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BACKGROUND: World falls guidelines recommend that hospitalised older patients receive individualised falls prevention education, yet no studies have sought older people's feedback on how best to deliver falls prevention education in hospitals. The objective of the study was to explore the perspectives of older people and their caregivers about barriers and enablers to implementation of a tailored hospital falls education program. METHODS: A qualitative descriptive design was used. Three focus groups and 16 semi-structured interviews were conducted. A purposive sample of older people who had previous hospital admissions and caregivers of older people were selected to review a co-designed patient falls education program (the revised Safe Recovery program). They provided feedback on how to implement the program in hospital settings. Data were thematically analysed taking an deductive-inductive approach. RESULTS: Participants were 37 older people [female n = 24 (64.9%), age range 64 to 89 years] and nine caregivers (female n = 8). The first theme was that the Safe Recovery Program resources were of high quality, enabling strong patient engagement and increased knowledge and awareness about falls prevention in hospitals. The second theme identified practical strategies to enable program delivery in hospital wards. The key enablers identified were: timing of delivery around wellness and the patient's mobility; tailoring messages for each older patient; key staff members being assigned to lead program delivery. Participants recommended that staff assist older patients to set appropriate behavioural goals in relation to preventing falls in hospitals. They also recommended that staff raise older patients' confidence and motivation to take action to reduce the risk of falls. Providing resources in other languages and alternative shorter versions was recommended to enable broad dissemination. CONCLUSIONS: Older people and their caregivers advised that implementing falls education in hospitals can be enabled by using high quality resources, delivering falls education in a timely manner and personalising the education and support to individual needs.
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BACKGROUND: There is an increasing focus on the development of research capacity and culture in Nursing, Midwifery and Allied Health Professions (NMAHP). However, better understanding of the existing research success and skills, motivators, barriers, and development needs of NMAHP professionals is required to inform this development. This study sought to identify such factors within a university and an acute healthcare organisation. METHODS: An online survey, incorporating the Research Capacity and Culture tool, was administered to NMAHP professionals and students at a university and an acute healthcare organisation in the United Kingdom. Ratings of success/skill levels of teams and individuals were compared between professional groups using Mann-Whitney U tests. Motivators, barriers, and development needs were reported using descriptive statistics. Descriptive thematic analysis was used for open-ended text responses. RESULTS: A total of 416 responses were received (N&M n = 223, AHP n = 133, Other n = 60). N&M respondents were more positive than their AHP counterparts about the success/skill levels of their teams. There were no significant differences between N&M and AHP in their ratings of individual successes/skills. Finding and critically reviewing relevant literature were identified as specific individual strengths; with weaknesses in securing research funding, submitting ethics applications, writing for publication, and advising less experienced researchers. The main motivators for research were to develop skills, increased job satisfaction, and career advancement; whilst barriers included lack of time for research and other work roles taking priority. Key support needs identified included mentorship (for teams and individuals) and in-service training. Open-ended questions generated main themes of 'Employment & staffing', 'Professional services support', 'Clinical & academic management', 'Training & development', 'Partnerships' and 'Operating principles'. Two cross-cutting themes described issues common to multiple main themes: 'Adequate working time for research' and 'Participating in research as an individual learning journey'. CONCLUSIONS: Rich information was generated to inform the development of strategies to enhance research capacity and culture in NMAHP. Much of this can be generic but some nuances may be required to address some specific differences between professional groups, particularly related to perceived team success/skills and priorities identified for support and development.
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Tocologia , Gravidez , Humanos , Feminino , Universidades , Pessoal Técnico de Saúde , Inquéritos e Questionários , Atenção à SaúdeRESUMO
Improving equity in women's health requires gender-specific and empowering approaches. However, health programs often disempower women by adopting a 'one-size-fits-all' approach that emphasizes diet, exercise and weight loss over other important aspects like sleep and mental wellbeing. This article reports on the design of Next Level Health (NLH), a program that aims to empower women through developing a wide range of health behaviors to support their holistic wellbeing. NLH is grounded by ethics, theory and evidence to support women to make achievable, sustainable changes that are relevant to their everyday lives. Women utilized the NLH framework to develop an integrative health routine across six domains: physical activity, sleep, nutrition, eating behavior, self-care and stress management. The framework guided them to set small, incremental goals that were adaptive to their needs and built from their existing circumstances. Participants reflected on their progress with a facilitator during monthly meetings, accessed a social media support page and received monthly text messages. Health programs remain an essential approach to improving women's health alongside community- and policy-level strategies. The development of NLH exemplifies how evidence may partner with modern health promotion values to inform relevant and ethical program design for women.
In western societies, health programs often focus on weight loss through exercise and diet to promote women's health. Such approaches disempower women by undervaluing important factors affecting their health like stress and sleep and narrow their scope for 'health success'. This article reports on the development of Next Level Health (NLH) that aims to help women gain greater health-related control by broadening their approach to health. The program is designed to support women to set small, achievable goals across six domains (physical activity, sleep, nutrition, eating behavior, self-care, and stress management) toward developing positive and sustainable health behaviors. Although women work with a facilitator each month to set goals, they are ultimately in control of formulating their health plans and their progression through NLH. Women can support each other by joining a community of other NLH participants through a social media group. NLH offers a novel program that is responsive to women's individual health needs and broadens their potential for health success.
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Nível de Saúde , Saúde Holística , Feminino , Humanos , Nova Zelândia , Saúde da Mulher , Promoção da SaúdeRESUMO
Vitamin D deficiency has adverse health effects in young children. Our aims were to determine predictors of vitamin D status and then to use these factors to develop a practical tool to predict low 25(OH)D concentrations in preschool New Zealand children. A cross-sectional sample of 1329 children aged 2 to <5 years were enrolled from throughout New Zealand in late-winter to spring 2012. 25-Hydroxyvitamin D (25(OH)D) was measured on dried blood spot (DBS) samples collected using finger-prick sampling. Caregivers completed a questionnaire. Mean (SD) DBS 25(OH)D concentration was 52(19)nmol/L. 25(OH)D < 25 nmol/L was present in 86(7%), 25(OH)D < 50 nmol/L in 642(48%), 25(OH)D 50- < 75 nmol/L in 541(41%) and 25(OH)D > 75 nmol/L in 146(11%) of children. Factors independently associated with the risk of 25(OH)D < 25 nmol/L were female gender (OR 1.92,95%CI 1.17-3.14), other non-European ethnicities (not including Maori or Pacific) (3.51,1.89-6.50), had olive-dark skin colour (4.52,2.22-9.16), did not take vitamin D supplements (2.56,1.06-6.18), had mothers with less than secondary-school qualifications (5.00,2.44-10.21) and lived in more deprived households (1.27,1.06-1.53). Children who drank toddler milk (vitamin D fortified cow's milk formula marketed to young children) had a zero risk of 25(OH)D < 25 nmol/L. The predictive tool identified children at risk of 25(OH)D < 25 nmol/L with sensitivity 42%, specificity 97% and ROC area-under-curve 0.76(95%CI 0.67-0.86, p < 0.001). Predictors of low vitamin D status were consistent with those identified in previous studies of New Zealand children. The tool had insufficient predictive ability for use in clinical situations, and suggests a need to promote safe, inexpensive testing to determine vitamin D status in preschool children.
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Alimentos Fortificados , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/administração & dosagem , Vitamina D/sangue , Animais , Pré-Escolar , Estudos Transversais , Suplementos Nutricionais , Feminino , Humanos , Masculino , Leite/química , Nova Zelândia/epidemiologia , Estado Nutricional , Instituições Acadêmicas , Estações do Ano , Pigmentação da PeleRESUMO
BACKGROUND: In the last number of years heightened interest has been attributed to the impact of hospital environments on children's psychosocial well-being. With policy largely built around adult assumptions, knowledge about what constitutes a child-friendly hospital environment from young children's perspectives has been lacking. If hospital environments are to aspire to being child friendly then the views of younger aged children must be taken into account. The current study investigated young children's perspectives of hospital social spaces to inform the design of the built environment of a new children's hospital. METHODS: An exploratory qualitative participatory design was employed. Data were collected through semi-structured interviews (one-to-one and group workshops) which incorporated art-based activities to actively engage young children. Fifty-five young children aged 5 to 8 years with various acute and chronic illnesses were recruited from inpatient, outpatient and emergency departments of three children's hospitals. RESULTS: Young children want a diversity of readily available, independently accessible, age, gender and developmentally appropriate leisure and entertainment facilities seamlessly integrated throughout the hospital environment. Such activities were invaluable for creating a positive hospital experience for children by combating boredom, enriching choice and control and reducing a sense of isolation through enhanced socialization. When in hospital, young children want to feel socially connected to the internal hospital community as well as to the outside world. Technology can assist to broaden the spectrum of children's social connectivity when in hospital - to home, school and the wider outside world. CONCLUSION: While technology offers many opportunities to support children's psychosocial well-being when in confined healthcare spaces, the implementation and operation of such services and systems require much further research in the areas of ethics, facilitation, organizational impact and evaluation.
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Ansiedade/prevenção & controle , Criança Hospitalizada , Arquitetura Hospitalar , Hospitais Pediátricos , Meio Social , Criança , Criança Hospitalizada/psicologia , Pré-Escolar , Feminino , Humanos , Decoração de Interiores e Mobiliário , Masculino , Inovação Organizacional , Jogos e Brinquedos , Formulação de Políticas , Pesquisa Qualitativa , Qualidade de VidaRESUMO
AIMS: The aim of the current study was to gain an understanding of the experiences and aspirations of young people living with Developmental Coordination Disorder (DCD) in their own words. METHODS: Eleven young people aged 11-16 years with a prior diagnosis of DCD were identified from child health records of two participating NHS trusts. The sample included seven boys and four girls, from different socio-economic backgrounds living in different parts of one large urban area in England. In depth one-to-one semi-structured interviews and subsequent follow-up small group interviews were carried out with the young people. Interviews were enhanced using participatory arts-based techniques. All interviews were recorded verbatim and transcribed. Narrative data were analysed using Lindseth's interpretive phenomenology. RESULTS: The central theme of 'We're all different' described how the young person saw themselves and encompassed the formation of identity. Subthemes illustrated the attitude of the young people to their day to day lives, their difficulties and strategies used by the young people to overcome these difficulties in school and at home. The attitude of the school to difference, the presence of bullying, the accepting nature of the class, teachers and peers were vitally important. Areas of life that encouraged a positive sense of identity and worth included being part of a social network that gave the young people a sense of belonging, potentially one that valued differences as well as similarities. CONCLUSION: The current work highlights the need for services to adopt a model of DCD where the young person talks about what they can do and considers strategies of overcoming their difficulties. This has implications for education and future intervention strategies that focus on fostering psychological resilience and educational coping strategies rather than simply attempting to improve motor skills.
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Transtornos das Habilidades Motoras/psicologia , Poder Psicológico , Autoimagem , Identificação Social , Adaptação Psicológica , Adolescente , Atitude Frente a Saúde , Criança , Feminino , Humanos , Relações Interpessoais , Entrevista Psicológica , Masculino , Transtornos das Habilidades Motoras/reabilitação , Instituições Acadêmicas , Apoio SocialRESUMO
Understanding the reproductive and fertility concerns of teenagers and young adults with cancer (TYA) is one aspect of comprehensive age appropriate care. However, limited options for fertility preservation, coupled with vague policy recommendations, give rise to variations in information-sharing between health care professionals and TYAs, particularly as it involves sensitive discussions regarding the short- and long-term effects of cancer and treatments on fertility and reproduction. This paper presents findings from a wider evaluation at a specialist unit for TYAs with cancer. Forty people participated in semi-structured interviews, including 20 young people, parents and partners. Young people were between 2 months and 4 years from finishing treatment. Most young people received mixed levels of information on fertility and counselling before treatment. Diagnosis in the early teens meant how, and from whom, young people received information varied. Young women tended to receive incomplete information. The majority of young people were unaware of their fertility status after treatment had finished. Findings point to the inherent challenges that exist in ensuring young people aged between 13 and 25 years receive comprehensive information on their fertility and potential risk, as well as advice on how to determine their fertility status after treatment has finished.
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Antineoplásicos/efeitos adversos , Revelação , Necessidades e Demandas de Serviços de Saúde , Infertilidade/etiologia , Neoplasias/terapia , Pais , Educação de Pacientes como Assunto , Radioterapia/efeitos adversos , Adolescente , Adulto , Criança , Feminino , Preservação da Fertilidade , Humanos , Masculino , Pesquisa Qualitativa , Adulto JovemRESUMO
BACKGROUND: Few studies exist reporting the experiences of parents of children with developmental co-ordination disorder (DCD) a common disorder with a prevalence of 1.8-6%. DCD is characterized by poor motor co-ordination, not caused by a general medical condition, but significantly affecting daily living. This study explores the experiences of parents living with a child with DCD in obtaining a diagnosis; the impact of the diagnosis on parenting and the effect on parents as individuals. METHODS: Semi-structured interviews with a purposive sample of 15 parents of children with DCD data were recorded and then transcribed. Data were analysed using a coding framework and themes identified similar to Attride-Stirling (2001, Qualitative Research, 1, 385-405). FINDINGS: DCD was an all-encompassing condition that dominated all aspects of family life and was a 'hidden disability'. Parents were frustrated by the poor knowledge and expertise of health and education professionals working with children with DCD and the lack of good quality accessible information and support services. Parents became by default the 'expert' on DCD for schools and other services; they were advocates for DCD and their own children. They provided additional support for longer to their child with DCD and had concerns for their future. Parenting a child with DCD was frustrating, exhausting, guilt-ridden as well as rewarding. There was little available time to provide for the needs of other family members. CONCLUSION: A better-trained, knowledgeable workforce would redress the balance for families with DCD by providing better information, support and advocacy freeing parents to parent their families.
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Crianças com Deficiência/psicologia , Transtornos das Habilidades Motoras/psicologia , Relações Pais-Filho , Pais/psicologia , Atividades Cotidianas , Adaptação Psicológica , Adolescente , Criança , Feminino , Humanos , Masculino , Transtornos das Habilidades Motoras/diagnóstico , Transtornos das Habilidades Motoras/epidemiologia , Psicometria , Apoio Social , Estresse Psicológico , Reino Unido/epidemiologiaRESUMO
There is a lack of evidence that improving vitamin D status, without changing calcium intake, has a positive effect on bone turnover as indicated by bone marker changes. The objective was to measure the effect of vitamin D supplementation, in vitamin D deficient women (25(OH)D concentration<50 nmol/L), on osteocalcin (OC) and C-telopeptide (CTX). The study design was a randomised controlled intervention administering 4000 IU vitamin D3 or placebo daily for 6 months to South Asian women, aged>20 years. Subjects were stratified by age and menopausal status. Median (25th, 75th percentile) serum 25(OH)D increased significantly from 21 (11, 40) to 75 (55, 84) nmol/L with supplementation. In women>49 years or postmenopausal (n=26), who were not supplemented (n=13), CTX and OC levels increased (P=0.001, P=0.004 respectively), indicating an increased rate of bone turnover. With supplementation CTX decreased (P=0.012) and there was no significant change in OC. In women who were under 49 years and premenopausal (n=55; 29 supplemented), there was no significant response to supplementation in either CTX or OC. We conclude that correcting vitamin D deficiency in older women suppresses the age-induced increase in bone turnover and reduces bone resorption which would normally be exacerbated in conditions of low serum 25(OH)D.
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Envelhecimento , Suplementos Nutricionais , Deficiência de Vitamina D/metabolismo , Vitamina D/uso terapêutico , Adulto , Densidade Óssea , Reabsorção Óssea , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Colágeno Tipo I/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Osteocalcina/metabolismo , Osteoclastos/efeitos dos fármacos , Peptídeos/metabolismoRESUMO
The impact of edge localized modes (ELMs) carrying energies of up to 450 kJ on carbon erosion in the JET inner divertor is assessed by means of time resolved measurements using an in situ quartz microbalance diagnostic. The inner target erosion is strongly nonlinearly dependent on the ELM energy: a single 400 kJ ELM produces the same carbon erosion as ten 150 kJ events. The ELM-induced enhanced erosion is attributed to the presence of codeposited carbon-deuterium layers on the inner divertor target, which are thermally decomposed under the impact of ELMs.
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AIMS: To determine whether Src homology phosphotyrosyl phosphatase 2 (SHP2) is up-regulated in breast cancer and, if so, to determine whether its up-regulation has any relationship with clinical variables of breast cancer. METHODS AND RESULTS: Immunoblotting, immunohistochemistry and immunofluorescence microscopy were used to assess the state of SHP2 expression in breast cancer cells and in infiltrating ductal carcinoma (IDC) of breast. The possible role of SHP2 in breast cancer cell transformation was determined by dominant-negative expression and anchorage-independent growth assays. All of the breast cancer cell lines tested and 72% of IDC breast tumours analysed had increased amounts of the SHP2 protein. In support of its positive role, dominant-negative SHP2 blocked anchorage-independent growth of breast cancer cells. Furthermore, overexpression of SHP2 seemed to have a positive relationship to HER2 overexpression, nuclear accumulation of hormone receptors, higher tumour grade and lymph node metastasis, but not to age of breast cancer patients. CONCLUSION: SHP2 is a widely overexpressed signalling protein in IDC breast tumours. Given SHP2's positive role in cell growth, transformation and stem cell survival, the positive relationship of its overexpression to lymph node metastasis, nuclear accumulation of hormone receptors and higher tumour grade suggests that SHP2 promotes breast oncogenesis.
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Neoplasias da Mama/enzimologia , Carcinoma Ductal de Mama/enzimologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Regulação para Cima , Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Feminino , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Invasividade Neoplásica/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Células Tumorais CultivadasRESUMO
Family members in multiple generations of an Irish-American family were investigated for moderate to severe microcytic anaemia, inherited in an autosomal dominant fashion. A novel frameshift mutation of the beta globin gene was discovered. This study highlights the importance of considering dominantly inherited beta thalassemia in the investigation of anaemia, even in patients with ethnic backgrounds not usually associated with beta thalassaemia.
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Mutação da Fase de Leitura , Globinas/genética , Talassemia beta/genética , Adulto , Anemia/etiologia , Anemia/genética , Sequência de Bases , Pré-Escolar , Feminino , Genes Dominantes , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Talassemia beta/sangue , Talassemia beta/complicaçõesRESUMO
Beta-elemene is a novel anticancer drug, which was extracted from the ginger plant. However, the mechanism of action of beta-elemene in non-small-cell lung cancer (NSCLC) remains unknown. Here we show that beta-elemene had differential inhibitory effects on cell growth between NSCLC cell lines and lung fibroblast and bronchial epithelial cell lines. In addition, beta-elemene was found to arrest NSCLC cells at G2-M phase, the arrest being accompanied by decreases in the levels of cyclin B1 and phospho-Cdc2 (Thr-161) and increases in the levels of p27(kip1) and phospho-Cdc2 (Tyr-15). Moreover, beta-elemene reduced the expression of Cdc25C, which dephosphorylates/activates Cdc2, but enhanced the expression of the checkpoint kinase, Chk2, which phosphorylates/ inactivates Cdc25C. These findings suggest that the effect of beta-elemene on G2-M arrest in NSCLC cells is mediated partly by a Chk2-dependent mechanism. We also demonstrate that beta-elemene triggered apoptosis in NSCLC cells. Our results clearly show that beta-elemene induced caspase-3, -7 and -9 activities, decreased Bcl-2 expression, caused cytochrome c release and increased the levels of cleaved caspase-9 and poly(ADP-ribose) polymerase in NSCLC cells. These data indicate that the effect of beta-elemene on lung cancer cell death may be through a mitochondrial release of the cytochrome c-mediated apoptotic pathway.
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Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Sesquiterpenos/farmacologia , Apoptose/efeitos dos fármacos , Proteína Quinase CDC2/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Caspases/metabolismo , Ciclo Celular/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quinase do Ponto de Checagem 2 , Inibidor de Quinase Dependente de Ciclina p27 , Citocromos c/metabolismo , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes bcl-2/fisiologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Poli(ADP-Ribose) Polimerases/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Fosfatases cdc25/metabolismoRESUMO
Minimally invasive microwave thermal therapies are being developed for the treatment of small renal cell carcinomas (RCC, d<3 cm). This study assessed the thermal history and corresponding tissue injury patterns resulting from microwave treatment of the porcine renal cortex. Three groups of kidneys were evaluated: (1) in vitro treated, (2) in vivo with 2-h post-treatment perfusion (acute) and (3) in vivo with 7-day post-treatment perfusion (chronic). The kidneys were treated with an interstitial water-cooled microwave probe (Urologix, Plymouth, MN) that created a lesion centered in the renal cortex (50 W for 10 min). The thermal histories were recorded at 0.5 cm radial intervals from the probe axis for correlation with the histologic cellular and vascular injury. The kidneys showed a reproducible 2 cm chronic lesion with distinct histologic injury zones identified. The thermal histories at the edge of these zones were found using Lagrangian interpolation. The threshold thermal histories for microvascular injury and stasis appeared to be lower than that for renal epithelial cell injury. The Arrhenius kinetic injury models were fit to the thermal histories and injury data to determine the kinetic parameters (i.e. activation energy and frequency factor) for the thermal injury processes. The resultant activation energies are consistent in magnitude with those for thermally induced protein denaturation. A 3-D finite element thermal model based on the Pennes bioheat equation was developed and solved using ANSYS (V7.0). The real geometry of the kidneys studied and temperature dependent thermal properties were used in this model. The specific absorption rate (SAR) of the microwave probe required for the thermal modelling was experimentally determined. The results from the thermal modelling suggest that the complicated change of local renal blood perfusion with temperature and time during microwave thermal therapy can be predicted, although a first order kinetic model may be insufficient to capture blood flow changes. The local blood perfusion was found to be a complicated function of temperature and time. A non-linear model based on the degree of vascular stasis was introduced to predict the blood perfusion. In conclusion, interstitial microwave thermal therapy in the normal porcine kidney results in predictable thermal and tissue injury behaviour. Future work in human kidney tissue will be necessary to confirm the clinical significance of these results.
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Rim/efeitos da radiação , Micro-Ondas/uso terapêutico , Algoritmos , Animais , Temperatura Corporal , Carcinoma de Células Renais/terapia , Simulação por Computador , Temperatura Alta/efeitos adversos , Temperatura Alta/uso terapêutico , Hipertermia Induzida/instrumentação , Hipertermia Induzida/métodos , Rim/lesões , Rim/patologia , Córtex Renal/lesões , Córtex Renal/patologia , Córtex Renal/efeitos da radiação , Cinética , Microcirculação/efeitos da radiação , Micro-Ondas/efeitos adversos , Modelos Animais , Modelos Biológicos , Necrose/etiologia , Circulação Renal/fisiologia , Suínos , TermodinâmicaRESUMO
The successful management of BPH with minimally invasive thermal therapies requires a firm understanding of the temperature-time relationship for tissue destruction. In order to accomplish this objective, the present in vitro study assesses the cellular viability of human BPH tissue subjected to an experimental matrix of different temperature-time combinations. Hyperplastic prostate tissue was obtained from 10 radical prostatectomy specimens resected for adenocarcinoma. A portion of hyperplastic tissue from the lateral lobe of each prostate was sectioned into multiple 1 mm thick tissue strips, placed on a coverslip and thermally treated on a controlled temperature copper block with various temperatures (45-70 degrees C) for various times (1-60 min). After heat treatment, the tissue slices were cultured for 72 h and viability was assessed using two independent assays: histology and dye uptake for stromal tissue and using histology alone for the glandular tissue. The hyperplastic human prostate tissue showed a progressive histological increase in irreversible injury with increasing temperature-time severity. The dye uptake and histology results for stromal viability were similar for all temperature-time combinations. In vitro thermal injury showed 85-90% stromal destruction (raw data) of human BPH for temperature-time combinations of 45 degrees C for 60 min, 50 degrees C for 30 min, 55 degrees C for 5 min, 60 degrees C for 2 min and 70 degrees C for 1 min. Apoptosis was also identified in the control and milder treated tissues with the degree of glandular apoptosis (about 20%) more than that seen in the stromal regions (< 5%). The Arrhenius model of injury was fitted to the data for conditions leading to a 90% drop in viability (normalized to control) obtained for stromal tissue. The activation energies (E) were 40.1 and 38.4 kcal/mole for the dye uptake study and histology, respectively, and the corresponding frequency factors (A) were 1.1 x 10(24) and 7.78 x 10(22)/s. This study presents the first temperature-time versus tissue destruction relation for human BPH tissue. Moreover, it supports the concept that higher temperatures can be used for shorter durations to induce tissue injury comparable with the current clinically recommended lower temperature-longer time treatments (i.e. 45 degrees C for 60 min) for transurethral microwave thermotherapy of the prostate.
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Temperatura Alta , Hipertermia Induzida/métodos , Hiperplasia Prostática/terapia , Resultado do Tratamento , Benzimidazóis , Sobrevivência Celular , Etídio/análogos & derivados , Corantes Fluorescentes , Previsões , Humanos , Masculino , Microscopia de Fluorescência , Modelos Biológicos , Próstata/patologia , Hiperplasia Prostática/patologia , Células Estromais/patologia , Fatores de Tempo , Técnicas de Cultura de TecidosRESUMO
To advance the utility of prostate thermal therapy, this study investigated the thermal thresholds (temperature-time) for prostate tissue destruction in vitro. The AT-1 Dunning prostate tumour model was chosen for the study. Three hundred micron thick sections were subjected to controlled temperature-time heating, which ranged from low (40 degrees C, 15 min) to high thermal exposures (70 degrees C, 2 min) (n = 6). After subsequent tissue culture at 37 degrees C, the sections were evaluated for tissue injury at 3, 24 and 72 h by two independent methods: histology and dye uptake. A graded increase in injury was identified between the low and high thermal exposures. Maximum histologic injury occurred above 70 degrees C, 1 min with >95% of the tissue area undergoing significant cell injury and coagulative necrosis. The control and 40 degrees C, 15 min sections showed histologic evidence of apoptosis following 24 and 72 h in culture. Similar signs of apoptosis were minimal or absent at higher thermal histories. Vital-dye uptake quantitatively confirmed complete cell death after 70 degrees C, 2 min. Using the dye data, Arrhenius analysis showed an apparent breakpoint at 50 degrees C, with activation energies of 135.8 kcal/mole below and 4.7 kcal/mole above the threshold after 3 h in culture. These results can be used as a conservative benchmark for thermal injury in the cancerous prostate. Further characterization of the response to thermal therapy in an animal model and in human tissues will be important in establishing the efficacy of the procedure