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Biomedical subjects

R Murphy

Publications and source records attributed to R Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Self-help and guided self-help for eating disorders.

BACKGROUND: Anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED) and eating disorder not otherwise specified (EDNOS) are common and disabling disorders. Many patients experience difficulties accessing specialist psychological treatments. Pure self-help (PSH: self-help material only) or guided self-help (GSH: self-help material with therapist guidance), may bridge this gap. OBJECTIVES MAIN OBJECTIVE: Evaluate evidence from randomised controlled trials (RCTs) / controlled clinical trials (CCTs) for the efficacy of PSH/GSH with respect to eating disorder symptoms, compared with waiting list or placebo/attention control, other psychological or pharmacological treatments (or combinations/augmentations) in people with eating disorders. SECONDARY OBJECTIVE: Evaluate evidence for the efficacy of PSH/GSH regarding comorbid symptomatology and costs. SEARCH STRATEGY: CCDANCTR-Studies and CCDANCTR-References were searched in November 2005, other electronic databases were searched, relevant journals and grey literature were checked, and personal approaches were made to authors. SELECTION CRITERIA: Published/unpublished RCTs/CCTs evaluating PSH/GSH for any eating disorder. DATA COLLECTION AND ANALYSIS: Data was extracted using a customized spreadsheet. Relative Risks (RR) were calculated from dichotomous data and weighted/standardized mean differences (WMD/SMD) from continuous data, using a random effects model. MAIN RESULTS: Twelve RCTs and three CCTs were identified, all focusing on BN, BED, EDNOS or combinations of these, in adults, using manual-based PSH/GSH across various settings. Primary comparisons:At end of treatment, PSH/GSH did not significantly differ from waiting list in abstinence from bingeing (RR 0.72, 95% CI 0.47 to 1.09), or purging (RR 0.86, 95% CI 0.68 to 1.08), although these treatments produced greater improvement on other eating disorder symptoms, psychiatric symptomatology and interpersonal functioning but not depression. Compared to other formal psychological therapies, PSH/GSH did not differ significantly at end of treatment or follow-up in improvement on bingeing and purging (RR 0.99, 95% CI 0.75 to 1.31), other eating disorder symptoms, level of interpersonal functioning or depression. There were no significant differences in treatment dropout. Secondary comparisons:One small study in BED found that cognitive-behavioural GSH compared to a non-specific control treatment produced significantly greater improvements in abstinence from bingeing and other eating disorder symptoms. Studies comparing PSH with GSH found no significant differences between treatment groups at end of treatment or follow-up. Comparison between different types of PSH/GSH found significant differences on eating disorder symptoms but not on bingeing/purging abstinence rates. AUTHORS' CONCLUSIONS: PSH/GSH may have some utility as a first step in treatment and may have potential as an alternative to formal therapist-delivered psychological therapy. Future research should focus on producing large well-conducted studies of self-help treatments in eating disorders including health economic evaluations, different types and modes of delivering self-help (e.g. computerised versus manual-based) and different populations and settings.

Anorexia Nervosa↗
PubMed2006

Life cycle assessment of wastewater treatment technologies treating petroleum process waters.

This paper describes the implementation of life cycle assessment to investigate the environmental impact of 20 technologies suitable for treating extensive volumes of water produced during the oil and gas extraction processes. Data on the physical and operational attributes of technologies under consideration were assembled and their life cycle environmental impacts estimated over 15 year time period. The results were then incorporated in a decision support system which allows identification and prioritisation of potential technology combinations capable of producing water for nine designated industrial and agricultural end uses. In total, more than 618 technology combinations were investigated for their environmental impacts. The identification and prioritisation of technologies were done on the basis of their environmental and technical performance. This analysis showed that dissolved air flotation, absorbents, dual media filtration and reverse osmosis technologies offer relatively low environmental impact parts of systems for cleaning such process waters. Furthermore, the environmental assessment combined within the decision support system has revealed potentially valuable indirect downstream "benefits" from effects such as evaporative losses from wetlands in terms of the overall environmental impact of a treatment system.

Extraction and Processing Industry↗
PubMed2006

Preclinical analysis of the analinoquinazoline AG1478, a specific small molecule inhibitor of EGF receptor tyrosine kinase.

The tyrphostin 4-(3-chloroanilino)-6,7-dimethoxyquinazoline (AG1478) is a potent and specific inhibitor of EGFR tyrosine kinase whose favourable preclinical profile supports progression towards clinical trials. Microphysiometric evaluation revealed a short (<24 min) effective inhibition of cellular receptor response to EGF challenge in BaF/ERX cells indicating a need to maintain sustained levels of inhibitor. Initial pharmacokinetic evaluation in mice of novel AG1478 formulations in a beta-cyclodextrin (Captisol) showed monoexponential elimination from plasma (half-life 30 min) following subcutaneous administration. A two-fold dose escalation gave a 2.4-fold increase in the total AUC. Bolus i.v. and 6 h continuous infusion were investigated in rats to mimic a more clinically relevant administration regimen. Drug elimination following bolus i.v. administration was biphasic (terminal elimination half-life 30-48 min). The linear relationship between dose and AUC(0-->infinity) (r2=0.979) enabled the prediction of infusion rates and doses for sustained delivery using continuous 6 h infusions, where steady state was reached in 120 min. Plasma levels of AG1478>10 microM were achieved over the duration of the infusion. At the lowest dose, plasma drug levels after the cessation of infusion declined with a half-life of approximately 43 min. EGFR activity, measured both by autophosphorylation and downstream signalling, was inhibited in a dose-dependent manner by injection of AG1478 in mice bearing xenografts of the human glioblastoma cell line U87MG.delta2-7, which expresses a constitutively active variant of the EGF receptor. Taken together, these experiments provide essential data to assess the anti-tumour efficacy of AG1478 and will assist in the rational design of dose regimens for clinical studies.

Animals↗
PubMed2006

Circulating levels of beta2-glycoprotein I in thrombotic disorders and in inflammation.

Beta2-glycoprotein I (beta2GPI) is a plasma protein suspected to have a role in inhibition of thrombosis. This suspicion is reinforced by the observation that beta2GPI is the major target for autoantibodies in the antiphospholipid syndrome. However, little is known about its circulating levels in common thrombotic diseases or inflammation. We measured beta2GPI levels in 344 healthy controls, 58 normal pregnancies, 102 patients with non-haemorrhagic stroke, 121 patients with acute coronary syndrome and 200 patients with elevated C-reactive protein (CRP). In healthy individuals, we found a strong positive correlation between age and beta2GPI concentration (r = 0.274, P < 0.001) and that beta2GPI levels fall significantly after the eighth week of pregnancy (P = 0.002). We also found significantly reduced levels of beta2GPI in patients with stroke and in elderly patients with myocardial syndrome (P = 0.013 and 0.043). However, in neither group did beta2GPI levels change in the following six months, suggesting that the reduced levels were not a transient post-event phenomenon. In patients with inflammation, beta2GPI levels showed a significant negative correlation with CRP (r = -0.284, P < 0.001) and positively correlated with albumin and transferrin (r = 0.372 and 0.453, respectively with P < 0.001 for both). Furthermore, the largest reduction in beta2GPI levels occurred in patients with the highest CRP values (P < 0.001).

Adult↗
PubMed2005

Zoledronic acid significantly improves pain scores and quality of life in breast cancer patients with bone metastases: a randomised, crossover study of community vs hospital bisphosphonate administration.

Patients with bone metastases from breast cancer often experience substantial skeletal complications -- including debilitating bone pain -- which negatively affect quality of life. Zoledronic acid (4 mg) has been demonstrated to reduce significantly the risk of skeletal complications in these patients and is administered via a short, 15-min infusion every 3 weeks, allowing the possibility for home administration. This study compared the efficacy and safety of zoledronic acid administered in the community setting vs the hospital setting in breast cancer patients with > or =1 bone metastasis receiving hormonal therapy. After a lead-in phase of three infusions of 4 mg zoledronic acid in the hospital setting, 101 patients were randomized to receive three open-label infusions in the community or hospital setting, followed by three infusions in the opposite venue (a total of nine infusions). The Brief Pain Inventory (BPI) and the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) were used to assess potential benefits of zoledronic acid therapy. At study end, analysis of the BPI showed significant reductions in worst pain (P=0.008) and average pain in the last 7 days (P=0.039), and interference with general activity (P=0.012). In each case, there were significantly greater improvements in pain scores after treatment in the community setting compared with the hospital crossover setting for worst pain (P=0.021), average pain (P=0.003), and interference with general activity (P=0.001). Overall global health status showed a significant median improvement of 8.3% (P=0.013) at study end. Physical, emotional, and social functioning also showed significant overall improvement (P=0.013, 0.005, and 0.043, respectively). Furthermore, physical, role, and social functioning showed significantly greater improvements after treatment in the community setting compared with the hospital crossover setting (P=0.018, 0.001, and 0.026, respectively). There was no difference between hospital and community administration in renal or other toxicity, with zoledronic acid being well tolerated in both treatment settings. These data confirm the safety and quality-of-life benefits of zoledronic acid in breast cancer patients with bone metastases, particularly when administered in the community setting.

Activities of Daily Living↗
PubMed2005

Recombinant NY-ESO-1 cancer antigen: production and purification under cGMP conditions.

The cancer-testis antigen, NY-ESO-1, has been engineered into a bacterial expression plasmid which incorporates a His6-tag. The plasmid was transfected into E. coli strain BL21 and Master and Working cell banks generated from this expression system. Three 15-litre fermentations were performed under cGMP (code of Good Manufacturing Practice) conditions and the crude NY-ESO-1 tagged protein isolated as solubilised inclusion bodies. A three-step cGMP chromatography process (immobilised metal affinity, anion exchange, and hydrophobic interaction) was utilised to purify the protein. The purified NY-ESO-1 is being used in early stage human cancer vaccine trials in Australia and the U.S.A.

Antigens, Neoplasm↗
PubMed2005

Oral lichen planus in childhood: a report of three cases.

Lichen planus is a common mucocutaneous condition in which the occurrence of oral lesions has been cited as between 0.5 and 1.9% of the adult population. It is rare in childhood. Here we report three cases of children with intra oral lesions of lichen planus. Lichen planus, although reportedly rare in childhood, should be considered in the diagnosis of hyperkeratotic or erosive lesions of the oral mucosa in children.

Adolescent↗
PubMed2005

Agreement between an arterial blood gas analyser and a venous blood analyser in the measurement of potassium in patients in cardiac arrest.

BACKGROUND AND OBJECTIVE: Rapid measurement of potassium is crucial in the resuscitation of patients in cardiac arrest. This is often done on an arterial blood gas sample taken during resuscitation and analysed in an emergency department based blood gas analyser. No-one has assessed how accurate or reliable this is when compared with the traditional method of sending a venous sample to the laboratory for standard analysis. This study looked at the agreement between potassium measurements in arterial blood gas samples and venous blood samples in patients in cardiac arrest. METHOD: Arterial and venous blood samples were taken at the same time and analysed in the usual way from 50 patients in cardiac arrest. It was found that the mean difference between each pair of arterial and venous potassium measurements was low at 0.106 mmol/l. However, the standard deviation of these differences and subsequently the 95% limits of agreement were wide (-1.182 mmol/l to 1.394 mmol/l)-that is, 95% of differences will lie between these limits. It is felt that these limits are too wide for safe use in clinical practice. CONCLUSION: Based on these results, it is advised that arterial blood gas analysers should be used with caution to measure potassium in patients in cardiac arrest.

Arteries↗
PubMed2005

The "OBS" chart: an evidence based approach to re-design of the patient observation chart in a district general hospital setting.

OBJECTIVE: The primary role of the patient bedside observation chart is to make clinicians aware of the deteriorating patient. Despite this, its performance has not been scrutinised. Many versions exist with different styles of data entry but the optimal format remains elusive. This paper hypothesised that chart design measurably influences function and that redesign and standardisation would improve the detection of physiological decline by clinical staff. DESIGN: Objective evaluation of existing charts (n = 5), evidence based redesign, and re-evaluation of new chart. SETTING: 250 bed district general hospital. RESULTS: Design of existing observation charts had a significant effect on the ability of clinical staff to detect patient deterioration, with detection rates of parameters indicating physiological decline ranging from 0% to 100%. Graphical plots portrayed information better than written values for all parameters being measured except tachypnoea. No single existing chart was best for all variables. A new chart was designed, implemented with training in its use, and re-evaluated. The new chart also incorporated an early warning scoring system. There were significant improvements in the average detection rates of parameters poorly identified on existing charts: detection rates of tachypnoea and hypoxia increased by 41% (p<0.05) and 45% (p<0.05) respectively. There were also significant improvements in detection rates of tachycardia and fever by 29% (p<0.05) and 16% (p<0.05) respectively. CONCLUSION: Evidence based redesign of the patient bedside observation chart coupled with specific training in its use significantly improves the detection of patient physiological deterioration.

England↗
PubMed2004

Conditional-associative learning in eating disorders: a comparison with OCD.

The acquisition of conditional associations using neutral and individually threatening verbal stimuli was assessed in 16 females with anorexia nervosa (AN), obsessive-compulsive disorder (OCD), bulimia nervosa and normal controls, respectively. Groups did not differ in terms of age, sex, intelligence, depression, verbal memory and verbal fluency measures. Patients and controls were widely comparable on tests assessing neuropsychological functioning. In the conditional-associative learning (CAL)-task only anorectic and OCD-patients displayed an impaired performance with neutral material but not with individually threatening material. Such a deficit was not evident in bulimics or in normal controls. These findings support the assumptions from functional neuroimaging investigations in AN and OCD and provide evidence that obsessive and compulsive behavior could have its origin within common neurobiological dysfunctions. The CAL possibly serves as a functional correlate of a neurophysiological dysfunction in obsessive-compulsive spectrum disorders.

Adolescent↗
PubMed2004

Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis.

Atopic dermatitis is a disease with an impaired skin barrier that affects 15%-20% of children. In the normal epidermis, the stratum corneum chymotryptic enzyme (SCCE) thought to play a central role in desquamation by cleaving proteins of the stratum corneum (e.g., corneodesmosin and plakoglobin). Genetic variations within the SCCE gene could be associated with dysregulation of SCCE activity leading to an abnormal skin barrier. We screened the SCCE gene for variations and performed a case-control study on 103 atopic dermatitis patients and 261 matched controls. 16 synonymous single nucleotide polymorphisms (SNPs) have been identified and a 4 bp (AACC) insertion has been found in the 3'UTR. We performed an association study of the SCCE AACC insertion in the 3'UTR, and found a significant trend between the AACC allele with the two insertions and disease in the overall data set [odds ratio (OR)=2.31; p=0.0007]. The AACC insertion in the SCCE gene may result in a change to SCCE activity within the skin barrier. These findings suggest that SCCE could have an important role in the development of atopic dermatitis.

3' Untranslated Regions↗
PubMed2003

Randomized controlled trial of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: the POPMACT study.

BACKGROUND: We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm. METHOD: Patients presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT patients received a booklet based on cognitive behaviour therapy (CBT) principles and were offered up to five plus two booster sessions of CBT from a therapist in the first 3 months of the study. Ratings of parasuicide risk, anxiety, depression, social functioning and global function, positive and negative thinking, and quality of life were measured at baseline and after 6 and 12 months. RESULTS: Four hundred and eighty patients were randomized. Sixty per cent of the MACT group had both the booklet and CBT sessions. There were seven suicides, five in the TAU group. The main outcome measure, the proportion of those repeating deliberate self-harm in the 12 months of the study, showed no significant difference between those treated with MACT (39%) and treatment as usual (46%) (OR 0.78, 95% CI 0.53 to 1.14, P=0.20). CONCLUSION: Brief cognitive behaviour therapy is of limited efficacy in reducing self-harm repetition, but the findings taken in conjunctin with the economic evaluation (Byford et al. 2003) indicate superiority of MACT over TAU in terms of cost and effectiveness combined.

Adult↗
PubMed2003

Comparison of parent knowledge, therapy utilization and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse.

BACKGROUND: The failure of patients to take medicines in a way that leads to clinical benefit is a major challenge. A consensus has emerged that, on average, compliance sufficient to obtain therapeutic objectives occurs about half the time, with noncompliance contributing to therapeutic failure in the other half. These figures refer to simple oral regimens. There has been little work assessing compliance/concordance with complex treatment regimens for atopic eczema. Asthma schools led by specialist nurses have been shown to improve knowledge, use of therapies and clinical outcome. OBJECTIVES: To determine the effect of education and demonstration of topical therapies by specialist dermatology nurses on therapy utilization and severity of atopic eczema. METHODS: Fifty-one children with atopic eczema attending a paediatric dermatology clinic were followed for up to 1 year. At each visit the parent's knowledge about atopic eczema and its treatment and therapy utilization was recorded. The severity of the eczema was recorded using the six area, six sign atopic dermatitis severity score (SASSAD) and parental assessment of itch, sleep disturbance and irritability. At the first visit a specialist dermatology nurse explained and demonstrated how to use all of the topical treatments. This education was repeated at subsequent visits depending on the knowledge of the parent. RESULTS: At baseline less than 5% of parents had received/recalled receiving any explanation of the causes of eczema or demonstration of how to apply topical treatments. The eczema was poorly controlled in all children (mean SASSAD 42.9). Of the children, 24% were not being treated with any emollient cream/ointment; the mean use was 54 g weekly. Of the children, 25% were being inappropriately treated with potent or very potent topical steroids. Following repeated education and demonstration of topical therapies by a specialist dermatology nurse, there was an 89% reduction in the severity of the eczema. The main change in therapy utilization was an 800% increase in the use of emollients (to 426 g weekly of emollient cream/ointment) and no overall increase in the use of topical steroids, accounting for potency and quantity used. CONCLUSIONS: This study reinforces the importance of specialist dermatology nurses in the management of atopic eczema. It also confirms the opinion of patients, patient support groups, dermatologists and best practice guidelines that the most important intervention in the management of atopic eczema is to spend time to listen and explain its causes and demonstrate how to apply topical therapies.

Administration, Topical↗
PubMed2003

Pregnancy related complications in women with hypertrophic cardiomyopathy.

OBJECTIVES: To determine whether pregnancy is well tolerated in hypertrophic cardiomyopathy. SETTING: Referral clinic. DESIGN: The study cohort comprised 127 consecutively referred women with hypertrophic cardiomyopathy. Forty (31.5%) underwent clinical evaluation before pregnancy. The remaining 87 (68.5%) were referred after their first pregnancy. All underwent history, examination, electrocardiography, and echocardiography. Pregnancy related symptoms and complications were determined by questionnaire and review of medical and obstetric records where available. RESULTS: There were 271 pregnancies in total. Thirty six (28.3%) women reported cardiac symptoms in pregnancy. Over 90% of these women had been symptomatic before pregnancy. Symptoms deteriorated during pregnancy in fewer than 10%. Of the 36 women with symptoms during pregnancy, 30 had further pregnancies. Symptoms reoccurred in 18 (60%); symptomatic deterioration was not reported. Heart failure occurred postnatally in two women (1.6%). No complications were reported in 19 (15%) women who underwent general anaesthesia and in 22 (17.4%) women who received epidural anaesthesia, three of whom had a significant left ventricular outflow tract gradient at diagnosis after pregnancy. Three unexplained intrauterine deaths occurred in women taking cardiac medication throughout pregnancy. No echocardiographic or clinical feature was a useful indicator of pregnancy related complications. CONCLUSIONS: Most women with hypertrophic cardiomyopathy tolerate pregnancy well. However, rare complications can occur and therefore planned delivery and fetal monitoring are still required for some patients.

Adult↗
PubMed2002

Transpulmonary speed of sound input into the supraclavicular space.

The transpulmonary speed of sound input at the mouth has been shown to vary with lung volume. To avoid the disadvantages that exist in certain clinical situations in inputting sound at the mouth, we input sound in the supraclavicular space of 21 healthy volunteers to determine whether similar information on the relationship of sound speed to lung volume could be obtained. We measured the transit time at multiple microphones placed over the chest wall using a 16-channel lung sound analyzer (Stethographics). There was a tight distribution of transit times in this population of subjects. At functional residual capacity, it was 9 +/- 1 (SD) ms at the apical sites and 13 +/- 1 ms at the lung bases. The sound speed at total lung capacity was 24 +/- 2 m/s and was 22 +/- 2 m/s at residual volume (P < 0.001). In all subjects, the speed of sound was faster at higher lung volume. This improved method of studying the mechanism of sound transmission in the lung may help in the development of noninvasive tools for diagnosis and monitoring of lung diseases.

Acoustic Stimulation↗