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Search Results: 1 - 10 of 1985 matches for " Iain Robertson "
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Alhossain A. Khalafallah,Kristina McDonnell,Hizb U. Dawar,Iain Robertson
Mediterranean Journal of Hematology and Infectious Diseases , 2011, DOI: 10.4084/mjhid.2011.
Abstract: Few studies exist that consider health-related quality of life (HR-QOL) in patients with multiple myeloma (MM) undergoing tandem autologous stem cell transplantation (TASCT). Eighteen patients with advanced MM who underwent dose-modified TASCT were enrolled in this study between March 2006 and March 2008. Patients <60 year old (10) received conditioning with melphalan 140 mg/m2 and patients who were ≥60 years (8) received 100 mg/m2. The median age was 57.5 years (range 35-69). We conducted the European Organization of Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire via interviews at presentation, after each ASCT and thereafter every 3 months for 24 months. Mean global health measure improved from 3.44 before transplant to 4.50 (1=very poor, 7=excellent) at the second and subsequent follow-up visits (P<0.001) and the mean global quality of life score improved from 3.61 to 4.71 (P<0.001). Pain symptom was reduced (P=0.001), and physical functioning improved (P<0.001) throughout the period of post-transplant follow-up. Our study showed that dose-reduced TASCT is well tolerated with low toxicity albeit the transient reduction in QOL during both transplants. Post-transplant follow-up showed significant improvement in overall HR-QOL that reflects positively in the overall disease-outcome. The EORTC-QLQ-C30 is a practical tool in measuring QOL in myeloma patients.
The Lipid lowering and Onset of Renal Disease (LORD) Trial: A randomized double blind placebo controlled trial assessing the effect of atorvastatin on the progression of kidney disease
Robert G Fassett, Madeleine J Ball, Iain K Robertson, Dominic P Geraghty, Jeff S Coombes
BMC Nephrology , 2008, DOI: 10.1186/1471-2369-9-4
Abstract: The Lipid lowering and Onset of Renal Disease (LORD) trial is a three-year, single center, multi-site, double blind, randomized, placebo controlled trial. The primary outcome measure is kidney function measured by eGFR calculated by both Modification of Diet in Renal Disease (MDRD) and Cockcroft and Gault equations. Secondary outcome measures include kidney function measured by 24-hour urine creatinine clearance and also 24-hour urinary protein excretion, markers of oxidative stress, inflammation and drug safety and tolerability.The results of this study will help determine the effectiveness and safety of atorvastatin and establish its effects on oxidative stress and inflammation in patients with CKD.ANZCTRN012605000693628End stage kidney disease (ESKD) is a major health problem resulting in a considerable increase in morbidity and mortality, decreased quality of life, and substantial health care costs [1]. Clinical trials attempting to slow the progression of kidney disease should be a major focus of research. As treatments directed at primary kidney diseases are few, therapies have been directed towards slowing the progression of kidney disease by controlling hypertension, using angiotensin converting enzyme inhibitors (ACEI's) and angiotensin receptor blockers (ARB's) and lowering the protein intake in the diet [2-6]. Dyslipidemia has been identified as an independent risk factor for the progression of kidney disease [7]. The deleterious effect of hyperlipidemia on the progression of kidney disease is based on a number of lines of evidence.In a large number of different animal models hyperlipidemia has been clearly shown to accelerate the progression of kidney disease [8]. There is extensive evidence for the processes involved in lipid induced kidney damage, where multiple mechanisms appear to be involved but a common initiation by hyperlipidemia is present. In addition, intervention studies have assessed the effects of statins on limiting kidney damage, again, i
erbB3 recruitment of insulin receptor substrate 1 modulates insulin-like growth factor receptor signalling in oestrogen receptor-positive breast cancer cell lines
Janice M Knowlden, Julia MW Gee, Denise Barrow, John F Robertson, Ian O Ellis, Robert I Nicholson, Iain R Hutcheson
Breast Cancer Research , 2011, DOI: 10.1186/bcr3018
Abstract: Immunoprecipitation and Western blot analysis were utilised to examine the potential association between erbB3 and IRS-1 in MCF-7, T47D and BT-474 cells in the absence and presence of the erbB3/4 ligand heregulin β1 (HRGβ1). Subsequently, the impact of a selective IGF-IR/IR inhibitor 4-anilino-5-bromo-2-[4-(2-hydroxy-3-(N, N-dimethylamino)propoxy)anilino]pyrimidine on this association and HRGβ1 signalling was assessed in these cell lines. Immunohistochemical analysis of a small cohort of ER+ breast cancer patient samples was also performed to determine the potential clinical relevance of this novel interaction.Immunoprecipitation and Western blot analysis revealed an interaction between erbB3 and IRS-1 in MCF-7, T47D and BT-474 cells, with HRGβ1 significantly enhancing this recruitment and promoting IRS-1 phosphorylation at Y612. IRS-1 participates in erbB3 signalling in MCF-7 and T47D cells as IRS-1 knockdown impaired HRGβ1 signalling. Importantly, recruitment of IRS-1 by erbB3 reduced IRS-1 association with IGF-IR in MCF-7 and T47D cells, whilst blockade of IGF-IR-enhanced erbB3-IRS-1 interaction and sensitised both cell lines to HRGβ1, allowing HRGβ1 to override IGF-IR blockade. Consequently, suppression of IRS-1 signalling enhanced the effects of IGF-IR inhibition in these cells. This novel interaction may have clinical relevance, as immunohistochemical analysis of a small ER+ breast tumour series revealed significant positive correlations between phosphorylated IRS-1 Y612 expression and total erbB3, phosphorylated Akt and Ki-67 expression.IRS-1 can be recruited to IGF-IR and erbB3 in ER+ breast cancer cells, and this provides an adaptive resistance mechanism when these receptors are targeted individually. Consequently, cotargeting IGF-IR and either erbB3 or IRS-1 should prove to be a more effective strategy for the treatment of ER+ breast cancer.There is strong experimental and clinical evidence implicating the insulin-like growth factor type I receptor (IGF-IR
Astaxanthin vs placebo on arterial stiffness, oxidative stress and inflammation in renal transplant patients (Xanthin): a randomised controlled trial
Robert G Fassett, Helen Healy, Ritza Driver, Iain K Robertson, Dominic P Geraghty, James E Sharman, Jeff S Coombes
BMC Nephrology , 2008, DOI: 10.1186/1471-2369-9-17
Abstract: This is a randomised, placebo controlled clinical trial. A total of 66 renal transplant recipients will be enrolled and allocated to receive either 12 mg/day of astaxanthin or an identical placebo for one-year. Patients will be stratified into four groups according to the type of immunosuppressant therapy they receive: 1) cyclosporine, 2) sirolimus, 3) tacrolimus or 4) prednisolone+/-azathioprine, mycophenolate mofetil or mycophenolate sodium. Primary outcome measures will be changes in 1) arterial stiffness measured by aortic pulse wave velocity (PWV), 2) oxidative stress assessed by plasma isoprostanes and 3) inflammation by plasma pentraxin 3. Secondary outcomes will include changes in vascular function assessed using the brachial artery reactivity (BAR) technique, carotid artery intimal medial thickness (CIMT), augmentation index (AIx), left ventricular afterload and additional measures of oxidative stress and inflammation. Patients will undergo these measures at baseline, six and 12 months.The results of this study will help determine the efficacy of astaxanthin on vascular structure, oxidative stress and inflammation in renal transplant patients. This may lead to a larger intervention trial assessing cardiovascular morbidity and mortality.ACTRN12608000159358Vascular disease is the leading cause of morbidity and mortality in renal transplant recipients [1]. Measures of arterial stiffness such as aortic pulse wave velocity (PWV) predict morbidity and mortality in patients with kidney disease [2]. In addition, numerous studies have reported elevated levels of oxidative stress and inflammation in this population [3-7] and this has been associated with arterial stiffness [8]. Our research group has shown that cyclosporine, a commonly used immunosuppressant taken by renal transplant recipients, increases markers of oxidative stress [9,10] and decreases vascular function [11]. In addition, antioxidant supplementation reduced oxidative stress and protected against the
Make Vitamin D While the Sun Shines, Take Supplements When It Doesn′t: A Longitudinal, Observational Study of Older Adults in Tasmania, Australia
Jane K. Pittaway, Kiran D. K. Ahuja, Jeffrey M. Beckett, Marie-Louise Bird, Iain K. Robertson, Madeleine J. Ball
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0059063
Abstract: Low vitamin D status has been associated with a number of chronic conditions, particularly in older adults. The aim of this study was to identify how best to maintain optimum vitamin D status throughout the year in this high-risk population. The main objectives of the study were to assess seasonal vitamin D status; identify the main determinants of vitamin D status; determine if taking part in the study led to alterations in participant behaviour and vitamin D status. A longitudinal design across four consecutive seasons observed ninety-one 60–85 year old community-dwelling adults in Tasmania (41π S) over 13 consecutive months, with a follow-up assessment at next winter's end. Associations between solar UVB exposure, sun protection behaviours, dietary and supplemental vitamin D with serum 25(OH)D concentrations were assessed. Variation in serum 25(OH)D demonstrated an identical pattern to solar UVB, lagging 8–10 weeks. Serum 25(OH)D was positively associated with summer UVB (mean 15.9 nmol/L; 95%CI 11.8–19.9 nmol/L, p<0.001) and vitamin D supplementation (100–600 IU/day: 95%CI 10.2 nmol/L; 0.8–19.6 nmol/L; p = 0.03; 800 IU/day: 21.0 nmol/L; 95%CI 8.1–34.0 nmol/L; p = 0.001). Seasonal variation in serum 25(OH)D was greatly diminished in supplement users. The most common alteration in participant behaviour after the study was ingesting vitamin D supplements. Post-study vitamin D supplementation ?800 IU/day was seven times more likely than during the study resulting in mean difference in serum 25(OH)D between supplement and non-supplement users of 30.1 nmol/L (95%CI 19.4–40.8 nmol/L; p<0.001). The main limitation was homogeneity of participant ethnicity. Solar exposure in summer and ingestion of vitamin D supplements in other seasons are the most effective ways of achieving and maintaining year-round vitamin D sufficiency in older adults in the Southern hemisphere. Vitamin D supplementation has greatest effect on vitamin D status if ingested during and after winter, i.e. between the autumn and spring equinoxes.
The Association between Seasonal Variation in Vitamin D, Postural Sway, and Falls Risk: An Observational Cohort Study
Marie-Louise Bird,Keith D. Hill,Iain Robertson,Madeleine J. Ball,Jane K. Pittaway,Andrew D. Williams
Journal of Aging Research , 2013, DOI: 10.1155/2013/751310
Abstract: Introduction. Low serum vitamin D levels are associated with increased postural sway. Vitamin D varies seasonally. This study investigates whether postural sway varies seasonally and is associated with serum vitamin D and falls. Methods. In a longitudinal observational study, eighty-eight independently mobile community-dwelling older adults (69.7 7.6 years) were evaluated on five occasions over one year, measuring postural sway (force platform), vitamin D levels, fall incidence, and causes and adverse outcomes. Mixed-methods Poisson regression was used to determine associations between measures. Results. Postural sway did not vary over the year. Vitamin D levels varied seasonally ( ), peaking in summer. Incidence of falls ( ) and injurious falls ( ) were lower in spring, with the highest fall rate at the end of autumn. Postural sway was not related to vitamin D ( ) or fall rates, but it was associated with fall injuries (IRR 1.59 (CI 1.14 to 2.24, ). Conclusions. Postural sway remained stable across the year while vitamin D varied seasonally. Participants with high values for postural sway demonstrated higher rates of injurious falls. This study provides important evidence for clinicians and researchers providing interventions measuring balance outcomes across seasons. 1. Introduction Balance impairment is an important fall-risk factor [1], and increases in range of postural sway in the mediolateral direction in older adults are associated with increased fall-risk and rates [2]. Postural sway has been shown in older adults to be strongly related to other measures of balance [3]. Multivariate analysis reveals serum vitamin D levels as an independent variable associated with postural sway [4]. In individuals with suboptimal levels of vitamin D, balance and strength improve after supplementation [5], in particular postural sway [6]. Epidemiological studies have shown that vitamin D levels show seasonal variation [7, 8]. Lowest levels of serum vitamin D are recorded towards the end of winter, approximately four weeks after the shortest day of the year [8]. Overall, vitamin D supplementation did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26, 747 participants) but may do so in people with lower vitamin D levels before treatment [9]. Older adults are at risk for lower levels of serum vitamin D because of age-related changes in UVB absorption and skin capacity to synthesize vitamin D, reduction in activation in the kidneys, and reduced expression of
Heregulin β1 drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells
Iain R Hutcheson, Janice M Knowlden, Steve E Hiscox, Denise Barrow, Julia MW Gee, John F Robertson, Ian O Ellis, Robert I Nicholson
Breast Cancer Research , 2007, DOI: 10.1186/bcr1754
Abstract: Tam-R cells, incubated with the selective EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839), were exposed to HRGβ1 and the effects on erbB receptor dimerization profiles and on activation of associated downstream signalling components were assessed by immunoprecipitation, western blotting and immunocytochemistry. The effects of HRGβ1 on gefitinib-treated Tam-R cell growth and invasion were also examined, and HRGβ1 expression levels were assessed in breast cancer tissue by immunohistochemistry to address the potential clinical relevance of such a resistance mechanism.In Tam-R cells, HRGβ1 promoted erbB3/erbB2 and erbB3/EGFR heterodimerization, promoted ERK1/2 and AKT pathway activation and increased cell proliferation and invasion. Gefitinib prevented HRGβ1-driven erbB3/EGFR heterodimerization, ERK1/2 activation and Tam-R cell proliferation, but HRGβ1-driven erbB3/erbB2 heterodimerization, AKT activation and Tam-R cell invasion were maintained. A combination of gefitinib and the phosphatidylinositol 3-kinase inhibitor LY294002 effectively blocked HRGβ1-mediated intracellular signalling activity, growth and invasion in Tam-R cells. Similarly, targeting erbB2 with trastuzumab in combination with gefitinib in Tam-R cells reduced HRGβ1-induced erbB2 and ERK1/2 activity; however, HRGβ1-driven AKT activity and cell growth were maintained while cell invasion was significantly enhanced with this combination. In clinical tissue all samples demonstrated cytoplasmic tumour epithelial HRGβ1 protein staining, with expression correlating with EGFR positivity and activation of both AKT and ERK1/2.HRGβ1 can overcome the inhibitory effects of gefitinib on cell growth and invasion in Tam-R cells through promotion of erbB3/erbB2 heterodimerization and activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. This may have implications for the effectiveness of anti-EGFR therapies in breast cancer as HRGβ1 is enriched in many EGFR-positive breast tumours.The epide
Comparison of markers of oxidative stress, inflammation and arterial stiffness between incident hemodialysis and peritoneal dialysis patients – an observational study
Robert G Fassett, Ritza Driver, Helen Healy, Dwarakanathan Ranganathan, Sharad Ratanjee, Iain K Robertson, Dominic P Geraghty, James E Sharman, Jeff S Coombes
BMC Nephrology , 2009, DOI: 10.1186/1471-2369-10-8
Abstract: This is an observational study. Eighty stage five CKD patients will be enrolled and followed for one-year. Primary outcome measures will be changes in 1) arterial stiffness measured by aortic pulse wave velocity, 2) oxidative stress assessed by plasma F2 isoprostanes and 3) inflammation measured by plasma pentraxin-3. Secondary outcomes will include additional measures of oxidative stress and inflammation, changes in vascular function assessed using the brachial artery reactivity technique, carotid artery intimal medial thickness, augmentation index and trans thoracic echocardiography to assess left ventricular geometry, and systolic and diastolic function. Patients will undergo these measures at baseline (6–8 weeks prior to starting dialysis therapy), then at six and 12 months after starting dialysis.The results of this study may guide the choice of dialysis modality in the first year of treatment. It may also lead to a larger study prospectively assessing the effect of dialysis modality on cardiovascular morbidity and mortality.ACTRN12609000049279End stage kidney disease (ESKD) patients undergoing dialysis have a substantially increased risk of cardiovascular morbidity and mortality[1] In 2007, 2311 new patients started dialysis in Australia and New Zealand but, unfortunately, many of these patients will die of cardiovascular disease. (ANZDATA 2007) The decision to undergo either peritoneal or haemodialysis is based on a number of factors. One of the important issues is the potential damage the renal replacement therapy may have on the cardiovascular system. Currently, little is known regarding the differential effects of the dialysis modalities on the cardiovascular system.Oxidative stress and inflammation are associated with the development of cardiovascular disease in dialysis patients [1,2]. The mechanisms are believed to involve arterial stiffening leading to impaired vascular function [3]. In addition, vascular and myocardial dysfunction are also prominent,
Impacts of Removing Badgers on Localised Counts of Hedgehogs
Iain D. Trewby, Richard Young, Robbie A. McDonald, Gavin J. Wilson, John Davison, Neil Walker, Andrew Robertson, C. Patrick Doncaster, Richard J. Delahay
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095477
Abstract: Experimental evidence of the interactions among mammalian predators that eat or compete with one another is rare, due to the ethical and logistical challenges of managing wild populations in a controlled and replicated way. Here, we report on the opportunistic use of a replicated and controlled culling experiment (the Randomised Badger Culling Trial) to investigate the relationship between two sympatric predators: European badgers Meles meles and western European hedgehogs Erinaceus europaeus. In areas of preferred habitat (amenity grassland), counts of hedgehogs more than doubled over a 5-year period from the start of badger culling (from 0.9 ha?1 pre-cull to 2.4 ha?1 post-cull), whereas hedgehog counts did not change where there was no badger culling (0.3–0.3 hedgehogs ha?1). This trial provides experimental evidence for mesopredator release as an outcome of management of a top predator.
Mapping the Self with Units of Culture  [PDF]
Lloyd H. Robertson
Psychology (PSYCH) , 2010, DOI: 10.4236/psych.2010.13025
Abstract: This study explored a method of representing the self graphically using elemental units of culture called memes. A diverse sample of eleven volunteers participated in the co-construction of individual “self-maps” during a series of interviews over a nine month period. Two of the resultant maps are presented as exemplars. Commonalities found in all eleven maps lend support to the notion that there are certain structures to the self that are cross-cultural. The use of memes in mapping those structures was considered useful but insufficient because emotive elements to the self emerged from the research that could not be represented in memetic form. Suggestions are made for future research.
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