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1.
Anaesthesia ; 74(6): 758-764, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30793278

RESUMO

Demand for critical care among older patients is increasing in many countries. Assessment of frailty may inform discussions and decision making, but acute illness and reliance on proxies for history-taking pose particular challenges in patients who are critically ill. Our aim was to investigate the inter-rater reliability of the Clinical Frailty Scale for assessing frailty in patients admitted to critical care. We conducted a prospective, multi-centre study comparing assessments of frailty by staff from medical, nursing and physiotherapy backgrounds. Each assessment was made independently by two assessors after review of clinical notes and interview with an individual who maintained close contact with the patient. Frailty was defined as a Clinical Frailty Scale rating > 4. We made 202 assessments in 101 patients (median (IQR [range]) age 69 (65-75 [60-80]) years, median (IQR [range]) Acute Physiology and Chronic Health Evaluation II score 19 (15-23 [7-33])). Fifty-two (51%) of the included patients were able to participate in the interview; 35 patients (35%) were considered frail. Linear weighted kappa was 0.74 (95%CI 0.67-0.80) indicating a good level of agreement between assessors. However, frailty rating differed by at least one category in 47 (47%) cases. Factors independently associated with higher frailty ratings were: female sex; higher Acute Physiology and Chronic Health Evaluation II score; higher category of pre-hospital dependence; and the assessor having a medical background. We identified a good level of agreement in frailty assessment using the Clinical Frailty Scale, supporting its use in clinical care, but identified factors independently associated with higher ratings which could indicate personal bias.


Assuntos
Cuidados Críticos/métodos , Fragilidade/diagnóstico , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Escócia , Índice de Gravidade de Doença , País de Gales
2.
J Pediatr Urol ; 15(1): 18-26, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30602417

RESUMO

INTRODUCTION: Robert Whitaker, inspired by Dr William W Scott at the Brady Institute at Johns Hopkins and by Sir David Innes Williams at Great Ormond Street Hospital for Children in the late 1960s, spent much of his career exploring the meaning of persistent dilatation of the upper urinary tract, in an attempt to define obstruction and to find a means of diagnosing it accurately. OBJECTIVE: This is a historical review of Bob Whitaker's journey from his definition of obstruction to the inception of his eponymous test. RESULTS: In 1975, he proposed a theory to explain the pathophysiology behind obstructive hydronephrosis and megaureter. He was among the first pediatric urologists to observe that 'it is wrong… to assume that dilatation necessarily indicates obstruction', a statement that was widely stated and even appeared in the textbooks at the time. He defined obstruction as 'an increased pressure in the pelvicalyceal system of the kidney at normal physiological flow rates such that the renal function is adversely affected'. This realization led to the development of a percutaneous pressure-measuring technique at controlled flows, later referred to as the Whitaker test. It predated and later assisted in the interpretation of diuretic renograms. DISCUSSION: Whitaker questioned the etiology of 'hydronephrosis' and challenged other hypotheses proposed at the time, which often included causes of mechanical occlusion at the ureteropelvic junction (UPJ) or ureterovesical junction (UVJ). Whitaker's hypothesis is that 'obstruction' at UPJ and UVJ levels is not mechanical but the result of a failure of normal peristalsis to form and propagate a bolus. This, in turn, depends on the potentially abnormal distensibility of the renal pelvic and ureteric wall whether it be congenital or acquired. The aim of this review is to recall the history of the development of a technique to evaluate dilated upper urinary tracts and to re-evaluate various theories that might explain the etiology of the dilatation in the light of more recent evidence. Robert (or Bob, to his colleagues) Whitaker was among the founder members of the British Association of Paediatric Urologists, which now has more than 50 members, in 1992. Together with his colleagues Philip Ransley and David Thomas, Whitaker established the annual pediatric urology course for pediatric surgery and urology trainees in Cambridge, U.K., which still runs to this day. He retired from his surgical practice in 1990 and up until the present time has taught clinical anatomy in the Cambridge University School of Medicine.


Assuntos
Terminologia como Assunto , Obstrução Ureteral/diagnóstico , Obstrução Ureteral/etiologia , Criança , Técnicas de Diagnóstico Urológico , Humanos
4.
Int J Obes (Lond) ; 41(10): 1459-1466, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28435162

RESUMO

OBJECTIVE: To examine, in a population-based cohort of 3-year-old children, the association between self-regulation and exposure to the household routines of regular bedtime, regular mealtime and limits on watching television/video, and to determine whether self-regulation and these routines predict the risk of obesity at age 11. METHODS: Analyses included 10 955 children in the nationally representative UK Millennium Cohort Study. When children were age 3, parents reported whether children had a regular bedtime and mealtime, and the amount of television/video watched. Emotional and cognitive self-regulation at age 3 were assessed by parent-report with the Child Social Behaviour Questionnaire. Children's height and weight were measured at age 11 and obesity was defined using the International Obesity Task Force (IOTF) criteria. RESULTS: At age 3, 41% of children always had a regular bedtime, 47% always had a regular mealtime and 23% were limited to ⩽1 h television/video daily. At age 11, 6.2% of children were obese. All three household routines were significantly associated with better emotional self-regulation, but not better cognitive self-regulation. In a multi-variable logistic regression model, including emotional and cognitive self-regulation, all routines and controlling for sociodemographic covariates, a 1-unit difference in emotional self-regulation at age 3 was associated with an OR (95% CI) for obesity of 1.38 (1.11, 1.71) at age 11, and inconsistent bedtimes with an OR (95% CI) for obesity of 1.87 (1.39, 2.51) at age 11. There was no evidence that emotional self-regulation mediated the relationship between regular bedtimes and later obesity. Cognitive self-regulation was not associated with later obesity. CONCLUSIONS: Three-year-old children who had regular bedtimes, mealtimes and limits on their television/video time had better emotional self-regulation. Lack of a regular bedtime and poorer emotional self-regulation at age 3 were independent predictors of obesity at age 11.


Assuntos
Comportamento Infantil , Educação Infantil , Estilo de Vida , Pais , Obesidade Infantil/epidemiologia , Autocontrole , Criança , Pré-Escolar , Exercício Físico , Características da Família , Comportamento Alimentar , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pais/educação , Obesidade Infantil/etiologia , Prevalência , Estudos Prospectivos , Comportamento Sedentário , Sono , Comportamento Social , Televisão , Fatores de Tempo , Reino Unido/epidemiologia
6.
Appetite ; 84: 61-7, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25240637

RESUMO

Snacking has become more frequent among US preschool-aged children in recent decades and represents a significant proportion of daily energy intake. Social influences on snacking among children, however, are not well understood. This qualitative research described low-income, urban mothers' perceptions of feeding snacks to their preschool-aged children using data from 7 focus groups with 32 participants. Focus group transcripts were analyzed using a constant comparative method to identify themes. Mothers described snacks as involving less preparation, balance, and sustenance than meals (Theme 1). Mothers also made reference to some snacks as not being "real food" (Theme 2). At the same time, snacks had significant hedonic value as reflected in mothers' enjoyment of those foods (Theme 3), the effectiveness of snacks to manage children's behavior (Theme 4), and the variety of restrictions that mothers placed on children's access to snacks, such as locking cabinets, offering small servings, and reducing the number of snacks in sight (Theme 5). Two overarching themes highlighted distinctions mothers made in feeding children snacks vs. meals as well as the powerful hedonic appeal of snacks for both mother and child. These observations suggest that low-income, urban mothers of preschool-aged children may perceive snacks as serving a more important role in managing children's behavior than in providing nutrition. Child feeding interventions should address non-food related ways of managing children's behavior as well as encouraging caregivers to see snacks as structured opportunities for nutrition and connecting with their children.


Assuntos
Atitude , Dieta , Comportamento Alimentar , Relações Mãe-Filho , Mães , Pobreza , Lanches , Adulto , Criança , Educação Infantil , Pré-Escolar , Ingestão de Energia , Feminino , Grupos Focais , Preferências Alimentares , Humanos , Renda , Refeições , Obesidade/etiologia , Poder Familiar , Percepção , Pesquisa Qualitativa , Estados Unidos , População Urbana , Adulto Jovem
7.
Child Care Health Dev ; 41(1): 122-31, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24602099

RESUMO

BACKGROUND: Efforts to improve the academic skills of preschool-aged children have resulted in approaches that tend to limit children's movement. However, movement experiences have long been considered important to children's learning and have received increased attention because of the obesity epidemic. Early childhood educators are important sources of information about if and how to promote learning and school readiness through movement, but little effort has been made to understand teachers' views on this topic. METHODS: We conducted six focus groups with 37 teachers from a Head Start programme with centres in three cities in eastern Pennsylvania. We inquired about: (1) how movement influences children's learning; (2) what types of movement experiences are most beneficial for children; (3) what settings best support children's movement; and (4) challenges related to children's movement. To identify key themes from the focus groups, transcripts were analysed using an inductive method of coding. RESULTS: Teachers' views were expressed in four major themes. First, young children have an innate need to move, and teachers respond to this need by using movement experiences to prepare children to learn and to teach academic concepts and spatial awareness. However, teachers wanted more training in these areas. Second, movement prepares children for school and for life by building children's confidence and social skills. Third, teachers and children benefit from moving together because it motivates children and promotes teacher-child relationships. Finally, moving outdoors promotes learning by engaging children's senses and promoting community interaction. CONCLUSIONS: More training may be required to help early childhood educators use movement experiences to teach academic concepts and improve children's spatial awareness. Future interventions could examine the impacts on children's movement and learning of having teachers move with children during outdoor free play and including more natural features in the design of outdoor play areas.


Assuntos
Intervenção Educacional Precoce/métodos , Docentes , Aprendizagem/fisiologia , Movimento , Pré-Escolar , Intervenção Educacional Precoce/normas , Grupos Focais , Humanos , Pennsylvania , Percepção , Áreas de Pobreza , Recursos Humanos
9.
Nature ; 503(7475): 238-41, 2013 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-24196713

RESUMO

Most large (over a kilometre in diameter) near-Earth asteroids are now known, but recognition that airbursts (or fireballs resulting from nuclear-weapon-sized detonations of meteoroids in the atmosphere) have the potential to do greater damage than previously thought has shifted an increasing portion of the residual impact risk (the risk of impact from an unknown object) to smaller objects. Above the threshold size of impactor at which the atmosphere absorbs sufficient energy to prevent a ground impact, most of the damage is thought to be caused by the airburst shock wave, but owing to lack of observations this is uncertain. Here we report an analysis of the damage from the airburst of an asteroid about 19 metres (17 to 20 metres) in diameter southeast of Chelyabinsk, Russia, on 15 February 2013, estimated to have an energy equivalent of approximately 500 (±100) kilotons of trinitrotoluene (TNT, where 1 kiloton of TNT = 4.185×10(12) joules). We show that a widely referenced technique of estimating airburst damage does not reproduce the observations, and that the mathematical relations based on the effects of nuclear weapons--almost always used with this technique--overestimate blast damage. This suggests that earlier damage estimates near the threshold impactor size are too high. We performed a global survey of airbursts of a kiloton or more (including Chelyabinsk), and find that the number of impactors with diameters of tens of metres may be an order of magnitude higher than estimates based on other techniques. This suggests a non-equilibrium (if the population were in a long-term collisional steady state the size-frequency distribution would either follow a single power law or there must be a size-dependent bias in other surveys) in the near-Earth asteroid population for objects 10 to 50 metres in diameter, and shifts more of the residual impact risk to these sizes.

10.
Health Technol Assess ; 17(39): 1-170, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24034150

RESUMO

BACKGROUND: Endoscopic ultrasonography is recommended for staging gastro-oesophageal cancers, but has never been evaluated. OBJECTIVE: COGNATE (Cancer of Oesophagus or Gastricus - New Assessment of Technology of Endosonography) therefore aimed to evaluate whether adding 'endoscopic ultrasound' (EUS) to the usual staging algorithm changes treatment, improves (quality-adjusted) survival, and uses resources cost-effectively. DESIGN: Pragmatic parallel-group trial. Patients with gastro-oesophageal cancer received standard staging algorithms. Multidisciplinary teams chose provisional management plans from endoscopic mucosal resection, immediate surgery, surgery after chemotherapy, or chemotherapy and radiotherapy. We used dynamic randomisation to allocate consenting patients remotely by telephone in equal proportions between EUS and not. Thereafter we recorded changes in management plan, use of health-care resources, and three aspects of participant-reported quality of life: generic [measured by European Quality of Life - 5 Dimensions (EQ-5D)], cancer related [Functional Assessment of Cancer Therapy - General scale (FACT-G)] and condition-specific [FACT - Additional Concerns scale (FACT-AC)]. We followed participants regularly until death or the end of the trial - for between 1 and 4.5 years. We devised a quality assurance programme to maintain standards of endosonographic reporting. SETTING: Eight British hospitals, of which two - one Scottish teaching hospital and one English district general hospital - contributed 80% of participants; we combined the other six for analysis. PARTICIPANTS: Patients were eligible if they had a diagnosis of gastro-oesophageal cancer, had not started treatment, were free of metastatic disease, were fit for surgery (even if not planned) and had American Society of Anesthesiologists and World Health Organization grades of less than 3. INTERVENTIONS: Intervention group: standard staging algorithm plus EUS; control group: standard staging algorithm. MAIN OUTCOME MEASURES: Primary: quality-adjusted survival. Secondary: survival; health-related quality of life (EQ-5D, FACT-G and FACT-AC scales); changes in management plan; and complete resection rate. Although blinding participants was neither possible nor desirable, those responsible for analysis remained blind until the Trial Steering Committee had reviewed the definitive analysis. RESULTS: We randomised 223 patients, of whom 213 yielded enough data for primary analysis. EUS improved survival adjusted for generic quality of life with a hazard ratio of 0.705 [95% confidence interval (CI) 0.499 to 0.995], and crude survival with a hazard ratio of 0.706 (95% CI 0.501 to 0.996). The benefits of EUS were significantly greater for those with poor initial quality of life, but did not differ between centres. EUS reduced net use of health-care resources by £2860 (95% 'bootstrapped' CI from -£2200 to £8000). Combining benefits and savings shows that EUS is likely to be cost-effective, with 96% probability of achieving the National Institute for Health and Care Excellence criterion of costing of < £20,000 to gain a QALY. There were no serious adverse reactions attributable to EUS. EUS enhanced the management plan for many participants, increased the proportion of tumours completely resected from 80% (44 out of 55) to 91% (48 out of 53), and improved the survival of those who changed plan; although underpinning the significant differences in outcome, none of these process differences was itself significant. CONCLUSION: Endoscopic ultrasound significantly improves (quality-adjusted) survival, has the potential to reduce health-care resource use (not statistically significant) and is probably cost-effective (with 96% probability). We recommend research into the best time to evaluate new technologies. TRIAL REGISTRATION: ISRCTN1444215. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 39. See the HTA programme website for further project information.


Assuntos
Endossonografia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Gastrointestinais/diagnóstico por imagem , Avaliação da Tecnologia Biomédica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Custo-Benefício , Endossonografia/economia , Inglaterra/epidemiologia , Neoplasias Esofágicas/mortalidade , Feminino , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Garantia da Qualidade dos Cuidados de Saúde , Qualidade da Assistência à Saúde , Inquéritos e Questionários
11.
J Microsc ; 241(1): 13-28, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21118201

RESUMO

Modern microscope automation permits the collection of vast amounts of continuous anatomical imagery in both two and three dimensions. These large data sets present significant challenges for data storage, access, viewing, annotation and analysis. The cost and overhead of collecting and storing the data can be extremely high. Large data sets quickly exceed an individual's capability for timely analysis and present challenges in efficiently applying transforms, if needed. Finally annotated anatomical data sets can represent a significant investment of resources and should be easily accessible to the scientific community. The Viking application was our solution created to view and annotate a 16.5 TB ultrastructural retinal connectome volume and we demonstrate its utility in reconstructing neural networks for a distinctive retinal amacrine cell class. Viking has several key features. (1) It works over the internet using HTTP and supports many concurrent users limited only by hardware. (2) It supports a multi-user, collaborative annotation strategy. (3) It cleanly demarcates viewing and analysis from data collection and hosting. (4) It is capable of applying transformations in real-time. (5) It has an easily extensible user interface, allowing addition of specialized modules without rewriting the viewer.


Assuntos
Células Amácrinas/ultraestrutura , Processamento de Imagem Assistida por Computador/métodos , Retina/ultraestrutura , Software , Rede Nervosa
12.
Injury ; 41(4): 385-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19880113

RESUMO

Mortality after hip fractures in the elderly is one of the most important patient outcome measures. Subclinical thyroid dysfunction is common in the elderly population. This is a prospective study of 131 elderly patients with a mean (SD) age of 82.0 (8.9) years (range: 61-94) admitted consecutively to our trauma unit. The aim of the study was to determine the prevalence of subclinical thyroid dysfunction in an elderly cohort of patients with hip fracture and to determine if this affects the one-year mortality. There were three times more women (n=100) than men (n=31) in this cohort. All patients underwent surgical treatment for the hip fracture. The prevalence of subclinical hypothyroidism (TSH>5.5 mU/L) was 15% (n=20) and of subclinical hyperthyroidism (TSH<0.35 mU/L) was 3% (n=4). Overall 18% (n=24) of patients had a subclinical thyroid dysfunction. The twelve-month mortality was 27% (n=36). Age, gender, heart rate at admission, pre-existing coronary heart disease, ASA grade and presence of overt or subclinical thyroid dysfunction were analysed for association with twelve-month mortality using a forward stepwise logistic regression analysis. Only ASA grade was found to significantly affect mortality at twelve months (chi(2)=3.98, df=1, p=0.046). Independently the presence of subclinical hypo- or hyperthyroidism was not associated with a higher mortality (p=0.477). We conclude that subclinical thyroid dysfunction does not affect the one-year mortality in elderly patients treated surgically for hip fracture.


Assuntos
Fraturas do Quadril/mortalidade , Doenças da Glândula Tireoide/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Frequência Cardíaca/fisiologia , Fraturas do Quadril/cirurgia , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , Doenças da Glândula Tireoide/diagnóstico , Testes de Função Tireóidea
13.
Philos Trans A Math Phys Eng Sci ; 367(1896): 2293-310, 2009 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-19414456

RESUMO

Many simulation studies in biomedicine are based on a similar sequence of processing steps, starting from images and running through geometric model generation, assignment of tissue properties, numerical simulation and visualization of the results--a process known as image-based geometric modelling and simulation. We present an overview of software systems for implementing such a sequence both within highly integrated problem-solving environments and in the form of loosely integrated pipelines. Loose integration in this case indicates that individual programs function largely independently but communicate through files of a common format and support simple scripting, so as to automate multiple executions wherever possible. We then describe three specific applications of such pipelines to translational biomedical research in electrophysiology.


Assuntos
Simulação por Computador , Eletrofisiologia , Software , Diagnóstico por Imagem
14.
Anaesthesia ; 64(1): 54-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19087008

RESUMO

A questionnaire survey examining rapid sequence induction techniques was sent to all anaesthetists in Wales. The questionnaire presented five common clinical scenarios: emergency appendicectomy; elective knee arthroscopy with a symptomatic hiatus hernia; elective knee arthroscopy with an asymptomatic hiatus hernia; elective Caesarean section; and emergency laparotomy for bowel obstruction. Completed surveys were received from 421 anaesthetists, a 68% response rate. Rapid sequence induction was chosen by 398/400 respondents (100%) for bowel obstruction, 392/399 (98%) for Caesarean section, 388/408 (95%) for appendicectomy, 328/395 (83%) for symptomatic hiatus hernia but only 98/399 (25%) for asymptomatic hiatus hernia (p < 0.001). Trainees were more likely to use a rapid sequence induction technique than consultants and staff grades for the appendicectomy (p = 0.025), symptomatic hiatus hernia (p = 0.004) and asymptomatic hiatus hernia (p = 0.001) scenarios and were also more likely to use a thiopental-suxamethonium combination for rapid sequence induction (p < 0.001).


Assuntos
Anestesia Geral/métodos , Intubação Intratraqueal/métodos , Bloqueio Neuromuscular/métodos , Prática Profissional/estatística & dados numéricos , Adulto , Idoso de 80 Anos ou mais , Anestesia Obstétrica/métodos , Apendicectomia , Cesárea , Emergências , Feminino , Pesquisas sobre Atenção à Saúde , Hérnia Hiatal/complicações , Humanos , Hipnóticos e Sedativos , Obstrução Intestinal/cirurgia , Masculino , Pneumonia Aspirativa/prevenção & controle , Gravidez , Tiopental , País de Gales
15.
Oncogene ; 28(2): 209-18, 2009 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-18836486

RESUMO

The cancer stem cell hypothesis posits that malignant growth arises from a rare population of progenitor cells within a tumor that provide it with unlimited regenerative capacity. Such cells also possess increased resistance to chemotherapeutic agents. Resurgence of chemoresistant disease after primary therapy typifies epithelial ovarian cancer and may be attributable to residual cancer stem cells, or cancer-initiating cells, that survive initial treatment. As the cell surface marker CD133 identifies cancer-initiating cells in a number of other malignancies, we sought to determine the potential role of CD133+ cells in epithelial ovarian cancer. We detected CD133 on ovarian cancer cell lines, in primary cancers and on purified epithelial cells from ascitic fluid of ovarian cancer patients. We found CD133+ ovarian cancer cells generate both CD133+ and CD133- daughter cells, whereas CD133- cells divide symmetrically. CD133+ cells exhibit enhanced resistance to platinum-based therapy, drugs commonly used as first-line agents for the treatment of ovarian cancer. Sorted CD133+ ovarian cancer cells also form more aggressive tumor xenografts at a lower inoculum than their CD133- progeny. Epigenetic changes may be integral to the behavior of cancer progenitor cells and their progeny. In this regard, we found that CD133 transcription is controlled by both histone modifications and promoter methylation. Sorted CD133- ovarian cancer cells treated with DNA methyltransferase and histone deacetylase inhibitors show a synergistic increase in cell surface CD133 expression. Moreover, DNA methylation at the ovarian tissue active P2 promoter is inversely correlated with CD133 transcription. We also found that promoter methylation increases in CD133- progeny of CD133+ cells, with CD133+ cells retaining a less methylated or unmethylated state. Taken together, our results show that CD133 expression in ovarian cancer is directly regulated by epigenetic modifications and support the idea that CD133 demarcates an ovarian cancer-initiating cell population. The activity of these cells may be epigenetically detected and such cells might serve as pertinent chemotherapeutic targets for reducing disease recurrence.


Assuntos
Antígenos CD/genética , Carcinoma/genética , Transformação Celular Neoplásica/genética , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica , Glicoproteínas/genética , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Peptídeos/genética , Antígeno AC133 , Animais , Antígenos CD/fisiologia , Líquido Ascítico/patologia , Carcinoma/metabolismo , Carcinoma/patologia , Divisão Celular , Linhagem Celular Tumoral , Cisplatino/farmacologia , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Perfilação da Expressão Gênica , Glicoproteínas/fisiologia , Histonas/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/fisiologia , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Peptídeos/fisiologia , Regiões Promotoras Genéticas/efeitos dos fármacos , Processamento de Proteína Pós-Traducional
16.
Arch Dis Child ; 92(1): 67-70, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16943260

RESUMO

OBJECTIVES: To see if perineal sensation in infants with open spina bifida is associated with a better long-term outcome, particularly in terms of survival, renal-related deaths and incontinence. METHODS: We conducted a prospective cohort study on a complete cohort of 117 consecutive patients with open spina bifida, whose backs were closed non-selectively at birth between 1963 and 1971. A meticulous neurological examination in infancy showed that 33 (28%) of them had perineal sensation, defined as intact sensation to pinprick in at least one dermatome on one side in the saddle area (S2-4). Data recorded within 48 h of birth and during six reviews between 1972 and 2002 were used. Details of deaths were obtained from medical records and from the Office of National Statistics. RESULTS: By December 2005, 57% (67/117) of the cohort had died. There were 50 survivors with a mean age 38 years (range 35-41). More of those with perineal sensation survived than those without (23/33 v 27/84, p<0.001). This difference was mainly caused by 19 renal deaths in those lacking perineal sensation. Crucially there were no renal-related deaths in those with perineal sensation (0/33 v 19/84, p = 0.003). Among the survivors, those with perineal sensation were more likely than the remainder to be continent of urine and faeces (10/23 v 1/27, p<0.001 and 18/23 v 9/27, p = 0.002 respectively). They were also more likely to be able to walk at least 50 m (11/23 v 5/27, p = 0.027) and never to have had pressure sores (15/23 v 9/27, p = 0.025). CONCLUSIONS: A simple assessment of perineal sensation in infancy predicts long-term outcome in terms of survival, renal prognosis and incontinence in open spina bifida.


Assuntos
Nefropatias/mortalidade , Períneo/fisiopatologia , Sensação/fisiologia , Espinha Bífida Cística/fisiopatologia , Adolescente , Adulto , Causas de Morte , Criança , Feminino , Humanos , Recém-Nascido , Masculino , Exame Neurológico , Estudos Prospectivos , Limiar Sensorial , Espinha Bífida Cística/mortalidade , Incontinência Urinária/mortalidade
17.
Int J Gynecol Cancer ; 16(5): 1733-45, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17009964

RESUMO

Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.


Assuntos
Genes Neoplásicos , Metástase Neoplásica/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Teorema de Bayes , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Epiteliais e Glandulares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Omento/patologia , Neoplasias Ovarianas/genética , Ovário/patologia , Reação em Cadeia da Polimerase
18.
Int J Gynecol Cancer ; 16(2): 470-7, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16681713

RESUMO

The objective of this study was to assess the adequacy of network cancer guidelines paying particular attention to referral criteria, referral routes, tumor diagnosis, staging, and suggested management and care pathways for ovarian and endometrial cancer. Guidelines from 15 regions in England and Wales were analyzed quantitatively and qualitatively as a prospective audit of predefined data items and subsequently agreed management recommendations. Details of unit and center clinicians were included in a minority of documents (2 to 5/15). Multidisciplinary team membership was not usually offered (6/15). Among the least reported data items were histopathology minimum dataset for endometrial cancer and an algorithm for management or summary and clinical symptoms and signs for both cancers. Among the most reported data items were hysteroscopy and ultrasound scanning for endometrial cancer and CA125 and chemotherapy for ovarian cancer. Qualitative analysis revealed differing criteria for the use of endometrial biopsy and radiotherapy in endometrial cancer, for lymphadenectomy and management of recurrent disease in ovarian cancer, and for referral pathways and the use of computed tomography/magnetic resonance (MR) scanning in the assessment of either disease. This study concludes that consideration should be given to the development of national guidelines or templates to ensure consistency of management for gynecological malignancy in England and Wales.


Assuntos
Neoplasias dos Genitais Femininos , Ginecologia/normas , Auditoria Médica , Oncologia/normas , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/terapia , Humanos , Reino Unido
19.
Chronic Illn ; 2(4): 311-20, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17212879

RESUMO

The biopsychosocial challenges of living with human immunodeficiency virus (HIV) have changed over time and they dictate the need for relevant medical services. The meaning of an HIV diagnosis has moved from a terminal to a manageable condition with the development of antiretrovirals, bringing profound changes to the experience of living with HIV and the meaning and use of diagnostic labels. Six biological stage-related categories in the literature of psychological medicine of HIV are critiqued. Long-term HIV highlights the inadequacy of physician-centred, acute-care medicine in chronic illness and its exclusion of preventive, psychological and rehabilitative modalities. 'Eupraxia' is presented as a conceptual framework for chronic care medicine, referring to best practice, wellbeing, best interests, and (public) welfare, through facilitated but collaborative approaches. A public-centred service model is proposed, using idiographic assessment and treatment by clinicians as patient delegates (proxies), monitoring joined-up care, providing group-based biopsychosocial treatment, facilitating autonomous and self-managing behaviour by the public, removing professional and practice hierarchies, and implementing real-time clinical and managerial accountability with public ownership and involvement. This model is superior in its health-and cost-effectiveness but can only work within a nationalized system that focuses equally on standardized outcomes and evidential and personalized health outcomes.


Assuntos
Doença Crônica/psicologia , Infecções por HIV/psicologia , Guias de Prática Clínica como Assunto/normas , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Humanos
20.
J Obstet Gynaecol ; 25(8): 765-8, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16368581

RESUMO

The surgical treatment of endometrial malignancy is based on pre-operative assessment of differentiation, myometrial and lymph node infiltration. Studies have reported the use of magnetic resonance imaging (MRI) with conflicting results. This study aims to review the pre-operative accuracy of MRI against the histology in endometrial cancer within a district hospital. A total of 112 women were identified from January 1997 to December 2004. The post-operative FIGO staging showed 76.2% Stage I, 7.6% Stage II, 14.3% Stage III and 1.7% Stage IV. A total of 57% (n = 60) had a pre-operative MRI. The myometrial infiltration was difficult to interpret in 31 MRIs. The time between hysteroscopy and MRI scan in those cases was shorter (Mean 3 weeks, SD +/- 1.5) than in reports with a clear interpretation (4.4 weeks, SD +/- 1.6). Sensitivity for MRI to detect deep myometrial infiltration was 35.7% (5/14) and specificity 50% (23/46). Accuracy was 46.6% (28/60). The presented data suggests a poor predictability of myometrial invasion by MRI but the numbers are small and MRI is a rapidly evolving modality. The conclusions must be treated with caution and cannot easily be applied to large gynaecological cancer units in general.


Assuntos
Carcinoma/patologia , Neoplasias do Endométrio/patologia , Imageamento por Ressonância Magnética , Miométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estudos Retrospectivos
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