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Biomedical subjects

S R Hill

Publications and source records attributed to S R Hill.

At least 19 recordsLinked to original sources
PubMed2006

Giving and receiving of gifts between pharmaceutical companies and medical specialists in Australia.

BACKGROUND: This study investigated the 'gift-relationship' between pharmaceutical companies and doctors. METHODS: The study was based on a survey questionnaire of 823 medical specialists from across Australia. The aim of this study was to investigate gifts offered to medical specialists in Australia by pharmaceutical companies, financial support actively sought by medical specialists for activities other than research and to consider what is ethically appropriate. RESULTS: A high percentage of specialists received offers of food (96%), items for the office (94%), personal gifts (51%) and journals or textbooks (50%). Most specialists were invited to product launches, symposia or educational events (75-84%) and 52% received offers of travel to conferences. A high proportion of offers were accepted (66-79%) except invitations to product launches (49%), sponsored symposia (53%) and offers of travel that included partners (27%). Fifteen per cent of specialists requested financial support from pharmaceutical companies for activities and items, including conferences, travel, educational activities, salaries and donations to specific funds. The study outlined guidelines on gifts from pharmaceutical companies and differing standards applying to gifts and grants for travel. We found that, although most gifts and requests for support complied with professional and pharmaceutical industry guidelines, some--including personal gifts, tickets to sporting events, entertainment and travel expenses for specialists' partners--did not. CONCLUSION: To ensure that physicians' judgements are free from real or perceived influence from industry and to maintain public trust, we support a shift towards more conservative standards on gifts and support for travel evident in recent guidelines.

Adult↗
PubMed2006

Maternal obesity in pregnancy: Is it time for meaningful research to inform preventive and management strategies?

The growing epidemic of obesity in our society has become a major public health issue, with serious social and psychological consequences in addition to the physical health implications. Obesity has reached epidemic proportions globally with a similar rise in prevalence among women in the reproductive age group. This has critical consequences for fetal and maternal health in the antepartum, intrapartum and postpartum periods. The aims of this study were to summarise the implications of maternal obesity on maternal, fetal and neonatal health and to recommend good practice guidelines on the management of this problem. The authors highlight the need for good quality interventional research on maternal obesity while identifying avenues with potential scope for future research in this context.

Biomedical Research↗
PubMed2005

Technical note: technique for dissection and analysis of the rumen in young calves.

This paper discusses a technique used to evaluate rumen development in young calves, including removal, dissection, and analysis of tissue. The method allowed for examination of the different sacs of the rumen (dorsal, ventral, cranial, and caudal) using scanning electron microscopy to measure papillae denseness and histology slides to measure papillae length and width. Computer software was used to produce accurate measurements of papillae. The rumens of young calves were dissected, and samples were taken from the cranial, caudal, ventral, and dorsal sections. Calves were part of a nutrition research study, and dietary treatments did have an effect on development measurements such as length, width, and papillae denseness.

Animal Nutritional Physiological Phenomena↗
PubMed2003

Use of pharmacoeconomics in prescribing research. Part 5: modelling--beyond clinical trials.

This paper provides an overview of modelling in the economic evaluation of pharmaceuticals, reflecting the increasing use of models in analyses prepared for reimbursement applications to national and local drug formularies. The paper seeks to demystify the most commonly encountered modelling techniques (extrapolation, decision analysis, Markov modelling and Monte Carlo simulation), and to provide guidance in assessing the quality of submitted or published modelled economic evaluations.

Clinical Trials as Topic↗
PubMed2003

Use of pharmacoeconomics in prescribing research. Part 3: Cost-effectiveness analysis--a technique for decision-making at the margin.

This is the third Research Note addressing pharmacoeconomics in prescribing research, reflecting the increasing use of economic evaluation in drug purchasing decisions in a variety of settings. In this segment we provide an overview of the theoretical basis, practical application and methodological limitations of cost-effectiveness analysis (CEA).

Cost-Benefit Analysis↗
PubMed2002

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

BACKGROUND: Most clinical practice guidelines recommend restrictive red cell transfusion practices with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). OBJECTIVES: To examine the evidence on the effect of transfusion thresholds, on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: Trials were identified by: computer searches of OVID Medline (1966 to December 2000), Current Contents (1993 to Week 48 2000), and the Cochrane Controlled Trials Register (2000 Issue 4). References in identified trials and review articles were checked and authors contacted to identify any additional studies. SELECTION CRITERIA: Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where the intervention groups were assigned on the basis of a clear transfusion "trigger", described as a haemoglobin (Hb) or haematocrit (Hct) level below which a RBC transfusion was to be administered. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al. (1995). Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials using a random effects model. MAIN RESULTS: Ten trials were identified that reported outcomes for a total of 1780 patients. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 42% (RR=0.58: 95%CI=0.47,0.71). This equates to an average absolute risk reduction (ARR) of 40% (95%CI=24% to 56%). The volume of RBCs transfused was reduced on average by 0.93 units (95%CI=0.36,1.5 units). However, heterogeneity between these trials was statistically significant (p<0.00001) for these outcomes. Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. Trials were of poor methodological quality. REVIEWER'S CONCLUSIONS: The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

Erythrocyte Transfusion↗
PubMed2001

Ikirara insertions reveal five new Anopheles gambiae transposable elements in islands of repetitious sequence.

Characterization of Anopheles gambiae genomic clones containing Ikirara inverted repeats revealed five novel sequences related to known transposable elements (TEs). One TE is related to the mariner/Tc1 superfamily of class II (DNA-to-DNA) transposons, while four are related to class I (RNA-mediated transposition) elements. Crusoe, the class II element; is most similar to the Caenorhabditis elegans transposon Tc1-like TEs. Vash elements, represented twice in our clones, are related to the Q/T1 family of A. gambiae non-LTR retrotransposable elements. Guildenstern is a member of the RT1 and RT2 non-LTR retrotransposon family. Although RT1 and RT2 elements normally have a highly stereotyped insertion preference for sequences within ribosomal genes, Guildenstern is not located in ribosomal sequence. JuanAg is the first anopheline member of the mosquito non-LTR retrotransposon family of Juan elements that previously had included just the culicine elements JuanA and JuanC. Approximately 753 bp is missing from the central portion of the JuanAg reverse transcriptase gene, where an Ikirara inverted repeat is found in its stead. Ozymandias, the only LTR retrotransposon found in the clones, is most similar to the Drosophila melanogaster 412 element. Single Ikirara inverted repeats were also found adjacent to nontransposable element repetitious sequences. Our analysis suggests that the A. gambiae genome organization could best be described as islands of short-period interspersion repetitious DNA in a sea of long-period interspersion, mostly unique sequence DNA.

Amino Acid Sequence↗
PubMed2001

Drug information for consumers: should it be disease or medication specific? Results of a community survey.

OBJECTIVE: To investigate the information-seeking behaviour of medicine users. METHODS: A telephone survey and follow-up in-depth interviews of a random sample of the adult population in the Hunter Region, NSW, Australia. The survey sought information on medicine use, information seeking, and satisfaction and understanding of the information received. In-depth interviews examined the barriers and facilitators of information seeking. RESULTS: Seven hundred and eighty-six people completed the telephone survey and 58 completed the follow-up interviews. Over half (51%) of the medicine users sought information, primarily to 'manage' their medicines, such as how to use the medicine. Over 30% of the questions asked by users related to 'therapeutic choices', such as how well the medicine worked for a particular condition. Doctors and pharmacists were the most frequent sources of information. A small proportion (10%) reported a potential unmet need for medicines information by indicating they would have liked to ask a question, but did not, or were dissatisfied with the information they received. Barriers to information seeking included perceptions that health care professionals were 'too busy', and that they were unwilling to provide information. CONCLUSIONS: Physicians and pharmacists continue to play an important role in providing consumers with medicines information. Although the reported level of unmet need was low, a significant proportion identified needs relating to information on therapeutic choice, rather than 'classical' drug information. IMPLICATIONS: Medicines-related information for the public should include advice on comparative performance of drugs, and be provided within the wider framework of general health information.

Adolescent↗
PubMed2000

Problems with the interpretation of pharmacoeconomic analyses: a review of submissions to the Australian Pharmaceutical Benefits Scheme.

CONTEXT: Pharmacoeconomic analyses are being used increasingly as the basis for reimbursement of the costs of new drugs. Reports of these analyses are often published in peer-reviewed journals. However, the analyses are complex and difficult to evaluate. OBJECTIVE: To describe the nature of problems encountered in the evaluation and interpretation of pharmacoeconomic analyses used as a basis for reimbursement decisions. DATA SOURCES: All major submissions to the Department of Health and Aged Care (DHAC) by the pharmaceutical industry for funding made under the Australian Pharmaceutical Benefits Scheme. Specifically, the DHAC's database of submissions that were received between January 1994 and December 1997 were reviewed. STUDY SELECTION: Of a total of 326 submissions, 218 had serious problems of interpretation and were included in the analysis. The nature of the serious problems reviewed were classified as estimates of comparative clinical efficacy, comparator issues, modeling issues, and calculation errors. DATA EXTRACTION: All submissions in the DHAC's database were reviewed and data were extracted if both the DHAC evaluators and technical subcommittee considered problems to have a significant bearing on the decisions of the parent committee. DATA SYNTHESIS: Of a total of 326 submissions, 218 (67%) had significant problems and 31 had more than 1 problem. Of the 249 problems identified, 154 (62%) related to uncertainty in the estimates of comparative clinical efficacy, and 71 (28.5%) related to modeling issues, which included clinical assumptions or cost estimates, used in the construction of the economic models. There were 15 instances of disagreement over the choice of comparator, and serious calculation errors were found on 9 occasions. Overall, 159 problems (64%) were considered to be avoidable. CONCLUSIONS: Significant problems were identified in these pharmacoeconomic analyses. The intensive evaluation process used in the Australian Pharmaceutical Benefits Scheme allowed for identification and correction of pharmacoecomomic analysis problems, but the resources that are required may be beyond the capacity of many organizations, including peer-reviewed journals.

Australia↗
PubMed2000

Enhancing care for people with asthma: the role of communication, education, training and self-management. 1998 World Asthma Meeting Education and Delivery of Care Working Group.

Reduction in the morbidity associated with asthma requires attention to several aspects of the behaviour of health professionals and patients, and to the interactions between these two groups. In this review, what has been learnt about health professional/patient communication and patient education (skills, settings and materials), lay and health professional liaison (including telephone helplines), patient education in low-income countries, the integration of patient education into clinical practice, health professional training and the implementation of guidelines, and the role of national asthma campaigns is drawn together. What changes in public policy would enhance asthma care, and whether the promotion of asthma self-management skills is cost effective are also considered. It is concluded that, although further research is necessary in many areas, well-educated health professionals who recognize the person with asthma as an individual, and who give advice about self-management, can significantly reduce the suffering and costs associated with asthma.

Asthma↗
PubMed1996

Oxidative inactivation of thioredoxin as a cellular growth factor and protection by a Cys73-->Ser mutation.

Thioredoxin (Trx) is a widely distributed redox protein that regulates several intracellular redox-dependent processes and stimulates the proliferation of both normal and tumor cells. We have found that when stored in the absence of reducing agents, human recombinant Trx undergoes spontaneous oxidation, losing its ability to stimulate cell growth, but is still a substrate for NADPH-dependent reduction by human thioredoxin reductase. There is a slower spontaneous conversion of Trx to a homodimer that is not a substrate for reduction by thioredoxin reductase and that does not stimulate cell proliferation. Both conversions can be induced by chemical oxidants and are reversible by treatment with the thiol reducing agent dithiothreitol. SDS-PAGE suggests that Trx undergoes oxidation to monomeric form(s) preceding dimer formation. We have recently shown by X-ray crystallography that Trx forms a dimer that is stabilized by an intermolecular Cys73-Cys73 disulfide bond. A Cys73-->Ser mutant Trx (C73S) was prepared to determine the role of Cys73 in oxidative stability and growth stimulation. C73S was as effective as Trx in stimulating cell growth and was a comparable substrate for thioredoxin reductase. C73S did not show spontaneous or oxidant-induced loss of activity and did not form a dimer. The results suggest that Trx can exist in monomeric forms, some of which are mediated by Cys73 that do not stimulate cell proliferation but can be reduced by thioredoxin reductase. Cys73 is also involved in formation of an enzymatically inactive homodimer, which occurs on long term storage or by chemical oxidation. Thus, although clearly involved in protein inactivation, Cys73 is not necessary for the growth stimulating activity of Trx.

Growth Substances↗
PubMed1995

Site-directed mutagenesis of Lys36 in human thioredoxin: the highly conserved residue affects reduction rates and growth stimulation but is not essential for the redox protein's biochemical or biological properties.

Previous studies have demonstrated that a recombinant form of the human redox protein thioredoxin can stimulate the growth rate of Swiss 3T3 murine fibroblasts and that this ability to promote cellular proliferation was dependent upon a redox-active form. A site-directed mutagenesis study of the highly conserved Lys36 adjacent to the two active site cysteines of thioredoxin was performed to determine whether the basic residue was essential for the biochemical and mitogenic properties of human thioredoxin. Two mutants were generated in which the lysine residue was replaced with either glutamic acid (K36E) or leucine (K36L). While K36E and K36L were both redox-active in a thioredoxin-specific assay, the mutants exhibited decreased affinities for thioredoxin reductase relative to wild-type thioredoxin since their respective KM values increased by a factor of 5 and 7. Examination of the secondary structure of the variants by circular dichroism spectroscopy revealed that both mutants had minor variations in the overall structural content when compared to thioredoxin, with K36L being most similar to the wild-type protein. Thermal equilibrium denaturation studies of the variants showed that K36E had a TM of 69.5 degrees C. A TM value for thioredoxin and K36L could not be established because the absence of a plateau above 83 degrees C rendered it difficult to establish an upper base line and, hence, the TM. The two mutants were able to stimulate cellular proliferation, albeit with reduced efficiency when compared with wild-type thioredoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1995

Inhibitors of phospholipid intracellular signaling as antiproliferative agents.

The improved understanding of oncogenesis and the involvement of oncogenes and tumor suppressor genes, has led to a rational approach of specific target-directed anti-cancer drug development. Cancer genes have been found to be important not only in the control of cell proliferation but also in the mediation of processes such as drug resistance, metastasis, neo-vascularization (angiogenesis), and apoptosis. These are all important targets in their own right and the development of drugs against specific "upstream" targets in oncogenic or growth factor signal transduction cascades it may be possible to inhibit multiple "downstream" targets. Ultimately, to test the hypothesis that signaling pathways offer good targets for anticancer drug development will take several years of careful clinical study and we cannot say at this time whether the approach will work. There are a small number of compounds in the early stages of clinical development as anticancer agents that may act by inhibiting growth factor signaling pathways. In all cases the activity of the compounds on intracellular signaling pathways was discovered after their identification as antiproliferative agents. There are also compounds in preclinical development that have been specifically developed as inhibitors of growth factor signaling, although their selectivity for tumor cells compared to normal tissue remains to be investigated fully in appropriate animal tumor models. It is possible that a single antisignaling drug by itself may not have the power to completely inhibit tumor growth and a combination of drugs may be needed. It may also take a combination of drugs to prevent the emergence of resistance. Clearly there are several challenges to developing this new class of anticancer drugs, and there will undoubtedly be others that must be faced.

Antineoplastic Agents↗
PubMed1994

5-Fluorouracil causes alterations in the pharmacokinetic profile of tauromustine in NMRI mice.

The pharmacokinetic profiles of 5-fluorouracil (5-FU) and tauromustine (TCNU) were investigated in NMRI mice following their administration either alone or as part of simultaneous or sequential combinations. The profile of 5-FU remained unaltered irrespective of the sequence of administration. However, following simultaneous administration of 5-FU and TCNU or pretreatment with 5-FU, plasma levels of TCNU were decreased by a factor of 2.5-3 as compared with those seen when TCNU was given alone. These decreased plasma levels were explained by an increase in the TCNU volume of distribution, although this was not due to alterations in TCNU plasma protein binding. These sequence-dependent alterations in the pharmacokinetic profile of TCNU correlate with and may explain previously reported differences in the anti-tumour activity and toxicity profile of this combination.

Animals↗
PubMed1994

The thioredoxin/thioredoxin reductase redox system and control of cell growth.

Thioredoxin is a redox protein that is important for a variety of intracellular functions, possibly including regulation of transcription factor activity. We have shown that human thioredoxin has the same predicted amino acid sequence as adult T-cell-derived leukemic cell growth factor. Recombinant human thioredoxin stimulates the proliferation of Swiss murine 3T3 fibroblasts with an EC50 of 100 nM and the proliferation of a number of human cancer cells. Site-directed mutagenesis of the active-site cysteines of thioredoxin has shown that redox activity is necessary for the stimulation of cell proliferation. Added 125I-thioredoxin is taken up by cells in culture and could have intracellular action. A series of alkyl 2-imidazolyl disulfides have been shown to be competitive inhibitors of human thioredoxin reductase with Ki values of 3.3 to 8.6 microM. The compounds inhibited Swiss 3T3 serum-dependent proliferation with IC50 values of 2.0 to 4.0 microM, and one compound inhibited Swiss 3T3 thioredoxin-dependent proliferation with an IC50 value of 60 nM.

3T3 Cells↗
PubMed1994

The response to arachidonic acid before and after non-steroidal anti-inflammatory drugs in normotensive and hypertensive rats.

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.

Animals↗