cell (MVEC) gene expression, and to determine if these differences could improve the understanding of ocular angiogenic diseases.

Methods: The gene expression profiles of HUVEC and matched unpassaged human choroidal, retinal and iris endothelial cells were conducted using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Selected differences were confirmed by real time PCR. Functional cell proliferation assays were used to support microarray findings.

Results: HUVEC showed enrichment for probe sets involved in embryological development while ocular MVEC demonstrated enrichment for probe sets for MHC classes I and II, immune responses and cell signal transduction. Comparison of human retinal and choroidal endothelial cells demonstrated significant differences in the expression of probe sets encoding insulin-like growth factor 1 (IGF-1) signalling. Cell proliferation assays demonstrated the stimulatory role of IGF-1 on retinal endothelial cells compared with choroidal endothelial cells.

Conclusions: Gene expression profiling has demonstrated that HUVEC are probably not a suitable surrogate for the study of ocular angiogenic disorders. There are also significant differences in the gene expression of human retinal and choroidal endothelial cells, which may be important in the mechanism and treatment of choroidal and retinal neovascularisation.
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http://dx.doi.org/10.1136/bjophthalmol-2011-300572DOI Listing
January 2012

Can vitamin C induce nucleotide excision repair? Support from in vitro evidence.

Br J Nutr 2010 Mar 10;103(5):686-95. Epub 2009 Dec 10.

Institute of Environment and Health, Cranfield Health, Cranfield University, Cranfield, Bedfordshire, MK43 0AL, UK.

Intracellular vitamin C acts to protect cells against oxidative stress by intercepting reactive oxygen species (ROS) and minimising DNA damage. However, rapid increases in intracellular vitamin C may induce ROS with subsequent DNA damage priming DNA repair processes. Herein, we examine the potential of vitamin C and the derivative ascorbate-2-phosphate (2-AP) to induce a nucleotide excision repair (NER) response to DNA damage in a model of peripheral blood mononuclear cells. Exposure of cells to elevated levels of vitamin C induced ROS activity, resulting in increased levels of deoxycytidine glyoxal (gdC) and 8-oxo-2'-deoxyguanosine (8-oxodG) adducts in DNA; a stress response was also induced by 2-AP, but was delayed in comparison to vitamin C. Evidence of gdC repair was also apparent. Measurement of cyclobutane thymine-thymine dimers (T < >T) in DNA and culture supernatant were included as a positive marker for NER activity; this was evidenced by a reduction in DNA and increases in culture supernatant levels of T < >T for vitamin C-treated cells. Genomics analysis fully supported these findings confirming that 2-AP, in particular, induced genes associated with stress response, cell cycle arrest, DNA repair and apoptosis, and additionally provided evidence for the involvement of vitamin C in the mobilisation of intracellular catalytic Fe.
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http://dx.doi.org/10.1017/S0007114509992285DOI Listing
March 2010

Antiserum detection of reactive carbonyl species-modified DNA in human colonocytes.

Free Radic Res 2008 Apr;42(4):344-53

Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK

Polyunsaturated fats have been linked to occurrences of sporadic colon cancer. One possible cause may be degradation of polyunsaturated fats during cooking, resulting in multiple reactive carbonyl species (RCS) that can damage nuclear DNA and proteins, particularly in rapidly dividing colon crypt cells. This study describes a novel antiserum against RCS-modified DNA, with apparent order of reactivity to DNA modified with 4-hydroxy-trans-2-nonenal > glyoxal > acrolein > crotonaldehyde > malondialdehyde; some reactivity was also observed against conjugated Schiff base-type structures. Anti-(RCS-DNA) antiserum was successfully utilised to demonstrate formation of RCS-DNA in a human colon cell model, exposed to RCS insult derived from endogenous and exogenous lipid peroxidation sources. Further utilisation of the antiserum for immunohistochemical analysis confirmed RCS-modified DNA in crypt areas of 'normal' colon tissue. These results fully support a potential role for dietary lipid peroxidation products in the development of sporadic colon cancer.
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http://dx.doi.org/10.1080/10715760802008106DOI Listing
April 2008

A comparison of the gene expression profiles of CRL-1807 colonocytes exposed to endogenous AAPH-generated peroxides and exogenous peroxides from heated oil.

Redox Rep 2007 ;12(1):86-90

Molecular Toxicology Group, Department of Forensic Science and Drug Monitoring, School of Health and Life Sciences, King's College London, London, UK.

Oxidation of PUFAs in the diet has the potential to be genotoxic and hence carcinogenic. Such carcinogenic processes originate within stem cells of the colon. These cells appear to be predisposed to the carcinogenic process. In colon cells (CRL-1807) exposed to chemical reactions simulating exogenous and endogenous peroxidation reactions, we have observed that undifferentiated cells could mount an effective recombinational repair/TCR response to an endogenous peroxidative DNA damage insult, but not to an external exogenous peroxidative insult as one would encounter from a dietary source. This may suggest that defects in such specific DNA repair may play a role in tumour development in undifferentiated colonocytes exposed to a diet-derived lipid peroxides.
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http://dx.doi.org/10.1179/135100007X162239DOI Listing
March 2007
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