Physiological and clinical consequences of relief of right ventricular outflow tract obstruction late after repair of congenital heart defects.

BACKGROUND: Right ventricular outflow tract obstruction (RVOTO) is a common problem after repair of congenital heart disease. Percutaneous pulmonary valve implantation (PPVI) can treat this condition without consequent pulmonary regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical and physiological response to relieving RVOTO. METHODS AND RESULTS: We studied 18 patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a total of 93 who had this procedure for various indications. All had a right ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without important pulmonary regurgitation (less than mild or regurgitant fraction <10% on magnetic resonance imaging [MRI]). Cardiopulmonary exercise testing, tissue Doppler echocardiography, and MRI were performed before and within 50 days of PPVI. PPVI reduced RVOT gradient (51.4 to 21.7 mm Hg, P<0.001) and right ventricular systolic pressure (72.8 to 47.3 mm Hg, P<0.001) at catheterization. Symptoms and aerobic (25.7 to 28.9 mL.kg(-1).min(-1), P=0.002) and anaerobic (14.4 to 16.2 mL.kg(-1).min(-1), P=0.002) exercise capacity improved. Myocardial systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P=0.05; mitral 4.7 to 5.5 cm/s, P=0.01), whereas isovolumic acceleration was unchanged. The tricuspid annular velocity was not maintained on intermediate follow-up. Right ventricular end-diastolic volume (99.9 to 89.7 mL/m2, P<0.001) fell, whereas effective stroke volume (43.7 to 48.3 mL/m2, P=0.06) and ejection fraction (48.0% to 56.8%, P=0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4 mL/m2, P=0.145), stroke volume (45.3 to 50.6 mL/m2, P=0.02), and ejection fraction (62.6% to 65.8%, P=0.03) increased. CONCLUSIONS: PPVI relieves RVOTO, which leads to an early improvement in biventricular performance. Furthermore, it reduces symptoms and improves exercise tolerance. These findings have important implications for the management of this increasingly common condition

Peripartum cardiomyopathy: diagnosis and management

No abstract available

Bimanual reach to grasp movements after cervical spinal cord injury

Injury to the cervical spinal cord results in bilateral deficits in arm/hand function reducing functional independence and quality of life. To date little research has been undertaken to investigate control strategies of arm/hand movements following cervical spinal cord injury (cSCI). This study aimed to investigate unimanual and bimanual coordination in patients with acute cSCI using 3D kinematic analysis as they performed naturalistic reach to grasp actions with one hand, or with both hands together (symmetrical task), and compare this to the movement patterns of uninjured younger and older adults. Eighteen adults with a cSCI (mean 61.61 years) with lesions at C4-C8, with an American Spinal Injury Association (ASIA) grade B to D and 16 uninjured younger adults (mean 23.68 years) and sixteen uninjured older adults (mean 70.92 years) were recruited. Participants with a cSCI produced reach-to-grasp actions which took longer, were slower, and had longer deceleration phases than uninjured participants. These differences were exacerbated during bimanual reach-to-grasp tasks. Maximal grasp aperture was no different between groups, but reached earlier by people with cSCI. Participants with a cSCI were less synchronous than younger and older adults but all groups used the deceleration phase for error correction to end the movement in a synchronous fashion. Overall, this study suggests that after cSCI a level of bimanual coordination is retained. While there seems to be a greater reliance on feedback to produce both the reach to grasp, we observed minimal disruption of the more impaired limb on the less impaired limb. This suggests that bimanual movements should be integrated into therapy

Mechanisms of toxic action and structure-activity relationships for organochlorine and synthetic pyrethroid insecticides.

The mechanisms and sites of action of organochlorine (DDT-types and chlorinated alicyclics) and synthetic pyrethroid insecticides are presented with discussion of symptoms, physiological effects, and selectivity. The structural requirements for toxicity are assessed, and structure-activity relationships are considered for each subclass. Lipophilicity is important for all the groups because it facilitates delivery of these neurotoxicants to the site of action in the nerve. Steric factors including molecular volume, shape, and isomeric configuration greatly influence toxicity. Electronic parameters also have been demonstrated to affect biological activity in some of the groups of insecticides, e.g., Hammett's sigma and Taft's sigma * as indicators of electronegativity. New synthetic pyrethroids continue to be developed, with varied structures and different physicochemical and biological properties

Theorizing healthy settings: a critical discussion with reference to Healthy Universities

The settings approach appreciates that health determinants operate in settings of everyday life. Whilst subject to conceptual development, we argue that the approach lacks a clear and coherent theoretical framework to steer policy, practice and research. Aims: To identify what theories and conceptual models have been used in relation to the implementation and evaluation of Healthy Universities. Methods: A scoping literature review was undertaken between 2010-2013, identifying 26 papers that met inclusion criteria. Findings: Seven theoretical perspectives or conceptual frameworks were identified: the Ottawa Charter; a socio-ecological approach (which implicitly drew on sociological theories concerning structure and agency); salutogenesis; systems thinking; whole system change; organisational development; and a framework proposed by Dooris. These were used to address interrelated questions on the nature of a setting, how health is created in a setting, why the settings approach is a useful means of promoting health, and how health promotion can be introduced into and embedded within a setting. Conclusion: Although distinctive, the example of Healthy Universities drew on common theoretical perspectives that have infused the settings discourse more generally. This engagement with theory was at times well-developed and at other times a passing reference. The paper concludes by pointing to other theories that offer value to healthy settings practice and research and by arguing that theorisation has a key role to play in understanding the complexity of settings and guiding the planning, implementation and evaluation of programmes

A consensus building exercise to determine research priorities for silver trauma

Background Emergency care research into ‘Silver Trauma’, which is simply defined as major trauma consequent upon relatively minor injury mechanisms, is facing many challenges including that at present, there is no clear prioritisation of the issues. This study aimed to determine the top research priorities to guide future research. Methods This consensus-based prioritization exercise used a three-stage modified Delphi technique. The study consisted of an idea generating (divergent) first round, a ranking evaluation in the second round, and a (convergent) consensus meeting in the third round. Results A total of 20 research questions advanced to the final round of this study. After discussing the importance and clinical significance of each research question, five research questions were prioritised by the experts; the top three research priorities were: (1). What are older people’s preferred goals of trauma care? (2). Beyond the Emergency Department (ED), what is the appropriate combined geriatric and trauma care? (3). Do older adults benefit from access to trauma centres? If so, do older trauma patients have equitable access to trauma centre compared to younger adults? Conclusion The results of this study will assist clinicians, researchers, and organisations that are interested in silver trauma in guiding their future efforts and funding toward addressing the identified research priorities

Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV)-infected cat

<p>Abstract</p> <p>Background</p> <p>FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF) and anti-inflammatory cytokines (IL-4, IL-5, and IL-10); CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor); the chemokine receptor CXCR4 (FIV co-receptor); SDF-1α, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy.</p> <p>Methods</p> <p>We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression.</p> <p>Results</p> <p>We detected IL-4, IL-5, IL-6, IL-1β, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens.</p> <p>Conclusion</p> <p>Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in normal tissues. Non-viable pregnancies were associated with decreased expression of immunomodulators which regulate trophoblast invasion in other species. The detection of FIV RNA in trophoblasts was rare, suggesting that the high rate of reproductive failure in FIV-infected queens was not a direct result of viral replication in trophoblasts. The influence of placental immune cells on trophoblast function and pregnancy maintenance in the FIV-infected cat requires additional study.</p