Emeritus Professor Anthony Smith

Emeritus Professor Anthony Smith

Emeritus Professor

Faculty of Health and Medicine (Clinical Pharmacology and Clinical Toxicology)

Career Summary

Biography

Born Birmingham, UK. 1931

Education : King Edward's School,Birmingham UK 1942-1949

Wadham College, Oxford  and Oxford Medical School 1949-1955. Gaduated. BA Animal Physiology (1952), MA (1954), BM, BCh (1955)

Member of the Royal College of Physicians, London 1959, DM( Oxon) 1965. Fellow of the Royal College of Physicians, London 1971.

Employmemt Junior hospital posts 1955-1957. Registrar in General Medicine, Sheffield Royal Infirmary, 1958-1959. John Stokes

Research Fellow in Medicine, University of Sheffield 1959-62.Lecturer in Medicine, University of Lagos, Nigeria 1963-65.Lecturer in

Pharmacology and Therapeutics, University of Sheffield 1965-7, Senior Lecturer in Pharmacology and Therapeutics, University of

Sheffield 1967-1975, Associate in Medicine, University of Sheffield 1975-1978. Foundation Professor of Clinical Pharmacology, University

of Newcastle, NSW, Australia 1978-97 , created  Emeritus Professor Clinical Pharmacology,University of Newcastle NSW, Australia1997.


Qualifications

  • Doctor of Medicine, University of Oxford - UK
  • Master of Arts, University of Oxford - UK
  • Bachelor of Medicine, Bachelor of Surgery, University of Oxford - UK

Keywords

  • clinical pharmacology
  • clinical toxicology
  • clinicla toxicology
  • medical education

Languages

  • English (Mother)

Fields of Research

Code Description Percentage
110399 Clinical Sciences not elsewhere classified 35
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified 65
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Chapter (1 outputs)

Year Citation Altmetrics Link
2008 Smith AJ, Suryawati S, 'Clinical pharmacokinetics', Drug Benefits and Risks: International Textbook of Clinical Pharmacology 123-163 (2008)

Journal article (172 outputs)

Year Citation Altmetrics Link
2019 Newby DA, Stokes B, Smith AJ, 'A pilot study of a pharmacist-led prescribing program for final-year medical students', BMC MEDICAL EDUCATION, 19 (2019) [C1]
DOI 10.1186/s12909-019-1486-1
Citations Scopus - 2Web of Science - 2
Co-authors Barrie Stokes, David Newby
2018 Smith AJP, Deloukas P, Munroe PB, 'Emerging applications of genome-editing technology to examine functionality of GWAS-associated variants for complex traits', Physiological Genomics, 50 510-522 (2018)

© 2018 American Physiological Society. All rights reserved. Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associat... [more]

© 2018 American Physiological Society. All rights reserved. Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning toward the function of these association signals, determining the causal variant(s) among those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilizing zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs), and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9) are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo. This review will discuss examples of how these technologies have begun to aid functional analysis of GWAS loci for complex traits such as cardiovascular disease, Type 2 diabetes, cancer, obesity, and autoimmune disease. We focus on analysis of variants occurring within noncoding genomic regions, as these comprise the majority of GWAS variants, providing the greatest challenges to determining functionality, and compare editing strategies that provide different levels of evidence for variant functionality. The review describes molecular insights into some of these potentially causal variants and how these may relate to the pathology of the trait and look toward future directions for these technologies in post-GWAS analysis, such as base-editing.

DOI 10.1152/physiolgenomics.00028.2018
Citations Scopus - 7
2017 Beaney KE, Smith AJP, Folkersen L, Palmen J, Wannamethee SG, Jefferis BJ, et al., 'Functional Analysis of the Coronary Heart Disease Risk Locus on Chromosome 21q22', Disease Markers, 2017 (2017)

© 2017 Katherine E. Beaney et al. Background. The coronary heart disease (CHD) risk locus on 21q22 (lead SNP rs9982601) lies within a "gene desert." The aim of this stud... [more]

© 2017 Katherine E. Beaney et al. Background. The coronary heart disease (CHD) risk locus on 21q22 (lead SNP rs9982601) lies within a "gene desert." The aim of this study was to assess if this locus is associated with CHD risk factors and to identify the functional variant(s) and gene(s) involved. Methods. A phenome scan was performed with UCLEB Consortium data. Allele-specific protein binding was studied using electrophoretic mobility shift assays. Dual-reporter luciferase assays were used to assess the impact of genetic variation on expression. Expression quantitative trait analysis was performed with Advanced Study of Aortic Pathology (ASAP) and Genotype-Tissue Expression (GTEx) consortium data. Results. A suggestive association between QT interval and the locus was observed (rs9982601 p=0.04). One variant at the locus, rs28451064, showed allele-specific protein binding and its minor allele showed 12% higher luciferase expression (p = 4.82 × 10-3) compared to the common allele. The minor allele of rs9982601 was associated with higher expression of the closest upstream genes (SLC5A3 1.30-fold increase p = 3.98 × 10-5; MRPS6 1.15-fold increase p = 9.60 × 10-4) in aortic intima media in ASAP. Both rs9982601 and rs28451064 showed a suggestive association with MRPS6 expression in relevant tissues in the GTEx data. Conclusions. A candidate functional variant, rs28451064, was identified. Future work should focus on identifying the pathway(s) involved.

DOI 10.1155/2017/1096916
Citations Scopus - 1
2016 Ehret GB, Ferreira T, Chasman DI, Jackson AU, Schmidt EM, Johnson T, et al., 'The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals', Nature Genetics, 48 1171-1184 (2016)

© 2016 Nature America, Inc. All rights reserved. To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from tar... [more]

© 2016 Nature America, Inc. All rights reserved. To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

DOI 10.1038/ng.3667
Citations Scopus - 179
2016 van't Hof FNG, Ruigrok YM, Lee CH, Ripke S, Anderson G, de Andrade M, et al., 'Shared genetic risk factors of intracranial, abdominal, and thoracic aneurysms', Journal of the American Heart Association, 5 (2016)

© 2016 The Authors. Background--Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given tha... [more]

© 2016 The Authors. Background--Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results--We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk singlenucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1910-5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1910-3). Conclusions--Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.

DOI 10.1161/JAHA.115.002603
Citations Scopus - 19
2016 Oldoni F, Palmen J, Giambartolomei C, Howard P, Drenos F, Plagnol V, et al., 'Post-GWAS methodologies for localisation of functional non-coding variants: ANGPTL3', Atherosclerosis, 246 193-201 (2016)

© 2015 The Authors. Genome-wide association studies have confirmed the involvement of non-coding angiopoietin-like 3 (ANGPTL3) gene variants with coronary artery disease, levels o... [more]

© 2015 The Authors. Genome-wide association studies have confirmed the involvement of non-coding angiopoietin-like 3 (ANGPTL3) gene variants with coronary artery disease, levels of low-density lipoprotein cholesterol (LDL-C), triglycerides and ANGPTL3 mRNA transcript. Extensive linkage disequilibrium at the locus, however, has hindered efforts to identify the potential functional variants. Using regulatory annotations from ENCODE, combined with functional in vivo assays such as allele-specific formaldehyde-assisted isolation of regulatory elements, statistical approaches including eQTL/lipid colocalisation, and traditional in vitro methodologies including electrophoretic mobility shift assay and luciferase reporter assays, variants affecting the ANGPTL3 regulome were examined. From 253 variants associated with ANGPTL3 mRNA expression, and/or lipid traits, 46 were located within liver regulatory elements and potentially functional. One variant, rs10889352, demonstrated allele-specific effects on DNA-protein interactions, reporter gene expression and chromatin accessibility, in line with effects on LDL-C levels and expression of ANGPTL3 mRNA. The ANGPTL3 gene lies within DOCK7, although the variant is within non-coding regions outside of ANGPTL3, within DOCK7, suggesting complex long-range regulatory effects on gene expression. This study illustrates the power of combining multiple genome-wide datasets with laboratory data to localise functional non-coding variation and provides a model for analysis of regulatory variants from GWAS.

DOI 10.1016/j.atherosclerosis.2015.12.009
Citations Scopus - 4
2015 Smith AJP, Humphries SE, Talmud PJ, 'Identifying functional noncoding variants from genome-wide association studies for cardiovascular disease and related traits', Current Opinion in Lipidology, 26 120-126 (2015)

© 2015 Wolters Kluwer Health, Inc. Purpose of review Genome-wide association studies have identified many novel loci for cardiovascular disease and related traits. Attention is no... [more]

© 2015 Wolters Kluwer Health, Inc. Purpose of review Genome-wide association studies have identified many novel loci for cardiovascular disease and related traits. Attention is now shifting towards the analysis of these loci for causal variants, with a view to identify the novel mechanisms leading to disease. Recent findings This review focuses on the approaches to identify causal, noncoding variants for coronary artery disease, lipid traits and other cardiovascular risk factors. Fine-mapping studies are discussed, along with the novel statistical approaches to produce 'credible sets'. The use of combining genome-wide association study datasets with experimental methods such as expression quantitative trait loci and allele-specific chromatin accessibility are explored, with recent examples discussed. Mapping long-range chromatin interactions and evolving genome-editing technologies such as clustered regularly interspaced short palindromic repeats combined with clustered regularly interspaced short palindromic repeats-associated (Cas9) nuclease promise to aid considerably the search for causal variants. Summary Identification of causal variants for cardiovascular disease and related traits is still in the early stages, but with technologies evolving and increasingly relevant tissue samples undergoing analysis, there are favourable prospects that many new mechanisms for disease will be uncovered by the end of this decade.

DOI 10.1097/MOL.0000000000000158
Citations Scopus - 6
2015 Boardman-Pretty F, Smith AJP, Cooper J, Palmen J, Folkersen L, Hamsten A, et al., 'Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant', Circulation: Cardiovascular Genetics, 8 696-706 (2015)

© 2015 American Heart Association, Inc. Background-Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events o... [more]

© 2015 American Heart Association, Inc. Background-Carotid intima-media thickness (IMT) is a marker of subclinical atherosclerosis that can predict cardiovascular disease events over traditional risk factors. This study examined the BCAR1-CFDP1-TMEM170A locus on chromosome 16, associated with carotid IMT and coronary artery disease in the IMT and IMT-Progression as Predictors of Vascular Events (IMPROVE) cohort, to identify the functional variant. Methods and Results-In analysis of the locus lead single nucleotide polymorphism (SNP; rs4888378, intronic in CFDP1) in Progressione della Lesione Intimale Carotidea (PLIC), the protective AA genotype was associated with slower IMT progression in women (P=0.04) but not in men. Meta-analysis of 5 cohort studies also supported a protective effect of the A allele on common carotid IMT in women only (women: ß=-0.0047, P=1.63×10-4; men: ß=-0.0029, P=0.0678). Two hundred fourteen noncoding variants in strong linkage disequilibrium (r2=0.8) with rs4888378 were identified from 1000 Genome Project. ENCODE regulatory chromatin marks were used to create a shortlist of 6 possible regulatory variants. Electrophoretic mobility shift assays on the shortlist detected allele-specific protein binding to the lead SNP rs4888378; multiplexed competitor electrophoretic mobility shift assays implicated FOXA as the protein. Luciferase reporter assays on rs4888378 showed a significant 35% to 92% (P=0.0057; P=4.0×10-22) decrease in gene expression with the A allele. Expression quantitative trait loci analysis confirmed previously reported associations of rs4888378 with BCAR1 in vascular tissues. Conclusions-Molecular studies suggest the lead SNP as a potentially causal SNP at the BCAR1-CFDP1-TMEM170A locus, and expression quantitative trait loci studies implicate BCAR1 as the causal gene. This variant showed stronger effects on common carotid IMT in women, raising questions about the mechanism of the causal SNP on atherosclerosis.

DOI 10.1161/CIRCGENETICS.115.001062
Citations Scopus - 9
2015 Adhikari K, Reales G, Smith AJP, Konka E, Palmen J, Quinto-Sanchez M, et al., 'A genome-wide association study identifies multiple loci for variation in human ear morphology', Nature Communications, 6 (2015)

© 2015 Macmillan Publishers Limited. All rights reserved. Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We fi... [more]

© 2015 Macmillan Publishers Limited. All rights reserved. Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10<sup>-8</sup> to 3 × 10<sup>-14</sup>). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.

DOI 10.1038/ncomms8500
Citations Scopus - 30
2015 Hamad IAY, Fei Y, Kalea AZ, Yin D, Smith AJP, Palmen J, et al., 'Demonstration of the presence of the "Deleted" MIR122 gene in HepG2 cells', PLoS ONE, 10 (2015)

© 2015 Hamad et al. MicroRNA 122 (miR-122) is highly expressed in the liver where it influences diverse biological processes and pathways, including hepatitis C virus replication ... [more]

© 2015 Hamad et al. MicroRNA 122 (miR-122) is highly expressed in the liver where it influences diverse biological processes and pathways, including hepatitis C virus replication and metabolism of iron and cholesterol. It is processed from a long non-coding primary transcript (~7.5 kb) and the gene has two evolutionarily-conserved regions containing the pri-mir-122 promoter and pre-mir-122 hairpin region. Several groups reported that the widely-used hepatocytic cell line HepG2 had deficient expression of miR-122, previously ascribed to deletion of the pre-mir-122 stem-loop region. We aimed to characterise this deletion by direct sequencing of 6078 bp containing the pri-mir-122 promoter and pre-mir-122 stem-loop region in HepG2 and Huh-7, a control hepatocytic cell line reported to express miR-122, supported by sequence analysis of cloned genomic DNA. In contrast to previous findings, the entire sequence was present in both cell lines. Ten SNPs were heterozygous in HepG2 indicating that DNA was present in two copies. Three validation isolates of HepG2 were sequenced, showing identical genotype to the original in two, whereas the third was different. Investigation of promoter chromatin status by FAIRE showed that Huh-7 cells had 6.2 ± 0.19- and 2.7 ± 0.01- fold more accessible chromatin at the proximal (HNF4a-binding) and distal DR1 transcription factor sites, compared to HepG2 cells (p=0.03 and 0.001, respectively). This was substantiated by ENCODE genome annotations, which showed a DNAse I hypersensitive site in the pri-mir-122 promoter in Huh-7 that was absent in HepG2 cells. While the origin of the reported deletion is unclear, cell lines should be obtained from a reputable source and used at low passage number to avoid discrepant results. Deficiency of miR-122 expression in HepG2 cells may be related to a relative deficiency of accessible promoter chromatin in HepG2 versus Huh-7 cells.

DOI 10.1371/journal.pone.0122471
Citations Scopus - 6
2013 Harrison SC, Smith AJP, Jones GT, Swerdlow DI, Rampuri R, Bown MJ, et al., 'Interleukin-6 receptor pathways in abdominal aortic aneurysm', European Heart Journal, 34 3707-3716 (2013)

MethodsWe conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous f... [more]

MethodsWe conducted a systematic review and meta-analysis of studies reporting circulating IL-6 in AAA, and new investigations of the association between a common non-synonymous functional variant (Asp358Ala) in the IL-6R gene (IL6R) and AAA, followed the analysis of the variant both in vitro and in vivo.Inflammation may play a role in the development of abdominal aortic aneurysms (AAA). Interleukin-6 (IL-6) signalling through its receptor (IL-6R) is one pathway that could be exploited pharmacologically. We investigated this using a Mendelian randomization approach.ResultsUp to October 2011, we identified seven studies (869 cases, 851 controls). Meta-analysis demonstrated that AAA cases had higher levels of IL-6 than controls [standardized mean difference (SMD) = 0.46 SD, 95% CI = 0.25-0.66, I2 = 70%, P = 1.1 × 10-5 random effects]. Meta-analysis of five studies (4524 cases/15 710 controls) demonstrated that rs7529229 (which tags the non-synonymous variant Asp358Ala, rs2228145) was associated with a lower risk of AAA, per Ala358 allele odds ratio 0.84, 95% CI: 0.80-0.89, I2 = 0%, P = 2.7 × 10-11). In vitro analyses in lymphoblastoid cell lines demonstrated a reduction in the expression of downstream targets (STAT3, MYC and ICAM1) in response to IL-6 stimulation in Ala358 carriers.ConclusionsA Mendelian randomization approach provides robust evidence that signalling via the IL-6R is likely to be a causal pathway in AAA. Drugs that inhibit IL-6R may play a role in AAA management. © The Author 2012.

DOI 10.1093/eurheartj/ehs354
Citations Scopus - 85
2013 Pang DX, Smith AJP, Humphries SE, 'Functional analysis of TCF7L2 genetic variants associated with type 2 diabetes', Nutrition, Metabolism and Cardiovascular Diseases, 23 550-556 (2013)

expression and T2D riskBackground and aims: Common non-coding variations within the TCF7L2 locus have a strong influence on type 2 diabetes (T2D) susceptibility through uncharacte... [more]

expression and T2D riskBackground and aims: Common non-coding variations within the TCF7L2 locus have a strong influence on type 2 diabetes (T2D) susceptibility through uncharacterised mechanisms. An islet-specific functional polymorphism has been identified, although this does not explain the association between genotype and gene expression in other cell types. This study sought to identify these other functional TCF7L2 variants. Methods and results: Alternative splicing and gene expression from TCF7L2 was examined from peripheral blood mononuclear cells from 100 healthy Caucasians using two T2D-associated SNPs, rs7903146 and rs12255372. Electrophoretic mobility shift assays and luciferase reporter assays were performed with these SNPs and those in strong LD to determine potential SNP functionality. Individuals homozygous for rs7903146 and rs12255372 T2D risk alleles (TT/TT) expressed 2.6-fold greater levels of TCF7L2 mRNA compared to individuals homozygous for the non-risk alleles (CC/GG, p=0.006), although differentially spliced TCF7L2 transcripts did not differ by T2D risk-associated genotype. From SNPs identified to be in strong LD with the T2D-associated SNPs, rs7903146 and rs12255372, five (rs4132670, rs4506565, rs7903146, rs7901695, rs17747324) demonstrated allele-specific binding in electrophoretic mobility shift assays (EMSA). In luciferase reporter assays, rs4132670 exhibited 1.3-fold higher levels of enhancer activity in the Huh7 cell line (p=3.8×10-5) and 2-fold higher levels in a WiDr colon carcinoma cell line (p=0.008). Conclusions: These results suggest that rs4132670, located in a region of chromatin accessibility, is a non-tissue-specific candidate functional SNP that has the potential to play a role in TCF7L2 gene expression and T2D risk. © 2012 Elsevier B.V.

DOI 10.1016/j.numecd.2011.12.012
Citations Scopus - 12
2013 Robertson J, Smith A, Forzley M, 'Legislation an essential tool for ensuring access to medicines policy goals', WHO South-East Asia Journal of Public Health, 2 69-69 (2013) [C2]
DOI 10.4103/2224-3151.115848
2012 Smith AJ, 'An Australian perspective', An Australian perspective, 73 939-942 (2012) [C1]
2012 Smith AJ, 'An agenda for UK clinical pharmacology: An Australian perspective', British Journal of Clinical Pharmacology, 73 939-942 (2012) [C3]
2012 Robertson J, Santoso B, Holloway KA, Dartnell J, Tisocki K, McLachlan A, Smith AJ, 'Asia Pacific Conference on National Medicines Policies', Australian Prescriber, 35 190-193 (2012) [C2]
Citations Scopus - 2Web of Science - 2
2012 Smith AN, 'Quality use of medicines - Are we nearly there yet?', Australian Prescriber, 35 174-175 (2012) [C3]
Citations Scopus - 2Web of Science - 3
2012 Smith AJP, Zheng D, Palmen J, Pang DX, Woo P, Humphries SE, 'Effects of genetic variation on chromatin structure and the transcriptional machinery: Analysis of the IL6 gene locus', Genes and Immunity, 13 583-586 (2012)

The presence of functional regulatory polymorphism at the interleukin 6 (IL6) locus is uncertain, with many conflicting in vitro findings. To examine the in vivo effect of the thr... [more]

The presence of functional regulatory polymorphism at the interleukin 6 (IL6) locus is uncertain, with many conflicting in vitro findings. To examine the in vivo effect of the three putative functional IL6 promoter variants, 174G>C, 572G>C and 6331T>C, two complementary techniques, allele-specific chromatin immunoprecipitation and allele-specific formaldehyde-assisted isolation of regulatory elements, were carried out using unrelated lymphoblast cell lines of known genotype. There were no allele-specific effects for all three single-nucleotide polymorphisms (SNPs) under basal conditions. Upon IL-1ß stimulation, however, allele-specific effects were seen for the 6331 allele, which showed both increased RNA polymerase II loading (56%, P0.001) and increased open chromatin (59%, P0.004) for the T allele, which is in line with previous reports of this SNP and the effects from acute inflammation. These studies highlight the importance of examining chromatin under different environmental conditions when studying the functionality of regulatory polymorphisms. © 2012 Macmillan Publishers Limited. All rights reserved.

DOI 10.1038/gene.2012.32
Citations Scopus - 5
2012 Smith AJP, Howard P, Shah S, Eriksson P, Stender S, Giambartolomei C, et al., 'Use of Allele-Specific FAIRE to Determine Functional Regulatory Polymorphism Using Large-Scale Genotyping Arrays', PLoS Genetics, 8 (2012)

Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases a... [more]

Following the widespread use of genome-wide association studies (GWAS), focus is turning towards identification of causal variants rather than simply genetic markers of diseases and traits. As a step towards a high-throughput method to identify genome-wide, non-coding, functional regulatory variants, we describe the technique of allele-specific FAIRE, utilising large-scale genotyping technology (FAIRE-gen) to determine allelic effects on chromatin accessibility and regulatory potential. FAIRE-gen was explored using lymphoblastoid cells and the 50,000 SNP Illumina CVD BeadChip. The technique identified an allele-specific regulatory polymorphism within NR1H3 (coding for LXR-a), rs7120118, coinciding with a previously GWAS-identified SNP for HDL-C levels. This finding was confirmed using FAIRE-gen with the 200,000 SNP Illumina Metabochip and verified with the established method of TaqMan allelic discrimination. Examination of this SNP in two prospective Caucasian cohorts comprising 15,000 individuals confirmed the association with HDL-C levels (combined beta = 0.016; p = 0.0006), and analysis of gene expression identified an allelic association with LXR-a expression in heart tissue. Using increasingly comprehensive genotyping chips and distinct tissues for examination, FAIRE-gen has the potential to aid the identification of many causal SNPs associated with disease from GWAS. © 2012 Smith et al.

DOI 10.1371/journal.pgen.1002908
Citations Scopus - 18
2012 Smith AJ, 'The efficacy of complementary medicines: Where is the evidence?', Journal of Pharmacy Practice and Research, 42 174-175 (2012) [C3]
Citations Scopus - 2
2011 Smith AJ, Newby DA, 'A most trusted profession ... ?', Medical Journal of Australia, 195 490-491 (2011) [C3]
DOI 10.5694/mja11.11309
Citations Scopus - 1Web of Science - 1
Co-authors David Newby
2011 Bown MJ, Jones GT, Harrison SC, Wright BJ, Bumpstead S, Baas AF, et al., 'Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1', American Journal of Human Genetics, 89 619-627 (2011)

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 p... [more]

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10 -5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression. © 2011 The American Society of Human Genetics.

DOI 10.1016/j.ajhg.2011.10.002
Citations Scopus - 57
2011 Kerkhof HJM, Doherty M, Arden NK, Abramson SB, Attur M, Bos SD, et al., 'Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis', Osteoarthritis and Cartilage, 19 265-271 (2011)

Objective: To clarify the role of common genetic variation in the Interleukin-1ß (IL1B) and Interleukin-1R antagonist (IL1RN) genes on risk of knee and hip osteoarthritis (OA) and... [more]

Objective: To clarify the role of common genetic variation in the Interleukin-1ß (IL1B) and Interleukin-1R antagonist (IL1RN) genes on risk of knee and hip osteoarthritis (OA) and severity of knee OA by means of large-scale meta-analyses. Methods: We searched PubMed for articles assessing the role of IL1B and IL1RN polymorphisms/haplotypes on the risk of hip and/or knee OA. Novel data were included from eight unpublished studies. Meta-analyses were performed using fixed- and random-effects models with a total of 3595 hip OA and 5013 knee OA cases, and 6559 and 9132 controls respectively. The role of ILRN haplotypes on radiographic severity of knee OA was tested in 1918 cases with Kellgren-Lawrence (K/L) 1 or 2 compared to 199 cases with K/L 3 or 4. Results: The meta-analysis of six published studies retrieved from the literature search and eight unpublished studies showed no evidence of association between common genetic variation in the IL1B or IL1RN genes and risk of hip OA or knee OA (P>0.05 for rs16944, rs1143634, rs419598 and haplotype C-G-C (rs1143634, rs16944 and rs419598) previously implicated in risk of hip OA). The C-T-A haplotype formed by rs419598, rs315952 and rs9005, previously implicated in radiographic severity of knee OA, was associated with reduced severity of knee OA (odds ratio (OR)=0.71 95%CI 0.56-0.91; P=0.006, I2=74%), and achieved borderline statistical significance in a random-effects model (OR=0.61 95%CI 0.35-1.06 P=0.08). Conclusion: Common genetic variation in the Interleukin-1 region is not associated with prevalence of hip or knee OA but our data suggest that IL1RN might have a role in severity of knee OA. © 2010 Osteoarthritis Research Society International.

DOI 10.1016/j.joca.2010.12.003
Citations Scopus - 59
2010 Orme M, Sjoqvist F, Birkett D, Brosen K, Cascorbi I, Gustafsson LL, et al., 'Clinical pharmacology in research, teaching and health care', Basic & Clinical Pharmacology & Toxicology, 107 531-559 (2010) [C1]
DOI 10.1111/j.1742-7843.2010.00602.x
Citations Scopus - 69Web of Science - 18
2010 Smith AJP, Palmen J, Putt W, Talmud PJ, Humphries SE, Drenos F, 'Application of statistical and functional methodologies for the investigation of genetic determinants of coronary heart disease biomarkers: Lipoprotein lipase genotype and plasma triglycerides as an exemplar', Human Molecular Genetics, 19 3936-3947 (2010)

Genome-wide association studies have proved very successful in identifying novel single-nucleotide polymorphisms (SNPs) associated with disease or traits, but the related, functio... [more]

Genome-wide association studies have proved very successful in identifying novel single-nucleotide polymorphisms (SNPs) associated with disease or traits, but the related, functional SNP is usually unknown. In this paper, we describe a methodology to locate and validate candidate functional SNPs using lipoprotein lipase (LPL), a gene previously associated with triglyceride levels, as an exemplar. Two thousand seven hundred and eighty-six healthy middle-aged men from the NPHSII UK prospective study (with up to six measures of plasma lipid levels) were genotyped for 20 LPL tagging (t)SNPs using Illumina Bead technology. Using model-selection procedures and haplotypes, we identified eight SNPs that consistently maximized the fit of the model to the phenotype. Fifteen SNPs in high linkage disequilibrium with these were identified, and functional assays were carried out on all 23 SNPs. Electrophoretic mobility shift assay (EMSA) was used to identify SNPs that had the potential to alter DNA-protein interactions, reducing the number to eight possible candidate SNPs. These were examined for ability to alter expression using a luciferase reporter assay, and two regulatory SNPs, showing genotype differences, rs327 and rs3289, were identified. Finally, multiplexed-competitor-EMSA (MC-EMSA) and supershift EMSA identified FOXA2 to rs327T, and CREB-binding protein (CBP) and CCAAT displacement protein (CDP) to rs3289C as the factors responsible for transcription binding. We have identified two novel candidate functional SNPs in LPL and presented a procedure aimed to efficiently detect SNPs potentially causal to genetic association. We believe that this methodology could be successfully applied to future re-sequencing data. © The Author 2010. Published by Oxford University Press. All rights reserved.

DOI 10.1093/hmg/ddq308
Citations Scopus - 21
2010 Moxley G, Meulenbelt I, Chapman K, van Diujn CM, Slagboom PE, Neale MC, et al., 'Interleukin-1 region meta-analysis with osteoarthritis phenotypes', OSTEOARTHRITIS AND CARTILAGE, 18 200-207 (2010)
DOI 10.1016/j.joca.2009.08.006
Citations Scopus - 24Web of Science - 19
2009 Akter SFU, Heller RD, Smith AJ, Milly AF, 'Impact of a training intervention on use of antimicrobials in teaching hospitals', Journal of Infection in Developing Countries, 3 447-451 (2009) [C1]
Citations Scopus - 15Web of Science - 14
2009 Pillay T, Smith AJ, Hill SR, 'A comparison of two methods for measuring anti-hypertensive drug use: Concordance of use with South African standard treatment guidelines', Bulletin of the World Health Organization, 87 466-471 (2009) [C1]
DOI 10.2471/blt.08.054619
Citations Scopus - 8Web of Science - 6
2009 Smith AJP, Humphries SE, 'Characterization of DNA-Binding Proteins Using Multiplexed Competitor EMSA', Journal of Molecular Biology, 385 714-717 (2009)

We describe a low-cost high-throughput technique to characterize nuclear protein DNA-binding interactions. This technique, known as Multiplexed Competitor Electrophoretic Mobility... [more]

We describe a low-cost high-throughput technique to characterize nuclear protein DNA-binding interactions. This technique, known as Multiplexed Competitor Electrophoretic Mobility Shift Assay, uses a series of multiplexed oligonucleotide DNA consensus competitors, in combination with a standard electrophoretic mobility shift assay procedure, to efficiently characterize DNA-binding proteins. We show utility for the method to identify a previously unreported hepatocyte nuclear factor-3 site created in intron 8 of the lipoprotein lipase gene by a common single-nucleotide polymorphism (rs327). © 2008 Elsevier Ltd. All rights reserved.

DOI 10.1016/j.jmb.2008.11.035
Citations Scopus - 29
2009 Smith AJP, Humphries SE, 'Cytokine and cytokine receptor gene polymorphisms and their functionality', Cytokine and Growth Factor Reviews, 20 43-59 (2009)

Cytokines, signaling proteins produced by a variety of cell types, are essential for the development and functioning of both innate and adaptive immune response. Cytokine gene exp... [more]

Cytokines, signaling proteins produced by a variety of cell types, are essential for the development and functioning of both innate and adaptive immune response. Cytokine gene expression is tightly regulated, and aberrant expression from environmental and genetic polymorphism has been implicated in a range of diseases, susceptibility to infections, and responses to treatment. This review concentrates on the functionality of cytokine and cytokine receptor gene polymorphisms; it is through these variants that genuine disease-associations are based. Several mechanisms for single nucleotide polymorphism (SNP) functionality are present within cytokine genes including: amino acid changes (IL-6R, IL-13, IL-1a), exon skipping (IL-7Ra), proximal promoter variants (IL-1ß, IL-Ra, IL-2, IL-6, IL-10, IL-12, IL-13, IL-16, TNF, IFN-¿, TGF-ß), distal promoter variants (IL-6, IL-18) and intronic enhancer variants (IL-8). © 2008 Elsevier Ltd. All rights reserved.

DOI 10.1016/j.cytogfr.2008.11.006
Citations Scopus - 235
2008 Smith AJP, D'Aiuto F, Palmen J, Cooper JA, Samuel J, Thompson S, et al., 'Association of serum interleukin-6 concentration with a functional IL6 -6331T>C polymorphism', Clinical Chemistry, 54 841-850 (2008)

BACKGROUND: Interleukin-6 (IL-6) concentrations vary substantially among individuals. This study aimed to identify novel genetic markers to explain these differences. METHODS: We ... [more]

BACKGROUND: Interleukin-6 (IL-6) concentrations vary substantially among individuals. This study aimed to identify novel genetic markers to explain these differences. METHODS: We sequenced a region 6-kb upstream of the IL6 [interleukin 6 (interferon, beta 2)] transcription start site in a search for functional variants and detected 3 common variants: -6331T>C, -6101A>T, and -5617/-5616C/A>T/G. IL6-6331T>C (C allele frequency, 0.20; 95% confidence interval, 0.16-0.24) showed strong negative linkage disequilibrium with -174G>C (D' = -0.97) and was studied further in 309 individuals who underwent coronary artery bypass grafting. RESULTS: Patients with the TT genotype had higher IL-6 concentrations 6 h after surgery than those with the CC genotype (mean, 199.4 ng/L vs 114.9 ng/L; P = 0.02). A similar association was seen in a cohort of 173 patients who underwent intensive periodontal therapy: Individuals with the CC genotype had significantly lower IL-6 concentrations 24 h after therapy than TT patients (mean, 0.78 ng/L vs 5.00 ng/L; P < 0.0001). A similar trend was observed in 203 healthy individuals from northern Europe (1.29 ng/L for the TT genotype vs 0.89 ng/L for the CC genotype; P = 0.07). Reporter assays that used a sequence flanking the -6331 single-nucleotide polymorphism spliced upstream to the IL-6 minimal promoter driving luciferase gene expression demonstrated a 1.3-fold increase in promoter activity (P<0.01) for constructs containing -6331T. Electrophoretic mobility shift assays revealed enhanced binding of transcription factor Oct-1 to the T allele. CONCLUSIONS: IL6 -6331T is associated with increased IL-6 concentrations in an acute inflammatory state via a mechanism involving binding of the Oct-1 transcription factor. This finding may help resolve conflicting studies based on the IL6 -174G>C variant. © 2008 American Association for Clinical Chemistry.

DOI 10.1373/clinchem.2007.098608
Citations Scopus - 80
2008 Palmen J, Smith AJP, Dorfmeister B, Putt W, Humphries SE, Talmud PJ, 'The functional interaction on in vitro gene expression of APOA5 SNPs, defining haplotype APOA5*2, and their paradoxical association with plasma triglyceride but not plasma apoAV levels', Biochimica et Biophysica Acta - Molecular Basis of Disease, 1782 447-452 (2008)

Plasma triglyceride (TG) and apoAV levels are reported to be positively correlated, yet SNPs defining haplotype APOA5*2 have consistently shown association with elevated plasma tr... [more]

Plasma triglyceride (TG) and apoAV levels are reported to be positively correlated, yet SNPs defining haplotype APOA5*2 have consistently shown association with elevated plasma triglyceride (TG) but not plasma apoAV levels. We previously reported that individually - 1131T>C, - 3A>G and + 1891T>C did not influence luciferase activity or in vitro translation efficiency. To investigate the combined effect of these SNPs additional constructs were examined. Compared to the wildtype - 1131T/- 3A/+ 1891T (TAT), the triple rare allele construct - 1131C/- 3G/+ 1891C (CGC) conferred 46% lower luciferase activity (p < 0.0001), showing these SNPs are acting co-operatively. Although only these two combinations occur in vivo, we experimentally altered the TAT construct one site at a time; - 3G (TGT) had the largest effect (94% lower luciferase), with lesser effects from CAT (- 77%) and TAC (- 70.3%) (all p < 0.0001). Deletion constructs excluding one site at a time showed that - 3G/1891C ( -GC) in combination, compared to - AT, was having the largest effect on luciferase activity (- 59%, p = 0.055). Using sequence homology and EMSA analysis no transcription factor binding at - 1131 or + 1891 was identified, though + 1891 lies within a putative mRNA stability motif. Taken together, these data identify - 3A>G in the Kozak sequence as functional, affecting translation initiation and driving the haplotype effects, while showing interaction with + 1891T>C and to a lesser extent - 1131T>C. A paradox arises since these results predict that APOA5*2 will lead to reduced apoAV with concomitant reduced LPL activation or lipoprotein-receptor interaction, resulting in higher plasma TG levels. We conclude that APOA5 expression, and not circulating plasma apoAV levels, is causatively associated with plasma TG levels. © 2008 Elsevier B.V. All rights reserved.

DOI 10.1016/j.bbadis.2008.03.003
Citations Scopus - 32
2008 Samuel JM, Kelberman D, Smith AJP, Humphries SE, Woo P, 'Identification of a novel regulatory region in the interleukin-6 gene promoter', Cytokine, 42 256-264 (2008)

Interleukin-6 (IL6) is an important pleiotropic cytokine that is regulated at the transcriptional level. To date, most work on its regulation has focused on a 1.2 kb region 5&apos... [more]

Interleukin-6 (IL6) is an important pleiotropic cytokine that is regulated at the transcriptional level. To date, most work on its regulation has focused on a 1.2 kb region 5' from the start of transcription, similar to published reports on other cytokine genes. This report demonstrates for the first time that a cytokine gene can be regulated by cis-acting regions much further upstream than previously examined. Comparative genomic analysis showed that a 120 kb region contains blocks of sequence conservation between human and rodent genomes, and that a 15 kb region proximal to the start of transcription contains 10 highly homologous sequence blocks of between 100 and 250 bp. By means of a reporter gene assay, a novel transcriptionally active region located between -5307 and -5202 bp upstream from the start of transcription was identified. Electrophoretic mobility shift assays showed nuclear protein(s) binding to this region, thus raising the possibility that the regulatory activity shown by the reporter gene constructs may be mediated by these proteins. These results suggest that the regulation of IL6 expression involves a much larger upstream region than previously examined and the control of IL6 transcription is likely to be regulated by a complex mechanism of modular cis-regulatory elements. © 2008 Elsevier Ltd. All rights reserved.

DOI 10.1016/j.cyto.2008.02.008
Citations Scopus - 24
2007 Smith AJ, 'Competency for new prescribers (Editorial)', Australian Prescriber, 30 58-59 (2007) [C3]
2007 Smith AJP, Cooper JA, Li LK, Humphries SE, 'INSIG2 gene polymorphism is not associated with obesity in Caucasian, Afro-Caribbean and Indian subjects', International Journal of Obesity, 31 1753-1755 (2007)

A common polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 transcription start site has been associated with obesity in Caucasian and African-American populati... [more]

A common polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 transcription start site has been associated with obesity in Caucasian and African-American populations, with the hypothesis that an alteration in gene expression results in elevated plasma triglyceride levels. The goal of this study was to verify the findings in a cohort of 2721 healthy Caucasian men (second Northwick Park Heart Study), and a separate study of 747 type 2 diabetic patients from Caucasian, Afro-Caribbean and Indian groups (University College London Diabetes and Cardiovascular Disease Study).The rs7566605 single-nucleotide polymorphism (SNP) was not related to plasma triglyceride levels in either study, and we found no association with body mass index or obesity in either cohort, despite having the power to detect the previously reported effect. This suggests that, at the least, the true size of the effect on obesity of this SNP is likely to be considerably less than reported previously. © 2007 Nature Publishing Group All rights reserved.

DOI 10.1038/sj.ijo.0803645
Citations Scopus - 44
2007 Smith AJP, Ahmed F, Nair D, Whittall R, Wang D, Taylor A, et al., 'A functional mutation in the LDLR promoter (-139C>G) in a patient with familial hypercholesterolemia', European Journal of Human Genetics, 15 1186-1189 (2007)

A novel sequence change in repeat 3 of the promoter of the low-density lipoprotein receptor (LDLR) gene, -139C&gt;G, has been identified in a patient with familial hypercholestero... [more]

A novel sequence change in repeat 3 of the promoter of the low-density lipoprotein receptor (LDLR) gene, -139C>G, has been identified in a patient with familial hypercholesterolemia (FH). LDLR -139G has been passed to one offspring who also shows an FH phenotype. Transient transfection studies using luciferase gene reporter assays revealed a considerable reduction (74±1.4% SEM) in reporter gene expression from the -139G variant sequence compared to the wild-type sequence, strongly suggesting that this change is the basis for FH in these patients. Analysis using electrophoretic mobility shift assay demonstrated the loss of Sp1 binding to the variant sequence in vitro, explaining the reduction of transcription.

DOI 10.1038/sj.ejhg.5201897
Citations Scopus - 18
2007 Suvarna S, Smith A, Stygall J, Kolvecar S, Walesby R, Harrison M, Newman S, 'An Intraoperative Assessment of the Ascending Aorta: A Comparison of Digital Palpation, Transesophageal Echocardiography, and Epiaortic Ultrasonography', Journal of Cardiothoracic and Vascular Anesthesia, 21 805-809 (2007)

Objectives: There are a number of techniques available to assess the aorta for atheromatous disease in the intraoperative period. This study compared the relationship among the fi... [more]

Objectives: There are a number of techniques available to assess the aorta for atheromatous disease in the intraoperative period. This study compared the relationship among the findings of digital palpation (DP), transesophageal echocardiography (TEE), and epiaortic ultrasound (EAU) in the detection of atheroma in the ascending aorta. Design: A prospective, observational study. Setting: A single-institution, cardiothoracic specialty hospital. Participants: One hundred fifty-four patients undergoing elective cardiac surgery. Interventions: The ascending aorta of patients undergoing elective coronary artery bypass surgery was assessed for atheroma by means of the 3 techniques. Atheroma was scored as present or absent. The sensitivity and specificity of the techniques were compared. Measurements and Main Results: Assuming EAU provides the "gold standard," the sensitivity of both TEE and DP were low. Digital palpation identified only 20 patients (12%); TEE 31 patients (20%); and, in contrast, EAU detected atheroma in 81 patients (53%). There were 3 and 6 false-positives by DP and TEE, respectively. Conclusion: Assuming EAU as the "gold standard" to detect atheroma, this study has shown that when assessing the ascending aorta neither DP nor TEE appear sensitive. This study supports the proposal that detection of atheroma should be performed by EAU. © 2007 Elsevier Inc. All rights reserved.

DOI 10.1053/j.jvca.2007.05.014
Citations Scopus - 34
2007 Smith A, 'Competency for new prescribers', Australian Prescriber, 30 58-59 (2007)
DOI 10.18773/austprescr.2007.032
Citations Scopus - 1
2006 Smith A, Tasioulas T, Cockayne N, Misan G, Walker G, Quick G, 'Construction and evaluation of a web-based interactive prescribing curriculum for senior medical students', British Journal of Clinical Pharmacology, 62 653-659 (2006)

Aims: To develop and evaluate for the National Prescribing Service (NPS) a web-based interactive prescribing curriculum for Australian senior medical students based on the World H... [more]

Aims: To develop and evaluate for the National Prescribing Service (NPS) a web-based interactive prescribing curriculum for Australian senior medical students based on the World Health Organization's Guide to Good Prescribing. Methods: Teachers of prescribing from all Australian medical schools in 2000 wrote 12 case-based modules which were converted to on-line format. Objective evidence was provided for selecting first-line medicines from available alternatives by comparing efficacy, safety, convenience and cost. The curriculum was made available to final year students in 2001 and was evaluated by measuring use from web statistics and by semistructured interviews with 15 teachers (2003) and on-line surveys of 363 students over 2003 and 2004. Results: By 2004 the curriculum was used by nine of 11 possible medical schools. Uptake increased each year from 2001 and all 12 modules were accessed consistently. Student access was significantly (P < 0.001) greater when prescribing was an assessable part of their course. Teachers' evaluations were uniformly supportive and the curriculum is seen as a valuable resource. Student responses came from a small proportion of those with password access but were also supportive. Over half of student respondents had created their own evidence-based formulary. Conclusions: A collaborative venture initiated by the NPS with Australian medical schools has been successfully implemented in most courses. Teachers find the resource of high quality. Student respondents find the curriculum valuable in developing their own prescribing skills. It is best delivered by self-directed study followed by tutorial discussion of prescribing decisions. © 2006 Blackwell Publishing Ltd.

DOI 10.1111/j.1365-2125.2006.02651.x
Citations Scopus - 31
2005 Hill SR, Smith AJ, 'First-line medicines in the treatment of hypertension', Australian Prescriber, 28 n.p. (2005) [C1]
Citations Scopus - 3
2005 Smith AJ, 'Unfinished business: Clinical Pharmacology and World Health', International Journal of Risk and Safety in Medicine, 17 65-71 (2005) [C1]
Citations Scopus - 2
2005 Carney SL, Gillies AH, Garvey L, Smith A, 'Direct comparison of repeated same-day self and ambulatory blood pressure monitoring', Nephrology, 10 151-156 (2005) [C1]
DOI 10.1111/j.1440-1797.2005.00364.x
Citations Scopus - 8Web of Science - 8
2005 Smith AJP, Elson CJ, Perry MJ, Bidwell JL, Meulenbelt I, Slagboom PE, Van Duijn CM, 'Accuracy of haplotype association studies is enhanced by increasing number of polymorphic loci examined: Comment on the article by Meulenbelt et al. [4] (multiple letters)', Arthritis and Rheumatism, 52 675 (2005)
DOI 10.1002/art.20813
Citations Scopus - 15
2005 Smith AJP, Gidley J, Sandy JR, Perry MJ, Kirwan JR, Spector TD, et al., 'Haplotypes of the low-density lipoprotein receptor-related protein 5 (LRP5) gene: Are they a risk factor in osteoarthritis?', Osteoarthritis and Cartilage, 13 608-613 (2005)

Objetive: Several genome-wide scans have revealed an osteoarthritis (OA)-susceptibility locus on chromosome 11q in close proximity to the low-density lipoprotein receptor-related ... [more]

Objetive: Several genome-wide scans have revealed an osteoarthritis (OA)-susceptibility locus on chromosome 11q in close proximity to the low-density lipoprotein receptor-related protein 5 (LRP5) gene. The regulation of bone mass is under the control of LRP5 and since increased bone mass is thought to play a role in the pathology of OA we examined LRP5 polymorphisms and haplotypes to determine if variants of this locus may predispose to OA. Methods: A UK control population of 187 individuals was examined for five commonly occurring polymorphisms against a cohort of 158 DNAs from patients with knee OA. An additional UK cohort was also examined to confirm the findings of the first study; this second group consisted of 110 knee OA patients. Haplotype analysis was also performed on patient and control DNAs. Results: A study of individual polymorphisms revealed no association with disease. However, haplotype analysis of the initial two populations revealed a common haplotype (C-G-C-C-A) that provided a 1.6-fold increased risk of OA (Pc = 0.021). The data obtained from the second cohort confirmed the initial findings, with a 1.6-fold increased risk observed within this cohort for the risk haplotype (P = 0.012). Conclusions: A closer investigation of LRP5 and associated Wnt signalling molecules in OA will help determine disease aetiology and the development of novel treatment strategies that specifically target the bone compartment. © 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

DOI 10.1016/j.joca.2005.01.008
Citations Scopus - 41
2005 Smith A, Hill S, Walkom E, Thambiran M, 'An evaluation of the World Health Organization problem-based pharmacotherapy teaching courses (based on the "Guide to Good Prescribing"), 1994-2001', EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 61 785-786 (2005)
DOI 10.1007/s00228-005-0990-x
Citations Scopus - 3Web of Science - 2
Co-authors Emily Walkom
2005 Ruse W, Hill S, Smith AJ, 'First-line medicines in the treatment of hypertension [2] (multiple letters)', Australian Prescriber, 28 114-115 (2005)
2004 Smith AJP, Keen LJ, Billingham MJ, Perry MJ, Elson CJ, Kirwan JR, et al., 'Extended haplotypes and linkage disequilibrium in the IL1R1-IL1A-IL1B-IL1RN gene cluster: Association with knee osteoarthritis', Genes and Immunity, 5 451-460 (2004)

The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in t... [more]

The interleukin-1 gene cluster is a key regulator in a number of chronic disease processes. We explored the linkage between nine polymorphic loci in the IL1R1 promoter, eight in the IL1A-IL1B-IL1RN gene complex, and their association with osteoarthritis (OA), a common complex disease associated with low-level inflammation. Using 195 healthy controls, we identified eight novel polymorphisms in the IL1R1 exon 1A region. We found limited LD between IL1R1 and the IL1A-IL1B-IL1RN cluster, although LD within these two individual groups was high. To test association with knee OA, we genotyped 141 patients from Bristol (UK) at the 17 loci. IL1R1 promoter haplotypes showed no association with disease. However, within the IL1A-IL1B-IL1RN complex, we identified a common haplotype conferring a four-fold risk of OA (P = 0.00043; Pc = 0.0043) and one IL1B-IL1RN haplotype conferring a four-fold reduced risk (P = 0.0036; Pc = 0.029). To replicate these associations, we subsequently examined 163 knee OA patients from London. Here, the effects of the haplotypes were confirmed: the risk IL1A-IL1B-IL1RN haplotype conferred a two-fold risk of OA (P = 0.02), and the protective IL1B-IL1RN haplotype conferred a five-fold reduced risk of OA (P = 0.0000008). These results may help to explain the genome-wide scan linkage data and functional observations concerning association between IL-1 and OA. © 2004 Nature Publishing Group. All rights reserved.

DOI 10.1038/sj.gene.6364107
Citations Scopus - 105
2004 Akter FU, Heller D, Smith A, Rahman MM, Milly AF, 'Antimicrobial use in paediatric wards of teaching hospitals in Bangladesh.', Mymensingh medical journal : MMJ, 13 63-66 (2004)

To ascertain the pattern of antimicrobial use and to assess its appropriateness a 4-month prospective study was conducted from January through April 1998 in paediatric wards of fi... [more]

To ascertain the pattern of antimicrobial use and to assess its appropriateness a 4-month prospective study was conducted from January through April 1998 in paediatric wards of five selected medical college hospitals in Bangladesh. The hospitals were selected by simple random technique. Every patient in the paediatric wards of the selected hospitals who was being treated with antimicrobials during the data collection period was considered for the study. The treatment charts of 2171 admitted paediatric patients were reviewed. Pneumonia and diarrhoea were the two most common infectious diseases among them. The most commonly used antimicrobials were ampicillin, gentamicin, amoxicillin, cloxacillin and ceftriaxone. The majority of the admitted paediatric patients (56.1%) included in this study received two or more antimicrobials in combination for their treatment. The percentages of appropriate antimicrobial treatment of pneumonia, and diarrhoea were 57.1% and 67.8% respectively across the hospitals. The evident of high percentages of inappropriate antimicrobial treatment for the most common infectious diseases suggested the need for intervention to improve antimicrobial use in hospitals.

Citations Scopus - 7
2003 Isbister GK, Hackett LP, Dawson AH, Whyte IM, Smith AJ, 'Moclobemide poisoning: toxicokinetics and occurrence of serotonin toxicity', British Journal of Clinical Pharmacology, 441-450 (2003) [C1]
DOI 10.1046/j.1365-2125.2003.01895.x
Citations Scopus - 55Web of Science - 43
Co-authors Geoffrey Isbister
2003 Smith AJ, Isbister GK, 'Antivenoms: Editorial Commentary', Journal of Toxicology, 41 261-262 (2003) [C3]
Citations Scopus - 4Web of Science - 4
Co-authors Geoffrey Isbister
2002 Robertson J, Fryer JL, O'Connell DL, Smith AN, Henry DA, 'Limitations of Health Insurance Commission (HIC) data for deriving prescribing indicators', Medical Journal of Australia, 176 419-424 (2002) [C1]
Citations Scopus - 16Web of Science - 15
Co-authors Mddah01
2002 Haukim N, Bidwell JL, Smith AJP, Keen LJ, Gallagher G, Kimberly R, et al., 'Cytokine gene polymorphism in human disease: On-line databases, supplement 2', Genes and Immunity, 3 313-330 (2002)
DOI 10.1038/sj.gene.6363881
Citations Scopus - 214
2002 Smith AJ, Tasioulas T, 'Education on prescribing can be improved [6]', British Medical Journal, 325 776-777 (2002)
Citations Scopus - 3
2001 Isbister G, Whyte IM, Smith AN, 'Olanzapine overdose', Anaesthesia, 56 400-401 (2001) [C3]
Citations Scopus - 6Web of Science - 5
Co-authors Geoffrey Isbister
2001 Robertson J, Fryer JL, O'Connell DL, Smith AN, Henry DA, 'Personal Formularies. An index of prescribing quality?', European Journal of Clinical Pharmacology, 57 333-341 (2001) [C1]
Citations Scopus - 17Web of Science - 18
Co-authors Mddah01
2001 Isbister G, Dawson AH, Whyte IM, Prior F, Clancy C, Smith AN, 'Neonatal paroxetine withdrawal syndrome or actually serotinin syndrome?', Archives of Disease in Childhood: Fetal & Neonatal Edition, 85(2) 147-148 (2001) [C3]
Citations Scopus - 54Web of Science - 39
Co-authors Geoffrey Isbister
2000 Smith AN, 'Quality use of medicines: where does pharmacology 'end'? Invited ASCEPT lecture', Clinical and Experimental Pharmacology and Physiology, 27(7) 516-519 (2000) [C1]
DOI 10.1046/j.1440-1681.2000.03286.x
Citations Scopus - 2
2000 Smith AN, McGettigan PG, 'Quality use of medicines in the community: the Australian experience', British Journal of Clinical Pharmacology, 50 515-519 (2000) [C1]
DOI 10.1046/j.1365-2125.2000.00291.x
Citations Scopus - 18
2000 Pearson S-A, Smith AN, Rolfe IE, Moulds R, Shenfield G, 'Intern Prescribing for Common Clinical Conditions', Advances in Health Sciences Education, 5 141-150 (2000) [C1]
Citations Scopus - 11Web of Science - 9
1999 Bailey B, Carney SL, Gillies AH, Smith AJ, 'Antihypertensive drug treatment: A comparison of usual care with self blood pressure measurement', Journal of Human Hypertension, 13 147-150 (1999) [C1]
Citations Scopus - 21Web of Science - 25
1999 Carney SL, Gillies AH, Green SL, Paterson O, Taylor MS, Smith AJ, 'Hospital blood pressure measurement: Staff and device assessment', Journal of Quality in Clinical Practice, 19 95-98 (1999) [C1]
Citations Scopus - 22
1999 Smith AN, 'Improving the quality of use of medicines: the Australian initiative', International Journal of Pharmaceutical Medicine, 13(2) 67-69 (1999) [C1]
1997 Smith A, McPherson J, Taylor M, Mason A, Carney S, Gillies A, 'Pro-haemorrhagic effects of calcium antagonists: a comparison of isradipine and atenolol on ex vivo platelet function in hypertensive subjects', JOURNAL OF HUMAN HYPERTENSION, 11 783-788 (1997)
DOI 10.1038/sj.jhh.1000449
Citations Scopus - 13Web of Science - 12
1997 Hill SR, Henry DD, Smith AJ, 'Rising prescription drug costs: Whose responsibility?', MEDICAL JOURNAL OF AUSTRALIA, 167 6-7 (1997)
DOI 10.5694/j.1326-5377.1997.tb138752.x
Citations Scopus - 12Web of Science - 8
1997 Bailey BJ, Carney SL, Gillies AH, McColm LM, Smith AJ, Taylor M, 'Hypertension treatment compliance: what do patients want to know about their medications?', Progress in cardiovascular nursing, 12 23-28 (1997)

While poor drug compliance is a significant impediment to the effective treatment of hypertension, knowledge of what patients wish to know about their medications in order to impr... [more]

While poor drug compliance is a significant impediment to the effective treatment of hypertension, knowledge of what patients wish to know about their medications in order to improve compliance is very limited. To develop a preliminary understanding of patients' medication requirements and expectations, a simple 30-item questionnaire was developed and administered to 66 patients who were either taking antihypertensive drugs, or about to commence antihypertensive drug treatment. Ninety percent of patients wanted to know about all possible side effects of medications as well as the most likely side effects. Ninety-six percent wanted to know if their drug treatment would keep them well. In addition, most patients wanted to avoid multiple medications, were concerned about the prospect of life-long treatment, and were worried about potential drug interactions. Effects of the drugs on their lifestyles as well as any lifestyle changes required to augment drug therapy were other issues of concern. The elderly were less interested in many of these issues. A strong desire for further knowledge about their disease was noted in most subjects (82%). If compliance with medication therapy is to be improved, a better understanding of patients' concerns and fears about medications is required, particularly in a relatively asymptomatic disease like hypertension.

Citations Scopus - 22
1996 Smith AJ, 'The quality (of) use of medicines', MEDICAL JOURNAL OF AUSTRALIA, 165 8-9 (1996)
DOI 10.5694/j.1326-5377.1996.tb124807.x
Citations Scopus - 2Web of Science - 3
1996 Buckley NA, Smith AJ, 'Evidence-based medicine in toxicology: Where is the evidence?', LANCET, 347 1167-1169 (1996)
DOI 10.1016/S0140-6736(96)90615-7
Citations Scopus - 7Web of Science - 16
1996 Buckley NA, Smith AJ, Dosen P, OConnell DL, 'Effects of catecholamines and diazepam in chloroquine poisoning in barbiturate anaesthetised rats', HUMAN & EXPERIMENTAL TOXICOLOGY, 15 909-914 (1996)
DOI 10.1177/096032719601501108
Citations Scopus - 1Web of Science - 1
1996 Buckley NA, Smith AJ, 'Evidence-based medicine in toxicology: Where is the evidence?', Lancet, 347 167-169 (1996)
Citations Scopus - 9
1996 Buckley NA, Smith AJ, 'Evidence-based medicine in toxicology: Where is the evidence?', Lancet, 347 1067-1069 (1996)
Citations Scopus - 2
1995 MYERS SP, SMITH AJ, 'EFFECTS OF GARLIC EXTRACT ON PLATELET-AGGREGATION', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 22 888-888 (1995)
DOI 10.1111/j.1440-1681.1995.tb01958.x
1995 SMITH AJ, WALTERS WA, BUCKLEY NA, GALLAGHER L, MASON A, MCPHERSON J, 'HYPERTENSIVE AND NORMAL-PREGNANCY - A LONGITUDINAL-STUDY OF BLOOD-PRESSURE, DISTENSIBILITY OF DORSAL HAND VEINS AND THE RATIO OF THE STABLE METABOLITES OF THROMBOXANE A(2) AND PROSTACYCLIN IN PLASMA', BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY, 102 900-906 (1995)
DOI 10.1111/j.1471-0528.1995.tb10879.x
Citations Scopus - 14Web of Science - 11
1995 ROLFE IE, ANDREN JM, PEARSON S, HENSLEY MJ, GORDON JJ, 'CLINICAL COMPETENCE OF INTERNS', MEDICAL EDUCATION, 29 225-230 (1995)
DOI 10.1111/j.1365-2923.1995.tb02835.x
Citations Scopus - 42Web of Science - 36
Co-authors Michael Hensley
1995 Carney SL, Gillies AHB, Smith AJ, Smitham S, 'Hospital sphygmomanometer use: An audit', Journal of Quality in Clinical Practice, 15 17-22 (1995)

Periodic evaluation over the past 20 years of the ability of clinical staff to accurately measure blood pressure, as well as the functional state of sphygmomanometers, has frequen... [more]

Periodic evaluation over the past 20 years of the ability of clinical staff to accurately measure blood pressure, as well as the functional state of sphygmomanometers, has frequently demonstrated significant deficiencies. The data presented here are the results of a recent audit in the Newcastle area. Medical (48) and nursing (217) staff in five general hospitals (3 public, 2 private), were questioned on sphygmomanometer use, observed taking a blood pressure reading and asked to record blood pressures from a videotape. In addition, all hospital sphygmomanometers were checked to see if they were in working order. Of 463 sphygmomanometers evaluated, 58% were in perfect working order. There was a marked variation in the state of equipment between institutions (40 to 94%). Staff knowledge and technical ability in sphygmomanometer use was similar in doctors and nurses, with 69% of doctors and 71% of nurses knowing that phase V Korotkoff sounds best approximated adult diastolic blood pressure. Knowledge of appropriate cuff size and ability to use a sphygmomanometer was also similar between the two groups. However, doctors performed better in measuring systolic and diastolic blood pressures from a videotape (9.3 ± 1.7 correct compared with 7.8 ± 1.9 for nurses; P<0.01). It was concluded that, with the exception of one hospital, the state of repair of sphygmomanometers was poor. Staff knowledge of sphygmomanometer usage and their ability to record blood pressure was satisfactory. However, not all practising health professionals are competent in using a sphygmomanometer.

Citations Scopus - 4
1995 de Vries TPGM, Henning RH, Hogerzeil HV, Bapna JS, Bero L, Kafle KK, et al., 'Impact of a short course in pharmacotherapy for undergraduate medical students: an international randomised controlled study', The Lancet, 346 1454-1457 (1995)

Summary. Irrational prescribing is a habit which is difficult to cure. However, prevention is possible and for this reason the WHO Action Programme on Essential Drugs aims to impr... [more]

Summary. Irrational prescribing is a habit which is difficult to cure. However, prevention is possible and for this reason the WHO Action Programme on Essential Drugs aims to improve the teaching of pharmacotherapy to medical students. The impact of a short problem-based training course in pharmacotherapy, using a WHO manual on the principles of rational prescribing, was measured in an international multi-centre randomised controlled study of 219 undergraduate medical students in Groningen (Netherlands), Kathmandu (Nepal), Lagos (Nigeria), Newcastle (Australia), New Delhi (India), San Francisco (USA), and Yogyakarta (Japan). The manual and the course presented the students, who were about to enter the clinical phase of their studies, with a normative model for pharmacotherapeutic reasoning in which they were taught to generate a "standard" pharmacotherapeutic approach to common disorders, resulting in a set of first-choice drugs called P(ersonal)-drugs. The students were then taught how to apply this set of P-drugs to specific patient problems on the symptomatic treatment of pain, using a six-step problem-solving routine. The impact of the course was measured by tests before training, immediately after, and six months later. After the course, students from the study group performed significantly better than controls in all patient problems presented (p<0·05). The students not only remembered how to solve old problems, but they could also apply their skills to new problems. Both retention and transfer effect were maintained at least six months after the training session in all seven medical schools. In view of the impossibiity of teaching students all basic knowledge on the thousands of drugs available, this approach seems to be an efficient way of teaching rational prescribing. However, the method should be accompanied by a change in teaching methods away from the habit of transferring knowledge about the drugs towards problem-based teaching of therapeutic reasoning. © 1995.

DOI 10.1016/S0140-6736(95)92472-8
Citations Scopus - 93
1995 SMITH AJ, HAMILTON JD, ROLFE IE, PEARSON SA, 'UNTITLED - REPLY', MEDICAL JOURNAL OF AUSTRALIA, 162 498-498 (1995)
DOI 10.5694/j.1326-5377.1995.tb140021.x
Citations Web of Science - 1
1995 ROLFE IE, PEARSON S, POWIS DA, SMITH AJ, 'TIME FOR A REVIEW OF ADMISSION TO MEDICAL-SCHOOL', LANCET, 346 1329-1333 (1995)
DOI 10.1016/S0140-6736(95)92344-6
Citations Scopus - 54Web of Science - 56
1994 Hill SR, Smith AJ, 'The response to arachidonic acid before and after non-steroidal anti-inflammatory drugs in normotensive and hypertensive rats', Journal of Hypertension, 12 891-899 (1994)

Objective: To establish equivalent doses of four non-steroidal anti-inflammatory drugs (NSAID) in normotensive and hypertensive rats using inhibition of the fall in blood pressure... [more]

Objective: To establish equivalent doses of four non-steroidal anti-inflammatory drugs (NSAID) in normotensive and hypertensive rats using inhibition of the fall in blood pressure produced by the injection of arachidonic acid as the measure of equivalence. Design: An experimental study using two rat models of hypertension and their normotensive controls. Methods: Two rat models of hypertension (spontaneously hypertensive rats and two-kidney, one clip rats) and their normotensive controls were studied. The change in blood pressure after intravenous injection of arachidonic acid was measured in anaesthetized rats. Blood pressure was measured from a carotid artery cannula, attached to a pen-recorder. Dose-response curves for the effect of arachidonic acid were established in each type of rat, then the effects of different doses of four NSAID (indomethacin, piroxicam, naproxen and sulindac) on these responses were measured. Results: Arachidonic acid produced a dose-dependent fall in blood pressure in all rats. However, both types of hypertensive rats sustained a larger fall in blood pressure for a given dose of arachidonic acid than did the normotensive controls. Doses of NSAID were found that inhibited this response in Wistar rats. However, the doses of NSAID that were equivalent in normotensive rats were not equivalent in either type of hypertensive rat; indomethacin had a greater inhibitory effect. As far as could be established, this was not due to differences in the metabolism of the NSAID between normotensive and hypertensive rats. Conclusions: The arachidonic acid response can be used as a method of establishing equivalent doses of NSAID in normotensive and hypertensive rats. Hypertensive rats appear to be more sensitive to the effects of arachidonic acid than normotensive rats, independent of the model of hypertension. Doses of NSAID that are equivalent in normotensive rats are not equivalent in hypertensive rats. Indomethacin is more effective in attenuating the effect of arachidonic acid, possibly due to actions other than inhibition of cyclo-oxygenase. © Current Science Ltd.

DOI 10.1097/00004872-199408000-00006
Citations Scopus - 1
1994 Smith AJ, Gerkens JF, Dosen P, 'WEB-2086 AND INDOMETHACIN DO NOT MODIFY BLOOD PRESSURE FALL ON UNCLIPPING HYPERTENSIVE RATS', Clinical and Experimental Pharmacology and Physiology, 21 413-416 (1994)

1. Pretreatment with intravenous WEB-2086 (0.5 mg/ kg; an antagonist of the actions of platelet activating factor; PAF) with or without indomethacin (2 mg/ kg) failed to prevent o... [more]

1. Pretreatment with intravenous WEB-2086 (0.5 mg/ kg; an antagonist of the actions of platelet activating factor; PAF) with or without indomethacin (2 mg/ kg) failed to prevent or modify the fall in blood pressure following unclipping of the renal artery of anaesthetized two-kidney, one-clip hypertensive rats. 2. The same medications given to two other groups of rats 60 min after unclipping when the blood pressure had fallen to stable levels failed to reverse the fall. 3. Despite evidence that both prostanoids and PAF can be detected in increased amounts in renal venous blood after unclipping, they do not appear to mediate the reduction in blood pressure in this model of reversible hypertension. Copyright © 1994, Wiley Blackwell. All rights reserved

DOI 10.1111/j.1440-1681.1994.tb02535.x
Citations Scopus - 2
1994 Smith AJ, Barnsley L, Cameron R, Engel CE, Feletti GI, Hazell P, et al., 'Ratings of Performance of Graduates from Traditional and Nontraditional Medical Schools', Teaching and Learning in Medicine, 6 179-184 (1994)

We compared clinical supervisors¿ ratings of intern competence in Newcastle University graduates (whose medical school emphasizes community relevance and interpersonal skills) and... [more]

We compared clinical supervisors¿ ratings of intern competence in Newcastle University graduates (whose medical school emphasizes community relevance and interpersonal skills) and in medical graduates of the Universities of Sydney and New South Wales, which have more traditional curricula. A 12-item anchored supervisor rating scale was used to assess the professional competence of 428 interns on five occasions throughout the intern year. Data analysis was performed using two factors of clinical competence and personal characteristics, as well as an average annual total score. linear regression analysis was employed to estimate the adjusted effects of age, sex, and graduating university on the three scores. All three scores were higher for interns who graduated at younger than 25 years, irrespective of university of graduation or sex. Women scored higher on average than men, and Newcastle graduates were rated significantly better on average than Sydney University graduates for the personal characteristics scores. At the beginning of the intern year, Newcastle graduates had higher total scores than graduates from the two other medical schools. By the end of the intern year, there was no difference in total scores for the three universities. The results of this study suggest that age, sex, and curriculum background are factors influencing aspects of performance at entry to the internship year and also the professional development of interns throughout that year. © 1994, Taylor & Francis Group, LLC. All rights reserved.

DOI 10.1080/10401339409539672
Citations Scopus - 17
1994 Garland HO, Birdsey TJ, Davidge CG, McLaughlin JT, Oakes LM, Smith AJ, Harpur ES, 'EFFECTS OF GENTAMICIN, NEOMYCIN AND TOBRAMYCIN ON RENAL CALCIUM AND MAGNESIUM HANDLING IN TWO RAT STRAINS', Clinical and Experimental Pharmacology and Physiology, 21 109-115 (1994)

1. Standard renal clearance techniques were used to compare the acute effects of gentamicin, neomycin and tobramycin on renal calcium and magnesium handling in Sprague-Dawley and ... [more]

1. Standard renal clearance techniques were used to compare the acute effects of gentamicin, neomycin and tobramycin on renal calcium and magnesium handling in Sprague-Dawley and Fischer 344 rats. 2. Significant hypercalciuric and hypermagnesiuric responses to all three drugs (P<0.01) were apparent within 30 min of the onset of drug infusion. 3. The magnitude of the acute hypercalciuric and hypermagnesiuric response to the three aminoglycosides was comparable. This contrasts with their nephrotoxic action where neomycin >> gentamicin > tobramycin. The magnitude of the acute physiological responses to these drugs do not therefore reflect their nephrotoxic potential. 4. Sprague-Dawley rats were at least as responsive as Fischer rats in their acute renal responses to gentamicin. If Fischer rats are more sensitive to aminoglycoside nephrotoxicity than Sprague-Dawley rats, this is not reflected in their acute responses to gentamicin. Copyright © 1994, Wiley Blackwell. All rights reserved

DOI 10.1111/j.1440-1681.1994.tb02476.x
Citations Scopus - 14
1994 Smith AJ, 'Doctors and homosexuality. Homophobia is the wrong word [8]', British Medical Journal, 308 854 (1994)
1994 HOWARTH DM, DAWSON AH, SMITH AJ, BUCKLEY N, WHYTE IM, 'CALCIUM-CHANNEL BLOCKING DRUG OVERDOSE - AN AUSTRALIAN SERIES', HUMAN & EXPERIMENTAL TOXICOLOGY, 13 161-166 (1994)
DOI 10.1177/096032719401300304
Citations Scopus - 65Web of Science - 53
1993 CARNEY S, GILLIES A, SMITH A, TAYLOR M, 'HYPERTENSION EDUCATION - PATIENT KNOWLEDGE AND SATISFACTION', JOURNAL OF HUMAN HYPERTENSION, 7 505-508 (1993)
Citations Scopus - 7Web of Science - 11
1993 SMITH AJ, GILLIES A, CARNEY S, TAYLOR M, HARVEY D, RATCLIFFE I, GANDY M, 'RANDOMIZED, DOUBLE-BLIND CROSSOVER COMPARISON OF ONCE-DAILY CAPTOPRIL AND LISINOPRIL IN PATIENTS WITH MILD TO MODERATE HYPERTENSION - A COMMUNITY-BASED STUDY', CLINICAL AND EXPERIMENTAL HYPERTENSION, 15 423-434 (1993)
DOI 10.3109/10641969309032944
Citations Scopus - 1Web of Science - 1
1992 CARNEY SL, MCCOLM GL, SMITH AJ, BRADBURY R, CHARLTON W, COLLINS K, et al., 'COMBINED EFFECT OF DOXAZOSIN AND PINDOLOL ON BLOOD-PRESSURE CONTROL AND LIPID CONCENTRATIONS IN PATIENTS WITH ESSENTIAL-HYPERTENSION SELECTED FROM GENERAL-PRACTICE', JOURNAL OF HUMAN HYPERTENSION, 6 181-184 (1992)
Citations Scopus - 4Web of Science - 3
1992 SMITH AJ, 'WHY DOES AUSTRALIA HAVE NO NATIONAL DRUG POLICY', MEDICAL JOURNAL OF AUSTRALIA, 156 299-300 (1992)
DOI 10.5694/j.1326-5377.1992.tb139778.x
Citations Scopus - 3Web of Science - 4
1992 SMITH AJ, 'WHY DOES AUSTRALIA HAVE NO NATIONAL DRUG POLICY - REPLY', MEDICAL JOURNAL OF AUSTRALIA, 156 739-739 (1992)
DOI 10.5694/j.1326-5377.1992.tb121524.x
Citations Scopus - 1Web of Science - 2
1992 HILL S, WHYTE IM, SMITH AJ, WHITE T, 'A COMPUTERIZED METHOD FOR MEASUREMENT AND ANALYSIS OF BLOOD-PRESSURE IN SMALL ANIMALS', JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 27 233-243 (1992)
DOI 10.1016/1056-8719(92)90046-4
Citations Scopus - 1Web of Science - 1
1991 SMITH AJ, 'PRESCRIPTION CHARGES AND THE EVALUATION OF HEALTH POLICIES', MEDICAL JOURNAL OF AUSTRALIA, 154 303-304 (1991)
DOI 10.5694/j.1326-5377.1991.tb112877.x
1991 SMITH AJ, ARONSON JK, THOMAS M, 'ANTIBIOTICS POLICIES IN THE DEVELOPING-WORLD', EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 41 85-87 (1991)
Citations Scopus - 10Web of Science - 6
1991 CARNEY SL, GILLIES AH, SMITH AJ, SMITHAM S, 'INCREASED DIETARY-SODIUM CHLORIDE IN PATIENTS TREATED WITH ANTIHYPERTENSIVE DRUGS', CLINICAL AND EXPERIMENTAL HYPERTENSION PART A-THEORY AND PRACTICE, 13 401-407 (1991)
DOI 10.3109/10641969109045059
Citations Scopus - 11Web of Science - 11
1990 SMITH AJ, 'TRENDS IN PRESCRIBING - THE DAWN OF DUSC', MEDICAL JOURNAL OF AUSTRALIA, 152 228-230 (1990)
DOI 10.5694/j.1326-5377.1990.tb120914.x
Citations Scopus - 1Web of Science - 4
1990 SMITH AJ, 'TRENDS IN PRESCRIBING - THE DAWN OF DUSC', MEDICAL JOURNAL OF AUSTRALIA, 152 504-504 (1990)
DOI 10.5694/j.1326-5377.1990.tb125342.x
1990 DAWSON AH, HARVEY D, SMITH AJ, TAYLOR M, WHYTE IM, JOHNSON CI, et al., 'LISINOPRIL OVERDOSE', LANCET, 335 487-488 (1990)
DOI 10.1016/0140-6736(90)90731-J
Citations Scopus - 11Web of Science - 13
1990 SMITH AJ, BRENT PJ, HENRY DA, FOY A, 'PLASMA NORADRENALINE, PLATELET ALPHA-2-ADRENOCEPTORS, AND FUNCTIONAL SCORES DURING ETHANOL WITHDRAWAL', ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 14 497-502 (1990)
DOI 10.1111/j.1530-0277.1990.tb01187.x
Citations Scopus - 28Web of Science - 21
1989 Carney SL, Gillies A, Heller RF, Smith AJ, Taylor M, Boyle CF, et al., 'Effects of pindolol, or a pindolol/clopamide combination preparation, on plasma lipid levels in essential hypertension', Medical Journal of Australia, 150 646-652 (1989)

In an open study that was conducted in general practice, 22 patients with previously-untreated mild hypertension received an average daily dose of 11.7 mg of pindolol over a 50-we... [more]

In an open study that was conducted in general practice, 22 patients with previously-untreated mild hypertension received an average daily dose of 11.7 mg of pindolol over a 50-week study period. The total cholesterol, high-density lipoprotein fraction and plasma triglyceride levels showed no significant change from baseline values at the conclusion of this period. A separate group of 18 patients were treated with 10 mg of pindolol a day for 12 weeks, to which regimen was added 5 mg of clopamide for the succeeding 38 weeks. A small rise in total plasma cholesterol levels in this group of patients at both 12 and 50 weeks did not achieve statistical significance, and no change was observed in either the high-density lipoprotein fraction or the plasma triglyceride levels. These results which were obtained in general practice and over a prolonged period of time accord with the general view that the treatment of hypertension with pindolol, a ß-receptor blocking drug with partial agonist activity, is not associated with either the increase in total plasma cholesterol levels or the falls in the high-density lipoprotein fraction that have been reported with other ß-blocking compounds.

DOI 10.5694/j.1326-5377.1989.tb136730.x
Citations Scopus - 1
1989 Shaw J, Bochner F, Brooks PM, McNeil JJ, Moulds RFW, Ravenscroft PJ, Smith AJ, 'Fluid management of shock in critically-ill patients', Medical Journal of Australia, 150 508-517 (1989)

This article summarizes the theoretical basis and practical applications of the fluid management of shock in critically-ill patients. It also draws attention to the differences in... [more]

This article summarizes the theoretical basis and practical applications of the fluid management of shock in critically-ill patients. It also draws attention to the differences in the aetiology and management of fluid disturbances in adult and paediatric practice. Some evidence suggests that colloidal solutions alone may be superior to crystalloid solutions alone in the resuscitation of patients with shock, but in most situations a combination of both types of fluid is more logical.

DOI 10.5694/j.1326-5377.1989.tb136598.x
Citations Scopus - 2
1989 SMITH AJ, POWIS DA, 'THE POLITICS OF THE SAND-PIT', MEDICAL JOURNAL OF AUSTRALIA, 150 543-544 (1989)
DOI 10.5694/j.1326-5377.1989.tb136682.x
1989 FORD FM, HUNTER M, HENSLEY MJ, GILLIES A, CARNEY S, SMITH AJ, et al., 'HYPERTENSION AND ASTHMA - PSYCHOLOGICAL-ASPECTS', SOCIAL SCIENCE & MEDICINE, 29 79-84 (1989)
DOI 10.1016/0277-9536(89)90130-5
Citations Scopus - 11Web of Science - 10
Co-authors Michael Hensley, Mick Hunter
1988 Gerkens JF, Armsworth SJ, Dosen PJ, Smith AJ, 'ENDOTHELIUM-DEPENDENT INHIBITION OF SYMPATHETIC VASOCONSTRICTION BY FRUSEMIDE ADMINISTRATION TO RATS', Clinical and Experimental Pharmacology and Physiology, 15 449-455 (1988)

1. Segments of the tail artery of the rat were cannulated at both ends and mounted in an organ bath filled with Krebs solution. 2. Using an extracorporeal circuit, blood was pumpe... [more]

1. Segments of the tail artery of the rat were cannulated at both ends and mounted in an organ bath filled with Krebs solution. 2. Using an extracorporeal circuit, blood was pumped at a constant 2 ml/min from the carotid artery of anaesthetized rats to perfuse the segment of tail artery, and returned to the donor rat via the jugular vein. 3. Peri-arterial electrical stimulation of the ex vivo blood perfused tail artery at 5 Hz produced vasoconstriction and an increase in perfusion pressure. 4. The intravenous administration of frusemide 5 mg/kg to the donor rat resulted in an inhibition of the vasoconstrictor responses of the perfused tail artery segment. Diuresis-induced losses of volume and frusemide were prevented by a urinary bladder-venous shunt. 5. Removal of the endothelium from the tail artery segment, by perfusion with dry gas for 4 min, prevented the vasoconstrictor-inhibitory effect of frusemide administration. Removal of the endothelium was confirmed histologically and by the absence of a vasodilator response to acetylcholine. 6. On the basis of these and previous results it is concluded that parenteral frusemide administration releases an unidentified but non-prostanoid hormone from the kidney which produces an endothelium-dependent inhibition of sympathetic vascoconstriction. Copyright © 1988, Wiley Blackwell. All rights reserved

DOI 10.1111/j.1440-1681.1988.tb01100.x
Citations Scopus - 11
1988 SMITH AJ, WHYTE IM, 'NEW DRUGS FOR OLD - AN ISSUE FOR DEBATE', MEDICAL JOURNAL OF AUSTRALIA, 149 581-582 (1988)
DOI 10.5694/j.1326-5377.1988.tb120794.x
Citations Scopus - 3Web of Science - 6
1988 BECKHOUSE MJ, WHYTE IM, BYTH PL, NAPIER JC, SMITH AJ, 'ALTERED AMINOGLYCOSIDE PHARMACOKINETICS IN THE CRITICALLY ILL', ANAESTHESIA AND INTENSIVE CARE, 16 418-422 (1988)
DOI 10.1177/0310057X8801600406
Citations Scopus - 45Web of Science - 45
1988 Dash BH, Blank RG, Schachtel BP, Smith AJ, 'Ibuprofen tablets dissolution versus bioavailability', Drug Development and Industrial Pharmacy, 14 1629-1645 (1988)

Dissolution studies and a 24 patient randomized double-blind crossover bioavailability study were performed using two commercially-sized batches of an ibuprofen 200 mg tablet form... [more]

Dissolution studies and a 24 patient randomized double-blind crossover bioavailability study were performed using two commercially-sized batches of an ibuprofen 200 mg tablet formulation (sugar-coated). The batches were equivalent with respect to the USP dissolution test, but differed, particularly from tablet-to-tablet, when a paddle at 50 rpm was substituted, one batch consistently giving a high dissolution and the other consistently giving a low dissolution. The bioavailability study showed the batches to be bioequivalent, thus prompting an investigation as to why the substitution of a paddle at 50 rpm gave no correlation with bioavailability and should therefore be unsuitable as a standard dissolution test. It was found that soaking tablets in acid prior to using the paddle at 50 rpm (thus simulating more closely the in vivo pH sequence) increased the dissolution rate. The increase is such that the maximum dissolution rate, which also approximates that given by the USP method, is achievable within five minutes, even when the presoak medium is an unbuffered solution of hydrochloric acid at pH 4. A standard presoak procedure was then developed consisting of soaking each tablet for five minutes in 5 ml of USP gastric fluid without pepsin at room temperature and with no agitation. A comprehensive application of this procedure to both batches consistently produced results equivalent to those obtained by the USP method. In particular, there was very little tablet to tablet variation. Studies with formulations of varying bioavailability will be necessary before it can be determined whether this new acid presoak procedure will provide a more meaningful dissolution test compared with the current USP method. © 1988 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

DOI 10.3109/03639048809151954
Citations Scopus - 4
1987 CHALMERS J, WING L, WEST M, BUNE A, JOHNSTON C, JACKSON B, et al., 'FELODIPINE COMPARED TO PRAZOSIN AS ADDITIONAL THERAPY TO A BETA-BLOCKING DRUG', JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 10 S82-S84 (1987)
Citations Scopus - 1Web of Science - 2
1987 Gerkens JF, Armsworth SJ, Bhagwandeen BS, Smith AJ, 'Chemical renal medullectomy prevents frusemide-induced inhibition of sympathetic vasoconstriction in the in situ blood perfused rat mesentery', Journal of Hypertension, 5 273-275 (1987)
Citations Scopus - 12Web of Science - 11
Co-authors Brahm Bhagwandeen
1987 GERKENS JF, ARMSWORTH SJ, SMITH AJ, 'INHIBITION OF SYMPATHETIC CONSTRICTION OF THE EXVIVO TAIL ARTERY PERFUSED WITH BLOOD FROM RATS GIVEN FRUSEMIDE', CLINICAL AND EXPERIMENTAL HYPERTENSION PART A-THEORY AND PRACTICE, 9 51-79 (1987)
DOI 10.3109/10641968709160030
Citations Scopus - 13Web of Science - 16
1987 SMART YC, GILLIES AHB, WAGA SW, CARNEY SL, SMITH AJ, BURTON RC, 'EFFECTS OF CAPTOPRIL ON CIRCULATING T-LYMPHOCYTE SUBSETS', INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS, 25 389-391 (1987)
Citations Scopus - 8Web of Science - 9
1987 Dawson AH, Smith AJ, 'Common prescribing errors.', Australian family physician, 16 915-916 (1987)
Citations Scopus - 1
1986 Armsworth SJ, Gerkens JF, Smith AJ, 'FRUSEMIDE INHIBITION OF SYMPATHETIC VASOCONSTRICTION IN THE RAT IN SITU BLOOD PERFUSED MESENTERY', Clinical and Experimental Pharmacology and Physiology, 13 495-503 (1986)

1. Mesenteric perfusion pressure was measured in the in situ blood-perfused mesentery of anaesthetized rats. Increases in perfusion pressure were produced by mesenteric periarteri... [more]

1. Mesenteric perfusion pressure was measured in the in situ blood-perfused mesentery of anaesthetized rats. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation at 3, 6 and 10 Hz before and after the administration of frusemide 5 mg/kg intravenously (i.v.) or vehicle. Loss of volume due to diuresis was prevented by replacement with intravenous saline. 2. Frusemide did not cause any changes in blood pressure or baseline perfusion pressure. Responses to electrical stimulation were inhibited by frusemide (P < 0.05) but unchanged by vehicle administration. 3. Acute bilateral nephrectomy or treatment with indomethacin (2 mg/kg i.v.) prevented the inhibitory effect of frusemide on responses to sympathetic nerve stimulation. 4. Responses to sympathetic nerve stimulation were potentiated by an infusion of angiotensin II (12 ng/min) into the mesenteric artery. This infusion did not alter either blood pressure or baseline perfusion pressure. Administration of frusemide 5 mg/kg i.v. attenuated the potentiating effect of angiotensin II on vasoconstrictor responses to electrical nerve stimulation. 5. Frusemide may lead to the release of a prostanoid or prostanoid precursor which inhibits vascular constrictor responses. Copyright © 1986, Wiley Blackwell. All rights reserved

DOI 10.1111/j.1440-1681.1986.tb00930.x
Citations Scopus - 13
1986 Mitchell A, Gillies AL, Carney S, Smith AJ, 'Cough and Captopril', Archives of Internal Medicine, 146 1017 (1986)
DOI 10.1001/archinte.1986.00360170275038
Citations Scopus - 12
1986 CARNEY SL, GILLIES AH, SMITH AJ, FLOATE LF, 'EFFECT OF TRIAL THERAPY ON SUBSEQUENT THERAPY - A REVIEW OF PATIENTS WITH HYPERTENSION WHO HAVE COMPLETED A PHARMACOLOGICAL INTERVENTION STUDY', MEDICAL JOURNAL OF AUSTRALIA, 144 315-316 (1986)
DOI 10.5694/j.1326-5377.1986.tb128384.x
1986 HARDWICKE C, HOLT L, JAMES R, SMITH AJ, 'TRENDS IN SELF-POISONING WITH DRUGS IN NEWCASTLE, NEW-SOUTH-WALES, 1980-1982', MEDICAL JOURNAL OF AUSTRALIA, 144 453-454 (1986)
DOI 10.5694/j.1326-5377.1986.tb101046.x
Citations Scopus - 31Web of Science - 36
1986 WIKSTRAND J, WESTERGREN G, BERGLUND G, BRACCHETTI D, VANCOUTER A, FELDSTEIN CA, et al., 'ANTIHYPERTENSIVE TREATMENT WITH METOPROLOL OR HYDROCHLOROTHIAZIDE IN PATIENTS AGED 60 TO 75 YEARS - REPORT FROM A DOUBLE-BLIND INTERNATIONAL MULTICENTER STUDY', JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 255 1304-1310 (1986)
DOI 10.1001/jama.255.10.1304
Citations Scopus - 74Web of Science - 72
1985 BRENT PJ, HALL S, HENRY DA, SMITH AJ, 'STABILITY OF NOREPINEPHRINE IN BLOOD', CLINICAL CHEMISTRY, 31 659-660 (1985)
Citations Scopus - 6Web of Science - 7
1985 Gerkens JF, Smith AJ, 'Effect of captopril and theophylline treatment on cyclosporine induced nephrotoxicity in rats', Transplantation, 40 213-214 (1985)
DOI 10.1097/00007890-198508000-00021
Citations Scopus - 16
1985 BRENT PJ, HALL S, SMITH AJ, AYLWARD J, 'A SIMPLIFIED LIQUID-CHROMATOGRAPHY AND ELECTROCHEMICAL DETECTION METHOD FOR MEASUREMENT OF PLASMA NORADRENALINE', JOURNAL OF PHARMACOLOGICAL METHODS, 14 243-248 (1985)
DOI 10.1016/0160-5402(85)90036-1
Citations Scopus - 9Web of Science - 14
1984 GILLIES AHB, CARNEY SL, SMITH AJ, WAGA SM, 'ADJUNCTIVE EFFECT OF SALT RESTRICTION ON ANTIHYPERTENSIVE EFFICACY', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 11 395-398 (1984)
DOI 10.1111/j.1440-1681.1984.tb00286.x
Citations Scopus - 4Web of Science - 5
1984 CARNEY SL, GILLIES AHB, SMITH AJ, WAGA S, 'EFFECT OF DIETARY-SODIUM RESTRICTION ON PATIENTS RECEIVING ANTIHYPERTENSIVE MEDICATION', CLINICAL AND EXPERIMENTAL HYPERTENSION PART A-THEORY AND PRACTICE, 6 1095-1105 (1984)
DOI 10.3109/10641968409039583
Citations Scopus - 11Web of Science - 9
1984 GERKENS JF, SMITH AJ, 'INHIBITION OF VASOCONSTRICTION BY FRUSEMIDE IN THE RAT', BRITISH JOURNAL OF PHARMACOLOGY, 83 363-371 (1984)
DOI 10.1111/j.1476-5381.1984.tb16496.x
Citations Scopus - 19Web of Science - 20
1984 GERKENS JF, BHAGWANDEEN SB, DOSEN PJ, SMITH AJ, 'THE EFFECT OF SALT INTAKE ON CYCLOSPORINE-INDUCED IMPAIRMENT OF RENAL-FUNCTION IN RATS', TRANSPLANTATION, 38 412-417 (1984)
DOI 10.1097/00007890-198410000-00019
Citations Scopus - 35Web of Science - 63
Co-authors Brahm Bhagwandeen
1984 SHAW J, SMITH AJ, 'A FURTHER LOOK AT DEXTROPROPOXYPHENE', MEDICAL JOURNAL OF AUSTRALIA, 140 193-193 (1984)
DOI 10.5694/j.1326-5377.1984.tb103992.x
1984 SMITH AJ, 'CLINICAL-TRIALS', MEDICAL JOURNAL OF AUSTRALIA, 140 720-723 (1984)
DOI 10.5694/j.1326-5377.1984.tb108361.x
1984 FELETTI GI, SAUNDERS NA, SMITH AJ, ENGEL CE, 'ASSESSMENT OF INDEPENDENT LEARNING', MEDICAL TEACHER, 6 70-73 (1984)
DOI 10.3109/01421598409034779
Citations Scopus - 7Web of Science - 6
1983 FELETTI GI, SAUNDERS NA, SMITH AJ, 'COMPREHENSIVE ASSESSMENT OF FINAL-YEAR MEDICAL-STUDENT PERFORMANCE BASED ON UNDERGRADUATE PROGRAM OBJECTIVES', LANCET, 2 34-37 (1983)
Citations Scopus - 19Web of Science - 16
1983 SMITH AJ, STEWART LM, 'BINDING OF (H-3)-LABELED RAUWOLSCINE TO INTACT HUMAN-BLOOD PLATELETS', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 10 702-703 (1983)
1983 SAUNDERS NA, SMITH AJ, FELETTI GI, CLARKE RM, 'EDUCATION, TRAINING AND PROFESSIONAL-DEVELOPMENT', MEDICAL EDUCATION, 17 138-139 (1983)
DOI 10.1111/j.1365-2923.1983.tb01115.x
1983 Feletti GI, Saunders NA, Smith AJ, 'Evaluation of a comprehensive non-traditional assessment for final year medical students.', Proceedings of the . Annual Conference on Research in Medical Education. Conference on Research in Medical Education, 22 32-37 (1983)
1982 Smith AJ, Bing RF, 'CATECHOLAMINES IN ESSENTIAL HYPERTENSION', The Lancet, 319 112-113 (1982)
DOI 10.1016/S0140-6736(82)90256-2
Citations Scopus - 5
1982 RATNARAJAH S, MEARRICK PT, MAJOR GAC, SMITH AJ, GLASS J, 'EFFICACY OF TWICE-DAILY VERSUS THRICE-DAILY CARPROFEN IN ACTIVE RHEUMATOID-ARTHRITIS', CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL, 32 59-64 (1982)
Citations Web of Science - 1
1981 MYERS JB, SMITH AJ, ELLIOTT RL, MACASKILL P, 'SELF-POISONING WITH DRUGS - A 3 1/2-YEAR STUDY IN NEWCASTLE, NSW', MEDICAL JOURNAL OF AUSTRALIA, 2 402-405 (1981)
DOI 10.5694/j.1326-5377.1981.tb101028.x
Citations Scopus - 20Web of Science - 33
1981 SMITH AJ, MACASKILL P, ELLIOTT RL, MYERS JB, 'SELF-POISONING WITH DRUGS IN NEWCASTLE, NSW, 1976-79', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 8 635-636 (1981)
1981 Bing RF, Smith AJ, 'Plasma and interstitial volumes in essential hypertension: Relationship to blood pressure', Clinical Science, 61 287-293 (1981)

Plasma and interstitial fluid volumes have been measured simultaneously in men with uncomplicated and untreated essential hypertension. Plasma volume (Evans blue) was reduced in e... [more]

Plasma and interstitial fluid volumes have been measured simultaneously in men with uncomplicated and untreated essential hypertension. Plasma volume (Evans blue) was reduced in essential hypertension and correlated inversely with blood pressure. Interstitial fluid volume, derived from bromine space and plasma volume, was also reduced in essential hypertension and correlated inversely with blood pressure. The mean reduction in both plasma and interstitial fluid volumes was 6-7%. There is no evidence for volume expansion in essential hypertension and the relationship between plasma and interstitial fluid volumes is preserved. The contraction of plasma and interstitial fluid volumes is more likely to reflect a natriuresis and diuresis secondary to the raised renal perfusion pressure, and sodium retention is unlikely to be a primary event in essential hypertension.

DOI 10.1042/cs0610287
Citations Scopus - 21
1979 Silas JH, Jones J, Tucker GT, Townshend MM, Phillips CA, Smith AJ, 'Dissociation of biochemical and hypotensive effects of debrisoquine in hypertensive patients', European Journal of Clinical Pharmacology, 16 81-86 (1979)

The 24 h urinary excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and vanillylmandelic acid, plasma renin activity and plasma and urinary debrisoquine were ... [more]

The 24 h urinary excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and vanillylmandelic acid, plasma renin activity and plasma and urinary debrisoquine were measured before and during chronic treatment with oral debrisoquine in 14 in-patients with essential hypertension. There was a significant fall (mean ±SD) in the 24 h urinary excretion of vanillylmandelic acid (15.3±2.8 to 6.7±1.9 µmol) noradrenaline (199.0±105.8 to 125.2±43.3 nmol) and plasma renin activity (0.71±0.47 to 0.40±0.20 pmol Angio I ml-1 h-1) while the urinary normetadrenaline/noradrenaline ratio increased (10.4±6.1 to 17.1±5.1). No significant change was seen in the output of adrenaline or of O-methylated metabolites. Debrisoquine produces extensive noncompetitive inhibition of platelet monoamine oxidase in vivo at low therapeutic plasma concentrations. These changes support the view that treatment with debrisoquine produces intraneuronal inhibition of monoamine oxidase and post-ganglionic blockage. There was a significant correlation between the change in standing diastolic blood pressure and the daily dose (rs=-0.52), pre-dose plasma concentration (rs=-0.85) and mean daily urinary recovery (rs=-0.80), of debrisoquine. The full extent of the biochemical changes were seen at low dose and low plasma concentration and were not directly correlated with the fall in standing or supine blood pressure. © 1979 Springer-Verlag.

DOI 10.1007/BF00563111
Citations Scopus - 6
1978 Martin MA, Phillips FC, Tucker GT, Smith AJ, 'Acebutolol in hypertension: Relationships between drug concentration and effects', European Journal of Clinical Pharmacology, 14 383-390 (1978)

Relationships between plasma concentrations of acebutolol (Ac) and its N-acetyl metabolite (Am) and pharmacological effects were studied in patients with essential hypertension. I... [more]

Relationships between plasma concentrations of acebutolol (Ac) and its N-acetyl metabolite (Am) and pharmacological effects were studied in patients with essential hypertension. In an acute study (N=7) 400 mg oral acebutolol produced similar peak plasma levels of Ac and Am but Am had a longer half life. Group mean pulse and blood pressure fell significantly, although the size of individual blood pressure fall varied five-fold. There was no significant change in plasma renin activity. Correlations were found between drug concentration and ß-blockade, assessed as % reduction in exercise tachycardia, and between both of these and the fall in post exercise systolic blood pressure. Similar comparisons were made in a chronic optimum dose study (N=11) both pre-dose and three hours post-dose. Am concentration was consistently higher than Ac at both times. Blood pressure was lowered equally pre-and post-dose when compared to placebo and plasma renin activity (PRA) was reduced on active treatment. Correlations were again shown between drug concentrations and ß-blockade but none were found with changes in blood pressure or PRA. Between subject differences in blood pressure response could not be fully explained in terms of the other measurements but it is unlikely that pharmacokinetic differences are the major source of this variability. © 1978 Springer-Verlag.

DOI 10.1007/BF00716378
Citations Scopus - 12
1978 Gulley BW, Smith AJ, 'WHAT IS HOUSEHOLD AND COMMERCIAL WASTE, ITS NATURE AND HANDLING CHARACTERISTICS? 1-6 (1978)

Household and commercial wastes are almost infinitely variable in composition, size distribution and moisture content and thus can be considered to be the most difficult feedstock... [more]

Household and commercial wastes are almost infinitely variable in composition, size distribution and moisture content and thus can be considered to be the most difficult feedstock that any process plant is called upon to handle. Composition, physical properties and handling characteristics are discussed together with suggestions for avoiding pitfalls in the design of plants. Some of the problems and uncertainties of marketing derived products are also discussed.

1977 Silas JH, Lennard MS, Tucker GT, Smith AJ, 'Why hypertensive patients vary in their response to oral debrisoquine', British Medical Journal, 1 422-425 (1977)

The relation between dose, systemic availability, and response to oral debrisoquine was studied in 13 hypertensive patients receiving no other treatment. In 11 who received the sa... [more]

The relation between dose, systemic availability, and response to oral debrisoquine was studied in 13 hypertensive patients receiving no other treatment. In 11 who received the same daily dose (40 mg) the fall in mean standing systolic blood pressure varied between 0.3 and 44.4 mm Hg. There was a ninefold difference in the daily urinary excretion and pre-dose plasma concentration of unchanged drug but an inverse correlation between daily urinary excretion of debrisoquine and its 4-hydroxy metabolite (r = ¿0.86), suggesting that a low recovery of debrisoquine occurs because of extensive metabolism. There was a significant correlation between the fall in standing systolic blood pressure and the mean daily urinary excretion (r = +0.82) and pre-dose plasma concentration (r = +0.82) of unchanged debrisoquine. In contrast, there was a significant inverse correlation between the urinary recovery of the metabolite and the fall in blood pressure (r =¿0.82). The availability of debrisoquine is the major determinant of response to this drug. In the absence of side effects a poor response may be an indication to increase the daily dose rather than add another hypotensive agent. © 1977, British Medical Journal Publishing Group. All rights reserved.

DOI 10.1136/bmj.1.6058.422
Citations Scopus - 36
1977 Lennard MS, Silas JH, Smith AJ, Tucker GT, 'Determination of debrisoquine and its 4-hydroxy metabolite in biological fluids by gas chromatography with flame-ionization and nitrogen-selective detection', Journal of Chromatography A, 133 161-166 (1977)

Specific methods have been devised for the simultaneous determination of the guanidino-type antihypertensive agent debrisoquine and its 4-hydroxy metabolite in human urine, involv... [more]

Specific methods have been devised for the simultaneous determination of the guanidino-type antihypertensive agent debrisoquine and its 4-hydroxy metabolite in human urine, involving in situ derivatisation with acetylacetone, extraction of the resulting pyrimidines, and gas chromatography using a flame-ionisation detector or a nitrogen-specific detector. Using the latter, a similar procedure was also developed to measure debrisoquine in human plasma and whole blood following prior extraction at pH 13.5 with chloroform. Concentrations down to 3 ng/ml can be measured accurately using a 1.0-ml sample. The methods were applied to the analysis of samples collected after a single 20-mg oral dose of debrisoquine hemisulphate. © 1977.

DOI 10.1016/S0021-9673(00)89216-X
Citations Scopus - 166
1977 Tucker GT, Silas JH, Iyun AO, Lennard MS, Smith AJ, 'POLYMORPHIC HYDROXYLATION OF DEBRISOQUINE', The Lancet, 310 718 (1977)
DOI 10.1016/S0140-6736(77)90527-X
Citations Scopus - 99
1977 Bing RF, Harlow J, Smith AJ, Townshend MM, 'The urinary excretion of catecholamines and their derivatives in primary hypertension in man', Clinical Science and Molecular Medicine, 52 319-323 (1977)

The 24 h urinary excretion of adrenaline, noradrenaline, normetadrenaline, metadrenaline and vanilloylmandelic acid has been compared in 17 male normotensive subjects and 25 age m... [more]

The 24 h urinary excretion of adrenaline, noradrenaline, normetadrenaline, metadrenaline and vanilloylmandelic acid has been compared in 17 male normotensive subjects and 25 age matched male hypertensive patients studied under similar in patient conditions. 24 h urinary metadrenaline was significantly lower in the hypertensive patients. With this exception, no significant differences were found between the two groups when the total 24 h excretion of free catecholamines and their metabolites was analysed. Diurnal variation in free catecholamine excretion was found in both normotensive and hypertensive subjects. There was no corresponding variation in metabolite excretion. No correlation could be established between systolic or diastolic blood pressure and the amounts of the catecholamines or their metabolites in the urine of either group. The results are considered in the light of recent work demonstrating high plasma catecholamine concentrations in hypertension. They lend no support to the concept that excessive circulating catecholamines are responsible for the elevated blood pressure in essential hypertension.

DOI 10.1042/cs0520319
Citations Scopus - 13
1975 Barnett DB, Edwards IR, Smith AJ, 'Antagonism by Indomethacin of Diuretic Response to Calcitonin in Man', British Medical Journal, 3 686 (1975)

The diuretic effects of porcine and human calcitonin in animals and man are associated with renal vasodilatation. The hormone itself may not be directly responsible for these effe... [more]

The diuretic effects of porcine and human calcitonin in animals and man are associated with renal vasodilatation. The hormone itself may not be directly responsible for these effects, however, and since intravenous calcitonin causes increased gastrointestinal activity and flushing in man, prostaglandins (particularly E2 and F2a) may act as intermediaries. If so, the prostaglandin synthetase inhibitor, indomethacin, might modify this response. © 1975, British Medical Journal Publishing Group. All rights reserved.

DOI 10.1136/bmj.3.5985.686
Citations Scopus - 4
1975 Smith AJ, 'The action of diuretics: influence of kinetic factors', Postgraduate Medical Journal, 51 19-22 (1975)

Difficulties in measurement have limited work on the kinetics of diuretics. Four recent studies are compared which indicate that differences between pharmacological effects in nor... [more]

Difficulties in measurement have limited work on the kinetics of diuretics. Four recent studies are compared which indicate that differences between pharmacological effects in normal subjects of bumetanide and frusemide on the one hand and metolazone and amiloride on the other are partly explained by their kinetics. The role of kinetic factors in diuretic response in disease remains to be investigated.

Citations Scopus - 1
1975 Gelsthorpe K, Doughty RW, Bing RF, O'Malley BC, Smith AJ, Talbot S, 'HL-A ANTIGENS IN ESSENTIAL HYPERTENSION', The Lancet, 305 1039-1040 (1975)
DOI 10.1016/S0140-6736(75)91991-1
Citations Scopus - 13
1975 Bird GWG, Wingham J, Gunstone RF, Smith AJ, 'ACUTE HÆMOLYTIC ANÆMIA DUE TO IgM AND IgA PENICILLIN ANTIBODY', The Lancet, 306 462 (1975)
DOI 10.1016/S0140-6736(75)90882-X
Citations Scopus - 6
1975 Talbot S, Smith AJ, 'Factors predisposing to postural hypotensive symptoms in the treatment of high blood pressure', Heart, 37 1059-1063 (1975)

Symptoms due to orthostatic and exertional hypotension occurred in 23.4 per cent of 448 hypertensive patients treated with guanethidine, debrisoquine, or bethanidine. Symptoms wer... [more]

Symptoms due to orthostatic and exertional hypotension occurred in 23.4 per cent of 448 hypertensive patients treated with guanethidine, debrisoquine, or bethanidine. Symptoms were significantly more frequent in patients treated with guanethidine than in those treated with bethanidine or debrisoquine. Women rather than men and patients with radiological evidence of cardiomegaly, electrocardiographic evidence of left ventricular hypertrophy, or STIT wave changes, developed these symptoms signifcantly more often than other patients. A raised blood urea wasfound morefrequently in patients with postural hypotensive symptoms. Characteristically guanethidine produced early morning postural hypotensive symptoms, whereas hypotensive symptoms caused by bethanidine and debrisoquine occurred at other times of the day and particularly one to two hours after tablet ingestion. Debrisoquine andguanethidine had a significantly greater negative chronotropic effect than bethanidine. It is suggested that negative chronotropic effects of these drugs may potentiate hypotensive symptoms in patients with cardiovascular, renal, or cerebrovascular disease. It should be possible to minimize symptoms of postural hypotension by attention to predisposing factors and selection of treatment accordingly.

DOI 10.1136/hrt.37.10.1059
Citations Scopus - 5
1974 Smith AJ, 'Drug treatment of hypertension', British Journal of Hospital Medicine, 11 533-550 (1974)
Citations Scopus - 3
1974 Davies DL, Lant AF, Millard NR, Smith AJ, Ward JW, Wilson GM, 'Renal action, therapeutic use, and pharmacokinetics o the diuretic bumetanide', Clinical Pharmacology and Therapeutics, 15 141-155 (1974)

The diuretic activity of bumetanide has been studied in 16 normal subjects and 40 hospitalized patients with fluid retention. The drug produced a rapid diuretic response with a pa... [more]

The diuretic activity of bumetanide has been studied in 16 normal subjects and 40 hospitalized patients with fluid retention. The drug produced a rapid diuretic response with a pattern of salt and water excretion resembling that of furosemide (Lasix). At the time of maximal natriuresis, which amounted to 13% to 23% of the filtered load of sodium, urinary calcium and magnesium also increased. Urinary urate was unchanged in the first 2 hours after bumetanide, following which there was a phase of urate retention. Free water clearance during maximal hydration was not significantly altered. Comparative studies in edematous patients showed that 1 mg bumetanide was equivalent to 60 mg furosemide. Oral doses of 15 mg bumetanide evoked effective diuresis without adverse effects in 3 edematous patients with advanced renal disease. Prolonged therapy over 7 to 14 weeks with daily doses of 0.25 to 4 mg bumetanide plus potassium supplements controlled edema in 12 patients; asymptomatic hyperuricemia occurred in most, and decreased carbohydrate tolerance in 1. There was no evidence of significant metabolism of bumetanide in vivo. The drug was distributed in a "central" compartment of approximately 5 L. The over-all elimination rate constant was high and indicated that despite rapid renal drug clearance, a substantial part of injected drug left the "central" compartment by one or more extrarenal routes. © 1974.

DOI 10.1002/cpt1974152141
Citations Scopus - 97
1973 SMITH AJ, SMITH RN, 'Kinetics and bioavailability of two formulations of amiloride in man', British Journal of Pharmacology, 48 646-649 (1973)

Two formulations of [14C]-amiloride were compared in six oedema-free subjects in single-dose (20 mg) studies separated by a two-week interval. Calculation of the elimination rate ... [more]

Two formulations of [14C]-amiloride were compared in six oedema-free subjects in single-dose (20 mg) studies separated by a two-week interval. Calculation of the elimination rate constant (Ke), half-life (T½) and apparent volume of distribution (Vd) from serum and urinary data showed no significant difference between the two formulations. The Vd values (350 to 380 litres) were greater than total body fluid volume suggesting extravascular sequestration of amiloride. Serum and urinary amiloride levels were similar with both formulations. Pharmacokinetic parameters were similar to those of an earlier report based on one formulation. The calculated amiloride concentration in the renal distal tubule (3 µm to 20 µm) was similar to, but higher than, reported in vitro concentrations of amiloride which reduced sodium transport in isolated membranes. 1973 British Pharmacological Society

DOI 10.1111/j.1476-5381.1973.tb08252.x
Citations Scopus - 32
1973 Townshend MM, Smith AJ, 'Factors influencing the urinary excretion of free catecholamines in man.', Clinical science, 44 253-265 (1973)
DOI 10.1042/cs0440253
Citations Scopus - 57
1973 Smith A, 'Oral contraceptives on N.H.S. prescription.', Lancet, 1 266 (1973)
1973 Davies DL, Lant AF, Millard NR, Smith AJ, Ward JW, Wilson GM, 'Some aspects of the clinical pharmacology of bumetanide, a new, potent oral diuretic', BRIT.J.PHARMACOL., 47 (1973)
Citations Scopus - 9
1972 Edwards IR, Smith AJ, 'The mechanism of the diuretic response to porcine calcitonin in normal subjects.', Clinical science, 42 (1972)
DOI 10.1042/cs042005pa
1972 Preston FE, Malia RG, Tipton RH, Smith AJ, 'INTRAVASCULAR COAGULATION AND PRE-ECLAMPTIC TOXÆMIA', The Lancet, 299 34-35 (1972)
DOI 10.1016/S0140-6736(72)90020-7
Citations Scopus - 2
1972 EDWARDS IR, SMITH AJ, 'PORCINE CALCITONIN AS A RENAL VASODILATOR IN MAN', Clinical Endocrinology, 1 337-344 (1972)

Porcine calcitonin in intravenous doses of 1, 5, 10 and 20 MRC units produced acute increases in urinary volume and sodium, potassium, chloride and bicarbonate excretion in four n... [more]

Porcine calcitonin in intravenous doses of 1, 5, 10 and 20 MRC units produced acute increases in urinary volume and sodium, potassium, chloride and bicarbonate excretion in four normal subjects. Infusion of 10 MRC units over a 30 min period in six normal men produced significant increases in urinary volume and sodium, calcium, magnesium, chloride and urea excretion. Urinary potassium, phosphate and bicarbonate were also increased but the increases were not significantly different from control values. These changes in urinary composition accompanied a significant increase in effective renal plasma flow (para-amino hippurate clearance) and a smaller increase in inulin clearance. It is suggested that porcine calcitonin acts as a renal vasodilator in man and that changes in renal electrolyte excretion occur as a consequence. It is possible that renal vasodilation is effected by an active intermediary released by calcitonin rather than by the hormone itself. Copyright © 1972, Wiley Blackwell. All rights reserved

DOI 10.1111/j.1365-2265.1972.tb00403.x
Citations Scopus - 11
1971 SALAKO LA, SMITH AJ, 'Effects of the diuretics, triamterene and mersalyl on active sodium transport mechanisms in isolated frog skin', British Journal of Pharmacology, 41 552-557 (1971)

Triamterene reduces the rate coefficients for sodium movement into the transporting system of the isolated frog skin. The isotopically measured ¿active sodium transport pool¿ is a... [more]

Triamterene reduces the rate coefficients for sodium movement into the transporting system of the isolated frog skin. The isotopically measured ¿active sodium transport pool¿ is also reduced. Mersalyl reduces the rate coefficient for sodium and the calculated sodium flux from the transporting system to the inner bathing solution. The ¿active sodium transport pool¿ is increased by this diuretic. The action of triamterene closely resembles that of amiloride and both reduce the entry of sodium into the system. In contrast, mersalyl limits the exit of sodium ions from the skin. 1971 British Pharmacological Society

DOI 10.1111/j.1476-5381.1971.tb08053.x
Citations Scopus - 7
1971 Grayson MF, Smith AJ, Smith RN, 'Absorption, distribution and elimination of 14 C-amiloride in normal human subjects.', British Journal of Pharmacology, 43 (1971)
Citations Scopus - 20
1971 Salako LA, Smith AJ, Smith RN, 'The effects of porcine calcitonin on renal function in the rabbit.', The Journal of endocrinology, 50 485-491 (1971)
DOI 10.1677/joe.0.0500485
Citations Scopus - 7
1971 Richter GA, Pailthorp RE, Sirrine KL, Rhame GA, Rickard MD, Brookman G, et al., 'PROCEEDINGS OF THE 26TH INDUSTRIAL WASTE CONFERENCE MAY 4, 5, AND 6, 1971, 2 PARTS.', Purdue Univ, Eng Bull, Eng Ext Ser, (1971)

Following is a continuation of the list of titles and authors of the papers presented: Aerobic Secondary Treatment of Potato Processing Wastes. By G. A. Richter, R. E. Pailthorp, ... [more]

Following is a continuation of the list of titles and authors of the papers presented: Aerobic Secondary Treatment of Potato Processing Wastes. By G. A. Richter, R. E. Pailthorp, and K. L. Sirrine. Treatment of Textile Finishing Wastes by Surface Aeration. By G. A. Rhame. Removal of Mercury from Industrial Wastewaters by Metal Reduction. By M. D. Rickard and G. Brookman. Cooling Towers - A Water Pollution Control Device. By P. B. Riegelman. Full Scale Pilot Plant Studies of a Sub-Surface Mixing and Aerating System for Treatment of Cannery Wastes. By W. W. Rose and A. Grinkevich. Waste Disposal at the Magmont Mine, Bixby, Missouri. By F. H. Sharp. Methods for Operators of Wastewater Treatment Plants to Determine BOD Parameters. By O. Sletten. Waste Treatment in the Liquor Distilling Industry. By A. J. Smith. Waste Treatment Facilities for Jones & Laughlin Steel Corporation, Hennepin Works. By L. B. Stoner.

1970 SALAKO LA, SMITH AJ, 'Effects of amiloride on active sodium transport by the isolated frog skin: evidence concerning site of action', British Journal of Pharmacology, 38 702-718 (1970)

Amiloride reduces short-circuit current and potential difference across the isolated frog skin. Isotopically measured sodium influx and efflux are diminished. Total electrical con... [more]

Amiloride reduces short-circuit current and potential difference across the isolated frog skin. Isotopically measured sodium influx and efflux are diminished. Total electrical conductance and partial sodium conductance are diminished, the reduction in total conductance being entirely accounted for by the reduction in partial sodium conductance. The effect of antidiuretic hormone (ADH), cyclic 3'5'-adenosine monophosphate (cyclic AMP) and theophylline can be antagonized by pretreatment with amiloride but the antagonism can be abolished by increasing the concentration of these compounds. Amiloride has no effect on oxygen consumption in concentrations which inhibit sodium transport. However, it prevents the stimulatory effect of ADH on oxygen consumption. The results are consistent with an action of amiloride at the passive outside membrane of the transporting cells of isolated frog skin. 1970 British Pharmacological Society

DOI 10.1111/j.1476-5381.1970.tb09878.x
Citations Scopus - 45
1970 SALAKO LA, SMITH AJ, 'Changes in sodium pool and kinetics of sodium transport in frog skin produced by amiloride', British Journal of Pharmacology, 39 99-109 (1970)

. Amiloride produces a decrease in size of the active sodium transport pool of isolated frog skin. . Rate coefficients for sodium movement into and out of the transporting cells a... [more]

. Amiloride produces a decrease in size of the active sodium transport pool of isolated frog skin. . Rate coefficients for sodium movement into and out of the transporting cells across the outside membrane are decreased by amiloride. The rate coefficient for sodium extrusion across the inside membrane is not significantly affected. . In the presence and in the absence of amiloride, the relation of sodium transport to outside sodium concentration exhibits similar saturation kinetics but amiloride reduces sodium transport rate at every sodium concentration of the outside solution. . Labelling of skin with 14C-amiloride from the outside solution is significantly greater than labelling with 14C-inulin. . The results of these studies suggest that amiloride reacts with sites on the outside membrane of the transporting cells as a result of which the rate of sodium movement across this membrane is diminished. 1970 British Pharmacological Society

DOI 10.1111/j.1476-5381.1970.tb09559.x
Citations Scopus - 53
1970 Salako LA, Smith AJ, Smith RN, 'Renal effects of porcine calcitonin in the rabbit.', Clinical science, 39 (1970)
DOI 10.1042/cs039002pb
1970 Salako LA, Smith AJ, 'Inhibition of active sodium transport in isolated frog skin by the diuretic, amiloride: site of action.', Journal of Physiology, 206 (1970)
Citations Scopus - 1
1969 Lant AF, Smith AJ, Wilson GM, 'Clinical evaluation of amiloride, a potassium-sparing diuretic', Clinical Pharmacology andTherapeutics, 10 50-63 (1969)

Amiloride (MK 870), a new potassium-sparing diuretic belonging to the pyrazine carboxamide class was evaluated in 34 hospitalized patients with fluid retention. The drug increased... [more]

Amiloride (MK 870), a new potassium-sparing diuretic belonging to the pyrazine carboxamide class was evaluated in 34 hospitalized patients with fluid retention. The drug increased the excretion of sodium, chloride, and water but decreased potassium excretion. The major natriuretic effects of the drug were complete within 24 hours but in a few patients some potassium-sparing lasted longer. The therapeutic efficacy of amiloride was compared with that of triamterene at ceiling dosages selected from the early portion of the dose-response plateaus of the 2 drugs. The natriuretic and potassium-sparing efficacies of 40 mg. amiloride were significantly greater than those of 200 mg. triamterene. At submaximal dosages, amiloride potentiated the natriuresis and reduced the potassium loss evoked by ethacrynic acid. The potassium-retaining action of amiloride was apparent even in the presence of full doses of spironolactone. © 1969.

DOI 10.1002/cpt196910150
Citations Scopus - 25
1968 Baba WI, Lant AF, Smith AJ, Townshend MM, Wilson GM, 'Pharmacological effects in animals and normal human subjects of the diuretic amiloride hydrochloride (MK-870)', Clinical Pharmacology &amp; Therapeutics, 9 318-327 (1968)

Amiloride is a new diuretic drug producing moderate natriuretic effects coupled with prominent potassium retention. Though chemically distinct, this compound has some structural s... [more]

Amiloride is a new diuretic drug producing moderate natriuretic effects coupled with prominent potassium retention. Though chemically distinct, this compound has some structural similaritites to triamterene, which it also resembles in its effects in normal human subjects, adrenalectomized rats, and on sodium transport across the isolated frog skin. It has no appreciable effect on the urinary concentrating mechanisms. These actions suggest a primary, direct effect upon the distal renal tubule. A dose-response relationship in man is obtained with little increase in effect above 40 mg. At lower doses the effects are manifested within the first IO hours after administration. Doses above 40 mg. prolong these effects to 24 hours. © 1968.

DOI 10.1002/cpt196893318
Citations Scopus - 32
1967 Baba WI, Smith AJ, Townshend MM, 'THE EFFECTS OF VASOPRESSIN, THEOPHYLLINE AND CYCLIC 3'-5'-ADENOSINE MONOPHOSPHATE (CYCLIC AMP) ON SODIUM TRANSPORT ACROSS THE FROG SKIN', Quarterly Journal of Experimental Physiology and Cognate Medical Sciences, 52 416-421 (1967)

The effects of vasopressin, theophylline and cyclic AMP on sodium transport across isolated frog skin have been studied using 24Na for the measurement of sodium fluxes. Both vasop... [more]

The effects of vasopressin, theophylline and cyclic AMP on sodium transport across isolated frog skin have been studied using 24Na for the measurement of sodium fluxes. Both vasopressin and theophylline produced consistent increases in short-circuit current, sodium influx and efflux, with a reduction in partial resistance of the skin. The same results were obtained with cyclic AMP only when it was combined with small (loses of theophylline which were by themselves ineffective. The similarity of effect of these three compounds on sodium transport mechanisms strengthens the hypothesis that the physiological activity of vasopressin may be mediated by cyclic AMP. © 1967 The Physiological Society

DOI 10.1113/expphysiol.1967.sp001936
Citations Scopus - 20
1966 Seriki O, Smith AJ, 'The electrocardiogram of young Nigerians', American Heart Journal, 72 153-157 (1966)

Examination of the electrocardiograms of 100 students and 202 school children in Lagos, Nigeria, revealed a high incidence of S-T segment elevation in precordial leads, increasing... [more]

Examination of the electrocardiograms of 100 students and 202 school children in Lagos, Nigeria, revealed a high incidence of S-T segment elevation in precordial leads, increasing with age and occurring more commonly in males. Biphasic or inverted T waves were found commonly in precordial leads on the right side, occasionally extending as far as Lead V4. This is less common in older subjects and may represent a persistence into young adult life of a juvenile form. These normal appearances deserve wider recognition in order to prevent confusion in interpretation of the electrocardiogram. © 1966.

DOI 10.1016/0002-8703(66)90438-8
Citations Scopus - 24
1966 Smith AJ, 'Arterial hypertension in the Lagos University Teaching Hospital.', The West African medical journal, 15 97-104 (1966)
Citations Scopus - 8
1966 BABA WI, SMITH AJ, TOWNSHEND MM, 'A COMPARISON OF THE EFFECTS OF ETHACRYNIC ACID AND A MERCURIAL DIURETIC (MERSALYL) ON SODIUM TRANSPORT ACROSS THE ISOLATED FROG SKIN', British Journal of Pharmacology and Chemotherapy, 28 238-245 (1966)
DOI 10.1111/j.1476-5381.1966.tb01890.x
Citations Scopus - 5
1965 SMITH AJ, 'FLUID RETENTION PRODUCED BY GUANETHIDINE; CHANGES IN BODY EXCHANGEABLE SODIUM, BLOOD VOLUME, AND CREATININE CLEARANCE.', Circulation, 31 490-496 (1965)
DOI 10.1161/01.CIR.31.4.490
Citations Scopus - 18
1965 SMITH AJ, 'CLINICAL FEATURES OF FLUID RETENTION COMPLICATING TREATMENT WITH GUANETHIDINE.', Circulation, 31 485-489 (1965)
DOI 10.1161/01.CIR.31.4.485
Citations Scopus - 11
1964 HOLMAN CA, SMITH AJ, WHIMSTER WF, BEALE D, LEHMANN H, 'A CASE OF HYPERTENSION WITH ISCHAEMIC KIDNEY DEMONSTRATED AT THE POSTGRADUATE MEDICAL SCHOOL OF LONDON.', British medical journal, 2 923-926 (1964)
1964 Baba WI, Smith AJ, 'THE EFFECT OF GUANETHIDINE ON SODIUM TRANSPORT ACROSS THE ISOLATED FROG SKINT', Quarterly Journal of Experimental Physiology and Cognate Medical Sciences, 49 194-198 (1964)

Guanethidine may cause fluid retention when it is used to treat hypertension in man. The possibility that this is due to an effect on sodium transport is examined in experiments o... [more]

Guanethidine may cause fluid retention when it is used to treat hypertension in man. The possibility that this is due to an effect on sodium transport is examined in experiments on isolated frog skin. Guanethidine consistently increased the rate of active sodium transport through the skin. © 1964 The Physiological Society

DOI 10.1113/expphysiol.1964.sp001719
Citations Scopus - 4
Show 169 more journal articles

Review (1 outputs)

Year Citation Altmetrics Link
2003 Smith AJ, 'Oxford textbook of clinical pharmacology and drug therapy', British Journal of Pharmacology (2003) [D2]

Conference (4 outputs)

Year Citation Altmetrics Link
2009 Wright IM, Smith AJ, Clifton VL, Stark MJ, 'Nappy urine collection for physiological measures: A current method', Journal of Paediatrics and Child Health, Darwin, NT (2009) [E3]
DOI 10.1111/j.1440-1754.2009.01475.x
Co-authors Ian Wright
1992 Smith AJ, Willington SE, Combes RD, 'Formation and repair of 2-acetylaminofluorene and 4-acetylaminofluorene DNA adducts in the Wistar rat and two mammalian cell lines', Human and Experimental Toxicology (1992)
1991 Smith AJ, 'Workshop on evaluating the undergraduate medical curriculum', Medical Journal of Australia (1991)
DOI 10.5694/j.1326-5377.1991.tb94024.x
Citations Scopus - 2
1971 Richter GA, Pailthorp RE, Sirrine KL, Rhame GA, Rickard MD, Brookman G, et al., 'PROCEEDINGS OF THE 26TH INDUSTRIAL WASTE CONFERENCE MAY 4, 5, AND 6, 1971, 2 PARTS.', Purdue Univ, Eng Bull, Eng Ext Ser (1971)

Following is a continuation of the list of titles and authors of the papers presented: Aerobic Secondary Treatment of Potato Processing Wastes. By G. A. Richter, R. E. Pailthorp, ... [more]

Following is a continuation of the list of titles and authors of the papers presented: Aerobic Secondary Treatment of Potato Processing Wastes. By G. A. Richter, R. E. Pailthorp, and K. L. Sirrine. Treatment of Textile Finishing Wastes by Surface Aeration. By G. A. Rhame. Removal of Mercury from Industrial Wastewaters by Metal Reduction. By M. D. Rickard and G. Brookman. Cooling Towers - A Water Pollution Control Device. By P. B. Riegelman. Full Scale Pilot Plant Studies of a Sub-Surface Mixing and Aerating System for Treatment of Cannery Wastes. By W. W. Rose and A. Grinkevich. Waste Disposal at the Magmont Mine, Bixby, Missouri. By F. H. Sharp. Methods for Operators of Wastewater Treatment Plants to Determine BOD Parameters. By O. Sletten. Waste Treatment in the Liquor Distilling Industry. By A. J. Smith. Waste Treatment Facilities for Jones & Laughlin Steel Corporation, Hennepin Works. By L. B. Stoner.

Show 1 more conference
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Grants and Funding

Summary

Number of grants 17
Total funding $832,613

Click on a grant title below to expand the full details for that specific grant.


19981 grants / $99,148

The Effective of Drug Guidelines as Decision Support in Computer Prescribing$99,148

Funding body: Commonwealth Department of Health & Aged Care

Funding body Commonwealth Department of Health & Aged Care
Project Team Dr Andrew Nolan, Professor Jill Cockburn, Dr K Harvey, Emeritus Professor Anthony Smith, Assoc. Prof A Mant
Scheme General Practice Evaluation Program (GPEP) (Defunct)
Role Investigator
Funding Start 1998
Funding Finish 1999
GNo G0177415
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y

19971 grants / $24,240

SH-AHM-003: CALM STUDY$24,240

Funding body: Astra Pharmaceuticals Pty Ltd

Funding body Astra Pharmaceuticals Pty Ltd
Project Team Associate Professor Shane Carney, Conjoint Associate Professor Alastair Gillies, Emeritus Professor Anthony Smith
Scheme Study Agreement
Role Investigator
Funding Start 1997
Funding Finish 1997
GNo G0177532
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

19961 grants / $2,500

VI World Congress on Clinical Pharmacology & Therapeutics, Buenos Aires, Argentina, 4-9 August 1996$2,500

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Emeritus Professor Anthony Smith
Scheme Travel Grant
Role Lead
Funding Start 1996
Funding Finish 1996
GNo G0176536
Type Of Funding Internal
Category INTE
UON Y

19955 grants / $194,504

LOSARTAN vs LOSARTAN HCTZ vs AMLODIPINE IN PATIENTS WITH HYPERTENSION$76,204

Funding body: Merck Sharp & Dohme Aust Pty Ltd

Funding body Merck Sharp & Dohme Aust Pty Ltd
Project Team Associate Professor Shane Carney, Conjoint Associate Professor Alastair Gillies, Emeritus Professor Anthony Smith
Scheme Research Grant
Role Investigator
Funding Start 1995
Funding Finish 1995
GNo G0175244
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

95APP. The effect of garlic on blood pressure, lipids and haemostasis.$62,300

Funding body: National Heart Foundation of Australia

Funding body National Heart Foundation of Australia
Project Team Emeritus Professor Anthony Smith, Conjoint Associate Professor Jonathan Silberberg, Dr Valerie McPherson
Scheme Grant-In-Aid
Role Lead
Funding Start 1995
Funding Finish 1996
GNo G0174645
Type Of Funding Aust Competitive - Non Commonwealth
Category 1NS
UON Y

Antihypertensive efficacy of the combination of ibesartan and hydrochlorothiazide as determined by 24hr ambulatory blood pressure monitoring.$39,000

Funding body: Society of Hospital Pharmacists of Australia

Funding body Society of Hospital Pharmacists of Australia
Project Team Emeritus Professor Anthony Smith
Scheme Bristol Myers Squibb Clinical Pharmacy Research Grant
Role Lead
Funding Start 1995
Funding Finish 1995
GNo G0175965
Type Of Funding International - Non Competitive
Category 3IFB
UON Y

The Effect of Benzodiazepine Agonists and Antagonists on Acute Chloroquine Toxicity in Rat Hearts$10,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Dr Nicholas Buckley, Emeritus Professor Anthony Smith
Scheme New Staff Grant
Role Investigator
Funding Start 1995
Funding Finish 1995
GNo G0175141
Type Of Funding Internal
Category INTE
UON Y

Comparative Evaluation of Attitudes and Skills in Relation to Community Medicine in Graduates of NSW Medical Schools$7,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Dr Isobel Rolfe, Emeritus Professor Anthony Smith
Scheme New Staff Grant
Role Investigator
Funding Start 1995
Funding Finish 1995
GNo G0175144
Type Of Funding Internal
Category INTE
UON Y

19944 grants / $263,950

94GRANT. Speciality grant for Pharmacoepidemiology.$120,000

Funding body: Commonwealth Department of Health & Aged Care

Funding body Commonwealth Department of Health & Aged Care
Project Team Emeritus Professor Anthony Smith, Conjoint Professor David Henry
Scheme Pharmaceutical Education Program (PEP)
Role Lead
Funding Start 1994
Funding Finish 1994
GNo G0174635
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

94,95 GRANT. Nitrergic mechanisms in pregnancy-induced hypertension$86,350

Funding body: National Heart Foundation of Australia

Funding body National Heart Foundation of Australia
Project Team Emeritus Professor Anthony Smith, Emeritus Professor William Walters
Scheme Grant-In-Aid
Role Lead
Funding Start 1994
Funding Finish 1995
GNo G0173348
Type Of Funding Aust Competitive - Non Commonwealth
Category 1NS
UON Y

Safety and efficacy of diltiazen CD in the treatement of essential hypertension.$48,000

Funding body: Marion Merrell Dow Australia Pty Ltd

Funding body Marion Merrell Dow Australia Pty Ltd
Project Team Associate Professor Shane Carney, Emeritus Professor Anthony Smith, Conjoint Associate Professor Alastair Gillies
Scheme Research Grant
Role Investigator
Funding Start 1994
Funding Finish 1994
GNo G0174568
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

Tissue Digoxin-like immunoreactivity levels in pregnancy$9,600

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Emeritus Professor William Walters, Emeritus Professor Anthony Smith, Professor Alan Boura
Scheme Project Grant
Role Investigator
Funding Start 1994
Funding Finish 1994
GNo G0174783
Type Of Funding Internal
Category INTE
UON Y

19932 grants / $69,830

RO 40-5967 Calcium antagonist protocol BC 14044.$60,000

Funding body: Roche Products Pty Limited

Funding body Roche Products Pty Limited
Project Team Associate Professor Shane Carney, Emeritus Professor Anthony Smith, Conjoint Associate Professor Alastair Gillies
Scheme Research Grant
Role Investigator
Funding Start 1993
Funding Finish 1993
GNo G0174284
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

Exploring Mechanisms for the rise in Blood Pressure Which May Complicate pregancy$9,830

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Emeritus Professor Anthony Smith
Scheme Project Grant
Role Lead
Funding Start 1993
Funding Finish 1993
GNo G0172789
Type Of Funding Internal
Category INTE
UON Y

19921 grants / $5,000

Programme Evaluation Workshop 9-10 Sept 1991$5,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Emeritus Professor Anthony Smith
Scheme Project Grant
Role Lead
Funding Start 1992
Funding Finish 1992
GNo G0174059
Type Of Funding Internal
Category INTE
UON Y

19912 grants / $173,441

Venous Distensibility And Vasocative Prostanglandins$135,889

Funding body: National Heart Foundation of Australia

Funding body National Heart Foundation of Australia
Project Team Emeritus Professor Anthony Smith
Scheme Grant-In-Aid
Role Lead
Funding Start 1991
Funding Finish 1993
GNo G0173918
Type Of Funding Aust Competitive - Non Commonwealth
Category 1NS
UON Y

Beta Scintillation Spectrometer$37,552

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Emeritus Professor David Powis, Emeritus Professor Peter Dunkley, Emeritus Professor John Rostas, Emeritus Professor Anthony Smith
Scheme Equipment Grant
Role Investigator
Funding Start 1991
Funding Finish 1991
GNo G0173965
Type Of Funding Aust Competitive - Commonwealth
Category 1CS
UON Y
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Emeritus Professor Anthony Smith

Position

Emeritus Professor
Faculty of Health and Medicine

Focus area

Clinical Pharmacology and Clinical Toxicology

Contact Details

Email anthony.smith@newcastle.edu.au

Office

Room NM2-542
Building Mater Hospital Level 5 - New Med 2
Location Other

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