PubMed Health⌕ Search

Biomedical subjects

G Murphy

Publications and source records attributed to G Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Human immunodeficiency virus (HIV) antibody avidity testing to identify recent infection in newly diagnosed HIV type 1 (HIV-1)-seropositive persons infected with diverse HIV-1 subtypes.

A guanidine-based antibody avidity assay for the identification of recently acquired human immunodeficiency virus type 1 (HIV-1) infection was evaluated. The kinetics of maturation of antibody avidity were determined prospectively in 23 persons undergoing acute seroconversion followed for up to 1,075 days. Avidity indices (AI) of <or=0.75 and <or=0.80 reproducibly identified seroconversion within the previous 125 (95% confidence interval [CI], 85 to 164) and 142 (95% CI, 101 to 183) days, respectively. To validate the assay, 432 serum samples from newly diagnosed patients were tested by both the avidity assay and the detuned assay. Results were highly concordant (kappa value for agreement, 0.85). The avidity assay was subsequently used to screen 134 consecutive newly diagnosed patients, including 55/134 (41%) infected with non-B subtypes (A, C, D, G, CRF01, CRF02, CRF06, CRF13, and CRF16). In this cohort, 25/79 (32%) persons with the B subtype and 7/55 (13%) with non-B subtypes showed an AI of <or=0.75, and there were 16/25 (64%) and 3/7 (43%) persons, respectively, with a documented history of acute seroconversion illness within the predicted seroconversion interval. An AI of <or=0.75 was also observed for four patients (three with the B subtype and one with a non-B subtype) who presented with AIDS-defining conditions. In multivariate analysis, an AI of <or=0.75 was associated with younger age, higher HIV-1 plasma RNA load, and being born in the United Kingdom or Ireland rather than in Africa but not with gender, ethnicity, risk group, HIV-1 subtype, or CD4 counts. In conclusion, HIV antibody avidity testing provides a reliable method for identifying recently acquired HIV-1 infection. Results are affected by advanced disease and should therefore be interpreted in the context of other clinical parameters.

Adult↗
PubMed2006

Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition.

p300 is a transcriptional cofactor and prototype histone acetyltransferase involved in regulating multiple cellular processes. We generated p300 deficient (p300-) cells from the colon carcinoma cell line HCT116 by gene targeting. Comparison of epithelial and mesenchymal proteins in p300- with parental HCT116 cells showed that a number of genes involved in cell and extracellular matrix interactions, typical of 'epithelial to mesenchyme transition' were differentially regulated at both the RNA and protein level. p300- cells were found to have aggressive 'cancer' phenotypes, with loss of cell-cell adhesion, defects in cell-matrix adhesion and increased migration through collagen and matrigel. Although migration was shown to be metalloproteinase mediated, these cells actually showed a downregulation or no change in the level of key metalloproteinases, indicating that changes in cellular adhesion properties can be critical for cellular mobility.

Cell Adhesion↗
PubMed2006

Comprehensive profiling and localisation of the matrix metalloproteinases in urothelial carcinoma.

The matrix metalloproteinases (MMPs) are endopeptidases which break down the extracellular matrix and regulate cytokine and growth factor activity. Several MMPs have been implicated in the promotion of invasion and metastasis in a broad range of tumours including urothelial carcinoma. In this study, RNA from 132 normal bladder and urothelial carcinoma specimens was profiled for each of the 24 human MMPs, the four endogenous tissue inhibitors of MMPs (TIMPs) and several key growth factors and their receptors using quantitative real time RT-PCR. Laser capture microdissection (LCM) of RNA from 22 tumour and 11 normal frozen sections was performed allowing accurate RNA extraction from either stromal or epithelial compartments. This study confirms the over expression in bladder tumour tissue of well-documented MMPs and highlights a range of MMPs which have not previously been implicated in the development of urothelial cancer. In summary, MMP-2, MT1-MMP and the previously unreported MMP-28 were very highly expressed in tumour samples while MMPs 1, 7, 9, 11, 15, 19 and 23 were highly expressed. There was a significant positive correlation between transcript expression and tumour grade for MMPs 1, 2, 8, 10, 11, 12, 13, 14, 15 and 28 (P < 0.001). At the same confidence interval, TIMP-1 and TIMP-3 also correlated with increasing tumour grade. LCM revealed that most highly expressed MMPs are located primarily within the stromal compartment except MMP-13 which localised to the epithelial compartment. This work forms the basis for further functional studies, which will help to confirm the MMPs as potential diagnostic and therapeutic targets in early bladder cancer.

Biomarkers, Tumor↗
PubMed2006

Oral retinoids for chemoprevention of skin cancers in organ transplant recipients: results of a survey.

Systemic retinoid therapy is thought to be beneficial for chemosuppression of skin cancers in solid organ transplant recipients. We present the results of a survey of 28 dermatologists with experience managing transplant recipients to clarify when and how systemic retinoids are used in this population. Almost 80% of respondents use retinoids in some transplant recipients. Factors influencing the use of retinoids include the incidence and aggressiveness of cutaneous squamous cell carcinomas and the extent of concomitant actinic keratoses. Patients are monitored more closely during periods of dose adjustment than during the maintenance phase of therapy. Adverse effects are variably managed symptomatically, with dose adjustment, by discontinuation of retinoids, or by referral to another specialist for further evaluation. In the absence of large randomized controlled trials, the practice habits of experienced physicians serve as a useful guide for the use of oral retinoids in transplant recipients.

Administration, Oral↗
PubMed2006

Tight regulation of transgene expression by tetracycline-dependent activator and repressor in brain.

Methods to temporally and spatially regulate gene mutations will provide a powerful strategy to investigate gene function in the brain. To develop these methods, we have established a tightly regulated system for transgene expression in the forebrain using both a tetracycline (Tc)-dependent transcription activator (rtTA) and a repressor (TetR-Kruppel-associated box). In this system, the repressor binds to the Tc-responsive element (TRE) in the absence of doxycycline (Dox), leading to the repression of leaky activation of TRE-mediated transcription caused by weak binding of rtTA to TRE. Upon Dox administration, only the activator binds to TRE and activates transcription. We tested this system in cultured cells by bicistronically expressing both the regulators using an internal ribosome entry site (IRES). In COS-1, HeLa and SHSY5Y cells, leaky transcription activation led by rtTA in the absence of Dox was repressed without decreasing the level of activated transcription in the presence of Dox. Using this system, transgenic mice were produced that express both the regulators using IRES in the forebrain under the control of the alphaCaMKII promoter and were bred with transgenic mice carrying the TRE-dependent reporter transgene. In reverse transcription-polymerase chain reaction and in situ hybridization analyses of the forebrain in adult double transgenic mice, the treatment of Dox induces reporter mRNA expression, which was not detected before the treatment and after the withdraw of Dox following the treatment. These results indicate that this system allows the tight regulation of transgene expression in a Dox-dependent fashion in the forebrain and will be useful in investigating gene function in the brain.

Animals↗
PubMed2006

Spatial test for agricultural pesticide "blow-in" effect on prevalence of Parkinson's disease.

The current study used Department of Veteran's Affairs (VA) clinical records, State of California pesticide application records, spatial maps of distribution of Parkinson's disease patients, and pesticide applications to determine if there was evidence for "blow-in" of pesticides as a factor in explaining the prevalence of Central Valley Parkinson's disease. The results did not support the hypothesis of increasing prevalence of Parkinsonism attributable to wind drift.

Agriculture↗
PubMed2006

Bioequivalence of an ezetimibe/simvastatin combination tablet and coadministration of ezetimibe and simvastatin as separate tablets in healthy subjects.

OBJECTIVE: To assess the bioequivalence of an ezetimibe/simvastatin (EZE/SIMVA) combination tablet compared to the coadministration of ezetimibe and simvastatin as separate tablets (EZE + SIMVA). METHODS: In this open-label, randomized, 2-part, 2-period crossover study, 96 healthy subjects were randomly assigned to participate in each part of the study (Part I or II), with each part consisting of 2 single-dose treatment periods separated by a 14-day washout. Part I consisted of Treatments A (EZE 10 mg + SIMVA 10 mg) and B (EZE/SIMVA 10/10 mg/mg) and Part II consisted of Treatments C (EZE 10 mg + SIMVA 80 mg) and D (EZE/SIMVA 10/80 mg/mg). Blood samples were collected up to 96 hours post-dose for determination of ezetimibe, total ezetimibe (ezetimibe + ezetimibe glucuronide), simvastatin and simvastatin acid (the most prevalent active metabolite of simvastatin) concentrations. Ezetimibe and simvastatin acid AUC(0-last) were predefined as primary endpoints and ezetimibe and simvastatin acid Cmax were secondary endpoints. Bioequivalence was achieved if 90% confidence intervals (CI) for the geometric mean ratios (GMR) (single tablet/coadministration) of AUC(0-last) and Cmax fell within prespecified bounds of (0.80, 1.25). RESULTS: The GMRs of the AUC(0-last) and Cmax for ezetimibe and simvastatin acid fell within the bioequivalence limits (0.80, 1.25). EZE/ SIMVA and EZE + SIMVA were generally well tolerated. CONCLUSIONS: The lowest and highest dosage strengths of EZE/SIMVA tablet were bioequivalent to the individual drug components administered together. Given the exact weight multiples of the EZE/SIMVA tablet and linear pharmacokinetics of simvastatin across the marketed dose range, bioequivalence of the intermediate tablet strengths (EZE/SIMVA 10/20 mg/mg and EZE/SIMVA 10/40 mg/mg) was inferred, although these dosages were not tested directly. These results indicate that the safety and efficacy profile of EZE + SIMVA coadministration therapy can be applied to treatment with the EZE/SIMVA tablet across the clinical dose range.

Adolescent↗
PubMed2006

Febuxostat for prevention of gout attacks.

(1) Febuxostat is a selective inhibitor of xanthine oxidase. Its use in the management of hyperuricemia and gout is being studied. (2) In a 52-week, phase III randomized clinical trial, febuxostat was superior to allopurinol for lowering uric acid levels. Its efficacy in preventing gout attacks was similar to that of allopurinol. Despite a similar rate of adverse effects, individuals on febuxostat were more likely to stop treatment than those on allopurinol. (3) The most commonly observed adverse effects with febuxostat include liver function test abnormalities, diarrhea, headache, nausea, vomiting, abdominal pain, and dizziness. (4) Given that renal dysfunction is a risk factor for hyperuricemia and gout, the safety and efficacy of febuxostat in this population should be considered, but only limited data are available. (5) The diffusion of febuxostat may be limited by its price relative to that of allopurinol, regardless of whether febuxostat proves to have advantages in specific populations.

Allopurinol↗
PubMed2006

The RAMBLER study: the role of ambulatory blood pressure measurement in routine clinical practice: a cross-sectional study.

Ambulatory blood pressure measurement (ABPM) is a useful and important way of guiding clinical decisions in the diagnosis and treatment of hypertension. There has been little research on how ABPM is actually used in the community where hypertension is mainly diagnosed and managed. We aimed to review the use of ABPM in daily community practice in terms of patient demographics, changes in pharmaceutical treatment and the proportion of patients achieving recommended levels. Six practices using the dabI device for ABPM participated in this cross-sectional study. Patients who had the ABPM performed over the preceding 12 months were included. We recorded demographic details, pre- and post-ABPM clinic blood pressure measurements, the ABPM result and treatment before and after the test. 381 patients were included in the study, of whom 38.6% were male. The mean age was 58 years (SD= 14) and 46.7% were GMS eligible. 33.8%/ had a normal BP result on ABPM. There was a statistically significant reduction in both the mean systolic pressure(10.4 mmHg, CI 7.2-12.9, P<0.001) and diastolic pressure (5.1 mmHg, CI 3.2-6.6, P< 0.05) between the pre and the post-ABPM clinic measurements. It was found that 38.1% had a change in their medication after the test, with 31.7% having a new medication started. This pragmatic study provides information about the use of ABPM in routine general practice in Ireland. ABPM readings appear to have an impact on General Practitioners' decision- making and on the medical management of hypertensive patients in the community.

Adolescent↗
PubMed2005

A cross-site vascular radiology on-call service: the Manchester experience.

AIM: A cross-site vascular radiology on-call service was established 5 years ago to cover two vascular centres in Manchester. We aimed to review the service. MATERIALS AND METHODS: A prospective audit of out-of hours referrals and procedures over a three month period (March-May 2003) was undertaken. RESULTS: There were 52 incidents in 49 patients (mean 4 calls per week). Nine involved telephone advice only, the remainder (82%) required a procedure. Angiography was performed on 88% of patients and therapeutic radiological intervention on 50%. 71% of calls occurred at a weekend. 50% of the calls were from vascular surgery and 50% from other sources. The consultant vascular radiologist was present for 93% of procedures. CONCLUSIONS: The workload suggests that a vascular radiology on call service is justified in Manchester. There have been no major problems with its implementation and operation. This is a consultant led service, with very few cases being devolved to a specialist registrar (SpR).

After-Hours Care↗
PubMed2005

The early development of self-injurious behaviour: evaluating the role of social reinforcement.

BACKGROUND: The potential role of social reinforcement in the development of self-injury has not yet been subjected to empirical analysis. In this 2-year prospective study, the pattern of social interactions related to the early presentation of self-injury were examined to identify a potential association with an increase in self-injury. METHODS: The self-injurious behaviour and social contact with adults of 16 children with intellectual disability (ID) with self-injury of recent onset were observed at 3-month intervals over 2 years. RESULTS: Increase in self-injury over a 2-year period was positively correlated with a distribution of social contact relative to episodes of self-injury that is consistent with a mutual social reinforcement paradigm. When this paradigm was operative, self-injury was evoked under stable antecedent conditions over time but tended to evoke increasing levels of social interaction. CONCLUSIONS: These results support the hypothesis that increases in the frequency of early self-injury in children with ID may be determined by social reinforcement with implications for early intervention and proactive identification of children at risk for increases in self-injury.

Adolescent↗
PubMed2005

Review of the potential photo-cocarcinogenicity of topical calcineurin inhibitors: position statement of the European Dermatology Forum.

Topical Calcineurin Inhibitors (TCIs) used for the treatment of atopic eczema modify the immune regulatory function of the skin and may have the potential to enhance immunosuppressive ultraviolet (UV) effects. Current recommendations on UV protection in eczema patients treated with PCIs are inconsistent and have given rise to uncertainty and anxiety in patients. Therefore, the European Dermatology Forum (EDF) developed a position statement which reviews critically the available data with regard to the problem, especially analysing and commenting the limitations of rodent models for the human situation. There is no conclusive evidence from rodent trials to indicate that long-term application of TCIs is photococarcinogenic. There is a need for further studies to investigate the validity of mouse models as well as long-term cohort studies in patients using TCIs. Available data suggest that long-term application of TCIs is safe, that there is no evidence of increased skin cancer risk and that it is ethical to treat patients with TCIs when indicated.

Administration, Topical↗
PubMed2005

What are the roles of metalloproteinases in cartilage and bone damage?

A role for metalloproteinases in the pathological destruction in diseases such as rheumatoid arthritis and osteoarthritis, and the irreversible nature of the ensuing cartilage and bone damage, have been the focus of much investigation for several decades. This has led to the development of broad spectrum metalloproteinase inhibitors as potential therapeutics. More recently it has been appreciated that several families of zinc dependent proteinases play significant and varied roles in the biology of the resident cells in these tissues, orchestrating development, remodelling, and subsequent pathological processes. They also play key roles in the activity of inflammatory cells. The task of elucidating the precise role of individual metalloproteinases is therefore a burgeoning necessity for the final design of metalloproteinase inhibitors if they are to be employed as therapeutic agents.

Arthritis↗
PubMed2005

Atrasentan for metastatic hormone refractory prostate cancer.

(1) Atrasentan (Xinlay(R)) is an anti-cancer drug from a new class of agents called selective endothelin-A receptor antagonists. The orally administered drug is being studied in a subset of patients with advanced prostate cancer. (2) Phase II and III studies evaluating time to clinical and radiographic progression failed to demonstrate a significant benefit with atrasentan versus placebo. (3) The adverse effects, observed more frequently in those treated with atrasentan than in placebo-treated patients, were peripheral edema, rhinitis, headache, infection, dyspnea, and heart failure. (4) Atrasentan's role in the various stages of advanced prostate cancer, and relative to the chemotherapeutic agent docetaxel, has not been determined.

Bone Neoplasms↗
PubMed2004

Lack of association between the -2518G/A polymorphism of the MCP-1 gene and ischaemic heart disease: a family-based investigation.

Using two recently described family-based tests of association, the possible role of the functional -2518G/A polymorphism in the promoter region of the monocyte chemoattractant protein-1 (MCP-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the MCP-1 -2518G/A polymorphism. Using the combined transmission disequilibrium test and the pedigree disequilibrium test, no association between the MCP-1 -2518G/A polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the MCP-1 -2518G/A polymorphism is not strongly associated with IHD.

Chemokine CCL2↗
PubMed2004

The intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism is not associated with ischaemic heart disease: an investigation using family-based tests of association.

The possible role of the K469E polymorphism in the intercellular adhesion molecule-1 (ICAM-1) gene in the susceptibility to ischaemic heart disease (IHD) was investigated in a well-defined Irish population using two recently described family-based tests of association. One thousand and twelve individuals from 386 families with at least one member prematurely affected with IHD were genotyped for the ICAM-1 K469E polymorphism. Using the combined transmission disequilibrium test (TDT)/sib-TDT and the pedigree disequilibrium test (PDT), no association between the ICAM-1 K469E polymorphism and IHD was found. Our data demonstrate that, in an Irish population, the ICAM-1 K469E polymorphism is not associated with IHD.

Adult↗
PubMed2004

Recent trends in HIV and other STIs in the United Kingdom: data to the end of 2002.

Sexual health in the United Kingdom has deteriorated in recent years with further increases in HIV and other sexually transmitted infections (STIs) reported in 2002. This paper describes results from the available surveillance data in the United Kingdom from the Health Protection Agency and its national collaborators. The data sources range from voluntary reports of HIV/AIDS from clinicians, CD4 cell count monitoring, a national census of individuals living with HIV, and the Unlinked Anonymous Programme, to statutory reports of STIs from genitourinary medicine (GUM) clinics and enhanced STI surveillance systems. In 2002, an estimated 49500 adults aged over 15 years were living with HIV in the United Kingdom, of whom 31% were unaware of their infection. Diagnoses of new HIV infections have doubled from 1997 to 2002, mainly driven by heterosexuals who acquired their infection abroad. HIV transmission also continues within the United Kingdom, particularly among homo/bisexual men who, in 2002, accounted for 80% of all newly diagnosed HIV infections acquired in the United Kingdom. New diagnoses of syphilis have increased eightfold, and diagnoses of chlamydia and gonorrhoea have doubled from 1997 to 2002 overall; STI rates disproportionately affect homo/bisexual men and young people. Effective surveillance is essential in the provision of timely information on the changing epidemiology of HIV and other STIs; this information is necessary for the targeting of prevention efforts and through providing baseline information against which progress towards targets can be monitored.

Bisexuality↗