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1.
Appetite ; 162: 105171, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33636217

RESUMO

Finding effective ways to increase acceptance of lower-energy swaps offered for snacks and non-alcoholic drinks may reduce population energy intake. We examined whether incrementally increasing the tangibility of information accompanying swaps offered increased their acceptance. UK adults (n = 3481) selected a sweet snack, a savoury snack, and a drink in an experimental online canteen after being equally randomised to receive one of four messages when swaps were offered; a control message providing no specific information, a vague calorie message, an exact numeric-calories message or, a physical activity calorie equivalent (PACE). Primary outcomes were the between-group differences in (i) the odds that a sweet, savoury, or drink swap would be accepted and (ii) the energy content for each type of item ordered. Compared with control, the numeric-calories and PACE messages significantly increased the odds of accepting a sweet snack swap. All interventions significantly increased the odds of accepting savoury swaps compared with control. Only the PACE message significantly increased the odds of drink swap acceptance. The numeric-calories and PACE messages significantly reduced the energy content of sweet snacks. All interventions significantly reduced the energy content of savoury snacks. None of the intervention messages significantly reduced the energy content of drinks compared with control. Increasing the tangibility of information provided when offering swaps increased swap acceptance. PACE messaging was the most promising.


Assuntos
Comportamento de Escolha , Lanches , Local de Trabalho , Adulto , Bebidas , Ingestão de Energia , Preferências Alimentares , Promoção da Saúde , Humanos , Paladar
2.
Philos Trans A Math Phys Eng Sci ; 377(2151): 20180182, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31230572

RESUMO

The 'Trojan Horse' underdense plasma photocathode scheme applied to electron beam-driven plasma wakefield acceleration has opened up a path which promises high controllability and tunability and to reach extremely good quality as regards emittance and five-dimensional beam brightness. This combination has the potential to improve the state-of-the-art in accelerator technology significantly. In this paper, we review the basic concepts of the Trojan Horse scheme and present advanced methods for tailoring both the injector laser pulses and the witness electron bunches and combine them with the Trojan Horse scheme. These new approaches will further enhance the beam qualities, such as transverse emittance and longitudinal energy spread, and may allow, for the first time, to produce ultrahigh six-dimensional brightness electron bunches, which is a necessary requirement for driving advanced radiation sources. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

3.
Artigo em Inglês | MEDLINE | ID: mdl-28707369

RESUMO

Psychological stress exacerbates many pathological conditions including inflammatory skin conditions. The effect of psychological stress on acute radiation-induced skin reactions has not been documented before. Here, we aimed to explore if psychological stress could aggravate skin reaction severity in breast cancer patients. We conducted a secondary analysis of patient data obtained during a randomised, controlled clinical trial for acute radiation-induced skin reaction severity in 78 breast cancer patients. Patients were assessed three times a week during treatment. Skin reaction severity was measured using the modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) and Radiation Therapy Oncology Group grades. Stress levels were determined using a 5-point LIKERT scale to rate physical well-being, managing stress levels, house, family, work and other commitments. A total of 20 patients (26%) of the 78-patient cohort were considered stressed. Skin reaction severity in stressed patients was twice that of non-stressed patients (p < 0.001) and stressed patients were five times more likely to develop moist desquamation. Our results show that psychological stress aggravates skin reaction severity during radiation therapy. This research needs to be validated in a more rigorous manner by incorporating a validated scale such as the Distress Thermometer and Impact Thermometer in future skin trials.


Assuntos
Neoplasias da Mama/radioterapia , Radiodermite/patologia , Estresse Psicológico/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bandagens , Neoplasias da Mama/patologia , Neoplasias da Mama/psicologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radiodermite/fisiopatologia , Radiodermite/psicologia , Radiodermite/terapia , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Silicones
4.
Br J Surg ; 103(2): e62-72, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26662845

RESUMO

BACKGROUND: Transplant surgery is facing a shortage of deceased donor organs. In response, the criteria for organ donation have been extended, and an increasing number of organs from older donors are being used. For recipients, the benefits of transplantation are great, and the growing ageing population has led to increasing numbers of elderly patients being accepted for transplantation. METHODS: The literature was reviewed to investigate the impact of age of donors and recipients in abdominal organ transplantation, and to highlight aspects of the fine balance in donor and recipient selection and screening, as well as allocation policies fair to young and old alike. RESULTS: Overall, kidney and liver transplantation from older deceased donors have good outcomes, but are not as good as those from younger donors. Careful donor selection based on risk indices, and potentially biomarkers, special allocation schemes to match elderly donors with elderly recipients, and vigorous recipient selection, allows good outcomes with increasing age of both donors and recipients. The results of live kidney donation have been excellent for donor and recipient, and there is a trend towards inclusion of older donors. Future strategies, including personalized immunosuppression for older recipients as well as machine preservation and reconditioning of donor organs, are promising ways to improve the outcome of transplantation between older donors and older recipients. CONCLUSION: Kidney and liver transplantation in the elderly is a clinical reality. Outcomes are good, but can be optimized by using strategies that modify donor risk factors and recipient co-morbidities, and personalized approaches to organ allocation and immunosuppression.


Assuntos
Transplante de Rim/métodos , Transplante de Fígado/métodos , Idoso , Previsões , Humanos , Terapia de Imunossupressão/métodos , Transplante de Rim/ética , Transplante de Fígado/ética , Doadores Vivos/ética , Doadores Vivos/estatística & dados numéricos , Doadores Vivos/provisão & distribuição , Prognóstico , Doadores de Tecidos/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/estatística & dados numéricos
5.
Scott Med J ; 61(2): 84-87, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27655773

RESUMO

INTRODUCTION: Recent work suggests that reconstruction of the ruptured anterior cruciate ligament within 12 months of injury results in better outcomes. We present a complete audit cycle examining the effect of establishment of an Acute Knee Clinic on time to surgery. METHODS: Records of 20 anterior cruciate ligament reconstructions undertaken by the senior author between June 2003 and May 2004 were examined to identify the time to surgery. The Acute Knee Clinic was established in December 2004. Prospectively collected data on patients attending the Acute Knee Clinic between May 2005 and July 2007 and patients undergoing anterior cruciate ligament reconstruction from September 2006 to 2007 were reviewed with respect to referral route, time from injury to specialist review and time to surgery. RESULTS: Mean time from injury to surgery of the initial cohort was 14 months (range 3-56). After establishment of the Acute Knee Clinic, 90% of referrals from Accident and Emergency (A&E) were seen by a specialist within four weeks. Between September 2006 and September 2007, 49 patients underwent anterior cruciate ligament reconstruction: 21 came via the Acute Knee Clinic, with a mean time from injury to surgery of 6 months; 28 patients from the elective clinic had a mean time to surgery of 25 months. 95% of Acute Knee Clinic patients and 53 % of elective clinic patients had surgery within 12 months of injury. DISCUSSION: The Acute Knee Clinic has been shown to reduce the time from injury to anterior cruciate ligament reconstruction. The Acute Knee Clinic only accounts for the referral of 40% of anterior cruciate ligament reconstructions in this series: Further education work is required with A&E staff and GPs regarding the referral of knee injuries. Access to the Acute Knee Clinic could be extended to GPs, although this could create service overload.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior/normas , Reconstrução do Ligamento Cruzado Anterior/estatística & dados numéricos , Auditoria Clínica , Estudos de Coortes , Humanos , Articulação do Joelho/cirurgia , Cirurgiões Ortopédicos , Encaminhamento e Consulta , Fatores de Tempo , Resultado do Tratamento
6.
Scott Med J ; 61(1): 26-31, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26721641

RESUMO

BACKGROUND: It has been suggested in the literature that raised heart rate in the early period after trauma is associated with the development of post-traumatic psychopathology, but little account has been taken of the potential confounding effect of injury severity. MATERIALS AND METHODS: A cohort of 154 patients, studied as part of a wider investigation of trauma outcomes, was included. Initial heart rate in the accident & emergency department, and injury severity score and new injury severity scores were recorded. Patients completed the General Health Questionnaire (GHQ-28) as a measure of psychopathology at presentation and again at two- and six-month follow-up. RESULTS: There was no relationship between psychopathology at presentation and initial heart rate or injury severity. Raised heart rate was associated with post-traumatic psychopathology at two months but not at six months. When the potential confounding effect of injury severity was controlled for, there was no independent correlation between heart rate and post-traumatic psychopathology. Injury severity score and new injury severity scores were strongly associated with GHQ-28 caseness. CONCLUSION: Post-traumatic tachycardia is not associated with development of psychopathology, but injury severity is. Previous studies that have suggested a link between tachycardia and development of psychopathology are flawed because they have not considered the confounding effect of severity of injury.


Assuntos
Taquicardia/complicações , Taquicardia/psicologia , Ferimentos e Lesões/complicações , Adolescente , Adulto , Idoso , Estudos de Coortes , Conselheiros , Feminino , Humanos , Escala de Gravidade do Ferimento , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Tempo , Ferimentos e Lesões/psicologia , Adulto Jovem
7.
Am J Transplant ; 14(7): 1481-7, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24909061

RESUMO

Hypoxia-inducible factors are the universal cellular oxygen-sensitive transcription factors that activate a number of hypoxia responsive genes, some of which are responsible for protective cellular functions. During organ donation, allografts are exposed to significant periods of hypoxia and ischemia. Exploiting this pathway during donor management and organ preservation could prevent and reduce allograft injury and improve the outcomes of organ transplantation. We review the evidence on this pathway in organ preservation, drawing on experimental studies on donor management and ischemia reperfusion injury focusing on kidney, liver, cardiac and lung transplantation. We review the major technical and experimental challenges in exploring this pathway and suggest potential future avenues for research.


Assuntos
Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Preservação de Órgãos , Transplante de Órgãos , Traumatismo por Reperfusão/prevenção & controle , Obtenção de Tecidos e Órgãos , Humanos , Traumatismo por Reperfusão/metabolismo
8.
Am J Transplant ; 14(3): 677-84, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24612687

RESUMO

mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6-year follow-up of 30 patients prospectively recruited to this single-arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin-inhibitor-based immunosuppression.Six-year patient and graft survival were 83% and 80%(alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p»0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p<0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Complicações Pós-Operatórias/prevenção & controle , Sirolimo/uso terapêutico , Alemtuzumab , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/fisiologia , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Projetos Piloto , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
9.
Nat Commun ; 14(1): 1054, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36828817

RESUMO

Electron beam quality is paramount for X-ray pulse production in free-electron-lasers (FELs). State-of-the-art linear accelerators (linacs) can deliver multi-GeV electron beams with sufficient quality for hard X-ray-FELs, albeit requiring km-scale setups, whereas plasma-based accelerators can produce multi-GeV electron beams on metre-scale distances, and begin to reach beam qualities sufficient for EUV FELs. Here we show, that electron beams from plasma photocathodes many orders of magnitude brighter than state-of-the-art can be generated in plasma wakefield accelerators (PWFAs), and then extracted, captured, transported and injected into undulators without significant quality loss. These ultrabright, sub-femtosecond electron beams can drive hard X-FELs near the cold beam limit to generate coherent X-ray pulses of attosecond-Angstrom class, reaching saturation after only 10 metres of undulator. This plasma-X-FEL opens pathways for advanced photon science capabilities, such as unperturbed observation of electronic motion inside atoms at their natural time and length scale, and towards higher photon energies.


Assuntos
Elétrons , Aceleradores de Partículas , Raios X , Lasers , Fótons
10.
BJOG ; 119(8): 906-14, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22703419

RESUMO

OBJECTIVE: To study the consequences of glucocorticoid treatment in fetal growth restriction (FGR) on cardiac function. SETTING: Laboratory. SAMPLE: Sheep. METHODS: Growth restriction was induced in sheep fetuses using single umbilical artery ligation (SUAL) on days 105-110 of gestation (term 147). Control fetuses were not ligated. Betamethasone (BM) (11.4 mg intramuscularly) or saline was administered to ewes on days 5 and 6 after surgery. Ewes were anaesthetised on day 7, the fetuses were removed, and their hearts were mounted on a Langendorff apparatus. Balloon catheters were inserted into the right and left ventricles. OUTCOME MEASURES: Ventricular contractile function and infarct area following ischaemia/reperfusion. RESULTS: The SUAL resulted in FGR (body weight 77% of control). The FGR was associated with increases in basal left ventricular pressure development and rates of contraction and relaxation. Right ventricular contraction was unaffected. Following brief ischaemia/reperfusion, the infarct area in FGR hearts was increased four-fold compared with controls. Antenatal BM resulted in a proportional increase in heart size and coronary flow, especially in FGR fetuses, and left ventricular pressure and heart rate responses to ß-adrenoceptor activation were increased. CONCLUSIONS: Fetal hearts rapidly adapt to FGR to maintain substrate delivery to the brain and heart. The FGR greatly enhanced the area of ischaemia, with implications for susceptibility in postnatal life. Antenatal BM treatment does not interfere with these cardiac changes but appears to increase left ventricle ß-adrenoceptor responsiveness, which may render the offspring vulnerable to subsequent cardiac dysfunction.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Betametasona/farmacologia , Retardo do Crescimento Fetal/fisiopatologia , Coração Fetal/efeitos dos fármacos , Glucocorticoides/farmacologia , Adaptação Fisiológica/fisiologia , Agonistas Adrenérgicos beta/farmacologia , Análise de Variância , Animais , Betametasona/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Circulação Coronária/efeitos dos fármacos , Feminino , Coração Fetal/fisiologia , Glucocorticoides/administração & dosagem , Frequência Cardíaca Fetal/efeitos dos fármacos , Isoproterenol/farmacologia , Ligadura , Contração Miocárdica/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/embriologia , Carneiro Doméstico , Artérias Umbilicais , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Direita/efeitos dos fármacos
11.
Knee Surg Sports Traumatol Arthrosc ; 19(10): 1709-15, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21445592

RESUMO

PURPOSE: Rupture of the anterior cruciate ligament is common and may necessitate surgical reconstruction. Surgical reconstruction aims to restore normal kinematics and biology within the knee. The acute phase response after surgical reconstruction remains poorly defined but may influence graft integration through modulation of host tissue remodelling. METHODS: The very early host production of key cytokines after surgery was studied. A consecutive series of 14 patients undergoing reconstructive surgery were studied per-operatively, 1 and 6 h after surgery, examining the hypothesis that the acute phase response would be non-specific but consistent between individuals, demonstrating increases of pro-inflammatory cytokines. RESULTS: A consistent increased release of monocyte-driven, non-specific, IL-1 and IL-6 release but not T cell-derived IL-2 was found. Perhaps, more interestingly, very early high concentrations of secondary growth factors PDGF and TGF-ß suggestive of an anabolic response were found. CONCLUSION: These data support the contention that an anabolic response starts earlier than previously thought within the surgically reconstructed knee.


Assuntos
Reação de Fase Aguda/etiologia , Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Citocinas/biossíntese , Traumatismos do Joelho/cirurgia , Articulação do Joelho/metabolismo , Reação de Fase Aguda/metabolismo , Adolescente , Adulto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Líquido Sinovial/metabolismo , Fatores de Tempo , Adulto Jovem
12.
J Environ Health ; 73(6): 34-46, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21306093

RESUMO

To evaluate historical exposure from wood treatment facilities, attic dust samples were collected from residential structures and blood samples were collected from current and past residents of four communities surrounding wood treatment facilities throughout the United States. The pattern of dioxin/furan congeners detected in both attic dust and blood samples was found to be consistent with exposure to contaminants generated during the wood treatment process. Levels in the U.S. population of 2,3,7,8-tetrachloro-p-dibenzodioxin toxic equivalents (2,3,7,8-TCDD TEQs) for all 17 carcinogenic dioxin/furan congeners as well as octa-chlorinated dibenzo-p-dioxin (OCDD) adjusted to its TEQ value and 1,2,3,4,6,7,8-hepta-chlorinated dibenzo-p-dioxin (1,2,3,4,6,7,8-HpCDD) adjusted to its TEQ value were compared to the TEQ levels in the combined data set for all four communities and in the data sets for each individual community. TEQ concentrations in these communities were found to be significantly greater than in the general U.S. population. The levels of dioxins in attic dust were compared to the U.S. Environmental Protection Agency's regional screening levels and found to far exceed the levels that are regarded as safe for the general population. These findings reveal that a very significant potential for contaminant-related health risks exists in communities surrounding wood treatment facilities.


Assuntos
Dioxinas/análise , Dioxinas/sangue , Poeira/análise , Exposição Ambiental/análise , Poluentes Ambientais/análise , Poluentes Ambientais/sangue , Furanos/sangue , Indústria Química , Habitação , Humanos , Estados Unidos , Madeira
13.
Knee Surg Sports Traumatol Arthrosc ; 18(6): 731-5, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19768454

RESUMO

Anterior cruciate ligament reconstruction (ACLR) has the potential for significant post-operative pain. Conventional systemic opiate treatment may cause nausea and drowsiness, which may delay recovery. The use of intra-articular local anaesthesia has been shown to be effective. We wished to examine the additional effect of intra-articular morphine. This is a prospective, randomised, double-blind trial. Sixty patients were randomised to receive 20 ml 0.5% bupivicaine (group L, n = 30) or bupivicaine with 10 mg morphine (group M, n = 30) by intra-articular injection at the end of the operation. Visual analogue scores (VAS) were recorded before ACLR (expected pain) and repeated at 6 and 24 h after surgery. Time to first analgesic request and total systemic opiate and other analgesic use in the first 24 h was recorded. Pre-operative VAS measurements did not predict pain or analgesic use post-operatively. There were no significant differences between groups L and M with regard post-operative VAS or time to first analgesic request. Group M required less opiate analgesic post-operatively (oral morphine equivalent 50 mg for group L and 27 mg for group M, P < 0.007). There were no complications associated with the intra-articular analgesic. The simple addition of morphine to the intra-articular injection of bupivicaine gives a significant reduction in opiate analgesic requirement after ACLR.


Assuntos
Analgésicos/administração & dosagem , Ligamento Cruzado Anterior/cirurgia , Bupivacaína/administração & dosagem , Cuidados Intraoperatórios/métodos , Morfina/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Medição da Dor , Estudos Prospectivos , Adulto Jovem
14.
J Orthop Traumatol ; 11(3): 149-54, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20835745

RESUMO

BACKGROUND: Anterior cruciate ligament (ACL) rupture has been implicated in the development of knee osteoarthritis (OA). This study aimed at determining the incidence of prior ACL deficiency in patients undergoing total knee replacement (TKR), the effect of prior ACL deficiency on function and the macroscopic and microscopic appearance of the ligament. MATERIALS AND METHODS: A total of 95 patients undergoing elective TKR for OA were recruited. Pre-operative knee assessment included questionnaires and KT1000 testing. The ACL was examined macroscopically at TKR in all patients, and 10 ACL specimens were examined histologically. RESULTS: The ACL was absent in 12% of the patients. There was no significant correlation between the pre-operative assessment or function and operative findings. The ACL samples all demonstrated degenerative change of varying severities. CONCLUSION: ACL deficiency is uncommon in patients undergoing TKR for OA, and does not worsen pre-operative function.


Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior/patologia , Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Amplitude de Movimento Articular/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Ligamento Cruzado Anterior/cirurgia , Estudos de Coortes , Intervalos de Confiança , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Instabilidade Articular/complicações , Instabilidade Articular/diagnóstico , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Exame Físico , Cuidados Pré-Operatórios/métodos , Recuperação de Função Fisiológica , Valores de Referência , Medição de Risco , Ruptura/complicações , Ruptura/cirurgia , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento
15.
J Cell Biol ; 106(4): 1331-48, 1988 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-2834405

RESUMO

Mouse-hatched blastocysts cultured in vitro will attach and form outgrowths of trophoblast cells on appropriate substrates, providing a model for implantation. Immediately after hatching, the surfaces of blastocysts are quiescent and are not adhesive. Over the period 24-36 h post-hatching, blastocysts cultured in serum-free medium become adhesive and attach and spread on the extracellular matrix components fibronectin, laminin, and collagen type IV in a ligand specific manner. Attachment and trophoblast outgrowth on these substrates can be inhibited by addition to the culture medium of an antibody, anti-ECMr (anti-extracellular matrix receptor), that recognizes a group of 140-kD glycoproteins similar to those of the 140-kD extracellular matrix receptor complex (integrin) recognized in avian cells by CSAT and JG22 monoclonal antibodies. Addition to the culture medium of a synthetic peptide containing the Arg-Gly-Asp tripeptide cell recognition sequence of fibronectin inhibits trophoblast outgrowth on both laminin and fibronectin. However, the presence of the peptide does not affect attachment of the blastocysts to either ligand. Immunoprecipitation of 125I surface-labeled embryos using anti-ECMr reveals that antigens recognized by this antibody are exposed on the surfaces of embryos at a time when they are spreading on the substrate, but are not detectable immediately after hatching. Immunofluorescence experiments show that both the ECMr antigens and the cytoskeletal proteins vinculin and talin are enriched on the cell processes and ventral surfaces of trophectoderm cells in embryo outgrowths, in patterns similar to those seen in fibroblasts, and consistent with their role in adhesion of the trophoblast cells to the substratum.


Assuntos
Blastocisto/fisiologia , Matriz Extracelular/metabolismo , Receptores de Superfície Celular/fisiologia , Animais , Antígenos/análise , Adesão Celular , Colágeno/metabolismo , Técnicas de Cultura , Fibronectinas/metabolismo , Imunoensaio , Laminina/metabolismo , Ligantes , Camundongos , Receptores de Superfície Celular/biossíntese , Receptores de Superfície Celular/imunologia
16.
Colorectal Dis ; 11(3): 282-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18513198

RESUMO

OBJECTIVE: Idiopathic pruritus ani is a common perianal condition that can be refractory to diligent perineal care. We wished to evaluate the efficacy and side effects of intradermal methylene blue for the treatment of refractory pruritus ani. METHOD: A prospective series of 49 patients with idiopathic pruritus ani, who had failed to improve with perineal care, were treated by a single surgeon. All patients received intradermal injections of methylene blue. Endpoints were patient symptom score, and complications (pain, dysaesthesia, skin necrosis, incontinence and anaphylaxis). RESULTS: Symptoms improved in 96% and resolved in 57% of patients after one treatment. All four patients who had a second treatment became symptom-free. Seven patients noticed changes in continence, all resolved between 10 days and 6 weeks. Two patients were distressed by their decrease in their perianal sensation. There was no skin necrosis or anaphylaxis. CONCLUSION: Treatment of refractory pruritus ani by intradermal injection of methylene blue is effective and generally well tolerated.


Assuntos
Azul de Metileno/uso terapêutico , Prurido Anal/tratamento farmacológico , Adulto , Idoso , Biópsia por Agulha , Doença Crônica , Colonoscopia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Intradérmicas , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Prurido Anal/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
17.
Am J Transplant ; 8(2): 338-47, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18211507

RESUMO

Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation. We found that after alemtuzumab induction the recovery of CD8(+) T cells was much faster than that of CD4(+) T cells. It was complete 6 months posttransplant while CD4(+) T cells did not fully recover even 15 months posttransplant. Repopulating CD8(+) T cells were mainly of immunosenescent CD28(-)CD8(+) phenotype. In a series of in vitro experiments we showed that CD28(-)CD8(+) T cells might suppress proliferation of CD4(+) T cells. There were three successfully treated acute rejections during the study (first at +70 day, two others +12 months) that occurred in patients with the lowest level of CD28(-)CD8(+) T cells. We hypothesize that expanded CD28(-)CD8(+) T cells might compete for 'immune space' with CD4(+) T cells suppressing their proliferation and therefore delaying CD4(+) T-cells recovery. This delay might be associated with the clinical outcome as CD4(+) T cells, notably CD4(+) T effector memory cells, were shown to be associated with rejection.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticorpos Antineoplásicos/uso terapêutico , Antígenos CD28/imunologia , Linfócitos T CD8-Positivos/imunologia , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Depleção Linfocítica , Linfócitos T Reguladores/imunologia , Alemtuzumab , Anticorpos Monoclonais Humanizados , Antígenos CD/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Interleucinas/sangue , Ativação Linfocitária , Reação em Cadeia da Polimerase
18.
Br J Sports Med ; 42(3): 183-8, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18182624

RESUMO

OBJECTIVE: To investigate the association of optic nerve sheath diameter (ONSD), as a correlate of intracranial pressure (ICP), with acute mountain sickness (AMS). DESIGN: Longitudinal cohort study of mountaineers from sea level to 6400 m. SETTING: Mount Everest (North side). PARTICIPANTS: 13 mountaineers (10 men, 3 women; aged 23-52 years) on a British expedition to climb Mount Everest. INTERVENTIONS: ONSD was measured ultrasonically, 3 mm behind the globe using B scans recorded with an OTI-Scan 3D scanner (Ophthalmic Technologies, Canada). Serial binocular scans were recorded at sea level, and 2000, 3700, 5200 and 6400 m. All ONSDs were measured by a blinded observer. MAIN OUTCOME MEASURES: ONSD, AMS score (using the Lake Louise scoring system), heart rate, and oxygen saturation levels. RESULTS: All results were analysed by regression analysis with adjustment. ONSD was positively associated with increasing altitude above sea level (0.10 mm increase in ONSD per 1000 m, 95% CI 0.05 to 0.14 mm) and AMS score (0.12 mm per score, 95% CI 0.06 to 0.18 mm); further associations were found with resting heart rate (0.29 mm per 20 beats/min, 95% CI 0.17 to 0.41 mm) and oxygen saturations (0.20 mm per 10% decrease, 95% CI 0.11 to 0.29 mm). CONCLUSIONS: ONSD increases at high altitude, and this increase is associated with more severe symptoms of AMS. Given the linkage between ONSD and ICP, these results strongly suggest that intracranial pressure plays an important role in the pathophysiology of AMS.


Assuntos
Doença da Altitude/etiologia , Altitude , Pressão Intracraniana/fisiologia , Montanhismo/fisiologia , Nervo Óptico/diagnóstico por imagem , Doença Aguda , Adulto , Doença da Altitude/fisiopatologia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia
19.
Cancer Gene Ther ; 14(10): 847-57, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17599091

RESUMO

Chemokines and their receptors play important roles in various aspects of tumoral processes, and evidence was provided for their critical involvement in determining the metastatic destination of tumor cells. Here, we analyzed in vitro and in vivo, how CCR6 expression could alter the behavior of Lewis lung carcinoma (LLC) cells, which were shown to express low levels of the CCR6 ligand, CCL20 (LARC), both in vitro and in vivo. The expression of CCR6 significantly decreased the number of metastases in immunocompetent C57BL/6 mice, without affecting the tumor-forming ability of LLC cells. This was correlated with a decrease in clonogenicity in soft and hard agar, and with increased adhesion to type-IV collagen. These two observations made in basal conditions were enhanced when CCL20 was added to the assay medium. Thus, expression of CCR6 in tumor cells, associated with the local production of CCL20, decreased the metastatic potential of the LLC line. We propose a model, in which the expression of a chemokine receptor in tumor cells can act as a metastasis-suppressor, or a metastasis-promoting factor, according to the expression, or the absence of expression of the cognate ligand(s) in the tumor.


Assuntos
Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/secundário , Regulação Neoplásica da Expressão Gênica/fisiologia , Receptores de Quimiocinas/genética , Animais , Cálcio/metabolismo , Carcinoma Pulmonar de Lewis/prevenção & controle , Adesão Celular , Proliferação de Células , Quimiocina CCL20 , Quimiocinas CC/genética , Quimiotaxia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Proteínas Inflamatórias de Macrófagos/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , Receptores CCR6 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Ensaio Tumoral de Célula-Tronco
20.
Geriatr Orthop Surg Rehabil ; 8(2): 99-103, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28540115

RESUMO

INTRODUCTION: Hip fracture is an increasingly common injury in the growing elderly population. The morbidity and mortality associated with this injury can be reduced by minimizing delays to surgical treatment. We describe the impact of a regional hospital service redesign project that utilized the principles of smart simplicity, a management strategy that lays emphasis on collaboration to achieve desired goals. METHODS: Prior to the redesign, patients with hip fractures were taking an average of 72 hours for surgical treatment. A hip fracture working group was created to examine closely the process of hip fracture care, and a single key performance indicator (KPI) of "surgery within 48 hours" was adopted. This allowed identification of processes that could be clarified and streamlined, with the agreement of relevant stakeholders, in the creation of a new hip fracture pathway. RESULTS: In the first 3 months of the pathway's implementation, 16 of 18 patients had surgery within 48 hours of presentation. In a 6-month follow-up audit after 2 years of implementation, 36 of 39 patients were treated within 48 hours. This was significantly different to the time to surgery seen in the 12 months prior to the redesign (P < .001, Student t test). The mean time to surgery was reduced from 72 hours to 36 hours, a saving in an annual acute bed stay cost of A$152 000. DISCUSSION: Decreased time to the operating room, the cost savings inherent to this, can be achieved with the introduction of the best standard of care. A redesign that mandates collaboration in achieving a single KPI has allowed a significant culture shift in the treatment of hip fractures in our institution in the months following its institution. CONCLUSION: Collaborative, multidisciplinary collaboration has facilitated a higher standard of care and demonstrated significant cost benefit.

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