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Biomedical subjects

Peter Hill

Publications and source records attributed to Peter Hill.

12 recordsLinked to original sources

Regulation of E-cadherin expression by VHL and hypoxia-inducible factor.

Mutations in von Hippel-Lindau tumor suppressor gene (VHL) underlie the VHL hereditary cancer syndrome and also occur in most sporadic clear cell renal cell cancers (CCRCC). Currently, the mechanism(s) by which VHL loss of function promotes tumor development in the kidney are not fully elucidated. Here, we show that VHL inactivation in precancerous lesions in kidneys from patients with VHL disease correlates with marked down-regulation of the intercellular adhesion molecule E-cadherin. Moreover, in VHL-defective cell lines (RCC4 and RCC10) derived from sporadic CCRCC, reexpression of VHL was found to restore E-cadherin expression. The product of the VHL gene has multiple reported functions, the best characterized of which is its role as the recognition component of an ubiquitin E3 ligase complex responsible for mediating oxygen-dependent destruction of hypoxia-inducible factor-alpha (HIF-alpha) subunits. We show that HIF activation is necessary and sufficient to suppress E-cadherin in renal cancer cells. Given the fundamental role of E-cadherin in controlling epithelial behavior, our findings give insight into how VHL inactivation/HIF activation may lead to kidney cancer and also indicate a mechanism by which reduced oxygenation could alter E-cadherin expression in other cancers and influence normal homeostasis in other epithelia.

Adult↗

Levels of spirituality and treatment outcome: a preliminary examination.

OBJECTIVE: The primary aim of this study was to examine whether admission differences in levels of spirituality predisposed alcohol-dependent individuals to favorable or unfavorable outcomes following admission to facilities that differed in the degree to which spirituality was emphasized. It was hypothesized that individuals whose admission level of spirituality was congruent with the treatment program's orientation and who as such were considered optimally placed (i.e., "matched") for treatment would evince better in-treatment outcomes. METHOD: Four hundred and five participants completed measures of spirituality and psychosocial well-being at intake and at end of treatment. RESULTS: In examining the entire sample, no matching effects were observed on discharge status, abstinence efficacy, or desire to drink. When analyses were restricted to those cases scoring in the upper or lower quartiles in spirituality, we observed a paradoxical effect, as individuals recording lower levels of spirituality at the less spiritual program evinced significantly poorer outcomes (i.e., less abstinence efficacy, greater desire to drink). CONCLUSIONS: These findings hint at the importance of spirituality in the environment of care, indicating that individuals low in spirituality were at risk for poorer outcomes, but exposure to a program that emphasized spirituality lowered that risk.

Alcoholism↗

Tailored education may reduce health literacy disparities in asthma self-management.

RATIONALE: Although inadequate health literacy has been associated with lower asthma medication knowledge and worse metered-dose inhaler (MDI) technique, the relationship between health literacy and the capacity to learn asthma self-management skills is unknown. OBJECTIVES: In this prospective cohort study of adults hospitalized for severe asthma exacerbations at two inner-city hospitals, we examined the relationship between inadequate health literacy and difficulties learning and retaining instructions about discharge medications and appropriate MDI technique. METHODS: At hospital discharge, participants received one-on-one, 30-min, guideline-based, written and oral instruction about their asthma discharge regimen as well as appropriate MDI technique. MEASUREMENTS AND MAIN RESULTS: Seventy-three patients were enrolled. Inadequate health literacy was identified in 16 (22%) participants. Before instruction, inadequate health literacy was associated with lower asthma medication knowledge (5.2/10 vs. 7.2/10, p < 0.001) and worse MDI technique (3.2/6 vs. 3.9/6, p = 0.03). However, inadequate health literacy was not associated with difficulty learning (p = 0.33) or retaining (p = 0.35) instructions about the discharge regimen. Similarly, inadequate health literacy was not associated with difficulty learning (p = 0.26) or retaining (p = 0.97) appropriate MDI technique. Results were similar in multivariable models adjusted for demographic characteristics and asthma severity indicators. CONCLUSIONS: These findings suggest that inadequate health literacy is a surmountable barrier to learning and remembering key asthma self-management skills.

Academic Medical Centers↗

Can we--and should we--have a Europsychiatry for Children and Adolescents? The work of the UEMS Section and Board for Child and Adolescent Psychiatry/Psychotherapy.

The Union of European Medical Specialists (UEMS) paves the way for harmonisation of training and free movement of medical doctors within the European Union. For more than 10 years, Child and Adolescent Psychiatry has been a distinct specialty at this European level--separate from Adult Psychiatry and Pediatrics. The article gives detailed information on the background of the section/board of Child and Adolescent Psychiatry/Psychotherapy (CAPP), training issues including the Training Log Book and the recent situation as well as future perspectives of Continuous Professional Development (CPD) in CAPP, all of which influence the corner stones of CAPP and its delineation from other medical and non-medical organisations. Child and Adolescent Psychiatry as the application of trained specialist medical practice to mental illnesses and psychological disorders in children and young people up to the age of about 18 years reflects more and more the growing research advances of the last years within the field with more progress to come. On the other hand, shortcomings of patient provision in Europe still have to be resolved and CAPP may help to do so.

Adolescent↗

Magnetocardiogram recordings in a nonshielded environment--reproducibility and ischemia detection.

BACKGROUND: Magnetocardiography (MCG) is a noninvasive technology that measures the magnetic field of the heart by superconducting quantum interference devices (SQUID) sensors. The novelty of the present system is that the sensors can be operated without electromagnetic shielding of the examination room, thus allowing the system to be easily installed in the emergency department or chest pain unit. Studies in shielded rooms, found that this imaging modality may have better sensitivity as compared to ECG in detecting ischemia. We aimed (1) to assess the reproducibility, intra-observer, and interobserver interpretation variability and (2) to assess the MCG maps in the presence of coronary narrowings. METHODS AND RESULTS: All measurements were performed in a nonshielded room. For the first part of the study, two MCG maps were recorded in 24 otherwise healthy volunteers (age 20-44 years, median 24, 16 male) in an interval ranging from 2 to 48 hours. The maps were interpreted using the CardioMag software for contour maps, averaged MCG time traces, and waveform morphology of repolarization by two observers blinded to each other. The parameters tested had low disagreement between repeated measurements. The correlations of the intra-observer and interobserver interpretation were excellent. Secondly, MCG maps were obtained in 29 patients referred for angiography due to suspected coronary artery disease. Nineteen of them had coronary narrowings defined as more than 50%. In this group, 16 (84.2%) had abnormal MCG maps as compared to only 5 (26.3%) who had abnormal ECGs (P < 0.01). CONCLUSIONS: MCG maps can be successfully obtained in a nonshielded room and allow feasible, accurate, and reproducible measurements with little intra-observer and interobserver variability. Ischemic changes in the heart's magnetic field may occur before electrical changes. Our pilot data suggests that this imaging modality may potentially offer better sensitivity as compared to rest ECG in detecting ischemia in a cohort of patients who had coronary narrowings identified by angiography.

Algorithms↗

Corticosteroid use after hospital discharge among high-risk adults with asthma.

Despite the efficacy of corticosteroid therapy, patients hospitalized for asthma exacerbations are at high risk for re-exacerbation and death after discharge. The objective of this prospective cohort study was to evaluate adherence to inhaled corticosteroids (ICS) and oral corticosteroids (OCS) after discharge in adults hospitalized for asthma exacerbations. ICS and OCS were equipped with electronic medication monitors and were provided at discharge. Adherence (use/prescribed use x 100%) was measured by self-report and canister weight (ICS), pill count (OCS), and electronic medication monitors (both ICS and OCS) 2 weeks after discharge. Poor adherence was defined as adherence of less than 50%. The Asthma Control Questionnaire was used to assess symptom control. Sixty patients were enrolled (age 42.2 years, 98.3% African American, 65.0% female, 46.7% with history of near-fatal asthma). Electronically measured adherence to both corticosteroids dropped to approximately 50% within 7 days of discharge. Poor adherence to both corticosteroids predicted significantly worse symptom control (p = 0.04). Self-report, canister weight, and pill count all had low sensitivity (29.2%, 65.0%, and 7.7%, respectively) for detecting poor adherence. We conclude that adherence to ICS and OCS deteriorates within days of hospital discharge but may not be recognized in a substantial proportion of patients.

Administration, Inhalation↗

Ethics and health systems research in 'post'-conflict situations.

Although considerable attention has been given to ethical issues related to clinical research in developing countries, in particular related to HIV therapy, there has been limited focus on health systems research, despite its increasing importance in the light of current trends in development assistance. This paper examines ethical issues related to health systems research in 'post'-conflict situations, addressing both generic issues for developing countries and those issues specific to 'post'-conflict societies, citing examples from the author's Cambodian experience. It argues that the destruction of health infrastructure results in a loss of structures and processes that would otherwise protect prospective research subjects who are part of vulnerable populations. It identifies the growth of health systems research as part of a trend towards sectoral and programmatic development assistance, the emergence of 'knowledge generation' as a form of research linked to development, and the potential for conflict where multilateral and bilateral donors are both primary funders and users of health systems research. It also examines the position of the health system researcher in relation to the sponsors of this research, and the health system being analysed.

Cambodia↗

Distribution and characteristics of in-patient child and adolescent mental health services in England and Wales.

BACKGROUND: Little is known about the current state of provision of child and adolescent mental health service in-patient units in the UK. AIMS: To describe the full number, distribution and key characteristics of child and adolescent psychiatric in-patient units in England and Wales. METHOD: Following identification of units, data were collected by a postal general survey with telephone follow-up. RESULTS: Eighty units were identified; these provided 900 beds, of which 244 (27%) were managed by the independent sector. Units are unevenly distributed, with a concentration of beds in London and the south-east of England. The independent sector, which manages a high proportion of specialist services and eating disorder units in particular, accentuates this uneven distribution. Nearly two-thirds of units reported that they would not accept emergency admissions. CONCLUSIONS: A national approach is needed to the planning and commissioning of this specialist service.

Adolescent↗

Forgiveness and justice: a research agenda for social and personality psychology.

Forgiveness and related constructs (e.g., repentance, mercy, reconciliation) are ripe for study by social and personality psychologists, including those interested in justice. Current trends in social science, law, management, philosophy, and theology suggest a need to expand existing justice frameworks to incorporate alternatives or complements to retribution, including forgiveness and related processes. In this article, we raise five challenging empirical questions about forgiveness. For each question, we briefly review representative research, raise hypotheses, and suggest specific ways in which social and personality psychologists could make distinctive contributions.

Attitude↗