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1.
BJS Open ; 5(2)2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33839751

RESUMO

BACKGROUND: Single-use negative-pressure wound therapy (sNPWT) has been reported to reduce the incidence of reconstruction failure in prepectoral breast reconstruction compared with standard surgical dressings. The aim of this economic evaluation was to investigate the cost-effectiveness of sNPWT compared with standard care for the prevention of reconstruction failure in prepectoral breast reconstruction in the UK. METHOD: A decision tree model was used to estimate the expected cost and effectiveness per patient. Effectiveness was measured both by the number of reconstruction failures avoided and the gain in quality-adjusted life-years (QALYs). The baseline incidence of reconstruction failure (8.6 per cent) was taken from a recently published study of 2655 mastectomies in the UK. The effectiveness of sNPWT used results from a clinical study comparing sNPWT with standard dressings. Previously published utility weights were applied. The cost of reconstruction failure was estimated from detailed resource data from patients with reconstruction failure, applying National Health Service reference costs. One-way, probabilistic, scenario and threshold analyses were conducted. RESULTS: The undiscounted cost per patient associated with reconstruction failure was estimated to be £23 628 (£22 431 discounted). The use of sNPWT was associated with an expected cost saving of £1706 per patient, an expected increase in QALYs of 0.0187 and an expected 0.0834 reconstruction failures avoided. Cost-effectiveness acceptability analysis demonstrated that, at a threshold of £20 000 per QALY, 99.94 per cent of the simulations showed sNPWT to be more cost-effective than standard care. CONCLUSION: Among patients undergoing immediate prepectoral breast reconstruction, the use of sNPWT is more cost-effective than standard dressings.


Assuntos
Mamoplastia/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa/métodos , Padrão de Cuidado/estatística & dados numéricos , Infecção da Ferida Cirúrgica/prevenção & controle , Bandagens , Análise Custo-Benefício , Feminino , Humanos , Mamoplastia/economia , Tratamento de Ferimentos com Pressão Negativa/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa/economia , Anos de Vida Ajustados por Qualidade de Vida , Padrão de Cuidado/economia , Medicina Estatal , Infecção da Ferida Cirúrgica/epidemiologia , Reino Unido
2.
Reproduction ; 158(5): 389-397, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31454786

RESUMO

Uterine spiral arteries undergo remodelling in normal pregnancy, with replacement of the musculoelastic arterial media by fibrinoid containing extravillous trophoblast cells. Deficient spiral artery remodelling is associated with several adverse pregnancy outcomes. Although there are distinct components of spiral artery remodelling, assessment is subjective and often based on an overall impression of morphology. We aimed to develop a quantitative approach for assessment of uterine spiral artery remodelling. Placental bed biopsies were immunostained using smooth muscle markers, digital images of spiral arteries were captured and Adobe Photoshop was used to analyse positive immunostaining. The method was then used to investigate variation in the same vessel at different levels within a paraffin block, and the effect of parity, pre-eclampsia or miscarriage on vascular smooth muscle cell content. Results were also compared with a more subjective morphology-based assessment system. There was good intra- and interobserver agreement and the method correlated well with the more subjective assessment system. There was an overall reduction in vascular smooth muscle, as detected by caldesmon 1 (h-caldesmon) immunopositivity, with increasing gestational age from 8 weeks to term. A previous pregnancy did not affect the amount of spiral artery smooth muscle. Comparison of pre-eclampsia and late miscarriage samples with controls of the appropriate gestational age demonstrated increased medial smooth muscle in pathological samples. This technique provides a simple, rapid, reproducible and inexpensive approach to quantitative assessment of spiral artery remodelling in normal and pathological human pregnancy, a process which although fundamental for successful pregnancy, is still incompletely understood.


Assuntos
Artérias/fisiologia , Diagnóstico por Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Placenta/irrigação sanguínea , Útero/irrigação sanguínea , Remodelação Vascular/fisiologia , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/patologia , Aborto Espontâneo/fisiopatologia , Anatomia Transversal/métodos , Artérias/diagnóstico por imagem , Artérias/patologia , Feminino , Humanos , Músculo Liso Vascular/diagnóstico por imagem , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Neovascularização Fisiológica/fisiologia , Placenta/diagnóstico por imagem , Placenta/patologia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/patologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Software , Útero/diagnóstico por imagem , Útero/patologia
3.
Geochem Geophys Geosyst ; 20(3): 1298-1318, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35860338

RESUMO

The flanks of the ultraslow-spreading Mid-Cayman Spreading Center (MCSC) are characterized by domal massifs or oceanic core complexes (OCCs). The most prominent of these, Mount Dent, comprises lower-crustal and upper-mantle lithologies and hosts the Von Damm vent field ~12 km west of the axial deep. Here, presented autonomous underwater vehicle-derived swath sonar (multibeam) mapping and deep-towed side-scan sonar imagery lead to our interpretation that: (i) slip along the OCC-bounding detachment fault is ceasing, (ii) the termination zone, where detachment fault meets the hanging wall, is disintegrating, (iii) the domed surface of the OCC is cut by steep north-south extensional faulting, and (iv) the breakaway zone is cut by outward facing faults. The Von Damm vent field and dispersed pockmarks on the OCC's south flank further suggest that hydrothermal fluid flow is pervasive within the faulted OCC. On the axial floor of the MCSC, bright acoustic backscatter and multibeam bathymetry reveal: (v) a volcanic detachment hanging wall, (vi) a major fault rifting the southern flank of Mount Dent, and (vii) a young axial volcanic ridge intersecting its northern flank. These observations are described by a conceptual model wherein detachment faulting and OCC exhumation are ceasing during an increase in magmatic intrusion, brittle deformation, and hydrothermal circulation within the OCC. Together, this high-resolution view of the MCSC provides an instructive example of how OCCs, formed within an overall melt-starved ultraslow spreading center, can undergo magmatism, hydrothermal activity, and faulting in much the same way as expected in magmatically more robust slow-spreading centers elsewhere.

4.
J Hosp Infect ; 97(2): 122-124, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28807639

RESUMO

This article reports audit data from the introduction of the PICO™ System for caesarean section patients with high body mass index (BMI) in four hospitals in the UK and Ireland. PICO was used on closed surgical incisions following caesarean section in 399 patients with BMI ≥35kg/m2. Thirty-six out of 399 patients (9.0%) developed signs of surgical site infection (SSI), a rate lower than a previously reported incidence of 19.3% in a similar population. The readmission incidence was 0.8%. Therefore the use of PICO on closed surgical incisions may be associated with low incidence of SSI and readmission in this high-risk group.


Assuntos
Cesárea/efeitos adversos , Tratamento de Ferimentos com Pressão Negativa , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Índice de Massa Corporal , Inglaterra/epidemiologia , Feminino , Humanos , Irlanda/epidemiologia , Tempo de Internação , Auditoria Médica , Tratamento de Ferimentos com Pressão Negativa/estatística & dados numéricos , Obesidade/complicações , Gravidez , Fatores de Risco
5.
Afr. j. health prof. educ ; 9(3): 111-115, 2017. tab
Artigo em Inglês | AIM (África) | ID: biblio-1256940

RESUMO

Background. Student departure from university without completing a qualification is a major concern in higher education. Higher Education South Africa reported that in undergraduate studies, 35% of students depart after the first year and only 15% of students who enrol complete their degree within the minimum permissible time. At postgraduate level, the departure from Masters programmes in South Africa (SA) ranged from 30% to 67% in 2010. Early departure refers to students who leave an academic programme within the first semester of commencing their studies. At one SA university, there were a total of 109 first-time Master of Public Health (MPH) student registrations in 2013 and 2014. By the end of the first semester in the respective years, a total of 27 students actively deregistered from the programme and 11 students did not sit the first-semester examinations, representing an aggregate 35% rate of early departure. The factors associated with early departure at the University of KwaZulu-Natal are not well understood.Objective. To understand factors associated with early departure in the MPH programme at the University of KwaZulu-Natal.Method. A mixed-methods design was implemented. Students who departed within the first semester of commencing the MPH programme in 2013/2014 were followed up. Data were collected using self-administered questionnaires and in-depth interviews.Results. Failure to balance work and academic obligations with poor time management, stress and academic demands related to the programme, and insufficient academic progress were found to be associated with student early departure from the MPH programme.Conclusion. Student early departure from the MPH programme was influenced by multifaceted factors. Senior students can mentor new students as early as possible in their programme. The orientation block should include development activities such as time management, stress management and effective study skills to assist mature students to cope with the demands of part-time postgraduate studies


Assuntos
Educação de Pós-Graduação , Faculdades de Saúde Pública , África do Sul , Estudantes de Saúde Pública
6.
J Wound Care ; 24(7): 312, 314-7, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26198553

RESUMO

OBJECTIVE: A collaborative project between Hull CHCP and Smith and Nephew wound management, which sought to enhance practice efficiency, specifically in relation to the optimisation of dressing change frequency. The project involved the use of a new foam dressing (Allevyn Life, Smith & Nephew, Hull) designed to manage wound exudate more effectively, be more acceptable to patients by masking staining of the dressing surface, and to provide both the patient and clinical staff with an indicator for dressing change. METHOD: The project comprised a targeted programme of training and education to promote appropriate use of the new product and encourage practice change in dressing change frequency. The frequency of nursing visits, dressing changes and, where applicable, the reasons for a dressing change were documented pre- and post-implementation to determine the effect of this approach. RESULTS: Switching to the new dressing was accompanied by a reduction in dressing change visit frequency in 97.3% (36/37) of patients. The mean reduction in dressing change frequency was 1.8 visits per week, representing a 50.0% reduction. Post-implementation the mean number of dressings used per patient per dressing change had fallen from 2.1 at baseline to 1.1 (a 47.6% reduction). Furthermore, at baseline an average of 9.8 dressings were used per week per patient. This fell to an average of 2.0 dressings per week per patient following implementation, a reduction in dressings per patient of 79.6%. CONCLUSION: The results illustrate that a much less complex approach to the use of dressing products can be achieved. Furthermore, they demonstrate that with the adoption of advanced practice-enhancing products, coupled with appropriate training, education and effective promotion of practice change, valuable nursing time can be released. DECLARATION OF INTEREST: Alistair Bielby is a contractor for Smith & Nephew. Richard Searle is an employee of Smith & Nephew. This project was supported by an unrestricted grant from Smith & Nephew.


Assuntos
Enfermagem em Saúde Comunitária , Poliuretanos/uso terapêutico , Cicatrização/fisiologia , Comorbidade , Eficiência Organizacional , Humanos , Capacitação em Serviço , Educação de Pacientes como Assunto , Fatores de Tempo , Reino Unido
7.
J Wound Care ; 23(11): 552, 554, 556-8 passim, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25375403

RESUMO

Demographic and epidemiological data suggest that health-care demand will increase considerably in the future as a result of an ageing population and a rise in the prevalence of chronic diseases such as diabetes. This phenomenon has come to be referred to as the 'health care time bomb' in the popular press and political discourse. The authors seek to look beyond the headlines and political rhetoric to clarify the extent to which they reflect the likely future reality with a specific focus on wound management. The present-day burden that wounds and current wound management practices place upon the health-care system are detailed and clarified, and the potential future implications of increasing wound prevalence on the current picture are explored. Possible opportunities to enhance current wound management practice as identified in the analysis are discussed.


Assuntos
Bandagens , Serviços de Saúde Comunitária/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/organização & administração , Úlcera da Perna/terapia , Úlcera por Pressão/terapia , Alocação de Recursos/organização & administração , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Doença Crônica , Feminino , Humanos , Lactente , Recém-Nascido , Úlcera da Perna/economia , Masculino , Pessoa de Meia-Idade , Úlcera por Pressão/economia , Fatores Socioeconômicos , Reino Unido , Cicatrização , Adulto Jovem
8.
Sci Total Environ ; 468-469: 1210-24, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23968738

RESUMO

The use of river basin modelling to guide mitigation of non-point source pollution of wetlands, estuaries and coastal waters has become widespread. To assess and simulate the impacts of alternate land use or climate scenarios on river washload requires modelling techniques that represent sediment sources and transport at the time scales of system response. Building on the mean-annual SedNet model, we propose a new D-SedNet model which constructs daily budgets of fine sediment sources, transport and deposition for each link in a river network. Erosion rates (hillslope, gully and streambank erosion) and fine sediment sinks (floodplains and reservoirs) are disaggregated from mean annual rates based on daily rainfall and runoff. The model is evaluated in the Burdekin basin in tropical Australia, where policy targets have been set for reducing sediment and nutrient loads to the Great Barrier Reef (GBR) lagoon from grazing and cropping land. D-SedNet predicted annual loads with similar performance to that of a sediment rating curve calibrated to monitored suspended sediment concentrations. Relative to a 22-year reference load time series at the basin outlet derived from a dynamic general additive model based on monitoring data, D-SedNet had a median absolute error of 68% compared with 112% for the rating curve. RMS error was slightly higher for D-SedNet than for the rating curve due to large relative errors on small loads in several drought years. This accuracy is similar to existing agricultural system models used in arable or humid environments. Predicted river loads were sensitive to ground vegetation cover. We conclude that the river network sediment budget model provides some capacity for predicting load time-series independent of monitoring data in ungauged basins, and for evaluating the impact of land management on river sediment load time-series, which is challenging across large regions in data-poor environments.


Assuntos
Agricultura/métodos , Recifes de Corais , Monitorização de Parâmetros Ecológicos/métodos , Poluição Ambiental/prevenção & controle , Sedimentos Geológicos/análise , Modelos Teóricos , Rios/química , Algoritmos , Simulação por Computador , Poluição Ambiental/análise , Queensland , Fatores de Tempo
9.
Br J Anaesth ; 109(2): 240-4, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22649184

RESUMO

BACKGROUND: Although postoperative pain is traditionally considered to be nociceptive in origin, a proportion of patients experience a significant neuropathic component to their pain experience. Diagnosing neuropathic pain in this setting is challenging, and there are no published guidelines or screening tools designed for use in the immediate postoperative setting. We hypothesized that acute pain specialists were diagnosing a neuropathic component to acute pain, and this study aimed to obtain an expert agreed list of pain characteristics that could be used to aid diagnosis. METHODS: A three-round Internet-based Delphi survey of acute pain specialists was used to generate a list of acute neuropathic pain characteristics, and achieve consensus on the importance of each item. Items were ranked on a 1-10 scale of importance, with a median score of ≥ 7 considered important and an inter-quartile range of ≤ 3 indicative of consensus. Cronbach's α was used to investigate internal consistency. RESULTS: Twenty-four items were generated by round 1 of the Delphi survey. Fourteen panellists participated in round 2, and 10 in round 3. After round 3, consensus of opinion was achieved for 13 items, with nine rated as important in the diagnosis of acute neuropathic pain. CONCLUSIONS: The Delphi survey suggests that neuropathic pain in the immediate postoperative period is diagnosed in a different way to chronic neuropathic pain, with items such as response to medications considered more useful than signs such as those representing autonomic changes.


Assuntos
Neuralgia/diagnóstico , Dor Pós-Operatória/diagnóstico , Doença Aguda , Técnica Delphi , Humanos , Neuralgia/etiologia , Medição da Dor/métodos
10.
J Wound Care ; 19(9): 396-402, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20852568

RESUMO

A survey of ward nurses in medical, surgical, orthopaedic and rehabilitation specialties in relation to their care of wounds and their choice and use of wound dressings was carried out in May and August 2009 at St Mary's Hospital. Isle of Wight, UK. The objectives were to find out the distribution of wound types, and their characteristics, that were treated by ward nurses in the hospital, and to assess clinical practice in the use of wound dressings, before and after a bespoke programme of education and training. A visual framework to aid the ward nurses in the choice of dressings and frequency of change was introduced after the May 2009 survey. Following the nurses' education and training programme a repeat survey, using the same methodology, was conducted in August 2009. In the initial survey, 172 wounds were included (mean number of wounds per patient 1.64) and in the repeat one, 159 (mean number of wounds per patient 1.54). In both phases of the survey, the most common wound type was pressure ulcers, followed by surgical wounds; over 60% of the wounds were pressure ulcers, of which around half were category 1, and one-third were category 2. No category 4 ulcers were recorded. About one-third of the wounds had a duration of more than 21 days. On average, wound dressings were left in place for between two and three days, with 35% of dressings being changed on a daily basis. The mean cost of dressings per wound per week was observed to be lower in the repeat survey than in the initial one (£9.02 and £11.23 respectively). The number of undesirable reasons for changing the dressing was lower in the second phase than the first. The methodology of the surveys provided meaningful and valuable results over a short timescale, and increased understanding of wound types, their characteristics, and clinical practice. The surveys showed that data that can be collected in a short period using a simple tool can yield complex and revealing data trends. They also showed that an education programme followed by a re-survey can improve practice and reduce the costs of wound care.


Assuntos
Bandagens , Educação Continuada em Enfermagem/organização & administração , Recursos Humanos de Enfermagem Hospitalar/educação , Padrões de Prática em Enfermagem/estatística & dados numéricos , Higiene da Pele/enfermagem , Ferimentos e Lesões/enfermagem , Algoritmos , Bandagens/economia , Bandagens/provisão & distribuição , Controle de Custos , Árvores de Decisões , Humanos , Avaliação em Enfermagem , Auditoria de Enfermagem , Pesquisa em Educação em Enfermagem , Recursos Humanos de Enfermagem Hospitalar/psicologia , Seleção de Pacientes , Avaliação de Programas e Projetos de Saúde , Higiene da Pele/economia , Higiene da Pele/instrumentação , Reino Unido , Ferimentos e Lesões/classificação
11.
Placenta ; 31(7): 595-601, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20483454

RESUMO

BACKGROUND: Extravillous trophoblast cell (EVT) invasion of maternal tissues is critical for successful pregnancy. Decidual factors, including uterine natural killer (uNK) and T cell derived cytokines play a role in regulating this process. Interleukin (IL) 8 has been implicated as a regulator of EVT invasion. HYPOTHESIS: uNK cell stimulation of EVT invasion is associated with IL-8 levels. METHODS: CD8+, total decidual and CD56(+) uNK cells (8-10 and 12-14 weeks gestational age) were cultured. IL-8 mRNA and protein levels were determined. IL-8 receptors (IL-8RA and IL-8RB) were localised in first trimester placental bed biopsies. The effect of IL-8 +/- IL-8 neutralising antibodies and CD8+ T cell or uNK cell supernatants +/- IL-8 neutralising antibodies on EVT invasion was assessed. EVT secreted levels of MMP-2, MMP-9, uPA, PAI-1 and PAI-2 were assessed by substrate zymography or Western Blot. RESULTS: High levels of IL-8 protein and mRNA were detected in all samples. IL-8RA and IL-8RB were expressed by EVT. Exogenous IL-8 stimulated EVT invasion in a paracrine manner. uNK cell supernatants, but not CD8+ cell supernatants, stimulated EVT invasion. IL-8 neutralising antibody partially abrogated this uNK cell stimulated invasion. IL-8 increased levels of secreted MMP-2, but did not alter any of the other proteases or protease inhibitors tested. CONCLUSION: uNK cell stimulation of EVT invasion is partially mediated by IL-8. Unstimulated CD8+ T cells do not alter EVT invasion despite secreting similar levels of IL-8 as uNK cells.


Assuntos
Interleucina-8/fisiologia , Células Matadoras Naturais/imunologia , Gravidez/imunologia , Trofoblastos/imunologia , Trofoblastos/fisiologia , Útero/imunologia , Linfócitos T CD8-Positivos/imunologia , Movimento Celular/fisiologia , Feminino , Humanos , Interleucina-8/imunologia , Metaloproteinase 2 da Matriz/metabolismo , Primeiro Trimestre da Gravidez/imunologia , Receptores de Interleucina-8A/metabolismo , Receptores de Interleucina-8B/metabolismo
12.
Placenta ; 31(6): 545-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20338637

RESUMO

Angiogenesis is a key feature of placental and uterine development in early pregnancy. We hypothesized that trophoblast cells produce angiogenic growth factors, and that expression differs between villous cytotrophoblast (CTB) and extravillous trophoblast (EVT) cells. Fourteen angiogenic growth factors were measured by multiplex growth factor analysis or ELISA in tissue culture supernatants from EVT and CTB from pregnancies at 8-10 and 12-14 weeks' gestation. Gestational age and cell type differences were observed. EVT and CTB are major producers of angiogenic growth factors that likely contribute to placental vascular development and spiral artery remodeling.


Assuntos
Proteínas Angiogênicas/metabolismo , Vilosidades Coriônicas/metabolismo , Neovascularização Fisiológica/fisiologia , Primeiro Trimestre da Gravidez/fisiologia , Trofoblastos/metabolismo , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Placentação/fisiologia , Gravidez , Trofoblastos/citologia
13.
J Reprod Immunol ; 82(1): 24-31, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19732959

RESUMO

Most research on human decidual leucocytes to date has focused on the predominant CD56+ uterine natural killer (uNK) cell population in early pregnancy. Few reports have documented decidual leucocyte populations after 13 weeks gestation and in late pregnancy. Placental bed (decidua basalis) and non-placental bed (decidua parietalis) biopsies from normal pregnancies were taken from women undergoing termination of pregnancy in the 1st and 2nd trimesters and following Caesarean section in the 3rd trimester. Immunohistochemistry was used to quantify the numbers of decidual cells expressing CD56, CD3, CD8, CD94, NKG2A and CD14 and double labelled CD161+CD3+ NKT-like cells. Although a significant reduction in CD56+ uNK cells was found in 3rd trimester samples compared with 1st and 2nd trimester decidua, a substantial residual CD56+ leucocyte population was identified in 3rd trimester decidua. Expression of the KIR CD94/NKG2A mirrored that of CD56 at all gestational ages, providing an explanation for the absence of cytotoxic responses at the fetal-maternal interface. There was no difference in leucocyte populations between decidua basalis and decidua parietalis. Double immunohistochemical labelling revealed small numbers of decidual CD3+CD56+ and CD8+CD56+ cells, which decreased in number at term, and CD161+CD3+ cells, which increased in number at term. No differences in leucocyte populations were detected between decidua parietalis and decidua basalis. In contrast to previous reports, a substantial residual CD56+ cell population was demonstrated in 3rd trimester decidua. Decidual cytotoxic T-lymphocytes did not alter in number during gestation, while in contrast CD14+ macrophages decreased at term, representing the smallest decidual population assessed.


Assuntos
Decídua/citologia , Decídua/imunologia , Células Matadoras Naturais/metabolismo , Macrófagos/metabolismo , Linfócitos T Citotóxicos/metabolismo , Antígenos CD/biossíntese , Contagem de Células , Decídua/metabolismo , Feminino , Idade Gestacional , Humanos , Tolerância Imunológica , Imuno-Histoquímica , Imunofenotipagem , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Macrófagos/imunologia , Macrófagos/patologia , Circulação Placentária/imunologia , Gravidez , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Fatores de Tempo
14.
Br J Anaesth ; 103(1): 14-25, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19482856

RESUMO

The concept of 'personalized medicine' in which a knowledge of genetic factors guides prescribing tailored to the individual is popularly considered to be an inevitable consequence of completion of the International Human Genome Project. We should not forget, however, that a personal or family history of one of several uncommon pharmacogenetic conditions has influenced the use of the implicated drug(s) during anaesthesia for the past 50 yr. Although this has been important for those affected, pharmacogenomics heralds the prospect of an individual's genetic profile informing every prescription. Progress has been rapid in some areas, notably cancer chemotherapy where response to treatment can be predicted on the basis of the genetic profile of the tumour cells. The situation is different for most currently available drugs, including those used by anaesthetists, where genetic variability to drug response is presumed to be the result of a complex interaction of multiple factors. We review the nature and investigation of pharmacogenomic variability and contrast the progress made with research into opioid variability with the more limited literature concerning i.v. and inhalation anaesthetics.


Assuntos
Anestesia/métodos , Farmacogenética/métodos , Analgésicos Opioides/farmacologia , Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Variação Genética , Humanos
15.
Placenta ; 30(5): 398-404, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19272641

RESUMO

The urokinase plasminogen activator (uPA) system plays pivotal roles in cell invasion, adhesion and migration. Roles for uterine natural killer (uNK) cells in regulating extravillous trophoblast (EVT) invasion and spiral artery remodeling have been proposed. Placental bed biopsies from early pregnancy were obtained from three gestational age groups (8-10, 12-14 and 15-20 weeks). Total caseinase activity in the placental bed was studied using casein in situ zymography. Localisation of uPA, uPA receptor (uPAR), plasminogen activator inhibitor (PAI)-1 and -2 in the placental bed was investigated by immunohistochemistry. CD56(+) uNK cells were separated from collagenase-digested decidual cells using an immunomagnetic technique, and uPA activity was measured in isolated cell culture supernatants by casein/plasminogen gel zymography (8-10 and 12-14 weeks' gestation, n=10 each group). uPAR in cell lysates and PAI-1 and -2 secretion in supernatants were measured by Western blotting. Caseinase activity was stronger in decidua than myometrium as shown by in situ zymography. uPA localised strongly to uNK cells, especially at 8-10 weeks. Moderate uPAR localisation on uNK cells also observed. There was very weak immunostaining of uNK cells for PAI-1 and PAI-2. In casein gel zymography, uPA activity was similar in uNK cell culture supernatant compared with total unseparated decidual cells. uPAR in uNK cell lysates was significantly stronger than in total decidual cell lysates. PAI-1 and PAI-2 were not detected in uNK cell culture supernatants by Western blot analysis. These results suggest that uNK cells may regulate EVT invasion and spiral artery remodeling via the uPA system.


Assuntos
Células Matadoras Naturais/fisiologia , Ativador de Plasminogênio Tipo Uroquinase/fisiologia , Biópsia , Caseínas/metabolismo , Decídua/citologia , Feminino , Idade Gestacional , Humanos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Inibidor 2 de Ativador de Plasminogênio/metabolismo , Gravidez , Receptores de Ativador de Plasminogênio Tipo Uroquinase/fisiologia
17.
Int J Obstet Anesth ; 17(3): 233-7, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18499438

RESUMO

BACKGROUND: Changes in the delivery of anaesthesia for caesarean section have meant that trainee experience in obstetric general anaesthesia has steadily declined. In the UK, working patterns for trainees have changed significantly with the introduction of the New Deal in 2000 and the European Working Time Directive in 2004. Because of an impression that training opportunities had worsened during this period we have reviewed data in obstetric general anaesthesia at St James's University Hospital since 1998. METHODS: Data were collected retrospectively from prospective audit information contained within annual reviews collated by the Department of Obstetric Anaesthesia, St James's University Hospital Leeds between 1998 and 2006. Results before and after the implementation of training changes in 2000 and 2004 were compared. RESULTS: Since 1998 the total number of obstetric general anaesthetics given per year has continued to decline. The number of trainees increased from 23 in 1998 to 40 in 2006, with the main increase occurring between 2002 and 2003. The mean number of obstetric general anaesthetics given per trainee fell to 1 per year in 2006. CONCLUSION: Since 1998 training opportunities in general anaesthesia for caesarean section at St James's Hospital have continued to decline. This reflects both changing trends in the delivery of anaesthesia for caesarean section and also changes in training hours and trainee numbers.


Assuntos
Anestesia Obstétrica/tendências , Anestesiologia/educação , Cesárea/estatística & dados numéricos , Educação de Pós-Graduação em Medicina/tendências , Anestesia Obstétrica/métodos , Anestesia Obstétrica/estatística & dados numéricos , Anestesiologia/tendências , Cesárea/métodos , Coleta de Dados , Educação de Pós-Graduação em Medicina/estatística & dados numéricos , Humanos , Estudos Longitudinais , Auditoria Médica , Estudos Retrospectivos , Reino Unido
18.
Placenta ; 28(5-6): 390-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-16905187

RESUMO

The applicability of trophoblast-like cell lines to the study of trophoblast function has been widely debated. The present study investigated the effect of oxygen on the invasiveness, apoptosis, proliferation and secreted proteases of four different trophoblast cell lines; HTR-8/SVneo, SGHPL-4, JEG3 and JAR. All experiments were performed at 20% and 3% oxygen for 24, 48 and 72h. Immunostaining for integrins alpha1, alpha6 and beta3, cytokeratin 7 and HLA-G was used to determine the phenotype of the different cell lines. Invasion was assessed using the Matrigel invasion assay. Immunostaining for M30 and Ki67 determined levels of apoptosis and proliferation, respectively. Gelatin and casein/plasminogen zymography were performed on conditioned media to determine levels of secreted matrix metalloproteinase (MMP) 2 and MMP9 and urokinase plasminogen activator (uPA), respectively. None of the cell lines immunostained for all markers normally expressed by extravillous trophoblast cells. Invasiveness of HTR-8/SVneo and JEG3 cells cultured in 3% oxygen was increased after 24h but was inhibited by 72h in culture. Invasion of SGHPL-4 cells was inhibited after culture in 3% oxygen for 24h. Invasion by JAR cells was not affected by changes in oxygen concentration. The different cell lines also displayed different responses to culture period in 3% oxygen with respect to apoptosis, proliferation and secreted proteases. Care should be taken before results obtained using cell lines as a model for EVT are extrapolated to extravillous trophoblast cell behaviour in vivo.


Assuntos
Hipóxia Celular , Consumo de Oxigênio , Trofoblastos/fisiologia , Animais , Apoptose , Divisão Celular , Linhagem Celular , Antígenos HLA/genética , Antígenos HLA-G , Antígenos de Histocompatibilidade Classe I/genética , Integrinas/genética , Queratinas/genética , Camundongos , Trofoblastos/citologia
19.
Placenta ; 28(1): 59-63, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16549200

RESUMO

Interleukin (IL)-17 is a proinflammatory cytokine with pleiotropic activities including inducing neovascularization and production of proangiogenic molecules. As pregnancy outcome depends on the balance of Th1-like/Th2-like cytokines and an increased blood supply to the fetoplacental unit, the expression of IL-17 mRNA and protein in human placental tissues was investigated. IL-17 mRNA was expressed by purified cytokeratin-positive term placental trophoblast cells, HLA-G+ extravillous trophoblast cells and placental macrophages (Hofbauer cells). IL-17 localized in both cyto- and syncytiotrophoblasts of normal term pregnancy, spontaneous miscarriage and in molar pregnancy. In spontaneous miscarriage and molar pregnancy extravillous trophoblast cells were consistently immunoreactive for IL-17. IL-17 expression in human placenta may play a key role in angiogenesis and/or immunoregulation in the establishment of pregnancy.


Assuntos
Interleucina-17/metabolismo , Placenta/metabolismo , Adolescente , Adulto , Células Cultivadas , Feminino , Expressão Gênica , Humanos , Placenta/química , Gravidez , Proteínas da Gravidez/análise , RNA Mensageiro/análise
20.
Clin Exp Immunol ; 138(2): 330-6, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15498045

RESUMO

Complete hydatidiform moles are totally paternally derived and represent complete allografts that might be expected to provoke maternal immune rejection. Our previous and other studies have shown expression of Fas by increased numbers of activated decidual CD4(+) T cells in both complete and partial molar pregnancy as well as increased FasL(+) expression by molar trophoblasts compared with trophoblasts in normal pregnancies. As the Fas/FasL system represents a major apoptotic pathway that can play a role in immune privilege, the aim of this study was to investigate whether apoptosis of decidual immune cells, particularly T cells, could be responsible for maternal immune tolerance in molar pregnancy. Using terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labelling (TUNEL), a significant increase in TUNEL(+) cells was demonstrated in decidua associated with partial (P = 0.0052) and complete (P = 0.0096) hydatidiform mole compared with normal early pregnancy. Co-labelling immunoperoxidase studies showed that the TUNEL(+) cells in both normal and molar pregnancies were not activated CD45RO(+) immune cells, CD3(+) T cells, CD56(+) uterine natural killer (NK) cells or CD14(+) CD68(+) macrophages. Double immunohistochemical labelling with antiactive caspase-3 and leucocyte markers confirmed the lack of leucocyte apoptosis. Double immunostaining with anticytokeratin to detect trophoblast and M30 CytoDeath, which detects a neoepitope of cytokeratin 18 revealed after caspase-mediated cleavage, revealed apoptotic extravillous trophoblast cells within decidual tissue. We conclude that there is no evidence that apoptosis of decidual leucocytes plays a role in maintaining maternal tolerance in either normal or molar pregnancy.


Assuntos
Apoptose/imunologia , Decídua/imunologia , Mola Hidatiforme/imunologia , Tolerância Imunológica/imunologia , Leucócitos/imunologia , Neoplasias Uterinas/imunologia , Antígenos CD/análise , Caspase 3 , Caspases/análise , Decídua/patologia , Precursores Enzimáticos/análise , Feminino , Humanos , Técnicas Imunoenzimáticas/métodos , Marcação In Situ das Extremidades Cortadas/métodos , Queratinas/análise , Células Matadoras Naturais/imunologia , Gravidez , Linfócitos T/imunologia
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