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1.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38892418

RESUMEN

Renal ischemia-reperfusion is a common cause of acute kidney injury leading to significant morbidity and mortality. There are no effective treatments available in clinical practice. This meta-analysis aims to assess the effect of IL-10 immunotherapy on renal ischemia-reperfusion injury. Medline, Embase, Cochrane-library, Google Scholar and clinicaltrials.gov were searched up to 31 March 2023. Preclinical and clinical interventional studies investigating IL-10 immunotherapy for renal ischemia-reperfusion were eligible for inclusion. The primary endpoint was renal function (serum creatinine) following ischemia-reperfusion. The secondary endpoints included mitochondrial integrity, cellular proliferation, regulated cell death (TUNEL assay), expression of inflammatory cytokines (TNF-α, IL-6 and IL-1ß), M1/M2 macrophage polarization, tissue integrity (tubular injury score), long-term kidney fibrosis (fibrotic area %) and adverse events (pulmonary toxicity, cardiotoxicity hepatotoxicity). The search returned 861 records. From these, 16 full texts were screened and subsequently, seven animal studies, corresponding to a population of 268 mice/rats, were included. Compared to the control treatment, IL-10 immunotherapy reduced serum creatinine more effectively within 24 h of administration (95% CI: -9.177, -5.601, I2 = 22.42%). IL-10 immunotherapy promoted mitochondrial integrity and cellular proliferation and reduced regulated cell death (95% CI: -11.000, -4.184, I2 = 74.94%). It decreased the expression of TNF-α, IL-6 and IL-1ß, led to M2 polarization of the local macrophages, reduced tubular injury score (95% CI: -8.917, -5.755, I2 = 22.71%), and long-term kidney fibrosis (95% CI: -6.963, -3.438, I2 = 0%). No adverse outcomes were captured. In Conclusion, IL-10 immunotherapy safely improves outcomes in animal models of renal ischemia-reperfusion; the translational potential of IL-10 immunotherapy needs to be further investigated in clinical trials.


Asunto(s)
Interleucina-10 , Daño por Reperfusión , Daño por Reperfusión/terapia , Animales , Interleucina-10/metabolismo , Humanos , Inmunoterapia/métodos , Riñón/patología , Riñón/metabolismo , Lesión Renal Aguda/terapia , Ratones
2.
Int J Mol Sci ; 25(9)2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38732257

RESUMEN

In transplantation, hypothermic machine perfusion (HMP) has been shown to be superior to static cold storage (SCS) in terms of functional outcomes. Ex vivo machine perfusion offers the possibility to deliver drugs or other active substances, such as Mesenchymal Stem Cells (MSCs), directly into an organ without affecting the recipient. MSCs are multipotent, self-renewing cells with tissue-repair capacities, and their application to ameliorate ischemia- reperfusion injury (IRI) is being investigated in several preclinical and clinical studies. The aim of this study was to introduce MSCs into a translational model of hypothermic machine perfusion and to test the efficiency and feasibility of this method. Methods: three rodent kidneys, six porcine kidneys and three human kidneys underwent HMP with 1-5 × 106 labelled MSCs within respective perfusates. Only porcine kidneys were compared to a control group of 6 kidneys undergoing HMP without MSCs, followed by mimicked reperfusion with whole blood at 37 °C for 2 h for all 12 kidneys. Reperfusion perfusate samples were analyzed for levels of NGAL and IL-ß by ELISA. Functional parameters, including urinary output, oxygen consumption and creatinine clearance, were compared and found to be similar between the MSC treatment group and the control group in the porcine model. IL-1ß levels were higher in perfusate and urine samples in the MSC group, with a median of 285.3 ng/mL (IQR 224.3-407.8 ng/mL) vs. 209.2 ng/mL (IQR 174.9-220.1), p = 0.51 and 105.3 ng/mL (IQR 71.03-164.7 ng/mL) vs. 307.7 ng/mL (IQR 190.9-349.6 ng/mL), p = 0.16, respectively. MSCs could be traced within the kidneys in all models using widefield microscopy after HMP. The application of Mesenchymal Stem Cells in an ex vivo hypothermic machine perfusion setting is feasible, and MSCs can be delivered into the kidney grafts during HMP. Functional parameters during mimicked reperfusion were not altered in treated kidney grafts. Changes in levels of IL-1ß suggest that MSCs might have an effect on the kidney grafts, and whether this leads to a positive or a negative outcome on IRI in transplantation needs to be determined in further experiments.


Asunto(s)
Trasplante de Riñón , Riñón , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Perfusión , Daño por Reperfusión , Animales , Porcinos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Riñón/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Perfusión/métodos , Humanos , Trasplante de Riñón/métodos , Daño por Reperfusión/terapia , Daño por Reperfusión/metabolismo , Preservación de Órganos/métodos , Investigación Biomédica Traslacional , Masculino , Hipotermia Inducida/métodos
3.
Eur Surg Res ; 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38081157

RESUMEN

The perpetual organ shortage crisis worldwide has meant a paradigm shift in global thinking with subsequent expansion of the accepted criteria for an organ donor to meet the demand. Robust pre-transplant organ viability assessment is the next great challenge in the field of transplantation today. Organ preservation in the nature of static cold storage has reached its limits, and machine perfusion both cold and warm offers theoretically superior preservation and the potential to assess organs. Microdialysis is a novel technique with proven ability to allow remote assessment of tissue biochemistry and metabolism. It has been used in various pre-clinical and clinical models of abdominal organ preservation and transplantation. This review focuses on the use of microdialysis in the assessment of the kidney, liver, and pancreas, and where this novel technology is heading in the context of the assessing organ viability prior to and after transplantation.

4.
Int J Mol Sci ; 22(3)2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33504032

RESUMEN

Mesenchymal Stromal Cells (MSC) have been shown to exhibit immuno-modulatory and regenerative properties at sites of inflammation. In solid organ transplantation (SOT), administration of MSCs might lead to an alleviation of ischemia-reperfusion injury and a reduction of rejection episodes. Previous reports have suggested 'MSC-preconditioning' of macrophages to be partly responsible for the beneficial effects. Whether this results from direct cell-cell interactions (e.g., MSC trans-differentiation at sites of damage), or from paracrine mechanisms, remains unclear. Immunosuppressive capacities of MSCs from donors of different age and from genetically modified donor animals, often used for in-vivo experiments, have so far not been investigated. We conducted an in vitro study to compare paracrine effects of supernatants from MSCs extracted from young and old wild-type Wystar-Kyoto rats (WKY-wt), as well as young and old WKY donor rats positive for the expression of green fluorescent protein (WKY-GFP), on bone marrow derived macrophages (BMDM). Expression levels of Mannose receptor 1 (Mrc-1), Tumor necrosis factor α (TNFα), inducible NO synthase (iNos) and Interleukin-10 (IL-10) in BMDMs after treatment with different MSC supernatants were compared by performance of quantitative PCR. We observed different expression patterns of inflammatory markers within BMDMs, depending on age and genotype of origin for MSC supernatants. This must be taken into consideration for preclinical and clinical studies, for which MSCs will be used to treat transplant patients, aiming to mitigate inflammatory and allo-responses.


Asunto(s)
Inmunomodulación , Células Madre Mesenquimatosas/metabolismo , Animales , Biomarcadores , Citocinas/metabolismo , Expresión Génica , Genes Reporteros , Inmunofenotipificación , Trasplante de Células Madre Mesenquimatosas , Ratas , Ratas Endogámicas WKY , Ratas Transgénicas
5.
Curr Diab Rep ; 19(8): 56, 2019 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-31292740

RESUMEN

PURPOSE OF REVIEW: Pancreas transplantation enables complete patient independence from exogenous insulin administration and increases both patient survival and quality of life. Despite this, there has been a decline in pancreas transplantation for the past 20 years, influenced by changing donor demographics with more high-risk extended criteria (ECD) and donation after cardiac death (DCD) donors. This review discusses whether the advent of machine perfusion (MP), if extended to the pancreas, can increase the pool of suitable donor organs. RECENT FINDINGS: Hypothermic and normothermic MP, as forms of preservation deemed superior to cold storage for high-risk kidney and liver donor organs, have opened the avenue for translation of this work into the pancreas. Recent experimental models of porcine and human ex-vivo pancreatic MP are promising. Applications of MP to the pancreas however need refinement-focusing on perfusion protocols and viability assessment tools. Emerging research shows pancreatic MP can potentially offer superior preservation capacity, the ability to both resuscitate and manipulate organs, and assess functional and metabolic organ viability. The future of MP will lie in organ assessment and resuscitation after retrieval, where ultimately organs initially considered high risk and unsuitable for transplantation will be optimised and transformed, making them then available for clinical use, thus increasing the pool of suitably viable pancreata for transplantation.


Asunto(s)
Preservación de Órganos , Trasplante de Páncreas , Animales , Humanos , Perfusión , Calidad de Vida , Porcinos , Donantes de Tejidos
6.
J Surg Res ; 223: 263-274, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29325720

RESUMEN

BACKGROUND: Hypothermic machine perfusion (HMP) is increasingly being used for extended criteria kidney grafts. Pancreatic HMP is challenging because physiologically the pancreas is a low-flow organ susceptible to edema. We report the successful development of preclinical HMP models using porcine pancreases, as well as human pancreases unsuitable for clinical transplantation. METHODS: Ten porcine pancreases were used in the development of these perfusion models. Pancreases underwent 24 h of static cold storage (SCS, n = 3) and then viability assessment on an isolated oxygenated normothermic reperfusion (NRP) circuit or 24-h SCS, 5 h of HMP, and then NRP (SCS-HMP, n = 3). Human pancreases (n = 3) were used in the development of a preclinical model. RESULTS: Porcine HMP demonstrated stable perfusion indices at low pressures, with a weight gain of between 15.3% and 27.6%. During NRP, SCS-HMP pancreases demonstrated stable perfusion flow indices (PFIs) throughout reperfusion (area under the curve was in the range of 0.49-2.04 mL/min/100 g/mm Hg), whereas SCS-only pancreases had deteriorating PFI with a decline of between 19% and 46%. Human pancreas models demonstrated stable PFI between 0.18 and 0.69 mL/min/100 g/mm Hg during HMP with weight gain of between 3.9% and 14.7%. NRP perfusion in porcine and human models was stable, and functional assessment via insulin secretion demonstrated beta cell viability. Exocrine function was intact with production of pancreatic secretions only in human grafts. CONCLUSIONS: Application of machine perfusion in preclinical porcine and human pancreas models is feasible and successful; the development of these translational models could be beneficial in improving pancreas preservation before transplantation and allowing organ viability assessment and optimization.


Asunto(s)
Preservación de Órganos/métodos , Trasplante de Páncreas , Animales , Humanos , Microdiálisis , Soluciones Preservantes de Órganos , Páncreas/patología , Páncreas/fisiología , Perfusión , Porcinos
7.
J Surg Res ; 208: 219-229, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27993213

RESUMEN

BACKGROUND: The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca2+, 16 mM Mg2+, and 4% albumin on kidney preservation compared with University Wisconsin solution (UW). METHODS: Twenty donation of organs after cardiac death porcine kidneys underwent HMP for 10 h (AL, n = 10; UW, n = 10) and then 2 h of normothermic reperfusion. Perfusion dynamics, functional parameters, histology, and real-time microdialysis were used to assess kidney responses and viability. RESULTS: During HMP, modified AL-perfused kidneys maintained higher flow rates (21.5 versus 17.9 mL/min/100 g, P = 0.01), with perfusion flow index during the first 3 h 25% greater than with UW (AL = 0.50 ± 0.2, UW = 0.40 ± 0.17 mL/min/100 g/mmHg; P = 0.03), followed by an increase in UW kidneys which was not significantly different to AL over the remaining 7 h (0.54 versus 0.55 mL/min/100 g/mmHg, respectively). During warm reperfusion, there were no significant differences between the two HMP groups in creatinine clearance, oxygen, and glucose consumption between groups. Modified AL kidneys had significantly lower perfusate lactates (3.1 versus 4.1 mmol/L, P = 0.04) during reperfusion and lower cortical lactate levels (AL = 0.66 ± 0.31, UW = 0.89 ± 0.53 mM, P = 0.33). Histology showed similar degrees of reperfusion injury. CONCLUSIONS: We conclude that HMP with modified AL solution showed improved perfusion compared with UW and lower perfusate lactate levels during warm reperfusion. Further modification of the AL composition is warranted and may lead to more rapid kidney stabilization and improved graft viability assessment, potentially expanding donor pools.


Asunto(s)
Adenosina , Riñón , Lidocaína , Soluciones Preservantes de Órganos , Perfusión , Alopurinol , Animales , Tasa de Filtración Glomerular , Glutatión , Hipotermia Inducida , Insulina , Microdiálisis , Consumo de Oxígeno , Rafinosa , Porcinos
8.
J Surg Res ; 200(1): 332-45, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26323367

RESUMEN

BACKGROUND: Viability assessment during preservation is imperative to avoid unnecessary discard of marginal organs maximizing graft outcomes in kidney transplantation. To address this need, we have developed a novel system based on a rapid sampling microdialysis (rsMD) analyzer allowing continuous tissue monitoring and measurement of metabolic markers of cell damage. Our aim was to develop a tool that allows for accurate assessment of tissue metabolism and organ viability in the preservation period. METHODS: Twenty-two porcine kidneys subjected to 15 min of warm ischemia underwent either 24 h of static cold storage (SCS) or 10 h of hypothermic machine perfusion (HMP). After preservation, tissue temperature was allowed to passively increase to ambient temperature as an ischemic challenge. Cortical and medullary metabolism was monitored throughout with online measurements of lactate concentrations made every 60 s. RESULTS: On commencement of monitoring, lactate concentrations were successfully detected within 15 mins. During the initial 1.5 h, lactate concentrations were similar during SCS (65 µM) and HMP (124 µM, P > 0.05) but lower after 10 h of SCS (SCS: 68 µM versus HMP: 230 µM, P < 0.001). Warming data suggest a resilience of HMP kidneys to subsequent temperature induced ischemia compared to SCS kidneys. CONCLUSIONS: This preliminary study provides the baseline ischemic profile for porcine kidneys while validating the technique of rsMD as a tool for organ viability assessment during preservation. The data characterize metabolic differences between SCS and HMP preserved allografts and can help elucidate why HMP is clinically superior to SCS allowing development of interventions to augment these benefits.


Asunto(s)
Criopreservación/métodos , Trasplante de Riñón , Riñón/metabolismo , Ácido Láctico/metabolismo , Microdiálisis/métodos , Preservación de Órganos/métodos , Perfusión/métodos , Animales , Biomarcadores/metabolismo , Estudios de Factibilidad , Porcinos , Isquemia Tibia
9.
Transplantation ; 105(8): 1760-1770, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33560723

RESUMEN

BACKGROUND: Hypothermic machine perfusion (HMP) is a well-established method for deceased donor kidney preservation. Normothermic machine perfusion (NMP) might offer similar or greater advantages. We compared the 2 methods in an ex vivo perfusion model using 34 porcine kidneys. METHODS: Thirty kidneys were stored on ice for 24 h before undergoing 4 h of HMP (n = 15) or NMP (n = 15) followed by 2 h of normothermic ex vivo reperfusion with whole blood. Four kidneys underwent 28 h of cold static storage followed by 2 h of normothermic ex vivo reperfusion. During the 2 h of normothermic ex vivo reperfusion, perfusate flow rates, urinary output, and oxygen consumption rates were compared between all groups. RESULTS: Porcine kidneys after HMP showed significantly higher urinary output (5.31 ± 2.06 versus 2.44 ± 1.19 mL/min; P = 0.002), oxygen consumption (22.71 ± 6.27 versus 11.83 ± 1.29 mL/min; P = 0.0016), and perfusate flow rates (46.24 ± 12.49 versus 26.16 ± 4.57 mL/min; P = 0.0051) than kidneys after NMP. TUNEL staining of tissue sections showed significantly higher rates of apoptosis in kidneys after NMP (P = 0.027). CONCLUSIONS: In our study, the direct comparison of HMP and NMP kidney perfusion in a translational model demonstrated superiority of HMP; however, further in vivo studies would be needed to validate those results.


Asunto(s)
Trasplante de Riñón/métodos , Preservación de Órganos/métodos , Animales , Consumo de Oxígeno , Perfusión/métodos , Porcinos
10.
J Plast Reconstr Aesthet Surg ; 72(1): 20-22, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30591142

RESUMEN

Ischemia reperfusion injury (IRI) is characterised initially by restriction of oxygenated blood flow to an organ bed, resulting in tissue hypoxia and ischaemic injury, followed by further 'reperfusion' injury upon restoration of perfusion, with an influx of oxygen, inflammatory cells and generation of free radicals. The culmination is a complex interplay between cellular and biochemical processes involved in inflammation and coagulation, exhibited as the 'no re-flow' phenomenon. Under ideal circumstances, autologous free tissue transfer is performed with short ischemic times. However, there are certain clinical scenarios where the ischaemic period can be prolonged due to technical and non-technical factors. IRI is inevitable and can be possibly more pronounced in such cases. In these cases, there may be a role for plastic surgeons to adopt some of the anti-ischaemia reperfusion injury (IRI) practices used in solid organ transplantation (SOT). Knowledge of the current trends in SOT IRI reduction should be discussed by plastic surgeons to assess whether certain facets can be extrapolated into the plastic and reconstructive armamentarium. These can be applicable to more challenging microsurgical cases, including composite free tissue transfer. Three important aspects are discussed further in this editorial: (1) cold flushing, (2) machine perfusion and pharmacological manipulation. Ongoing research will need to study the impact these potential interventions will have on the acute complications but also in which subset of patients they would be most beneficial. This area is novel and exciting but cautious implementation is advised with careful scrutiny of future data.


Asunto(s)
Aloinjertos Compuestos , Trasplante de Órganos/métodos , Anticoagulantes/uso terapéutico , Humanos , Precondicionamiento Isquémico/métodos , Microcirugia/métodos , Reperfusión/métodos , Daño por Reperfusión/prevención & control
11.
Obes Surg ; 29(7): 2255-2262, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30895507

RESUMEN

BACKGROUND: Secondary bariatric procedures represent a challenge to both patients and surgeons. The objective of this study was to explore the patterns of recurrence and modalities of secondary bariatric procedures in a tertiary bariatric centre. MATERIALS AND METHODS: A retrospective analysis of patients who underwent secondary bariatric procedures after laparoscopic adjustable gastric band (AGB), sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) from April 2007 to March 2017. RESULTS: Overall, 3266 bariatric procedures were performed, and secondary bariatric procedures were required for 45 (1.4%) patients (28 AGB, 14 SG, 3 RYGB). Twenty-six (57.8%) patients underwent conversion to RYGB, eight (17.8%) patients underwent conversion to SG, seven (15.6%) patients were converted to duodenal switch (DS), two (4.4%) patients had revision of gastrojejunal anastomosis, one (2.2%) patient underwent revision of gastric pouch and one (2.2%) patient had replacement of AGB. Mean change in BMI and %TWL at 18 months were 8.5 ± 3.9 kg/m2 and 17.6 ± 8.2 respectively after revision of AGB. Mean change in BMI and %TWL at 18 months were 11.7 ± 11.2 kg/m2 and 18.4 ± 13.2 respectively after revision of SG. Mean change in BMI and %TWL at 18 months were 2.6 ± 3.0 kg/m2 and 6.9 ± 6.8 respectively after revision of RYGB. No mortality was reported after revision procedures. CONCLUSION: Weight regain, inadequate weight loss and reflux were the main reasons for performing secondary bariatric procedures. The main revision procedures performed were RYGB and SG especially for failed AGB.


Asunto(s)
Cirugía Bariátrica , Reoperación , Cirugía Bariátrica/efectos adversos , Cirugía Bariátrica/métodos , Cirugía Bariátrica/estadística & datos numéricos , Humanos , Obesidad Mórbida/cirugía , Prevalencia , Reoperación/efectos adversos , Reoperación/métodos , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Resultado del Tratamiento , Pérdida de Peso
12.
Anal Methods ; 10(44): 5273-5281, 2018 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-31490460

RESUMEN

Online organ monitoring could provide clinicians with critical information regarding organ health prior to transplantation and could aid clinical decision-making. This paper presents the methodology of online microdialysis for real-time monitoring of human organs ex vivo. We describe how rapid sampling microdialysis can be incorporated with organ perfusion machines to create a robust organ monitoring system and demonstrate its use in monitoring human and porcine kidneys as well as human and porcine pancreases. In this paper we also show the potential usefulness of this methodology for evaluating novel interventions in a research setting. The analysis system can be configured either to analyse two analytes in one organ, allowing for ratiometric analysis, or alternatively to monitor one analyte in two organs simultaneously, allowing direct comparison. It was found to be reliable over long monitoring periods in real clinical use. The results clearly show that the analysis system is sensitive to differences between organs and therefore has huge potential as an ex vivo organ monitoring tool.

13.
Ann N Y Acad Sci ; 1075: 258-70, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17108219

RESUMEN

Diabetes mellitus is a major health problem across the world. Diabetic retinopathy (DR) and nephropathy are two of the major complications of diabetes. DR is the leading cause of blindness and diabetic nephropathy is the leading cause of end-stage renal failure. We have examined the potential value of circulating nucleic acids in the detection and monitoring of these two complications of diabetes. mRNA for nephrin was significantly higher in all diabetics compared to healthy controls and it was significantly higher in normoalbuminuric patients compared to healthy controls. This may indicate progression to microalbuminuric stage. Circulating rhodopsin mRNA was detectable in healthy subjects and in diabetic patients. It was significantly raised in diabetic patients with retinopathy. Higher rhodopsin mRNA in diabetic patients without retinopathy suggests that some of them may go on to develop it or already have it subclinically. Circulating nucleic acids have the potential to be noninvasive molecular tests for diabetic complications.


Asunto(s)
Complicaciones de la Diabetes , Diabetes Mellitus , Ácidos Nucleicos/sangre , Adulto , Anciano , Complicaciones de la Diabetes/sangre , Complicaciones de la Diabetes/genética , Diabetes Mellitus/sangre , Diabetes Mellitus/genética , Humanos , Proteínas de la Membrana/genética , Persona de Mediana Edad , Rodopsina/genética
14.
Transplantation ; 100(12): e128-e139, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27861293

RESUMEN

BACKGROUND: Hypothermic machine organ perfusion (HMP) offers opportunity to manipulate grafts with pharmacological agents prior to transplantation. Pretreating organs with novel cytotopic anticoagulant peptides that localize to endothelial cell membranes could ameliorate microvascular thrombotic sequelae posttransplantation. We describe experiments testing thrombalexin (TLN), a novel cell binding thrombin inhibitor, using porcine and unused human kidneys in a series of ex vivo normothermic hemoreperfusion models. METHODS: Thirty-eight porcine kidneys were used. Control kidneys underwent pretreatment via HMP with either unmodified perfusion solution (n = 15) or solution with inactive-TLN (absent anticoagulant effect, n = 4). Test kidneys were perfused with TLN-treated solution (n = 19). All kidneys then underwent hemoreperfusion. Two unused human kidneys underwent a similar protocol. RESULTS: Hypothermic machine perfusion pretreatment facilitated delivery and tethering of TLN in the organ microvasculature. Hemoreperfusion challenge demonstrated improved perfusion in TLN-treated kidneys compared with controls: 26.4% superior flow (30.6 vs. 23.1 mL/min per 100 g, P = 0.019) and 28.9% higher perfusion flow indices (0.43 vs. 0.32 mL/min per 100 g mm Hg, P = 0.049). Orthogonal polarization spectral imaging demonstrated superior microvascular capillary perfusion in TLN-treated organs versus controls (9.1 vs 2.8 pl/s per mm, P = 0.021). Rapid-sampling microdialysis for cortical [lactate] as a marker of tissue ischemia/metabolism detected lower levels in TLN-treated kidneys. Perfusate analysis demonstrated reduced fibrin generation in TLN-treated kidneys correlating with perfusion data. CONCLUSIONS: Our data suggest that HMP graft pretreatment with cytotopic anticoagulants is feasible and ameliorates perfusion deficits seen in ex vivo hemoreperfusion models. There is potential for further development and application of this translational strategy to deliver locally active anticoagulants directly within grafts and decrease microvascular thrombotic sequelae, while avoiding systemic anticoagulation and its associated risks.


Asunto(s)
Anticoagulantes/farmacología , Endotelio Vascular/patología , Preservación de Órganos/métodos , Péptidos/farmacología , Reperfusión , Trombosis/patología , Animales , Isquemia Fría , Humanos , Riñón/patología , Trasplante de Riñón , Microcirculación , Soluciones Preservantes de Órganos , Porcinos , Trombina/antagonistas & inhibidores
15.
Ann N Y Acad Sci ; 1022: 152-6, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15251955

RESUMEN

Diabetic retinopathy is the commonest complication of diabetes and is the biggest single cause of registered blindness in the UK. No biochemical tests exist to determine the precise state and rate of change of the eyes in the diabetic patient. In the present study, using real-time quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we measured mRNA encoding the retina-specific pigment protein rhodopsin (RHO) in the peripheral blood of healthy individuals (n = 20) and diabetic patients (n = 46) with and without retinopathy. Beta-actin mRNA was also assayed and results are expressed as a ratio of RHO to beta-actin mRNA. Peripheral blood was taken by venipucture directly into PAXgene Blood RNA collection tubes and RNA extracted by use of the PAXgene Blood RNA extraction kit, as per the manufacturer's (Qiagen) instructions. Diabetic patients were divided into three groups defined by the severity of retinopathy as assessed by fundoscopy: A, diabetic without retinopathy; B, background retinopathy; and C, preproliferative retinopathy. Medians of the ratios between groups were compared. RHO mRNA was successfully detected and quantified in peripheral blood in all healthy and diabetic groups, with levels shown to be significantly higher in diabetic patients than in healthy controls (2.54 x 10(-5) vs. 1.29 x 10(-5); P = 0.002). Significant differences in RHO mRNA levels were also seen between healthy control subjects and diabetic groups A (2.52 x 10(-5); P = 0.022), B (1.98 x 10(-5); P = 0.028), and C (5.08 x 10(-5); P = 0.002). The results suggest that there is an increase in circulatory RHO mRNA with the severity of diabetic retinopathy.


Asunto(s)
Retinopatía Diabética/sangre , ARN Mensajero/sangre , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rodopsina/sangre , Biomarcadores de Tumor/sangre , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/genética , Retinopatía Diabética/patología , Humanos , ARN Mensajero/genética , Juego de Reactivos para Diagnóstico , Rodopsina/genética , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad
16.
Clin Teach ; 11(3): 179-83, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24802917

RESUMEN

BACKGROUND: Changes in undergraduate medical curricula, combined with reforms in postgraduate education, have training implications for surgical skills acquisition in a climate of reduced clinical exposure. Confidence and prior experience influences the educational impact of learning. Currently there are limited formal basic surgical skills programmes integrated into UK undergraduate curricula. CONTEXT: Early skills targeting is valuable for students entering surgical, related allied specialties and even traditionally non-surgical specialties, such as General Practice. Such experience can make students more confident and subsequently competent future junior doctors and trainees. INNOVATION: The integration of skills training through the use of simple low-fidelity training models can bridge the gap between undergraduate skills education and postgraduate training, whereas approaches involving more recent advances in simulation may prepare students further by making available more contextualised and scenario-based learning environments. IMPLICATIONS: We suggest that it is an ideal time for the introduction of dedicated basic surgical skills programmes into UK undergraduate medical curricula. Training will benefit all students. Importantly, training can inspire confidence, clinical interest, and can also provide a solid foundation of skills that can support and enable junior doctors' further postgraduate training.


Asunto(s)
Competencia Clínica , Educación de Pregrado en Medicina/organización & administración , Procedimientos Quirúrgicos Operativos/educación , Simulación por Computador , Curriculum , Humanos , Reino Unido
17.
J Educ Eval Health Prof ; 11: 3, 2014 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-24699448

RESUMEN

PURPOSE: To date no studies have specifically evaluated the use of handovers amongst core surgical trainees (CSTs) in the United Kingdom. We examined handover practice at the Oxford School of Surgery to assess and improve CSTs'perception of handover use as well as its quality, and ultimately patient care. METHODS: Based on guidelines published by the British Medical Association and Royal College of Surgeons, a 5-point Likert style questionnaire that collected data on handover practice, its educational value, and the CSTs'satisfaction with handover was given to 50 CSTs in 2010. RESULTS: Forty CSTs (80.0%) responded to the questionnaire. The most striking findings revolved around the perceived educational value, formal training, and auditing practice of handovers throughout various units, which were all remarkably lower than expected. As a result, handover practice amongst CSTs was targeted and revised at the University Hospital's Department of Plastic Surgery, with the implementation of targeted changes to improve handover practice. CONCLUSION: The execution of daily handovers was an underused educational tool amongst surveyed CSTs and may be an important modality to target, particularly in the competency-based, time-limited training CSTs receive. We recommend modifications to current practice based on our results and the literature and encourage the assessment of handover practice at other institutions.

18.
Artículo en Inglés | MEDLINE | ID: mdl-24498471

RESUMEN

PURPOSE: Changes in undergraduate medical curricula, combined with reforms in postgraduate education, have training implications for surgical skills acquisition in a climate of reduced clinical exposure. Confidence and prior experience influences the educational impact of learning. Currently there is no basic surgical skills (BSS) programme integrated into undergraduate curricula in the United Kingdom. We explored the role of a dedicated BSS programme for undergraduates in improving confidence and influencing careers in King's College London School of Medicine, and the programme was evaluated. METHODS: A programme was designed in-line with the established Royal College of Surgeons course. Undergraduates were taught four key skills over four weeks: knot-tying, basic-suturing, tying-at-depth and chest-drain insertion, using low-fidelity bench-top models. A Likert-style questionnaire was designed to determine educational value and influence on career choice. Qualitative data was collected. RESULTS: Only 29% and 42% of students had undertaken previous practice in knot-tying and basic suturing, respectively. 96% agreed that skills exposure prior to starting surgical rotations was essential and felt a dedicated course would augment undergraduate training. There was a significant increase in confidence in the practice and knowledge of all skills taught (p<0.01), with a greater motivation to be actively involved in the surgical firm and theatres. CONCLUSION: A simple, structured BSS programme can increase the confidence and motivation of students. Early surgical skills targeting is valuable for students entering surgical, related allied, and even traditionally non-surgical specialties such as general practice. Such experience can increase the confidence of future junior doctors and trainees. We advocate the introduction of a BSS programme into United Kingdom undergraduate curricula.

19.
Int J Surg ; 10(9): 458-62, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22935356

RESUMEN

INTRODUCTION: Simulation occupies a central position in surgical education. It offers a safe environment for trainees to develop and improve their skills through sustained deliberate self-practice and appropriate feedback. This review explores the role of simulators and the simulation environment in light of educational theory to promote effective learning. DATA SOURCES: Information was obtained from peer-reviewed publications, books and online material. CONCLUSION: A simplistic perspective frames simulation as a means of gaining technical skills on basic models by offering a safe alternative to carrying out procedures on real patients. Although necessary, that aspect of simulation requires greater depth to satisfy the growing demand for alternatives to traditional clinical learning. A more realistic view should frame simulation as a means to gaining mastery within a complex clinical world. In order to strike the balance on simulating an ideal clinical scenario, alignment of the simulator and the simulation environment in the appropriate context appears crucial.


Asunto(s)
Cirugía General/educación , Cirugía Asistida por Computador/educación , Simulación por Computador , Humanos
20.
Exp Clin Transplant ; 10(2): 87-100, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22432750

RESUMEN

Solid organ transplant constitutes the definitive treatment for end-stage organ failure. Better organ preservation methods have enabled use of marginal grafts, thereby expanding the donor pool to meet the growing demand for organs. Static cold storage as a preservation method has been superseded largely by machine perfusion in kidney transplant, with work regarding its use in other organ transplants ongoing. We hope that machine perfusion will allow better graft preservation, and pretransplant assessment, and optimization. The most extensive laboratory, preclinical, and clinical research into machine perfusion organ preservation has focused on kidneys. Successful outcomes in its use in renal transplant have sparked interest for its development and application to the liver, pancreas, heart, and lungs. This article reviews the current state of machine perfusion in abdominal and thoracic organ transplant, focusing on the recent developments in assessing graft viability.


Asunto(s)
Supervivencia de Injerto , Trasplante de Órganos/métodos , Trasplante de Órganos/tendencias , Perfusión/métodos , Perfusión/tendencias , Trasplante de Corazón/métodos , Trasplante de Corazón/tendencias , Humanos , Trasplante de Riñón/métodos , Trasplante de Riñón/tendencias , Trasplante de Hígado/métodos , Trasplante de Hígado/tendencias , Trasplante de Pulmón/métodos , Trasplante de Pulmón/tendencias , Trasplante de Páncreas/métodos , Trasplante de Páncreas/tendencias
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