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Biomedical subjects

R Taylor

Publications and source records attributed to R Taylor.

At least 73 records · Page 4Linked to original sources

Suicide and political regime in New South Wales and Australia during the 20th century.

STUDY OBJECTIVE: Australia has had a two party parliamentary political system for most of the period since its Federation in 1901, dominated either by a social democratic (Labor) or a conservative ideological perspective. This paper investigates whether such political differences at Federal and State levels have influenced suicide rates in the state of New South Wales (NSW) for the period 1901-1998. DESIGN: Federal government type, NSW State government type, and combinations of both Federal and NSW State government type were examined. Poisson regression models were stratified by sex and controlled for the effects of age, annual change in gross domestic product, sedative availability, drought, and both world wars. RESULTS: When both Federal and NSW State governments were conservative the relative risk of suicide for NSW men was 1.17 (p<0.001) and for women 1.40 (p<0.001) compared with both governments being Labor (1.00). A statistically significant linear trend (p<0.001) in suicide risk was evident across the continuum of Federal/State government combinations, from both Labor (lowest), to mixed (intermediate), to both conservative (highest). CONCLUSION: Significantly higher suicide risk was associated with conservative government tenures compared with social democratic incumbents. Results are discussed in terms of the differences underpinning conservative and social democratic government programme ideology, and their relevance to Durkheim's theories of suicide, social regulation, and integration.

Adolescent↗

Interval breast cancers in New South Wales, Australia, and comparisons with trials and other mammographic screening programmes.

OBJECTIVE: To present information on 1st year interval breast cancer from the New South Wales mammographic screening programme and to compare with published results from trials and services. SETTING: New South Wales data were derived from a population based biennial mammographic screening programme, which achieved statewide coverage in 1995. Women aged 50-69 years screened during 1995-7 were included. METHODS: Bilateral two view mammography with reading by two radiologists is used for biennial screening examinations. Interval cancers were detected by the screening programme and by linkage with the statewide cancer registry. In situ carcinoma was excluded. Incidence of interval cancer was estimated as a proportion of the expected underlying incidence of breast cancer. Comparative data were derived from the published literature and meta-analyses were performed. RESULTS: Although randomised trials of screening have a proportional incidence by meta-analysis of 19% (95% confidence interval (95% CI) 12% to 25%), service studies yield a proportional incidence by meta-analysis of 27% (95% CI 25% to 30%), and more than half report proportional incidences greater than 25%. In the New South Wales mammographic screening programme the proportional incidence of interval breast cancer was 33% (95% CI 29% to 38%) for ages 50-59 years, 28% (95% CI 24% to 32%) for ages 60-69 years, and 31% (95% CI 28% to 34%) for ages 50-69 years combined. Proportional incidence in the New South Wales programme for ages 50-69 years was not significantly different from the rate for service studies by meta-analysis. CONCLUSIONS: Effectiveness of mammographic screening for reducing mortality from breast cancer needs to be examined relative to rates of interval cancer from actual service situations as trials may concentrate resources and expertise in ways which may be less replicable in routine delivery of the service.

Aged↗

Early cervical cancer rescreening.

INTRODUCTION: The extent of early cervical rescreening, defined as rescreening earlier than the recommended interval for a given initial test result, is difficult to determine mainly because the testing history of women is incomplete, especially with newer population based screening registers. METHODS: Estimation of early rescreening is based on analysis of a 1 month cohort of women (February 1997) recorded on the New South Wales Pap Test Register (PTR) who initially tested negative and who had no recorded history of a positive test result. For the purposes of estimating early rescreening rates and sources of multiple screening occurring within the recommended 2 yearly screening interval for New South Wales, the cohort excluded the estimated proportion of women with an unrecorded history of a positive result. Approaches to exclusion were different for women with a history of a high grade result (CIN2 or higher) or a low grade result (CIN1 or lower). RESULTS: Characteristic rescreening peaks occurred at 6, 12, 18, 24 and 27 months according to negative result category. The rescreening peak at 27 months illustrates the effect of the PTR late reminder system. After adjusting the cohort for estimated proportions of women with a history of a lesion, the number of women estimated to have rescreened early was approximately 156 000 over 1997-8, and the early rescreening rate was estimated as 15.3% of women who have a Pap test. A feasible target for reducing rescreening through service provider interventions was estimated to be a reduction of 7.4%, based on reducing the overscreening proportion from 15.3% to 7.9% through truncating characteristic rescreening peaks to background levels of rescreening. This represents just under 200 000 screens that could be performed over 2 years on New South Wales women who are underscreened or unscreened without incurring additional costs due to screening. CONCLUSIONS: Reasonable estimates of early cervical rescreening can be derived but some assumptions in estimating the proportion of women with a positive test result history may be needed particularly if a screening programme is new and universal recording of screening data is only recent. Characteristic peaks, as departures from a background of random noise in time plots of rescreening indicate that a component of early rescreening is systemic and the chief source of such variation in screening behaviour would be service providers.

Adult↗

Exhaled nitric oxide correlates with airway eosinophils in childhood asthma.

BACKGROUND: Exhaled nitric oxide has been proposed as a marker for airway inflammation in asthma. The aim of this study was to compare exhaled nitric oxide levels with inflammatory cells and mediators in bronchoalveolar lavage fluid from asthmatic and normal children. METHODS: Children were recruited from elective surgical lists and a non-bronchoscopic bronchoalveolar lavage (BAL) was performed after induction of anaesthesia. Exhaled nitric oxide (parts per billion) was measured by two techniques: tidal breathing and restricted breath. RESULTS: Median (interquartile range) exhaled nitric oxide measured by restricted breath was increased in asthmatics compared with normal children (24.3 (10.5-66.5) v 9.7 (6.5-16.5), difference between medians 14.6 (95% CI 5.1 to 29.9), p=0.001). In asthmatic children exhaled nitric oxide correlated significantly with percentage eosinophils (r=0.78, p<0.001 (tidal breathing) and r=0.78, p<0.001 (restricted breath)) and with eosinophilic cationic protein (r=0.53, p<0.01 (restricted breath)), but not with other inflammatory cells in the BAL fluid. The area under the receiver operator characteristic curves for the prediction of the presence of eosinophilic airways inflammation by exhaled nitric oxide (tidal and restricted) was 0.80 and 0.87, respectively. CONCLUSIONS: Exhaled nitric oxide correlates closely with percentage eosinophils in BAL fluid in asthmatic children and is therefore likely to be a useful non-invasive marker of airway inflammation.

Asthma↗

Outgrown asthma does not mean no airways inflammation.

Although some asthmatic children seem to recover from their asthma, 30-80% develop asthma again in later life. The underlying risk factors are unknown. The hypothesis for this study was that children with apparently outgrown asthma would have underlying airway inflammation. Nonbronchoscopic bronchoalveolar lavage was performed on normal children (n=35) and children who had wheezed previously (n=35). Eosinophils were raised in the lavage fluid of atopic children who had apparently outgrown asthma (median (interquartile range) 0.36 (0.05-0.74) compared to controls 0.10 (0-0.18), p=0.002). There was no relationship between length of remission and degree of airways eosinophilia. Thus, there is persistent airways inflammation in some children with outgrown asthma and this may be a risk factor for future relapse.

Asthma↗

Rules governing the crystal packing of mono- and dialcohols.

A new program, Mercury, has been used to survey 144 monoalcohol (C(m)H(n)OH) and 101 dialcohol [C(m)H(n)(OH)(2)] crystal structures. Results show that their hydrogen-bonding patterns are strongly correlated with steric effects. Primary monoalcohols have a strong preference to form infinite ...OH...OH... chains. Secondary monoalcohols form chains and rings of hydrogen bonds with about equal facility. Tertiary monoalcohols very often form isolated OH...O hydrogen bonds or structures containing no OH...O hydrogen bonds at all. In the latter case, however, the structures almost invariably contain CH...O and/or OH...pi interactions. Substitution on the beta-carbon(s) of monoalcohols has a profound effect on packing patterns, with increased substitution disfavouring chains and rings. Dialcohols show a much stronger preference for chains of hydrogen bonds, compared with monoalcohols. This is particularly so when at least one of the hydroxyl groups is primary, in which case chains are overwhelmingly preferred. Once again, substitution on the beta-C atoms is influential, heavy substitution tending to lead to packing arrangements that involve isolated or intramolecular OH...O hydrogen bonds. Dialcohols almost never crystallize without at least some OH...O hydrogen-bond formation. In both monoalcohols and dialcohols, chains show a stronger preference to be helical (usually threefold helices) as steric hindrance increases. Hydrogen-bonded rings usually contain four OH...O hydrogen bonds. It is possible that empirical observations such as these may aid crystal-structure prediction.

Journal Article↗

Treatment implications of a positive sentinel lymph node biopsy for patients with early-stage breast carcinoma.

BACKGROUND: Sentinel lymph node (SLN) mapping and biopsy is emerging as an alternative to axillary lymph node dissection (ALND) in determining the lymph node status of patients with early-stage breast carcinoma. The hypothesis of the technique is that the SLN is the first lymph node in the regional lymphatic basin that drains the primary tumor. Non-SLN (NSLN) metastasis in the axilla is unlikely if the axillary SLN shows no tumor involvement, and, thus, further axillary interference may be avoided. However, the optimal treatment of the axilla in which an SLN metastasis is found requires ongoing evaluation. The objectives of this study were to evaluate the predictors for NSLN metastasis in the presence of a tumor-involved axillary SLN and to examine the treatment implications for patients with early-stage breast carcinoma. METHODS: Between June 1998 and May 2000, 167 patients participated in the pilot study of SLN mapping and biopsy at Westmead Hospital. SLNs were identified successfully and biopsied in 140 axillae. All study patients also underwent ALND. The incidence of NSLN metastasis in the 51 patients with a SLN metastasis was correlated with clinical and pathologic characteristics. RESULTS: Of 51 patients with a positive SLN, 24 patients (47%) had NSLN metastases. The primary tumor size was the only significant predictor for NSLN involvement. NSLN metastasis occurred in 25% of patients (95% confidence interval [95%CI], 10-47%) with a primary tumor size </= 20 mm and in 67% of patients (95%CI, 46-83%) with a primary tumor size > 20 mm (P = 0.005). The size of the SLN metastasis was not associated significantly with NSLN involvement. Three of 7 patients (43%) with an SLN micrometastasis (< 1 mm) had NSLN involvement compared with 38 of 44 patients (48%) with an SLN macrometastasis (> or = 1 mm). CONCLUSIONS: The current study did not identify a subgroup of SLN positive patients in whom the incidence of NSLN involvement was low enough to warrant no further axillary interference. At present, a full axillary dissection should be performed in patients with a positive SLN.

Adult↗

Fluorinated fullerenes.

Recent developments in fluorination of fullerenes coupled with HPLC separation have permitted the isolation and subsequent structural characterisation of many derivatives, a number of which have novel and unexpected structures. The good solubility of fluorofullerenes, high reactivity towards nucleophiles and enhanced dienophilicity of the unsubstituted part of the cage, as a result of electron withdrawal by the fluorines, makes fluorofullerenes promising synthons. In particular that may have enhanced performance in donor-acceptor complexes with respect to bare fullerenes.

Journal Article↗

A structure-based design approach to the development of novel, reversible AChE inhibitors.

Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further.

Acetophenones↗

Isolation and characterization of unsymmetrical C(60)Me(5)O(3)H, a cage-opened bisepoxide ketone: tautomerism involving a fullerene cage bond.

Bisepoxide ketone C(60)Me(5)O(3)H, possessing a nine-membered hole in the cage, has been isolated from the reaction of C(60)Cl(6) with methyllithium followed by hydrolysis. It is a tautomer of the recently isolated bisepoxide fullerenol, this tautomerism being the first example involving a cage C-C bond, and may be driven by cage strain. Like the fullerenol, the ketone gives a high C(58)(+) fragmentation ion intensity during EI mass spectrometry.

Journal Article↗

Multipathways for transdifferentiation of human prostate cancer cells into neuroendocrine-like phenotype.

The neuroendocrine (NE) cell is a minor cell population in normal human prostate glands. The number of NE cells is increased in advanced hormone-refractory prostate carcinomas (PCA). The mechanism of increased NE cell population in these advanced tumors is poorly understood. We examined molecular mechanisms which may be involved in the regulation of the transdifferentiation process of human PCA cells leading to a NE phenotype. We compared PCA cell lines LNCaP and PC-3 in the following medium conditions: steroid-reduced (SR), interleukin-6 (IL-6)-supplemented, or dibutyrate cAMP (db-cAMP)-supplemented. We found that androgen-responsive C-33 LNCaP cells responded to all treatments, having a neuronal-like morphology. In contrast, C-81 LNCaP cells, having a decreased androgen responsiveness, had a less pronounced effect although followed a similar trend. Androgen-unresponsive PC-3 cells showed little change in their morphology. Grown in the SR condition, the level of neuron-specific enolase (NSE), a marker of neuronal cells, was upregulated in C-33 LNCaP cells, while to a lesser degree in the presence of IL-6. In the presence of db-cAMP, the NSE level in C-33 cells was decreased, lower than that in control cells. An opposite effect was observed for C-81 LNCaP cells. Nevertheless, the NSE level was only elevated in db-cAMP-treated PC-3 cells, but no change was found in PC-3 cells grown in the SR- or IL-6-supplemented medium. Thus, a similar gross phenotypic change may correlate with differential molecular expressions. We also analyzed the expression of protein tyrosine phosphatase alpha (RPTPalpha) since it plays a critical role in normal neuronal differentiation and signaling. Our results showed that the expression of RPTPalpha correlates with the NE phenotypic change of LNCaP cells in the SR condition. In summary, our data clearly show that the molecular process by which cultured human prostate cancer cells undergo a transdifferentiation process to a NE cell-like phenotype is accompanied by differential expressions of different markers, and a gross NE cell-like phenotype can occur by exposing PCA cells to different pharmacological agents.

Androgens↗

Removal of nail polish and finger rings to prevent surgical infection.

BACKGROUND: Surgical wound infection may be caused by transfer of bacteria from the hands of the surgical team during operative procedures. Careful surgical scrubbing is therefore performed to reduce the number of bacteria on the skin. The wearing of finger rings and nail polish is thought to reduce the efficacy of the scrub as they are thought to harbour bacteria in microscopic imperfections of nail polish and on the skin beneath finger rings. OBJECTIVES: To assess the effect of removal of finger rings and nail polish by the surgical scrub team, on postoperative wound infection rates. SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Trials Register up to November 2000 using the search strategy developed by the Cochrane Wounds Group. We wrote to manufacturers of surgical scrubbing agents for ongoing and unpublished research. Reference lists of articles were searched and relevant journals outside the electronic databases were hand searched. No restriction was placed on literature based on date of publication, language or publication status. SELECTION CRITERIA: Randomised controlled trials evaluating the effect of wearing or removal of finger rings and nail polish by the surgical scrub team on post operative wound infections and number of bacteria on the hands of the surgical scrub team. DATA COLLECTION AND ANALYSIS: The abstracts of studies identified were scanned by all reviewers. All abstracts were checked against a checklist to determine whether they fulfilled the inclusion criteria. Full reports of relevant studies were obtained and checked against the checklist by two reviewers. The full reports of all excluded trials were checked by all reviewers independently to ensure appropriate exclusion. MAIN RESULTS: We found no randomised controlled trials that compared the wearing of finger rings with the removal of finger rings. We found no trials of nail polish wearing / removal that measured patient outcomes, including surgical infection. We found one small randomised controlled trial which evaluated the effect of nail polish on the number of bacterial colony forming units on the hands after pre-operative hand washing (also called surgical scrubbing). Nurses were allocated to: unpolished nails, freshly applied nail polish (less than two days old), or old nail polish (more than four days old). Both before and after surgical scrubbing, there was no significant difference in the number of bacteria on the hands. REVIEWER'S CONCLUSIONS: There is no evidence of the effect of removing nail polish or finger rings on the rate of surgical wound infection. There is insufficient evidence of the effect of wearing nail polish on the number of bacteria on the skin. However, the one trial making this comparison trial was too small to exclude anything other than a very large difference in the number of bacteria on the skin.

Bacteria↗

Positron emission tomography in the evaluation of stage III and IV head and neck cancer.

BACKGROUND: Detection of metastatic disease in head and neck cancer patients is critical to preoperative planning, because patients with distant metastasis will not benefit from surgical therapy. Conventional radiographic modalities, such as CT and MR, give excellent anatomic detail but poorly identify unenlarged lymph nodes harboring metastatic disease. OBJECTIVE: A pilot study was conducted to evaluate the usefulness of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) detection of metastatic disease in patients with advanced-stage head and neck cancer. METHODS: Total body FDG-PET imaging was performed in a prospective manner on 12 consecutive patients with a new diagnosis of stage III or IV mucosal squamous cell carcinoma of the head and neck. Chest CT was also performed on all 12 patients. Patients found to have metastatic disease on either CT or PET imaging underwent procedures to obtain histopathologic confirmation of disease. RESULTS: Three patients (25%) had FDG-PET scans demonstrating metastatic disease. Two of these patients had no evidence of disease on chest radiograph or chest CT but were noted to have positive FDG-PET imaging within the mediastinal lymphatics. Mediastinoscopy was performed confirming metastatic disease in these patients. The third patient had a peripheral lung lesion detected on chest radiograph, CT, and FDG-PET. This nodule was diagnosed by CT-guided biopsy as squamous cell carcinoma. CONCLUSION: FDG-PET scanning detected mediastinal disease in two patients (17%) with advanced-stage head and neck squamous cell carcinoma that was not identified with conventional imaging techniques. PET imaging seems to have significant potential in the detection of occult metastatic disease, particularly in the mediastinal lymphatics.

Aged↗

Lipoprotein lipase D9N, N291S and S447X polymorphisms: their influence on premature coronary heart disease and plasma lipids.

Lipoprotein lipase (LPL) plays a pivotal role in lipoprotein metabolism. Three recently described exonic polymorphisms of the gene, D9N, N291S and S447X, have been variably found to influence plasma lipids while effects on coronary heart disease (CHD) are less well documented. Two predominantly Caucasian groups were studied: CHD patients <50 years of age, with angiographically documented CHD; and a randomly recruited community control group without a history of heart disease. The 9N allele of the D9N polymorphism was present in 25 of 428 (5.8%) of Caucasian males with CHD and in seven of 291 (2.4%) of corresponding community subjects (odds ratio, 2.5; 95% confidence interval (CI), 1.1-5.9; P=0.03) and was also significantly over-represented in the Caucasian males with myocardial infarction (MI) (21 of 308 or 6.8%; odds ratio, 2.6; 95% CI, 1.1-5.9; P=0.01). The distributions of the other two polymorphisms were similar in the CHD and community groups. In multivariate models adjusted for age, sex, diabetes, body mass index, smoking, lipid levels and race, the D9N polymorphism remained significantly related to both CHD and MI, with an odds ratio >2. There were, generally, trends to more adverse fasting plasma high-density lipoprotein (HDL) cholesterol and triglycerides in carriers of the 291S and 9N alleles, and the opposite trends for triglycerides in 447X carriers. In the community group, male carriers of 291S (n=13) had significantly (20%) lower HDL cholesterol than corresponding non-carriers (n=323), 0.98+/-0.07 mmol/l (mean+/-S.E.) versus 1.22+/-0.02 mmol/l (P<0.005), while HDL cholesterol was not different in male carriers (n=8) and non-carriers (n=296) of 9N (1.23+/-0.13 mmol/l versus 1.22+/-0.02 mmol/l). Multivariate analysis confirmed that the 291S allele carrier status conferred a significantly lower HDL cholesterol (P=0.001) and the 447X allele lower triglyceride (P<0.01) in the community group. In conclusion, LPL 9N carrier status was unequivocally related to premature CHD and to MI in males, strongly supporting recent results in older aged males. The somewhat different effects of the D9N and N291S polymorphisms on plasma lipids, and the absence of a clear effect of the N291S on CHD, raise the possibility that the effect of 9N carrier status might be mediated through effects on LPL function in addition to those influencing fasting plasma lipids.

Adult↗

Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals.

The base of the cochlea is more vulnerable to trauma than the apex as seen in the pattern of hair cell damage by cisplatin or aminoglycosides. The differential vulnerability is maintained in organotypic cultures exposed directly to these drugs, suggesting there may be an intrinsic difference in sensitivity to damage along the cochlear spiral. We therefore investigated the survival capacity of isolated outer hair cells and strips dissected from different turns of the guinea pig organ of Corti in short-term culture. Cells were stained with fluorescent indicators of viable or dead cells, calcein-AM and ethidium homodimer. After 5 h at room temperature, up to 90% of outer hair cells from the apex survived, but less than 30% from the base. In contrast, basal inner hair cells remained viable, and supporting cells survived for at least 20 h. The difference in survival capacity between basal and apical outer hair cells coincided with a significantly lower level of the antioxidant glutathione in basal outer hair cells compared with apical outer hair cells. This suggested that basal outer hair cells may be more vulnerable to free-radical damage than apical outer hair cells. The survival of basal outer hair cells was significantly improved by addition of the radical scavengers n-acetyl cysteine, p-phenylenediamine, glutathione, mannitol or salicylate. The protection by antioxidants implies that the accelerated death of basal outer hair cells is due to free-radical damage. The results support an intrinsic susceptibility to free radicals that differs among cochlear cell populations. This differential provides a rational explanation for base-to-apex gradients observed in various forms of cochlear pathology.

Animals↗

The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes.

OBJECTIVES: The purpose of this study was to examine whether exercise training stimulates a generalized improvement in vascular function in patients with type 2 diabetes mellitus. BACKGROUND: Exercise is often recommended for patients with type 2 diabetes to improve physical conditioning and glycemic control. This study examined the effect of eight weeks of exercise training on conduit and resistance vessel function in patients with type 2 diabetes, using a randomized crossover design. METHODS: Both resistance vessel endothelium-dependent and -independent functions were determined by forearm plethysmography and intrabrachial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively, in 16 patients with type 2 diabetes. Conduit vessel endothelial function was assessed in 15 of these patients using high-resolution ultrasound and flow-mediated dilation of the brachial artery; glyceryl trinitrate (GTN) was used as an endothelium-independent dilator. RESULTS: Flow-mediated dilation increased from 1.7 +/- 0.5% to 5.0 +/- 0.4% following training (p < 0.001). The forearm blood flow ratio to ACh was significantly improved (analysis of variance, p < 0.05). Responses to SNP and GTN were unchanged. Endothelium-dependent vasodilation was enhanced in both conduit and resistance vessels. CONCLUSIONS: If endothelial dysfunction is an integral component of the pathogenesis of vascular disease, as currently believed, this study supports the value of an exercise program in the management of type 2 diabetes.

Diabetes Mellitus, Type 2↗