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1.
Acta Neurochir (Wien) ; 164(6): 1453-1458, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35212798

RESUMO

BACKGROUND: Endoscopic third ventriculostomy success score (ETVss) is widely utilised to predict outcomes for ETV. Accurate prediction of success for a procedure is of vital importance both for selecting the optimal management plan and for obtaining informed consent. Existing literature demonstrates a variety of opinions on the accuracy of the currently utilised ETVss and recommends a range of techniques to reduce the number of subsequent ventriculo-peritoneal (VP)-shunt insertions, prompting the present study. METHODS: We retrospectively analysed data for ETV cases since 2007 to review success rate in our regional paediatric neurosurgical centre and if the currently utilised ETVss successfully predicted outcomes. Failed ETV cases were defined as any patient who received a VP-shunt at any time following ETV. Data was analysed with MS ExcelR and RStudioR. RESULTS: 44 ETVs were performed over 13 years with approximately equal distribution between male and female patients; median age 7 years (IQR 4-13 years). Overall, mean ETVss for these 44 procedures was 78%; actual success rate was 70% with no statistically significant difference between them (p = 0.286; Welch two sample t-test). Accuracy of ETVss varied with pathology: tectal gliomas (mean ETVss 75% and actual success 78%); cerebellar tumours (mean ETVss 85% and actual success 81%); other tumours (mean ETVss 75% and actual success 81%); aqueduct stenosis (mean ETVss 71% and actual success 69%); and other pathologies (mean ETVss 70% and actual success 60%). < 1 month and 1-6 months and 1-10 years and > 10 years contributed equally to the accuracy of ETVss. CONCLUSION: Non-telencephalon tumours and obstruction at the level of the mid-brain are most strongly associated with successful ETV outcome. These findings can be used to modify the currently utilised ETVss to further improve accuracy of outcome prediction. We recommend a modified-ETVss (m-ETVss) and a future larger adequately powered prospective study to validate this.


Assuntos
Hidrocefalia , Neuroendoscopia , Terceiro Ventrículo , Adolescente , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Humanos , Hidrocefalia/patologia , Hidrocefalia/cirurgia , Lactente , Masculino , Neuroendoscopia/métodos , Estudos Prospectivos , Estudos Retrospectivos , Terceiro Ventrículo/patologia , Terceiro Ventrículo/cirurgia , Resultado do Tratamento , Ventriculostomia/métodos
2.
J Oncol Pharm Pract ; 25(6): 1336-1342, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30058442

RESUMO

Myeloablative chemotherapy administered prior to autologous stem cell transplantation (auto-SCT) is associated with a significant amount of chemotherapy-induced nausea and vomiting (CINV). We conducted a phase II trial to assess the safety, efficacy, and impact on quality of life when palonosetron (PAL) 0.25 mg combined with dexamethasone were given on the final or only day of myeloablative chemotherapy for auto-SCT. The primary end point of this study was the incidence of achieving a delayed CINV complete response defined as no emetic episode and no use of rescue medications during the 24-120 h period post chemotherapy. Eighty-five patients were enrolled in the study and received PAL. A delayed CINV complete response was achieved in 15% of patients. A multivariate analysis demonstrated no associated differences between age, gender, diagnosis, or regimen. By day 5 after PAL, the mean nausea severity was 0.91 ± 2.45 vs. 0.09 ± 1.58 at baseline (p = 0.012). Quality of life measurements demonstrated similar quality of life between baseline and day 3. By day 6 however, nausea alone had a statistically significant impact on quality of life. In our study, PAL controlled nausea severity and sustained quality of life, but further strategies are needed to control delayed CINV associated with the auto-SCT process.


Assuntos
Antieméticos/administração & dosagem , Dexametasona/administração & dosagem , Náusea/prevenção & controle , Ondansetron/administração & dosagem , Palonossetrom/administração & dosagem , Vômito/prevenção & controle , Adulto , Idoso , Esquema de Medicação , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/efeitos adversos , Náusea/induzido quimicamente , Qualidade de Vida , Índice de Gravidade de Doença , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Vômito/induzido quimicamente , Adulto Jovem
3.
Sci Rep ; 6: 36415, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27808175

RESUMO

Estimating the abundance of pelagic fish species is a challenging task, due to their vast and remote habitat. Despite the development of satellite, archival and acoustic tagging techniques that allow the tracking of marine animals in their natural environments, these technologies have so far been underutilized in developing abundance estimations. We developed a new method for estimating the abundance of tropical tuna that employs these technologies and exploits the aggregative behavior of tuna around floating objects (FADs). We provided estimates of abundance indices based on a simulated set of tagged fish and studied the sensitivity of our method to different association dynamics, FAD numbers, population sizes and heterogeneities of the FAD-array. Taking the case study of yellowfin tuna (Thunnus albacares) acoustically-tagged in Hawaii, we implemented our approach on field data and derived for the first time the ratio between the associated and the total population. With more extensive and long-term monitoring of FAD-associated tunas and good estimates of the numbers of fish at FADs, our method could provide fisheries-independent estimates of populations of tropical tuna. The same approach can be applied to obtain population assessments for any marine and terrestrial species that display associative behavior and from which behavioral data have been acquired using acoustic, archival or satellite tags.


Assuntos
Comportamento Animal/fisiologia , Atum/fisiologia , Algoritmos , Animais , Ecossistema , Pesqueiros , Havaí , Densidade Demográfica
4.
Br J Dermatol ; 170(4): 895-900, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24341905

RESUMO

BACKGROUND: Morphoea is a rare fibrosing disease of the skin and subcutaneous tissue with an unpredictable disease course, running the spectrum from mild skin involvement to severe disfigurement or extracutaneous complications. OBJECTIVES: Our objective was to describe the natural history of paediatric morphoea and determine patient variables that were associated with severe disease. PATIENTS AND METHODS: We conducted a retrospective chart review of patients with morphoea seen in one paediatric hospital system. Information about demographics, clinical characteristics, disease course and treatment were collected. Statistical analysis was performed using appropriate univariate tests and a multivariable model. RESULTS: One hundred and fourteen patients met study inclusion criteria. The female : male ratio was 2·6 : 1, and the median age of onset was 7 years old. There were 55 patients (48%) with linear morphoea, 38 patients (33%) with circumscribed morphoea, 12 patients (11%) with generalized morphoea, and nine patients (8%) with mixed morphoea. Neurological symptoms and joint involvement were present in 27 subjects (24%). Extracutaneous manifestations occurred in 38% of subjects with linear morphoea, compared with 15% with generalized morphoea and 3% with circumscribed morphoea (P = 0·0001). Thirty-six per cent of children with disease onset prior to 10 years of age and 5% of children with disease onset after 10 years of age had extracutaneous manifestations (P = 0·0002). Both linear morphoea and early-onset disease were significantly associated with extracutaneous involvement in a multivariable model. CONCLUSIONS: Children with linear morphoea and disease onset before 10 years of age should be monitored closely for extracutaneous manifestations and need early treatment with systemic medications to prevent disease complications.


Assuntos
Esclerodermia Localizada/epidemiologia , Administração Cutânea , Adolescente , Idade de Início , Criança , Fármacos Dermatológicos/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Masculino , Estudos Retrospectivos , Fatores de Risco , Esclerodermia Localizada/complicações , Esclerodermia Localizada/tratamento farmacológico , Wisconsin/epidemiologia
5.
Ecol Appl ; 23(5): 999-1016, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23967571

RESUMO

Investment in and operation of flow control infrastructure such as dams, weirs, and regulators can help increase both the health of regulated river ecosystems and the social values derived from them. This requires high-quality and high-resolution spatiotemporal ecohydrological and socioeconomic information. We developed such an information base for integrated environmental flow management in the River Murray in South Australia (SA). A hydrological model was used to identify spatiotemporal inundation dynamics. River ecosystems were classified and mapped as ecohydrological units. Ecological response models were developed to link three aspects of environmental flows (flood duration, timing, and inter-flood period) to the health responses of 16 ecological components at various life stages. Potential infrastructure investments (flow control regulators and irrigation pump relocation) were located by interpreting LiDAR elevation data, digital orthophotography, and wetland mapping information; and infrastructure costs were quantified using engineering cost models. Social values were quantified at a coarse scale as total economic value based on a national survey of willingness-to-pay for four key ecological assets; and at a local scale using mapped ecosystem service values. This information was integrated using a constrained, nonlinear, mixed-integer, compromise programming optimization model and solved using a stochastic Tabu search algorithm. We tested the model uncertainty and sensitivity using 390 Monte Carlo model runs at varying weights of ecological health vs. social values. Integrating ecohydrological and socioeconomic information identified environmental flow management regimes that efficiently achieved both ecological and social objectives. Using an ecologically weighted efficient and socially weighted efficient scenario, we illustrated model outputs including a suite of cost-effective infrastructure investments and an operational plan for new and existing flow control structures including dam releases, weir height manipulation, and regulator operation on a monthly time step. Both the investments and management regimes differed substantially between the two scenarios, suggesting that the choice of weightings on ecological and social objectives is important. This demonstrates the benefit of integrating high-quality and high-resolution spatiotemporal ecohydrological and socioeconomic information for guiding the investment in and operational management of environmental flows.


Assuntos
Ecossistema , Monitoramento Ambiental , Abastecimento de Água , Animais , Austrália , Conservação dos Recursos Naturais , Inundações , Humanos , Modelos Teóricos , Fatores de Tempo , Movimentos da Água
6.
Br J Dermatol ; 169(2): 428-33, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23601021

RESUMO

BACKGROUND: Paediatric cutaneous lupus erythematosus (CLE) is uncommon and inadequately described in the literature. Similar to adults, children with CLE develop LE-specific and/or LE-nonspecific skin findings. Similarities and differences in demographics and clinical course between paediatric and adult CLE have not been sufficiently described. OBJECTIVES: To detail the demographic and clinical features of paediatric CLE and compare these findings with those reported in the adult literature. METHODS: A retrospective chart review was performed of 53 children seen in a paediatric dermatology clinic with cutaneous manifestations of LE. RESULTS: Patients presented with all five major subtypes of CLE, with some notable differences from adult CLE and previously published reports of paediatric CLE. Progression from discoid LE to systemic LE (SLE) did not occur in our cohort. Patients with subacute CLE were more likely than adults to have lesions below the waist as well as concomitant SLE. Sex distribution for CLE in our study was equal prior to puberty and female predominant in post-pubertal patients. CONCLUSIONS: Children with CLE have variable clinical presentations and progression to SLE that may be different from adult disease. Specifically, children with acute and subacute CLE may be more likely than adults to have systemic disease; therefore, patients with these subtypes should be monitored closely for evidence of SLE. Study limitations included small patient numbers that may limit the ability to generalize these data and relatively short follow-up intervals.


Assuntos
Lúpus Eritematoso Cutâneo/epidemiologia , Doença Aguda , Adolescente , Idade de Início , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Lactente , Recém-Nascido , Lúpus Eritematoso Cutâneo/etnologia , Lúpus Eritematoso Cutâneo/patologia , Masculino , Estudos Retrospectivos , Distribuição por Sexo , Wisconsin/epidemiologia
7.
Neuroscience ; 228: 361-70, 2013 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-23107618

RESUMO

To maximize reward, we are faced with the dilemma of having to balance the exploration of new response options and the exploitation of previous choices. Here, we sought to determine if the event-related brain potential (ERP) in the P300 time range is sensitive to decisions to explore or exploit within the context of a sequential risk-taking task. Specifically, the task we used required participants to continually explore their options-whether they should "push their luck" and keep gambling or "take the money and run" and collect their winnings. Our behavioral analysis yielded two distinct distributions of response times: a larger group of short-decision times and a smaller group of long-decision times. Interestingly, these data suggest that participants adopted one of two modes of control on any given trial: a mode where they quickly decided to keep gambling (i.e. exploit), and a mode where they deliberated whether to the take the money they had already won or continue gambling (i.e. explore). Importantly, we found that the amplitude of the ERP in the P300 time range was larger for explorative decisions than for exploitative decisions and, further, was correlated with decision time. Our results are consistent with a recent theoretical account that links changes in ERP amplitude in the P300 time range with phasic activity of the locus coeruleus-norepinephrine system and decisions to engage in exploratory behavior.


Assuntos
Comportamento de Escolha/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados P300/fisiologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/fisiologia , Assunção de Riscos , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Adulto Jovem
8.
Ecology ; 93(8): 1816-29, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22928411

RESUMO

Effects of anthropogenic nitrogen (N) deposition and the ability of terrestrial ecosystems to store carbon (C) depend in part on the amount of N retained in the system and its partitioning among plant and soil pools. We conducted a meta-analysis of studies at 48 sites across four continents that used enriched 15N isotope tracers in order to synthesize information about total ecosystem N retention (i.e., total ecosystem 15N recovery in plant and soil pools) across natural systems and N partitioning among ecosystem pools. The greatest recoveries of ecosystem 15N tracer occurred in shrublands (mean, 89.5%) and wetlands (84.8%) followed by forests (74.9%) and grasslands (51.8%). In the short term (< 1 week after 15N tracer application), total ecosystem 15N recovery was negatively correlated with fine-root and soil 15N natural abundance, and organic soil C and N concentration but was positively correlated with mean annual temperature and mineral soil C:N. In the longer term (3-18 months after 15N tracer application), total ecosystem 15N retention was negatively correlated with foliar natural-abundance 15N but was positively correlated with mineral soil C and N concentration and C:N, showing that plant and soil natural-abundance 15N and soil C:N are good indicators of total ecosystem N retention. Foliar N concentration was not significantly related to ecosystem 15N tracer recovery, suggesting that plant N status is not a good predictor of total ecosystem N retention. Because the largest ecosystem sinks for 15N tracer were below ground in forests, shrublands, and grasslands, we conclude that growth enhancement and potential for increased C storage in aboveground biomass from atmospheric N deposition is likely to be modest in these ecosystems. Total ecosystem 15N recovery decreased with N fertilization, with an apparent threshold fertilization rate of 46 kg N x ha(-1) x yr(-1) above which most ecosystems showed net losses of applied 15N tracer in response to N fertilizer addition.


Assuntos
Ecossistema , Ciclo do Nitrogênio , Nitrogênio/química , Altitude , Amônia/química , Vazamento de Resíduos Químicos , Nitratos/química , Isótopos de Nitrogênio , Chuva , Temperatura
9.
Neurology ; 76(1): 41-8, 2011 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-21205694

RESUMO

OBJECTIVES: To evaluate the diagnostic value of individual noninvasive presurgical modalities and to study their role in surgical management of nonlesional pediatric epilepsy patients. METHODS: We retrospectively studied 14 children (3-18 years) with nonlesional intractable focal epilepsy. Clinical characteristics, surgical outcome, localizing features on 3 presurgical diagnostic tests (subtraction peri-ictal SPECT coregistered to MRI [SISCOM], statistical parametric mapping [SPM] analysis of [18F] FDG-PET, magnetoencephalography [MEG]), and intracranial EEG (iEEG) were reviewed. The localization of each individual test was determined for lobar location by visual inspection. Concordance of localization between each test and iEEG was scored as follows: 2=lobar concordance; 1=hemispheric concordance; 0=discordance or nonlocalization. Total concordance score in each patient was measured by the summation of concordance scores for all 3 tests. RESULTS: Seven (50%) of 14 patients were seizure-free for at least 12 months after surgery. One (7%) had only rare seizures and 6 (43%) had persistent seizures. MEG (79%, 11/14) and SISCOM (79%, 11/14) showed greater lobar concordance with iEEG than SPM-PET (13%, 3/14) (p<0.05). SPM-PET provided hemispheric lateralization (71%, 10/14) more often than lobar localization. Total concordance score tended to be greater for seizure-free patients (4.7) than for non-seizure-free patients (3.9). CONCLUSIONS: Our data suggest that MEG and SISCOM are better tools for lobar localization than SPM analysis of FDG-PET in children with nonlesional epilepsy. A multimodality approach may improve surgical outcome as well as selection of surgical candidates in patients without MRI abnormalities.


Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Diagnóstico por Imagem/métodos , Epilepsia/diagnóstico , Epilepsia/cirurgia , Adolescente , Encéfalo/cirurgia , Criança , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Magnetoencefalografia/métodos , Masculino , Testes Neuropsicológicos , Estudos Retrospectivos , Gravação em Vídeo
10.
Nurse Educ Pract ; 11(2): 131-5, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21094090

RESUMO

Changes to the pedagogy of pre-registration nurse education and training have become a global phenomenon. However, the evidence base to inform responses to these changes and the impact on nursing practice is limited. This paper explores the outcomes of an innovative approach aimed at ensuring responses to these drivers for change, particularly in curriculum development, the organisation, management and delivery of programmes and the enhancement of the student experience, are evidence based. This paper reports on an organisational change project undertaken in a School of Nursing in the North West of England, UK. The project involved 12 interrelated work streams used to explore aspects of the student journey from recruitment through progression to eventual employment. An evidence base was developed through a methodological bricolage that drew upon a robust and authentic mixture of systematic literature reviews, contemporaneous analysis of educational practice and evaluation of the student experience. This was used to underpin the decision making processes required to promote innovation in programme design, to increase the involvement of students in the facilitation and evaluation of their learning experiences, and helped shape the organisational changes required for embedding an evidenced-based culture in the School. Consistent and transformational leadership has been key to the project's success in communicating and managing the changes.


Assuntos
Bacharelado em Enfermagem/métodos , Pesquisa em Educação em Enfermagem/métodos , Escolas de Enfermagem/organização & administração , Currículo/normas , Currículo/tendências , Bacharelado em Enfermagem/normas , Bacharelado em Enfermagem/tendências , Inglaterra , Prática Clínica Baseada em Evidências , Humanos , Pesquisa em Educação em Enfermagem/normas , Estudos de Casos Organizacionais , Inovação Organizacional , Escolas de Enfermagem/tendências , Ensino/métodos , Ensino/tendências
11.
Acta Neurol Scand ; 121(3): 149-53, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20055770

RESUMO

OBJECTIVES: Sparse information on dose-response characteristics for initial antiepileptic drug monotherapy in children with idiopathic generalized epilepsy (IGE) is available. The aim of this study is to characterize the therapeutic dose of valproate in children with newly diagnosed IGE. MATERIALS AND METHODS: Effect of initial valproate monotherapy and doses associated with seizure freedom were examined in consecutive children with IGE identified from a New Onset Seizure Clinic. RESULTS: Of 84 patients identified, 48 (57%) became seizure-free on valproate monotherapy and another 10 patients became seizure-free but discontinued VPA because of adverse effects. The mean dose in seizure-free children was 15.7 mg/kg/day and over 95% of IGE patients will respond below 25 mg/kg/day. CONCLUSIONS: Half of children became seizure-free on valproate monotherapy and did so at modest doses.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Generalizada/tratamento farmacológico , Ácido Valproico/uso terapêutico , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Eletroencefalografia/métodos , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Razão de Chances , Estudos Retrospectivos
12.
Br J Pharmacol ; 151(1): 115-27, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17351655

RESUMO

BACKGROUND AND PURPOSE: The pro-inflammatory cytokine, interleukin-1beta (IL-1beta), has been implicated in the pathogenesis of atherosclerosis, potentially via its release from vascular endothelium. Endothelial cells (EC) synthesize IL-1beta in response to inflammatory stimuli, but the demonstration and mechanism of release of IL-1 from ECs remains unclear. In activated monocytes, efficient release of bioactive IL-1beta occurred via activation of ATP-gated P2X(7) receptors (P2X(7)Rs). Activation of P2X(7)R in ECs from human umbilical vein (HUVECs) released IL-1 receptor antagonist (IL-1Ra). The purpose of this study was to provide a quantitative investigation of P2XR expression and function, in parallel with IL-1beta and IL-1Ra synthesis, processing and release, in HUVECs under pro-inflammatory conditions. EXPERIMENTAL APPROACH: Quantitative RT-PCR, immunoblotting, ELISA, flow cytometry, and whole-cell patch clamp recordings were used to determine protein expression and receptor function. IL-8-luciferase-reporter was used as an IL-1 sensitive bioassay. KEY RESULTS: HUVECs expressed P2X(4)R and P2X(7)R subtypes and both were significantly up-regulated under inflammatory conditions. P2X(7)R currents were increased 3-fold by inflammatory stimuli, whereas no P2X(4)R-mediated currents were detected. Caspase-1, but not IL-1beta, was present intracellularly under basal conditions; inflammatory stimuli activated the synthesis of intracellular pro-IL-1beta and increased caspase-1 levels. Activation of P2X(7)Rs resulted in low-level release of bioactive IL-1beta and simultaneous release of IL-1Ra. The net biological effect of release was anti-inflammatory. CONCLUSIONS AND IMPLICATIONS: Endothelial P2X(7)Rs induced secretion of both pro- and anti-inflammatory IL-1 receptor ligands, the balance of which may provide a means for altering the inflammatory state of the arterial vessel wall.


Assuntos
Células Endoteliais/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Interleucina-1beta/metabolismo , Receptores Purinérgicos P2/análise , Células Endoteliais/química , Humanos , Potenciais da Membrana , RNA Mensageiro/análise , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/fisiologia , Receptores Purinérgicos P2X4 , Receptores Purinérgicos P2X7
13.
Nurse Educ Today ; 27(8): 947-54, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17391812

RESUMO

The sustained modernisation of the UK primary health care service has resulted in individuals and organisations having to develop more integrated ways of working. This has resulted in changes to the structure and functioning of primary care organisations, changes to the traditional workforce, and an increase in scope of primary care practice. These changes have contributed to what for many staff has become a constantly turbulent organisational and practice environment. Data from a three-year project, commissioned by the North West Development Agency is used to explore how staff involved in these changes dealt with this turbulence. Three hundred and fifty staff working within primary care participated in the study. A multimethods approach was used which facilitated an iterative analysis and data collection process. Thematic analysis revealed a high degree of congruence between the perceptions of all staff groups with evidence of a generally well-articulated, but often rhetorical view of the organisational and professional factors involved in how these changes were experienced. This rhetoric was used by individuals as a way of containing both the good and bad elements of their experience. This paper discusses how these defense mechanisms need to be recognised and understood by managers so that a more supportive organisational culture is developed.


Assuntos
Atitude do Pessoal de Saúde , Comportamento Cooperativo , Relações Interprofissionais , Atenção Primária à Saúde/organização & administração , Serviço Social/organização & administração , Medicina Estatal/organização & administração , Adaptação Psicológica , Comunicação , Serviços de Saúde Comunitária/organização & administração , Mecanismos de Defesa , Inglaterra , Reforma dos Serviços de Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Relações Interinstitucionais , Liderança , Pesquisa Metodológica em Enfermagem , Cultura Organizacional , Inovação Organizacional , Papel Profissional/psicologia , Interpretação Psicanalítica , Inquéritos e Questionários
14.
Br J Dermatol ; 156(3): 460-5, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17300234

RESUMO

BACKGROUND: Propionibacterium acnes has been strongly implicated in inflammatory acne. However, its role in the disease is unclear. It has been hypothesized that an immune response to P. acnes and/or P. acnes heat shock proteins (HSPs) may play a role in the pathogenesis of inflammatory acne. OBJECTIVES: To compare the cell-mediated immune response to P. acnes and HSPs in acne patients, nonacne controls and individuals with resolved acne. METHODS: The proliferative response of peripheral blood mononuclear cells (PBMC) from acne patients, resolved acne donors and healthy controls to P. acnes, P. acnes HSP60 and HSP70, and mycobacterial HSPs was assessed by lymphocyte transformation assay (LTA). The proliferative response of purified CD4+ T cells was further analysed by limiting dilution analysis (LDA). Contingency tables (G-test) were used to analyse the proportion of individuals in each group showing a positive proliferative response for LTA or data fitting single-hit kinetics for LDA. RESULTS: Analysis of stimulation of PBMC with P. acnes, P. acnes HSP60 and HSP70 in the LTA showed the proportion of positive responders to be independent of subject group. However, the proportion of acne patients with a positive response to mycobacterial HSPs was significantly higher than those for the other subject groups. Analysis of LDA data showed the proportion of resolved donors with responses to P. acnes fitting the single-hit kinetics model to be significantly lower than those of the other groups. There were no significant differences in responses to other antigens. CONCLUSIONS: The significantly lower proportion of resolved donors demonstrating a single-hit kinetics response to P. acnes by LDA may represent negative regulation of the CD4+ T-cell response to P. acnes in these subjects.


Assuntos
Acne Vulgar/imunologia , Linfócitos T CD4-Positivos/imunologia , Propionibacterium acnes/imunologia , Acne Vulgar/microbiologia , Adolescente , Adulto , Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Proliferação de Células , Células Cultivadas , Chaperonina 60/imunologia , Proteínas de Choque Térmico HSP70/imunologia , Humanos , Ativação Linfocitária
15.
Biochem Soc Trans ; 33(Pt 6): 1405-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16246130

RESUMO

Multiple cellular proteins have been identified as participating in Toll/interleukin-1 receptor-mediated inflammatory gene expression. The continuing isolation of novel components, based on sequence similarities, protein-protein interactions and protein purification, suggests that many elements of this signalling network remain to be identified. We report here the development of a high-throughput functional screening platform and its application for the identification of components of inflammatory signalling networks. Our results enable us to estimate that 100-150 gene products are involved in controlling the transcription of the human interleukin 8 gene. The approach, which is simple and robust, constitutes a general method for mapping signal transduction systems and for rapid isolation of a large number of signalling components based on the control of pathways leading to regulation of gene expression.


Assuntos
Clonagem Molecular/métodos , Interleucina-1/metabolismo , Transdução de Sinais/fisiologia , Receptores Toll-Like/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Interleucina-1/genética , Interleucina-8/genética , Interleucina-8/metabolismo , Receptores Toll-Like/genética
16.
Br J Ophthalmol ; 89(7): 812-4, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15965156

RESUMO

AIMS: To document loss of central field in patients with scars from toxoplasmic retinochoroiditis close to the disc after resolution of disease. METHODS: Patients with a clinical diagnosis of toxoplasmic retinochoroiditis were enrolled from four centres. Automated central visual field testing was performed when their disease had settled and retinal photographs of the lesions were taken. The type of central field defect (whether absolute or relative) and whether it broke out to the periphery were correlated with the size of the retinochoroidal scar and its proximity to the optic nerve head. RESULTS: 69 eyes were enrolled; 16 (26%) were discarded because of poor field performance. Of the 53 remaining eyes, 31 showed absolute defects and 20 relative defects. Scars within one disc diameter of the disc were more likely to be associated with absolute defects breaking out to the periphery. CONCLUSION: The scarring induced by toxoplasmic retinochoroiditis is associated with considerable field loss when it occurs close to the optic nerve head. Current treatment is unlikely to ameliorate this situation. The degree of visual field loss should be an outcome measure for future trials of the efficacy of treatment trials for the disease.


Assuntos
Coriorretinite/fisiopatologia , Toxoplasmose Ocular/fisiopatologia , Transtornos da Visão/fisiopatologia , Campos Visuais/fisiologia , Adolescente , Adulto , Idoso , Criança , Coriorretinite/complicações , Coriorretinite/patologia , Estudos Transversais , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Disco Óptico/patologia , Estudos Prospectivos , Escotoma/complicações , Escotoma/patologia , Escotoma/fisiopatologia , Toxoplasmose Ocular/complicações , Toxoplasmose Ocular/patologia , Transtornos da Visão/complicações , Transtornos da Visão/patologia , Testes Visuais , Acuidade Visual/fisiologia
17.
J Appl Microbiol ; 98(5): 1191-7, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15836489

RESUMO

AIMS: The aim of this work was to engineer a gut commensal bacterium, Bacteroidesovatus, to produce and secrete a biologically active cytokine in a regulated manner as a basis for novel immunotherapies for chronic gut disorders. METHODS AND RESULTS: Bacteroides ovatus was engineered to produce murine interleukin-2 (MuIL2) intracellularly in response to xylan in culture media by inserting the MuIL2 gene into the xylanase operon of the organism. A second strain was engineered to secrete MuIL2 by adding Bacteroides fragilis enterotoxin secretion signal sequence to the protein. The recombinant strains produced MuIL2 only in the presence of xylan as determined by ELISA of cell lysates and culture supernatants. The IL2-dependent cell line CTLL-2 was used to demonstrate that MuIL2 produced by both B. ovatus strains was biologically active. This activity could be blocked by an anti-IL2 neutralizing antibody. The xylan-inducible nature of this system was demonstrated by RT-PCR. CONCLUSIONS: Bacteroides ovatus was successfully engineered to produce and secrete biologically active MuIL2 in a xylan-inducible manner. SIGNIFICANCE AND IMPACT OF THE STUDY: The production and secretion of a biologically active mammalian protein by a member of the gut microflora could lead to the development of new long-term immunotherapies for inflammatory gut diseases.


Assuntos
Bacteroides/genética , Bacteroides/imunologia , Reatores Biológicos , Engenharia Genética , Interleucina-2/biossíntese , Xilanos/farmacologia , Animais , Linhagem Celular , Humanos , Imunoterapia , Interleucina-2/análise , Interleucina-2/genética , Enteropatias/terapia , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Philos Trans A Math Phys Eng Sci ; 362(1822): 1987-2001, 2004 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-15306426

RESUMO

Sediment transport in oscillatory boundary layers is a process that drives coastal geomorphological change. Most formulae for bed-load transport in nearshore regions subsume the smallest-scale physics of the phenomena by parametrizing interactions amongst particles. In contrast, we directly simulate granular physics in the wave-bottom boundary layer using a discrete-element model comprised of a three-dimensional particle phase coupled to a one-dimensional fluid phase via Newton's third law through forces of buoyancy, drag and added mass. The particulate sediment phase is modelled using discrete particles formed to approximate natural grains by overlapping two spheres. Both the size of each sphere and the degree of overlap can be varied for these composite particles to generate a range of non-spherical grains. Simulations of particles having a range of shapes showed that the critical angle--the angle at which a grain pile will fail when tilted slowly from rest--increases from approximately 26 degrees for spherical particles to nearly 39 degrees for highly non-spherical composite particles having a dumbbell shape. Simulations of oscillatory sheet flow were conducted using composite particles with an angle of repose of approximately 33 degrees and a Corey shape factor greater than about 0.8, similar to the properties of beach sand. The results from the sheet-flow simulations with composite particles agreed more closely with laboratory measurements than similar simulations conducted using spherical particles. The findings suggest that particle shape may be an important factor for determining bed-load flux, particularly for larger bed slopes.


Assuntos
Modelos Teóricos , Disciplinas das Ciências Naturais/métodos , Oscilometria , Física/métodos , Movimentos da Água , Algoritmos , Cinética , Modelos Estatísticos , Fatores de Tempo
19.
J Eur Acad Dermatol Venereol ; 18(4): 450-4, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15196160

RESUMO

BACKGROUND: Propionibacterium acnes is primarily associated with the pathogenesis of acne vulgaris but reports are increasing in number implicating P. acnes in other diseases such as abscess formation, meningitis and endocarditis. The pathogenicity of P. acnes is thought to be partly due to the interaction of the bacterium with the immune system. Historically, investigations have focused on humoral and cell-mediated immune responses to P. acnes antigens without attention to the possibility that different antigens may be expressed by different isolates. OBJECTIVE: Investigations were performed to determine whether there were differences between a laboratory strain of P. acnes (P-37) and fresh clinical isolates in their ability to stimulate naive and adult lymphocytes. MATERIAL AND METHODS: The fresh isolates were collected from a patient with inflammatory acne and a patient with P. acnes-induced prosthetic valve endocarditis. The lymphocyte transformation assay was used to detect responses to whole-cell suspensions of stationary phase P. acnes isolates during 7 days of incubation. RESULTS: The acne isolate was significantly more stimulatory for cord blood mononuclear cells (CBMNCs) than the laboratory isolate (P. acnes P-37) at day 4 of incubation. There were no significant differences between the three strains at any other time points. However, the isolate cultivated from inflammatory acne was significantly more stimulatory for peripheral blood mononuclear cells (PBMNCs) from acne donors than the endocarditis isolate or the laboratory strain at most time points. There were no significant differences between the endocarditis strain and the laboratory strain. CONCLUSION: It can be hypothesized that in case of P. acnes-induced endocarditis lymphocyte stimulation is a disadvantage for the microorganism and therefore a lack of lymphocyte stimulation may be relevant to the pathogenesis of endocarditis.


Assuntos
Acne Vulgar/microbiologia , Endocardite Bacteriana/microbiologia , Ativação Linfocitária , Propionibacterium acnes/imunologia , Adulto , Feminino , Sangue Fetal , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Propionibacterium acnes/isolamento & purificação
20.
Lett Appl Microbiol ; 38(6): 470-5, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15130141

RESUMO

AIMS: A wide range of lipids are present on the skin surface of human beings and bacterial lipases are known to modify them. The microflora of the underarm (axilla) is often dominated by aerobic coryneforms and whilst many require lipids for growth, they appear not to be utilized as carbon sources. The aim of this study was to investigate the adherence aerobic coryneforms to lipids present on the skin surface of the human axilla to determine whether they contribute to colonization of the skin. METHODS: Aerobic coryneforms were grown in a defined synthetic medium in the presence of (14)C-glucose to produce radio-labelled cells. Adherence to lipids was tested using a thin layer chromatography plate-based assay. SIGNIFICANCE AND IMPACT OF THE STUDY: The mechanism of bacterial adhesion to skin lipids is unknown. The results of this study show that a significant proportion of cutaneous aerobic coryneform isolates from the axilla interact with skin lipids resulting in increased adherence, which may contribute to skin colonization.


Assuntos
Actinomycetales/fisiologia , Axila/microbiologia , Bactérias Aeróbias/fisiologia , Aderência Bacteriana/fisiologia , Metabolismo dos Lipídeos , Pele/química , Actinomycetales/isolamento & purificação , Bactérias Aeróbias/isolamento & purificação , Isótopos de Carbono/metabolismo , Colesterol/metabolismo , Ésteres do Colesterol/metabolismo , Diglicerídeos/metabolismo , Glicerídeos/metabolismo , Ácido Linoleico/metabolismo , Ácido Oleico/metabolismo , Pele/microbiologia , Esqualeno/metabolismo , Ácidos Esteáricos/metabolismo , Triglicerídeos/metabolismo , Trioleína/metabolismo
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