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Biomedical subjects

J Ward

Publications and source records attributed to J Ward.

At least 109 records · Page 6Linked to original sources
PubMed1999

Implementation of nationally developed guidelines in cardiology: a survey of NSW cardiologists and cardiothoracic surgeons.

BACKGROUND: In July 1996, the National Health and Medical Research Council (NHMRC) published clinical practice guidelines for 'The Procedural and Surgical Management of Coronary Heart Disease'. Despite increasing interest in dissemination and implementation of guidelines, initial reactions to these specific Guidelines and factors critical to their successful implementation had not been determined until our study. AIMS: To determine views of New South Wales (NSW) clinicians towards these NHMRC Guidelines; to identify perceptions about local relevance, usefulness and likely impact and to elicit preferred implementation strategies. METHODS: A postal survey in November 1997 of all cardiologists and cardiothoracic surgeons in NSW. RESULTS: One hundred and ten of 174 clinicians returned the questionnaire (63% response rate). Forty-eight per cent indicated that they were aware of the Guidelines before receiving a copy with the questionnaire while 26% had commented on the draft version of the Guidelines when distributed in November 1995. More than half of respondents 'agreed' or 'strongly agreed' with six of nine statements about potential strengths of the Guidelines. While at least 25% 'disagreed' or 'strongly disagreed' on 11 out of the 13 statements about potential criticisms of the Guidelines, more than half agreed or 'strongly' agreed that the Guidelines did not tell them 'anything they didn't already know'. Fifty-two per cent 'agreed' or 'strongly agreed' that guidelines will be misinterpreted by lawyers. At least 30% rated nine out of 11 implementation strategies as important. Local audits of care and regular feedback, reports from colleagues at conferences and hospital workshops outranked other implementation strategies in encouraging uptake of the Guidelines. CONCLUSIONS: Clinicians in NSW have generally positive views about the Guidelines, however, medicolegal concerns are apparent. To strengthen evidence-based decision-making as exemplified by the Guidelines, audits, presentations by opinion leaders and hospital-based workshops are recommended.

Attitude of Health Personnel↗
PubMed1999

Obtaining resources for evidence-based public health initiatives at the local level: insights from the Central Sydney Tobacco Control Plan.

OBJECTIVE: In response to inquiries regarding the processes of developing a Tobacco Control Plan (TCP) for the Central Sydney Area Health Service (which in 1997 allocated dedicated funding of $ 800,000 over 2 1/2 years to implement the plan), this article describes the strengths and weaknesses of the TCP and outlines the process which contributed to its funding. CONCLUSIONS: Consistent with national and state priorities, the TCP recommended strategies based on best available evidence in the four action areas: reducing sales of cigarettes to minors, marketing, passive smoking and smoking cessation. Funding of this amount for a single public health issue at a local level represents a unique achievement in the application of an evidence-based approach to population health. IMPLICATIONS: Key elements of our advocacy methods included the involvement of all key primary health care and clinical stakeholders; comprehensive background research to identify evidence-based strategies; careful attention to budget options; strategic lobbying of senior staff and decision makers; the proposal for a multidisciplinary management structure for the TCP and specifications for funding allocation and evaluation. Early achievements and other reflections are discussed.

Adolescent↗
PubMed1999

Cervical screening among immigrant Vietnamese women seen in general practice: current rates, predictors and potential recruitment strategies.

OBJECTIVE: To ascertain cervical screening rates among Vietnamese women attending Vietnamese-speaking general practitioners (GPs) in Sydney, their recall of opportunistic recruitment by these GPs and their preferences for strategies to encourage screening. METHOD: Women born in Vietnam aged 18-69 years were recruited through the waiting room of their GP and completed questionnaires in either Vietnamese or Chinese before and after their consultation. RESULTS: Of 355 women seen during the survey period, 170 were ineligible. Of those eligible, 118 women (64% response rate) completed waiting room questionnaires. Of 86 women 'at risk', 56 (65%) reported having a cervical smear within two years or due on that day; 26 (86%) of those 30 women overdue for screening reported visiting a GP at least twice in the past six months. After adjustment for age and education, women who were more acculturated or had resided in Australia for the most years remained significantly more likely to be screened (p = 0.027 and p = 0.037 respectively). In the follow-up questionnaire, returned by 49 women (52%) who agreed to receive it, recall of opportunistic advice from the GP was low. Female GPs, free screening and more information in Vietnamese were the three most popular recruitment strategies. CONCLUSION: Study confirms low participation rates in cervical screening by Vietnamese women using self-report. Recent immigrants and the least acculturated are least likely to be screened. IMPLICATIONS: A community-based strategy involving Vietnamese-speaking GPs shows promise, inviting behavioural evaluation.

Adolescent↗
PubMed1999

Population-based mammographic screening: does 'informed choice' require any less than full disclosure to individuals of benefits, harms, limitations and consequences?

Mammographic screening is a public health intervention with benefits, harms and consequences. Assuming technical excellence and at least 70% participation, mammographic screening of women aged 50 years or over will reduce breast cancer mortality by 24%. Before the introduction of mammographic screening in Australia, the mortality rate from breast cancer for women in the target age group was 69.0 per 100,000. On the basis of this relative risk reduction, breast cancer mortality would be reduced to 46 per 100,000. However, for every breast cancer death averted, 10 additional cases of breast cancer will be diagnosed. As it is unknowable who will benefit from mammographic screening, it is unethical to claim that any given individual has been 'saved' through participation, especially in the absence of evidence that all-cause mortality will change. As women misunderstand their risks of breast cancer and the benefits and limitations of mammographic screening, public education is needed. As an individual's choice about screening is affected by the way benefits are framed, our public messages must be carefully scrutinised. It is impossible otherwise to assert that women are making an 'informed choice'. The decision of women who decline to participate must be respected. Public health expertise is crucial to ensure the rhetoric of 'informed choice' in cancer screening is realised.

Aged↗
PubMed1999

Hepatic lesion detection: comparison of MR imaging after the administration of superparamagnetic iron oxide with dual-phase CT by using alternative-free response receiver operating characteristic analysis.

PURPOSE: To compare the performance of magnetic resonance (MR) imaging after the administration of superparamagnetic iron oxide (SPIO) and dual-phase computed tomography (CT) in the depiction of liver metastases. MATERIALS AND METHODS: Fifty-one hepatic resection candidates with known colorectal metastases were examined. MR imaging comprised fast spin-echo (SE) T2-weighted imaging, T1-weighted gradient-echo (GRE) fast low-angle shot imaging before SPIO enhancement, dual-echo SE imaging, T2-weighted fast low-angle shot imaging, and T1-weighted GRE imaging after SPIO enhancement. CT was performed with 8-mm collimation and 1:1 pitch; imaging commenced 20 seconds and 65-70 seconds after injection of 150 mL of contrast medium. All images were reviewed independently by four blinded observers. The alternative-free response receiver operating characteristic (ROC) method was used to analyze the results, which were correlated with findings from surgery, intraoperative ultrasonography, and histopathologic studies in 31 patients and with consensus review together with all other imaging and clinical follow-up in 20 patients. Sensitivities were also calculated. RESULTS: The mean sensitivity of MR was significantly higher than that of CT (p < .02): 79.8% for MR and 75.3% for CT for all lesions, and 80.6% for MR and 73.5% for CT for malignant lesions. The mean areas under the alternative-free response ROC curves were 0.83 for MR and 0.78 for CT (difference not significant). CONCLUSION: SPIO-enhanced MR imaging was more sensitive than dual-phase CT in the depiction of colorectal metastases.

Colorectal Neoplasms↗
PubMed1999

Target dyspnea ratings predict expected oxygen consumption as well as target heart rate values.

A target heart rate (THR) is the traditional method to prescribe and monitor exercise training intensity in healthy individuals. However, patients with chronic obstructive pulmonary disease (COPD) are limited by ventilatory impairment and dyspnea rather than cardiovascular factors. An alternative approach is to use dyspnea ratings as a target for exercise training in patients with respiratory disease just as ratings of perceived exertion have been used in healthy individuals. The study was a randomized, parallel group trial comparing the ability of patients with COPD to accurately and reliably produce an exercise intensity using a target dyspnea rating (TDR) versus a THR. At Visit 1 patients performed an incremental exercise test on the cycle ergometer, and target values were calculated at approximately 75% of maximal oxygen consumption (V O2). At Visits 2 (3 to 5 d later) and 3 (2 wk later) each patient was instructed to produce a TDR or a THR for 10 min of submaximal exertion. Anthropometric characteristics, lung function, and exercise performance were similar for the 22 patients in each group at Visit 1. For the TDR group the dyspnea target was 2.5 +/- 1.5 at an expected V O2 of 0.88 +/- 0.28 L/min; for the THR group the heart rate (HR) target was 114 +/- 15 beats/min at an expected V O2 of 0.76 +/- 0.29 L/min (p = 0.18 for V O2 between groups). Compared with the expected V O2 from Visit 1, the individual percent differences in V O2 at Visit 2 were -3.9 +/- 18.1% (TDR) and -0.5 +/- 23.2% (THR) (p = 0.58); at Visit 3 the individual percent differences in V O2 were -2.3 +/- 17.0% (TDR) and 2.6 +/- 30.6% (THR) (p = 0.52). The number of patients < 10% and >/= 10% of the expected V O2 were similar for the two groups at Visits 2 (p = 0.38) and 3 (p = 0.27). There were no significant differences for V O2 values (absolute or individual percent) at Visits 2 and 3 for each group and between the groups (p = 0.79). In conclusion, patients with symptomatic COPD demonstrated a comparable ability to use dyspnea ratings and HR as a target to accurately and reliably produce an expected exercise intensity (approximately 75% of V O2max) for 10 min of submaximal exertion.

Aged↗
PubMed1999

Dynamic contrast-enhanced MR imaging and dual-phase helical CT in the preoperative assessment of suspected pancreatic cancer: a comparative study with receiver operating characteristic analysis.

OBJECTIVE: The purpose of this study was to compare dynamic contrast-enhanced MR imaging and dual-phase helical CT in the preoperative assessment of patients with suspected pancreatic carcinoma. SUBJECTS AND METHODS: Thirty-three consecutive surgical candidates (20 men, 13 women; 39-81 years old) were included. MR imaging comprised fast spin-echo (TR/TE 4000/91), fat-suppressed T1-weighted spin-echo (500/15), and T1-weighted breath-hold gradient-echo fast low-angle shot (100/4; flip angle, 80 degrees) images before and after the administration of gadopentetate dimeglumine. Helical CT used 5-mm collimation with a pitch of 1:1.5-1.7; images were obtained 20 and 65-70 sec after injection of 150 ml of contrast material. Two pairs of interpreters who were unaware of the results of the other imaging method independently scored each examination for the presence of a lesion and for surgical resectability using a five-point scale. Results were correlated with surgery (n = 25) or consensus review (n = 8). Receiver operating characteristic methodology was used to analyze the results for resectability, and positive predictive values were calculated. RESULTS: Both MR imaging and helical CT revealed 29 of 31 lesions. In determining lesion resectability, the mean areas under the receiver operating characteristic curves were 0.96 and 0.81 (p = .01) and the positive predictive values were 86.5% and 76% (p = .02) for MR imaging and helical CT, respectively. CONCLUSION: MR imaging and helical CT performed equally well in lesion detection. MR imaging was significantly better in the assessment of resectability of pancreatic tumors.

Adenocarcinoma↗
PubMed1998

Targeted disruption of the acid alpha-glucosidase gene in mice causes an illness with critical features of both infantile and adult human glycogen storage disease type II.

We have used gene targeting to create a mouse model of glycogen storage disease type II, a disease in which distinct clinical phenotypes present at different ages. As in the severe human infantile disease (Pompe Syndrome), mice homozygous for disruption of the acid alpha-glucosidase gene (6(neo)/6(neo)) lack enzyme activity and begin to accumulate glycogen in cardiac and skeletal muscle lysosomes by 3 weeks of age, with a progressive increase thereafter. By 3.5 weeks of age, these mice have markedly reduced mobility and strength. They grow normally, however, reach adulthood, remain fertile, and, as in the human adult disease, older mice accumulate glycogen in the diaphragm. By 8-9 months of age animals develop obvious muscle wasting and a weak, waddling gait. This model, therefore, recapitulates critical features of both the infantile and the adult forms of the disease at a pace suitable for the evaluation of enzyme or gene replacement. In contrast, in a second model, mutant mice with deletion of exon 6 (Delta6/Delta6), like the recently published acid alpha-glucosidase knockout with disruption of exon 13 (Bijvoet, A. G., van de Kamp, E. H., Kroos, M., Ding, J. H., Yang, B. Z., Visser, P., Bakker, C. E., Verbeet, M. P., Oostra, B. A., Reuser, A. J. J., and van der Ploeg, A. T. (1998) Hum. Mol. Genet. 7, 53-62), have unimpaired strength and mobility (up to 6.5 months of age) despite indistinguishable biochemical and pathological changes. The genetic background of the mouse strains appears to contribute to the differences among the three models.

Alleles↗
PubMed1998

A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system.

Nuclear receptors transduce hormonal signals by binding directly to DNA target sites in promoters and modulating the transcription of linked genes. Receptor-mediated transactivation appears to be potentiated in response to ligand by a number of coactivators that may provide key interactions with components of the transcription preinitiation complex and/or alter chromatin structure. Here, we use the vitamin D3 receptor ligand-binding domain (VDR LBD) as an affinity matrix to identify components of a transcriptionally active nuclear extract that interact with VDR in response to ligand. We describe the purification of a complex of at least 10 VDR interacting proteins (DRIPs) ranging from 65 to 250 kD that associate with the receptor in a strictly 1,25-dihydroxyvitamin D3-dependent manner. These proteins also appear to interact with other, but not all, nuclear receptors, such as the thyroid hormone receptor. The DRIPs are distinct from known nuclear receptor coactivators, although like these coactivators, their interaction also requires the AF-2 transactivation motif of VDR. In addition, the DRIP complex contains histone acetyltransferase activity, indicating that at least one or more of the DRIPs may function at the level of nucleosomal modification. However, we show that the DRIPs selectively enhance the transcriptional activity of VDR on a naked DNA template utilizing a cell-free, ligand-dependent transcription assay. Moreover, this activity can be specifically depleted from the extract by liganded, but not unliganded, VDR-LBD. Overexpression of DRIP100 in vivo resulted in a strong squelching of VDR transactivation, suggesting the sequestration of other limiting factors, including components of the DRIP complex. These results demonstrate the existence of a new complex of novel functional nuclear receptor coactivators.

Acetyltransferases↗
PubMed1998

Rational engineering of the TOL meta-cleavage pathway

The meta-cleavage pathway of Pseudomonas putida mt-2 was simulated using a biochemical systems simulation developed by Regan (1996). A non-competitive inhibition term for catechol-2,3-dioxygenase (C23O) by 2-OH-pent-2,4-dienoate (Ki = 150 μM) was incorporated into the model. The simulation predicted steady state accumulation levels in the μM range for metabolites pre-meta-cleavage, and in the mM range for metabolites post-meta-cleavage. The logarithmic gains L[V-i, Xj] and L[X-i, Xj] clearly indicated that the pathway was most sensitive to the concentration of the starting substrate, benzoate, and the first enzyme of the pathway, toluate-1, 2-dioxygenase (TO). The simulation was validated experimentally; it was found that the amplification of TO increased the steady state flux from 0.024 to 0.091 (mmol/g cell dwt)/h. This resulted in an increased accumulation of a number of the pathway metabolites (intra- and extracellularly), especially cis-diol, 4-OH-2-oxovalerate, and 4-oxalocrotonate. Metabolic control analysis indicated that C23O was, in fact, the major controling enzymic step of the pathway with a scaled control coefficient of 0.83. The amplification of TO resulted in a shift of some of the control away from C23O. Catechol-2,3-dioxygenase, however, remained as the major controling element of the pathway. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗
PubMed1998

Effects of the M1 agonist xanomeline on processing of human beta-amyloid precursor protein (FAD, Swedish mutant) transfected into Chinese hamster ovary-m1 cells.

Complementary DNA (cDNA) encoding human beta-amyloid precursor protein familial Alzheimer's disease (FAD) Swedish mutant (beta APPSM) form was cloned into a mammalian expression vector (PK255) containing the CMV promoter. The vector was transfected into Chinese hamster ovary cells containing human muscarinic m1 receptors (CHO-m1), and clonal cells stably expressing beta APPSM were isolated. The effects of m1-receptor activation by the selective m1 agonist xanomeline and the non-selective muscarinic agonist carbachol on processing of beta APPSM to release soluble APP (APPs) and beta-amyloid peptide (A beta) were compared. Xanomeline stimulated APP release with a potency 1000-fold greater than that observed for carbachol. Concentrations of carbachol and xanomeline producing maximal effects on APPs release reduced the secretion of A beta by 28 and 46%, respectively. These results extend previous studies with xanomeline and suggest that cholinergic replacement therapy for Alzheimer's disease may reduce amyloid deposition.

Alzheimer Disease↗
PubMed1998

Assessment of resectability of pancreatic cancer with dynamic contrast-enhanced MR imaging: technique, surgical correlation and patient outcome.

The aim of our work was to investigate the use of a dynamic contrast-enhanced MR (DCEMR) technique for staging apparently localised pancreatic cancer, and to determine the patterns of tumour and vascular enhancement with this technique. Thirty-five consecutive patients were examined. The MR findings were correlated with surgical findings in 13 patients and with clinical outcome in 22 patients. Breath-hold gradient-echo fast low angle shot (TR = 100, TE = 4, flip angle 80 degrees ) acquisitions were obtained at 10 and 40 s (right anterior coronal oblique plane) and at 90 s (axial plane) following intravenous gadolinium. Mean contrast-to-noise ratio was higher on the first than the second acquisition (p < 0. 001) and higher on the second acquisition than the third (p < 0.005). Tumour conspicuity was greatest and arterial anatomy was best demonstrated on the first acquisition and the portal venous anatomy on the second. Small tumours were isointense by the third acquisition. Maximal intensity projections were helpful. The MR findings correctly predicted the surgical findings in 11 of 13 cases (85 %) and the clinical course in the other 22 patients. The DCEMR imaging technique is valuable in the staging of patients with pancreatic cancer. Capillary and portal venous phase images are both required for complete local staging.

Aged↗