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Biomedical subjects

M Kearney

Publications and source records attributed to M Kearney.

At least 19 recordsLinked to original sources
PubMed2005

Mainstreaming prevention: prescribing fruit and vegetables as a brief intervention in primary care.

This paper examines a brief preventive intervention as a model for embedding public health action in primary care. BACKGROUND: Low fruit and vegetable intake is a major risk factor for cancer, coronary heart disease and stroke. The recommended intake of five portions per day would reduce death rates from these causes by 20%. However, average daily consumption in the UK is under three portions, and it is significantly lower in men, young people and lower socio-economic groups. In order to tackle risk factors such as poor diet, the white paper Choosing Health promises action and funding to mainstream prevention and transform the NHS from a sickness service to a genuine health service. THE INTERVENTION: To promote increased fruit and vegetable consumption, primary care professionals working in a deprived area issue prescriptions which offer the patient discounts on fruit and vegetable purchases. Hand over of each prescription to the patient is linked explicitly to key five a day messages. This brief intervention takes 1-2 min to deploy. IMMEDIATE OUTCOMES: Evaluation is ongoing. However, early feedback suggests that the intervention of prescription plus key messages has a significant impact on patients in highlighting the connection between food and health. Clinicians express satisfaction at having a preventive intervention that can be deployed with confidence and consistency in routine primary care consultations. DISCUSSION: This brief intervention is presented as a potential model for embedding prevention in the day-to-day work of health professionals. Primary care is a natural setting for the promotion of health, but despite success in implementing some public health programmes, it has a patchy record in primary prevention. The reasons for this are examined, the impact of new contractual and commissioning levers is explored, and a general framework for mainstreaming public health action in primary care is proposed.

Cardiovascular Diseases↗
PubMed2005

Lower fecundity in parthenogenetic geckos than sexual relatives in the Australian arid zone.

Theoretical models of the advantage of sexual reproduction typically assume that reproductive output is equal in sexual and parthenogenetic females. We tested this assumption by comparing fecundity between parthenogenetic and sexual races of gekkonid lizards in the Heteronotia binoei complex, collected across a 1200 km latitudinal gradient through the Australian arid zone. Under laboratory conditions, parthenogenetic geckos had approximately 30% lower fecundity when compared with their sexual progenitors, irrespective of body size. Reflecting clutch-size constraints in gekkonids, this fecundity difference was mainly because of fewer clutches over a shorter period. When parthenogens were compared more broadly with all coexisting sexual races across the latitudinal gradient, parthenogens had lower fecundity than sexuals only when corrected for body size. Differences in fecundity between parthenogens and coexisting sexual races depended on which sexual race was considered. There was no significant relationship between fecundity and parasite (mite) load, despite significantly higher mite loads in parthenogens than in sexual races.

Analysis of Variance↗
PubMed2004

A robust measure of HIV-1 population turnover within chronically infected individuals.

A simple nonparameteric test for population structure was applied to temporally spaced samples of HIV-1 sequences from the gag-pol region within two chronically infected individuals. The results show that temporal structure can be detected for samples separated by about 22 months or more. The performance of the method, which was originally proposed to detect geographic structure, was tested for temporally spaced samples using neutral coalescent simulations. Simulations showed that the method is robust to variation in samples sizes and mutation rates, to the presence/absence of recombination, and that the power to detect temporal structure is high. By comparing levels of temporal structure in simulations to the levels observed in real data, we estimate the effective intra-individual population size of HIV-1 to be between 10(3) and 10(4) viruses, which is in agreement with some previous estimates. Using this estimate and a simple measure of sequence diversity, we estimate an effective neutral mutation rate of about 5 x 10(-6) per site per generation in the gag-pol region. The definition and interpretation of estimates of such "effective" population parameters are discussed.

Evolution, Molecular↗
PubMed2002

Relations between desire for early death, depressive symptoms and antidepressant prescribing in terminally ill patients with cancer.

Some patients with advanced cancer express the wish for an early death. This may be associated with depression. We examined the relations between depressive symptoms and desire for early death (natural or by euthanasia or physician-assisted suicide) in 142 terminally ill patients with cancer being cared for by a specialist palliative care team. They completed the Hospital Anxiety and Depression Scale questionnaire and answered four supplementary questions on desire for early death. Only 2 patients expressed a strong wish for death by some form of suicide or euthanasia. 120 denied that they ever wished for early release. The desire for early death correlated with depression scores. Depressive symptoms were common in the whole group but few were on antidepressant therapy. Better recognition and treatment of depression might improve the lives of people with terminal illness and so lessen desire for early death, whether natural or by suicide.

Adult↗
PubMed2002

A prospective study of preferred versus actual place of death among patients referred to a palliative care home-care service.

In this first such study in an Irish setting, patients referred to a Hospice Home Care Team were asked where they would prefer to die, and were then followed until death to determine actual place of death, and factors that influenced same. Over 80% expressed a preference to die at home. Almost 50% of those who expressed a preference for a home death actually died there. Of those admitted to hospital or hospice to die, uncontrolled symptoms and inability of family to cope were the main reasons precipitating admission. On closer assessment, it was felt that a significant minority of those admitted could have been cared for at home had additional resources been available in the community. Facilitating choice in place of care for the dying is acknowledged government policy and, as such, greater resources should be made available to community health and social services to support ongoing care at home.

Attitude to Death↗
PubMed2001

Estrogen receptor-mediated, nitric oxide-dependent modulation of the immunologic barrier function of the endothelium: regulation of fas ligand expression by estradiol.

BACKGROUND: Premenopausal women have a lower incidence of coronary artery disease than postmenopausal women or same-age men. Although the mechanisms of this apparent relative protection against atherosclerosis remain ill defined, estradiol, which is present in higher concentrations before menopause, is considered to play a central role. Recently, Fas ligand (FasL) expression by the vascular endothelium has been shown to inhibit the migration of inflammatory cells into the vessel wall, an event that is considered crucial for the development of atherosclerosis. METHODS AND RESULTS: The regulation of endothelial FasL expression by estradiol was investigated in vivo and in vitro. In an ovariectomized, cholesterol-clamped rabbit model, FasL expression was shown to be downregulated by elevations in serum cholesterol, which also resulted in invasion of the arterial wall by macrophages. Estradiol replacement resulted in restoration of FasL expression, with resultant inhibition of leukocyte traffic across the endothelium. Inhibition of NO production by addition of L-NAME to the drinking water of the estradiol-treated rabbits abrogated these effects. In vitro, estradiol is shown to regulate FasL expression at the transcriptional level via an estrogen receptor-mediated, NO-dependent mechanism. CONCLUSIONS: Estradiol transcriptionally regulates endothelial FasL expression by a mechanism involving at least one of the estrogen receptors. In an animal model of atherosclerosis, estradiol restores FasL expression, which is suppressed by atherogenic levels of serum cholesterol. The maintenance of endothelial FasL expression by estradiol may represent a mechanism of estrogen's apparent antiatherogenic effect.

Animals↗
PubMed2001

In vivo blockade of tumor necrosis factor-alpha accelerates functional endothelial recovery after balloon angioplasty.

BACKGROUND: Tumor necrosis factor-alpha (TNF) is expressed locally in arteries at sites of balloon injury. In vitro studies have shown that TNF inhibits cell cycle progression and induces apoptosis in endothelial cells. Accordingly, we performed a series of experiments to test the hypothesis that inhibiting TNF could accelerate endothelial recovery after angioplasty. METHODS AND RESULTS: TNF soluble receptor (TNFsr) has been shown to neutralize the actions of TNF in vitro and in vivo. Sprague-Dawley rats received TNFsr versus control IgG through an intraperitoneal injection. De-endothelializing balloon injury was then performed, and animals were killed after 1 week to evaluate re-endothelialization (Evans blue dye staining) and after 2 weeks to evaluate re-endothelialization and endothelial function. At both time points, blockade of TNF using TNFsr resulted in an increase in re-endothelialization, as measured as absolute area and percent area re-endothelialized. TNFsr also accelerated functional endothelial recovery, which manifest as an increase in nitric oxide production. Neointimal thickening was also shown inhibited. CONCLUSIONS: In vivo blockade of TNF accelerates functional endothelial recovery after barotraumatic de-endothelializing injury. These findings suggest that locally expressed TNF acts to inhibit functional endothelial recovery after angioplasty and that transient blockade of TNF may improve the long-term success of angioplasty.

Angioplasty, Balloon↗
PubMed2001

Therapeutic potential of ex vivo expanded endothelial progenitor cells for myocardial ischemia.

BACKGROUND: We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. METHODS AND RESULTS: Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 10(6) EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 10(6) EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells. CONCLUSIONS: Ex vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.

Animals↗
PubMed2001

Effectiveness of a teaching programme in pain and symptom management for junior house officers.

The objectives of this study were (i) to assess the level of knowledge with respect to pain and symptom management among doctors in their first year after graduation and (ii) to measure the impact of a structured teaching programme on their level of knowledge. All 34 newly qualified junior house officers in one teaching hospital were offered a six-session teaching programme in pain and symptom management. A multiple-choice questionnaire was used to assess their level of knowledge at the beginning and at the end of a 6-month period over which the teaching sessions took place. Attendance at and satisfaction with the programme were high. There was a significant improvement in the level of knowledge at the end of the programme, with the greatest improvement in those who attended most sessions. The low scores recorded for the questionnaire administered before the teaching programme suggest that there is a critical need for improved education in palliative care amongst newly qualified doctors. We have shown that a simple in-service case-based teaching programme can meet this need effectively.

Education, Medical, Graduate↗
PubMed2001

The morphogen Sonic hedgehog is an indirect angiogenic agent upregulating two families of angiogenic growth factors.

Sonic hedgehog (Shh) is a prototypical morphogen known to regulate epithelial/mesenchymal interactions during embryonic development. We found that the hedgehog-signaling pathway is present in adult cardiovascular tissues and can be activated in vivo. Shh was able to induce robust angiogenesis, characterized by distinct large-diameter vessels. Shh also augmented blood-flow recovery and limb salvage following operatively induced hind-limb ischemia in aged mice. In vitro, Shh had no effect on endothelial-cell migration or proliferation; instead, it induced expression of two families of angiogenic cytokines, including all three vascular endothelial growth factor-1 isoforms and angiopoietins-1 and -2 from interstitial mesenchymal cells. These findings reveal a novel role for Shh as an indirect angiogenic factor regulating expression of multiple angiogenic cytokines and indicate that Shh might have potential therapeutic use for ischemic disorders.

Angiopoietin-1↗
PubMed2001

Screening for abuse: barriers and opportunities.

Domestic abuse is the leading cause of injuries and death among women of childbearing age in the United States. The broad purpose of this research is to discover how pregnant women's psychological and behavioral responses to abuse affect birth outcomes. To select a diverse sample of women, we identified 8 prenatal care sites and completed the human subjects approval process with each. Rates of screening for abuse range from all but 12 women over a 2-1/2-year period at one site to no screening for abuse at another site. In this article, we will review pertinent literature and discuss the supports and barriers we observed when implementing an abuse screening program using the Abuse Assessment Screen, a well-tested and valid clinical instrument. Suggestions will be made for improving the screening rates at those sites where screening is absent or inconsistent.

Attitude of Health Personnel↗
PubMed2001

The origin of snakes: limits of a scientific debate.

The origin of snakes has recently become a palaeontological 'hot potato'. Two groups of scientists have come to very different conclusions from the studying the same fossils. Are there tests capable of rejecting wither one of these alternative conclusions or will human interpretation always allow such differences of opinion?

Animals↗
PubMed2000

Age-dependent defect in vascular endothelial growth factor expression is associated with reduced hypoxia-inducible factor 1 activity.

Previous studies have indicated that advanced age is associated with impaired angiogenesis in part because of reduced levels of vascular endothelial growth factor (VEGF) expression. To investigate potential mechanisms responsible for this age-dependent defect in VEGF expression, aortic smooth muscle cells isolated from young rabbits (ages 6-8 months) or old rabbits (ages 4-5 years) were exposed to normoxic (21% oxygen) or hypoxic (0.1% oxygen) conditions. Hypoxia-induced VEGF expression was significantly lower in old versus young cells. VEGF mRNA stability in hypoxic conditions was similar in both young and old cells. However, transient transfection with a luciferase reporter gene that was transcriptionally regulated by the VEGF promoter revealed a significant defect in VEGF up-regulation following hypoxia in old versus young cells (a 43 versus 117% increase in luciferase activity, p < 0.05); this difference was not seen when a deletion construct lacking the hypoxia-inducible 1 (HIF-1) binding site was used. Moreover, although HIF-1 alpha-mRNA expression was shown to be similar in young and old smooth muscle cells, HIF-1 alpha protein and DNA binding activity were significantly reduced in old versus young smooth muscle cells that were exposed to hypoxia. We propose that age-dependent reduction in hypoxia-induced VEGF expression results from reduced HIF-1 activity and may explain the previously described age-dependent impairment of angiogenesis in response to ischemia.

Aging↗
PubMed2000

Lower-extremity edema associated with gene transfer of naked DNA encoding vascular endothelial growth factor.

BACKGROUND: Vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability. The extent to which VEGF may cause tissue edema in humans has not been established. OBJECTIVE: To evaluate patients undergoing VEGF gene transfer for evidence of lower-extremity edema. DESIGN: Prospective consecutive case series. SETTING: Hospital outpatient clinic. PATIENTS: 62 patients with critical limb ischemia and 28 patients with claudication. INTERVENTION: Gene transfer of VEGF DNA. MEASUREMENTS: Semiquantitative analysis of lower-extremity edema. RESULTS: Lower-extremity edema was observed in 31 of 90 (34%) patients. Edema was less common in patients with claudication than in those with pain at rest (P = 0.016) or ischemic ulcers (P < 0.001), and it was less common in patients with pain at rest than in those with ischemic ulcers (P= 0.017). Treatment was typically limited to a brief course of oral diuretics. CONCLUSIONS: Vascular endothelial growth factor may enhance vascular permeability in humans. At the doses of plasmid DNA used in this study, lower-extremity edema responded to oral diuretic therapy and did not seem to be associated with serious sequelae.

Administration, Oral↗
PubMed2000

Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization.

Animal studies and preliminary results in humans suggest that lower extremity and myocardial ischemia can be attenuated by treatment with angiogenic cytokines. The resident population of endothelial cells that is competent to respond to an available level of angiogenic growth factors, however, may potentially limit the extent to which cytokine supplementation enhances tissue neovascularization. Accordingly, we transplanted human endothelial progenitor cells (hEPCs) to athymic nude mice with hindlimb ischemia. Blood flow recovery and capillary density in the ischemic hindlimb were markedly improved, and the rate of limb loss was significantly reduced. Ex vivo expanded hEPCs may thus have utility as a "supply-side" strategy for therapeutic neovascularization.

Animals↗
PubMed2000

Sociodemographic determinants of perceived influences on food choice in a nationally representative sample of Irish adults.

OBJECTIVE: To identify the most important motivations for food choice from the point of view of the consumer in the Irish population, and to characterize those subjects who do and do not regard nutrition as a significant consideration in food choice. DESIGN: As part of a pan-European Union (EU) survey on consumer attitudes to food, nutrition and health, a quota-controlled, nationally representative sample of Irish adults (n = 1009) aged 15 years upwards, completed an interview-assisted, close-ended questionnaire. Subjects selected three factors, from a list of 15, which they believed had the greatest influence on their food choice. SETTING: The interviews for the survey were conducted in subjects' homes. RESULTS: 'Quality/freshness of food' was the most frequently selected food choice factor (51%) followed by 'taste' (43%) and 'trying to eat a healthy diet' (36%). Female gender, increasing age and higher levels of education were found to be independent sociodemographic factors affecting the selection of 'trying to eat a healthy diet' as an important factor in food choice. CONCLUSIONS: Although included in the top five most frequently selected factors affecting food choice, nutrition/healthy eating does not appear to have top priority for the majority of Irish adults. There are differences between the various sociodemographic groups within the population; males and younger subjects appear to require specific nutrition promotion messages.

Adolescent↗
PubMed2000

Favorable effect of VEGF gene transfer on ischemic peripheral neuropathy.

Ischemic peripheral neuropathy is a frequent, irreversible complication of lower extremity vascular insufficiency. We investigated whether ischemic peripheral neuropathy could be prevented and/or reversed by gene transfer of an endothelial cell mitogen designed to promote therapeutic angiogenesis. Intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor (VEGF) simultaneously with induction of hindlimb ischemia in rabbits abrogated the substantial decrease in motor and sensory nerve parameters, and nerve function recovered promptly. When gene transfer was administered 10 days after induction of ischemia, nerve function was restored earlier and/or recovered faster than in untreated rabbits. These findings are due in part to enhanced hindlimb perfusion. In addition, however, the demonstration of functional VEGF receptor expression by Schwann cells indicates a direct effect of VEGF on neural integrity as well. These findings thus constitute a new paradigm for the treatment of ischemic peripheral neuropathy.

Animals↗