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Biomedical subjects

David Thomas

Publications and source records attributed to David Thomas.

At least 19 recordsLinked to original sources
PubMed2006

Multidisciplinary approach to diagnosis and management of osteosarcoma - a review of the St Vincent's Hospital experience.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumour in children and young adults. Despite advances in the diagnosis and management of osteosarcoma, there have been few recent studies describing the experiences of tertiary referral centres. This paper aims to describe and discuss the clinical features, pre-operative work-up, management and outcomes of these patients at St Vincent's Hospital (Melbourne, Australia). METHODS: Retrospective study of fifty-nine consecutive patients managed for osteosarcoma at St Vincent's Hospital between 1995 and 2005. RESULTS: Median age at diagnosis was 21 (range, 11-84) years. Gender distribution was similar, with thirty-one male and twenty-eight female patients.Twenty-five patients had osteosarcoma in the femur, eleven each were located in the humerus and tibia, six were identified in the pelvis, and one each in the clavicle, maxilla, fibula, sacrum, ulna and radius.Pre-operative tissue diagnosis of osteosarcoma was obtained through computed tomography-guided percutaneous biopsy in over ninety percent of patients. Following initial therapy, over fifty percent of patients remained relapse-free during the follow-up period, with twelve percent and twenty-seven percent of patients documented as having local and distant disease recurrence, respectively. Of patients with recurrent disease, sixty-two percent remained disease-free following subsequent surgical intervention (most commonly, pulmonary metastatectomy). CONCLUSION: Patient outcomes can be optimised through a multidisciplinary approach in a tertiary referral centre. At St Vincent's Hospital, survival and relapse rates of patients managed for osteosarcoma compare favourably with the published literature.

Journal Article↗
PubMed2006

Role of the human supplementary eye field in the control of saccadic eye movements.

The precise function of the supplementary eye field (SEF) is poorly understood. Although electrophysiological and functional imaging studies are important for demonstrating when SEF neurones are active, lesion studies are critical to establish the functions for which the SEF is essential. Here we report a series of investigations performed on an extremely rare individual with a highly focal lesion of the medial frontal cortex. High-resolution structural imaging demonstrated that his lesion was confined to the region of the left paracentral sulcus, the anatomical locus of the SEF. Behavioural testing revealed that the patient was significantly impaired when required to switch between anti- and pro-saccades, when there were conflicting rules governing stimulus-response mappings for saccades. Similarly, the results of an arbitrary stimulus-response associative learning task demonstrated that he was impaired when required to select the appropriate saccade from conflicting eye movement responses, but not for limb movements on an analogous manual task. When making memory-guided saccadic sequences, the patient demonstrated hypometria, like patients with Parkinson's disease, but had no significant difficulties in reproducing the order of saccades correctly on a task that emphasized accuracy with a wide temporal segregation between responses. These findings are consistent with the hypothesis that the SEF plays a key role in implementing control when there is conflict between several, ongoing competing saccadic responses, but not when eye movements need to be made accurately in sequence.

Association Learning↗
PubMed2006

Gas sensor array based on metal-decorated carbon nanotubes.

Here we demonstrate design, fabrication, and testing of electronic sensor array based on single-walled carbon nanotubes (SWNTs). Multiple sensor elements consisting of isolated networks of SWNTs were integrated into Si chips by chemical vapor deposition (CVD) and photolithography processes. For chemical selectivity, SWNTs were decorated with metal nanoparticles. The differences in catalytic activity of 18 catalytic metals for detection of H(2), CH(4), CO, and H(2)S gases were observed. Furthermore, a sensor array was fabricated by site-selective electroplating of Pd, Pt, Rh, and Au metals on isolated SWNT networks located on a single chip. The resulting electronic sensor array, which was comprised of several functional SWNT network sensors, was exposed to a randomized series of toxic/combustible gases. Electronic responses of all sensor elements were recorded and the sensor array data was analyzed using pattern-recognition analysis tools. Applications of these small-size, low-power, electronic sensor arrays are in the detection and identification of toxic/combustible gases for personal safety and air pollution monitoring.

Journal Article↗
PubMed2006

Cortical serotonin7, 1D and 1F receptors: effects of schizophrenia, suicide and antipsychotic drug treatment.

Abnormalities in serotonergic function are thought to be important in the pathology of schizophrenia. Postmortem CNS studies suggest that levels of serotonin receptors may be altered in the cortex of subjects with schizophrenia. Seeking to expand this hypothesis we have examined the effect of schizophrenia and antipsychotic drug treatments on the levels of cortical serotonin7, 1D and 1F receptors. There was a significant decrease in the binding of [3H]SB 269970 to the serotonin7 receptor in Brodmann's area 9 from subjects with schizophrenia compared to controls (Mean+/-S.E.M.: 8.3+/-0.76 vs. 11.0+/-0.64 fmol/mg ETE; p<0.05) and an increase in the binding of that radioligand in the cortex of rats treated with haloperidol (p=0.03). There were no significant differences in [3H]sumatriptan binding to the serotonin1D or serotonin1F receptor in Brodmann's area 9 from subjects with schizophrenia. There was a significant increase in [3H]sumatriptan binding to the serotonin1D in binding Layer 2 from subjects who had potentially died by suicide that was not present in other binding layers or for the serotonin1F or serotonin7 receptors. There was decrease in [3H]sumatriptan binding to the serotonin1D, but not serotonin1F, receptors across all cortical binding layers in rats treated with haloperidol. These data would be consistent with the hypothesis that decreased levels of serotonin7 receptors in Brodmann's area 9 may be involved in the pathological processes of schizophrenia and that levels of cortical serotonin7 and 1D receptors can be affected by antipsychotic drug treatment.

Adult↗
PubMed2006

The use of a Monte Carlo method for uncertainty calculation, with an application to the measurement of neutron ambient dose equivalent rate.

This paper is concerned with the use of a Monte Carlo method for uncertainty calculation as an implementation of the propagation of distributions. It reviews the basic principles of the propagation of distributions and numerical aspects of a Monte Carlo implementation. It also discusses the possible advantages in some circumstances of the propagation of distributions over the GUM uncertainty framework, and how the results obtained in any particular instance can be compared with those provided by that framework. To illustrate these various aspects, an application to the measurement of neutron dose equivalent rate is given. A key consideration in this application is the manner in which the dominant source of uncertainty, namely that associated with the field-specific correction factor, is treated. The information available concerning this factor constitutes the correction factors for a set of fields of the same type as that in which a measurement is being made. This information is encoded as a probability density function (PDF) for the correction factor. This PDF constitutes an input to both methods of evaluation.

Anisotropy↗
PubMed2006

Epigenetic modifications in osteogenic differentiation and transformation.

Almost all tumors are characterized by both architectural and cellular abnormalities in differentiation. Osteoblast development is relatively well understood, making osteosarcoma a good model for understanding how tumorigenesis perturbs normal differentiation. We argue that there are two key transition points in normal cellular differentiation that are the focus of oncogenic events, in both of which epigenetic processes are critical. The first is the transition from an uncommitted pluripotent precursor (mesenchymal stem cell) to the 'transit-amplifying compartment' of the osteoblast lineage. This transition, normally exquisitely regulated in space and time, is abnormal in cancer. The second involves termination of lineage expansion, equally tightly regulated under normal circumstances. In cancer, the mechanisms that mandate eventual cessation of cell division are almost universally disrupted. This model predicts that key differentiation genes in bone, such as RUNX2, act in an oncogenic fashion to initiate entry into a proliferative phase of cell differentiation, and anti-oncogenically into the post-mitotic state, resulting in ambivalent roles in tumorigenesis. Polycomb genes exemplify epigenetic processes in the stem cell compartment and tumorigenesis, and are implicated in skeletal development in vivo. The epigenetic functions of the retinoblastoma protein, which plays a key role in tumorigenesis in bone, is discussed in the context of terminal cell cycle exit.

Animals↗
PubMed2006

Quality-of-life valuations of advanced breast cancer by New Zealand women.

OBJECTIVES: To obtain health-related quality-of-life (HR-QOL) valuations (or 'utilities') from New Zealand women for four health states representative of advanced (metastatic) breast cancer, suitable for use in cost-utility analysis, and to compare four valuation methodologies. METHODS: Written case descriptions of four health states representative of advanced breast cancer (hormonal therapy, chemotherapy, radiotherapy and hypercalcaemia) were developed in consultation with nine oncology professionals. Time trade-off (TTO) and visual analogue scale (VAS) valuations were obtained via interviews from a sample of 50 women, aged 25-69 years, randomly selected from the New Zealand general public and through informal networks. Representations of the four health states on the EQ-5D health state classification system were also obtained from the respondents and later valued using New Zealand and UK EQ-5D social tariffs. RESULTS: The four valuation methods ranked the four states' mean valuations identically: hormonal therapy > chemotherapy > or = radiotherapy > hypercalcaemia. All methods except the TTO distinguished between chemotherapy and radiotherapy. In order of the VAS and TTO methods and the EQ-5D with NZ and UK tariffs, respectively, the valuations [mean (95% CI)] were: hormonal therapy 0.54 (0.48, 0.59); 0.65 (0.57, 0.73); 0.54 (0.51, 0.58); 0.60 (0.54, 0.65); chemotherapy 0.46 (0.41, 0.51); 0.49 (0.40, 0.57); 0.48 (0.43, 0.53); 0.51 (0.43, 0.59); radiotherapy for severe bone pain 0.35 (0.30, 0.40); 0.45 (0.37, 0.54); 0.31 (0.27, 0.35); 0.25 (0.18, 0.33); and moderate to severe hypercalcaemia 0.13 (0.09, 0.17); -0.17 (-0.29, -0.05); -0.05 (-0.07, -0.03); -0.52 (-0.56, -0.48). The four valuation methods gave similar results for chemotherapy, but for the three other states the TTO valuations differed from those obtained from the VAS method and the NZ and UK EQ-5D tariffs. There were significant pairwise correlations between the four methods across all four health states, although the valuation for hypercalcaemia obtained from the UK EQ-5D tariff was very low compared with the three other methods, and the VAS valuation was positive rather than negative. CONCLUSION: Our study suggests that women in the New Zealand general public are able to consistently evaluate and value case descriptions of advanced breast cancer using either direct methods (VAS or TTO) or the EQ-5D health state classification system. Some of the valuations elicited using the four methods differ quantitatively, especially for hypercalcaemia. As our sample size was modest (50) and it turned out to be unrepresentative of the New Zealand female population, this study serves as a pilot study.

Adult↗
PubMed2006

Brain tumors and occupational exposures in a cohort of female textile workers in Shanghai, China.

OBJECTIVES: This study assessed the associations between brain tumors and specific processes and exposures among female textile workers in Shanghai, China. METHODS: A case-cohort study was conducted that was nested in a cohort of textile workers originally included in a randomized trial of breast self-examination. Incident brain tumor cases (N=114) were identified from 1989 to 1998 from a tumor and death registry operated by the Shanghai Textile Industry Bureau. A subcohort (N=3188), representing an age-stratified random sample of the entire cohort, was selected as a comparison group. Job-exposure matrices were created to assess historical exposures to specific agents, including quantitative assessments for cotton dust and endotoxin exposure. Cox proportional hazards modeling, modified according to a case-cohort design, was used to analyze associations between jobs and exposures and the risk of brain tumors. RESULTS: Employment in maintenance workshops was associated with an increased brain tumor incidence (ever-never exposed hazard ratio 2.36, 95% confidence interval 1.12-4.97), with increasing hazard ratios by duration of employment in maintenance jobs. Handling or processing wool fibers was associated with an increased risk of brain tumors, as was specific exposure to wool fibers; however, estimates did not increase with duration of employment. CONCLUSIONS: These results provide some preliminary suggestion that employment in textile industry maintenance jobs and exposure to wool products may be associated with an increased risk of brain tumors.

Aged↗
PubMed2006

Hepatitis C infection among drug users in northern Thailand.

Illicit drug users are commonly infected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV). We evaluated the prevalence, incidence, and risk behaviors associated with HCV infection in 1,859 drug users in northern Thailand. The HCV prevalence was 27.3%: 86.0% among drug injectors (IDUs) and 5.3% among those who did not inject. Sexual behavior was not significantly associated with HCV among IDUs or drug users who used but didn't inject illicit drugs; only injection behaviors were independently associated with HCV in multivariate analysis. Among men, a history and increasing frequency of injecting drugs, older age, and a history of incarceration were associated with HCV infection. Among 514 opiate users who were HCV and HIV seronegative at baseline, 41 incident HCV infections and 6 HIV infections occurred on follow-up; the HCV incidence was 5.43/100 person-years; it was 44.3/100 person-years in IDUs and 1.9/100 person-years in non-injectors. HCV and HIV among drug users in Thailand are common and primarily associated with injection behavior.

Adolescent↗
PubMed2005

Femoral mesenchymal chondrosarcoma with secondary aneurysmal bone cysts mimicking a small-cell osteosarcoma.

Mesenchymal chondrosarcoma is a rare but aggressive, high-grade malignancy of primitive cartilage-forming mesenchyme that arises most commonly from skeletal sites. Although there are radiological findings suggestive of the diagnosis, imaging features often overlap with those of other skeletal sarcomas. The definitive diagnosis relies on the histological finding of a typical bimorphic appearance, consisting of nests of small, round, poorly differentiated cells and more mature cartilaginous tissue. To highlight this, we present the case of a 21-year-old man who was referred to our institution with a history of right knee pain. Initial imaging and histological evaluation of a core biopsy of the lesion suggested osteosarcoma of the distal right femur; after review, however, the correct diagnosis of mesenchymal chondrosarcoma was made. Adequate tissue sampling and thorough histological evaluation of biopsy specimens is vital for the accurate diagnosis of primary bone malignancies, especially those of chondroid origin.

Adult↗
PubMed2005

Comparison of the uptake of health assessment items for Aboriginal and Torres Strait Islander people and other Australians: implications for policy.

BACKGROUND: Health Assessment (HA) items were introduced in 1999 for Aboriginal and Torres Strait Islander people aged at least 55 years and all Australians aged over 75 years. In 2004 a new item was introduced for HAs among adult Aboriginal and Torres Strait Islander people aged 15-54 years. The new item has been applauded as a major policy innovation however this enthusiasm has been tempered with concern about potential barriers to its uptake. In this study we aim to determine whether there are disparities in uptake of HA items for Aboriginal and Torres Strait Islander people compared to other Australians. METHOD: The analysis was based on Health Insurance Commission data. Indigenous status was ascertained based on the item number used. Logistic regression was used to compare uptake of HA items for older people among Aboriginal and Torres Strait Islander people compared to other Australians. Adjustments were made for dual eligibility. Uptake of the HA items for older people was compared to the uptake of the new item for Aboriginal and Torres Strait Islander people aged 15-44 years. RESULTS: Our analyses suggest a significant and persistent disparity in the uptake of items for older patients among Aboriginal and Torres Strait Islander people compared to other Australians. A similar disparity appears to exist in the uptake of the new adult Aboriginal and Torres Strait Islander HA item. CONCLUSION: Further engagement of primary care providers and the community around the uptake of the new HA items may be required to ensure that the anticipated health benefits eventuate.

Journal Article↗
PubMed2005

A VEGF/JAK2/STAT5 axis may partially mediate endothelial cell tolerance to hypoxia.

Perturbation of oxygen flow occurs in disease states such as diabetic retinopathy and cancer. To maintain oxygen homoeostasis, the mammalian microvascular endothelium undergoes a dramatic reorganization to assist in bringing oxygen and nutrients to oxygen-starved tissues. This process is termed angiogenesis and is common in certain cancers with hypoxic foci and in areas of focal ischaemia in the diabetic retina. In the present study, we report on the activation of the JAK2/STAT5 pathway (where JAK stands for Janus kinase and STAT stands for signal transduction and activator of transcription) by low oxygen in microvascular endothelial cells. This activation appears to occur downstream of VEGF (vascular endothelial growth factor), a well-known proangiogenic factor, and is related to repression of proapoptotic FAS(CD95)/FASL(CD95L). These results indicate that the JAK/STAT pathway may play a pivotal role during tumour-associated or retinal angiogenesis in which endothelial cell survival during tissue hypoxia is critical for maintaining either the growth of neoplasms or the inappropriate retinal neovascularization common in diabetic retinopathy.

Animals↗
PubMed2005

Essential oil poisoning: N-acetylcysteine for eugenol-induced hepatic failure and analysis of a national database.

UNLABELLED: We present a 15-month-old boy who developed fulminant hepatic failure after ingesting 10 ml of clove oil. After 24 h, the ALT level was in excess of 13,000 U/l, with blood urea and creatinine of 11.8 mmol and 134 micromol/l respectively. The hepatic impairment resolved after intravenous administration of N-acetylcysteine so that 6 h later, the ALT level was approximately 10,000 U/l. His liver synthetic function and clinical status improved over the next 4 days. This is the first such case report of its kind in Europe. Analysis of a national database revealed a 14-fold increase in home accidents related to aromatherapy from 1994-1999. Clove oil has important hepatotoxic effects. CONCLUSION: Recent growth in aromatherapy sales has been accompanied by an unfortunate increase in accidental poisoning from these products. Clove oil warrants special attention. Ingesting as little as 10 ml causes hepatotoxicity which can be treated with N-acetylcysteine.

Accidents, Home↗
PubMed2005

Association of sex, hygiene and drug equipment sharing with hepatitis C virus infection among non-injecting drug users in New York City.

BACKGROUND: Hepatitis C virus (HCV) rates are higher in non-injecting drug users (NIDUs) than general population estimates. Whether this elevated HCV rate is due to drug use or other putative risk behaviors remains unclear. METHODS: Recent non-injection drug users of heroin, crack and/or cocaine were street-recruited from 2000 to 2003 and underwent an interview and venipuncture for HCV antibody assays. Multiple logistic regression analyses were used to assess correlates for HCV infection. RESULTS: Of 740 enrollees, 3.9% were HCV positive. The median age (intraquartile range) was 30 (35-24) years, 70% were male and 90% were Black or Hispanic. After adjustment, HCV seropositives were significantly more likely than seronegatives to be older than 30 [adjusted odds ratio (AOR)=5.71], tattooed by a friend/relative/acquaintance [AOR=3.61] and know someone with HCV [AOR=4.29], but were less likely to have shared nail or hair clippers, razors or a toothbrush [AOR=0.32]. CONCLUSIONS: Non-commercial tattooing may be a mode of HCV transmission among NIDUs and education on the potential risk in using non-sterile tattooing equipment should be targeted toward this population. While no evidence was found for HCV transmission through NIDU equipment sharing or sexual risk behavior, further research is still warranted.

Adult↗
PubMed2005

Discovery of functionally selective 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazines as GABA A receptor agonists at the alpha3 subunit.

We have previously identified the 7,8,9,10-tetrahydro-7,10-ethano-1,2,4-triazolo[3,4-a]phthalazine (1) as a potent partial agonist for the alpha(3) receptor subtype with 5-fold selectivity in binding affinity over alpha(1). This paper describes a detailed investigation of the substituents on this core structure at both the 3- and 6-positions. Despite evaluating a wide range of groups, the maximum selectivity that could be achieved in terms of affinity for the alpha(3) subtype over the alpha(1) subtype was 12-fold (for 57). Although most analogues showed no selectivity in terms of efficacy, some did show partial agonism at alpha(1) and antagonism at alpha(3) (e.g., 25 and 75). However, two analogues tested (93 and 96), both with triazole substituents in the 6-position, showed significantly higher efficacy for the alpha(3) subtype over the alpha(1) subtype. This was the first indication that selectivity in efficacy in the required direction could be achieved in this series.

Animals↗