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Biomedical subjects

S Neville

Publications and source records attributed to S Neville.

At least 19 recordsLinked to original sources

External quality assurance of molecular analysis of haemochromatosis gene mutations.

BACKGROUND: The Royal College of Pathologists of Australasia Quality Assurance Programs has conducted an external quality assurance programme for the testing of the haemochromatosis gene (HFE) mutations C282Y and H63D. METHODS: A total of 10 surveys have been undertaken over a period of 6 years from 2000 to 2005. RESULTS: Of the 3016 responses received, the overall success rate was found to be 99.47% (3000/3016). A total of 16 errors were found, 6 for C282Y and 10 for H63D. Only one sample was associated with more than one error, in which 2 of 23 respondents classified a normal sample as heterozygotic for H63D. Overall performance was observed to vary minimally between surveys, from a low of 91.3% correct (21/23 responses) for a normal sample to 100% correct in most (85/100) samples. Of the 10 complete surveys, four returned a 0% error rate. In one survey in 2004, seven incorrect responses were returned by one laboratory, all of which were secondary to transcriptional errors. Overall success rates per assay were 99.61% (1532/1538) for C282Y and 99.32% (1468/1478) for H63D. Over a period of 6 years from 2000 to 2005, the proportion of respondents using polymerase chain reaction (PCR) and restriction enzyme analysis fell from 85% to around 30%, whereas the proportion of laboratories using real-time PCR rose from 5% to around 55%, as indicated by the questionnaire surveys of methods used by participants. DISCUSSION: Encouraging levels of testing proficiency for two common genetic mutations are indicated by these data, but they also confirm the need for participation of molecular diagnostic laboratories in external quality assurance programmes to ensure the ongoing provision of high-quality genetic testing services.

Australia↗

Effect of cataract extraction on frequency doubling technology perimetry in patients with glaucoma.

AIM: To evaluate the effect of cataract surgery on frequency doubling technology (FDT) perimetry in patients with co-existing cataract and glaucoma. METHODS: In this consecutive prospective cohort study 27 patients with open angle glaucoma scheduled for cataract extraction alone or combined with trabeculectomy were enrolled. All patients underwent FDT threshold C-20 visual fields within 3 months before and 3 months after surgery. Changes in mean deviation (MD) and pattern standard deviation (PSD) were evaluated. Additionally, changes in best corrected logMAR visual acuity (VA), intraocular pressure (IOP), and number of glaucoma medications were also studied. RESULTS: 22 patients completed the study. VA improved after surgery, from 0.47 (SD 0.19) to 0.12 (0.17) (p<0.001). The visual indexes changed after cataract extraction: MD improved (from -10.9 (SD 4.6) dB to -7.0 (4.6) dB; p<0.001) while PSD worsened (from 7.1 (SD 3.5) dB to 8.5 (3.8) dB; p = 0.001). CONCLUSION: In patients with co-existing cataract and glaucoma, examined with FDT, MD improved and PSD worsened after cataract surgery. Global indexes of FDT should be interpreted with caution in patients with glaucoma and cataracts.

Aged↗

Introduction to the DAPPLE Air Pollution Project.

The Dispersion of Air Pollution and its Penetration into the Local Environment (DAPPLE) project brings together a multidisciplinary research group that is undertaking field measurements, wind tunnel modelling and computer simulations in order to provide better understanding of the physical processes affecting street and neighbourhood-scale flow of air, traffic and people, and their corresponding interactions with the dispersion of pollutants at street canyon intersections. The street canyon intersection is of interest as it provides the basic case study to demonstrate most of the factors that will apply in a wide range of urban situations. The aims of this paper are to introduce the background of the DAPPLE project, the study design and methodology for data collection, some preliminary results from the first field campaign in central London (28 April-24 May 2003) and the future for this work. Updated information and contact details are available on the web site at http://www.dapple.org.uk.

Air Pollution↗

Loneliness, health and depression in older males.

Loneliness and social isolation, particularly in the older adult, have been shown to influence psychosocial well-being. Loneliness has been related to chronic illness and self-rated health in older adults, and researchers suggest there is an important relationship between loneliness and psychological well-being in older adults particularly in the area of depression. This study investigated relationships between loneliness, health, and depression in 217 older men (> 65 years). Participants completed self-report measures of loneliness, social support, depression, and physical health. Regression analysis showed that a diagnosis of illness or disability was unrelated to depression, however self-reported health was associated with depression, with those reporting poorer health experiencing greater depression. Social support variables were unrelated to depression. The most significant relationship to depression was that of loneliness, with lonelier men reporting higher scores on the Geriatric Depression Scale (GDS). Although research suggests that depression is often a response to declining health and functional impairment in the older adult, the present findings suggest that social isolation may also influence the experience of depression. Age-related losses such as loss of professional identity, physical mobility and the inevitable loss of family and friends can affect a person's ability to maintain relationships and independence, which in turn may lead to a higher incidence of depressive symptoms.

Aged↗

Health assessment and its relationship to nursing practice in New Zealand.

Health assessment has been an integral component of nursing education in Australia for over a decade. New Zealand has only recently embarked down this path and might benefit from the Australian experience. This article will discuss health assessment in the context of three issues currently topical in nursing in New Zealand. The issues are annual registration based on evidence of competence to practice, a review of undergraduate curricula, and the development of nurse practitioner/advanced nurse practitioner roles. The meaning of the concept 'health assessment' is also clarified in order to provide consistency as new initiatives in nursing are currently being developed.

Education, Nursing↗

Factors influencing health and well-being in the older adult.

Both in New Zealand and internationally there are increasing numbers of people living well into their senior years. Not only are more individuals reaching late adulthood, more are living beyond this stage. Because of corresponding increases in illness and/or disability this phenomenon has implications for the provision of health care to communities. This article offers a literature review of selected factors influencing the health and well-being of older people, with a particular emphasis on the older male. Implications for nursing practice in New Zealand are discussed.

Aged↗

A cluster of meningococcal disease in western Sydney, Australia initially associated with a nightclub.

Fourteen cases of meningococcal disease (MD) occurred in August September 1996 in western Sydney, Australia. Seven of the 10 young adults affected had a direct or indirect link with a local nightclub. Ten of 11 systemic meningococcal isolates had the phenotype C:2a:P1.5 and showed close genetic relationship by pulsed-field gel electrophoresis (PFGE). Organisms of this phenotype have not previously caused outbreaks in Australia, but have been associated with outbreaks and hyperendemic serogroup C MD in Europe, Canada, and the United States. This is the largest cluster of serogroup C MD reported in urban Australia, and the first involving a nightclub. The strain differentiation results were available rapidly enough to augment epidemiological investigations on a daily basis. Public health staff could thus establish links between cases quickly, follow the spread of new cases in the community, give accurate information to health officials and the press, and utilize existing knowledge about the characteristics of this phenotype to predict likely developments during the outbreak and afterwards. The strain differentiation data was also very helpful when the role of vaccination was considered, and existing guidelines on the management of outbreaks of MD could be used effectively for the first time in western Sydney.

Adolescent↗

Peritonitis associated with a CDC group EO-3 organism.

A 63-year-old female with chronic renal failure on continuous ambulatory peritoneal dialysis developed chronic peritonitis. A CDC group EO-3 organism was isolated from the peritoneal dialysis fluid on five occasions over a period of 4 months. This is the first reported isolation of this organism in which it is associated with a patient on continuous ambulatory peritoneal dialysis.

Ascitic Fluid↗

An evaluation of the in vitro activity of piperacillin/tazobactam.

Tazobactam is a new, irreversible inhibitor of bacterial beta-lactamases of staphylococci, plasmid-mediated beta-lactamases of the TEM and SHV types found in Escherichia coli and Klebsiella species and beta-lactamases of anerobes such as Bacteroides species. Its combination with piperacillin, a broad spectrum ureido-penicillin, would be expected to improve the activity of piperacillin against staphylococci, TEM and SHV beta-lactamase producing Gram negative bacteria and anerobes. Minimal inhibitory concentrations (MIC) of piperacillin/tazobactam were determined for 1952 individual patient isolates of Gram positive and negative bacteria causing significant infections and compared with MIC values for cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/clavulanic acid. MICs were determined by agar dilution (NCCLS 1990 and 1992). Piperacillin/tazobactam had excellent activity against methicillin susceptible staphylococci, Streptococcus pneumoniae, Haemophilus influenzae, enterococci and organisms of the Bacteroides fragilis group. It was also active against the majority of Enterobacteriaceae and Pseudomonas aeruginosa isolates tested. It was not active against extended spectrum beta-lactamase (ESBL) producing Klebsiella species and some high level TEM and SHV beta-lactamase producing E. coli and Klebsiella species. Activity against Gram negative organisms capable of producing chromosomally mediated beta-lactamases was good, since in most organisms tested, the enzymes were not induced in sufficient quantities to cause antibiotic resistance. However some Enterobacter species were derepressed hyperproducing mutants; these isolates showed resistance to piperacillin/tazobactam since tazobactam does not inhibit these Class I beta lactamases. Activity was superior to ticarcillin/clavulanic acid for Gram negative rods. Imipenem was the most active agent against ESBL producing Klebsiella species. Piperacillin/tazobactam has a suitable spectrum of activity in vitro to suggest its use in monotherapy of mixed anerobic infections, mixed respiratory infections such as aspiration pneumonia and, in combination with an aminoglycoside, it would provide Gram positive as well as Gram negative cover of febrile episodes in immunosuppressed patients.

Bacteroides fragilis↗

Microbiological aspects of an outbreak of Legionnaires' disease in south western Sydney.

In April 1992 an outbreak of Legionnaires' disease occurred in south western Sydney. Twenty four patients were diagnosed as having Legionnaires' disease either on the basis of a positive culture of Legionella pneumophila serogroup I from a respiratory specimen (14 patients) or a four-fold or greater rise in antibody titre or isolated convalescent titre > 1024 with IgM antibodies present (10 patients). This is the largest outbreak in New South Wales since 44 cases of Legionnaires' disease were reported in Wollongong in 1987. Culture and direct immunofluorescent staining (DFA) were performed for early laboratory diagnosis. The DFA test and a set of defined clinical criteria were then used to classify patients as probable cases of Legionnaires' disease for subsequent Public Health investigations. The DFA test had a predictive value for a positive culture of 45.8% and for a negative culture of 97.1%. Its positive predictive value for a definite diagnosis of Legionnaires' disease (either positive culture or seroconversion), however, was 78.3% with a negative predictive valve of 95.1%. During a 27 day period DFA and culture for Legionella species were performed on 198 specimens from 127 patients. Cultures became positive after a mean of 5 days incubation (range 1-11 days). The use of both selective and non-selective media is recommended for optimal recovery of L. pneumophila since some isolates were obtained on only one culture plate. After an initial evaluation of heat decontamination of specimens this process was abandoned, since in 8/63 specimens so treated, L. pneumophila was recovered prior to but not following heat decontamination and was not grown only in heated specimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Disease Outbreaks↗

Effect of cooked meat on micronucleus frequency.

The possibility that inclusion of cooked meat in the diet could elevate chromosome damage risk was investigated in mice fed either a cereal diet only or a cereal diet supplemented with mutton cooked by microwaving, pan-frying or charcoal-barbecueing. The meat was provided as a supplement to the standard cereal-based diet on an approximately one-to-one basis. Chromosome damage indices included the cytokinesis-block micronucleus assay in spleen lymphocytes, the bone marrow micronucleus assay in erythrocytes and two versions of the colonic micronucleus assay. These indices were assessed after 3 or 6 months of feeding, and under each circumstance no increment in the micronucleus frequency in any of the tissues could be detected in the groups fed cooked meat when compared with each other or with the group fed the cereal diet only. There was also no correlation between the micronucleus index in lymphocytes and body weight. These data suggest that, over the time-frame studied, inclusion of meat in the diet and the extent to which meat is cooked are unlikely to be important variables affecting the micronucleus index.

Animals↗

Mutagenicity testing of 9-N-substituted adenines and their N-oxidation products.

Adenine together with certain 9-N-substituted derivatives such as 9-methyl, 9-benzyl, 9-benzhydryl, and 9-trityl were tested against Salmonella typhimurium strains TA97, TA98, and TA100 in the absence and presence of rat hepatic S9 prepared from Aroclor 1254 pretreated rats. All compounds were positive toward TA98 in the presence of the metabolic activating system, whereas they all lacked mutagenic activity in the absence of S9, and toward TA97 and TA100 with or without S9 when tested at 100 ng/plate. A similar pattern was observed for the corresponding 1-N-oxides. 6-Hydroxylaminopurine was not mutagenic toward TA100 at 100 ng/plate, whereas it was toxic toward TA97 and TA98 at this level. When tested at 1 ng/plate, hydroxylaminopurine was still toxic to TA98 but produced twice the spontaneous reversion rate to TA97 without metabolic activation. Surprisingly, 9-methyl-6-hydroxylaminopurine was only active toward TA98 in the presence of S9, whereas 9-benzyl-6-hydroxylaminopurine was highly active toward TA97 and TA100 in the absence of S9 and even more active in the presence of S9. This compound was inactive toward TA98 in the absence of S9. The results generally support the concept that nuclear N-oxidation of aminoazaheterocycles is a detoxication process, whereas N-hydroxylation of the exo amino group is a toxication reaction.

Adenine Nucleotides↗

Conversion of excision-repairable DNA lesions to micronuclei within one cell cycle in human lymphocytes.

The human lymphocyte micronucleus (MN) assay is relatively insensitive to genotoxic agents that predominantly induce excision-repairable lesions such as adducts and abasic sites. In this study we have explored the possibility of using cytosine arabinoside (ARA) to convert excision-repairable DNA lesions to micronuclei (MN) within one cell cycle. The system consisted of human lymphocytes as target cells, the cytokinesis-block (CB) method for identifying cells that had completed one nuclear division only, and X-rays, methylnitrosourea (MNU), and ultraviolet light (UV) as mutagens. With each mutagen we have observed significant increments in induced MN in the cultures that had also been treated with ARA during G1. The slope of the dose-response curves for induction of MN was increased by a factor of approximately 1.8 for X-rays and 10.3 for UV and significant MNU induction of MN was only achieved in the cultures treated with ARA. Furthermore, a 24-hr gap between mutagen exposure and the start of the assay did not abolish the increased sensitivity in the cultures treated with ARA. These observations suggested that the combined ARA and cytokinesis-block micronucleus (CBMN) method may enhance the detection of exposure to genotoxic agents that predominantly induce excision-repairable lesions.

Adult↗

Cytosolic activation of 2-aminoanthracene: implications in its use as diagnostic mutagen in the Ames test.

The metabolic activation of 2-aminoanthracene to mutagens in the Ames test was investigated using hepatic S9, microsomal and cytosolic fractions from control and Aroclor 1254-treated rats as activation systems. Microsomal and S9 preparations from control animals could activate 2-aminoanthracene, but the efficiency of activation was suppressed by pretreatment of animals with Aroclor 1254. Cytosolic fractions from Aroclor 1254-treated rats could readily activate the promutagen more readily than microsomes. The cytosolic activation of 2-aminoanthracene required NADPH and could not be accounted for by possible microsomal contamination. The molybdenum oxygenases appear not to contribute to the cytosolic activation of this promutagen. It is concluded that (a) the microsomal activation of 2-aminoanthracene is catalysed more effectively by enzyme systems other than the P450 I family and (b) an enzyme system capable of activating this carcinogen in vitro is present in the hepatic cytosol. The implications of these findings in the use of 2-aminoanthracene as a positive control in the Ames test are discussed.

Animals↗