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Biomedical subjects

D Murphy

Publications and source records attributed to D Murphy.

At least 19 recordsLinked to original sources
PubMed2007

Fear appeals and treatment side-effects: an effective combination for HIV prevention?

Recent rises in the incidence of HIV infections among gay men in Australia have produced widespread discussion about appropriate health promotion responses. This has sometimes included calls for a return to fear-based campaigns, exemplified by the Grim Reaper advertisements in HIV. This paper discusses results from four focus groups that tested mock campaign material based on an appeal to fear. Five different poster images were tested among groups distinguished by age and HIV serostatus. Three posters used side-effects from treatments as the fear trigger and two used death from AIDS. A number of themes arose in response to the material including 'othering', shame and scepticism about HIV treatments. The meanings of these themes are explored in the light of current health-promotion theory. This data demonstrates that fear is an ineffective tool for HIV health promotion. It further demonstrates that feelings of shame and stigma are likely to be exacerbated in gay men, leading to poorer health outcomes in various ways.

Adult↗
PubMed2006

How has legislation restricting paracetamol pack size affected patterns of deprivation related inequalities in self-harm in Scotland?

OBJECTIVE: To describe how changes in legislation to control sales and thus restrict the general availability of paracetamol have affected deprivation-related inequalities in deliberate self-harm associated with the drug in Scotland. DESIGN AND SETTING: A descriptive analysis of routine death and hospital discharge data for the entire Scottish population between 1995 and 2002. PARTICIPANTS: Patients in Scotland admitted to hospital with a diagnosis of poisoning and deaths in Scotland due to poisoning 1995-2002. OUTCOME MEASURES: Changes in mortality and overdose rates by deprivation quintile, and case fatality rates due to poisoning involving paracetamol. RESULTS: Rates of overdose involving paracetamol, while much higher in disadvantaged quintiles, fell in each deprivation quintile following the 1998 legislation. They then returned to levels similar, or above those in the mid 1990s. All quintiles were affected to a similar extent with the relationship between them remaining constant over time. Case fatality rates were significantly higher in more disadvantaged quintiles. CONCLUSIONS: Marked inequalities exist in paracetamol related harm in Scotland. The most disadvantaged groups (both male and female) have higher overdose and death rates, as well as higher case fatality rates. Following the restrictions all social groups saw similar reductions in paracetamol related harm. This effect has been short-lived and rates have returned to pre-legislation levels. Legislation has not permanently affected overall use of paracetamol in overdose in Scotland or reduced the proportion of patients taking paracetamol as a component of the overdose in the longer term. An important public health policy has failed to achieve its objective and it is not clear why. We need a better understanding of why this measure had only short-term benefits if its full potential is to be achieved.

Acetaminophen↗
PubMed2006

A spinal vasopressinergic mechanism mediates hyperosmolality-induced sympathoexcitation.

An elevation in plasma osmolality elicits a complex neurohumoral response, including an activation of the sympathetic nervous system and an increase in arterial pressure. Using a combination of in vivo and in situ rat preparations, we sought to investigate whether hypothalamic vasopressinergic spinally projecting neurones are activated during increases in plasma osmolality to elicit sympathoexcitation. Hypertonic saline (HS, i.v. bolus), which produced a physiological increase in plasma osmolality to 299 +/- 1 mosmol (kg water)(-1), elicited an immediate increase in mean arterial pressure (MAP) (from 101 +/- 1 to 121 +/- 3 mmHg) in vivo. Pre-treatment with prazosin reversed the HS-induced pressor response to a hypotensive response (from 121 +/- 3 to 68 +/- 2 mmHg), indicating significant activation of the sympathetic nervous system. In an in situ arterially perfused decorticate rat preparation, hyperosmotic perfusate consisted of either 135 mm NaCl, or a non-NaCl osmolyte, mannitol (0.5%); both increased lumbar sympathetic nerve activity (LSNA) by 32 +/- 5% (NaCl) and 21 +/- 1% (mannitol), which was attenuated after precollicular transection (7 +/- 3% and 1 +/- 1%, respectively). Remaining experiments used the NaCl hyperosmotic stimulus. In separate preparations the hyperosmotic-induced sympathoexcitation (21 +/- 2%) was also significantly attenuated after transection of the circumventricular organs (2 +/- 1%). Either isoguvacine (a GABA(A) receptor agonist) or kynurenic acid (a non-selective ionotropic glutamate receptor antagonist) microinjected bilaterally into the paraventricular nucleus (PVN) attenuated the increase in LSNA induced by the hyperosmotic stimulus (control: 25 +/- 2%; after isoguvacine: 7 +/- 2%; after kynurenic: 8 +/- 3%). Intrathecal injection of a V(1a) receptor antagonist also reduced the increase in LSNA elicited by the hyperosmotic stimulus (control: 29 +/- 6%; after blocker: 4 +/- 1%). These results suggest that a physiological hyperosmotic stimulus produces sympathetically mediated hypertension in conscious rats. These data are substantiated by the in situ decorticate preparation in which sympathoexcitation was also evoked by comparable hyperosmotic stimulation. Our findings demonstrate the importance of vasopressin acting on spinal V(1a) receptors for mediating sympathoexcitatory response to acute salt loading.

Adrenergic alpha-Antagonists↗
PubMed2006

Chest drain insertion may result in the acute scrotum.

Pneumoscrotum is an extremely rare occurrence following a variety of procedural and pathological causes. We describe a case following multiple chest drain insertions which was managed conservatively. It is important to differentiate pneumoscrotum from other causes of acute scrotum as it may precede a serious pathology and may require medical or surgical intervention.

Acute Disease↗
PubMed2006

Legislation restricting paracetamol sales and patterns of self-harm and death from paracetamol-containing preparations in Scotland.

AIMS: To describe how changes in legislation to restrict paracetamol sales have affected overdose discharges and death associated with the drug in Scotland. METHODS: A descriptive analysis of routine death and hospital discharge data for the entire Scottish population between 1995 and 2004. Patients in Scotland participated who were discharged from hospital with a diagnosis of poisoning; deaths in Scotland from diagnosis of poisoning 1995-2003 were also analysed. Outcome measures were changes in mortality and overdose due to poisoning involving paracetamol. A comparison was made of in-hospital and out-of-hospital mortality in fatalities involving paracetamol. RESULTS: The majority of paracetamol-associated deaths were due to co-proxamol. Deaths associated with paracetamol alone or with ethanol occurred principally in hospital and were a minority of deaths overall. The proportion of in-hospital deaths attributed to paracetamol increased (post/pre ratio 1.347; 95% confidence interval 1.076, 1.639; P = 0.013). Overall numbers of cases discharged with poisoning fell. The proportion of these involving paracetamol in any form increased significantly in all groups except young men aged 10 to <20 years. CONCLUSIONS: Legislation has not reduced mortality or proportional use of paracetamol in overdose, both of which appear to have increased in Scotland since pack-size limitations. Other approaches are necessary to reduce the death rate from overdoses involving paracetamol.

Acetaminophen↗
PubMed2006

Exaggerated response of arginine vasopressin-enhanced green fluorescent protein fusion gene to salt loading without disturbance of body fluid homeostasis in rats.

We examined the effects of chronic salt loading on the hypothalamic expressions of the enhanced green fluorescent protein (eGFP), arginine vasopressin (AVP) and oxytocin (OXT) genes in AVP-eGFP transgenic rats that expressed eGFP in the hypothalamic AVP-containing neurones. In these rats, salt loading for 5 days caused a marked increase of the eGFP fluorescence in the magnocellular divisions of the paraventricular nucleus (PVN), the supraoptic nucleus (SON) and the internal layer of the median eminence. Expression of the eGFP gene was increased seven- to eight-fold in the PVN and SON of salt-loaded rats in comparison with euhydrated rats. By contrast, none of these changes were observed in the suprachiasmatic nucleus. The expression of the AVP and OXT genes was increased 1.5- to two-fold in the PVN and SON of salt-loaded nontransgenic (control) and transgenic rats. There were no differences in the expression levels of the AVP and OXT genes in the PVN and SON between nontransgenic (control) and transgenic animals under normal conditions and after salt loading. In the posterior pituitary gland, the intensity of the eGFP fluorescence did not change after salt loading for 5 days, but increased after 10 days of salt loading. Upon salt loading, significant increases in the plasma AVP concentrations, plasma osmolality and plasma Na+ were observed. Furthermore, there were no significant differences in changes of water intake, food intake, urine volume, urine osmolality, urine Na+ concentrations, and the body weights in both models under normal or salt-loaded conditions. Our results show that the response of the AVP-eGFP fusion gene to chronic salt loading is exaggerated, and humoral responses such as AVP and OXT and the body fluid homeostasis are maintained in AVP-eGFP transgenic rats. The AVP-eGFP transgenic rat gives us a new opportunity to study the dynamics of the AVP system in vivo.

Animals↗
PubMed2006

Robotic technology in urology.

Urology has increasingly become a technology-driven specialty. The advent of robotic surgical systems in the past 10 years has led to urologists becoming the world leaders in the use of such technology. In this paper, we review the history and current status of robotic technology in urology. From the earliest uses of robots for transurethral resection of the prostate, to robotic devices for manipulating laparoscopes and to the current crop of master-slave devices for robotic-assisted laparoscopic surgery, the evolution of robotics in the urology operating theatre is presented. Future possibilities, including the prospects for nanotechnology in urology, are awaited.

Humans↗
PubMed2005

T-cell responses to human papillomavirus type 16 among women with different grades of cervical neoplasia.

Infection with high-risk genital human papillomavirus (HPV) types is a major risk factor for the development of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The design of effective immunotherapies requires a greater understanding of how HPV-specific T-cell responses are involved in disease clearance and/or progression. Here, we have investigated T-cell responses to five HPV16 proteins (E6, E7, E4, L1 and L2) in women with CIN or cervical carcinoma directly ex vivo. T-cell responses were observed in the majority (78%) of samples. The frequency of CD4+ responders was far lower among those with progressive disease, indicating that the CD4+ T-cell response might be important in HPV clearance. CD8+ reactivity to E6 peptides was dominant across all disease grades, inferring that E6-specific CD8+ T cells are not vitally involved in disease clearance. T-cell responses were demonstrated in the majority (80%) of cervical cancer patients, but are obviously ineffective. Our study reveals significant differences in HPV16 immunity during progressive CIN. We conclude that the HPV-specific CD4+ T-cell response should be an important consideration in immunotherapy design, which should aim to target preinvasive disease.

Adult↗
PubMed2005

The role of radiotracer imaging in Parkinson disease.

Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [18F]fluorodopa PET, (+)-[11C]dihydrotetrabenazine PET, [123I]beta-CIT SPECT, and [18F]fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer.

Biomarkers↗
PubMed2005

Hypothesis: epithelial-to-mesenchymal transition is a common cause of chronic allograft failure.

Renal, hepatic, and lung allografts are compromised by aggressively deteriorating function. This chronic process is produced by an overall burden of organ damage, but the pathophysiology remains poorly understood. Rates of chronic rejection in the lung, for example, have not substantially improved over the last decade, despite new immunosuppressive drugs and improvements in surgical procedure. We present a hypothesis that epithelial-to-mesenchymal transition is a common cause of chronic allograft failure. Research in this area may provide insights into chronic rejection of kidney, liver, and lung allografts that impact on future therapeutic strategies.

Cell Differentiation↗
PubMed2005

Oncogene-dependent tumor suppression: using the dark side of the force for cancer therapy.

Cancers arise by an evolutionary process that involves the protracted acquisition by somatic cells of suites of interlocking mutations that uncouple proliferation, survival, migration, and damage responses from the mechanisms (selective pressures) that normally restrain or restrict them in time and space. The relative rareness of cancer cells within the soma, in the face of huge numbers of available cell targets, substantial rates of mutation, and an abundance of proto-oncogenes and tumor suppressor gene targets, indicates that the evolutionary space available to incipient tumor cells is highly restricted. The principal way in which this is achieved is through intrinsic tumor suppression pathways-innate growth arrest and apoptotic programs that fulfill an essentially analogous functional role to checkpoints in the cell cycle machinery by antagonizing the tumorigenic potential of oncogenic mutations. Using switchable transgenic and knockin mouse models, it is possible to identify these various tumor suppressor programs and establish where, when, how, and why they act to forestall neoplasia in each tissue type and, consequently, how and why their failure leads to cancer.

Animals↗
PubMed2004

Surfactant-facilitated crystallization of dihydrate carbamazepine during dissolution of anhydrous polymorph.

The influence of two structurally different anionic surfactants on the anhydrous-to-dihydrate transformation of carbamazepine (CBZ) was investigated. The surfactants studied were sodium lauryl sulfate (SLS), a surfactant commonly used in compendial dissolution methods, and sodium taurocholate (STC), an important surfactant in the solubilization and absorption of drugs and lipids in the gastrointestinal tract. Results show that both surfactants promoted the crystallization of CBZ dihydrate [CBZ(D)] during dissolution of the anhydrous monoclinic polymorph [CBZ(A)]). Examination of crystal surfaces showed that SLS facilitated the surface-mediated nucleation of CBZ(D) on CBZ(A) crystals at surfactant concentrations below the critical micelle concentration (cmc). Solubilization of a dye and related color changes provided visual evidence for adsorbed SLS assemblies on CBZ(A) crystal faces below the cmc. Above the cmc, both surfactants promoted the transformation by increasing the bulk nucleation of CBZ(D). STC changed the crystal morphology of CBZ(D) from acicular to prismatic, depending on STC concentration. Such morphology changes originate from interactions between STC and molecular structures of CBZ(D) crystal faces that interfere with the formation of a hydrogen-bonded chain of water molecules and carboxamide dimers.

Calorimetry, Differential Scanning↗
PubMed2004

Inflammatory pseudotumour of the caecum: a case report.

Inflammatory pseudotumors of the caecum are uncommon. They pose problems with diagnosis. We report on a 35 year old female who presented with clinical signs of acute appendicitis. Intra-operatively, a caecal tumour was found with normal appendix and multiple enlarged mesenteric lymph nodes. A right hemicolectomy was performed. Histopathology findings revealed an inflammatory mass with abundant fibroblast proliferation with associated collagen formation, infiltrating bowel wall and pericaecal adipose tissue. She recovered well and was discharged home 5 days post-operatively. At present, she is free of symptoms.

Adult↗
PubMed2004

Operational characteristics of tractors driven by children on farms in the United States and Canada.

Farm tractors are an important source of traumatic injury for children on farms. There is, however, no documentation about the age and size of tractors that children are operating and little information about the frequency with which rollover protective structures (ROPS) are used. This study described tractors that children on farms in the U.S. and Canada were operating by age, horsepower, and the presence of ROPS, according to the age and gender of the farm children involved. As a sub-analysis of data compiled during a randomized controlled trial, a descriptive analysis was completed on work exposure data collected by telephone interview. Of the 1,113 children involved in the trial, 522 (47%) were reported to perform at least one job that involved the operation of a farm tractor, and 408 (36.7%) were operating tractors of at least 20 horsepower. The majority of these children were male. There was a wide range of ages and sizes of tractors operated. However, the majority of tractors were between 20 and 70 horsepower and manufactured after 1970. Nearly one-half of the tractors were equipped with ROPS, and these tended to be newer and larger tractors. This analysis provides new data about the broad range of tractors driven by farm children in the U.S. and Canada. The findings point to a need to re-examine the reliance on a single voluntary standard to mitigate the hazard of tractor rollovers and the need for an enhanced safety policy requiring all tractors operated by children be equipped with ROPS.

Accidents, Occupational↗
PubMed2004

Manipulating sorting signals to generate co-expression of somatostatin and eGFP in the regulated secretory pathway from a monocistronic construct.

Targeted overexpression of biologically active peptides represents a powerful approach to the functional dissection of neuroendocrine systems. However, the requirement to generate separate, biologically active and reporter molecules necessitates the use of internal ribosome entry site (IRES) technology, which often results in preferential translation of the second cistron. We report here a novel approach in which the proteolytic processing machinery of the regulated secretory pathway (RSP) has been exploited to generate multiple mature proteins from a monocistronic construct that encodes a single precursor. This was achieved by duplication of the pre-pro cleavage sites in pre-prosomatostatin cDNA. The duplicated site included 10 flanking amino acids on either side of the Gly-Ala cleavage position. This enabled the incorporation of a foreign protein-coding sequence (in this case, enhanced green fluorescent protein (eGFP)) between these sites. The pre-eGFP-prosomatostatin (PEPS) construct generated co-localized expression of fully processed eGFP and somatostatin to the RSP of transiently transfected AtT20 cells. This approach represents an advance upon bicistronic and other extant approaches to the targeting of multiple, biologically active proteins to neuroendocrine systems, and, importantly, permits the co-expression of fluorescent markers with biologically active neuropeptides. In this study, our demonstration of the fusion of the first 10 amino acids of the prosomatostatin sequence to the N-terminus of eGFP shows that this putative sorting sequence is sufficient to direct expression to the RSP.

Animals↗
PubMed2003

Outcome after acetabular fracture. Prognostic factors and their inter-relationships.

The aim of this study was to examine how commonly implicated prognostic factors are associated with late clinical outcome after reconstruction of acetabular fractures. The clinical outcomes of 180 fractures, treated by a single surgeon over a 10-year period, were assessed using the scoring system of Merle d'Aubigné and Postel. A statistical model was constructed comprising the clinical outcome and nine postulated prognostic factors. The association between these factors and sub-optimal outcome was explored by logistic regression and log linear analysis, and a model of causality was postulated. Associated fracture type, imperfect reduction (>3mm), the presence of local complications and heterotopic bone were prognostic factors independently associated with a sub-optimal outcome. The sex or age of the patient, the presence of hip dislocation, sciatic palsy, or an interval from injury to surgery of 1-18 days were factors which were not directly associated with a poor outcome. Imperfect reduction was itself affected by associated fracture type and increasing age, and it is the latter connection that may explain any apparent association between sub-optimal outcome and increasing age.

Acetabulum↗