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Timothy J. Wess - One of the best experts on this subject based on the ideXlab platform.
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bimodal collagen fibril diameter distributions direct age related variations in tendon resilience and resistance to rupture
Journal of Applied Physiology, 2012Co-Authors: David F Holmes, Yinhui Lu, Daniel Béchet, Karl E Kadler, Peter P. Purslow, Timothy J. WessAbstract:Scaling relationships have been formulated to investigate the influence of collagen fibril diameter (D) on age-related variations in the strain energy density of tendon. Transmission electron microscopy was used to quantify D in tail tendon from 1.7- to 35.3-mo-old (C57BL/6) male mice. Frequency histograms of D for all age groups were modeled as two normally distributed subpopulations with smaller (DD1) and larger (DD2) mean Ds, respectively. Both DD1 and DD2 increase from 1.6 to 4.0 mo but decrease thereafter. From tensile tests to rupture, two strain energy densities were calculated: 1) uE [from initial loading until the yield stress (σY)], which contributes primarily to tendon resilience, and 2) uF [from σY through the maximum stress (σU) until rupture], which relates primarily to resistance of the tendons to rupture. As measured by the normalized strain energy densities uE/σY and uF/σU, both the resilience and resistance to rupture increase with increasing age and peak at 23.0 and 4.0 mo, respectively, before decreasing thereafter. Multiple regression analysis reveals that increases in uE/σY (resilience energy) are associated with decreases in DD1 and increases in DD2, whereas uF/σU (rupture energy) is associated with increases in DD1 alone. These findings support a model where age-related variations in tendon resilience and resistance to rupture can be directed by subtle changes in the bimodal distribution of Ds.
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bimodal collagen fibril diameter distributions direct age related variations in tendon resilience and resistance to rupture
Journal of Applied Physiology, 2012Co-Authors: David F Holmes, Yinhui Lu, Daniel Béchet, Karl E Kadler, Peter P. Purslow, Timothy J. WessAbstract:Scaling relationships have been formulated to investigate the influence of collagen fibril diameter (D) on age-related variations in the strain energy density of tendon. Transmission electron microscopy was used to quantify D in tail tendon from 1.7- to 35.3-mo-old (C57BL/6) male mice. Frequency histograms of D for all age groups were modeled as two normally distributed subpopulations with smaller (DD1) and larger (DD2) mean Ds, respectively. Both DD1 and DD2 increase from 1.6 to 4.0 mo but decrease thereafter. From tensile tests to rupture, two strain energy densities were calculated: 1) uE [from initial loading until the yield stress (σY)], which contributes primarily to tendon resilience, and 2) uF [from σY through the maximum stress (σU) until rupture], which relates primarily to resistance of the tendons to rupture. As measured by the normalized strain energy densities uE/σY and uF/σU, both the resilience and resistance to rupture increase with increasing age and peak at 23.0 and 4.0 mo, respectively, before decreasing thereafter. Multiple regression analysis reveals that increases in uE/σY (resilience energy) are associated with decreases in DD1 and increases in DD2, whereas uF/σU (rupture energy) is associated with increases in DD1 alone. These findings support a model where age-related variations in tendon resilience and resistance to rupture can be directed by subtle changes in the bimodal distribution of Ds.
David F Holmes - One of the best experts on this subject based on the ideXlab platform.
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bimodal collagen fibril diameter distributions direct age related variations in tendon resilience and resistance to rupture
Journal of Applied Physiology, 2012Co-Authors: David F Holmes, Yinhui Lu, Daniel Béchet, Karl E Kadler, Peter P. Purslow, Timothy J. WessAbstract:Scaling relationships have been formulated to investigate the influence of collagen fibril diameter (D) on age-related variations in the strain energy density of tendon. Transmission electron microscopy was used to quantify D in tail tendon from 1.7- to 35.3-mo-old (C57BL/6) male mice. Frequency histograms of D for all age groups were modeled as two normally distributed subpopulations with smaller (DD1) and larger (DD2) mean Ds, respectively. Both DD1 and DD2 increase from 1.6 to 4.0 mo but decrease thereafter. From tensile tests to rupture, two strain energy densities were calculated: 1) uE [from initial loading until the yield stress (σY)], which contributes primarily to tendon resilience, and 2) uF [from σY through the maximum stress (σU) until rupture], which relates primarily to resistance of the tendons to rupture. As measured by the normalized strain energy densities uE/σY and uF/σU, both the resilience and resistance to rupture increase with increasing age and peak at 23.0 and 4.0 mo, respectively, before decreasing thereafter. Multiple regression analysis reveals that increases in uE/σY (resilience energy) are associated with decreases in DD1 and increases in DD2, whereas uF/σU (rupture energy) is associated with increases in DD1 alone. These findings support a model where age-related variations in tendon resilience and resistance to rupture can be directed by subtle changes in the bimodal distribution of Ds.
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bimodal collagen fibril diameter distributions direct age related variations in tendon resilience and resistance to rupture
Journal of Applied Physiology, 2012Co-Authors: David F Holmes, Yinhui Lu, Daniel Béchet, Karl E Kadler, Peter P. Purslow, Timothy J. WessAbstract:Scaling relationships have been formulated to investigate the influence of collagen fibril diameter (D) on age-related variations in the strain energy density of tendon. Transmission electron microscopy was used to quantify D in tail tendon from 1.7- to 35.3-mo-old (C57BL/6) male mice. Frequency histograms of D for all age groups were modeled as two normally distributed subpopulations with smaller (DD1) and larger (DD2) mean Ds, respectively. Both DD1 and DD2 increase from 1.6 to 4.0 mo but decrease thereafter. From tensile tests to rupture, two strain energy densities were calculated: 1) uE [from initial loading until the yield stress (σY)], which contributes primarily to tendon resilience, and 2) uF [from σY through the maximum stress (σU) until rupture], which relates primarily to resistance of the tendons to rupture. As measured by the normalized strain energy densities uE/σY and uF/σU, both the resilience and resistance to rupture increase with increasing age and peak at 23.0 and 4.0 mo, respectively, before decreasing thereafter. Multiple regression analysis reveals that increases in uE/σY (resilience energy) are associated with decreases in DD1 and increases in DD2, whereas uF/σU (rupture energy) is associated with increases in DD1 alone. These findings support a model where age-related variations in tendon resilience and resistance to rupture can be directed by subtle changes in the bimodal distribution of Ds.
P J Friend - One of the best experts on this subject based on the ideXlab platform.
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urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis a proteomics study
American Journal of Transplantation, 2020Co-Authors: P J Friend, Annemarie Weissenbacher, Honglei Huang, T Surik, Letizia Lo M Faro, Rutger J Ploeg, Constantin C Coussios, Benedikt M KesslerAbstract:We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n = 8 donors after brain death [DBD], n = 8 donors after circulatory death [DCD]) and three with UR (n = 2 DBD, n = 1 DCD), followed by quantitative analysis by mass spectrometry. Damage-associated molecular patterns (DAMPs) were decreased in kidney tissue after 6 hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilization. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after 12 and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic-oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalizes metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys.
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Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis – a proteomics study
'Royal College of Obstetricians & Gynaecologists (RCOG)', 2020Co-Authors: Bm Kessler, P J Friend, Constantin C Coussios, Weissenbacher A, Rj Ploeg, Ml ,lo Faro, Huang H, Surik TAbstract:We describe a proteomics analysis to determine the molecular differences between normothermically perfused (normothermic machine perfusion, NMP) human kidneys with urine recirculation (URC) and urine replacement (UR). Proteins were extracted from 16 kidney biopsies with URC (n=8 donors after brain death (DBD), n=8 donors after circulatory death (DCD)) and three with UR (n=2 DBD, n=1 DCD), followed by quantitative analysis by mass spectrometry. Damage‐associated molecular patterns (DAMPs) were decreased in kidney tissue after six hours NMP with URC, suggesting reduced inflammation. Vasoconstriction was also attenuated in kidneys with URC as angiotensinogen levels were reduced. Strikingly, kidneys became metabolically active during NMP, which could be enhanced and prolonged by URC. For instance, mitochondrial succinate dehydrogenase enzyme levels as well as carbonic anhydrase were enhanced with URC, contributing to pH stabilisation. Levels of cytosolic and the mitochondrial phosphoenolpyruvate carboxykinase were elevated after 24 hours of NMP, more prevalent in DCD than DBD tissue. Key enzymes involved in glucose metabolism were also increased after twelve and 24 hours of NMP with URC, including mitochondrial malate dehydrogenase and glutamic‐oxaloacetic transaminase, predominantly in DCD tissue. We conclude that NMP with URC permits prolonged preservation and revitalises metabolism to possibly better cope with ischemia reperfusion injury in discarded kidneys
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pancreas transplantation from donors after circulatory death from the united kingdom
American Journal of Transplantation, 2012Co-Authors: A S R Muthusamy, Lisa Mumford, Alex Hudson, Susan V Fuggle, P J FriendAbstract:This study reports the comparative short-term results of pancreas transplantation from donors after circulatory death (DCD) (Maastricht III & IV), and pancreases from brainstem deceased donors (DBD). Between January 2006 and December 2010, 1009 pancreas transplants were performed in the United Kingdom, with 134 grafts from DCD and 875 from DBD. DCD grafts had no premortem pharmacological interventions performed. One-year pancreas and patient survival was similar between DCD and DBD, with pancreas graft survival significantly better in the DCD cohort if performed as an SPK. Early graft loss due to thrombosis (8% vs. 4%) was mainly responsible for early graft loss in the DCD cohort. These results from donors with broader acceptance criteria in age, body mass index, premortem interventions, etc. suggest that DCD pancreas grafts may have a larger application potential than previously recognized.
Nigel Heaton - One of the best experts on this subject based on the ideXlab platform.
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minimization of ischemic cholangiopathy in donation after cardiac death liver transplantation is it thrombolytic therapy or warm ischemic time stringency and donor bile duct flush
American Journal of Transplantation, 2018Co-Authors: Wayel Jassem, Shirin Elizabeth Khorsandi, Emmanouil Giorgakis, Nigel HeatonAbstract:Donation after cardiac death (DCD) liver transplantation (LT) is the fastest expanding donor pool. Despite the promise, initial DCD experience showed discouraging outcomes1. Cumulative experience from aggressive LT centers re-ignited the interest in DCD LT2, culminating in outstanding outcomes, comparable to that of donation after brain death (DBD)3. This article is protected by copyright. All rights reserved.
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the impact of ischemia reperfusion injury on liver allografts from deceased after cardiac death versus deceased after brain death donors
PLOS ONE, 2016Co-Authors: Susan V Fuggle, Parthi Srinivasan, Nigel Heaton, Blayne A Sayed, Ana Maria Casasferreira, Mohammed Rela, Cristina Legidoquigley, Wayel JassemAbstract:Background and aims The shortage of organs for transplantation has led to increased use of organs procured from donors after cardiac death (DCD). The effects of cardiac death on the liver remain poorly understood, however. Using livers obtained from DCD versus donors after brain death (DBD), we aimed to understand how ischemia/reperfusion (I/R) injury alters expression of pro-inflammatory markers ceramides and influences graft leukocyte infiltration.
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biliary complications after liver transplantation using grafts from donors after cardiac death results from a matched control study in a single large volume center
Annals of Surgery, 2011Co-Authors: Michelle L Deoliveira, Wayel Jassem, R Valente, Shirin Elizabeth Khorsandi, Gregorio Santori, Andreas Prachalias, Parthi Srinivasan, Mohamed Rela, Nigel HeatonAbstract:Abstract To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death (DCD) at one single large institution. Shortage of available cadaveric organs is a significant limiting factor in liver transplantation (LT). The use of DCD offers the potential to increase the organ pool. However, early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy (IC), leading to several programs to abandoning this source of organs. A retrospective analysis of a prospective database from April 2001 to 2010 focused on 167 consecutive DCD-LT. Each DCD transplant was matched with 2 brain death donors (DBD) grafts (n = 333) according to the period of transplantation. Primary outcome measures were biliary complications including the severity of complications, graft survival and patient survival. Minimum follow-up was 3 months. Anastomotic stricture was the most common biliary complication (DCD = 30, 19% vs. DBD = 41, 13%). Most were treated endocoscopically (grade IIIa = 72%), whereas hepatico-jejunostomy (grade IIIb) was performed in 22%. Primary IC occurred in 4 (2.5%) recipients from the DCD group and was absent in the DBD group (P = 0.005). However, none of these patients required retransplantation. Patient and graft survival at 1, 3, and 5 years were similar between DCD and DBD groups (P = 0.106, P = 0.138, P = 0.113, respectively). The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia.
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biliary complications after liver transplantation using grafts from donors after cardiac death results from a matched control study in a single large volume center
Annals of Surgery, 2011Co-Authors: Michelle L Deoliveira, Wayel Jassem, R Valente, Shirin Elizabeth Khorsandi, Gregorio Santori, Andreas Prachalias, Parthi Srinivasan, Mohamed Rela, Nigel HeatonAbstract:OBJECTIVE To assess the incidence and impact of biliary complications in recipients transplanted from donors after cardiac death (DCD) at one single large institution. BACKGROUND Shortage of available cadaveric organs is a significant limiting factor in liver transplantation (LT). The use of DCD offers the potential to increase the organ pool. However, early results with DCD liver grafts were associated with a greater incidence of ischemic cholangiopathy (IC), leading to several programs to abandoning this source of organs. METHODS A retrospective analysis of a prospective database from April 2001 to 2010 focused on 167 consecutive DCD-LT. Each DCD transplant was matched with 2 brain death donors (DBD) grafts (n = 333) according to the period of transplantation. Primary outcome measures were biliary complications including the severity of complications, graft survival and patient survival. Minimum follow-up was 3 months. RESULTS Anastomotic stricture was the most common biliary complication (DCD = 30, 19% vs. DBD = 41, 13%). Most were treated endocoscopically (grade IIIa = 72%), whereas hepatico-jejunostomy (grade IIIb) was performed in 22%. Primary IC occurred in 4 (2.5%) recipients from the DCD group and was absent in the DBD group (P = 0.005). However, none of these patients required retransplantation. Patient and graft survival at 1, 3, and 5 years were similar between DCD and DBD groups (P = 0.106, P = 0.138, P = 0.113, respectively). CONCLUSIONS The encouraging results with DCD-LT are probably due to the selection of DCD grafts and clear definition of warm ischemia.
J W Marsh - One of the best experts on this subject based on the ideXlab platform.
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liver transplantation using donation after cardiac death donors long term follow up from a single center
American Journal of Transplantation, 2009Co-Authors: M E De Vera, R Lopezsolis, Igor Dvorchik, S Campos, W Morris, A J Demetris, P Fontes, J W MarshAbstract:There is a lack of universally accepted clinical parameters to guide the utilization of donation after cardiac death (DCD) donor livers and it is unclear as to which patients would benefit most from these organs. We reviewed our experience in 141 patients who underwent liver transplantation using DCD allografts from 1993 to 2007. Patient outcomes were analyzed in comparison to a matched cohort of 282 patients who received livers from donation after brain death (DBD) donors. Patient survival was similar, but 1-, 5- and 10-year graft survival was significantly lower in DCD (69%, 56%, 44%) versus DBD (82%, 73%, 63%) subjects (p 20 min, cold ischemia time >8 h and donor age >60 were associated with poorer DCD outcomes. There was a lack of survival benefit in DCD livers utilized in patients with model for end-stage liver disease (MELD) ≤30 or those not on organ-perfusion support, as graft survival was significantly lower compared to DBD patients. However, DCD and DBD subjects transplanted with MELD >30 or on organ-perfusion support had similar graft survival, suggesting a potentially greater benefit of DCD livers in critically ill patients.
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liver transplantation using donation after cardiac death donors long term follow up from a single center
American Journal of Transplantation, 2009Co-Authors: M E De Vera, R Lopezsolis, Igor Dvorchik, S Campos, W Morris, A J Demetris, P Fontes, J W MarshAbstract:There is a lack of universally accepted clinical parameters to guide the utilization of donation after cardiac death (DCD) donor livers and it is unclear as to which patients would benefit most from these organs. We reviewed our experience in 141 patients who underwent liver transplantation using DCD allografts from 1993 to 2007. Patient outcomes were analyzed in comparison to a matched cohort of 282 patients who received livers from donation after brain death (DBD) donors. Patient survival was similar, but 1-, 5- and 10-year graft survival was significantly lower in DCD (69%, 56%, 44%) versus DBD (82%, 73%, 63%) subjects (p 20 min, cold ischemia time >8 h and donor age >60 were associated with poorer DCD outcomes. There was a lack of survival benefit in DCD livers utilized in patients with model for end-stage liver disease (MELD) 30 or on organ-perfusion support had similar graft survival, suggesting a potentially greater benefit of DCD livers in critically ill patients.