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Biomedical subjects

N Murphy

Publications and source records attributed to N Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Survey of acute hospital infection control resources and services in the Republic of Ireland.

Following the development of national guidelines on the control of antimicrobial resistance in 2001, a survey was carried out in 2003 of all 68 acute hospitals in the Republic of Ireland on resources available and current practice to control and prevent nosocomial infection. Completed questionnaires were received from 66 hospitals (97%). The median number of acute inpatient beds per hospital was 156; this was 522 in regional/tertiary referral centres. Only 31 (47%) hospitals had on-site consultant microbiologist sessions, and there was an infection control nurse in 56 (85%) hospitals. Eighteen (29%) hospitals had an occupational health physician, and 48 (73%) hospitals had an infection control committee. There was a median of one isolation room for every 16 acute beds, and a median of five rooms with en-suite bathroom facilities per hospital in those hospitals that provided data. All hospitals had documented infection control policies, and these were available in electronic format in 25 (38%) hospitals. Fifty-five (83%) hospitals undertook surveillance of nosocomial infection, and alcohol-based hand hygiene facilities were available, either at a handwashing sink or at the entrance to a ward, in 57 (86%) hospitals. In the Republic of Ireland, there remains a significant shortage of microbiologists/infection control doctors, occupational health physicians and infection control nurses. Isolation facilities are also inadequate. Although there is much agreement internationally on the importance of nosocomial infection and the priorities for surveillance, there are no agreed basic minimum standards for the resources and facilities necessary to control and prevent nosocomial infection.

Cross Infection↗
PubMed2006

Donor methylenetetrahydrofolate reductase genotype is associated with graft-versus-host disease in hematopoietic stem cell transplant patients treated with methotrexate.

Methotrexate (MTX), used as a graft-versus-host disease (GvHD) prophylactic agent in hematopoietic stem cell transplantation (HSCT), exerts its effect via folate cycle inhibition. A critical enzyme involved in folate metabolism is 5,10-methylenetetrahydrofolate reductase (MTHFR). We examined the association of a single nucleotide polymorphism (SNP) at position 677 in the MTHFR gene on GvHD outcomes in allogeneic HSCT patients administered MTX. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 193 HSCT patients and donors. A total of 140 patients were transplanted with an HLA-matched related donor and 53 with an unrelated donor. GvHD outcomes were compared between genotypes by univariate and multivariate analysis. The combined donor 677CT and TT genotypes were associated with a decreased incidence of GvHD (acute and chronic combined) in HSCT recipients with an HLA-matched related donor (75% at 1 year in the CT and TT group compared with 91% in the wild type CC group, P=0.01), increased time to onset of first GvHD (P=0.001) and time to first GvHD treated with systemic therapy (P=0.022). Unrelated donor MTHFR genotype was not associated with outcome parameters and no associations of recipient genotype in either related or unrelated donor cohorts were observed.

Adolescent↗
PubMed2005

Gene expression profiling in breast cancer: towards individualising patient management.

Breast cancer is a complex and clinically heterogeneous disease. The increase in knowledge of breast cancer biology has led to a number of clinical advances in the treatment of breast cancer, most notably the implementation of widespread mammography screening and advances in adjuvant treatment of early-stage disease. In the last 20 years, arrays of potential prognostic and/or predictive markers of breast cancer have been analysed. However, relatively few have proven to be clinically useful. To date, the only widely accepted markers for routine use in breast cancer are the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor, HER-2 (c-erbB2/neu). Expression microarray technology and laser capture microdissection have now been employed to further our understanding of the molecular pathogenesis of breast cancer. Recently reported advances in array technology and RNA amplification methods are having a considerable impact in this field, allowing the analysis of pre-malignant and pre-invasive lesions. A number of studies have identified prognostic and predictive gene 'signatures', whose prediction of disease outcome and response to treatment is superior to conventional prognostic indicators. Despite major technological advances, a number of confounding issues remain concerning the potential clinical utility of gene expression profiling, including differences in study design, patient selection, array technology, chemistry, and methods of analysis. It seems likely, however, that following careful 'hypothesis driven' validation studies and clinical trials, expression profiling will be applied in the future to identify patient-specific disease profiles and provide rationale for individualised treatment. This review focuses on the current use and future potential of microarray profiling in breast cancer.

Breast Neoplasms↗
PubMed2005

p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer.

AIM: To analyse and compare expression patterns of three potential biomarkers-p16(INK4A), CDC6, and MCM5-and evaluate their use as predictive biomarkers in squamous and glandular cervical preinvasive neoplasia. METHODS: Immunocytochemical analysis of p16(INK4A), MCM5, and CDC6 expression was performed on 20 normal, 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, 10 squamous cell carcinoma, 19 cervical glandular intraepithelial neoplasia (cGIN), and 10 adenocarcinoma samples. Staining intensity was assessed using a 0-3 scoring system. p16(INK4A), MCM5, and CDC6 expression was also examined in ThinPrep slides exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) was detected using a modified SYBR green assay. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. RESULTS: All three markers showed a linear correlation between expression and grade of dysplasia. p16(INK4A) and MCM5 protein expression was upregulated in all grades of squamous and glandular dysplasia. CDC6 protein was preferentially expressed in high grade lesions and in invasive squamous cell carcinoma. CONCLUSION: p16(INK4A) expression was closely associated with high risk HPV infection-all grades of squamous and glandular cervical lesions were immunohistochemically positive. MCM5 staining intensity was independent of high risk HPV infection, highlighting its potential as a biomarker in both HPV dependent and independent cervical dysplasia. CDC6 may be a biomarker of high grade and invasive lesions of the cervix, with limited use in low grade dysplasia. p16(INK4A) was the most reliable marker of cervical dysplasia. Combinations of dysplastic biomarkers may be useful in difficult diagnostic cases.

Adenocarcinoma↗
PubMed2004

p16INK4A positivity in benign, premalignant and malignant cervical glandular lesions: a potential diagnostic problem.

A wide array of immunohistochemical markers have been evaluated with respect to their specificity in staining dysplastic cervical cells in cervical biopsies and cervical cytological smears. However, there is still a significant demand for better biomarkers to identify neoplastic cervical glandular and squamous epithelial cells precisely. The CDKN2A gene, located on chromosome 9p21, encodes the tumour suppressor protein, p16INK4A, which decelerates the cell cycle by inactivating CDK4 and CDK6. The aim of this study was to compare and contrast the expression pattern of p16INK4A in benign and neoplastic glandular lesions and tubo-endometrioid metaplasia. All cases in each category displayed some p16INK4A expression. Adenocarcinoma and in situ cases showed a combination of intense nuclear and cytoplasmic staining. It was observed that all cases of tubo-endometrioid metaplasia showed occasional nuclear positivity and definite cytoplasmic staining. These findings may have important implications for the potential utility of p16INK4A as a biomarker for glandular dysplastic lesions. While p16INK4A has been demonstrated to be an excellent marker of cervical dysplasia in squamous neoplastic lesions of the cervix, it has potential pitfalls in cervical glandular lesions that may limit the utility of this biomarker in resolving the nature of suspicious glandular lesions, particularly in cytopathology.

Adenocarcinoma↗
PubMed2004

An investigation into how community mental health nurses assess the risk of violence from their clients.

Part of the community mental health nurse's (CMHN) role is the assessment of violence posed by clients. It explores factors such as the reduction of inpatient beds and the predictability of violent acts towards nursing staff. This study outlines how the risk of violence is assessed by generic CMHNs, by examining their awareness, understanding and perceptions of violence posed by their clients. The data were collected in one Trust, using questionnaire and focus groups. The findings emphasize the importance of historical evidence but also raise the issue of gut feelings of the nurse. They further identify that clinical judgement can be accurate in assessing for violence, and CMHNs relied upon experience and personal impressions of the presenting evidence, rather than through the use of a standardized instrument.

Community Mental Health Services↗
PubMed2004

Cost of an emerging epidemic: an economic analysis of atrial fibrillation in the UK.

OBJECTIVE: To evaluate the cost of atrial fibrillation (AF) to health and social services in the UK in 1995 and, based on epidemiological trends, to project this estimate to 2000. DESIGN, SETTING, AND MAIN OUTCOME MEASURES: Contemporary estimates of health care activity related to AF were applied to the whole population of the UK on an age and sex specific basis for the year 1995. The activities considered (and costs calculated) were hospital admissions, outpatient consultations, general practice consultations, and drug treatment (including the cost of monitoring anticoagulant treatment). By adjusting for the progressive aging of the British population and related increases in hospital admissions, the cost of AF was also projected to the year 2000. RESULTS: There were 534 000 people with AF in the UK during 1995. The "direct" cost of health care for these patients was 244 million pounds sterling (approximately 350 million euros) or 0.62% of total National Health Service (NHS) expenditure. Hospitalisations and drug prescriptions accounted for 50% and 20% of this expenditure, respectively. Long term nursing home care after hospital admission cost an additional 46.4 million pounds sterling (approximately 66 million euros). The direct cost of AF rose to 459 million pounds sterling (approximately 655 million euros) in 2000, equivalent to 0.97% of total NHS expenditure based on 1995 figures. Nursing home costs rose to 111 million pounds sterling (approximately 160 million euros). CONCLUSIONS: AF is an extremely costly public health problem.

Aged↗
PubMed2003

The current cost of angina pectoris to the National Health Service in the UK.

OBJECTIVE: To calculate the cost of angina pectoris to the UK National Health Service (NHS) in the year 2000. METHODS: Calculation of the cost of hospital admissions, revascularisation procedures, hospital outpatient consultations, general practice (GP) consultations, and prescribed drug treatment. RESULTS: 634 000 individuals (1.1% of the UK population) consulted GPs 2.35 million times, costing pound 60.5 million. They required 16.0 million prescriptions (cost pound 80.7 million) and 254 000 hospital outpatient referrals (cost pound 30.4 million). There were 149 000 hospital admissions, 117 000 coronary angiograms, 21 400 coronary artery bypass operations, 17 700 percutaneous coronary interventions, and 516 000 outpatient visits, at a cost of pound 208.4 million, pound 69.9 million, pound 106.2 million, pound 60.7 million, and pound 52.2 million, respectively. The direct cost of angina was therefore pound 669 million (1.3% of total NHS expenditure), with hospital bed occupancy and procedures accounting for 32% and 35% of this total, respectively. CONCLUSIONS: Angina is a common and costly public health problem. It consumed over 1% of all NHS expenditure in the year 2000, mainly because of hospital bed occupancy and revascularisation procedures. This is likely to be a conservative estimate of its true cost.

Ambulatory Care↗
PubMed2003

p16INK4A as a marker for cervical dyskaryosis: CIN and cGIN in cervical biopsies and ThinPrep smears.

AIM: To examine the potential of p16(INK4A) as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and ThinPrep smears. METHODS: Immunocytochemical analysis of p16(INK4A) expression was performed on 22 normal cervical tissue samples, five cervical glandular intraepithelial neoplasia (cGIN), 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, and 10 invasive cancer cases (eight squamous and two adenocarcinomas). All samples were formalin fixed and paraffin wax embedded, and immunohistochemical analysis was carried out using a mouse monoclonal anti-p16(INK4A) antibody after antigen unmasking. The staining intensity was assessed using a 0 to 3 scoring system. In addition, the expression status of p16(INK4A) was examined in 12 normal ThinPrep smears, one smear exhibiting cGIN, and a total of 20 smears exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) detection was carried out using a modified SYBR green assay system. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. RESULTS: p16(INK4A) immunoreactivity was absent in all normal cervical tissues examined. Dysplastic squamous and glandular cells were positive for p16(INK4A) expression in all cases included in this study, except for one CIN3 case. p16(INK4A) expression was mainly nuclear in CIN1 cases, and both nuclear and cytoplasmic in CIN2, CIN3, cGIN, and invasive cases. All cases positive for HPV expressed the p16(INK4A) protein, although not all cases found positive for p16(INK4A) were HPV positive. In general, the p16(INK4A) staining intensity was lower in cases negative for HPV or those containing a low risk HPV type. CONCLUSION: This pattern of overexpression demonstrates the potential use of p16(INK4A) as a diagnostic marker for cervical squamous and also glandular neoplastic lesions. In addition, the technique can be used to identify individual dyskaryotic cells in ThinPrep smears. Thus, p16(INK4A) is a useful marker of cervical dyskaryosis.

Biomarkers↗
PubMed2002

The potential role of prehospital administration of activated charcoal.

OBJECTIVES: Activated charcoal is now the mainstay of non-specific treatment for self poisoning in accident and emergency (A&E) departments and should be administered within one hour of ingestion of an overdose. This study aimed to investigate if compliance with treatment guidelines may be improved by the prehospital administration of activated charcoal. METHOD: Ambulance report forms and case notes were reviewed in all patients presenting to A&E by ambulance after self poisoning. Information was gathered using a standardised abstraction form. The times collected were: time of ingestion, time of call to ambulance control, time picked up, time of arrival in A&E and time seen by doctor. RESULTS: 201 patient records were reviewed. Twenty six were excluded because of incomplete data on report forms or case notes. The median time between ingestion and pick up by an ambulance crew was 77 minutes. This compares with a median of 140 minutes for the time to assessment by medical staff. Seventy three patients were picked up by an ambulance within one hour of overdose, only 11 (15%) of these were seen by medical staff within an hour of ingestion. Forty nine of these 73 patients would have been suitable candidates to receive activated charcoal. CONCLUSIONS: The prehospital administration of charcoal provides an opportunity to comply with international guidelines on reducing the absorption of a potentially fatal overdose. The administration of charcoal results in few side effects provided the patient can adequately protect their airway and ambulance staff could be trained in its use. Further studies would be necessary to investigate if this would effect clinical outcome.

Charcoal↗
PubMed2001

A high-performance liquid chromatography based strategy for rapid, sensitive sequencing of N-linked oligosaccharide modifications to proteins in sodium dodecyl sulphate polyacrylamide electrophoresis gel bands.

The majority of biologically active proteins are glycosylated, therefore any approach to proteomics which fails to address the analysis of oligosaccharides is necessarily incomplete. To appreciate the structure of a glycoprotein fully, to understand the roles for the attached oligosaccharides and to monitor disease associated changes it is necessary to visualise the sugars as well as the protein. To achieve this aim when biological samples are available at the low microgram level or less has involved increasing the sensitivity of the technology for glycan analysis. Since one protein may have many different oligosaccharides attached to it (glycoforms) this is a major technical challenge. CD59, for example, has over 100 different sugars at one N-linked glycosylation site. Applications of recently developed technology suggest that it is now becoming realistic to extend the proteomics analysis of glycoproteins to include details of glycosylation. This is achieved by releasing the N-glycans from the protein in a gel by optimised peptide-N-glycosidase F digestion. The released glycans are then tagged with the fluorophore, 2-amino benzamide. The labelled glycan pools (containing 50-100 femtomoles of glycans) are resolved by predictive normal phase high performance liquid chromatography (HPLC) on an amide based column or by reverse phase HPLC on a C18 column. Preliminary structural assignments are confirmed by exoglycosidase array digestions of the entire glycan pool. Complementary matrix-assisted laser desorption/ionization-mass spectrometry, which requires 10-20 times as much sugar for a single run, can be used where there is sufficient material. This provides a composition analysis but not linkage information.

Amidohydrolases↗
PubMed2001

Ethno-veterinary medicine: screening of Nigerian medicinal plants for trypanocidal properties.

Trypanosoma congolense and T. brucei bloodstream form parasites were propagated axenically in suitable standard media at 34 degrees C. The effects of 33 plant extracts, fractions and pure compounds were evaluated on two clones of T. brucei and drug-sensitive and multi-drug-resistant clones of T. congolense. The cytotoxic activity of the trypanocidal extracts was also evaluated on calf aorta endothelial cells in vitro. Of the extracts tested, 22% killed T. congolense IL 1180 at a concentration of 100 microg/ml while 18% killed 90-100% of T. brucei ILTat 1.4 at the same concentration. However, 6% of the active extracts killed 93% of a dyskinetoplastid form of T. brucei IL Tat 1.1, indicating that the intact kinetoplast is a target of some of the compounds tested. Of the 12 extracts that displayed activity against drug sensitive trypanosomes, 66.7% had trypanocidal activity on a multi-drug-resistant clone, T. congolense IL 3338. The extracts of Eugenia uniflora, Acacia artaxacantha, Terminalia ivorensis, T. superba and Alchornea cordifolia had median lethal concentrations of between 13 and 69 microg/ml on both the drug-sensitive, IL 1180 and multi-drug-resistant clone, IL 3338. The median lethal doses of the active plant extracts on the calf aorta endothelial cells varied between 112 and 13750 microg/ml while the calculated selective indices ranged between 0.71 and 246.8 indicating bright prospects for the development of some of these extracts as potential trypanocidal agents.

Animals↗
PubMed2001

Saliva alcohol concentrations in accident and emergency attendances.

OBJECTIVES: Although alcohol is known to play a key part in accidents, no UK study has assessed alcohol concentrations in a comprehensive sample of accident and emergency (A&E) attenders. This study set out to do this, and examine the relation between alcohol concentrations and the severity, type and circumstances of presentation, and the sociodemographic characteristics of patients. METHODS: A survey was conducted of all new A&E attenders (aged 10 years or over). Two 24 hour periods for each day of the week were covered in 6, 7 or 11 hour sessions over a two month period. Alcohol concentrations were assessed from saliva samples using a disposable device. Data were collected from 638 attenders, of whom 544 provided saliva samples; the remainder refused or were unable to participate. RESULTS: Positive saliva alcohol readings were obtained in 22% of attenders (95%CI 19% to 26%); this increased to 25% if others were included (for example, those who refused to participate but were judged to be intoxicated). Alcohol was associated with 94% of incidents of self harm, 54% of non-specific/multiple complaints, 47% of collapses, 50% of assaults, and 50% of patients admitted to hospital. Higher concentrations of alcohol were found from Friday to Sunday, between midnight and 0900, and in patients aged 41 to 60. Among people with positive alcohol results, those attending with a companion had higher concentrations than those attending alone. There were no significant differences between men and women in alcohol concentrations. DISCUSSION: These findings show that alcohol use is an important factor in A&E attendance, but it should not be assumed that there is a causal relation between alcohol use and injury. Several accident related and sociodemographic variables were predictive of alcohol use before attending. The overall level of prediction was too weak to permit accurate identification of drinkers for screening purposes, but routine alcohol concentration assessments may be justified in the high risk groups identified in this study. A&E departments may be convenient and fruitful settings for brief interventions with early problem drinkers.

Adolescent↗
PubMed2001

Ethnic classification in primary dental care and dental health services research: time to pause for thought.

'Ethnicity' is an important concept in dental health services research and in enabling general dental practitioners to gain insight into their patients values and expectations. Since more health services research is being undertaken in primary dental care settings it is becoming an important issue for dental professionals and researchers in primary care to be aware of. Ethnicity is thought to be related to dental health inequalities and access and is often used as a stratifying variable in many dental studies. The meaning and use of the term however differs among researchers and among the public. It is clear that researchers and professionals need to pause for thought when considering what this often bandied about term actually means and the impact of different definitions. This is illustrated using examples from the authors' own research and published papers in the medical and dental literature. There is also much debate about whether ethnicity--however defined--is an important predictor of differences in dental health in itself or is merely a marker for other factors such as social deprivation or the impact of 'place' on dental health. While the jury on this debate is out we suggest guidelines on the reporting of ethnicity should be outlined in the dental literature--perhaps updating those published in 1996 in the British Medical Journal.

Cultural Characteristics↗
PubMed2001

A critical analysis of compliance.

In nursing the word compliance has competing meanings. In order to understand these meanings, nursing literature was reviewed and a critical analysis of this concept was undertaken. This included an examination of how nursing was located in relation to the historical controversy surrounding the term compliance. The philosophy that undergirds this analysis is critical theory scholarship, which focuses on language as a vehicle for social control and domination. Literature was critically analyzed according to how nurse authors define the term compliance and the historical context in which the term was used. Analysis of the literature revealed three distinct categories: evaluative, rationalization, and acceptance. Each of these categories is described and the selection criteria identified. We recommend that, nurses intent on conducting future compliance research, consider emancipatory models for their investigations.

Health Knowledge, Attitudes, Practice↗