Biomedical subjects

Kevin Murphy

Publications and source records attributed to Kevin Murphy.

28 records · Page 2Linked to original sources

PubMed2003

A role for arcuate cocaine and amphetamine-regulated transcript in hyperphagia, thermogenesis, and cold adaptation.

We have recently shown that injection of the hypothalamic peptide cocaine and amphetamine regulated transcript (CART) into discrete hypothalamic nuclei stimulates food intake. This stimulation was particularly marked in the arcuate nucleus. Here we show that twice daily intra-arcuate injection of 0.2 nmole CART peptide for 7 days was associated with a 60% higher daytime food intake, an 85% higher thermogenic response to the beta3 agonist BRL 35135, and a 60% increase in brown adipose tissue UCP-1 mRNA. In a separate study, using stereotactically targeted gene transfer, a CART transgene was delivered by using polyethylenimine to the arcuate nucleus of adult rats. Food intake was increased significantly during ad libitum feeding and following periods of food withdrawal and food restriction in CART over-expressing animals. CART over-expressing animals lost 12% more weight than controls following a 24-h fast. Brown adipose tissue uncoupling protein-1 (UCP-1) mRNA levels (collected Day 25) were 80% higher in CART over-expressing animals. Finally, by using quantitative in situ hybridization, we found that chronic cold exposure (20 days at 4oC) increased arcuate nucleus CART mRNA by 124%. Together with the orexigenic and thermogenic effects of CART, this finding suggests a role for arcuate nucleus CART in cold adaptation.

Adaptation, Physiological↗

PubMed2003

Effects of galanin-like peptide on food intake and the hypothalamo-pituitary-thyroid axis.

Galanin-like peptide (GALP) is a novel hypothalamic peptide synthesised in neurons in the arcuate nucleus which project to the paraventricular nucleus (PVN). GALP has recently been identified as an orexigenic peptide. In this study we aimed to further characterise the hypothalamic action of this peptide in energy homeostasis. Firstly, we investigated the orexigenic effect of GALP in the PVN and compared its effects with galanin and galanin 2-29. Secondly, we examined the effect of PVN administration of GALP and galanin on circulating thyroid-stimulating hormone (TSH). PVN administration of GALP significantly increased the food intake of satiated rats 1 h after administration at doses of 0.3, 1 and 3 nmol. In comparison with paraventricular administration of galanin, GALP was a more potent orexigen, whereas galanin 2-29, the relatively selective GAL R2 agonist, had no effect on food intake. Both GALP and galanin administration (1 nmol) into the PVN significantly decreased the level of circulating TSH. To investigate the mechanism of these effects, we examined the effect of GALP and galanin application on neuropeptide release from hypothalamic explants in vitro. GALP peptide (100 nM) stimulated the release of the orexigenic peptide neuropeptide Y from hypothalamic explants and decreased the release of the anorectic peptide cocaine-and-amphetamine-regulated transcript, whereas galanin (100 nM) peptide had no significant effect on the release of either peptide. Both GALP (100 nM) and galanin (100 nM) inhibited the release thyrotrophin-releasing hormone. These data suggest that in the PVN, GALP may play a role in energy homeostasis by stimulating food intake and suppressing TSH release.

Animals↗

PubMed2003

Distribution of fluorescence following injection of recombinant adeno-associated virus encoding green fluorescent protein into the paraventricular nucleus.

We have used recombinant type 2 adeno-associated virus to deliver the gene encoding green fluorescent protein into the central nervous system of adult rats. Gene expression, determined by fluorescent microscopy, was observed not only at the site of injection but also in axons following known neuroanatomical pathways. We have demonstrated a spread of enhanced green fluorescent protein from the paraventricular nucleus of the hypothalamus into the median eminence and neurohypophysis. Cell bodies containing enhanced green fluorescent protein were also visualized in the paraventricular nucleus contralateral to the side of injection. These findings suggest that gene transfer by recombinant adeno-associated virus could be used as a tool to investigate hypothalamic-pituitary interactions and, elsewhere in the central nervous system, to trace axonal pathways.

Animals↗

PubMed2003

Diminishing returns? The costs and benefits of improving health.

In this paper, we develop and apply an economic framework for valuing improvements in health, based on Murphy and Topel (2002). Past improvements in health and longevity have had enormous social value. By our estimation, the contributions to the economic well-being of longer lifetimes have been worth about dollar 73 trillion since 1970, or about dollar 2.6 trillion per year. The average 50-year-old man gained additional life-years worth roughly dollar 350,000, while a 50-year-old woman gained about dollar 180,000. Looking ahead, prospective benefits from further progress are also large: a 10 percent reduction in mortality from heart disease would be worth over dollar 4 trillion, and even a 1 percent reduction in cancer deaths would be worth over dollar 400 billion. These values suggest that public investments in basic medical research may yield huge social returns, but distortions in the allocation of medical care and in research incentives may yield future benefits that are smaller than the costs of achieving them. While the average net health benefits of increased medical expenditures are large, costs may have greatly exceeded benefits in certain periods and age groups.

Aged↗

PubMed2002

The effects of centrally administered apelin-13 on food intake, water intake and pituitary hormone release in rats.

Apelin is the recently identified endogenous ligand for the G-protein-coupled receptor, APJ. Preproapelin and APJ mRNA are found in hypothalamic regions known to be important in the regulation of food and water intake, and pituitary hormone release. The effects of intracerebroventricular (ICV) administration of pyroglutamylated apelin-13 on food and water intake and pituitary hormone release in rats were investigated. Apelin-13 had little effect on food intake, but dose-dependently increased drinking behaviour and water intake at 1 h. Apelin-13 (10 nmol) increased water intake by up to sixfold compared to saline. Compared to saline control, apelin-13 (10 nmol) significantly increased plasma ACTH and corticosterone and decreased plasma prolactin, LH and FSH at 30 min. In vitro, apelin-13 stimulated the release of CRH and AVP from hypothalamic explants, but had no effect on NPY release. These results suggest that apelin may play an important role in the hypothalamic regulation of water intake and endocrine axes.

Animals↗

PubMed2002

Areas of the brain concerned with ventilatory load compensation in awake man.

There is broad agreement that the awake human ventilatory response to a moderate inspiratory load consists of a prolongation of inspiratory time (T(I)) with a maintenance of tidal volume (V(T)) and end-tidal P(C)(O(2)) (P(ET,C)(O(2))), the response being severely blunted in sleep. There is no agreement on the mechanisms underlying this ventilatory response. Six naive healthy males (aged 39-44) were studied supine with their heads in a positron emission tomography (PET) scanner to allow relative regional cerebral blood flow (rCBF) to be measured with H(2)(15)O given intravenously. A linearised resistive load (24 cmH(2)O (l s(-1))(-1)) could be added to the inspiratory limb of a breathing valve inserted into a tightly fitting facemask; inspiratory flow was measured with a pneumotachograph. The load was applied, without alerting the subject, when the radioactivity first reached the head. Six scans were performed with and without the load, in each subject. Relative rCBF contrasts between the loaded and unloaded breathing states showed significant activations in inferior parietal cortex, prefrontal cortex, midbrain, basal ganglia and multiple cerebellar sites. No activations were found in the primary sensorimotor cortex. The findings suggest that there is a pattern of motor behavioural response to the uncomfortable sensation that inspiration is impeded. This results in a prolongation of T(I), the maintenance of V(T) and a reduction in the degree of discomfort, presumably because of the reduction of mean negative pressure in the airways.

Adaptation, Physiological↗

PubMed2002

Speech production: Wernicke, Broca and beyond.

We investigated the brain systems engaged during propositional speech (PrSp) and two forms of non- propositional speech (NPrSp): counting and reciting overlearned nursery rhymes. Bilateral cerebral and cerebellar regions were involved in the motor act of articulation, irrespective of the type of speech. Three additional, left-lateralized regions, adjacent to the Sylvian sulcus, were activated in common: the most posterior part of the supratemporal plane, the lateral part of the pars opercularis in the posterior inferior frontal gyrus and the anterior insula. Therefore, both NPrSp and PrSp were dependent on the same discrete subregions of the anatomically ill-defined areas of Wernicke and Broca. PrSp was also dependent on a predominantly left-lateralized neural system distributed between multi-modal and amodal regions in posterior inferior parietal, anterolateral and medial temporal and medial prefrontal cortex. The lateral prefrontal and paracingulate cortical activity observed in previous studies of cued word retrieval was not seen with either NPrSp or PrSp, demonstrating that normal brain- language representations cannot be inferred from explicit metalinguistic tasks. The evidence from this study indicates that normal communicative speech is dependent on a number of left hemisphere regions remote from the classic language areas of Wernicke and Broca. Destruction or disconnection of discrete left extrasylvian and perisylvian cortical regions, rather than the total extent of damage to perisylvian cortex, will account for the qualitative and quantitative differences in the impaired speech production observed in aphasic stroke patients.

Aphasia, Broca↗

PubMedDate not supplied

ADA-based accommodations in higher education: a survey of clinicians about documentation requirements and diagnostic standards.

The expansion of the number of students requesting accommodations in postsecondary settings compels clinicians to become knowledgeable about the legal definitions and documentation requirements of the Americans with Disabilities Act (ADA). Because the law is relatively new, courts and regulatory agencies have only recently begun to clarify what constitutes a disability. In this study, 147 clinicians completed a questionnaire developed to assess their understanding of the law and the diagnostic approaches they used to justify claims of learning disability (LD), attention-deficit/hyperactivity disorder (ADHD), and psychiatric disability. Whereas the clinicians agreed on certain points (e.g., the right of institutions to formulate specific policies regarding documentation), they substantially disagreed on several fundamental issues. Clinician consensus was lowest on items that asked about the basic intent of the law, the metrics for assessing impairment, and the criteria for assessing ADHD in adulthood. Judged against the legislative history of the ADA and the body of regulatory rulings and legal decisions, many clinicians' responses showed a need for clarification regarding the distinction between special education law and the antidiscrimination intent of the ADA. The respondents also expressed a nearly uniform wish for more training in this fast-growing area of clinical practice.

Attention Deficit Disorder with Hyperactivity↗

PubMedDate not supplied

Implications of non-medical prescribing of controlled drugs.

Mental health nurses working in the substance misuse field will soon be able to prescribe controlled drugs as part of their role. This article discusses the implications of this and its potentially positive impact on the existing prescribing services.

Drug Prescriptions↗

PubMedDate not supplied

A "next generation" ethics committee. St. Joseph Health system has integrated performance-improvement features into its ethics work.

Understanding the limitations that accompany the traditional model of ethics committees, St. Joseph Health System (SJHS), Orange, CA, has been working to integrate ethics expertise and quality-improvement methodology into its "Next Generation Model" (NG Model) for such committees. However, moving from a traditional structure to the NG Model (introduced to SJHS facilities in 1999) brought some challenges, not the least of which was a deep-rooted culture of resistance to change. Following a 2004 audit of how the NG model was working, some common challenges were identified. To deal with those challenges, SJHS developed some tools and techniques that have helped ease the ongoing transition. These tools have helped the system's ethics committees address such issues as collaboration for the sake of organizational integration, setting goals, and measuring performance of various ethics roles.

California↗