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Biomedical subjects

M Simpson

Publications and source records attributed to M Simpson.

At least 19 recordsLinked to original sources
PubMed2004

Quality use of medicines in the rural ambulant elderly: a pilot study.

INTRODUCTION: Australia has a rapidly ageing population, especially in rural areas, and strategies to address medicines and the elderly are particularly relevant. The aims of this 18 month study, therefore, were to: (1) determine the influence of a medication review on the quality of life of elderly ambulatory patients managed by a general practitioner; and (2) assess the impact of the medication review process on health outcomes such as medication-related hospital admissions in ambulant elderly patients actively managed by their GP. METHODS: The study was conducted within the area serviced by the rural Riverina Division of General Practice, New South Wales, Australia. Patients were identified by clinical audit, and recruited to the study if they met the inclusion criteria of being: older than 65 years, ambulant, living independently and on five or more medications. The study sample consisted of 402 participants (156 men, 38.8%; 246 women, 61.2%). Fifty-eight participants withdrew from the study for a variety of reasons. A two-group (intervention, control) pre- and post-intervention randomized study design was utilized. Quality of life was assessed using SF-36. The medication history and clinical details of the 202 study participants were reviewed by the project pharmacist and their GP. Medication changes were suggested to patients by their GP and follow-up SF36 and review of hospitalisation episodes were conducted after 6 months. RESULTS: 3382 medications were identified as being taken, an average of 8.4 medications per patient. After the initial medication review, the study pharmacist suggested an alteration in dose, form or frequency for 687 medications in the intervention group. The GPs recommended an alteration in 243 of patient medications. Of the entire study population (n = 402), only two participants' admission to hospital was specifically attributed to medication-related issues. There were no significant differences between the quality of life assessments for the combined groups; however, the intervention group recorded significantly higher scores in two of the nine dimensions measured: vitality (p 0.009) and mental health (p 0.0001), at the post-intervention assessment. CONCLUSION: While the intervention did not reduce hospitalisation episodes and only led to a modest improvement in quality of life, the development of a mutually acceptable form of face-to-face pharmacist/GP medication review, identification of potentially serious adverse drug reactions, identification of previously unreported complementary medicine use, and enhanced GP awareness of the risks of polypharmacy were positive outcomes of the study.

Journal Article↗
PubMed2002

Acute renal failure requiring renal replacement therapy: incidence and outcome.

BACKGROUND: Renal replacement therapy (RRT) for acute renal failure (ARF) may be provided in many settings within the hospital. Such patients require a high level of care and often have a poor prognosis. No prospective studies have accurately defined this population, making the prediction of necessary resources and the planning of services difficult. AIM: To ascertain the incidence, causes and outcomes of acute renal failure requiring renal replacement therapy in Scotland. DESIGN: A prospective observational census of all clinical areas providing renal replacement therapy in three Scottish health boards (Grampian, Highland, Tayside). METHODS: Patients were identified by liaison with each unit providing RRT. Factors precipitating renal failure and reasons for RRT were recorded at the time of initiation. Comorbid disease burden was scored using the Charlson index. Patient status at 90 days was assessed from case-notes, contacting general practitioners where necessary. RESULTS: 375 patients per million population per year received RRT; 203 per million per year for either ARF or acute-on-chronic renal failure. 73.5% of patients receiving RRT for ARF died within 90 days, 23.5% became independent of RRT. The median duration of hospital admission was 19 days. DISCUSSION: The annual incidence of ARF requiring RRT is just over 200 per million population, almost twice that of end-stage renal disease requiring RRT. Such treatment places high demands upon health care resources.

Acute Kidney Injury↗
PubMed2002

Section 136, The Mental Health Act 1983; levels of knowledge among accident and emergency doctors, senior nurses, and police constables.

OBJECTIVES: Section 136 of the Mental Health Act 1983 empowers the police to detain those suspected of being mentally ill in public places, and convey them to a place of safety. In practice, accident and emergency (A&E) departments are often used. The authors assessed levels of knowledge of section 136 between A&E doctors, senior nurses, and police constables. METHODS: Doctors and senior nurses in all (A&E) departments in the Yorkshire region were asked to complete a multiple choice tick box type questionnaire, as were police constables from the Humberside Police Force. RESULTS: 179 completed questionnaires were returned, of which 16 were completed by consultants, 14 by SpRs, 24 by SHOs, 33 by senior nurses, and 92 by police officers. Some 24.1% of A&E staff and 10.9% of police failed to recognise that a person has to appear to be suffering from a mental disorder to be placed on a section 136; 40.2% of police did not know that section 136 is a police power; 55.2% of A&E staff and 14.1% of police incorrectly thought that a person could be placed on a section 136 in their own home; 43.75% of consultants and 50% of SpRs did not consider A&E departments to be a place of safety; 49.4% of A&E staff and 29.3% of police thought that patients could be transferred on a section 136. Only 10.3% of A&E staff and 22.8% of police had received any formal training. CONCLUSIONS: The knowledge among A&E staff and the police of this difficult and complex piece of mental health legislation is poor and requires action through formal education and training. This study not only reflects the levels of knowledge within the groups, it may also reflect the different perceptions of each group as to their role and duties within section 136 of the Mental Health Act 1983.

Emergency Service, Hospital↗
PubMed2001

Correlation between histone lysine methylation and developmental changes at the chicken beta-globin locus.

Methylation of histones at specific residues plays an important role in transcriptional regulation. Chromatin immunoprecipitation of dimethylated lysine 9 on histone H3 across 53 kilobases of the chicken beta-globin locus during erythropoiesis shows an almost complete anticorrelation between regions of elevated lysine 9 methylation and acetylation. Lysine 9 is methylated most over constitutive condensed chromatin and developmentally inactive globin genes. In contrast, lysine 4 methylation of histone H3 correlates with H3 acetylation. These results lead us to propose a mechanism by which the insulator in the beta-globin locus can protect the globin genes from being silenced by adjacent condensed chromatin.

Acetylation↗
PubMed2001

Transitions in histone acetylation reveal boundaries of three separately regulated neighboring loci.

We have studied developmentally regulated patterns of histone acetylation at high resolution across approximately 54 kb of DNA containing three independently regulated but neighboring genetic loci. These include a folate receptor gene, a 16 kb condensed chromatin region, the chicken beta-globin domain and an adjacent olfactory receptor gene. Within these regions the relative levels of acetylation appear to fall into three classes. The condensed chromatin region maintains the lowest acetylation at every developmental stage. Genes that are inactive show similarly low levels, but activation results in a dramatic increase in acetylation. The highest levels of acetylation are seen at regulatory sites upstream of the genes. These patterns imply the action of more than one class of acetylation. Notably, there is a very strong constitutive focus of hyperacetylation at the 5' insulator element separating the globin locus from the folate receptor region, which suggests that this insulator element may harbor a high concentration of histone acetylases.

5' Untranslated Regions↗
PubMed2001

Vertebrate LTR retrotransposons of the Tf1/sushi group.

LTR retrotransposons of the Tf1/sushi group from a diversity of vertebrates, including fish, amphibians, and mammals (humans, mice, and others), are described as full-length or partial elements. These elements are compared, and the mechanisms involved in self-priming of reverse transcriptase and programmed phase shifting are inferred. Evidence is presented that in mammals these elements are still transcriptionally active and are represented as proteins. This suggests that members of the Tf1/sushi group are present as functional elements (or incorporated as partial elements into host genes) in diverse vertebrate lineages.

Amino Acid Sequence↗
PubMed2000

Structural and functional conservation at the boundaries of the chicken beta-globin domain.

We show that the 3' boundary of the chicken beta-globin locus bears striking structural similarities to the 5' boundary. In erythroid cells a clear transition in DNase I sensitivity of chromatin at the 3' end of the locus is observed, the location of this transition is marked by a constitutive DNase I hypersensitive site (HS), and DNA spanning this site has the enhancer-blocking capacity of an insulator. This HS contains a binding site for the transcription factor CTCF. As in the case of the 5' insulator, the CTCF site is both necessary and sufficient for the enhancer-blocking activity of the 3' boundary. The position of this insulator is consistent with our proposal that it may function to maintain the distinct regulatory programs of the globin genes and their closely appended 3' neighbor, an odorant receptor gene. We conclude that both boundaries of the chicken beta-globin domain are capable of playing functionally similar roles and that the same protein is a necessary component of the molecular mechanism through which these boundaries are defined.

Animals↗
PubMed2000

The history of dermatologic surgical reconstruction.

Over the last 40-50 years, reconstructive surgery in dermatology has undergone expansive growth and development. As dermatologists began to provide a greater array of surgical services during this period, it became apparent that new skills and techniques in the area of reconstruction would be required. Initially many of the procedures and concepts were adopted from other specialties, however, in the years since, significant contributions have been made by dermatologists which in turn have benefited other specialties as well. This review attempts to summarize some of the significant historical events and innovations that have established and supported dermatologic surgical reconstruction.

Dermatologic Surgical Procedures↗
PubMed2000

Local delivery of nadroparin for the prevention of neointimal hyperplasia following stent implantation: results of the IMPRESS trial. A multicentre, randomized, clinical, angiographic and intravascular ultrasound study.

BACKGROUND: We hypothesized that intramural delivery of nadroparin, a low molecular weight heparin, would prevent in-stent restenosis by inhibiting neointimal hyperplasia in an angioplasty model free of arterial remodelling. METHODS AND RESULTS: In a prospective randomized multicentre trial, 250 patients submitted to balloon angioplasty followed by stent implantation were randomized into control group (no local drug delivery) or intramural delivery of nadroparin (2 ml of 2500 anti-Xa-units/ml with a microporous catheter). An ancillary intravascular ultrasound substudy was performed to supplement angiographic data with specific measurements of in-stent neointimal hyperplasia. The primary end-point was the late loss in minimal luminal diameter on the 6 month follow-up angiogram. Secondary end-points included feasibility and safety of local nadroparin delivery, and major adverse cardiac events at 8 weeks and 6 months follow-up. Local delivery of nadroparin was successful in 124 patients (99.2% success rate) and was not associated with an increase in stent thrombosis, coronary artery dissection, side branch occlusion, distal embolization or abrupt arterial closure. At angiographic follow-up, the late loss in lumen diameter was 0.84 +/- 0.62 mm in the control group compared to 0.88 +/- 0.63 mm in the nadroparin group (P=0.56). Angiographic restenosis rate (defined as a >50% diameter stenosis) did not differ in the control group (20%) compared to the nadroparin group (24%). The average area of neointimal tissue within the stent was 2.86 +/- 0.64 mm(2) vs 2.90 +/- 0.53 mm(2) (P=0.57), control vs nadroparin groups. There was no difference in major adverse cardiac events at any time (88.8% vs 89.6% event free survival at 6 months, control vs nadroparin). CONCLUSION: Intramural delivery of nadroparin with a microporous catheter after stent deployment was feasible and safe but had no effect in reducing restenosis or the occurrence of major adverse clinical events over 6 months.

Adult↗
PubMed2000

Effects of liposome-encapsulated ciprofloxacin on phagocytosis, nitric oxide and intracellular killing of Staphylcoccus aureus by murine macrophages.

The effects of liposome-encapsulated ciprofloxacin on phagocytosis, nitric oxide production and intracellular killing of Staphylococcus aureus in murine macrophages were evaluated in this study. Mice were pretreated with three daily doses of liposome-encapsulated ciprofloxacin (45 mg/kg body weight/dose, intraperitoneal injection). At day 3 post drug administration, peritoneal macrophages were harvested by peritoneal lavage, and the phagocytic activity of the macrophages was determined by a chemiluminescence assay using opsonized zymosan particles. The phagocytic activity was found to be 7-fold higher in the liposome-encapsulated ciprofloxacin-treated group when compared to the untreated control group. For S. aureus-infected macrophages incubated with liposomes containing subinhibitory concentrations of ciprofloxacin (0.05 to 0.25 microg/mL), there were significant increases (up to 40 microM) in the levels of nitrite (NO2-, an end product of nitric oxide synthesis), and concommitant decreases (2-3 log) in the intracellular concentrations of S. aureus. Peak nitrite levels (20-40 microM) were produced when concentrations of liposome-encapsulated ciprofloxacin used were 0.1 to 0.25 microg/mL. These results suggest that liposome-encapsulated ciprofloxacin may have profound effects on the immunological functions of macrophages.

Animals↗
PubMed2000

Blame NSW education.

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Animal Nutritional Physiological Phenomena↗
PubMed1999

Activation-induced CD4+ T cell death in HIV-positive individuals correlates with Fas susceptibility, CD4+ T cell count, and HIV plasma viral copy number.

The relevance of activation-induced cell death (AICD) of CD4+ T cells to AIDS pathogenesis is unknown. The present study investigates the relationship of AICD to a defined molecular mechanism regulating peripheral T cell homeostasis, Fas-mediated apoptosis, and clinical correlates of the pathogenesis of AIDS. Increased pokeweed mitogen (PWM)-induced AICD (22.8 versus 4.4%, p = 0.006) and Fas-mediated apoptosis (27.7 versus 12.0%, p = 0.002) of CD4+ T cells were observed in HIV+ versus HIV- individuals. Similarly, increased PWM-mediated AICD (16.2 versus 2.2%, p < 0.001) and Fas-mediated apoptosis (25.8 versus 7.6%, p = 0.005) were noted in CD8+ T cells from HIV+ versus HIV- individuals. PWM-induced AICD of CD4+ T cells was blocked (83% median specific inhibition) by Fas-blocking antibodies, whereas PWM-induced AICD of CD8+ T cells was Fas independent. Comparison between PWM- and anti-CD3-mediated AICD of CD4+ T cells indicated that PWM- and not CD3-induced AICD is Fas dependent. HIV+ individuals with an HIV RNA copy number of <30,000 copies/ml had lower PWM-induced AICD of CD4+ T cells than did those with an HIV RNA copy number of >30,000 copies/ml (5.7 versus 22.1%, p = 0.034), and PWM-induced AICD inversely correlated with CD4+ T cell count (R = -0.567, p = 0.043). Initiation of HAART decreased PWM-induced CD4+ T cell AICD from 24.4 to 9.4% posttreatment (p = 0.035). These results demonstrate that PWM-induced AICD of CD4+ T cells from HIV+ individuals is mediated by Fas/FasL, parallels the in vivo susceptibility of the CD4+ T cell to Fas-mediated apoptosis, and correlates with clinical markers of AIDS pathogenesis and response to HAART.

Anti-HIV Agents↗
PubMed1999

An insulator element and condensed chromatin region separate the chicken beta-globin locus from an independently regulated erythroid-specific folate receptor gene.

We have identified a folate receptor gene upstream of the chicken beta-globin locus and separated from it by a 16 kbp region of silent chromatin. We find that this receptor is expressed only at a stage of erythroid differentiation (CFU-E) preceding the activation of beta-globin genes, consistent with the role of folate receptors in proliferation. This discovery raises the question of how these two loci are regulated during erythropoiesis. Our data suggest that the folate receptor gene and the beta-globin locus are regulated independently. We show that a 3.3 kbp DNA region upstream of the folate receptor gene is sufficient to induce strong expression of a transgene in CFU-E stage cells. We also find that the region between the beta-globin locus and the folate receptor gene is fully methylated and condensed at this stage of differentiation. Its 3' boundary coincides with the 5' beta-globin insulator. We speculate that the 5' beta-globin boundary element might be important for the proper regulation of two adjacent domains activated at two different stages during differentiation.

Amino Acid Sequence↗
PubMed1999

Arginine activity in the proton-motive photocycle of bacteriorhodopsin: solid-state NMR studies of the wild-type and D85N proteins.

15N solid-state NMR (SSNMR) spectra of guanidyl-15N-labeled bacteriorhodopsin (bR) show perturbation of an arginine residue upon deprotonation of the retinal Schiff base during the photocycle. At the epsilon position, an upfield shift of 4 ppm is observed while the eta nitrogens develop a pair of 'wing' peaks separated by 24 ppm. Proton-driven spin diffusion between the two 'wing' peaks indicates that they arise from a single Arg residue. An unusually asymmetric environment for this residue is indicated by comparison with guanidyl-15N chemical shifts in a series of arginine model compounds. The 'wing' peaks are tentatively assigned to Arg-82 on the basis of the SSNMR investigations of the alkaline and neutral dark-adapted forms of the D85N bacteriorhodopsin mutant. Another, less asymmetric pair of eta signals, that is not affected by Schiff base deprotonation or D85 mutation, is tentatively assigned to Arg-134. The results are discussed in relation to existing models of bR structure and function.

Amino Acid Substitution↗
PubMed1999

Raspberry leaf and its effect on labour: safety and efficacy.

The purpose of this study was to examine the safety and efficacy of raspberry leaf products consumed by a group of mothers during their pregnancy, by comparison with a group of mothers who did not. A retrospective observational design was used. Subjects were women who birth their babies at Westmead Hospital between January 1998-July 1998. The sample consisted of 108 mothers; 57 (52.8%) consumed raspberry leaf products while 51 (47.2%) were in the control group. The findings suggest that the raspberry leaf herb can be consumed by women during their pregnancy for the purpose for which it is taken, that is, to shorten labour with no identified side effects for the women or their babies. The findings also suggest ingestion of the drug might decrease the likelihood of pre and post-term gestation. An unexpected finding in this study seems to indicate that women who ingest raspberry leaf might be less likely to receive an artificial rupture of their membranes, or require a caesarean section, forceps or vacuum birth than the women in the control group.

Adolescent↗