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Biomedical subjects

A Cox

Publications and source records attributed to A Cox.

At least 19 recordsLinked to original sources
PubMed2006

Can we predict which patients are at risk of having an ungradeable digital image for screening for diabetic retinopathy?

PURPOSE: We aimed to determine the reasons for, and variables which predicted, ungradeable retinal photographs during screening patients for diabetic retinopathy. MATERIALS AND METHODS: Age, duration of diabetes, visual acuity, and HbA1c were recorded. Following dark adaptation, a single 45 degrees nonmydriatic photograph was taken of each fundus. The pupils were then dilated and the photograph repeated. Using slit lamp biomicroscopy, lenticular changes (LOCS III), and fundus appearance were recorded. RESULTS: In ungradeable photographs the fovea could not be visualised in 98% of cases of images from nonmydriatic photography, and in 88% if mydriasis was used. Poor definition in the nonmydriatic image was associated with a subsequent ungradeable mydriatic photograph (P=0.001), however, the positive predictive value was poor (34%). Age, posterior subcapsular cataract, and near vision predicted ungradeable status of nonmydriatic photographs (P<0.001, P=0.004, P=0.006, respectively; regression analysis). Nuclear colour and poor definition of the nonmydriatic photograph predicted ungradeable status of mydriatic photographs (P=0.006 & P=0.001, respectively). CONCLUSION: Inability to visualise the fovea is the commonest cause of an ungradeable image from digital retinal photography. Age and posterior subcapsular cataract were best predictors of ungradeable status of nonmydriatic fundus photographs. Nuclear colour was the strongest predictor for ungradeable mydriatic photography.

Adolescent↗
PubMed2006

Interleukin gene polymorphisms and breast cancer: a case control study and systematic literature review.

BACKGROUND: Interleukins and cytokines play an important role in the pathogenesis of many solid cancers. Several single nucleotide polymorphisms (SNPs) identified in cytokine genes are thought to influence the expression or function of these proteins and many have been evaluated for their role in inflammatory disease and cancer predisposition. The aim of this study was to evaluate any role of specific SNPs in the interleukin genes IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 in predisposition to breast cancer susceptibility and severity. METHODS: Candidate single nucleotide polymorphisms (SNPs) in key cytokine genes were genotyped in breast cancer patients and in appropriate healthy volunteers who were similar in age, race and sex. Genotyping was performed using a high throughput allelic discrimination method. Data on clinico-pathological details and survival were collected. A systematic review of Medline English literature was done to retrieve previous studies of these polymorphisms in breast cancer. RESULTS: None of the polymorphisms studied showed any overall predisposition to breast cancer susceptibility, severity or to time to death or occurrence of distant metastases. The results of the systematic review are summarised. CONCLUSION: Polymorphisms within key interleukin genes (IL1A, IL1B, IL1RN, IL4R, IL6 and IL10 do not appear to play a significant overall role in breast cancer susceptibility or severity.

Aged↗
PubMed2006

Synthesis, binding studies and in vivo biological evaluation of novel non-peptide antihypertensive analogues.

AT(1) antagonists (SARTANs) constitute the last generation of drugs for the treatment of hypertension, designed and synthesized to mimic the C-terminal segment of the vasoconstrictive hormone angiotensin II (AngII). They exert their action by blocking the binding of AngII on the AT(1) receptor. Up to date eight AT(1) antagonists have been approved for the regulation of high blood pressure. Although these molecules share common structural features and are designed to act under the same mechanism, they have differences in their pharmacological profiles and antihypertensive efficacy. Thus, there is still a need for novel analogues with better pharmacological and financial profiles. An example of a novel synthetic non peptide AT(1) antagonist which devoids the classical template of SARTANs is MM1. In vivo studies showed that MMK molecules, which fall in the same class of MM1, had a significant antihypertensive (40-80% compared to the drug losartan) activity. However, in vitro affinity studies showed that losartan has considerably higher affinity. The theoretical docking studies showed that MM1 acts on the same site of the receptor as losartan. They exert hydrophobic interactions with amino acid Val108 of the third helix of the AT(1) receptor and other hydrophobic amino acids in spatial vicinity. In addition, losartan favours multiple hydrogen bondings between its tetrazole group with Lys199. These additional interactions may in part explain its higher in vitro binding affinity.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Quantitative analysis of corneal microstructure in keratoconus utilising in vivo confocal microscopy.

PURPOSE: To establish and quantify the in vivo confocal microscopic features of moderate to advanced keratoconus. METHODS: Nineteen keratoconus subjects were catergorised using Orbscan-derived corneal apex power and pachymetry as exhibiting moderate (n=7) and advanced (n=12) keratoconus. Control subjects included 23 noncontact lens wearers (Group A) and 15 contact lens wearers (Group B). All subjects underwent Confoscan slit scanning in vivo confocal microscopy. RESULTS: Compared with Group A (4912+/-434 cells/mm(2)), basal epithelial density was significantly lower in both moderate (4592+/-414 cells/mm(2), P<0.05) and advanced keratoconus (4530+/-596 cells/mm(2), P=0.01). In comparison to Group A (761+/-118 cells/mm(2)), anterior stroma keratocyte density was significantly greater in both moderate keratoconus (883+/-111 cells/mm(2), P=0.001) and advanced keratoconus (952+/-122 cells/mm(2), P<0.001). Compared to Group A (504+/-80 cells/mm(2)) posterior stroma keratocyte density was also significantly greater in advanced keratoconus (599+/-97 cells/mm(2), P<0.001) and posterior stromal keratocyte density appeared to increase with increasing severity of keratoconus (P<0.05). However, comparing control Groups A and B, contact lens wear per se, was associated with significantly reduced (P=0.000) keratocyte density in the anterior stroma (609+/-66 cells/mm(2)) and demonstrated a trend (P=0.056) in the posterior stroma (470+/-63 cells/mm(2)). Keratoconic corneas (429+/-72 microm) were significantly thinner than control Groups A (508+/-77 mm) and B (495+/-80 microm). The presence of keratoconus did not affect the endothelial cell density (P=0.54). CONCLUSION: In vivo confocal microscopy can provide insight into the microstructural changes that occur in keratoconus.

Adult↗
PubMed2006

Reversal in fatigued athletes of a defect in interferon gamma secretion after administration of Lactobacillus acidophilus.

BACKGROUND: Fatigue and impaired performance in athletes is well recognised and has been loosely linked to "overtraining". Reduced concentration of IgA in the saliva and increased shedding of Epstein Barr virus (EBV) have been associated with intense training in elite athletes. OBJECTIVE: To determine whether athletes presenting with fatigue and impaired performance had an immune defect relevant to defective containment of EBV infection, and whether a probiotic preparation (Lactobacillus acidophilus) shown to enhance mucosal immunity in animal models could reverse any detected abnormality. RESULTS: The fatigued athletes had clinical characteristics consistent with re-activation of EBV infection and significantly (p = 0.02) less secretion of interferon (IFN) gamma from blood CD4 positive T cells. After one month of daily capsules containing 2 x 10(10) colony forming units of L acidophilus, secretion of IFNgamma from T cells had increased significantly (p = 0.01) to levels found in healthy control athletes. A significant (p = 0.03) increase in salivary IFNgamma concentrations in healthy control athletes after the one month course of L acidophilus demonstrated in man the capacity for this probiotic to enhance the mucosal IFNgamma concentration. CONCLUSION: This is the first evidence of a T cell defect in fatigued athletes, and of its reversal following probiotic therapy.

Adolescent↗
PubMed2006

Quantitative risk assessment case study: smuggled meats as disease vectors.

Outbreaks of foot and mouth disease (FMD), African swine fever (ASF), classical swine fever (CSF) and swine vesicular disease (SVD) can cause significant economic and social costs and severe trade limitations. A number of commodities may be contaminated with these hazards, including meat and meat products derived from infected animals. Great Britain (GB) enforces a number of regulations to prevent the importation of such pathogens. However, the illegal importation of meat provides a route by which controls may be circumvented and pathogens imported. This paper discusses a series of risk assessments examining the disease risk to the GB livestock population of FMD, CSF, ASF and SVD from the illegal importation of any meat product from any region in the world. This paper describes the development of a quantitative risk assessment model designed to identify the major contributors to this risk, and discusses the challenges posed when undertaking such complex risk assessments.

African Swine Fever↗
PubMed2005

The informational roles and psychological health of members of 10 oncology multidisciplinary teams in the UK.

We report here the different roles undertaken by the members of 10 multidisciplinary cancer teams in conveying information to patients during their care. Team members completed an Informational Roles Questionnaire measuring an individual's perception of their major role and that of their colleagues in giving information to patients. They also completed two standard psychological health measures, the General Health Questionnaire and Maslach Burnout Inventory. The information giving roles of the surgeon, oncologist, radiologist and clinical nurse specialist were well recognised by their colleagues; however, other team members' roles were more ambiguous and less well understood. The clinical nurse specialist provided the broadest information coverage for patients. Few professional groups regularly informed patients about clinical trials and family history and the clinical nurse specialist was often the only person to deal with patients' sexual well being, consequently these areas are likely to receive poor coverage. Probable psychiatric morbidity (GHQ> or =4) in teams ranged from 5 to 27%. High levels of emotional exhaustion were particularly apparent in team leaders and nurses and feelings of low levels of personal accomplishment were prevalent in the histopathologists and radiologists. Putative benefits to patients and healthcare professionals from multidisciplinary team working may not be realised without investment in team training.

Burnout, Professional↗
PubMed2005

Patients' preference for administration of endocrine treatments by injection or tablets: results from a study of women with breast cancer.

BACKGROUND: Endocrine therapies for advanced breast cancer include tablets and intramuscular injections. When treatments have similar efficacy and tolerability profiles, addressing preferences about routes of administration is important. PATIENTS AND METHODS: Two hundred and eight women>2 years post-breast cancer diagnosis were interviewed about their preferences for daily tablets or monthly intramuscular injections. Health-care professionals treating the women estimated patients' preferences. RESULTS: Sixty-three per cent of patients preferred tablets, 24.5% preferred the injection and 12.5% had no preference. The most cited reasons for tablet preference were convenience and dislike of needles; for injection preference, adherence and convenience. Variables associated with preferences were body mass index, educational level, attitudes towards injections and efficacy perceptions. Estimates about patients' preferences by health-care professionals varied widely. When asked to imagine scenarios where injections produced fewer hot flushes, or where two injections monthly improved efficacy, injection preference increased to 60.6% and 74.5%, respectively. Disturbingly, approximately 50% of patients admitted they sometimes forgot or chose not to take their current oral medication. CONCLUSIONS: The majority of breast cancer patients preferred hormone therapy via daily tablets rather than monthly injections. Information about side-effects or improved efficacy altered these preferences. Adherence to treatment cannot be assumed; patients' preferences about drug administration may influence this.

Administration, Oral↗
PubMed2005

Endoscopic-assisted probing for congenital nasolacrimal duct obstruction.

PURPOSE: To determine the success rate of initial probing in children with congenital nasolacrimal duct obstruction (CNLDO) at different ages using nasal endoscopy, and to identify the anatomical sites of blockage within the drainage system. METHODS: A total of 87 eyes from 67 consecutive children with CNLDO underwent endoscopic nasolacrimal duct (NLD) probing under general anaesthetic. Patients who had had previous probings were excluded from the study. Diagnosis was based on history of epiphora since birth or shortly after, and fluorescein dye disappearance test (FDDT). Cure was judged as complete or near-complete remission of symptoms and signs and a normal FDDT. RESULTS: The age range was 12-91 months (mean 32.3 months). The success rates of probing were: 100% (58/58) for atresia and stenosis at the lower NLD, 100% (13/13) for punctal stenosis, 55.6% (5/9) for functional epiphora, and 0% (0/7) for canalicular and upper NLD obstruction. Age was not found to significantly affect the outcome of probing, whereas site did. Obstruction at canalicular or upper NLD level became more common with increasing age. CONCLUSION: Probing of the nasolacrimal system using the endoscopic approach allows direct visualisation of the distal nasolacrimal duct, which facilitates diagnosis of the anomaly at this site. More complex proximal anomalies became increasingly prevalent in older children, which accounted for the poorer results with increasing age. Site of obstruction has a greater bearing on outcome than patient age.

Age Factors↗
PubMed2005

The preferences of 600 patients for different descriptions of randomisation.

A total of 600 patients from cancer centres throughout the UK identified their most preferred and most disliked descriptions of randomisation found in current patient information sheets and websites. The CancerBACUP description, which describes both the process of randomisation and why it is done, was most preferred 151 out of 533 (28%) patients. The NCI description was viewed as overly technical and most disliked 185 out of 483 (38%) patients.

Health Knowledge, Attitudes, Practice↗
PubMed2005

Visual impairment in elderly patients with hip fracture: causes and associations.

AIMS: To evaluate the current visual status and ophthalmic history of a sample of elderly patients with fractured neck of femur and to study the relationship between visual status and demographic factors. METHODS: A four-centre study of all patients admitted to hospital with fractured neck of femur. The setting was two district (Ayr, Dunfermline) and two teaching (Glasgow, Dundee) hospitals in Scotland. The study examined 537 patients aged 65 years and over admitted with acute fractured neck of femur to hospital. RESULTS: Bilateral visual impairment (binocular visual acuity worse than 6/12) was found in 239 of 518 patients (46%). Of this group, the principal causes for visual deficit were untreated cataract (49%), macular degeneration (21%), uncorrected refractive error (17%), and glaucoma (3%). The visually impaired group were more likely to have symptomatic visual complaints (58 vs 26%), however, were less likely to be under optometric care (71 vs 85%). A higher proportion of the group with visual impairment lived in areas of social deprivation (40 vs 26%). CONCLUSIONS: Patients with fractured neck of femur represent a frail elderly group that have poorer vision than that documented in any other elderly population. The visual defect was potentially remediable in the majority of cases but this group of individuals are not generally in touch with the ophthalmic services. Social deprivation appears to be associated with this groups' inability to access ophthalmic care.

Aged↗
PubMed2005

Evidence of a pharmacogenomic response to interleukin-l receptor antagonist in rheumatoid arthritis.

Biological activity of the IL-1 system depends on the balance between two proinflammatory proteins (IL-1alpha and IL-1beta) and the related anti-inflammatory protein, the IL-1 receptor antagonist (IL-1Ra). The genes for these proteins lie within 430 kb on human chromosome 2. Based on a clinical trial of human recombinant IL-1ra in rheumatoid arthritis, we tested whether IL-1 genotype might be related to the likelihood of response to anti-IL-1 therapy. A positive response was defined as a reduction of at least 50% in the number of swollen joints by week 24, following treatment with either 150 mg/day IL-1ra or placebo. The response rate to treatment, independent of genotype, was 48% (44/91). A highly significant association was found between carriage of the rarer allele at IL1A(+4845) and response to treatment (P=0.0009; OR=4.85 (1.85,12.70)). The response rate in patients carrying this allele was 63.4% compared with 26.3% in noncarriers. A weaker association was found for IL1B(+3954) (P=0.02). There was a highly significant interaction between treatment (150 mg/day or placebo) and the composite genotype across IL1A(+4845) and IL1B(+3954) (P=7.6 x 10(-5)). No associations with IL-1 genotypes were found in patients receiving placebo. Thus, a significant pharmacogenomic effect was found in the treatment of RA patients with recombinant IL-1ra.

Alleles↗
PubMed2005

Optometric and ophthalmic contact in elderly hip fracture patients with visual impairment.

AIM: To describe previous contact with optometry and ophthalmic services in a group of elderly patients with and without visual impairment (VI) who had fallen and sustained a fractured neck of femur. METHOD: A cross sectional study of 537 patients aged 65 and over who had undergone hip fracture surgery in four Scottish centres (Glasgow, Ayr, Dundee and Fife). All patients had an in-depth optometric history, ophthalmic history and examination. RESULTS: Three hundred and ninety-three (79%) patients reported optometric contact in the 3 years preceding surgery and 107 (21%) patients had not seen an optometrist for more than 3 years. In the latter group, 64 had VI, which was due to uncorrected refractive error in 17 (27%) and untreated cataract in 20 (31%). VI (best binocular visual acuity of 6/18 or less) was found in 239 (46%) patients. A past ophthalmic history was present in 257 (50%) patients. Only 39 (16%) patients with VI were under ophthalmic care at the time of the study. CONCLUSIONS: There was significantly poor optometric and ophthalmic contact in patients who had VI and had fallen and sustained hip fracture. A proportion of the VI (66%) was due to uncorrected refractive error and untreated cataract. Public health providers should be made aware of the fact that current optometric and ophthalmic care pathways are not accessed by this group of elderly patients with VI and at risk of falling.

Accidental Falls↗
PubMed2004

Candidate gene polymorphisms in solid cancers.

Accumulation of information from scientific advances in genetics and biotechnology has accelerated research investigating the inherent individual variation in disease susceptibility and severity. Gene polymorphisms, in particular single nucleotide polymorphisms, are being evaluated for their role in multi-factorial diseases such as cancer and inflammation. Most surgical diseases are multi-factorial and a better understanding and utilization of the information gained from such studies by clinicians/surgeons is likely to favorably influence patient outcome. In this article, we illustrate the types of genetic variation and the complexities involved in their study and discuss their potential in predicting both the occurrence and outcomes of solid cancers.

Genetic Predisposition to Disease↗
PubMed2004

Functional correlates of the interleukin-1 receptor antagonist gene polymorphism in the colonic mucosa in ulcerative colitis.

Association studies have identified the interleukin-1 receptor antagonist gene allele 2(IL-1RN*2) as a marker of susceptibility in ulcerative colitis (UC). This study investigated the significance of the IL-1RN genotype with respect to protein and mRNA expression in the colonic mucosa. Homogenates of rectal biopsies from 99 UC and 54 controls were assayed for cytokines IL-1ra, IL-1a and IL-1b using ELISA. IL1RN, IL1A and IL1B genotypes were determined using restriction-enzyme analysis. The ability of the two IL1RN alleles to generate steady-state mRNA accumulation was assessed in the colonic mucosa of seven heterozygous patients. Stepwise linear regression demonstrated that IL-1RN genotype (P=0.001), diagnosis (P<0.0001) and treatment (P<0.03) were independent factors associated with the IL-1ra protein level whilst IL1RN genotype (P=0.005) and macroscopic inflammatory grade (P<0.0001) were associated with the IL-1ra/ total IL-1 ratio. The IL1RN*2 correlated with reduced IL-1ra and IL-1ra/IL-1 ratio with a gene dosage effect. In heterozygous UC patients the ratio of allele 1 mRNA / allele 2 steady state mRNA was always greater than 1 (range: 1.2-3.1) (P=0.018). The IL-1RN*2 is associated with reduced levels of IL-1ra protein and IL-1RN mRNA in the colonic mucosa, providing a biologically plausible explanation for the observed association of the allele with the disease.

3' Untranslated Regions↗
PubMed2004

Association of HLA-DM polymorphism with the production of antiphospholipid antibodies.

OBJECTIVE: To investigate whether variation in the HLA-DM gene is important in producing a group of pathogenic autoantibodies-antiphospholipid antibodies (aPL)-on the basis that HLA class II restricted antigen presentation is involved in the production of aPL. METHODS: HLA-DMA and DMB polymorphisms were genotyped by polymerase chain reaction combined with restriction enzyme digestion in 51 white patients with primary antiphospholipid syndrome (APS), 82 with systemic lupus erythematosus (SLE) (42 with APS and 40 without APS), and 109 healthy white controls. The association with the aPL profile was examined. RESULTS: The distribution of DMA alleles in APS patients and in patients with APS associated with SLE was significantly different from that in controls by 4x2 chi(2) test with 3 degrees of freedom (p = 0.035 and 0.011, respectively), but it was not different between SLE patients without APS and controls. The allelic distribution of DMA was also different between patients with IgG class anticardiolipin antibody or those with lupus anticoagulant (LA) and controls (p = 0.012 and 0.007, respectively) and between patients with and without LA among SLE patients (p = 0.035). All these differences included the increase in DMA*0102 in the former groups. CONCLUSIONS: The results suggest that HLA-DMA*0102 or its linked gene(s) form one of the genetic risks for the production of aPL.

Adult↗
PubMed2004

Effect of mydriasis and different field strategies on digital image screening of diabetic eye disease.

AIMS: To assess the effects of (1) mydriasis and (2) single versus three field photography on screening for diabetic eye disease using digital photography METHOD: Slit lamp examination findings were compared to digital fundal photographs for the detection of any retinopathy and for referable retinopathy in 398 patients (794 eyes). A Topcon TRC-NW6S digital non-mydriatic fundus camera was used. Three photographic strategies were used: undilated single field, dilated single field, and dilated multiple fields. The photographs were presented in random order to one of two retinal screeners. For the single field photographs the screeners were masked to the use of mydriatics. In 13% of fundal photographs, grading was performed by both, rather than just one grader. RESULTS: Mydriasis reduced the proportion of ungradable photographs from 26% to 5% (p<0.001). Neither mydriasis nor three field photography improved the sensitivity or specificity for the detection of any retinopathy or of referable retinopathy when compared with undilated single field photography. The sensitivity and specificity for detecting referable retinopathy using undilated single field photography was 77% (95% CI 71 to 84) and 95 % (95% CI 93 to 97) respectively. Using dilated single field photography the figures were 81% (95% CI 76 to 87) and 92% (95% CI 90 to 94) respectively. Using dilated three field photography the figures were 83% (95% CI 78 to 88) and 93% (95% CI 91 to 96) respectively. Intergrader reliability for the detection of referable retinopathy in gradable photographs was excellent (Kappa values 0.86-1.00). CONCLUSIONS: Mydriasis reduces the technical failure rate. Mydriasis and the three field photography as used in this study do not increase the sensitivity or specificity of detecting diabetic retinopathy.

Adolescent↗