PubMed Health⌕ Search

Biomedical subjects

Ian Anderson

Publications and source records attributed to Ian Anderson.

At least 19 recordsLinked to original sources
PubMed2006

A potent human anti-eotaxin1 antibody, CAT-213: isolation by phage display and in vitro and in vivo efficacy.

The CC chemokine, eotaxin1 (CCL11) is an important regulator of eosinophil function. A marked accumulation of eosinophils in tissues has been correlated with the up-regulation of eotaxin1 expression in several diseases. The potential therapeutic value of neutralizing the effects of eotaxin1 in inflammatory conditions (including asthma) is under investigation. A human single-chain fragment variable antibody that neutralizes human eotaxin1 (CAT-212) was produced using antibody phage display and converted to whole antibody IgG4 format (CAT-213). A novel approach to lead optimization in which the length of the variable heavy chain complementarity-determining region 3 was reduced by one amino acid resulted in an increase in potency of >1000-fold compared with the parent anti-eotaxin1 antibody. The optimized antibody binds eotaxin1 with high affinity (80.4 pM) and specificity. CAT-213 and CAT-212 do not bind or neutralize a range of other human proteins including human monocyte chemoattractant protein-1, a structurally similar chemokine. CAT-213 neutralizes the ability of eotaxin1 to cause an increase in intracellular calcium signaling (with an IC(50) value of 2.86 nM), migration of CCR3-expressing L1.2 cells (with an IC(50) value of 0.48 nM), and inhibition of the eotaxin1-evoked shape change of human eosinophils in vitro (with an IC(50) of 0.71 nM). Local administration of CAT-213 to mice (1-100 microg kg(-1)) attenuates dermal eosinophilia induced by human eotaxin1, achieving >90% inhibition of eosinophil influx. CAT-213 may therefore be of therapeutic value in inhibiting diseases in which eotaxin1 and eosinophils play a major role, for example, severe asthma.

Algorithms↗
PubMed2006

Indigenous health in Australia, New Zealand, and the Pacific.

We survey Indigenous health issues across the Pacific with a case study approach that focuses on Australia, New Zealand, Hawai'i, and US Associated Micronesia. For each case study, we provide an overview of the Indigenous population, its colonial history, and current health and social outcomes. In the discussion that follows, we flag some of the key policy initiatives that have been developed to address Indigenous health disadvantage, albeit within the context of continuing debates about Indigenous rights and policy.

Aged↗
PubMed2006

Improving access to medicines among clients of remote area Aboriginal and Torres Strait Islander Health Services.

Despite unequivocally worse health, expenditure on Indigenous people through the Pharmaceutical Benefits Scheme (PBS) is considerably less than for other Australians. We report on the effectiveness of a program to supply PBS medicines to remote Aboriginal and Torres Strait Islander Health Services (ATSIHSs) under section 100 (s. 100) of the National Health Act 1953. THE PROGRAM: Under the special PBS arrangements (SPBSAs), approved ATSIHSs are able to order PBS medicine in bulk through local pharmacies and supply them as needed to patients on-site. The usual co-payment associated with PBS medicine is not charged and the pharmacist remuneration structure is different. METHODS: The project involved consultation with the evaluation reference group and other stakeholders at all stages. There were six main data collection components: public submissions; interviews with government and other key stakeholders; pharmacist survey; medicine utilisation and expenditure data; national ATSIHS minimum dataset; and case studies of ATSIHSs. RESULTS: These SPBSA potentially benefit 36% of the Aboriginal and Torres Strait Islander population. They have resulted in improved access to much-needed medicines, representing an increase of dollar 36.5 million in expenditure on Aboriginal and Torres Strait Islander people through the PBS between 2000/01 and 2002/03. They have further ensured that dollar 8.3 million of State and Territory expenditure formerly directed at medicine can be spent on prevention and primary care. CONCLUSION: Overall, the SPBSAs have been very successful and demonstrates an effective model for the development of Indigenous health policy.

Australia↗
PubMed2006

Differential regulation of key stages in early corneal wound healing by TGF-beta isoforms and their inhibitors.

PURPOSE: Inhibition of TGF-beta reduces myofibroblast differentiation and fibrosis in the cornea. Determining the actions of distinct TGF-beta isoforms and their inhibitors during early corneal wound healing is an essential step in guiding therapeutic intervention. METHODS: Bovine serum-free corneal cell and wounded organ cultures were challenged with a range of concentrations of TGF-beta1, -beta2, and -beta3; IL-10; and neutralizing human monoclonal antibodies (mAbs) against TGF-beta1 (CAT-192) or -beta2, (CAT-152). Cultures were assessed for re-epithelialization, proliferation (cell counts and cresyl violet assay), morphology (histologic examination), repopulation of the area under the wound, and myofibroblast transformation (alpha-smooth muscle actin) between 0 and 5 days. RESULTS: TGF-beta1 delayed re-epithelialization, increased repopulation of the stroma, increased keratocyte proliferation and was the only isoform to promote myofibroblast differentiation. The anti-TGF-beta1 mAb, CAT-192 promoted re-epithelialization and reduced repopulation of the stroma. Exogenous TGF-beta3 had little effect on re-epithelialization but reduced repopulation of the stroma. IL-10 promoted corneal re-epithelialization at low doses but inhibited this response at high doses. Stromal repopulation was prevented by all doses of IL-10. TGF-beta2 or the anti-TGF-beta2 mAb, CAT-152 had little effect on any repair parameter. CONCLUSIONS: The results confirm TGF-beta1 as the principal isoform in corneal wound healing and suggest that inhibition of the action of TGF-beta1 can promote corneal wound healing. Treatment with the anti-TGF-beta1 mAb CAT-192 accelerates corneal re-epithelialization but reduces cell repopulation of the stroma. The cytokines TGF-beta3 and IL-10 have opposing actions to that of TGF-beta1.

Animals↗
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

Moving beyond good intentions: indigenous participation in aboriginal and Torres Strait islander health research.

Indigenous participation in every aspect of health research is increasingly recognised as an important element of any research project that aims to improve Indigenous health. Despite the acceptance of its importance, when the concept of 'Indigenous participation' is mentioned, authors are often imprecise as to the nature and purpose of participation, and its relationship to improved health outcomes. This report attempts to bring some clarity to the variety of meanings we might give Indigenous participation in research. For the purposes of stimulating further debate, we identify four distinct, but overlapping, rationales: pragmatic, moral, interventionist, and epistemological. Each has different implications for how Indigenous participation should be implemented and evaluated. More debate on the meanings and purposes of Indigenous participation will contribute to a refined understanding of its potential benefits to health research.

Decision Making↗
PubMed2004

Neurobiological substrates of antisocial and borderline personality disorder: preliminary results of a functional fMRI study.

BACKGROUND: Neuropsychological and imaging studies of patients with antisocial (ASPD) and borderline personality disorder (BPD) are suggestive of frontal lobe dysfunction in these individuals. In normal subjects functional brain imaging has been used to investigate the neuroanatomy of impulse control. There are no such imaging studies in personality-disordered populations. AIM: This study aimed to investigate which neuronal networks are involved in response inhibition in Cluster B personality disorders and whether these are different from healthy subjects. HYPOTHESIS: We hypothesized that the personality-disordered sample would have attenuated orbitofrontal cortex responses during performance of a Go/NoGo task compared with healthy controls. METHOD: Eight inpatients with a DSM-IV diagnosis of borderline or antisocial personality disorder and eight healthy controls were scanned using fMRI while performing a Go/NoGo task. Impulsivity was assessed using the Barratt Impulsivity Scale (BIS) and the Impulsiveness-Venturesomeness-Empathy (IVE) inventory. RESULTS: In the control group the main focus of activation during response inhibition was in the prefrontal cortex, specifically the right dorsolateral and the left orbitofrontal cortex. Active regions in the patient group showed a more bilateral and extended pattern of activation across the medial, superior and inferior frontal gyri extending to the anterior cingulate. CONCLUSIONS: fMRI is a useful tool to detect brain activation during response inhibition. ASPD and BPD patients activate different neural networks to successfully inhibit pre-potent responses.

Adult↗
PubMed2004

Treatment of irregular astigmatism with a 213 nm solid-state, diode-pumped neodymium:YAG ablative laser.

PURPOSE: To present the outcome of photorefractive keratectomy (PRK) using a new neodymium:YAG (Nd:YAG) laser in patients with irregular astigmatism. SETTING: Claremont Eye Clinic, Claremont, and the University of Western Australia, Perth, Australia. METHODS: In 3 patients with irregular astigmatism, PRK was performed with a solid-state, 213 nm wavelength, 300 Hz scanning-spot, diode-pumped Nd:YAG ablative laser (CustomVis Pulzar laser system). The 3 patients had had previous PRK with penetrating keratoplasty, astigmatic keratotomy, or limbal relaxing incisions. At 3 and 6 months, best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), manifest refraction, contrast sensitivity, and corneal topography were measured. RESULTS: The first patient had a 1-line improvement in BSCVA and a 4-line improvement in UCVA, a 3.00 diopter (D) decrease in keratometric cylinder, and improvement in contrast sensitivity. The second patient had a 7.00 D decrease in myopia in 1 meridian and a 4.25 D decrease in the refractive cylinder in the other meridian. The third patient had a 2-line improvement in BSCVA, a 5-line improvement in UCVA, a 2.00 D decrease in the refractive cylinder, and improvement in contrast sensitivity. CONCLUSION: The laser's combination of a small spot, a fast pulse rate, and ultrafast tracking/scanning resulted in good results in 3 patients with difficult irregular astigmatism.

Adult↗
PubMed2004

Combining TGF-beta inhibition and angiotensin II blockade results in enhanced antifibrotic effect.

BACKGROUND: Although angiotensin II (Ang II) blockade is rapidly becoming standard antifibrotic therapy in renal diseases, current data suggest that Ang II blockade alone cannot stop fibrotic disease. New therapies, such as antibodies to transforming growth factor-beta (TGF-beta), or drug combinations will be required to further slow or halt disease progression. Here, using the anti-Thy1 model of glomerulonephritis, the maximally therapeutic dose of the TGF-beta neutralizing mouse monoclonal antibody (1D11) was determined and compared with the maximally effective dose of enalapril. Then, the effect of combining both treatments at maximal doses was determined. METHODS: After disease induction with the anti-Thy1 antibody, OX-7, increasing doses of 1D11 were given intraperitoneally (IP) on days 1, 3, and 5. Enalapril was administered in drinking water from day 1. The fibrotic response was assessed at day 6. RESULTS: 1D11 dose-dependently reduced fibrosis, with the 0.5 and 5 mg/kg doses showing maximal therapeutic effects, reducing period-acid Schiff (PAS) staining by 56% and 45%, respectively. Fibronectin and collagen I staining was reduced by 32% to 36%, respectively. Glomerular mRNA and production of fibronectin, plasminogen activator inhibitor-1 (PAI-1), TGF-beta1, and p-Smad2 protein were also reduced. The maximal therapeutic effects of 1D11 and enalapril alone were very similar. However, combination therapy led to further reduction in disease. Notably, matrix deposition was reduced by 80%. CONCLUSION: While 1D11 or enalapril at maximal doses reduce fibrosis equally, simultaneous blockade of Ang II and TGF-beta reduces fibrotic disease considerably more, offering hope that such drug combinations may confer a therapeutic advantage over angiotensin blockade alone.

Angiotensin II↗
PubMed2003

Ethics guidelines, health research and Indigenous Australians.

In this paper we overview the findings of a literature review that was undertaken to guide the revision of the Guidelines on Ethical Matters in Aboriginal and Torres Strait Islander Health Research (NH&MRC, 1991). The literature reviewed, in general, supported the development of specific research guidelines for Aboriginal and Torres Strait Islander contexts. The findings of this review were analysed thematically, and a number of key issues were identified for consideration in the review process. We present a summary of these key issues. In the final section of the paper we consider in more detail two of the key issues raised in the review process (the assessment of relevance or benefit of proposed research; and the process of consultation and negotiation of collective consent) in order to critically consider how these issue should be engaged in revised guidelines. On the basis of this analysis, it is our contention that specific guidelines on key issues are limited to the extent to which they can anticipate all possible research contexts. In order to address this problem, and guide researchers, guidelines should also explicitly outline the values, from an Aboriginal and Torres Islander perspective that are foundational to an ethical research process.

Advisory Committees↗
PubMed2002

Researching Aboriginal health: experience from a study of urban young people's health and well-being.

European colonisation had a devastating effect on the health and well-being of indigenous people in Australia. The history of Aboriginal health research has reflected the history of colonisation; research has understandably been viewed with distrust. The need for accurate statistics and improved understanding of health problems is clear, but obtaining them is not easy. In this paper we describe the first stage of a study of the health and well-being of urban young people that was initiated and carried out by the Victorian Aboriginal Health Service (VAHS), a community controlled organisation. This longitudinal study aims to describe the prevalence and incidence of a range of health problems, to explore their interrelated determinants, and to increase the capacity of the VAHS to carry out research. The process of planning and carrying out this study raised a number of interesting ethical, cultural and methodological issues. These issues include the establishment of an appropriate and properly constituted local ethics committee, the difficulty of obtaining a representative sample, the need for ongoing negotiation, attention to language, the use of a subject-generated identity code, and the need to recruit a wide range of peer interviewers. Achievements include a series of community reports of the findings, the establishment of a cohort of young people for a longitudinal study; a shift in attitudes toward research; a strengthened network of young Kooris; increased use of the health service by young people and the establishment of an after-hours clinic service and meeting place for young people. The aim of this analysis of our achievements and constraints is to assist others planning similar research, and to demonstrate the value for process and outcomes of research conducted under Aboriginal community control.

Adolescent↗
PubMed2002

Linking acute care to a strategy for improving Aboriginal health.

In this paper we consider the extent to which strategies to improve access to acute care services have been integrated with national strategies to improve Aboriginal health outcomes. To do this we review the primary and secondary sources and provide an overview of current national strategy in Aboriginal health and identify where policy and strategic issues relevant to acute care have been developed. In particular we consider the extent to which national policy processes have focussed on the interface between the primary and acute sectors. It is our contention that nationally integrated strategies to improve access to the acute care sector require the development of an Aboriginal health focus in hospital based quality assurance processes and a comprehensive engagement with Aboriginal issues across the acute care sector.

Australia↗
PubMed2002

Efficacy and tolerability of venlafaxine compared with selective serotonin reuptake inhibitors and other antidepressants: a meta-analysis.

BACKGROUND: In individual studies and limited meta-analyses venlafaxine has been reported to be more effective than comparator antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). AIMS: To perform a systematic review of all such studies. METHOD: We conducted a systematic review of double-blind, randomised trials comparing venlafaxine with alternative antidepressants in the treatment of depression. The primary outcome was the difference in final depression rating scale value, expressed as a standardised effect size. Secondary outcomes were response rate, remission rate and tolerability. RESULTS: A total of 32 randomised trials were included. Venlafaxine was more effective than other antidepressants (standardised effect size was -0.14, 95% Cl -0.07 to -0.22). A similar significant advantage was found against SSRIs (20 studies) but not tricyclic antidepressants (7 studies). CONCLUSIONS: Venlafaxine has greater efficacy than SSRIs although there is uncertainty in comparison with other antidepressants. Further studies are required to determine the clinical importance of this finding.

Adult↗